Beta Fulltext view is in preview — article structure may vary. Browse all articles
Contents
Neurology & Neurotherapy Open Access Journal Research Article 52 min read

Endocrinology of Sleep and Appetite

Reyna-Echeveste EI, Tolentino Ferrel MR, García Campos ML, Blancarte-Fuentes E, Jiménez-García SN, Ramírez-Gómez XS and Beltrán-Campos V*
* Corresponding author
ISSN: 2639-2178  10.23880/nnoaj-16000141  Received: November 20, 2019  Published: December 16, 2019
 — views
 204 references
PDF
Keywords
Sleep Circadian Rhythm Receptor Feeding Leptin
Abstract

Sleep is an indispensable restoration process for organic homeostasis and endocrine regulation, which consists of 2 phases: REM and NREM, the latter consists in turn of 4 stages, being in the N3 stage of non-rapid eye movement sleep (NREM) where hormonal secretion takes place. Circadian rhythms are responsible for the sleep-wake and feeding-fasting cycle, as well as endocrine regulation, within the suprachiasmatic nucleus, which is usually modified by different factors, causing them to be disrupted causing changes in the same way. Although the sleep process is essential for organic homeostasis, it is currently considered a waste of time for many young adults, so it is becoming a more common problem, the emergence of sleep results in changes in hormones regulators of sleep and appetite, resulting in chronic degenerative diseases, among which is obesity, as it is well known that these diseases generate high costs in health care due to the multiple complications that they bring with increasing the morbidity and mortality rate, for which it is essential to create health strategies. The objective of this study was to collect the most relevant data that allow us to demonstrate the relationship between sleep and hormones involved in its regulation; as well as its relationship with food intake.

Introduction

Sleep is a physiological state, characterized by a decrease in consciousness, reversible, regulated by the surrounding rhythms; these two are carried out in the suprachiasmatic nucleus, it is essential to carry out Thesis various functions such as memory consolidation, restoration of Tissues and endocrine regulation.

Neuroendocrine regulation is carried out in stage N3 of NREM sleep, in various areas of the Central Nervous System (CNS), including the hypothalamus, area involved in sleep and food regulation, as well as organic homeostatic regulation, involved in the latter, circadian rhythms, which, due to fluctuations in these hormones as well as changes in the sleep-wake, feeding-fasting cycle, usually present disruption and therefore contribute to the generation of chronic diseases.

In recent years, various strategies and treatments to combat obesity have been sought and generated, in the same way, it has been the main topic in multiple investigations in which appetite and sleep regulatory hormones are related. The purpose of this review is to show the most recent research related to regulatory hormones, giving guidance to the generation of new research involving both neuropeptides, for the establishment of new treatments.

The objective of this review was to gather the most current information about the hormones that regulate sleep and their relationship with appetite.

Methodology

A search was made in different databases PUBMED, EMBASE, DATABASE, in relation to hormones related to sleep and appetite, determining the period of publication from 2013 to 2018, with the exception of base studies showing historical part of the document. Publications were specified in different languages that included Portuguese, English, Japanese, Russian, Spanish. The terms used for the search included sleep, hormones, appetite, Obesity, physiology, neurophysiology, neurobiology, biosynthesis, endocrinology, circadian Rhythm, receptor, feeding, leptin, Melatonin, cortisol, orexin, ghrelin, POMC, AgRP, NPY, obestatin, serotonin, Dopamine, norepinephrine, epinephrin, GABA and the Boolean operators AND, OR. Finding a total of 12,578 articles of which were discarded based on the title, reading of the summary and content leaving a total of 200 articles included.

Sleep Overview

Sleep is a reversible physiological state, characterized by decreased consciousness and low perceptions of the environment, where relaxation and postural changes muscle are involved, presenting with a circadian periodicity [1, 2, 3]. Which aims at molecular replacement, memory consolidation [4] restoration of metabolic processes and tissues, waste disposal promoting organic homeostasis [1, 5, 6].

Regulatory factors such as endocrines are involved in these repair and homeostasis processes, due to the fact that environmental factors, demands for sleep- wakefulness, feeding-fasting or stimuli-internal responses from target tissues show fluctuations of various hormones; same that are directed by circadian rhythms [4, 7, 8].

Circadian rhythms generated in the suprachiasmatic nucleus (NSC) [9, 10] are essential to maintain physiological mechanisms under sleep regulation, which comprises 2 phases, one consisting of rapid eye movements (REM) and one of the non-rapid eye movements (NREM), [11] with a duration of 60 to 90 minutes each, [12] going through different stages of wakefulness, N1, N2, N3 and R, considering N1 to N3 characteristic of the NREM phase. In stage N3 the sleep is deep and the awakening in this period is difficult, here the tissue repair is carried out in addition to strengthening the immune system [13].

The cortical activity comes from corticotalomocortical interconnections, involving a series of neuronal assemblies, which involve the synchronization and desynchronization of the cortical activity itself that distinguishes the NREM dream for awakening and REM sleep [14, 15]. Daily sleep is preceded by waking rhythms, which arise from the interactions between the circadian cycle regulated by the hypothalamus and a sleep homeostat, of which its anatomical control center has not been recognized. However, it is known that this sleep- wake cycle involves multiple systems and that these are dependent on internal and external regulators [16].

An imbalance in the sleep-wake cycle brings oscillations in the hormonal levels that regulate food intake, being proposed as one of the main causes of obesity and diabetes [10, 17, 18, 19, 20, 21, 22].

Sleep Metabolism

The metabolism is an essential component for the health of living beings; Thus, metabolic health depends largely on the lifestyle of each individual, where sleep health is a primary part of the repair processes in each of the body systems and is essential for the restoration of the central nervous system and its functions [23]. Alterations in physiological sleep, such as those changes in sleep patterns associated with endocrinological changes or diet and age, can have consequences that affect the biological clock that is the center of circadian regulation of sleep and therefore can influence the food intake, energy expenditure and body fat. During evolution, mammals have developed endogenous clocks, characterized by cycles of approximately 24 hours called circadian clocks; which, are maintained by a regulator in the central nervous system (CNS) at the level of the hypothalamus, the suprachiasmatic nucleus (SCN) [24]. The SCN as the main regulator is able to synchronize changes in our body, thanks to the induction of external factors such as light information that serves as the most powerful synchronizer [25]. In contrast, food has a synchronizing influence on the SNA, [26] with the exception of foods with high palatability [27]. So the modification or alteration in any of them is capable of inducing disease in humans.

The SCN receives information from the nerve cells located in the retina that detect the light to regulate the circadian rhythm and regulate sleep through the activation of multiple pathways allowing the nocturnal release of ACTH, prolactin, melatonin and norepinephrine. One of the most commonly recognized pathways by which this occurs is through the simulation of the release of norepinephrine by the CNS, which in turn stimulates the pineal gland to release melatonin [28].

It has been shown that insufficient sleep and feeding in inadequate circadian times have been identified as risk factors for weight gain, prevalent in modern society, McHill, et al. [29] Investigated how chronic insufficient sleep impacts the circadian moment of hunger. subjective and fasting metabolic hormones; in a 32-day randomized single-blind randomized control study, in healthy participants (range, 20-34 years) randomized distributed under two conditions (control group and sleep restriction group (CRS) of 4.67 hours of sleep. Participants lived in a "20 h day" designed to distribute all behaviors and food intake equally in all phases of the circadian cycle every six consecutive days of the 20 h protocol. For every 20 hours a day, participants received an isocaloric diet designed by a nutritionist consisting of 45-50% carbohydrates, 30- 35% fat and 15-20% protein adjusted for sex, weight and age Non-numerical subjective assessments of hunger were recorded before and after meals , and fasting blood samples were taken 5 minutes after waking, subjective hunger levels and fasting concentrations of leptin, ghrelin, insulin, glucose, adiponectin and cortisol they showed circadian patterns; however, there were no differences between CSR conditions and control in subjective hunger ratings or any fasting hormone concentration. These findings suggest that chronic insufficient sleep may have a limited role in altering the robust circadian profile of subjective hunger and fasting metabolic hormones [29].

Among the various studies conducted in recent years it has been seen that there are hormones related to sleep; one of them performed by Blouin, et al. [30] in laboratory and human rats, where changes in the levels of two hypothalamic neuropeptides, hypocretin-1 (Hcrt-1) and melanin concentrating hormone (MCH), in the amygdala were measured human They showed that MCH increased at the beginning of sleep induction; while Hcrt-1 levels increased in the induction of wakefulness, so it is thought that these hormones are involved in the induction and stabilization of sleep [30, 31].

Melatonin

Melatonin is a hormone activated during the dark, synthesized by pinealocytes from 5-hydroxytryptamine, cataloged as an indoleamine because it contains an indole ring, replaced by an amino group [32]. Melatonin exerts its effects thanks to two membrane receptors coupled to G protein (MT1 and MT2), expressed in various areas of the central nervous system (CNS), [33] such as the suprachiasmatic nucleus (NSC), hippocampus, prefrontal cortex, ganglia basals among others; as well as in various peripheral organs [34]. By this, the receptors promote changes in cell signaling that involve the regulation of pubertal development, [35] seasonal adaptation [36] and the sleep-wake cycle, [37] so that the alteration of these receptors and Melatonin production is manifested by surrounding disorders of sleep, memory and learning; [38] in addition, she is involved in the progression of chronic degenerative, metabolic and obesity diseases [39].

The maximum concentration of melatonin is during stage N3 of NREM sleep, [36] produced and secreted by the pineal gland through a signaling pathway that goes from the suprachiasmatic nucleus who acts as a receptor of light from the retina [6, 37] to the paraventricular nucleus towards the upper thoracic spinal cord and from there to the cervical ganglion [38, 39] following a zirconic pattern, this melatonin will activate the MT1 receptors factor that induces neuronal inactivation related to induction of sleep, [40] while MT2 has been linked to neuronal activation in the NSC [41].

It seems that the mechanism of melatonin once coupled to its specific ligand in the MT1 receptor, allows this receptor to combine with Gi / 11G proteins and Gq /

11G protein, inhibiting cAMP, stimulated by phosphocholine, signaling protein kinase A and phosphorylation of CREB. In addition, it increases mitogen-activated protein kinase½ and kinase½ regulated by extracellular signals, potassium mediated conductance; on the other hand, MT2 seems to exert the opposite action [33] which would appear that the activity of melatonin is self-regulated in itself and is dependent on binding to the specific type of receptor.

This mechanism of the MT1 and MT2 receptors plays an essential role in the circadian rhythm [42] and in the secretion phase of melatonin, so an increase in this phase contributes to the disruption of the surrounding rhythms, causing a delay in them and decreased sleep time, [33, 43] which results in various chronic degenerative diseases [40, 33, 44], such as diabetes and obesity [45, 46, 47, 48, 49].

In a study conducted in male rats of the 10-month-old Sprague Dawley strain for 12 weeks, by Wolden-Hason, et al. [50] it begins investigations into possible mechanisms that involve daily administration of melatonin with suppression of intra-abdominal visceral fat, showed a 7% reduction in body weight, so it is considered that the decrease of melatonin by age leads to the development of obesity [50].

Cortisol

In contrast to melatonin, Cortisol prepares the body for wakefulness, being at higher levels during the light phase, [7] is associated with stress and is produced by the adrenal cortex [51]. The levels of this hormone fluctuate with the sleep-wake cycle [52], it is believed that low cortisol levels during deep sleep lead to sleep inertia [53, 54, 55]. Some studies mention that a decrease in sleep hours elevates cortisol, causes an overload of glucocorticoids and as a consequence pernicious effects on the body [56, 57], such as obesity since interacting with insulin allows the accumulation of triglycerides and leads to an increase in central adiposity [58].

Cortisol is synthesized by cells in the fascicular zone of the adrenal cortex by stimulating adrenocorticotropic hormone (ACTH) [58, 7]. In addition, it has been shown that cytosines or adipocytes also stimulate the hypothalamus, pituitary, adrenal axis, through its three levels, hypothalamus, anterior pituitary gland and adrenal cortex. The cortisol produced under this activation is transported bound to the corticosteroid binding globulin at the plasma level and is directed to the peripheral tissues, remaining available by the action of the enzyme 11β-hydroxysteroid dehydrogenase, also being able to bind to the glucosteriodes receptor forming a complex which translocates to the nucleus, modulating the transcription of the genes that respond to cortisol [59].

In experimental animals it has been observed that the pathway that activates melatonin formation is capable of activating the hypothalamus-anterior pituitary-adrenal cortex axis through the transmission of light from the retina to the suprachiasmatic nucleus (NSC) that sends the signal to the hypothalamus medial dorsum (HDM) and periventricular nucleus and from there to the dorsal part of the paraventricular nucleus (NPV) and medial parvocellular nucleus along with corticotrophin-releasing hormone (CRH) neurons to stimulate the secretion of adrenocorticotropic hormone (ACTH) that will stimulate the adrenal cortex for corticosterone secretion [60].

Cortisol maintains glucose balance, inflammatory responses [61] is responsible for controlling the metabolism of lipids and proteins [62]. Tomiyama, et al. [63] evaluated in 45 women with obesity and healthy weight stigmatization associated with physiological risk factors related to stress and obesity, finding a significant relationship between weight stigma and central obesity with cortisol levels [63] Another study by Himmelstein, et al. [64] in 110 women with Body Mass Index (BMI), where the relationship between weight stigma and psychological and physiological consequences was assessed, a significant relationship was found between weight perceptions with a sustained cortisol elevation, these Results suggest that elevated cortisol levels are a factor that stimulates eating and contribute to obesity [64].

On the other hand, Lucaseen, et al. [65] assessed the relationship of the sleep chronotype, food intake, endocrine and metabolic parameters in 27 men with obesity and 92 postmenopausal women, both with lack of sleep for 6.5 hours. An elevation of morning ACTH plasma levels is found in those with evening chronotype and those who add obesity as a variable are associated with a greater tendency to increase cortisol [65].

Studies in experimental animals determine that cortisone and cortisol promote the production of leptin by associating directly with its plasma concentration; that is, the higher the concentration of cortisol, the higher and the concentration of plasma leptin [66].

Leptin

Leptin is a hormone with anorexigenic function, produced mainly in adipocytes, and secondarily in other tissues such as the mammary gland, ovary, among others [67]. Various research works have linked her to functions such as appetite regulation, as a mediator in the reward for food and energy expenditure; [68, 69] as well as, it has been involved in glucose homeostasis [70] and in the initial phase of sleep where there has been an increase in the levels of said hormone [71].

Within its mechanism of action, an activation of the pro-opio-melanocortin neurons (POMC) and the cocaine and amphetamine transcript (CART), related to the suppression of food intake, has been proposed through the inhibition of the peptide related to Agouti (AgRP) and neuropeptide Y (NPY) [69, 72, 73, 74]. So that the activation of POMC reacts by enzymatic cleavage, to derive in ACTH (adrenocorticotropic hormone), stimulating the HHA axis, for cortisol secretion [75]. It seems that this activity is influenced by the aging process, gender [76] and the stress response [77] as well as, for exercise, food and sleep among other factors [78, 79, 80].

It seems that when the secretion of leptin is modified, it affects functions such as the processing of the ingested nutrients, the precision in the size of the food portion and inhibits the digestive and restrictive anabolic effects [81].

On the other hand, the loss of sleep not related to stressors influences the levels of leptin in the opposite way to the loss related to stress in which the pituitary, hypothalamus, adrenal axis will be activated leading to an increase in appetite and hormonal changes, which favors the consumption of foods rich in carbohydrates and therefore obesity [82].

Hart et. al., conducted a study in 2015 on 12 women between 25 and 55 years of age, overweight and obese, in which they examined experimental sleep changes on hunger, food intake and appetite-regulating hormones, they expected that under the restriction of sleep the leptin was at low levels, unlike the ghrelin, insulin and glucose that were expected to be elevated; however, no differences were found between energy intake and appetite-regulating hormones, only in protein restriction did protein intake rise [83]. Unlike this study in 2013, in 37 children from 8 to 11 years of age with overweight and obesity, they assessed the effect that occurs when changing the duration of sleep, on food intake, food reinforcement , appetite and weight regulating hormones, participants were subjected to decreased and increased sleep in different weeks, during the sleep increase condition there was a decrease in food consumption of 134 kcal, weight; as well as, a relationship with low fasting leptin levels in contrast to the condition of decreased sleep time, while with fasting ghrelin or food reinforcement there were no differences in both conditions [84].

Ghrelina

Ghrelin, also known as the appetite hormone, is an acylated peptide composed of 28 amino acids produced primarily in the P / D1 and X / A type cells, [85, 86] at the level of the gastric fund's ointment glands, [87, 88] in the duodenum, jejunum, lungs, urogenital organs and pituitary gland [89]. Its production is promoted through the union of the preproghrelin gene to the ghrelin messenger (mRNA), becoming a preprocessor of 117 amino acid preproghrelin, which is cleaved to form obestatin and ghrelin [90]. In addition, the presence of ghrelin has been detected in various brain areas such as the neurons of the hypothalamic arcuate nucleus (ARC) [91], the ventromedial hypothalamic nucleus (VMN) and the NPV paraventricular nucleus), relevant areas for the control of Hormone secretion of growth (GH) and appetite [92].

Among its functions, it promotes the release of growth hormone, intervenes in fat deposition, regulates glucose homeostasis and collaborates in gluconeogenesis / glycogenolysis, metabolism and energy expenditure, among others [93, 94, 95], It has also been seen to participate in the sleep-wake cycle, learning, memory, neuroprotective effect [96] triglyceride synthesis, modulation of reproductive functions, decreased blood pressure, modulation of endocrine and exocrine secretion of the pancreas and orexigenic [94].

Its orexigenic activity is mediated by the intestine that sends neuronal signals of hunger to the arcuate nucleus through the bloodstream where they are integrated to establish neuronal signals through vagal afferents to activate the hypothalamic circuits in the arcuate nucleus (ARC) and NPV, the dorsomedial region, the central nucleus of the amygdala and the nucleus of the solitary tract (NTS) [92, 96, 97], in the ARC orexigenic neurons expressing NPY and AgRP and anorexigenic neurons expressing POMC and the POMC peptide product (α-MSH) as well as cocaine and amphetamine-regulated transcription (CART) [98]. NPY binds to Y1 and Y5 receptors by stimulating food intake, while AgRP inhibits the anorexic actions of αMSH that is secreted by POMC neurons [99, 100].

This signaling occurs is observed with lack of sleep, ghrelin has high rates during the night, synergizing with leptin [101] therefore the surrounding rhythms affected due to lack of sleep bring about the modification in food intake and hormonally regulated hedonic factors between relating to ghrelin as a possible causative factor [102].

A study by Szentirmai, et al. [103] In male rats of the Sprague-Dawley strain, where the effects of the administration of 0.04, 0.2 or 1 µg of ghrelin were studied by microinjections in different hypothalamic areas involved in feeding regulation and sleep (lateral hypothalamus, medial preoptic area and paraventricular nucleus) during the sleep stage. Their results showed effects that promoted wakefulness, increased food intake in addition to decreased sleep in the first hour after injection at a dose of 0.2 µg. [103].

On the other hand Broussard, et al. [104] conducted a study in 19 men with normal and healthy BMI with and without sleep restriction, in which it was evaluated whether sleep restriction alters the 24-hour profiles of ghrelin appetite regulating hormones, leptin and pancreatic polypeptide when administering a standardized diet and if these alterations predict the intake of food with an ad libitum diet, the results showed elevation of ghrelin levels with sleep restriction, an increase in caloric intake, mainly carbohydrates, thus considering that elevated ghrelin due to sleep restriction leads to increased food intake and obesity development [104]. Such results suggest that ghrelin is related both in the regulation of food consumption and the type of food ingested, indirectly related to the increase in energy consumption and that it contributes secondarily to the development of exogenous obesity.

Orexins (Hypocretins)

Orexin A and orexin B are hypothalamic neuropeptides, derived from the proteolytic cleavage of preproorexin consisting of 131 amino acids; [105, 106, 107] orexin A is composed of 33 amino acids with an amino terminal in the pyroglutamyl residue and two intra-chain disulphide and amidation bonds of the carboxyl terminal, while orexin B is formed of 28 amino acids with an aminated carboxy terminal [106, 108]. Regarding its place of synthesis, there is still great controversy. Several authors have found their expression in neurons of the hypothalamic mediolateral nucleus, hypothalamic nucleus, medial dorsum, perifornian area to lateral hypothalamus, using immunohistological techniques [107, 109, 110, 111, 112].

Two receptors have been found: OX1R expressed in locus coeruleus, [113] in ventromedial and dorsomedial hypothalamic nucleus, while OX2R is expressed in the arcuate nucleus and mammillary nucleus, OX2R has affinities to both neuropeptides, while OX1R is exclusive to Orexin A, both neuropeptides are expressed in the paraventricular nucleus of the thalamus, medial dorsal and medial tegmental area [114], it has been described that both receptors have effects on the regulation of the physiological mechanisms of energy metabolism, sleep regulator and wakefulness, [115] reward, autonomous function, [116, 117, 118, 119, 120] stress modulators [113] mating and behavior maternal, feeding; [121] same that may be sensitive to experience-dependent effects [116].

Orexin A and its receptor appear to have a greater participation in the regulation of intake, [121] when activated by environmental signals increase the feeding; In addition to participating in reward feeding [122]. It seems that high concentrations of glucose and leptin inhibit the activity of orexin A, while low concentrations of glucose and ghrelin allow its activation favoring food consumption [108, 123].

In the dream the levels of the orexin system decrease due to the inhibitory action of the GABAergic hormones in the antero-basal brain and median ventrolateral preotic hypothalamus, they are also responsible for the control of breathing and muscle tone in the sleep phases [124]. The orexin system allows the stability of wakefulness that can be interrupted due to environmental stimulation, which is why the lack of these peptides causes loss of consciousness, seen in patients diagnosed with narcolepsy [125].

Studies in transgenic mice for orexin expression show that the pharmacogenetic activation of orexin neurons is related to an increase in locomotor activity, food intake and water. However, when ablation of orexin neurons is not found changes in the previous relationship or in the expected modifications of the regulation in the sleep- wake cycle; The authors conclude that only some neurons are required to cause the effect on the metabolism [126].

On the other hand, a study conducted by Collet et al., Where the relationship between the energy balance and the sleep-wake cycle was assessed in 12 healthy men, subjected to sleep restriction and caloric restriction for 2 days and subsequently subjected to diet Ad libitum on demand (AL), measuring the levels of different hormones, finding that leptin decreases by 20% after the restriction and an increase during AL feeding, cortisol and ghrelin levels were not affected during the restriction caloric The orexins decreased with caloric restriction maintaining a direct correlation with the duration of sleep in stage 4, these data make it clear that changes in energy levels affect the sleep-wake cycle, giving guidance to generate new research to assess the lack of I dream about the risk of obesity [127].

**Obestatin**

Obestatin is a 23 amino acid peptide, a translational result of the cleavage of residues 76 and 98 of preproghrelin [128, 129]. It is produced in the gastrointestinal mucosa [130, 131] and in smaller amounts in pancreatic islets as well as in different tissues such as mammary gland, testicles, skeletal muscle, adipose tissue, lung, liver [132, 133, 134]. In several studies, obestatin has been linked to the GPR39 receptor, expressed in white adipose tissue, duodenum, jejunum, colon, pancreas, large and small intestine, heart, cerebellum, spleen, lungs [135]. Other studies have shown that this receptor is not specific for obestatin uptake, so controversy continues in trying to establish a specific receptor for this peptide [133, 134, 136, 137].

Obestatin has been linked to the decrease in food intake [129, 131, 136, 138] as well as, with increased body weight and gastrointestinal motility, it mediates cell survival and prevents apoptosis, [131, 129] gastric emptying, jejunal motility [129]. In addition, it promotes lipid accumulation, leptin secretion in preadipocytes, adipocyte differentiation, lipolysis modulation [139] and glucose uptake [140].

It is considered the ghrelin antagonist by promoting the inhibition of jejunal contraction, through an afferent vagal signal [136]. In a study conducted by Yuan et al., in experimental herbivorous carp, it was observed that by an intraperitoneal injection of obestatin, the effects of NPY and its receptors are reduced, leading to the elevation of mRNA levels of the Regulated Transcript of Cocaine and Amphetamine (CART) and POMC [141]. Therefore, it is proposed that obestatin plays a partial role in inhibiting food intake.

Several peptides involved in appetite regulation have implications for sleep; Szentirmai et al., assessed the effect of obestatin on the sleep of male rats of the Sprague-Dawley strain, applying intraperitoneal (16 and 64 µg/kg) or intracerebroventricular (1, 4 and 16 µg in a 4 µl volume) injections of obestatin, showing that in the animals treated intracerebroventricularly with the dose of 1 µg there were no changes in sleep, in those treated at a dose of 4 µg they had a decrease in REM sleep after the first three hours, while one dose of 16 µg, obestatin produced a 58% increase in NREMS sleep time one hour after administration, compared with the dose of 64 µg/kg intraperitoneally in which NREM sleep decreased in patients two hours after administration, but not at the dose of 16 µg/kg in which the sleep-wake cycle did not affect or interfere with NREM sleep, concluding that the effect shown in the dose of 16 µg by intracerebroventricular route was due to the interaction of obestatin with the central receptors [142]. It seems that these findings suggest that obestatin increases NREM sleep and decreases food intake when injected at the beginning of the activity period of rats.

**Pro-Opiomelanocortin (POMC)**

POMC is a polypeptide of 241 amino acid residues [143], composed of arginine / lysine and glutamate / aspartate. It is a precursor of the adenocorticotropic hormone, β-endorphin, a melanocyte stimulating hormone α, β and γ (MSH), N-POMC 1-48, β-lipotropin [144, 145, 146]. It forms part of the melanocortin system in conjunction with the neuropeptide of the regulated transcription of cocaine and amphetamine (CART), Neuropeptide Y (NPY), Agouti-related Peptide (AgRP), and gamma-aminobutyric acid (GABA) [147]. It is synthesized in the anterior and intermediate lobe of the pituitary and arched nucleus [144]. They are expressed in the arcuate nucleus of the hypothalamus and the nucleus of the solitary tract; areas where the satiety signal is perceived [148, 149]. Its activity is related to glucose regulation, [150] fasting and weight loss [151, 152].

The role of POMC as an anorexigenic hormone, was proposed by Zhan et al., Examined the behavior of POMC neurons by stimulation and ablation in the arcuate nucleus and nucleus of the solitary tract in POMC-Cre transgenic mice from 8 to 16 weeks of age, they found that chronic activation reduced food intake, acute activation in the nucleus of the solitary tract rapidly suppressed food consumption, as far as ablation produced hyperphagia and metabolic disorders among which obesity is found [153].

In feeding, ghrelin activates AgRP neurons in the face of energy shortages by inhibiting POMC neurons creating a “hunger boost” [151]. POMC inhibition is modulated by serotonin and leptin, [144, 152, 154] the latter by stimulating POMC neurons activates the central pathways of melanocortin due to the release of melanocyte stimulating hormones that in turn cause the release of α and β of melanocortins to activate the melanocortin 3 and 4 receptors (MC3R and MC4R, respectively), increasing energy expenditure and reducing food intake [148, 155, 156, 157]. During the feeding process glucose levels rise, promoting the neuronal activity of POMC and the satiety signal [145].

A recent study revealed that POMC could also have an orexigenic effect by releasing β-endorphin, and by activating a µ opioid receptor, causing feeding induced by cannabinoid receptor 1 CB1R [158].

Neuropeptide Y (NPY)

Neuropeptide Y, is a pancreatic peptide composed of 36 amino acids with a linkage a tyrosine Y at the carboxyl end, this neuropeptide is derived from the pre-pro-NPY precursor, is distributed in the Central Nervous System (CNS) and Parasympathetic Nervous System (SNP)), [169] expressing itself in the hypothalamus, cerebral cortex and brainstem, [170, 171] its synthesis is carried out in the arcuate nucleus, solitary tract nucleus, locus coeruleus and septohippocampal nucleus [172]. Of the receptors found only in humans, function Y1, Y2, Y4 and Y5 [173, 174] have been seen, some of them related to feeding behavior such as Y1 and Y5. In addition, it is involved in energy homeostasis, surrounding rhythm, cognition and as a stress modulator, since it has been implicated in the regulation of the hypothalamus, pituitary, adrenal axis [175].

The role of NPY in food and sleep has already been mentioned in previous paragraphs [60, 63, 64, 65, 88, 89, 90, 127, 176].

It has been shown that NPY by inhibiting norepinephrine increases sleep, this mechanism is carried out due to the overexpression of NPY that decreases the level of mRNA of dopamine beta hydroxylase, in the Locus Coreulus, decreasing the levels of Noradrenaline [177].

Serotonin

Serotonin (5-hydroxytryptamine, 5-HT), is produced by tryptophan hydroxylase (TPH) that catalyze the formation of 1-5 hydroxytryptophan from an essential amino acid 1- tryptophan [178, 179, 180, 181]. It is synthesized by cells of the gastrointestinal tract and only 5% in the CNS, [182] has 15 receptors of which only 5-HT3R, 5-HT4R and 5-HT7R work at the intestinal level [183].

It performs functions as a neurotransmitter and as a hormone in the intestinal vascular system [184]. Contributes to energy regulation and glucose balance through suppression of food [147] in addition to relating to depression, [185] sleep, [185, 186] sex and temperature control [178]. Serotonin can activate primary afferent neurons as part of gastro intestinal motility and influence the transmission of information to the CNS, [187, 188] specifically in the rafe nuclei, sending projections to the thalamus, striatum, nucleus accumbens, hippocampus and hypothalamus [181].

Serotonin in the regulation of appetite activates POMC neurons through the 5- HT2C receptor and the 5HT1 B receptor that is responsible for inhibiting NPY / AgRP neuropeptides contributing to the inhibition of food intake, [179] so decrease in serotonin levels could inhibit the satiety signal and stimulate food intake, it has been seen that this signal varies according to the type of food that is being consumed in some cases favoring hedonic feeding and therefore obesity [180].

Norepinephrine

It is a catecholamine that acts as a hormone or neurotransmitter, is released in the locus coeruleus [188, 189]. It is synthesized from tyrosine, in the synaptic neuron, where it is converted to dopamine due to the action of tyrosine hydroxylase, dopamine is transported to storage vesicles, where it is converted to norepinephrine by dopamine-β- hydroxylase [190] It is activated by G1-adrenergic, α2-adrenergic and β- adrenergic G protein-coupled receptors (GPCR) [188]. It is associated with memory, [191] food intake, energy homeostasis [192] and wakefulness [193].

In food intake, the expression of AgRP and NPY mRNA acts in the arcuate nucleus in response to glucose deprivation, [176] also inhibits POMC neurons, [194] due to binding to different receptors. In sleep, it is activated to promote wakefulness, [193] the elevation of norepinephrine causes the release of corticotropin- releasing hormone, which will stimulate the pituitary gland to release the adenocorticotropic hormone and the hypothalamus, pituitary, adrenal and therefore the production of cortisol, [195] which has been seen promotes vigilance, so low levels have been seen during NREM sleep while in REM they are almost imperceptible [193]. In the same way it has been seen that interaction with orexins can also induce wakefulness, when norepinephrine is stimulated optogenetically, the activity of orexins is induced by inducing wakefulness, so that the loss of signaling between norepinephrine and orexin receptors alter the sleep-wake cycle [188].

Dopamine (DA)

It is a catecholamine, synthesized in the synaptic neuron from L-Tyrosine and the tetrahydrobiopterin and oxygen cofactors [196]. It exerts its function through 5 receptors coupled to the G protein, grouped into two D1- like (D1 and D5) and D2-like (D2, D3 and D4) families [188]. Low levels of DA induce vasodilation and increase blood flow; high levels cause vasoconstriction and therefore a decrease in abdominal blood flow [182]. She has been involved in decision making, learning [197]. with intestinal homeostasis, gastric emptying, hedonic feeding [196], motivation and body movement coordination [186].

Its release in the ventral tegmental area and in the left black substance is modulated by glucose, increasing in hypoglycemia in the striatum and inhibiting its release in hyperglycemia in the middle brain [198] influencing the behavior of hedonic feeding since in hypoglycemia, preference has been seen in the consumption of foods high in sugar and fat [199, 200].

Epinephrine

It is a catecholamine, it is produced in sympathetic nerve fibers and in chromaffin cells of the adrenal medulla, it is synthesized after the formation of dopamine in norepinephrine by the action of phenylethanolamine N- methyltransferase together with the cofactor S- adenosylmethionine [196]. The receptors under which it performs its function are primarily α 1 and β 2; It has similar functions to norepinephrine, including vasoconstriction with high levels and vasodilation at low levels, increasing blood flow, collaborating with glucose absorption.

Gamma-Aminobutyric Acid (GABA)

It is a CNS inhibitory neurotransmitter; it is expressed in the brain. They occur in the sublaterodorsal nucleus or subcoeruleus. It is synthesized by decarboxylation of glutamate mediated by glutamic acid decarboxylase, it is also produced by AgRP neurons, the release of GABA by this neuropeptide is essential for energy expenditure and food intake stimulated by ghrelin. It has been linked to the release of CRH, activation of HHA and the search for food [186, 193, 201, 202, 203, 204, 205].

It participates in the inhibition of POMC neurons due to their antagonistic actions in conjunction with neuropeptide Y in the ARC; while in sleep it has been seen that inhibition of GABA in the subcoeruleus nucleus reduces REM sleep and promotes wakefulness [193, 201].

Conclusion

Sleep is an important factor for the development of obesity as seen in previous studies; the hormones involved in the regulation of appetite and sleep are usually modified in terms of secretion and production due to various internal and external factors that lead to having pernicious effects on health, sleep so far is not considered as a health problem in Mexico, however, chronic degenerative diseases that occupy the first places in morbidity and mortality. Lack of sleep and deregulation in the surrounding rhythms are considered among the main factors for the development of these diseases that generate a greater demand for health care at all levels and an increase in health expenditures, research is essential future that clearly establishes the effects of some of the hormones in terms of weight gain. Conflict of Interest: The authors declare no conflict of interest

References

  1. Buysse D (2014) Sleep health: Can we define it? Does it matter? Sleep 37(1): 9-17.
  2. Aguirre-Navarrete R (2007) Bases anatómicas y fisiológicas del sueño. Rev Ecuat Neurol 15(2-3).
  3. Carrillo-Mora P, Ramírez-Peris J, Magaña-Vázquez K (2013) Neurobiología del sueño y su importancia: antología para el estudiante universitario. Revista de la facultad de medicina de la UNAM 56(4): 5-15.
  4. Archer S, Oster H (2015) How sleep and wakefulness influence Circadian rhythmicity: efects of insufficient and mistimed sleep on the animal and human transcriptome. J Sleep Res 24(5): 476-493.
  5. Xie L, Kang H, Xu Q, Chen M, Liao Y, et al. (2013) Sleep Drives Metabolite Clearance from the Adult Brain. Science 342(6156): 1-11.
  6. Musiek E, Holtzman D (2016) Mechanics linking circadian cloks, sleep and neurodegeneration. Science 354(6315): 1004-1008.
  7. Gamble K, Berry R, Frank S, Young M (2014) Circadian clock control of endocrine factors. Nat Rev Endocrinol 10(8): 466-475.
  8. Becutti G, Pannain S (2011) Sleep and Obesity. Curr Opin Clin Nutr Metab Care 14(4): 402-412.
  9. Silver R, Kriegsfeld L (2014) Circadian rhythms have broad inmplications for understanding brain and behavior. Eur J Neurosci 39(11): 1866-1880.
  10. Glazer K, Reid JK (2014) Circadian Misalignment and Health. Int Rev Psychiatry 26(2): 139-154.
  11. Kamdar B, Needham D, Collop N (2012) Sleep deprivation in critical illness: its role in physical and psychological recovery. J Intensive Care Med 27(2): 97-111.
  12. Coeytaux A, Wong K, Grunstein R, Lewis S (2013) REM sleep behaviour disorder-more than just a parasomnia. Clinical 42(11): 785-788.
  13. Patel A, Araujo J (2018) Physiology, sleep stages, StatPearls Publishing.
  14. Brown R, Basher R, Mckenna J, Strecker R, McCarley R (2012) Control of sleep and wakefulness. Rev Physiol 92(3): 1087-1187.
  15. Saper C, Fuller P, Pedersen N, Lu J, Scamell T (2010) Sleep state switching. Neuron 68(6): 1023-1042.
  16. Schwartz M, Kilduff T (2015) The neurobiology of sleep and wakefulness. Psychiatr Clin North Am 38(4): 615-644.
  17. Won T, Jeong J, Hong S (2015) The impact of sleep and Circadian disturbance on hormones and metabolism. International Journal of Endocrinology, Article ID 591729.
  18. Cerdenaes J, Schiöth H, Benedict C (2015) Determinats of shortened, disrupted, and MIstimed sleep and asociates metabolic health consequences in healthy humans. Diabetes 64(4): 1073-1080.
  19. St-Onge MP, Wolfe S, Sy M, Shechter A, Hirsch J (2014) Sleep restriction increases the neuronal response to unhealthy food in normal- weight individuals. Int J Obes (Lond) 38(3): 411-416.
  20. Dashti H, Scheer F, Jacques P, Lamon Fava S, Ordovás J (2015) Short sleep duration and dietary intake: epidemiologic evidence, mechanisms, and health implications. American Society for Nutrition. 6(6): 648-659.
  21. Panda S (2016) Circadian physiology of metabolism. Science 354(6315): 1008-1015.
  22. Paschos G (2015) Circadian cloks, feeding time, and metabolic homeostasis. Frontiers in pharmacology 6(112): 4.
  23. Kravitz HM, Kazlauskaite R, Joffe H (2018) Sleep, Health, and Metabolism in Midlife Women and Menopause: Food for Thought. Obstet Gynecol Clin North Am 45(4): 679-694.
  24. Eastman C, Mistlberger E, Rechtschaffen A (1984) Suprachiasmatic nuclei lesions eliminate circadian temperature and sleep rhythms in the rat. Physiology & Behavior 32(3): 357-368.
  25. Mendoza J (2007) Circadian clocks: Setting time by food. Journal of Neuroendocrinology 19(2): 127-137.
  26. Suzuki K, Jayasena C, Bloom S (2012) Obesity and Appetite Control. Experimental Diabetes Research Article ID 824305: 19.
  27. Mendoza J, Angeles-Castellanos M, Escobar C (2005) A daily palatable meal without food deprivation entrains the suprachiasmatic nucleus of rats. European Journal of Neuroscience 22(11): 2855- 2862.
  28. Carley DW, Farabi SS (2016) Physiology of Sleep. Diabetes Spectr 29(1): 5-9.
  29. McHill AW, Hull JT, McMullan CJ, Klerman EB (2018) Chronic Insufficient Sleep Has a Limited Impact on Circadian Rhythmicity of Subjective Hunger and Awakening Fasted Metabolic Hormones. Front Endocrinol (Lausanne) 12(9): 319.
  30. Blouin A, Fried I, Wilson C, Staba R, Behnke E, et al. (2013) Human hypocretin and melanin concentrating hormone levels are linked to emotion and social interaction. Nat Commun 4: 1547.
  31. Fraigne J, Peever J (2013) Melanin-concentrating hormone neurons promote and stabilize sleep. Sleep 36(12): 1767-1768.
  32. Acuña- Castroviejo D, Escames G, Venegas C (2014) Extrapineal melatonin: sources, regulation and potential functions. Cell Mol Life Sci 71(16): 2997- 3025.
  33. Liu C, Weaver D, Jin X, Shearman L, Pleschi R, et al. (1997) Molecular Dissection of Two Distinct Actions of Melatonin on the Suprachiasmatic Circadian Clock. Neuron 19(1): 91-102.
  34. Pandi-Perumal S, Srinivasan V, Maestroni G, Cardinali D, Poeggeler B (2006) Melatonin: Nature´s most versatile biological signal? FEBS Journal 273(13): 2813-2838.
  35. Salti R, Galluzzi F, Bindi G, Perfetto F, Traquini R, et al. (2000) Nocturnal Melatonin Patterns in Children 85(6): 2137-2144.
  36. Cardinali D, Pevet P (1998) Basic aspects of melatonin action. Sleep Medicine Reviews 2(3): 175- 190.
  37. Pandi-Perumal S, Zisapel N, Srinivasan V, Cardinali D (2005) Melatonin and sleep in aging population. Experimental Gerontology 40(12): 911-925.
  38. Srinivasan V, Maestroni GJM, Cardinali DP, Esquifino AI, Pandi-Perumal SR, et al. (2005) Melatonin, immune function and aging. Inmnity & Ageing 2(17): 10.
  39. Mc Fadden E, Jones M, Schoemaker M, Ashworth A, Swerdlon A (2014) The relationship between Obesity and exposure to light at night: cross- sectional analyses of over 100,000 women in the breakthrough generations study. American Journal epidemiology 180(3): 245-250.
  40. Dobocovich M (2007) Melatonin receptors: role on sleep and Circadian Rhythm regulation. Sleep Medicine 8: S34-S42.
  41. Liu J, Clough S, Hutchinson A, Adamah- Biassi E (2016) MT1 and MT2 Melatonin Receptors: A Therapeutic Perpective. Annu Rev Pharmacol Toxicol 56: 361-383.
  42. Tordjman S, Chokron S, Delorme R, Charrier A, Bellissant E, et al. (2017) Melatonin: Pharmacology, functions and therapeutic benefits. Current Neuropharmacology 15(3): 434-443.
  43. Kunz D, Mahlberg R, Müller C, Tilmann A, Bes F (2004) Melatonin in patients with reduced REM sleep duration: two randomized controlled trials. The Journal of Clinical endocrinology & metabolism 89(1): 128-134.
  44. Bonmati- Carrion M, Arguelles- Prieto R, Martinez- Madrid M, Reiter R, Hardeland R, et al. (2014) Protection the melatonin rythm trough Circadian healthy light exposure. International Journal Molecular Sciences 15(12): 23448-23500.
  45. Comai S, Gobbi G (2014) Unveiling the role of melatonin MT2 receptors in sleep, anxiety and other neuropsyquuiatric diseases: a novel target in psychopharmacology. J Psychiatric Neurosci 39(1): 6- 21.
  46. Donga E, Mariek van Dijik, Biermasz N, Lammers G, van Kralingen K, et al. (2010) A single night of partial sleep deprivation induces insulin resistance in multiple metabolic pathways in healthy subjects. Endocrine Research 95(6): 2963-2968.
  47. Nedeltcheva A, Scheer F (2014) Metabolic effects of sleep disruption, links to Obesity and diabetes. Curr Opin Endocrinol Diabetes Obes 21(4): 293-298.
  48. Jenwitheesuk A, Nopparat C, Mukda S, Wongchitrat P, Govitrapong P (2014) Melatonin regulates aging and neurodegeneration through energy metabolism, epigenetics, autophagy and Circadian Rhythm pathways. International Journal of molecular sciences 15(9): 16848-16884.
  49. Silva T, Cunha A, Sandra A, Chimin P, André Ricardo Alves de, et al. (2015) Pinealectomy interferes with the circadian clock genes expression in White adipose tissue. Journal of pineal research 58: 251-261.
  50. Wolden- Hason T, Mitton D, McCants R, Yellon S, Wilkinson C, et al. (2000) Daily Melatonin administration to middle-aged male rats suppresses body weight, intraabdominal adiposity, and plasma leptin and insulin independentof food intake and total body fat. Endocrinology 141(2): 487-497.
  51. Pistollato F, Sumalla S, Elio I, Masias M, Giampieri F, et al. (2016) Associations between sleep, cortisol regulation and diet: posible implications for the risk of alzheimer disease. American society for Nutrition 7(4): 679-689.
  52. Garaulet M, Madrid A (2015) Methods for monitoring the functional status of the circadian system in dietary surveys studies: application criteria and interpretation of results. Nutr Hosp 31(3): 279-289.
  53. Hilditch C, Dorrian J, Banks S (2016) Time to wake up: reactive countermeasures to sleep inertia. Industrial Health 54(6): 528-541.
  54. Kassi E, Chrousos G (2013) The central clock system and the stress axis in health and disease. Hormones 12(2): 172-191.
  55. Leproult R, Van E (2010) Role of sleep and sleep loss in hormonal release and metabolism. Endocr Dev 17: 11-21.
  56. Hirotsu C, Tufik S, Levy M (2015) Interactions between sleep, stress and metabolism: from physiological to phatological conditions. Sleep science 8(3): 142-152.
  57. Baudrand R, Vaidya A (2015) Cortisol dysregulation in Obesity- related metabolic disorders. Curr Opin Endocrinol Diabetes Obes 22(3): 143-149.
  58. Spencer R, Deak T (2017) A users guide to HPA axis research. Physiol Behav 178: 43-65.
  59. Bose M, Oliván B, Laferrére B (2009) Stress and Obesity: the role of the hypotalamic-pitiutary- adrenal axis in metabolic disease. Curr Opin Endocrinol Diabetes Obes 16(5): 340-346.
  60. Bujis R, Wortel J, Heerikhuize J, Feenstra M, Horts G, et al. (1999) Anatomical and functional demostration of a multisynaptic suprachiasmatic nucleus adrenal (cortex) pathway. European Journal of Neuroscience 11(5): 1535-1544.
  61. Benfield R, Newton E, Tanner C, Heitkemper M (2014) Cortisol as a biomarker of stress in term human labor: Physiological and methodological Issues. Biol Res Nurs 16(1): 64-71
  62. Baudrand R, Arteaga E, Moreno M (2010) El tejido graso como modulador endocrino: cambios hormonales asociados a la obesidad. Rev Med Chile 138(10): 1294-1301.
  63. Tomiyama J, Epel E, McClatchey T, Poelke G, Kemeny M, et al. (2014) Associations of weight stigma with cortisol and oxidative stress independient of adiposity. Health Psychol 33(8): 862-867.
  64. Himmelstein M, Incollingo A, Tomiyama J (2015) The weight of stigma: Cortisol reactivity to manipulated weight stigma. Obesity 23(2): 368-374.
  65. Lucassen E, Zhao X, Rother K, Mattingly M, Courville A, et al. (2013) Evening chronotype is associated with changes in eating behavior, more sleep apnea, and increased stress hormones in short sleeping obese individuals. Plos One 8(3): 10.
  66. Tomabechi Y, Tsuruta T, Saito S, Wabitschi M, Sonomaya K (2018) Extra-adrenal glucocorticoids contribute to the postpandrial increase of circulating leptin in mice. J Cell Commun Signal 12(2): 433-439.
  67. Ramos-Loboy A, Donato J (2017) The role of leptine in health and disease. Comprehensive Review 4 (3): 258-291.
  68. Molica F, Morel S, Kwak B, Rohner-Jeanrenaud F, Steffens S (2015) Adipokines at the crossroad Obesity and cardiovascular disease. Thrombosis and Haemostasis 113(3): 553-566.
  69. Hussain Z, Ali J (2017) Food intake regulation by leptin: mechanisms mediating gluconeogénesis and energy expenditure. Asian Pacific Journal of tropical medicine 10(10): 940-944.
  70. Flak J, Myers M (2015) CNS Mechanism of Leptin action. Mol Endocrinol 30(1): 3-12.
  71. Simon C, Gronfier J, Schlienger L, Brandenberger G (1998) Circadian and Ultradian Variations of Leptin in Normal Man under Continuous Enteral Nutrition: Relationship to Sleep and Body Temperature. Journal Clinical Endocrinology and metabolism 83(6): 1893- 1899.
  72. Chen Y, Knight Z (2016) Making sense of the sensory regulation of hungers neurons. Bioessays 38(4): 316- 324.
  73. Moehlecke M, Canani L, Oliveira L, Maciel M, Friedman R, et al. (2016) Determinations of body weight regulation in humans. Arch Endocrinol Metab 60(2): 152-162.
  74. Park H, Ahima R (2015) Physiology of leptine: energy homeostasis, neuroendocrine Function and metabolism. Metabolism 64(1): 24-34.
  75. Lim C, khoo B, Chir B (2017) Normal physiology of ACTH and GH reléase in the hypothalamus and anterior pituitary in Man. Endotex (Internet).
  76. Gaffey A, Bergeman C, Clark L, Wirth M (2016) Aging and the HPA axis: Stress and resilience in older adults. Neurosci Biobehav 68(1): 928-945.
  77. Flak N (2017) A role for Leptine-Regulated neurocircuitry in subordination stress. Physiol Behav 178(1): 144-150.
  78. Brandenberger G, Follenius M (1975) Influence of timing and Intensity of muscular exercise on temporal patterns of plasma Cortisol levels. JCE & M 40(5): 845-849.
  79. Follenius M, Brandenberger G (1982) Diurnal cortisol peaks and their relationships to meal. Journal of Clinical Endocrinology and metabolism 55(4): 757- 761.
  80. Gronfier C, Simon C, Piquard F, Ehrhart J, Brandenberger G (1999) Neuroendocrine processes underlying ultradian sleep regulation in man. The Journal of Clinical endocrinology & Metabolism 84(8): 2686-2690.
  81. Borer K (2014) Counterregulation of insulin by leptin as key component of autonomic regulation of body weight. World J Diabetes 5(5): 606-629.
  82. Pejovic S, Vgontzas A (2010) Leptin and hunger levels in Young healthy adults one night of sleep loss. J Sleep Res 19(4): 552-558.
  83. Hart C, Carskadon M, Demos K, Reen E, Sharkey K, et al. (2015) Acute changes in sleep duration on eating behaviors apettite- regulating hormones in overweight/obese adults. Behav Sleep Med 13(5): 424-436.
  84. Hart C, Carskadon M, Considine R, Fava J, Lawton J, et al. (2013) Changes in children´sleep duration on food intake, weight, and leptine. Pediatrics 132(6): e1473- e1480.
  85. Mosinka P, Zatorski H, Sotrr M, Fichna J (2017) Future tratment of constipation-associated disorders: role of relamorelin and other ghrelin receptors agonists. J Neurogastroenterol Motil 23(2): 171-179.
  86. Khatib N, Gaidhane S, Gaidhane A, Khatib M, Simkhada P, et al. (2014) Ghrelin: ghrelin as a regulatory peptide in growth hormone secretion. Journal of Clinical and Diagnostic Research 8(88): MC13-MC17.
  87. Mihalache L, Gherasim A, Nita O, Ungureanu M, Padureanu S, et al. (2016) Effects of ghrelin in energy balance and body weight homeostasis. Hormones 15(2): 186-196.
  88. Kim C, Kim S, Park S (2017) Neurogenic effects of ghrelin on the hippocampus. International Journal of Molecular Sciences 18(3): E588.
  89. Makris M, Alexandrou A, Papatsoutsos E, Malietzis G, Tsilimigras D, et al. (2017) Ghrelin and Obesity; identifying gaps and dispelling myths a reappraisal. In vivo 31(6): 1047-1050.
  90. Abdalla M (2015) Ghrelin- Physiological functions and regulation. European Endocrinology 11(2): 90- 95.
  91. Kojima M, Hosada H, Date Y, Nakazato M, Matsuo H, et al. (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402(6762): 656-660.
  92. Cowley M, Smith R, Diano S, Tschöp M, Pronchuk N, et. al. (2003) The disruption and mechanism of action of ghrelin in the CNS demostrates a novel Hypothalamic circuit regulating energy homeostasis. Neuron 37(4): 649-661.
  93. Pradham G, Samson S, Sun Y (2013) Ghrelin: much more than a hunger hormone. Curr Opin Clin Nutr Metab Care 16(6): 619-624.
  94. Delporte C (2013) Structure and physiological actions of ghrelin. Scientifica.
  95. You Lv, Liang T, Wang G, Li Z (2018) Ghrelin, a gastrointestinal hormone, regulates energy balance and lipid metabolism. Bioscience reports 38(5): 1-13.
  96. Stoyanova I (2014) Ghrelin: a link between ageing, metabolism and neurodegenerative disorders. Neurobiology of Disease 72: 72-83.
  97. Cabral A, López E, Epelbaum J, Perello M (2017) Is ghrelin synthesized in the central nervous system?. International Journal of Molecular Sciences 18(3): E638.
  98. Delgado M, Cerdá-Reverter J, Soengas J (2017) Hypothalamic integration of metabolic, endocrine and circadian signals in fish: involvement in the control of food intake. Frontiers in Neuroscience 11: 354.
  99. Andrews Z (2011) Central mechanisms involved in the orexigenic actios of ghrelin. Peptides 32(11): 2248-2255.
  100. Zigman J, Bouret S, Andrews Z (2016) Obesity impairs the action of the neuroendocrine ghrelin system. Trends Endocrinol Metab 27(1): 54-63.
  101. Inoue Y (2014) Sleep‐related eating disorder and its associated conditions. PCN Frontier Review 69(6): 309-320.
  102. Mason B, Wang Q, Zigman J (2014) The central nervous system sites mediating the orexigenic actions of ghrelin. Annu Rev Physiol 76: 519-533.
  103. Szentirmai E, Kapás L, Krueger J (2007) Ghrelin microinjection into forebrain sites induces wakelfuness and feedign rats. Am J Physiol Regul Integr Comp Physiol 292(1): R575-R585.
  104. Broussard J, Kilkus J, Delebecque F, Abraham V, Day A, et al. (2016) Elevated ghrelin predicts food intake during experimental sleep restriction. Obesity (Silver Spring) 24(1): 132-138.
  105. Gotter A, Webber A, Coleman P, Renger J, Winrow C (2012) Interbnational unión af basic and Clinical pharmacology. LXXXVI. Orexin receptor Function, nomenclature and pharmacology. Pharmacology reviews 64(389): 389-420.
  106. Shakurai T, Moringuchi T, Furuya K, Kajiwara N, Nakamura T, et al. (1999) Structure and Function of human prepro-orexin gene. The Journal of biological chemestry 274(25): 17771-17776.
  107. Lecea L, Kilduff T, Peyron C, Gao XB, Foye P, et al. (1998) The hypocretines: Hypotalamus- specific peptides neuroexcitatory Activity. Proc Natl Acad Sci 95(1): 322-327.
  108. Chieffi S, Carotenuto M, Monda V, Valenzano A, Villano I, et al. (2017) Orexin system: the key for a healthy life. Frontiers in Physiology 8(357): 1-9.
  109. James M (2017) A Decade of Orexin/Hypocretin and Addiction: Where Are We Now?. Curr Top Behav Neurosci 33(1): 247-281.
  110. Giardino W, Lecea L (2014) Hypocretin (orexin) neuromodulation of stress and reward pathways. Curr Opin Neurobiol 29(1): 103-108.
  111. Zheng H, Patterson L, Berthoud H (2005) Orexin- A projections to the caudal medulla and orexin- induced c- Fos Expression, food intake and autonomic Function. The Journal of comparative Neurology 485(2): 127-142.
  112. Peyron C, Tighe D, Van den Pol A, Lecea L, Heller C, et al. (1998) Neurons Containing Hypocretin (Orexin) Project to Multiple Neuronal Systems. The Journal of Neuroscience 18(23): 9996-10015.
  113. Wang C, Wang Q, Ji B, Pan Y, Xu C, et al. (2018) The Orexin/Receptor System: Molecular Mechanism and Therapeutic Potential for Neurological Diseases. Frontiers in molecular Neuroscience 11(220): 1-16.
  114. Marcus J, Aschkenasi C, Lee C, Chemelli R, Saper C, et al. (2001) Differential Expression of Orexin Receptors 1 and 2 in the Rat Brain. The Journal of comparative Neurology 435(1): 6-25.
  115. Barson J, Leibowitz SF (2017) Orexin/hypocretin system: Role in food and drug overconsumption. Int Rev Neurobiol 136: 199-237.
  116. Nixon J, Mavanji V, Butterick T, Billintong C, Kotz C, et al. (2015) Sleep disorders, Obesity, and aging: the role of orexin. Agening Res Rev 20: 63-73.
  117. Shukla C, Basheer R (2016) Metabolic signals in sleep regulation: recent insights. Nature and science of sleep 8: 9-29.
  118. Latifi B, Adamantidis A, Bassetti C, Schmidt M (2018) Sleep-Wake Cycling and Energy Conservation: Role of Hypocretin and the Lateral Hypothalamus in Dynamic State Dependent Resource Optimization. Frontiers in Neurology 9(790): 1-16.
  119. Schöne C (2017) Orexin/Hypocretin and Organizing Principles for a Diversity of Wake-Promoting Neurons in the Brain. Curr Top Behav Neurosci 33: 51-74.
  120. Li J, Hu Z, Lecea L (2013) The hypocretins/orexins: integrators of multiple physiological functions. BJP 171(2): 332-350.
  121. Hyanes A, Jakson B, Chapman H, Tadayyon M, Johns A, et al. (2000) A selective orexin-1 receptor antagonist reduces food compsumption in male and female rats. Regulatory Paptides 96(1-2): 45-51.
  122. Choi D, Davis J, Fitzergerald M, Benoit S (2010) The role of orexin- A in food motivation, reward- based feeding behavior and food-induce neuronal activation in rats. Neuroscience 167(1): 11-20.
  123. Messina G, Dalia C, Tafuri D, Monda V, Palmeri F, et al. (2014) Orexin-A controls sympathetic Activity and eating behavior. Frontiers in Psychology 5(997): 1-7.
  124. Hauw JJ, Hausser- Hauw C, Girolami U, Hasboun D, Seilhean D (2011) Neuropathology of Sleep Disorders: A Review. Journal of Neuropathology & Experimental Neurology 70(4): 243-252.
  125. Shöne C, Burdakov D (2016) Orexin/Hypocretin and Organizing Principles for a Diversity of Wake- Promoting Neurons in the Brain. Springer Link 33: 51-74.
  126. Intsunka A, Inui A, Tabuchi S, Tsunematsu T, Lazarus M, et al. (2014) Concurrent and robust regulation of feeding behaviors and metabolism by orexin neurons. Neuropharmacology 85: 451-460.
  127. Collet T, Van Der Klaauw A, Henning E, Keogh J, Suddaby D, et al. (2016) The sleep/wake cycle is directly modulated by changes in energy balance. Sleep and metabolism 39(9): 1691-1700.
  128. Zhang S, Zhai G, Zhang J, Zhou J, Chen C (2014) Ghrelin and obestatin plasma levels and ghrelin/obestatin prepropeptide gene polymorphisms in small for gestational age infants. Journal international medical research 42(6): 1232- 1242.
  129. Zhang J, Ren P, Avsian- Krerchmer, Luo C, Rauch R, et al. (2005) Obestatin, a Peptide Encoded by the Ghrelin Gene, Opposes Ghrelin’s Effects on Food Intake. Science 310(5750): 996-999.
  130. Ren A, Guo Z, Wang Y, Wang L, Wang W, et al. (2008) Inhibitory effect of obestatin on glucose-induced insulin secretion in rats. Biochemical and Biophysical research communications 369(3): 969-972.
  131. Cowan E, Burch K, Green B, Grieve D (2016) Obestatin, a Peptide Encoded by the Ghrelin Gene, Opposes Ghrelin’s Effects on Food Intake. BJP 173(14): 2165-2181.
  132. Xing Y, Yang L, Kuang H, Yuan X, Liu H (2017) Function of obestatin in the digestive system. life- sciences literature 34: 21-28.
  133. Green B, Grieve D (2018) Biochemical properties and biological actions of obestatin and its relevence in type 2 diabetes. Peptides 100(1): 249-259.
  134. Granata R, Settanni F, Gallo D, Trovato L, Biancome L, et al. (2008) Obestatin Promotes Survival of Pancreatic -Cells and Human Islets and Induces Expression on Genes Involved in the Regulation of Cell Mass and Function. Diabetes 57: 967-979.
  135. Kolodziejski P, Pruszynska- Oszmalek E, Sassek M, Kaczmarek P, Szczepankiewicz D, et al. (2017) Changes in obestatin gene and GPR39 receptor expression in peripheral tissues of rat models of obesity, type 1 and type 2 diabetes. Journal of Diabetes 9(4): 353-361.
  136. Zizzari P, Longchamps R, Epelbaum J, Bluet- Pajot M (2007) Obestatin Partially Affects Ghrelin Stimulation of Food Intake and Growth Hormone Secretion in Rodents. Endocrinology 184(4): 1648-1653.
  137. Gesmundo I, Gallo D, Favoro E, Ghigo E, Granata R
  138. Xu Y, Elquimist J, Fukuda M (2011) Central nervous control of energy and glucose balance: focus on the central melanocortin system. Ann N Y Acad Sci 1243: 1-14.
  139. Morton G, Cummings D, Baskin D, Barsh G, Schwartz (2013) Obestatin Partially Affects Ghrelin Stimulation of Food Intake and Growth Hormone Secretion in Rodents. IUBMB Life 65(12): 976-982.
  140. Hassouna R, Zizzari P, Viltart O, Yang S, Gardette R, et al. (2012) A Natural Variant of Obestatin, Q90L, Inhibits Ghrelin’s Action on Food Intake and GH Secretion and Targets NPY and GHRH Neurons in Mice. Plos One 7(12): e51135.
  141. Wojciechowicz T, Skrzypski M, Kołodziejski P, Szczepankiewicz D, Pruszynska-Oszmalek E, et al. (2015) Obestatin stimulates differentiation and regulates lipolysis and leptin secretion in rat preadipocytes. Molecular Medicine Reports 12(6): 8169-8175.
  142. Pruszynska-Oszmalek E, Szczepankiewicz D, Hertig I, Skrypski M, Sassek M, et al. (2013) Obestatin inhibits lipogenesis and glucose uptake in isolated primary rat adipocytes. J Biol Regul Homeost Agents 27(1): 23-33.
  143. Yuan X, Cai W, Liang X, Su H, Yuan Y, et al. (2015) Obestatin partially suppresses ghrelin stimulation of appetite in “high-responders” grass carp, Ctenopharyngodon idellus. Comparative Biochemestry and Physiology 184(1): 144-149.
  144. Szentirmai E, Krueger J (2006) Obestatin alters sleep in rats. Neuroscience letters 404(1-2): 222-226.
  145. Yang Y, Harmon C (2017) Molecular signatures of human melanocortin receptors for ligand binding and signaling. Moecular Basis of Disease 1863(10): 2436- 2447.
  146. Cawley N, Li Z, Loh Y (2016) Biosynthesis, Trafficking and Secretion of Pro-opiomelanocortin-derived peptides. J Mol Endocrinol 56(4): T77-T97.
  147. Toda C, Santoro A, Dae J, Diano S (2017) POMC neurons: from birth to death. Annu Rev Physiol 79(1): 209-236.
  148. Kim J, Leyva S, Diano S (2014) Hormonal regulation of the hypothalamic melanocortin system. Frontiers in Physiology 5(480): 1-7. (1998) Authentic Cell-Specific and Developmentally Regulated Expression of Pro-Opiomelanocortin Genomic Fragments in Hypothalamic and Hindbrain Neurons of Transgenic Mice. The Journal of Neuroscience 18(17): 6631-6640.
  149. Berglund E, Vianna C, Donato J, Kim M, Chuang J, et al. (2012) Direct leptin action on POMC neurons regulates glucose homeostasis and hepatic insulin sensitivity in mice. The Journal of Clinical Investigation 122(3): 1000-1009.
  150. Chen Y, Knight Z (2016) Making sense of the sensory regulation of hunger neurons. Boiessays 38(4): 316- 324.
  151. Lanfray D, Richard D (2017) Emerging Signaling Pathway in Arcuate Feeding-Related Neurons: Role of the Acbd7. Frontiers in Neuroscience 11: 328.
  152. Zhan C, Zhou J, Feng Q, Zhang J, Lin S, et al. (2013) Acute and long-term suppression of feeding behavior by POMC neurons in the brainstem and hypothalamus, respectively. The Journal of Neuroscience 33(8): 3624-3632.
  153. Williams K, Margatho L, Lee C, Choi M, Lee S, et al. (2010) Segregation of acute leptin and insulin effects in distinct populations of arcuate POMC neurons. J Neurosci 30(7): 2472-2479.
  154. Balthasar N, Coppari R, Mc Minn J, Liu S, Lee C, et al. (2004) Leptin Receptor Signaling in POMC Neurons Is Required for Normal Body Weight Homeostasis. Neuron 42(6): 983-991.
  155. Diano S (2011) New aspects of melanocortin signaling: a role for prcp in alpha-msh degradation. Front Neuroendocrinol 32(1): 70-83.
  156. Cone R (2006) Studies on the physiological functions of the melanocortin system. Endocrine Reviews 27(7): 736-749.
  157. Koch M, Varela L, Geum J, Dae J, Hernández- Nuño F, et al. (2015) Hypothalamic POMC neurons promote cannabinoid induced feeding. Nature 519(7541): 45- 50.
  158. Shutter J, Graham M, Kinsey A, Scully S, Lüthy R, et al. (1997) Hypothalamic expression of ART, a novel gene related to agouti, is up regulated in obese and diabetic mutant mice. Genes & Development 11: 593-602.
  159. Stütz A, Morrison C, Argyropoulos G (2005) The Agouti-related protein and its role in energy homeostasis. Peptides 26(10): 1771-1781.
  160. Vehapoğlu A, Türkmen S, Terzioğlu S (2016) Alpha- melanocyte-stimulating hormone and agouti-related protein: Do they play a role in appetite regulation in childhood obesity? J Clin Res Pediatr Endocrinol 8(1): 40-47.
  161. Belgardt B, Okumara T, Brüning J (2009) Hormone and glucose signalling in POMC and AgRP neurons. J Physiol 587(22): 5305-5314.
  162. Sohn J, Elquimist J, Williams K (2013) Neuronal circuits that regulate feeding behavior and metabolism. Trends Neurosci 36(9): 504-512.
  163. Ollman M, Wilson B, Yang Y, Kerns J, Chen Y, et al. (1997) Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Sience 278(5335): 135-138.
  164. Chen Y, Lin Y, Kuo T, Knight Z (2015) Sensory detection of food rapidly modulates arcuate feeding circuits. Cell 160(5): 829-841.
  165. Liu T, Kong D, Shah B, Ye C, Koda S, et al. (2012) Fasting activation of AgRP neurons requires NMDA receptors and involves spinogenesis and increased excitatory tone. Neuron 73(3): 511-522.
  166. Hagan M, Rushing P, Pritchard L, Schwartz M, Strack A, et al. (2000) Long-term orexigenic effects of AgRP- (83O132) involve mechanisms other than melanocortin receptor blockade. Am J Physiol Regulated Integrative Comp Physiology 279(1): R47- R52.
  167. Goldstein N, Levine B, Loy K, Meyerson O, Jamnik A, et al. (2018) Hypothalamic neurons that regulate feeding can influence sleep/wake states based on homeostatic need. Current Biology 28(23): 3736- 3747.
  168. Carniglia L, Ramirez D, Durand D, Saba J, Turati J, et al. (2017) Neuropeptides and microglial activation in inflammation, pain, and neurodegenerative diseases. Mediators of Inflamation 2017: 5048616.
  169. Baraban S (1998) Neuropeptide Y and limbic Seizures. Reviews in the Neurosciences 9(2): 117- 128.
  170. Jeong I, Kim E, Kim S, Kim H, Lee D, et al. (2018) mRNA expression and metabolic regulation of npy and agrp1/2 in the zebrafish brain. Neuroscience Letters 668(6): 73-79.
  171. Kask A, Harro J, Hörsten S, Redrobe J, Dumont Y, et al. (2002) The neurocircuitry and receptor subtypes mediating anxiolytic- like effects of neuropeptide Y. Neuroscience and Biobehavioral Reviews 26(3): 259- 283.
  172. Bromée T, Sjödin P, Fredriksson R, Boswell T, Larsson T, et al. (2006) Neuropeptide Y-family receptors Y6 and Y7 in chicken cloning, pharmacological characterization, tissue distribution and conserved synteny with human chromosome región. The FEBS Journal 273(9): 2048-2063.
  173. Holzer P, Farzi A (2014) Neuropeptides and the Microbiota-Gut-Brain Axis. Adv Exp Med Biol 817(1): 195-219.
  174. Reichmann F, Holzer P (2016) Neuropeptide Y: a stressful review. Neuropeptides 55(1): 99-109.
  175. Fraley G, Ritter S (2002) Immunolesion of Norepinephrine and Epinephrine Afferents to Medial Hypothalamus Alters Basal and 2- deoxy-d-glucose- induced neuropeptide y and agouti gene-related protein messenger ribonucleic acid expression in the arcuate nucleus. Endocrinology 144(1): 75-83.
  176. Singh C, Rihel J, Prober D (2017) Neuropeptide Y Regulates Sleep by Modulating Noradrenergic Signaling. Current Biology 27(24): 3796-3811.e5.
  177. Gershon M (2013) 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr Opin Endocrinol Diabetes Obes 20(1): 14-21.
  178. Myung C, Park S, Kim H (2016) Serotonin as a New Therapeutic Target for Diabetes Mellitus and Obesity. Diabetes and Metabolism Journal 40(2): 89-98.
  179. Versteeg R, Serlie M, Kalbeesk A, Fleur S (2015) Serotonin, a possible intermediate between disturbed circadian rhythms and metabolic disease. Neuroscience 301: 155-167.
  180. Cordeiro L, Rabelo P, Moraes M, Teixeira- Coelho F, Wanner S, et al. (2017) Physical exercise-induced fatigue: the role of serotonergic and dopaminergic systems. Brazilian Journal Medical and Biological Research 50(12): e6432.
  181. Fernández-Reina A, Urdiales J, Sanchez-Jimenez F (2018) What we know and what we need to know about aromatic and cationic biogenic amines in the gastrointestinal tract. Foods 7(9): E135.
  182. Wang S, Sharkey K, McKay D (2018) Modulation of the immune response by helminths: a role for serotonin? Bioscience Reports 38(5): 1-16.
  183. Sikander A, Vati S, Kishor K (2009) Role of serotonin in gastrointestinal motility and irritable bowel síndrome. Clinical Chimica Acta 403(1-2): 47-55.
  184. Miyazaki KW, Doya K (2012) Role of serotonin in gastrointestinal motility and irritable bowel síndrome. Mol Neurobiol 45: 213-224.
  185. Briguglio M, Dell´Osso B, Panzica G, Malgaroli A, Banfi G, et al. (2018) Dietary neurotransmitters: a narrative review on current knowledge. Nutrients 10(5): E591.
  186. Holtmann G, Shah A, Morrison M (2017) Pathophysiology of functional gastrointestinal disorders: a holistic Overview. Digestive Disease 35(S1): 5-13.
  187. Palacios-Filardo J, Mellor J (2018) Neuromodulation of hippocampal long-term synaptic plasticity. Current opinión in Neurobiology 54(1): 37-43.
  188. Li S, Franken P, Vassalli A (2018) Bidirectional and context-dependent changes in theta and gamma oscillatory brain activity in noradrenergic cell-specific Hypocretin/Orexin receptor 1-KO mice. Scientific Reports 8(1): 15474.
  189. Ghimire L, Kohli U, Li C, Sofowora G, Muszkat M, et al. (2012) Catecholamine pathway gene variation is associated with norepinephrine and epinephrine concentrations at rest and exercise. Pharmacogenet Genomics 22(4): 254-260.
  190. Murchison C, Zhang X, Zhang W, Ouyang M, Lee A, et al. (2004) A distinct role for norepinephrine in memory retrieval. Cell 117(1): 131-143.
  191. Wellman P (2000) Norepinephrine and the Control of Food Intake. Ingestive behavior and Obesity 16(10): 837-842.
  192. España R, Scammell T (2011) Sleep neurobiology from a Clinical perpesctive. Sleep 34(7): 845-858.
  193. Paeger L, Karakasilioti I, Altmüller J, Frommolt P, Brüning J, et al. (2017) Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenalin. ELife 6: e25770.
  194. Dayan R, Rauchs G, Guillery-Girard B (2016) Rhythms dysregulation: a new perspective for understanding PTSD? Journal of physiology- Paris 110(4): 453-460.
  195. Mittal R, Debs L, Patel A, Nguyen D, Patel K, et al. (2017) Neurotransmitters. The critical regulation gut- brain axis. J Cell Physiol 232(9): 2359-2372.
  196. Schwartenbeck P, FitzGerald T, Mathys C, Dolan R, Friston K (2014) The dopaminergic midbrain encodes the expected certainty about desired outcomes 25(10): 3434-3445.
  197. Page K, Seo D, Belfort- DeAguiar R, Lacadie C, Dzuira J, et al. (2011) Circulating glucose levels modulate neural control of desire for high-calorie foods in humans. The Journal Clinical investigation 121(10): 4161- 4169.
  198. Thompson D, Campbell R (1977) Hunger in Humans Induced by 2-Deoxy-D Glucose: Glucoprivic Control of-Taste Preference and Food Intake. Sience 198(4321): 1065-1668.
  199. Dewan S, Gillet A, Mugarza J, Halford J, Wilding J (2004) Effects of insulin-induced hypoglycaemia on energy intake and food choice at a subsequent test meal. Diabetes/metabolism research and reviews 20(5): 405-410.
  200. Wu Q, Palmiter R (2011) GABAergic signaling by AgRP neurons prevents anorexia via a melanocortin- independent mechanism. Eur J Pharmacol 660(1): 21- 27.
  201. Rowley N, Madsen K, Schousboe A, White H (2012) Glutamate and GABA synthesis, release, transport and metabolism as targets for seizure control. Neurochemistry International 61(4): 546-558.
  202. Tong Q, Ye C, Jones J, Elmquist J, Lowell B (2008) Synaptic release of GABA by AgRP neurons is required for normal regulation of energy balance. Nat Neurosci 11(9): 998-1000.
  203. Contoreggi C (2015) Corticotropin Releasing Hormone and Imaging, rethinking the stress Axis. Nucl Med Biol 42(4): 323-339.
  204. Farrar A, Pereira M, Mingote S, Bunce J, Chrobak J, et al. (2008) Forebrain circuitry involved in effort- related choice: injections of the GABA a agonist muscimol into ventral pallidum alter response allocation in foodseeking behavior. Neuroscience 152(2): 321-330.
More from this journal

Cite this article

BibTeX
APA
RIS
@article{reynaecheveste2019,
  title   = {Endocrinology of Sleep and Appetite},
  author  = {Reyna-Echeveste EI, Tolentino Ferrel MR, García Campos ML, Blancarte-Fuentes E, Jiménez-García SN, Ramírez-Gómez XS and
Beltrán-Campos V},
  journal = {Neurology & Neurotherapy Open Access Journal},
  year    = {2019},
  volume  = {4},
  number  = {2},
  doi     = {10.23880/nnoaj-16000141}
}
Reyna-Echeveste EI, Tolentino Ferrel MR, García Campos ML, Blancarte-Fuentes E, Jiménez-García SN, Ramírez-Gómez XS and
Beltrán-Campos V (2019). Endocrinology of Sleep and Appetite. Neurology & Neurotherapy Open Access Journal, 4(2). https://doi.org/10.23880/nnoaj-16000141
TY  - JOUR
TI  - Endocrinology of Sleep and Appetite
AU  - Reyna-Echeveste EI, Tolentino Ferrel MR, García Campos ML, Blancarte-Fuentes E, Jiménez-García SN, Ramírez-Gómez XS and
Beltrán-Campos V
JO  - Neurology & Neurotherapy Open Access Journal
PY  - 2019
VL  - 4
IS  - 2
DO  - 10.23880/nnoaj-16000141
ER  -