Multifaceted actions of melanin-concentrating hormone on mammalian energy homeostasis

2021 ◽  
Author(s):  
Omar Al-Massadi ◽  
Carlos Dieguez ◽  
Marc Schneeberger ◽  
Miguel López ◽  
Markus Schwaninger ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Melanin Concentrating Hormone

scholarly journals Melanin-concentrating hormone in peripheral circulation in the human

2017 ◽  
Vol 232 (3) ◽  
pp. 513-523 ◽  
Author(s):  
J Naufahu ◽  
F Alzaid ◽  
M Fiuza Brito ◽  
B Doslikova ◽  
T Valencia ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Reference Range ◽  
Resting Metabolic Rate ◽  
Peripheral Circulation ◽  
Reference Ranges ◽  
Older Individuals ◽  
Rp Hplc ◽  
Melanin Concentrating Hormone ◽  
Males And Females

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide with a well-characterised role in energy homeostasis and emergent roles in diverse physiologic functions such as arousal, mood and reproduction. Work to date has predominantly focused on its hypothalamic functions using animal models; however, little attention has been paid to its role in circulation in humans. The aims of this study were to (a) develop a radioimmunoassay for the detection of MCH in human plasma; (b) establish reference ranges for circulating MCH and (c) characterise the pattern of expression of circulating MCH in humans. A sensitive and specific RIA was developed and cross-validated by RP-HPLC and MS. The effective range was 19.5–1248 pg MCH/mL. Blood samples from 231 subjects were taken to establish a reference range of 19.5–55.4 pg/mL for fasting MCH concentrations. There were no significant differences between male and female fasting MCH concentrations; however, there were correlations between MCH concentrations and BMI in males and females with excess fat (P < 0.001 and P = 0.020) and between MCH concentrations and fat mass in females with excess fat (P = 0.038). Plasma MCH concentrations rose significantly after feeding in a group of older individuals (n = 50, males P = 0.006, females P = 0.023). There were no robust significant correlations between fasting or post-prandial MCH and resting metabolic rate, plasma glucose, insulin or leptin concentrations although there were correlations between circulating MCH and leptin concentrations in older individuals (P = 0.029). These results indicate that the role of circulating MCH may not be reflective of its regulatory hypothalamic role.

scholarly journals Expanding the Scales: The Multiple Roles of MCH in Regulating Energy Balance and Other Biological Functions

2006 ◽  
Vol 27 (6) ◽  
pp. 606-620 ◽  
Author(s):  
Pavlos Pissios ◽  
Richard L. Bradley ◽  
Eleftheria Maratos-Flier
Keyword(s):  
Skin Color ◽  
Energy Homeostasis ◽  
Cyclic Peptide ◽  
Multiple Roles ◽  
Peptide Structure ◽  
Fish Scales ◽  
Biological Functions ◽  
Melanin Concentrating Hormone ◽  
Response To Stress ◽  
Neuroectodermal Origin

Melanin-concentrating hormone (MCH) is a cyclic peptide originally identified as a 17-amino-acid circulating hormone in teleost fish, where it is secreted by the pituitary in response to stress and environmental stimuli. In fish, MCH lightens skin color by stimulating aggregation of melanosomes, pigment-containing granules in melanophores, cells of neuroectodermal origin found in fish scales. Although the peptide structure between fish and mammals is highly conserved, in mammals, MCH has no demonstrable effects on pigmentation; instead, based on a series of pharmacological and genetic experiments, MCH has emerged as a critical hypothalamic regulator of energy homeostasis, having effects on both feeding behavior and energy expenditure.

scholarly journals Determination of the Interaction and Pharmacological Modulation of MCHR1 Signaling by C Terminus of MRAP2 Protein

2021 ◽  
Author(s):  
Meng Wang ◽  
Yue Zhai ◽  
Xiaowei Lei ◽  
Jing Xu ◽  
Bopei Jiang ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Transmembrane Protein ◽  
Melanocortin Receptor ◽  
Pharmacological Modulation ◽  
C Terminus ◽  
Melanin Concentrating Hormone ◽  
The Central Nervous System

Abstract Background: Melanin concentrating hormone (MCH), an orexigenic neuropeptide, is primarily secreted by the hypothalamus and acts at its receptor, the melanin-concentrating hormone receptor 1 (MCHR1), to regulate energy homeostasis and body weight. The Melanocortin Receptor Accessory Protein 2 (MRAP2), a small single transmembrane protein broadly expressed in multiple tissues, has been defined as a vital endocrine pivot of five melanocortin receptors (MC1R-MC5R) and several other GPCRs in the regulation of central neuronal appetite and peripheral energy homeostasis. However, the regulatory and relationship between MCHR1 and MRAP2 is unknown.Results: In this study, we show that MRAP2 interacts with MCHR1 and suppresses MCHR1 signaling in vitro. We also identified the C-terminal domains of MRAP2 protein required for pharmacological modulation of intracellular Ca2+ cascades and membrane transport.Conclusions: These findings elucidated the broad regulatory profile of MRAP2 protein in the central nervous system and may provide implications for the modulation of central MCHR1 function in vivo.

scholarly journals In Silico Studies on Structural Function of Melanin Concentrating Hormone Receptor 1 Through Docking Approach, Towards Designing Drug for Treating Obesity

2020 ◽  
Vol 3 (2) ◽  
Author(s):  
Mutangana Dieudonne ◽  
Musafili Narcisse ◽  
Nyurahayo Jean Gaetan ◽  
Munyampundu Jean Pierre
Keyword(s):  
Hormone Receptor ◽  
In Silico ◽  
Energy Homeostasis ◽  
3D Structure ◽  
Zona Incerta ◽  
Structural Function ◽  
Potential Candidate ◽  
In Silico Studies ◽  
Melanin Concentrating Hormone ◽  
Predicted Model

Melanin concentrating hormone receptor 1 is a G-protein coupled protein receptor expressed in the lateral hypothalamus and zona incerta, part of the nervous system that regulates feeding behavior and energy homeostasis. It is involved in the stimulation of appetite, this was seen when synthetic MCHR1 or MCH was administered to mice and it resulted in induced obesity due to the enhanced feeding. Many researchers have successfully find out the functions of several proteins, using computational approach. It is in this context that in this study the structural function of melanin concentrating hormone receptor 1 through docking studies has been done to make sure that those who are working to address the problem of obesity while trying to discover the effective drugs gain much insight about this receptor. The in silico methods have been used to predict the model of melanin concentrating hormone receptor 1. The template used for model prediction was human delta opioid receptor with the accession number 4N6H. The predicted model has been evaluated and found to be of good quality. Docking was done to investigate the interaction between the ligand; a bifunctional peptide ‘1-oleoyl-r-glycerol’ and the predicted model of melanin concentrating hormone receptor 1 which showed that fourteen residues interacted between the predicted model and ligand. Among interacting residues, it was realized that some of them are involved in sugar metabolism. Thus this study suggests a potential candidate for drug design against cancer and diabetes. Keywords: obesity, MCHR-1, docking, structural function, 3D structure, phylogenetic analysis, interacting residues

Melanin-concentrating hormone stimulates human growth hormone secretion: a novel effect of MCH on the hypothalamic-pituitary axis

2006 ◽  
Vol 290 (5) ◽  
pp. E982-E988 ◽  
Author(s):  
Gabriella Segal-Lieberman ◽  
Hadara Rubinfeld ◽  
Moran Glick ◽  
Noga Kronfeld-Schor ◽  
Ilan Shimon
Keyword(s):  
Growth Hormone ◽  
Energy Homeostasis ◽  
Hormone Secretion ◽  
Growth Hormone Secretion ◽  
Pituitary Hormones ◽  
Thyroid Stimulating Hormone ◽  
Pituitary Cells ◽  
Human Pituitary ◽  
Gh Secretion ◽  
Melanin Concentrating Hormone

Melanin-concentrating hormone (MCH), a 19-amino acid orexigenic (appetite-stimulating) hypothalamic peptide, is an important regulator of energy homeostasis. It is cleaved from its precursor prepro-MCH (ppMCH) along with several other neuropeptides whose roles are not fully defined. Because pituitary hormones such as growth hormone (GH), ACTH, and thyroid-stimulating hormone affect body weight and composition, appetite, insulin sensitivity, and lipoprotein metabolism, we investigated whether MCH exerts direct effects on the human pituitary to regulate energy balance using dispersed human fetal pituitaries (21–22 wk gestation) and cultured GH-secreting adenomas. We found that MCH receptor-1 (MCH-R1), but not MCH receptor-2, is expressed in both normal (fetal and adult) human pituitary tissues and in GH cell adenomas. MCH (10 nM) stimulated GH release from human fetal pituitary cultures by up to 62% during a 4-h incubation ( P < 0.05). Interestingly, neuropeptide EI (10 nM), which is also cleaved from ppMCH, increased human GH secretion by up to 124% in fetal pituitaries. A milder, albeit significant, induction of GH secretion by MCH (20%) was seen in cultured GH-secreting pituitary adenomas. A comparable stimulation of GH secretion was seen when cultured mouse pituitary cells were treated with MCH. Treatment of cultured GH adenoma cells with MCH (100 nM) induced extracellular signal-regulated kinases 1 and 2 phosphorylation, suggesting activation of MCH-R1. In aggregate, these data suggest that MCH may regulate pituitary GH secretion and imply a potential cross-talk mechanism between appetite-regulating neuropeptides and pituitary hormones.

MCH Neuron Activity Is Sufficient for Reward and Reinforces Feeding

2019 ◽  
Vol 110 (3-4) ◽  
pp. 258-270 ◽  
Author(s):  
Pelin Dilsiz ◽  
Iltan Aklan ◽  
Nilufer Sayar Atasoy ◽  
Yavuz Yavuz ◽  
Gizem Filiz ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Glucose Tolerance ◽  
Energy Homeostasis ◽  
Neuron Activity ◽  
Physiological Effects ◽  
Short Term ◽  
Direct Role ◽  
Reward Function ◽  
Melanin Concentrating Hormone

Background: Melanin-concentrating hormone (MCH)-expressing neurons have been implicated in regulation of energy homeostasis and reward, yet the role of their electrical activity in short-term appetite and reward modulation has not been fully understood. Objectives: We investigated short-term behavioral and physiological effects of MCH neuron activity manipulations. Methods: We used optogenetic and chemogenetic approaches in Pmch-cre transgenic mice to acutely stimulate/inhibit MCH neuronal activity while probing feeding, locomotor activity, anxiety-like behaviors, glucose homeostasis, and reward. Results: MCH neuron activity is neither required nor sufficient for short-term appetite unless stimulation is temporally paired with consumption. MCH neuronal activation does not affect short-term locomotor activity, but inhibition improves glucose tolerance and is mildly anxiolytic. Finally, using two different operant tasks, we showed that activation of MCH neurons alone is sufficient to induce reward. Conclusions: Our results confirm diverse behavioral/physiological functions of MCH neurons and suggest a direct role in reward function.

scholarly journals Leptin receptor neurons in the mouse hypothalamus are colocalized with the neuropeptide galanin and mediate anorexigenic leptin action

2013 ◽  
Vol 304 (9) ◽  
pp. E999-E1011 ◽  
Author(s):  
Amanda Laque ◽  
Yan Zhang ◽  
Sarah Gettys ◽  
Tu-Anh Nguyen ◽  
Kelly Bui ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Fluorescent Protein ◽  
Inhibitory Function ◽  
Reporter Mice ◽  
Brainstem Nucleus ◽  
Melanin Concentrating Hormone ◽  
Regulate Food Intake ◽  
Receptor Neurons ◽  
Green Fluorescent

Leptin acts centrally via leptin receptor (LepRb)-expressing neurons to regulate food intake, energy expenditure, and other physiological functions. LepRb neurons are found throughout the brain, and several distinct populations contribute to energy homeostasis control. However, the function of most LepRb populations remains unknown, and their contribution to regulate energy homeostasis has not been studied. Galanin has been hypothesized to interact with the leptin signaling system, but literature investigating colocalization of LepRb and galanin has been inconsistent, which is likely due to technical difficulties to visualize both. We used reporter mice with green fluorescent protein expression from the galanin locus to recapitulate the colocalization of galanin and leptin-induced p-STAT3 as a marker for LepRb expression. Here, we report the existence of two populations of galanin-expressing LepRb neurons (Gal-LepRb neurons): in the hypothalamus overspanning the perifornical area and adjacent dorsomedial and lateral hypothalamus [collectively named extended perifornical area (exPFA)] and in the brainstem (nucleus of the solitary tract). Surprisingly, despite the known orexigenic galanin action, leptin induces galanin mRNA expression and stimulates LepRb neurons in the exPFA, thus conflicting with the expected anorexigenic leptin action. However, we confirmed that intra-exPFA leptin injections were indeed sufficient to mediate anorexic responses. Interestingly, LepRb and galanin-expressing neurons are distinct from orexin or melanin-concentrating hormone (MCH)-expressing neurons, but exPFA galanin neurons colocalized with the anorexigenic neuropeptides neurotensin and cocaine- and amphetamine-regulated transcript (CART). Based on galanin's known inhibitory function, we speculate that in exPFA Gal-LepRb neurons galanin acts inhibitory rather than orexigenic.

Chronic intracerebroventricular infusion of MCH causes obesity in mice

2003 ◽  
Vol 284 (3) ◽  
pp. E583-E588 ◽  
Author(s):  
Akira Gomori ◽  
Akane Ishihara ◽  
Masahiko Ito ◽  
Satoshi Mashiko ◽  
Hiroko Matsushita ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Control ◽  
Energy Homeostasis ◽  
The Body ◽  
Intracerebroventricular Infusion ◽  
Melanin Concentrating Hormone ◽  
Important Regulator ◽  
Obesity In Mice ◽  
Body Weight Control

Melanin-concentrating hormone (MCH) is a cyclic amino acid neuropeptide localized in the lateral hypothalamus. Although MCH is thought to be an important regulator of feeding behavior, the involvement of this peptide in body weight control has been unclear. To examine the role of MCH in the development of obesity, we assessed the effect of chronic intracerebroventricular infusion of MCH in C57BL/6J mice that were fed with regular or moderately high-fat (MHF) diets. Intracerebroventricular infusion of MCH (10 μg/day for 14 days) caused a slight but significant increase in body weight in mice maintained on the regular diet. In the MHF diet-fed mice, MCH more clearly increased the body weight accompanied by a sustained hyperphagia and significant increase in fat and liver weights. Plasma glucose, insulin, and leptin levels were also increased in the MCH-treated mice fed the MHF diet. These results suggest that chronic stimulation of the brain MCH system causes obesity in mice and imply that MCH may have a major role in energy homeostasis.

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