Skip Navigation
Skip to contents

Diabetes Metab J : Diabetes & Metabolism Journal

Search
OPEN ACCESS

Articles

Page Path
HOME > Diabetes Metab J > Volume 36(6); 2012 > Article
Review
Pathophysiology Molecular Mechanisms of Appetite Regulation
Ji Hee Yu, Min-Seon Kim
Diabetes & Metabolism Journal 2012;36(6):391-398.
DOI: https://doi.org/10.4093/dmj.2012.36.6.391
Published online: December 12, 2012
  • 9,698 Views
  • 233 Download
  • 81 Crossref
  • 103 Scopus

Division of Endocrinology and Metabolism, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

Corresponding author: Min-Seon Kim. Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. mskim@amc.seoul.kr

Copyright © 2012 Korean Diabetes Association

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

  • The prevalence of obesity has been rapidly increasing worldwide over the last several decades and has become a major health problem in developed countries. The brain, especially the hypothalamus, plays a key role in the control of food intake by sensing metabolic signals from peripheral organs and modulating feeding behaviors. To accomplish these important roles, the hypothalamus communicates with other brain areas such as the brainstem and reward-related limbic pathways. The adipocyte-derived hormone leptin and pancreatic β-cell-derived insulin inform adiposity to the hypothalamus. Gut hormones such as cholecystokinin, peptide YY, pancreatic polypeptide, glucagon-like peptide 1, and oxyntomodulin transfer satiety signals to the brain and ghrelin relays hunger signals. The endocannabinoid system and nutrients are also involved in the physiological regulation of food intake. In this article, we briefly review physiological mechanisms of appetite regulation.
The prevalence of obesity continues to increase at an alarming rate around the globe. The World Health Organization has forecasted that approximately 2.3 billion adults worldwide will be overweight and more than 700 million will be obese by 2015 [1]. Since obesity is associated with increased risks for type 2 diabetes, cardiovascular events, stroke, certain types of cancer, and neurodegenerative diseases [2], an obesity epidemic will threaten human health in the upcoming years.
Obesity is a state in which energy intake exceeds energy expenditure over a prolonged period. Food intake is promoted by hormones signaling hunger, the availability of high calorie palatable foods, and learned food preferences. It is inhibited by leptin and other hormones that generate satiety, including insulin and gut-derived hormones. A chronic imbalance between hunger and satiety signals leads to long term alterations in food intake and body weight.
Hypothalamus
The hypothalamus, a small area of the brain located just below the thalamus, is the regulating center of appetite and energy homeostasis. The hypothalamus consists of several interconnecting nuclei: the arcuate nucleus (ARC), paraventricular nucleus (PVN), lateral hypothalamic area (LHA), ventromedial nucleus (VMN), and the dorsomedial nucleus (DMN) (Fig. 1). The ARC of the hypothalamus is adjacent to the median eminence, a circumventricular organ having defective blood-brain barriers (BBB). Thus, circulating hormones and nutrients can access the ARC without passing the BBB. Moreover, the ARC surrounds the third cerebroventricle. Hormones and nutrients in the cerebrospinal fluid can diffuse into the extracellular fluids of the ARC. Due to these anatomical features, the ARC is considered to be a hypothalamic area primarily sensing peripheral metabolic signals. In the ARC, there are two distinct neuronal populations: one is a group of neurons coexpressing orexigenic neuropeptides, including neuropeptide Y (NPY) and agouti-related peptide (AgRP), and the other is a subset of neurons expressing anorexigenic neuropeptides, including proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART). These neurons are first-order neurons where peripheral metabolic signals including leptin, insulin, ghrelin, and nutrients are primarily transferred. Anorexigenic monoamine serotonin also acts on POMC neurons through the 5HT-2C receptor to induce anorexia [3]. POMC neurons send axonal projections to the second-order neurons in other hypothalamic areas, the PVN, VMN, and LHA.
The α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide, is produced by the posttranscriptional processing of POMC and released from presynaptic terminals of POMC neurons. By binding to the melanocortin-3 and -4 receptor (MC3R, MC4R) on the second order neurons, α-MSH activates catabolic pathways: reduced food intake and enhanced energy expenditure [4]. Targeted deletion of the MC4R in mice resulted in hyperphagia, reduced energy expenditure, and obesity [4]. In humans, MC4R mutations account for about 6% of severe early-onset obesity [5], supporting an important role for the central melanocortin system in the control of energy metabolism.
Endogenous melanocotin receptor antagonist AgRP is released from the terminals of ARC NPY/AgRP-producing neurons to the synaptic space on the second order neurons where it competes with α-MSH on MC3R and MC4R and antagonizes the effects of α-MSH [6]. Selective ablation of NPY/AgRP neurons in young mice resulted in a significant decrease in food intake and body weight [7], suggesting that these neurons are critical for promoting food intake and preventing weight loss.
The PVN neurons synthesize and secrete neuropeptides that have a net catabolic action, including the corticotrophin-releasing hormone, thyrotropin-releasing hormone, somatostatin, vasopressin, and oxytocin. In addition, PVN sends sympathetic outflow to the peripheral metabolic organs, including liver and adipose tissue, resulting in increased fatty acid oxidation and lipolysis [8]. Destruction of PVN and haploinsufficiency of Sim1, a critical transcriptional factor in the development of PVN, caused hyperphagia and obesity [9], implying a inhibitory role for PVN in food intake and weight gain.
The VMN mainly receives neuronal projections from the ARC, and projects their axons to the ARC, DMN and LHA, as well as brainstem regions. The VMN contains neurons that sense glucose and leptin [10]. Moreover, anorexigenic neuropeptide, a brain-derived neurotrophic factor (BDNF), is produced in the VMN [11]. Destruction of the VMN caused hyperphagia and obesity, as well as hyperglycemia [12]. Thus, the VMN is regarded as a pivotal area in generating satiety and maintaining glucose homeostasis. The DMN contains a high level of NPY terminals and α-MSH terminals originating from the ARC [13]. Destruction of DMN also results in hyperphagia and obesity [14].
In contrast to PVN, VMN, and DMN, destruction of LHA leads to hypophagia and weight loss. Therefore, LHA has been considered to be a feeding center. LHA contains two neuronal populations producing orexigenic neuropeptides, the melanin concentrating hormone (MCH) and orexin, also called hypocretin. NPY/AgRP- and α-MSH-immunoreactive terminals from ARC neurons are in contact with MCH- and orexin-expressing neurons. Orexin-producing neurons are also involved in glucose sensing and the regulation of sleep-awake cycles [15]. Mice with orexin receptor 2 displayed canine narcolepsy. On the other hand, depletion of MCH or the MCH 1 receptor in mice attenuated body weight, suggesting that MCH acts as endogenous orexigenic molecules [16].
Brainstem
The brainstem is another key brain area involved in regulation of food intake and energy balance. Satiety signals from the gastrointestinal (GI) tract primarily relay to the solitary tract nucleus (NTS) through the sensory vagus nerve, a major neuronal link between the gut and the brain. Transaction of sensory vagal fibers resulted in increased meal size and meal duration, confirming that vagal afferents transfer satiety signals to the brain [17]. Like the ARC, the NTS is anatomically close to the circumventricular organ area postrema (AP). Therefore, the NTS is located in a perfect place for receiving both humoral and neural signals. Meanwhile, the NTS receives extensive neuronal projections from the PVN and vice versa, indicating that there is intimate communication between the hypothalamus and the brainstem. Similarly to hypothalamic neurons, NTS neurons produce glucagon-like peptide 1 (GLP-1), NPY, and POMC, as well as sensing peripheral metabolic signals. For instance, POMC neurons in the NTS show the signal transduction activated transcript 3 (STAT3) activation in response to leptin [18]. Thus, circulating hormones and nutrients may inform metabolic signals to the brain by acting on the hypothalamus and brainstem.
Midbrain
The brain rewarding system is involved in the control of hedonic feeding, i.e., the intake of palatable foods. Like other addition behaviors, the mesolimbic and mesocortical dopaminergic pathways are involved in hedonic feeding. Intake of palatable foods elicits a dopamine release in the ventral tegmental area (VTA), which in turn activates the neural pathways from the VTA to the nucleus accumbens (NA) via the medial forebrain bundles. Interestingly, hedonic feeding is modulated by metabolic signals. Leptin acts on the dopaminergic neurons in the VTA to suppress feeding [19]. Conversely, hedonic feeding can override satiety signals. Mice lacking a D2 receptor were more sensitive to leptin [20].
Leptin
The obese gene coding leptin was first identified by positional gene cloning of ob/ob mice in 1994 [21]. Leptin is exclusively produced in white adipocytes and released to systemic circulation. Plasma leptin concentrations increase in proportion to body fat mass and thus can be used as biomarker of adiposity. Circulating leptin enters the brain through BBB and the blood-CSF barriers through receptor-mediated mechanisms. Leptin receptors are highly expressed in the neurons of the hypothalamus, especially the ARC. Leptin binds the long form leptin receptors, Ob-Rb, on the ARC neurons which subsequently induces activation of Janus kinase 2 (JAK2)-STAT3 signaling and inhibition of AMP-activated protein kinase (AMPK) activity [22]. Activation of hypothalamic leptin signaling causes an increase in neuronal activity of POMC/CART neurons while it decreases activity of NPY/AgRP neurons [23], resulting in reduced food intake and enhanced energy expenditure. Interestingly, leptin is also produced in the gastric epithelium and locally amplifies gut satiation signals such as cholecystokinin (CCK) [24]. Leptin also affects the thresholds of sweet taste perception in the tongue [25].
Leptin administration has successfully treated hyperphagia and obesity in humans and rodents with leptin deficiency [26]. However, most obese humans have elevated plasma leptin levels, implying they may have leptin resistance rather than leptin deficiency. Moreover, leptin treatment in obese subjects has proven to be ineffective. One possible mechanism underlying leptin resistance is reduced leptin transport to the brain, which may be due to saturation of leptin transporters at the BBB [24]. Furthermore, elevated plasma proinflammatory cytokines and free fatty acids in obese subjects may impair leptin transport [27]. On the other hand, leptin resistance may result from reduced leptin signaling in hypothalamic neurons. Notably, leptin-induced STAT3 activation was selectively impaired in the hypothalamic ARC [28]. Several mechanisms, including the suppressor of cytokine signaling (SOCS)-3, protein tyrosine phosphatase (PTP)-1B, I-kappa B kinase (IKK), nuclear factor-kappa B (NF-κB), c-Jun kinase (JNK), endoplasmic reticulum stress, and defective autophagy have been shown to contribute to impaired leptin signaling in the hypothalamus of obese mice [29].
Insulin
Insulin is rapidly secreted from pancreatic β-cells following a meal and transported to the brain. Fasting plasma insulin levels have a good positive relation with body fat mass. Thus, insulin is considered to be a surrogate marker for adiposity. In the CNS, insulin receptors are expressed in hypothalamic nuclei, such as the ARC, DMN, and the PVN, well-known areas involved in feeding regulation [30]. Like leptin, insulin binds insulin receptors on ARC neurons, resulting in activation of POMC neurons and inhibition of NPY/AgRP neurons through the insulin receptor substrate (IRS)-2, the phosphatidyl inositol-3-kinase (PI3K)-Akt-FoxO1 signaling pathway [31]. Through these effects, insulin relays an anorexigenic signal to the brain. The role of insulin in the regulation of energy balance was supported by finding that deletion of the neuron-specific insulin receptor and IRS-2 causes an obesity phenotype in mice [32].
The GI tract is considered to be the largest endocrine organ in the body. In addition to its original function as a digestive and absorptive organ, the gut plays an important role in the control of energy homeostasis, particularly in short-term regulation of food intake.
Cholecystokinin (CCK)
CCK is the first gut hormone which has been shown to have anorexigenic action [33]. Intravenous injection of CCK reduces meal size and duration in humans and rats [34], and affects the total amount of food intake per day. CCK is secreted from I-type enteroendocrine cells in the duodenum and small intestine to intestinal lamina propria where it binds to CCK receptors on the vagus nerve terminal, transferring satiety signals to the hypothalamus via the brainstem and pontine parabrachial nucleus [34]. There are two different subtypes of CCK receptors, CCK-A and CCK-B. CCK-A is primarily expressed in the GI tract, while CCK-B is predominant in the CNS [35]. Otsuka Long-Evans Tokushima Fatty rats, an animal model of obese type 2 diabetes, have mutations in CCK-A [36].
Pancreatic polypeptide (PP)
Meal intake induces PP secretion from pancreatic islet PP cells via a vagal-mediated mechanism. A rise in circulating PP levels following a meal is in proportion to the calorific load and lasts for up to 6 hours [37]. Acute and chronic peripheral administration of PP reduces food intake in mice [38]. These anorectic effects of PP are thought to be mediated via the Y4 receptor in the brainstem and hypothalamus [38].
In humans, anorexigenic effects of PP persisted for 24 hours post-infusion, suggesting that PP may be involved in longer-term control of appetite [39]. Plasma PP levels were shown to be lower in obese subjects [40]. Interestingly, both basal and postprandial release of PP was reduced in patients with Prader-Willi syndrome, suggesting that defective PP secretion may account for hyperphagia in obese patients [41].
Peptide tyrosine-tyrosine (PYY)
PYY is secreted postprandially from the L cells of the ileum, colon, and rectum as a form of PYY1-36 [42], which is rapidly metabolized to PYY3-36 by the dipeptidyl peptidase (DPP)-4 in circulation. Circulating PYY3-36 binds to the Y2 receptor on presynaptic terminals of hypothalamic NPY/AGRP neurons with a high affinity [43], which results in inactivation of NPY/AgRP-producing neurons and induction of anorexia. Infusion of PYY3-36 in humans reduced consumption of food during test meals [44]. Obese subjects had lower plasma PYY3-36 levels compared to lean subjects [44]. Therefore, it has been suggested that reduced PYY secretion in the postprandial period may contribute to impaired satiety generation and development of obesity. Interestingly, the polymorphism of the PYY gene (Q62P), which impaired binding of PYY to the Y2 receptor, was associated with higher body weight [45].
GLP-1
GLP-1 is produced from a large precursor peptide preproglucagon in L cells of the ileum and colon. GLP-1 is secreted to systemic circulation where it is rapidly inactivated by DPP-4 [46]. Thus, the half-life of plasma GLP-1 is about 1 to 2 minutes. According to a recent meta-analysis [47], intravenous infusion of GLP-1 induced a reduction in food intake in both lean and obese humans with a lower effect in obese subjects. GLP-1 exerts anorexigenic effects through the GLP-1 receptor (GLP-1R), which is widely distributed in the brain, GI tract, and pancreas [48]. Administration of exendin-4, a DPP-4 resistant long-acting GLP-1R agonist, suppresses food intake in humans and rodents [49]. In addition to anorexigenic action, GLP-1 stimulates glucose-dependent insulin secretion by acting on pancreatic β-cells. Thus, DPP-4 inhibitors and degradation-resistant GLP-1 analogues are now used for the treatment of obese type 2 diabetes.
Oxyntomodulin (OXM)
OXM is produced from preproglucagon along with GLP-1 in intestinal L cells and has modest anorexigenic actions in rodents and humans [50]. The anorexic effects of OXM were antagonized by coadministration of GLP-1R antagonist and abolished in GLP-1R null mice [51], suggesting that OXM signals anorexia through GLP-1R.
Ghrelin
Ghrelin is a unique gut hormone in that it has an orexigenic effect. It was originally isolated from the rat stomach as an endogenous ligand of the growth hormone secretagogue receptor (GHS-R) and has been shown to have a GH-releasing effect [52]. Subsequently, ghrelin was identified as orexigenic hormone. Ghrelin administration stimulates food intake and body weight gain when administered centrally and peripherally [52]. Moreover, plasma ghrelin concentrations are elevated during a fast. Thus, ghrelin is considered to be a physiological hunger hormone. Of note, plasma ghrelin concentrations display a circadian rhythm: a rise before each meal and a rapid fall after eating, supporting a role for ghrelin in meal initiation. Fasting morning ghrelin concentrations have a negative correlation with fat mass index. Obese subjects displayed lower ghrelin levels compared with lean subjects [53]. Diet-induced weight loss in obese individuals increased plasma ghrelin levels [54]. These findings suggest that plasma ghrelin levels may represent a compensatory response to altered energy metabolism.
GI endocannabinoids system
The central and peripheral endogenous cannabinoid system appears to play a role in feeding regulation. Endocannabinoid receptors, CB1 and CB2, are expressed in the GI tract [55]. Administration of CB1 agonist increased food intake and reduced gastric motility [56]. Conversely, administration of a selective CB1 antagonist suppressed food intake and weight gain in obese animals [56], suggesting that endogenous endocannabinoids may have an orexigenic effect. Consistently, fasting elevated CB1 expression in the vagus and levels of endogenous CB1 ligand anandamide in the small intestine [56].
In addition to hormones, nutrients by themselves can relay satiety signals to the hypothalamus. Glucose signals satiety by acting on the hypothalamic glucose responsive neurons in the ARC and VMH [10] that have glucose-sensing machinery such as glucose transporter-2, glucokinase, and ATP-dependent potassium (KATP) channel as in pancreatic β-cells. Likewise, exogenous free fatty acids have an anorexigenic effect which is mediated through KATP channels [57]. In the hypothalamic neurons, fatty acid intermediates malonyl CoA and long chain fatty acyl-CoA are shown to signal satiety [58]. In the gut, oleoylethanolamide is released after a meal and generates satiety signals through the G-protein coupled receptor GPR119 [59]. In addition, the amino acid leucine can induce satiety by activating the mTOR and S6K signaling pathway in hypothalamic neurons [60].
We briefly illustrated the physiological mechanisms of appetite regulation with a focus on appetite regulators derived from the periphery (Fig. 2). In the CNS, the hypothalamus and brainstem play a central role in appetite regulation. Defective satiety generation in these areas leads to overeating and progression of obesity, although detailed mechanisms for this phenomenon are not completely understood. In addition, the recent epidemic of obesity is also associated with hedonic feeding. Therefore, future studies are needed to understand the modes of interaction between the metabolic center (hypothalamus, brain stem) and reward center (VTA, NA, forebrain) under normal-weight and obese conditions.
In recent decades, the gut has emerged as an important metabolic organ due to the fact that severe human obesity and combined metabolic disorders are successfully treated by bariatric surgery. Although changes in GLP-1, PYY, and ghrelin after bariatric surgery may explain a portion of the beneficial effects of nutritional bypass, the mechanisms of this phenomenon are largely unknown. Further research is needed to expand our understanding of the mechanisms of normal and abnormal regulation of food intake and eventually enable us to overcome obesity and its related metabolic disorders.
Acknowledgements
This work is supported by a grant from the National Research Foundation of Korea (2007-0056866, 2009-0079566).

No potential conflict of interest relevant to this article was reported.

  • 1. World Health Organization (WHO). Obesity. 2008. Geneva: WHO.
  • 2. Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH. The disease burden associated with overweight and obesity. JAMA 1999;282:1523-1529. ArticlePubMed
  • 3. Heisler LK, Cowley MA, Tecott LH, Fan W, Low MJ, Smart JL, Rubinstein M, Tatro JB, Marcus JN, Holstege H, Lee CE, Cone RD, Elmquist JK. Activation of central melanocortin pathways by fenfluramine. Science 2002;297:609-611. ArticlePubMed
  • 4. Huszar D, Lynch CA, Fairchild-Huntress V, Dunmore JH, Fang Q, Berkemeier LR, Gu W, Kesterson RA, Boston BA, Cone RD, Smith FJ, Campfield LA, Burn P, Lee F. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 1997;88:131-141. ArticlePubMed
  • 5. Tao YX. Molecular mechanisms of the neural melanocortin receptor dysfunction in severe early onset obesity. Mol Cell Endocrinol 2005;239:1-14. ArticlePubMed
  • 6. Ollmann MM, Wilson BD, Yang YK, Kerns JA, Chen Y, Gantz I, Barsh GS. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science 1997;278:135-138. ArticlePubMed
  • 7. Bewick GA, Gardiner JV, Dhillo WS, Kent AS, White NE, Webster Z, Ghatei MA, Bloom SR. Post-embryonic ablation of AgRP neurons in mice leads to a lean, hypophagic phenotype. FASEB J 2005;19:1680-1682. ArticlePubMedPDF
  • 8. Foster MT, Song CK, Bartness TJ. Hypothalamic paraventricular nucleus lesion involvement in the sympathetic control of lipid mobilization. Obesity (Silver Spring) 2010;18:682-689. ArticlePubMedPDF
  • 9. Leibowitz SF, Hammer NJ, Chang K. Hypothalamic paraventricular nucleus lesions produce overeating and obesity in the rat. Physiol Behav 1981;27:1031-1040. ArticlePubMed
  • 10. Gonzalez JA, Reimann F, Burdakov D. Dissociation between sensing and metabolism of glucose in sugar sensing neurones. J Physiol 2009;587(Pt 1):41-48. ArticlePubMed
  • 11. Xu B, Goulding EH, Zang K, Cepoi D, Cone RD, Jones KR, Tecott LH, Reichardt LF. Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat Neurosci 2003;6:736-742. ArticlePubMedPMCPDF
  • 12. Shimizu N, Oomura Y, Plata-Salaman CR, Morimoto M. Hyperphagia and obesity in rats with bilateral ibotenic acid-induced lesions of the ventromedial hypothalamic nucleus. Brain Res 1987;416:153-156. ArticlePubMed
  • 13. Jacobowitz DM, O'Donohue TL. Alpha-Melanocyte stimulating hormone: immunohistochemical identification and mapping in neurons of rat brain. Proc Natl Acad Sci U S A 1978;75:6300-6304. ArticlePubMedPMC
  • 14. Bernardis LL, Bellinger LL. The dorsomedial hypothalamic nucleus revisited: 1986 update. Brain Res 1987;434:321-381. ArticlePubMed
  • 15. Ohno K, Sakurai T. Orexin neuronal circuitry: role in the regulation of sleep and wakefulness. Front Neuroendocrinol 2008;29:70-87. ArticlePubMed
  • 16. Marsh DJ, Weingarth DT, Novi DE, Chen HY, Trumbauer ME, Chen AS, Guan XM, Jiang MM, Feng Y, Camacho RE, Shen Z, Frazier EG, Yu H, Metzger JM, Kuca SJ, Shearman LP, Gopal-Truter S, MacNeil DJ, Strack AM, MacIntyre DE, Van der Ploeg LH, Qian S. Melanin-concentrating hormone 1 receptor-deficient mice are lean, hyperactive, and hyperphagic and have altered metabolism. Proc Natl Acad Sci U S A 2002;99:3240-3245. ArticlePubMedPMC
  • 17. Schwartz GJ. The role of gastrointestinal vagal afferents in the control of food intake: current prospects. Nutrition 2000;16:866-873. ArticlePubMed
  • 18. Ellacott KL, Halatchev IG, Cone RD. Characterization of leptin-responsive neurons in the caudal brainstem. Endocrinology 2006;147:3190-3195. ArticlePubMedPDF
  • 19. Hommel JD, Trinko R, Sears RM, Georgescu D, Liu ZW, Gao XB, Thurmon JJ, Marinelli M, DiLeone RJ. Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Neuron 2006;51:801-810. ArticlePubMed
  • 20. Kim KS, Yoon YR, Lee HJ, Yoon S, Kim SY, Shin SW, An JJ, Kim MS, Choi SY, Sun W, Baik JH. Enhanced hypothalamic leptin signaling in mice lacking dopamine D2 receptors. J Biol Chem 2010;285:8905-8917. ArticlePubMedPMC
  • 21. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994;372:425-432. ArticlePubMedPDF
  • 22. Minokoshi Y, Alquier T, Furukawa N, Kim YB, Lee A, Xue B, Mu J, Foufelle F, Ferre P, Birnbaum MJ, Stuck BJ, Kahn BB. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 2004;428:569-574. ArticlePubMedPDF
  • 23. Sahu A. Leptin signaling in the hypothalamus: emphasis on energy homeostasis and leptin resistance. Front Neuroendocrinol 2003;24:225-253. ArticlePubMed
  • 24. Munzberg H. Leptin-signaling pathways and leptin resistance. Forum Nutr 2010;63:123-132. PubMed
  • 25. Nakamura Y, Sanematsu K, Ohta R, Shirosaki S, Koyano K, Nonaka K, Shigemura N, Ninomiya Y. Diurnal variation of human sweet taste recognition thresholds is correlated with plasma leptin levels. Diabetes 2008;57:2661-2665. ArticlePubMedPMCPDF
  • 26. Licinio J, Caglayan S, Ozata M, Yildiz BO, de Miranda PB, O'Kirwan F, Whitby R, Liang L, Cohen P, Bhasin S, Krauss RM, Veldhuis JD, Wagner AJ, DePaoli AM, McCann SM, Wong ML. Phenotypic effects of leptin replacement on morbid obesity, diabetes mellitus, hypogonadism, and behavior in leptin-deficient adults. Proc Natl Acad Sci U S A 2004;101:4531-4536. ArticlePubMedPMC
  • 27. Banks WA. Anorectic effects of circulating cytokines: role of the vascular blood-brain barrier. Nutrition 2001;17:434-437. ArticlePubMed
  • 28. Munzberg H, Flier JS, Bjorbaek C. Region-specific leptin resistance within the hypothalamus of diet-induced obese mice. Endocrinology 2004;145:4880-4889. ArticlePubMedPDF
  • 29. Zhang X, Zhang G, Zhang H, Karin M, Bai H, Cai D. Hypothalamic IKKbeta/NF-kappaB and ER stress link overnutrition to energy imbalance and obesity. Cell 2008;135:61-73. ArticlePubMedPMC
  • 30. Corp ES, Woods SC, Porte D Jr, Dorsa DM, Figlewicz DP, Baskin DG. Localization of 125I-insulin binding sites in the rat hypothalamus by quantitative autoradiography. Neurosci Lett 1986;70:17-22. ArticlePubMed
  • 31. Taniguchi CM, Emanuelli B, Kahn CR. Critical nodes in signalling pathways: insights into insulin action. Nat Rev Mol Cell Biol 2006;7:85-96. ArticlePubMedPDF
  • 32. Bruning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orban PC, Klein R, Krone W, Muller-Wieland D, Kahn CR. Role of brain insulin receptor in control of body weight and reproduction. Science 2000;289:2122-2125. ArticlePubMed
  • 33. Gibbs J, Young RC, Smith GP. Cholecystokinin decreases food intake in rats. J Comp Physiol Psychol 1973;84:488-495. ArticlePubMed
  • 34. Liddle RA, Goldfine ID, Rosen MS, Taplitz RA, Williams JA. Cholecystokinin bioactivity in human plasma. Molecular forms, responses to feeding, and relationship to gallbladder contraction. J Clin Invest 1985;75:1144-1152. ArticlePubMedPMC
  • 35. Wank SA. Cholecystokinin receptors. Am J Physiol 1995;269(5 Pt 1):G628-G646. ArticlePubMed
  • 36. Miyasaka K, Kanai S, Ohta M, Kawanami T, Kono A, Funakoshi A. Lack of satiety effect of cholecystokinin (CCK) in a new rat model not expressing the CCK-A receptor gene. Neurosci Lett 1994;180:143-146. ArticlePubMed
  • 37. Adrian TE, Bloom SR, Bryant MG, Polak JM, Heitz PH, Barnes AJ. Distribution and release of human pancreatic polypeptide. Gut 1976;17:940-944. ArticlePubMedPMC
  • 38. Asakawa A, Inui A, Yuzuriha H, Ueno N, Katsuura G, Fujimiya M, Fujino MA, Niijima A, Meguid MM, Kasuga M. Characterization of the effects of pancreatic polypeptide in the regulation of energy balance. Gastroenterology 2003;124:1325-1336. ArticlePubMed
  • 39. Batterham RL, Le Roux CW, Cohen MA, Park AJ, Ellis SM, Patterson M, Frost GS, Ghatei MA, Bloom SR. Pancreatic polypeptide reduces appetite and food intake in humans. J Clin Endocrinol Metab 2003;88:3989-3992. ArticlePubMed
  • 40. Lassmann V, Vague P, Vialettes B, Simon MC. Low plasma levels of pancreatic polypeptide in obesity. Diabetes 1980;29:428-430. ArticlePubMed
  • 41. Zipf WB, O'Dorisio TM, Cataland S, Dixon K. Pancreatic polypeptide responses to protein meal challenges in obese but otherwise normal children and obese children with Prader-Willi syndrome. J Clin Endocrinol Metab 1983;57:1074-1080. ArticlePubMed
  • 42. Adrian TE, Ferri GL, Bacarese-Hamilton AJ, Fuessl HS, Polak JM, Bloom SR. Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology 1985;89:1070-1077. ArticlePubMed
  • 43. Michel MC, Beck-Sickinger A, Cox H, Doods HN, Herzog H, Larhammar D, Quirion R, Schwartz T, Westfall T. XVI. International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY, and pancreatic polypeptide receptors. Pharmacol Rev 1998;50:143-150. PubMed
  • 44. Batterham RL, Cohen MA, Ellis SM, Le Roux CW, Withers DJ, Frost GS, Ghatei MA, Bloom SR. Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med 2003;349:941-948. ArticlePubMed
  • 45. Ahituv N, Kavaslar N, Schackwitz W, Ustaszewska A, Collier JM, Hebert S, Doelle H, Dent R, Pennacchio LA, McPherson R. A PYY Q62P variant linked to human obesity. Hum Mol Genet 2006;15:387-391. ArticlePubMed
  • 46. Mentlein R, Gallwitz B, Schmidt WE. Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur J Biochem 1993;214:829-835. ArticlePubMed
  • 47. Verdich C, Flint A, Gutzwiller JP, Naslund E, Beglinger C, Hellstrom PM, Long SJ, Morgan LM, Holst JJ, Astrup A. A meta-analysis of the effect of glucagon-like peptide-1 (7-36) amide on ad libitum energy intake in humans. J Clin Endocrinol Metab 2001;86:4382-4389. ArticlePubMed
  • 48. Yamato E, Ikegami H, Takekawa K, Fujisawa T, Nakagawa Y, Hamada Y, Ueda H, Ogihara T. Tissue-specific and glucose-dependent expression of receptor genes for glucagon and glucagon-like peptide-1 (GLP-1). Horm Metab Res 1997;29:56-59. ArticlePubMed
  • 49. Edwards CM, Stanley SA, Davis R, Brynes AE, Frost GS, Seal LJ, Ghatei MA, Bloom SR. Exendin-4 reduces fasting and postprandial glucose and decreases energy intake in healthy volunteers. Am J Physiol Endocrinol Metab 2001;281:E155-E161. ArticlePubMed
  • 50. Dakin CL, Gunn I, Small CJ, Edwards CM, Hay DL, Smith DM, Ghatei MA, Bloom SR. Oxyntomodulin inhibits food intake in the rat. Endocrinology 2001;142:4244-4250. ArticlePubMed
  • 51. Baggio LL, Huang Q, Brown TJ, Drucker DJ. Oxyntomodulin and glucagon-like peptide-1 differentially regulate murine food intake and energy expenditure. Gastroenterology 2004;127:546-558. ArticlePubMed
  • 52. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999;402:656-660. ArticlePubMedPDF
  • 53. le Roux CW, Patterson M, Vincent RP, Hunt C, Ghatei MA, Bloom SR. Postprandial plasma ghrelin is suppressed proportional to meal calorie content in normal-weight but not obese subjects. J Clin Endocrinol Metab 2005;90:1068-1071. ArticlePubMedPDF
  • 54. Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, Purnell JQ. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 2002;346:1623-1630. ArticlePubMed
  • 55. Sanger GJ. Endocannabinoids and the gastrointestinal tract: what are the key questions? Br J Pharmacol 2007;152:663-670. ArticlePubMedPMCPDF
  • 56. Fride E, Bregman T, Kirkham TC. Endocannabinoids and food intake: newborn suckling and appetite regulation in adulthood. Exp Biol Med (Maywood) 2005;230:225-234. ArticlePubMedPDF
  • 57. Obici S, Feng Z, Morgan K, Stein D, Karkanias G, Rossetti L. Central administration of oleic acid inhibits glucose production and food intake. Diabetes 2002;51:271-275. ArticlePubMedPDF
  • 58. Morton GJ, Cummings DE, Baskin DG, Barsh GS, Schwartz MW. Central nervous system control of food intake and body weight. Nature 2006;443:289-295. ArticlePubMedPDF
  • 59. Overton HA, Babbs AJ, Doel SM, Fyfe MC, Gardner LS, Griffin G, Jackson HC, Procter MJ, Rasamison CM, Tang-Christensen M, Widdowson PS, Williams GM, Reynet C. Deorphanization of a G protein-coupled receptor for oleoylethanolamide and its use in the discovery of small-molecule hypophagic agents. Cell Metab 2006;3:167-175. ArticlePubMed
  • 60. Cota D, Proulx K, Smith KA, Kozma SC, Thomas G, Woods SC, Seeley RJ. Hypothalamic mTOR signaling regulates food intake. Science 2006;312:927-930. ArticlePubMed
Fig. 1
Hypothalamic nuclei involved in appetite regulation. ARC, arcuate nucleus; AM, amygdala; CC, corpus callosum; CCX, cerebral cortex; DMN, dorsomedial nucleus; FX, fornix; HI, hippocampus; LHA, lateral hypothalamic area; ME, median eminence; OC, optic chiasm; PFA, perifornical area; PVN, paraventricular nucleus; SE, septum; 3V, third ventricle; TH, thalamus; VMN, ventromedial nucleus.
dmj-36-391-g001.jpg
Fig. 2
A schematic representation of the multiple systems regulating appetite. AgRP, agouti-related peptide; ARC, arcuate nucleus; CCK, cholecystokinin; GLP-1, glucagon-like peptide 1; LHA, lateral hypothalamic area; NPY, neuropeptide Y; NTS, nucleus of the solitary tract; OXM, oxyntomodulin; POMC, pro-opiomelanocortin; PP, pancreatic polypeptide; PVN, paraventricular nucleus; PYY, peptide YY.
dmj-36-391-g002.jpg

Figure & Data

References

    Citations

    Citations to this article as recorded by  
    • Regulation of glycose and lipid metabolism and application based on the colloidal nutrition science properties of konjac glucomannan: A comprehensive review
      Pengkui Xia, Ying Zheng, Li Sun, Wenxin Chen, Longchen Shang, Jing Li, Tao Hou, Bin Li
      Carbohydrate Polymers.2024; 331: 121849.     CrossRef
    • Weight Regain after Metabolic Surgery: Beyond the Surgical Failure
      Juan Salazar, Pablo Duran, Bermary Garrido, Heliana Parra, Marlon Hernández, Clímaco Cano, Roberto Añez, Henry García-Pacheco, Gabriel Cubillos, Neidalis Vasquez, Maricarmen Chacin, Valmore Bermúdez
      Journal of Clinical Medicine.2024; 13(4): 1143.     CrossRef
    • Thylakoid supplementation and hunger and fullness perception: a systematic review and dose-response meta-analysis of randomized controlled trials
      Negin Nikrad, Mehdi Ghaffari Sarghein, Mahdieh Abbasalizad Farhangi
      Nutrition Reviews.2024;[Epub]     CrossRef
    • Stomach clusterin as a gut-derived feeding regulator
      Cherl NamKoong, Bohye Kim, Ji Hee Yu, Byung Soo Youn, Hanbin Kim, Evonne Kim, So Young Gil, Gil Myoung Kang, Chan Hee Lee, Young-Bum Kim, Kyeong-Han Park, Min-Seon Kim, Obin Kwon
      BMB Reports.2024; 57(3): 149.     CrossRef
    • Anorexigenic neuropeptides as anti-obesity and neuroprotective agents
      Veronika Strnadová, Andrea Pačesová, Vilém Charvát, Zuzana Šmotková, Blanka Železná, Jaroslav Kuneš, Lenka Maletínská
      Bioscience Reports.2024;[Epub]     CrossRef
    • UV Irradiation Increases Appetite and Prevents Body Weight Gain through the Upregulation of Norepinephrine in Mice
      Qing-Ling Quan, Eun Ju Kim, Sungsoo Kim, Yeon Kyung Kim, Min Hwa Chung, Yu-Dan Tian, Chang-Yup Shin, Dong Hun Lee, Jin Ho Chung
      Journal of Investigative Dermatology.2024;[Epub]     CrossRef
    • The non-conventional edible plant foroba (Parkia biglobosa) has anti-obesity effect, improves lipid peroxidation and reverses colon and hippocampal lesions in healthy and obese rats
      Mirela Gouveia-Nhanca, Maria Luiza Rolim Bezerra, Kamila Sabino Batista, Rafael Oliveira Pinheiro, Naís Lira Soares, Maria Carolina de Paiva Sousa, Adriano Francisco Alves, Mateus Duarte Ribeiro, Alexandre Sergio Silva, Marciane Magnani, Marcos dos Santos
      Journal of Functional Foods.2023; 108: 105745.     CrossRef
    • Aberrant bone marrow-derived microglia in the hypothalamus may dysregulate appetite in diabetes
      Miwako Katagi, Yuki Nakae, Junko Okano, Kazunori Fujino, Tomoki Tanaka, Itsuko Miyazawa, Natsuko Ohashi, Takahiko Nakagawa, Hideto Kojima
      Biochemical and Biophysical Research Communications.2023; 682: 132.     CrossRef
    • Proteins and peptides from vegetable food sources as therapeutic adjuvants for the type 2 diabetes mellitus
      Ivan Chan-Zapata, Carlos Sandoval-Castro, Maira Rubí Segura-Campos
      Critical Reviews in Food Science and Nutrition.2022; 62(10): 2673.     CrossRef
    • Differential effects of citalopram on the intake of high fat or high carbohydrates diets in female and male rats
      Amparo L. De la Fuente-Reynoso, Eliana Barrios De Tomasi, Jorge Juárez
      Nutritional Neuroscience.2022; 25(7): 1477.     CrossRef
    • Egzersizin iştah ve iştah hormonları üzerine etkisinin incelenmesi: PubMed üzerinden yapılmış sistematik derleme
      Esmanur Kaya, Şerife Vatansever
      Turkish Journal of Sports Medicine.2022; 57(1): 51.     CrossRef
    • Role of Leu72Met of GHRL and Gln223Arg of LEPR Variants on Food Intake, Subjective Appetite, and Hunger-Satiety Hormones
      Tania Sanchez-Murguia, Nathaly Torres-Castillo, Lisset Magaña-de la Vega, Saraí Citlalic Rodríguez-Reyes, Wendy Campos-Pérez, Erika Martínez-López
      Nutrients.2022; 14(10): 2100.     CrossRef
    • Appetite ratings and ghrelin concentrations in young adults after administration of a balanced meal. Does sex matter?
      Alessandro Leone, Ramona De Amicis, Marta Pellizzari, Simona Bertoli, Simone Ravella, Alberto Battezzati
      Biology of Sex Differences.2022;[Epub]     CrossRef
    • Interplay between fatty acid desaturase2 (FADS2) rs174583 genetic variant and dietary antioxidant capacity: cardio-metabolic risk factors in obese individuals
      Mahdieh Khodarahmi, Parisa Javidzade, Mahdieh Abbasalizad Farhangi, Ahmad Hashemzehi, Houman Kahroba
      BMC Endocrine Disorders.2022;[Epub]     CrossRef
    • Appetite-regulating hormones in bipolar disorder: A systematic review and meta-analysis
      Błażej Misiak, Krzysztof Kowalski, Bartłomiej Stańczykiewicz, Francesco Bartoli, Giuseppe Carrà, Jerzy Samochowiec, Agnieszka Samochowiec, Dorota Frydecka
      Frontiers in Neuroendocrinology.2022; 67: 101013.     CrossRef
    • Association of plasma brain-derived neurotrophic factor levels and frailty in community-dwelling older adults
      Eun Roh, Soon Young Hwang, Eyun Song, Min Jeong Park, Hye Jin Yoo, Sei Hyun Baik, Miji Kim, Chang Won Won, Kyung Mook Choi
      Scientific Reports.2022;[Epub]     CrossRef
    • Gut Hormones in Health and Obesity: The Upcoming Role of Short Chain Fatty Acids
      Habeeb Alhabeeb, Ali AlFaiz, Emad Kutbi, Dayel AlShahrani, Abdullah Alsuhail, Saleh AlRajhi, Nemer Alotaibi, Khalid Alotaibi, Saad AlAmri, Saleh Alghamdi, Naji AlJohani
      Nutrients.2021; 13(2): 481.     CrossRef
    • Asprosin ve Glikoz Metabolizması Üzerine Etkileri
      M. Gizem KESER, Nurhan ÜNÜSAN
      Turkish Journal of Diabetes and Obesity.2021; 5(1): 89.     CrossRef
    • Recent Advances in Understanding Peripheral Taste Decoding I: 2010 to 2020
      Jea Hwa Jang, Obin Kwon, Seok Jun Moon, Yong Taek Jeong
      Endocrinology and Metabolism.2021; 36(3): 469.     CrossRef
    • Association of increased abdominal adiposity at birth with altered ventral caudate microstructure
      Dawn X. P. Koh, Mya Thway Tint, Peter D. Gluckman, Yap Seng Chong, Fabian K. P. Yap, Anqi Qiu, Johan G. Eriksson, Marielle V. Fortier, Patricia P. Silveira, Michael J. Meaney, Ai Peng Tan
      International Journal of Obesity.2021; 45(11): 2396.     CrossRef
    • The Crosstalk Between Brain Mediators Regulating Food Intake Behavior in Birds: A Review
      Behrouz Rahmani, Elham Ghashghayi, Morteza Zendehdel, Mina Khodadadi, Behnam Hamidi
      International Journal of Peptide Research and Therapeutics.2021; 27(4): 2349.     CrossRef
    • Oral Semaglutide, the First Ingestible Glucagon-Like Peptide-1 Receptor Agonist: Could It Be a Magic Bullet for Type 2 Diabetes?
      Hwi Seung Kim, Chang Hee Jung
      International Journal of Molecular Sciences.2021; 22(18): 9936.     CrossRef
    • Potential Role of Hypothalamic and Plasma Ghrelin in the Feeding Behavior of Obese Type 2 Diabetic Rats with Intraventricular Glucagon-Like Peptide-1 Receptor Agonist Intervention
      Ke Lu, Xiaoyan Chen, Xuelian Deng, Juan Long, Jianhua Yan
      Obesity Facts.2021; 14(1): 10.     CrossRef
    • Managing obesity through natural polyphenols: A review
      Manisha Singh, Thilini Thrimawithana, Ravi Shukla, Benu Adhikari
      Future Foods.2020; 1-2: 100002.     CrossRef
    • Neurochemical Regulators of Food Behavior for Pharmacological Treatment of Obesity: Current Status and Future Prospects
      Gayane Sargis Vardanyan, Hasmik Samvel Harutyunyan, Michail Iosif Aghajanov, Ruben Sargis Vardanyan
      Future Medicinal Chemistry.2020; 12(20): 1865.     CrossRef
    • Modulation of feeding behavior and metabolism by dynorphin
      Aishwarya Ghule, Ildiko Rácz, Andras Bilkei-Gorzo, Este Leidmaa, Meike Sieburg, Andreas Zimmer
      Scientific Reports.2020;[Epub]     CrossRef
    • Possible role of peptide YY (PYY) in the pathophysiology of irritable bowel syndrome (IBS)
      Magdy El-Salhy, Jan Gunnar Hatlebakk, Trygve Hausken
      Neuropeptides.2020; 79: 101973.     CrossRef
    • Prolactin-releasing peptide increases food intake and affects hypothalamic physiology in Japanese quail (Coturnix japonica)
      B.R. McConn, T. Tachibana, E.R. Gilbert, M.A. Cline
      Domestic Animal Endocrinology.2020; 72: 106464.     CrossRef
    • Obesity induced by Borna disease virus in rats: key roles of hypothalamic fast-acting neurotransmitters and inflammatory infiltrates
      Georg Gosztonyi, Hanns Ludwig, Liv Bode, Moujahed Kao, Manfred Sell, Peter Petrusz, Béla Halász
      Brain Structure and Function.2020; 225(5): 1459.     CrossRef
    • D‐methionine improves cisplatin‐induced anorexia and dyspepsia syndrome by attenuating intestinal tryptophan hydroxylase 1 activity and increasing plasma leptin concentration
      Yi‐Sin Wong, Meei‐Yn Lin, Pei‐Fen Liu, Jiunn‐Liang Ko, Guan‐Ting Huang, Dom‐Gene Tu, Chu‐Chyn Ou
      Neurogastroenterology & Motility.2020;[Epub]     CrossRef
    • Effects of oral, smoked, and vaporized cannabis on endocrine pathways related to appetite and metabolism: a randomized, double-blind, placebo-controlled, human laboratory study
      Mehdi Farokhnia, Gray R. McDiarmid, Matthew N. Newmeyer, Vikas Munjal, Osama A. Abulseoud, Marilyn A. Huestis, Lorenzo Leggio
      Translational Psychiatry.2020;[Epub]     CrossRef
    • Role of Paraventricular Nucleus in Regulation of Feeding Behaviour and the Design of Intranuclear Neuronal Pathway Communications
      Shiba Yousefvand, Farshid Hamidi
      International Journal of Peptide Research and Therapeutics.2020; 26(3): 1231.     CrossRef
    • Self-Reported Eating Speed and Incidence of Gestational Diabetes Mellitus: the Japan Environment and Children’s Study
      Jia-Yi Dong, Satoyo Ikehara, Takashi Kimura, Meishan Cui, Yoko Kawanishi, Tadashi Kimura, Kimiko Ueda, Hiroyasu Iso
      Nutrients.2020; 12(5): 1296.     CrossRef
    • Effects of a high-fat-diet supplemented with probiotics and ω3-fatty acids on appetite regulatory neuropeptides and neurotransmitters in a pig model
      D. Valent, L. Arroyo, E. Fàbrega, M. Font-i-Furnols, M. Rodríguez-Palmero, J.A. Moreno-Muñoz, J. Tibau, A. Bassols
      Beneficial Microbes.2020; 11(4): 347.     CrossRef
    • Electro-Acupuncture Alleviates Cisplatin-Induced Anorexia in Rats by Modulating Ghrelin and Monoamine Neurotransmitters
      Ji Yun Baek, Tuy An Trinh, Wonsang Huh, Ji Hoon Song, Hyun Young Kim, Juhee Lim, Jinhee Kim, Hyun Jin Choi, Tae-Hun Kim, Ki Sung Kang
      Biomolecules.2019; 9(10): 624.     CrossRef
    • Interleukin-6 Expression by Hypothalamic Microglia in Multiple Inflammatory Contexts: A Systematic Review
      Vanessa C. D. Bobbo, Carlos P. Jara, Natália F. Mendes, Joseane Morari, Lício A. Velloso, Eliana P. Araújo
      BioMed Research International.2019; 2019: 1.     CrossRef
    • Abnormalities in Glucose Metabolism, Appetite-Related Peptide Release, and Pro-inflammatory Cytokines Play a Central Role in Appetite Disorders in Peritoneal Dialysis
      Lorena Avila-Carrasco, Mario A. Pavone, Elena González, Álvaro Aguilera-Baca, Rafael Selgas, Gloria del Peso, Secundino Cigarran, Manuel López-Cabrera, Abelardo Aguilera
      Frontiers in Physiology.2019;[Epub]     CrossRef
    • Branched chain amino acids stimulate gut satiety hormone cholecystokinin secretion through activation of the umami taste receptor T1R1/T1R3 using an in vitro porcine jejunum model
      Min Tian, Jinghui Heng, Hanqing Song, Yufeng Zhang, Fang Chen, Wutai Guan, Shihai Zhang
      Food & Function.2019; 10(6): 3356.     CrossRef
    • Multi-Omic Biological Age Estimation and Its Correlation With Wellness and Disease Phenotypes: A Longitudinal Study of 3,558 Individuals
      John C Earls, Noa Rappaport, Laura Heath, Tomasz Wilmanski, Andrew T Magis, Nicholas J Schork, Gilbert S Omenn, Jennifer Lovejoy, Leroy Hood, Nathan D Price, David Le Couteur
      The Journals of Gerontology: Series A.2019; 74(Supplement): S52.     CrossRef
    • The impact of sugar consumption on stress driven, emotional and addictive behaviors
      Angela Jacques, Nicholas Chaaya, Kate Beecher, Syed Aoun Ali, Arnauld Belmer, Selena Bartlett
      Neuroscience & Biobehavioral Reviews.2019; 103: 178.     CrossRef
    • Leptin Signaling in the Control of Metabolism and Appetite: Lessons from Animal Models
      Alberto A. Barrios-Correa, José A. Estrada, Irazú Contreras
      Journal of Molecular Neuroscience.2018; 66(3): 390.     CrossRef
    • Role of paraventricular hypothalamic dopaminergic D1 receptors in food intake regulation of food-deprived rats
      Zahra. Mirmohammadsadeghi, Masoud. Shareghi Brojeni, Abbas. Haghparast, Afsaneh. Eliassi
      European Journal of Pharmacology.2018; 818: 43.     CrossRef
    • Integrating Thyroid Hormone Signaling in Hypothalamic Control of Metabolism: Crosstalk Between Nuclear Receptors
      Soumaya Kouidhi, Marie-Stéphanie Clerget-Froidevaux
      International Journal of Molecular Sciences.2018; 19(7): 2017.     CrossRef
    • Review article: Role of satiety hormones in anorexia induction by Trichothecene mycotoxins
      Chloé Terciolo, Marc Maresca, Philippe Pinton, Isabelle P. Oswald
      Food and Chemical Toxicology.2018; 121: 701.     CrossRef
    • Obezite ve Ghrelin/Leptin İlişkisi
      Aliye Sağkan Öztürk, Abdullah ARPACI
      Mustafa Kemal Üniversitesi Tıp Dergisi.2018; 9(35): 136.     CrossRef
    • Overexpression of Wild-Type Human Alpha-Synuclein Causes Metabolism Abnormalities in Thy1-aSYN Transgenic Mice
      Elodie Cuvelier, Mathieu Méquinion, Coline Leghay, William Sibran, Aliçia Stievenard, Alessia Sarchione, Marie-Amandine Bonte, Christel Vanbesien-Mailliot, Odile Viltart, Kevin Saitoski, Emilie Caron, Alexandra Labarthe, Thomas Comptdaer, Pierre Semaille,
      Frontiers in Molecular Neuroscience.2018;[Epub]     CrossRef
    • Aetiology of eating behaviours: A possible mechanism to understand obesity development in early childhood
      Nikki Boswell, Rebecca Byrne, Peter S.W. Davies
      Neuroscience & Biobehavioral Reviews.2018; 95: 438.     CrossRef
    • Clinical Phenotype of Depression Affects Interleukin-6 Synthesis
      Łukasz Zadka, Piotr Dzięgiel, Michał Kulus, Marcin Olajossy
      Journal of Interferon & Cytokine Research.2017; 37(6): 231.     CrossRef
    • Altered Adipogenesis in Zebrafish Larvae Following High Fat Diet and Chemical Exposure Is Visualised by Stimulated Raman Scattering Microscopy
      Marjo Den Broeder, Miriam Moester, Jorke Kamstra, Peter Cenijn, Valentina Davidoiu, Leonie Kamminga, Freek Ariese, Johannes De Boer, Juliette Legler
      International Journal of Molecular Sciences.2017; 18(4): 894.     CrossRef
    • SIFamide Translates Hunger Signals into Appetitive and Feeding Behavior in Drosophila
      Carlotta Martelli, Ulrike Pech, Simon Kobbenbring, Dennis Pauls, Britta Bahl, Mirjam Vanessa Sommer, Atefeh Pooryasin, Jonas Barth, Carmina Warth Perez Arias, Chrystalleni Vassiliou, Abud Jose Farca Luna, Haiko Poppinga, Florian Gerhard Richter, Christian
      Cell Reports.2017; 20(2): 464.     CrossRef
    • Effect of Mulberry Extract on the Lipid Profile and Liver Function in Mice Fed a High Fat Diet
      Kyung-Soon Choi, Yong-Hwan Kim, Kyung-Ok Shin
      The Korean Journal of Food And Nutrition.2016; 29(3): 411.     CrossRef
    • Helicobacter pylori Infection in Children: Nutritional Status and Associations with Serum Leptin, Ghrelin, and IGF‐1 Levels
      Gulin Erdemir, Tanju Basarir Ozkan, Taner Ozgur, Derya Altay, Sinan Cavun, Guher Goral
      Helicobacter.2016; 21(4): 317.     CrossRef
    • Dietary Capsaicin Protects Cardiometabolic Organs from Dysfunction
      Fang Sun, Shiqiang Xiong, Zhiming Zhu
      Nutrients.2016; 8(5): 174.     CrossRef
    • Effects of Short-Term Exenatide Treatment on Regional Fat Distribution, Glycated Hemoglobin Levels, and Aortic Pulse Wave Velocity of Obese Type 2 Diabetes Mellitus Patients
      Ju-Young Hong, Keun-Young Park, Byung-Joon Kim, Won-Min Hwang, Dong-Ho Kim, Dong-Mee Lim
      Endocrinology and Metabolism.2016; 31(1): 80.     CrossRef
    • The role of the neuropeptide Y (NPY) family in the pathophysiology of inflammatory bowel disease (IBD)
      Magdy El-Salhy, Trygve Hausken
      Neuropeptides.2016; 55: 137.     CrossRef
    • Proactive and Progressive Approaches in Managing Obesity
      Robert H. Eckel, Harold E. Bays, Samuel Klein, Deborah Bade Horn
      Postgraduate Medicine.2016; 128(sup1): 21.     CrossRef
    • The role of food intake regulating peptides in cardiovascular regulation
      B. Mikulášková, L. Maletínská, J. Zicha, J. Kuneš
      Molecular and Cellular Endocrinology.2016; 436: 78.     CrossRef
    • Altered gut and adipose tissue hormones in overweight and obese individuals: cause or consequence?
      M E J Lean, D Malkova
      International Journal of Obesity.2016; 40(4): 622.     CrossRef
    • Expression of NUCB2/nesfatin-1 in the taste buds of rats
      Xun Cao, Xiao Zhou, Yang Cao, Xiao-Min Liu, Li-Hong Zhou
      Endocrine Journal.2016; 63(1): 37.     CrossRef
    • Brain Regulation of Energy Metabolism
      Eun Roh, Min-Seon Kim
      Endocrinology and Metabolism.2016; 31(4): 519.     CrossRef
    • Stopped-Flow Studies of the Reduction of the Copper Centers Suggest a Bifurcated Electron Transfer Pathway in Peptidylglycine Monooxygenase
      Shefali Chauhan, Parisa Hosseinzadeh, Yi Lu, Ninian J. Blackburn
      Biochemistry.2016; 55(13): 2008.     CrossRef
    • Potential role of bioactive compounds of Phaseolus vulgaris L. on lipid-lowering mechanisms
      Aurea K. Ramírez-Jiménez, Rosalía Reynoso-Camacho, M. Elizabeth Tejero, Fabiola León-Galván, Guadalupe Loarca-Piña
      Food Research International.2015; 76: 92.     CrossRef
    • Recent developments in the pathophysiology of irritable bowel syndrome
      Magdy El-Salhy
      World Journal of Gastroenterology.2015; 21(25): 7621.     CrossRef
    • Lifestyle Changes Followed by Bariatric Surgery Lower Inflammatory Markers and the Cardiovascular Risk Factors C3 and C4
      Torunn Kristin Nestvold, Erik Waage Nielsen, Judith Krey Ludviksen, Hilde Fure, Anne Landsem, Knut Tore Lappegård
      Metabolic Syndrome and Related Disorders.2015; 13(1): 29.     CrossRef
    • Diet in irritable bowel syndrome
      Magdy El-Salhy, Doris Gundersen
      Nutrition Journal.2015;[Epub]     CrossRef
    • 3p22.1p21.31 microdeletion identifies CCK as Asperger syndrome candidate gene and shows the way for therapeutic strategies in chromosome imbalances
      Ivan Y. Iourov, Svetlana G. Vorsanova, Victoria Y. Voinova, Yuri B. Yurov
      Molecular Cytogenetics.2015;[Epub]     CrossRef
    • The effect of slow spaced eating on hunger and satiety in overweight and obese patients with type 2 diabetes mellitus
      Theodoros Angelopoulos, Alexander Kokkinos, Christos Liaskos, Nicholas Tentolouris, Kleopatra Alexiadou, Alexander Dimitri Miras, Iordanis Mourouzis, Despoina Perrea, Constantinos Pantos, Nicholas Katsilambros, Stephen R Bloom, Carel Wynard le Roux
      BMJ Open Diabetes Research & Care.2014; 2(1): e000013.     CrossRef
    • Bisphenol A is related to circulating levels of adiponectin, leptin and ghrelin, but not to fat mass or fat distribution in humans
      Monika Rönn, Lars Lind, Jan Örberg, Joel Kullberg, Stefan Söderberg, Anders Larsson, Lars Johansson, Håkan Ahlström, P. Monica Lind
      Chemosphere.2014; 112: 42.     CrossRef
    • The modulatory role of alpha-melanocyte stimulating hormone administered spinally in the regulation of blood glucose level in d-glucose-fed and restraint stress mouse models
      Yun-Beom Sim, Soo-Hyun Park, Sung-Su Kim, Su-Min Lim, Jun-Sub Jung, Hong-Won Suh
      Neuropeptides.2014; 48(4): 207.     CrossRef
    • The forgotten members of the glucagon family
      Dominique Bataille, Stéphane Dalle
      Diabetes Research and Clinical Practice.2014; 106(1): 1.     CrossRef
    • Incretin mimetics as pharmacologic tools to elucidate and as a new drug strategy to treat traumatic brain injury
      Nigel H. Greig, David Tweedie, Lital Rachmany, Yazhou Li, Vardit Rubovitch, Shaul Schreiber, Yung-Hsiao Chiang, Barry J. Hoffer, Jonathan Miller, Debomoy K. Lahiri, Kumar Sambamurti, Robert E. Becker, Chaim G. Pick
      Alzheimer's & Dementia.2014;[Epub]     CrossRef
    • Fatty acid analysis and regulatory effects of citron (Citrus junosSieb. ex TANAKA) seed oil on nitric oxide production, lipid accumulation, and leptin secretion
      Tae Woo Kim, Kyoung Kon Kim, Yun Hwan Kang, Dae Jung Kim, Myeon Choe
      Journal of Nutrition and Health.2014; 47(4): 221.     CrossRef
    • Analysis of Pine Nut Oil Composition and Its Effects on Obesity
      Kyoung Kon Kim, Yun Hwan Kang, Dae Jung Kim, Tae Woo Kim, Myeon Choe
      Korean Journal of Food Science and Technology.2014; 46(5): 630.     CrossRef
    • Anti-obesity effects of KR-66195, a synthetic DPP-IV inhibitor, in diet-induced obese mice and obese-diabetic ob/ob mice
      Eun Young Lee, Yeon Wook Kim, Hyunhee Oh, Cheol Soo Choi, Jin Hee Ahn, Byung-Wan Lee, Eun Seok Kang, Bong Soo Cha, Hyun Chul Lee
      Metabolism.2014; 63(6): 793.     CrossRef
    • Position and Length of Fatty Acids Strongly Affect Receptor Selectivity Pattern of Human Pancreatic Polypeptide Analogues
      Veronika Mäde, Kathrin Bellmann‐Sickert, Anette Kaiser, Jens Meiler, Annette G. Beck‐Sickinger
      ChemMedChem.2014; 9(11): 2463.     CrossRef
    • Regulation of food intake after surgery and the gut brain axis
      Nilanjana Tewari, Sherif Awad, Dileep N. Lobo
      Current Opinion in Clinical Nutrition and Metabolic Care.2013; 16(5): 569.     CrossRef
    • Effect of ambient temperature during acute aerobic exercise on short-term appetite, energy intake, and plasma acylated ghrelin in recreationally active males
      Lucy K. Wasse, James A. King, David J. Stensel, Caroline Sunderland
      Applied Physiology, Nutrition, and Metabolism.2013; 38(8): 905.     CrossRef
    • Peripheral Pathways in the Food-Intake Control towards the Adipose-Intestinal Missing Link
      Hugo Mendieta Zerón, Ma. Victoria Domínguez García, María del Socorro Camarillo Romero, Miriam V. Flores-Merino
      International Journal of Endocrinology.2013; 2013: 1.     CrossRef
    • Alteration of sweet taste in high-fat diet induced obese rats after 4 weeks treatment with exenatide
      Xiao-juan Zhang, Yu-qing Wang, Yang Long, Lei Wang, Yun Li, Fa-bao Gao, Hao-ming Tian
      Peptides.2013; 47: 115.     CrossRef
    • Decrease of Obesity by Allantoin via Imidazoline I1-Receptor Activation in High Fat Diet-Fed Mice
      Hsien-Hui Chung, Kung Shing Lee, Juei-Tang Cheng
      Evidence-Based Complementary and Alternative Medicine.2013; 2013: 1.     CrossRef
    • Hunger Hormone Profile Monitoring after Gastroplication in an Adolescent
      Valeria Calcaterra, Gloria Pelizzo, Ghassan Nakib, Daniela Larizza, Maria Luisa Fonte, Mara De Amici, Hellas Cena
      Hormone Research in Paediatrics.2013; 80(3): 213.     CrossRef

    • PubReader PubReader
    • Cite this Article
      Cite this Article
      export Copy Download
      Close
      Download Citation
      Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

      Format:
      • RIS — For EndNote, ProCite, RefWorks, and most other reference management software
      • BibTeX — For JabRef, BibDesk, and other BibTeX-specific software
      Include:
      • Citation for the content below
      Molecular Mechanisms of Appetite Regulation
      Diabetes Metab J. 2012;36(6):391-398.   Published online December 12, 2012
      Close
    • XML DownloadXML Download
    Figure
    Yu JH, Kim MS. Molecular Mechanisms of Appetite Regulation. Diabetes Metab J. 2012;36(6):391-398.
    DOI: https://doi.org/10.4093/dmj.2012.36.6.391.

    Diabetes Metab J : Diabetes & Metabolism Journal
    Close layer