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 Proopiomelanocortin, a polypeptide precursor with multiple functions: from physiology to pathological conditions

2003 ◽  
Vol 149 (2) ◽  
pp. 79-90 ◽  
Author(s):  
ML Raffin-Sanson ◽  
Y de Keyzer ◽  
X Bertagna
Keyword(s):  
Anterior Pituitary ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Single Gene ◽  
Local Production ◽  
Biological Functions ◽  
Multiple Functions ◽  
Pathological Conditions ◽  
Recent Developments ◽  
The Brain

Proopiomelanocortin (POMC) is the polypeptide precursor of ACTH. First discovered in anterior pituitary corticotroph cells, it has more recently been revealed to have many other physiological aspects. The fine molecular mechanisms of ACTH biosynthesis show that ACTH is but one piece of a puzzle which contains many other peptides. Present in various tIssues, among which are pituitary, hypothalamus, central nervous system and skin, POMC undergoes extensive post-translational processing. This processing is tIssue-specific and generates, depending on the case, various sets of peptides involved in completely diverse biological functions. POMC expressed in corticotroph cells of the pituitary is necessary for adrenal function. Recent developments have shown that POMC-expressing neurons in the brain play a major role in the control of pain and energy homeostasis. Local production of POMC-derived peptides in skin may influence melanogenesis. A still unknown function in the placenta is likely.POMC has become a paradigmatic polypeptide precursor model illustrating the variable roles of a single gene and its various products in different localities.

scholarly journals Nucleus, Mitochondrion, or Reticulum? STAT3 à La Carte

2018 ◽  
Vol 19 (9) ◽  
pp. 2820 ◽  
Author(s):  
Lidia Avalle ◽  
Valeria Poli
Keyword(s):  
Energy Production ◽  
Energy Homeostasis ◽  
Multiple Roles ◽  
Pharmaceutical Companies ◽  
Signal Transducer ◽  
Post Translational Modifications ◽  
Pathological Conditions ◽  
Different Types ◽  
Tumor Transformation ◽  
Context Specific

The transcription factor signal transducer and activator of transcription (STAT)3 mediates the functions of cytokines, growth factors, and oncogenes under both physiological and pathological conditions. Uncontrolled/constitutive STAT3 activity is often detected in tumors of different types, where its role is mostly that of an oncogene, contributing in multiple ways to tumor transformation, growth, and progression. For this reason, many laboratories and pharmaceutical companies are making efforts to develop specific inhibitors. However, STAT3 has also been shown to act as a tumor suppressor in a number of cases, suggesting that its activity is strongly context-specific. Here, we discuss the bases that can explain the multiple roles of this factor in both physiological and pathological contexts. In particular, we focus on the following four features: (i) the distinct properties of the STAT3α and β isoforms; (ii) the multiple post-translational modifications (phosphorylation on tyrosine or serine, acetylation and methylation on different residues, and oxidation and glutathionylation) that can affect its activities downstream of multiple different signals; (iii) the non-canonical functions in the mitochondria, contributing to the maintenance of energy homeostasis under stress conditions; and (iv) the recently discovered functions in the endoplasmic reticulum, where STAT3 contributes to the regulation of calcium homeostasis, energy production, and apoptosis.

scholarly journals Hydrolysis of rat melanin-concentrating hormone by endopeptidase 24.11 (neutral endopeptidase)

1992 ◽  
Vol 286 (1) ◽  
pp. 217-221 ◽  
Author(s):  
F Checler ◽  
P Dauch ◽  
H Barelli ◽  
J L Nahon ◽  
J P Vincent
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Cyclic Peptide ◽  
Degradation Products ◽  
Neutral Endopeptidase ◽  
Converting Enzyme ◽  
Carboxypeptidase A ◽  
Disulphide Bridge ◽  
Melanocyte Stimulating Hormone ◽  
Melanin Concentrating Hormone ◽  
Hydrolysis Of

Melanin-concentrating hormone (MCH) is a cyclic peptide which behaves as an antagonist of the pituitary melanotropic hormone alpha-melanocyte-stimulating hormone in fishes. Cloning of the rat MCH cDNA precursor recently revealed the presence of an additional putative peptide named NEI. The present work examined the susceptibility of these novel peptides to hydrolysis by various purified exo- and endo-peptidases including endopeptidases 24.11 (NEP), 24.15, 24.16, angiotensin-converting enzyme, leucine aminopeptidase and carboxypeptidase A. NEP attacked MCH at three sites of the molecule with an apparent affinity of about 12 microM and a kcat. of 4 min-1. The first site of cleavage was at Cys-7-Met-8, i.e. within the peptide loop formed by the internal disulphide bridge. NEP could therefore be considered as an MCH-inactivating peptidase since the degradation products generated are probably devoid of biological activity. In contrast, NEI neither inhibited the degradation of the NEP chromogenic substrate glutaryl-Phe-Ala-Phe-p-aminobenzoate nor was susceptible to proteolysis by NEP. Unlike NEP, angiotensin-converting enzyme, endopeptidase 24.15 and endopeptidase 24.16 appeared totally unable to cleave MCH, whereas the peptide was readily degraded by aminopeptidase M and carboxypeptidase A.

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 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 Early control of viral load by favipiravir promotes survival to Ebola virus challenge and prevents cytokine storm in non-human primates

2021 ◽  
Vol 15 (3) ◽  
pp. e0009300
Author(s):  
Stéphanie Reynard ◽  
Emilie Gloaguen ◽  
Nicolas Baillet ◽  
Vincent Madelain ◽  
Jérémie Guedj ◽  
...  
Keyword(s):  
Viral Load ◽  
Ebola Virus ◽  
Virus Disease ◽  
Strongly Correlated ◽  
Cytokine Storm ◽  
Biological Functions ◽  
Crucial Importance ◽  
Immunological Parameters ◽  
Virus Challenge ◽  
Response To Stress

Ebola virus has been responsible for two major epidemics over the last several years and there has been a strong effort to find potential treatments that can improve the disease outcome. Antiviral favipiravir was thus tested on non-human primates infected with Ebola virus. Half of the treated animals survived the Ebola virus challenge, whereas the infection was fully lethal for the untreated ones. Moreover, the treated animals that did not survive died later than the controls. We evaluated the hematological, virological, biochemical, and immunological parameters of the animals and performed proteomic analysis at various timepoints of the disease. The viral load strongly correlated with dysregulation of the biological functions involved in pathogenesis, notably the inflammatory response, hemostatic functions, and response to stress. Thus, the management of viral replication in Ebola virus disease is of crucial importance in preventing the immunopathogenic disorders and septic-like shock syndrome generally observed in Ebola virus-infected patients.

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

scholarly journals Altering the sex determination pathway in Drosophila fat body modifies sex-specific stress responses

2014 ◽  
Vol 307 (1) ◽  
pp. R82-R92 ◽  
Author(s):  
Kathryn J. Argue ◽  
Wendi S. Neckameyer
Keyword(s):  
Sex Determination ◽  
Stress Responses ◽  
Energy Homeostasis ◽  
Fat Body ◽  
Dependent Manner ◽  
Ideal System ◽  
Opposite Sex ◽  
Response To Stress ◽  
Targeted Expression ◽  
And Oxidative Stress

The stress response in Drosophila melanogaster reveals sex differences in behavior, similar to what has been observed in mammals. However, unlike mammals, the sex determination pathway in Drosophila is well established, making this an ideal system to identify factors involved in the modulation of sex-specific responses to stress. In this study, we show that the Drosophila fat body, which has been shown to be important for energy homeostasis and sex determination, is a dynamic tissue that is altered in response to stress in a sex and time-dependent manner. We manipulated the sex determination pathway in the fat body via targeted expression of transformer and transformer-2 and analyzed these animals for changes in their response to stress. In the majority of cases, manipulation of transformer or transformer-2 was able to change the physiological output in response to starvation and oxidative stress to that of the opposite sex. Our data also uncover the possibility of additional downstream targets for transformer and transformer-2 that are separate from the sex determination pathway and can influence behavioral and physiological responses.

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