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Melanocortin 4 receptor

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https://www.readbyqxmd.com/read/28333235/ovarian-hormones-and-obesity
#1
Brigitte Leeners, Nori Geary, Philippe N Tobler, Lori Asarian
BACKGROUND: Obesity is caused by an imbalance between energy intake, i.e. eating and energy expenditure (EE). Severe obesity is more prevalent in women than men worldwide, and obesity pathophysiology and the resultant obesity-related disease risks differ in women and men. The underlying mechanisms are largely unknown. Pre-clinical and clinical research indicate that ovarian hormones may play a major role. OBJECTIVE AND RATIONALE: We systematically reviewed the clinical and pre-clinical literature on the effects of ovarian hormones on the physiology of adipose tissue (AT) and the regulation of AT mass by energy intake and EE...
March 2, 2017: Human Reproduction Update
https://www.readbyqxmd.com/read/28327432/feedback-from-arctic-charr-feed-flavour-stimulation-and-re-feeding-after-feed-deprivation-stimulate-genes-encoding-both-orexigenic-and-anorexigenic-neuropeptides
#2
Anja Striberny, Even H Jørgensen
Despite vast research attention, the knowledge about central mechanisms of appetite regulation in teleost remains inconclusive. A common strategy in studies on appetite regulating mechanisms is to measure the response to feed restriction or - deprivation, but responses vary between fish species and between experiments, and are also likely dependent on the degree of energy perturbation. The anadromous Arctic charr is an interesting model for studying appetite regulation as its feeding cycle comprises months of winter anorexia, and hyperphagia during summer...
March 18, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28324105/thyroid-hormone-dependent-epigenetic-regulation-of-melanocortin-4-receptor-levels-in-female-offspring-of-obese-rats
#3
T Tabachnik, T Kisliouk, A Marco, N Meiri, A Weller
Maternal obesity is a risk factor for offspring obesity. Melanocortin 4 receptor (Mc4r) is one of the mediators of food intake and energy balance. This study examines epigenetic mechanisms underlying altered Mc4r levels in the hypothalamic paraventricular nucleus in offspring of high-fat diet (HFD)-induced obese dams, and aims to elucidate the role of thyroid hormones in epigenetic regulation and tagging of their nucleosome at the Mc4r promoter. Female Wistar rats were fed HFD or chow from weaning through gestation and lactation...
January 9, 2017: Endocrinology
https://www.readbyqxmd.com/read/28303974/antifibrotic-effect-of-pirfenidone-in-a-mouse-model-of-human-nonalcoholic-steatohepatitis
#4
Chikara Komiya, Miyako Tanaka, Kyoichiro Tsuchiya, Noriko Shimazu, Kentaro Mori, Shunsaku Furuke, Yasutaka Miyachi, Kumiko Shiba, Shinobu Yamaguchi, Kenji Ikeda, Kozue Ochi, Kazuhiko Nakabayashi, Ken-Ichiro Hata, Michiko Itoh, Takayoshi Suganami, Yoshihiro Ogawa
Non-alcoholic steatohepatitis (NASH) is characterized by steatosis with lobular inflammation and hepatocyte injury. Pirfenidone (PFD) is an orally bioavailable pyridone derivative that has been clinically used for the treatment of idiopathic pulmonary fibrosis. However, it remains unknown whether PFD improves liver fibrosis in a mouse model with human NASH-like phenotypes. In this study, we employed melanocortin 4 receptor-deficient (MC4R-KO) mice as a mouse model with human NASH-like phenotypes to elucidate the effect and action mechanisms of PFD on the development of NASH...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28284973/pharmacological-chaperones-for-the-misfolded-melanocortin-4-receptor-associated-with-human-obesity
#5
Hui Huang, Wei Wang, Ya-Xiong Tao
The melanocortin-4 receptor (MC4R) plays a vital role in regulating energy homeostasis. Mutations in the MC4R cause early-onset severe obesity. The majority of loss of function MC4R mutants are retained intracellularly, many of which are not terminally misfolded and can be stabilized and targeted to the plasma membrane by different chaperones. Some of the mutants might be functional once coaxed to the cell surface. Molecular chaperones and chemical chaperones correct the misfolding of some mutant MC4Rs. However, their therapeutic application is very limited due to their non-specific mechanism of action and, for chemical chaperone, high dosage needed to be effective...
March 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28274841/role-of-the-brain-melanocortins-in-blood-pressure-regulation
#6
Jussara M do Carmo, Alexandre A da Silva, Zhen Wang, Taolin Fang, Nicola Aberdein, Cecilia E Perez de Lara, John E Hall
Melanocortins play an important role in regulating blood pressure (BP) and sympathetic nervous system (SNS) activity as well as energy balance, glucose and other metabolic functions in humans and experimental animals. In experimental models of hypertension with high SNS activity, blockade of the melanocortin-4 receptor (MC4R) reduces BP despite causing marked hyperphagia and obesity. Activation of the central nervous system (CNS) pro-opiomelanocortin (POMC)-MC4R pathway appears to be an important link between obesity, SNS activation and hypertension...
March 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28273060/mc4r-dependent-suppression-of-appetite-by-bone-derived-lipocalin-2
#7
Ioanna Mosialou, Steven Shikhel, Jian-Min Liu, Antonio Maurizi, Na Luo, Zhenyan He, Yiru Huang, Haihong Zong, Richard A Friedman, Jonathan Barasch, Patricia Lanzano, Liyong Deng, Rudolph L Leibel, Mishaela Rubin, Thomas Nicholas, Wendy Chung, Lori M Zeltser, Kevin W Williams, Jeffrey E Pessin, Stavroula Kousteni
Bone has recently emerged as a pleiotropic endocrine organ that secretes at least two hormones, FGF23 and osteocalcin, which regulate kidney function and glucose homeostasis, respectively. These findings have raised the question of whether other bone-derived hormones exist and what their potential functions are. Here we identify, through molecular and genetic analyses in mice, lipocalin 2 (LCN2) as an osteoblast-enriched, secreted protein. Loss- and gain-of-function experiments in mice demonstrate that osteoblast-derived LCN2 maintains glucose homeostasis by inducing insulin secretion and improves glucose tolerance and insulin sensitivity...
March 16, 2017: Nature
https://www.readbyqxmd.com/read/28267582/melanocortin-4-receptor-ligands-modulate-energy-homeostasis-through-urocortin-1-neurons-of-the-centrally-projecting-edinger-westphal-nucleus
#8
Nóra Füredi, Ákos Nagy, Alexandra Mikó, Gergely Berta, Tamás Kozicz, Erika Pétervári, Márta Balaskó, Balázs Gaszner
The role of the urocortin 1 (Ucn1) expressing centrally projecting Edinger-Westphal (EWcp) nucleus in energy homeostasis and stress adaptation response has previously been investigated. Morphological and functional studies have proven that orexigenic and anorexigenic peptidergic afferents and receptors for endocrine messengers involved in the energy homeostasis are found in the EWcp. The central role of the hypothalamic melanocortin system in energy homeostasis is well known, however, no data have been published so far on possible crosstalk between melanocortins and EWcp-Ucn1...
March 3, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28246458/associations-between-single-nucleotide-polymorphisms-in-multiple-candidate-genes-and-body-weight-in-rabbits
#9
Karim El-Sabrout, Sarah A Aggag
AIM: In this study, we examined parts of six growth genes (growth hormone [GH], melanocortin 4 receptor [MC4R], growth hormone receptor [GHR], phosphorglycerate mutase [PGAM], myostatin [MSTN], and fibroblast growth factor [FGF]) as specific primers for two rabbit lines (V-line, Alexandria) using nucleotide sequence analysis, to investigate association between detecting single nucleotide polymorphism (SNP) of these genes and body weight (BW) at market. MATERIALS AND METHODS: Each line kits were grouped into high and low weight rabbits to identify DNA markers useful for association studies with high BW...
January 2017: Veterinary World
https://www.readbyqxmd.com/read/28243712/altered-sucrose-self-administration-following-injection-of-melanocortin-receptor-agonists-and-antagonists-into-the-ventral-tegmental-area
#10
Laranci Shanmugarajah, Anna I Dunigan, Kyle J Frantz, Aaron G Roseberry
RATIONALE AND OBJECTIVES: Alpha-melanocyte stimulating hormone (αMSH) and agouti-related protein (AgRP) are antagonistic neuropeptides that play an important role in the control of feeding and body weight through their central actions on the melanocortin-3 and melanocortin-4 receptors. Increasing evidence indicates that αMSH and AgRP can interact with the mesolimbic dopamine system to regulate feeding as well as other behaviors. For example, we have shown previously that injection of melanocortin receptor agonists and antagonists into the ventral tegmental area (VTA) alters both normal home-cage feeding and the intake of sucrose solutions, but it remains unknown whether αMSH and AgRP can also act in the VTA to affect reward-related feeding...
February 27, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28242830/suppressed-sympathetic-outflow-to-skeletal-muscle-muscle-thermogenesis-and-activity-energy-expenditure-with-calorie-restriction
#11
Tariq I Almundarij, Chaitanya K Gavini, Colleen M Novak
During weight loss, adaptive thermogenesis occurs where energy expenditure (EE) is suppressed beyond that predicted for the smaller body size. Here, we investigated the contributions of resting and nonresting EE to the reduced total EE seen after 3 weeks of 50% calorie restriction (CR) in rats, focusing on activity-associated EE, muscle thermogenesis, and sympathetic outflow. Prolonged food restriction resulted in a 42% reduction in daily EE, through a 40% decrease in resting EE, and a 48% decline in nonresting EE These decreases in EE were significant even when the reductions in body weight and lean mass were taken into account...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28229938/participation-of-ghrelin-signalling-in-the-reciprocal-regulation-of-hypothalamic-npy-pomc-mediated-appetite-control-in-amphetamine-treated-rats
#12
Ching-Han Yu, Shu-Chen Chu, Pei-Ni Chen, Yih-Shou Hsieh, Dong-Yih Kuo
Hypothalamic neuropeptide Y (NPY) and proopiomelanocortin (POMC) have been documented to participate in amphetamine (AMPH)-induced appetite suppression. This study investigated whether ghrelin signalling is associated with changes in NPY/POMC-mediated appetite control. Rats were given AMPH daily for four days, and changes in food intake, body weight, plasma ghrelin, hypothalamic NPY, melanocortin 3 receptor (MC3R), ghrelin O-acyltransferase (GOAT), acyl ghrelin (AG) and ghrelin receptor (GHSR1a) were examined and compared...
February 14, 2017: Appetite
https://www.readbyqxmd.com/read/28218067/melanocortin-4-receptor-gene-mutations-in-a-group-of-turkish-obese-children-and-adolescents
#13
Selma Tunç, Korcan Demir, Fatma Ajlan Tükün, Cihan Topal, Filiz Hazan, Burcu Sağlam, Özlem Nalbantoğlu, Melek Yıldız, Behzat Özkan
OBJECTIVE: Melanocortin-4 receptor (MC4R) mutations are the most common known cause of monogenic obesity but there is limited data regarding MC4R mutations in Turkish subjects. To determine the prevalence of MC4R mutations in a group of Turkish morbid obese children and adolescents. METHODS: MC4R was sequenced in 47 consecutive morbidly obese children and adolescents (28 girls and 19 boys, aged 1-18 years) who presented during a 1-year period. Inclusion criterion was a BMI ≥120% of the 95th percentile or ≥35 kg/m2...
February 20, 2017: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/28214221/relationship-between-the-melanocortin-1-receptor-mc1r-variant-r306ter-and-physiological-responses-to-mechanical-or-thermal-stimuli-in-labrador-retriever-dogs
#14
Tania E Perez, Katrina L Mealey, Neal S Burke, Tamara L Grubb, Michael H Court, Stephen A Greene
OBJECTIVE: Variants in the MC1R gene have been associated with red hair color and sensitivity to pain in humans. The study objective was to determine if a relationship exists between MC1R genotype and physiological thermal or mechanical nociceptive thresholds in Labrador Retriever dogs. STUDY DESIGN: Prospective experimental study. ANIMALS: Thirty-four Labrador Retriever dogs were included in the study following public requests for volunteers...
January 11, 2017: Veterinary Anaesthesia and Analgesia
https://www.readbyqxmd.com/read/28213370/promiscuity-among-the-mraps
#15
Adrian J L Clark, Li F Chan
The melanocortin 2 receptor accessory protein (MRAP) was originally discovered to be an essential co-receptor for the ACTH receptor/melanocortin 2 receptor, and it physically interacts with this receptor and is required for receptor trafficking and ligand binding. A related molecule, MRAP2, is mainly expressed in the CNS and appears to have a role with the melanocortin 4 receptor. Consistent with this is the observation that a massively obese phenotype develops when the Mrap2 gene is deleted in mice. However, the characteristics of this phenotype differ from those of Mc4r deleted mice, and suggest that an additional role, possibly resulting from an interaction with other receptors is possible...
February 17, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28207798/altered-hepatic-lipid-metabolism-in-mice-lacking-both-the-melanocortin-type-4-receptor-and-low-density-lipoprotein-receptor
#16
Vera Lede, Andrej Meusel, Antje Garten, Yulia Popkova, Melanie Penke, Christin Franke, Albert Ricken, Angela Schulz, Wieland Kiess, Daniel Huster, Torsten Schöneberg, Jürgen Schiller
Obesity is often associated with dyslipidemia and hepatosteatosis. A number of animal models of non-alcoholic fatty liver disease (NAFLD) are established but they significantly differ in the molecular and biochemical changes depending on the genetic modification and diet used. Mice deficient for melanocortin type 4 receptor (Mc4rmut) develop hyperphagia, obesity, and subsequently NAFLD already under regular chow and resemble more closely the energy supply-driven obesity found in humans. This animal model was used to assess the molecular and biochemical consequences of hyperphagia-induced obesity on hepatic lipid metabolism...
2017: PloS One
https://www.readbyqxmd.com/read/28197776/effects-of-melanocortin-4-receptor-agonists-and-antagonists-on-expression-of-genes-related-to-reproduction-in-spotted-scat-scatophagus-argus
#17
Dong-Neng Jiang, Jian-Tao Li, Ya-Xiong Tao, Hua-Pu Chen, Si-Ping Deng, Chun-Hua Zhu, Guang-Li Li
Melanocortin-4 receptor (Mc4r) function related to reproduction in fish has not been extensively investigated. Here, we report on gene expression changes by real-time PCR following treatment with Mc4r agonists and antagonists in the spotted scat (Scatophagus argus). Using in vitro incubated hypothalamus, the Mc4r nonselective agonist NDP-MSH ([Nle(4), D-Phe(7)]-α-melanocyte stimulating hormone; 10(-6) M) and selective agonist THIQ (N-[(3R)-1, 2, 3, 4-Tetrahydroisoquinolinium-3-ylcarbonyl]- (1R)-1-(4-chlorobenzyl)-2-[4-cyclohexyl-4-(1H-1,2,4-triazol-1-ylmethyl) piperidin-1-yl]-2-oxoethylamine; 10(-7) M) significantly increased the expression of gnrh (Gonadotropin releasing hormone), while the Mc4r nonselective antagonist SHU9119 (Ac-Nle-[Asp-His-DPhe/DNal(2')-Arg-Trp-Lys]-NH2; 10(-6) M) and selective antagonist Ipsen 5i (compound 5i synthesized in Ipsen Research Laboratories; 10(-6) M) significantly inhibited gnrh expression after 3 h of incubation...
February 14, 2017: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
https://www.readbyqxmd.com/read/28152402/molecular-cloning-tissue-distribution-and-pharmacological-characterization-of-melanocortin-4-receptor-in-grass-carp-ctenopharyngodon-idella
#18
L Li, Z Yang, Y-P Zhang, S He, X-F Liang, Y-X Tao
Melanocortin-4 receptor (MC4R) plays a pivotal role in the mediation of leptin action on food intake and energy expenditure in mammals. The MC4R has also been identified in several teleosts, and its importance in the regulation of fish energy homeostasis is emerging. We herein reported on the molecular cloning, tissue distribution, and pharmacological characterization of MC4R in grass carp (Ctenopharyngodon idella), an economically and ecologically important fish. We showed that grass carp MC4R (ciMC4R) consisted of a 981 bp open reading frame encoding a protein of 326 amino acids, highly homologous (>95%) to several teleost MC4Rs...
November 21, 2016: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/28150230/melanocortin-receptor-4-gene-polymorphisms-in-glioblastoma-patients-treated-with-concomitant-radio-chemotherapy
#19
Francesco Pasqualetti, Paola Orlandi, Vittorio Simeon, Martina Cantarella, Daniela Giuliani, Teresa Di Desidero, Alessandra Gonnelli, Durim Delishaj, Giuseppe Lombardi, Andrea Sechi, Marc Sanson, Vittorina Zagonel, Fabiola Paiar, Romano Danesi, Salvatore Guarini, Guido Bocci
Melanocortins are peptides with well-recognized antiinflammatory and neuroprotective activity. No data are currently available on melanocortin receptor-4 (MC4R) gene polymorphisms and tumors, including glioblastomas (GBMs), or their relationship with radiotherapy or chemotherapy. The aim of this study was to evaluate the possible predictive/prognostic role of the MC4R SNPs on GBM patients. Fifty-five patients with a proven diagnosis of GBM, treated with radiotherapy and temozolomide, were consecutively enrolled...
February 1, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28148682/dietary-protein-modifies-the-effect-of-the-mc4r-genotype-on-2-year-changes-in-appetite-and-food-craving-the-pounds-lost-trial
#20
Tao Huang, Yan Zheng, Adela Hruby, Donald A Williamson, George A Bray, Yiru Shen, Frank M Sacks, Lu Qi
BACKGROUND: The melanocortin-4 receptor (MC4R) plays a pivotal role in the regulation of appetite and eating behavior. Variants in the MC4R gene have been related to appetite and obesity. OBJECTIVE: We aimed to examine whether weight-loss diets modified the effect of the "obesity-predisposing" MC4R genotype on appetite-related measures in a randomized controlled trial. METHODS: A total of 811 overweight and obese subjects [25 ≤ body mass index (BMI; kg/m(2)) ≤ 40] aged 30-70 y were included in the 2-y POUNDS Lost (Preventing Overweight Using Novel Dietary Strategies) trial...
February 1, 2017: Journal of Nutrition
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