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Melanocortin 4 receptor

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https://www.readbyqxmd.com/read/28520814/rs12970134-near-mc4r-is-associated-with-appetite-and-beverage-intake-in-overweight-and-obese-children-a-family-based-association-study-in-chinese-population
#1
Shuo Wang, Jieyun Song, Yide Yang, Nitesh V Chawla, Jun Ma, Haijun Wang
BACKGROUND: Recent studies indicated that eating behaviors are under genetic influence, and the melanocortin 4 receptor (MC4R) gene polymorphisms can affect the total energy intake and the consumption of fat, protein and carbohydrates. Our study aims at investigating the association of the MC4R polymorphism with appetite and food intake among Chinese children. METHODS: A family-based association study was conducted among 151 Chinese trios whose offsprings were overweight/obese children aged 9-15 years...
2017: PloS One
https://www.readbyqxmd.com/read/28512117/the-interaction-of-mc3r-and-mc4r-with-mrap2-acth-%C3%AE-msh-and-agrp-in-chickens
#2
Jiannan Zhang, Xin Li, Yawei Zhou, Lin Cui, Jing Li, Chenlei Wu, Yiping Wan, Juan Li, Yajun Wang
The interaction of melanocortin-4 (MC4R) and melanocortin-3 (MC3R) receptors with proopiomelanocortin (POMC)-derived peptides (e.g. α-MSH), agouti-related protein (AgRP), and melanocortin-2 receptor accessory protein 2 (MRAP2) is suggested to play critical roles in energy balance of vertebrates. However, evidence on their interaction in birds remains scarce. Our study aims to reveal their interaction in chickens and the results showed that: 1) chicken (c-)MC3R and cMC4R expressed in CHO cells can be activated by α-MSH and ACTH1-39 equipotently, monitored by a pGL3-CRE-luciferase reporter system; 2) cMC3R and cMC4R, when co-expressed with cMRAP2 (or cMRAP, a cMRAP2 homolog), show increased sensitivity to ACTH treatment and thus likely act as ACTH-preferring receptors, and the interaction between cMC3R/cMC4R and cMRAP2 was demonstrated by co-immunoprecipitation assay; 3) both cMC3R and cMC4R display constitutive activity when expressed in CHO cells, as monitored by Dual-luciferase reporter assay, and cMRAP2 (and cMRAP) can modulate their constitutive activity; 4) AgRP inhibits the constitutive activity of cMC3R/cMC4R, and it also antagonizes ACTH/α-MSH action on cMC4R/cMC3R, indicating that AgRP functions as the inverse agonist and antagonist for both receptors...
May 16, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28500249/maternal-high-fat-diet-induces-metabolic-stress-response-disorders-in-offspring-hypothalamus
#3
Long The Nguyen, Sonia Saad, Yi Tan, Carol Pollock, Hui Chen
Maternal obesity has been shown to increase the risk of obesity and related disorders in the offspring, which has been partially attributed to changes of appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic reticulum (ER) stress and autophagy have been implicated in hypothalamic neuropeptide dysregulation, thus may also play important roles in such transgenerational effect.  In this study, we show that offspring born to HFD-fed dams showed significantly increased body weight and glucose intolerance, adiposity and plasma triglyceride level at weaning...
May 12, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28499988/melanocortin-neurons-multiple-routes-to-regulation-of-metabolism
#4
REVIEW
Wen-Jie Shen, Ting Yao, Xingxing Kong, Kevin W Williams, Tiemin Liu
The burden of disability, premature death, escalating health care costs and lost economic productivity due to obesity and its associated complications including hypertension, stroke, cardiovascular disease and type 2 diabetes is staggering [1, 2]. A better understanding of metabolic homeostatic pathways will provide us with insights into the biological mechanisms of obesity and how to fundamentally address this epidemic [3-6]. In mammals, energy balance is maintained via a homeostatic system involving both peripheral and central melanocortin systems; changes in body weight reflect an unbalance of the energetic state [7-9]...
May 9, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28495271/the-melanocortin-2-receptor-of-the-rainbow-trout-identifying-a-role-for-critical-positions-in-transmembrane-domain-4-extracellular-loop-2-and-transmembrane-domain-5-in-the-activation-of-rainbow-trout-mc2r
#5
Liang Liang, Perry V Davis, Michael R Dores, Robert M Dores
The activation of either teleost or tetrapod melanocortin-2 receptor (MC2R) orthologs requires interaction between the HFRW motif and R/KKRRP motif in the primary sequence of ACTH, and two corresponding sites on the melanocortin 2 receptor. While the HFRW contact site on MC2R appears to involve residues in TM2, TM3, and TM6, several studies on human MC2R point to the EC2/TM5 region of MC2R as a possible location for the R/KKRRP contact site. In this study nineteen single-alanine mutants of rainbow trout (rt) MC2R were made beginning at V(153) in TM4, at all positions in EC2 (extracellular loop 2), to F(175) in TM5...
May 8, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28491052/receptor-mediated-melanoma-targeting-with-radiolabeled-%C3%AE-melanocyte-stimulating-hormone-relevance-of-the-net-charge-of-the-ligand
#6
Jean-Philippe Bapst, Alex N Eberle
A majority of melanotic and amelanotic melanomas overexpress melanocortin type 1 receptors (MC1Rs) for α-melanocyte-stimulating hormone. Radiolabeled linear or cyclic analogs of α-MSH have a great potential as diagnostic or therapeutic tools for the management of malignant melanoma. Compounds such as [(111)In]DOTA-NAP-amide exhibit high affinity for the MC1R in vitro, good tumor uptake in vivo, but they may suffer from relatively high kidney uptake and retention in vivo. We have shown previously that the introduction of negative charges into radiolabeled DOTA-NAP-amide peptide analogs may enhance their excretion and reduce kidney retention...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28453292/discovery-of-mixed-pharmacology-melanocortin-3-agonists-and-melanocortin-4-receptor-tetrapeptide-antagonist-compounds-tacos-based-on-the-sequence-ac-xaa-1-arg-pi-dphe-xaa-4-nh2
#7
Skye R Doering, Katie T Freeman, Sathya M Schnell, Erica M Haslach, Marvin Dirain, Ginamarie Debevec, Phaedra Geer, Radleigh G Santos, Marc A Giulianotti, Clemencia Pinilla, Jon R Appel, Robert C Speth, Richard A Houghten, Carrie Haskell-Luevano
The centrally expressed melanocortin-3 and -4 receptors (MC3R/MC4R) have been studied as possible targets for weight management therapies, with a preponderance of studies focusing on the MC4R. Herein, a novel tetrapeptide scaffold [Ac-Xaa(1)-Arg-(pI)DPhe-Xaa(4)-NH2] is reported. The scaffold was derived from results obtained from a MC3R mixture-based positional scanning campaign. From these results, a set of 48 tetrapeptides were designed and pharmacologically characterized at the mouse melanocortin-1, -3, -4, and -5 receptors...
May 15, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28438719/chick-subcutaneous-and-abdominal-adipose-tissue-depots-respond-differently-in-lipolytic-and-adipogenic-activity-to-%C3%AE-melanocyte-stimulating-hormone-%C3%AE-msh
#8
Steven L Shipp, Guoqing Wang, Mark A Cline, Elizabeth R Gilbert
In birds, α-MSH is anorexigenic, but effects on adipose tissue are unknown. Four day-old chicks were intraperitoneally injected with 0 (vehicle), 5, 10, or 50μg of α-MSH and subcutaneous and abdominal adipose tissue collected at 60min for RNA isolation (n=10). Plasma was collected post-euthanasia at 60 and 180min for measuring non-esterified fatty acids (NEFA) and α-MSH (n=10). Relative to the vehicle, food intake was reduced in the 50μg-treated group. Plasma NEFAs were greater in 10μg than vehicle-treated chicks at 3h...
July 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/28434791/neuronal-cells-derived-from-human-induced-pluripotent-stem-cells-as-a-functional-tool-of-melanocortin-system
#9
Nobuko Yamada-Goto, Yukari Ochi, Goro Katsuura, Yui Yamashita, Ken Ebihara, Michio Noguchi, Junji Fujikura, Daisuke Taura, Masakatsu Sone, Kiminori Hosoda, Paul E Gottschall, Kazuwa Nakao
BACKGROUND: The preparation of human neurons derived from human induced pluripotent stem (iPS) cells can serve as a potential tool for evaluating the physiological and pathophysiological properties of human neurons and for drug development. METHODS: In the present study, the functional activity in neuronal cells differentiated from human iPS cells was observed. RESULTS: The differentiated cells expressed mRNAs for classical neuronal markers (microtubule-associated protein 2, β-tubulin III, calbindin 1, synaptophysin and postsynaptic density protein 95) and for subunits of various excitatory and inhibitory transmitters (NR1, NR2A, NR2B, GABAA α1)...
April 7, 2017: Neuropeptides
https://www.readbyqxmd.com/read/28433713/biased-signaling-at-neural-melanocortin-receptors-in-regulation-of-energy-homeostasis
#10
Li-Kun Yang, Ya-Xiong Tao
The global prevalence of obesity highlights the importance of understanding on regulation of energy homeostasis. The central melanocortin system is an important intersection connecting the neural pathways controlling satiety and energy expenditure to regulate energy homeostasis by sensing and integrating the signals of external stimuli. In this system, neural melanocortin receptors, melanocortin-3 and -4 receptors (MC3R and MC4R), play crucial roles in the regulation of energy homeostasis. Recently, multiple intracellular signaling pathways and biased signaling at neural MCRs have been discovered, providing new insights into neural MCR signaling...
April 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28426141/melanocortin-2-3-and-4-receptor-gene-expressions-are-downregulated-in-cd8-t-cytotoxic-lymphocytes-and-cd19-b-lymphocytes-in-rheumatoid-arthritis-responding-to-tnf%C3%AE-inhibition
#11
Marlene Andersen, Ivan Nagaev, Michael Kruse Meyer, Olga Nagaeva, Jarl Wikberg, Lucia Mincheva-Nilsson, Grethe Neumann Andersen
Melanocortin signaling in leukocyte subsets elicits anti-inflammatory and immune tolerance inducing effects in animal experimental inflammation. In man, however, the effects of melanocortin signaling in inflammatory conditions have scarcely been examined. We explored the differential reactions of melanocortin 1-5 receptor (MC1-5R) gene expressions in pathogenetic leukocyte subsets in rheumatoid arthritis (RA) to treatment with TNFα inhibitor adalimumab. Seven patients with active RA donated blood at start and at three months treatment...
April 20, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28409883/melanocortin-4-receptor-activation-attenuates-mitochondrial-dysfunction-in-skeletal-muscle-of-diabetic-rats
#12
Hao-Hao Zhang, Jiao Liu, Gui-Jun Qin, Xia-Lian Li, Pei-Jie Du, Xiao Hao, Tian-Tian Tian, Jing- Wu, Meng- Yun, Yan-Hui Bai
Backgroud: A previous study has confirmed that the central melanocortin system was able to mediate skeletal muscle AMP-activated protein kinase (AMPK) activation in mice fed a high-fat diet, while activation of the AMPK signaling pathway significantly induced mitochondrial biogenesis. Our hypothesis was that melanocortin 4 receptor (MC4R) was involved in the development of skeletal muscle injury in diabetic rats. METHODS: In this study, we treated diabetic rats intracerebroventricularly with MC4R agonist R027-3225 or antagonist SHU9119, respectively...
April 14, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28403939/melanocortin-4-receptor-is-not-required-for-estrogenic-regulations-on-energy-homeostasis-and-reproduction
#13
Pingwen Xu, Liangru Zhu, Kenji Saito, Yongjie Yang, Chunmei Wang, Yanlin He, Xiaofeng Yan, Ilirjana Hyseni, Qingchun Tong, Yong Xu
BACKGROUND: Brain estrogen receptor-α (ERα) is essential for estrogenic regulation of energy homeostasis and reproduction. We previously showed that ERα expressed by pro-opiomelanocortin (POMC) neurons mediates estrogen's effects on food intake, body weight, negative regulation of hypothalamic-pituitary-gonadal axis (HPG axis) and fertility. RESULTS AND CONCLUSIONS: We report here that global deletion of a key downstream receptor for POMC peptide, the melanocortin 4 receptor (MC4R), did not affect normal negative feedback regulation of estrogen on the HPG axis, estrous cyclicity and female fertility...
May 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28396685/associations-of-two-obesity-related-single-nucleotide-polymorphisms-with-adiponectin-in-chinese-children
#14
Lijun Wu, Liwang Gao, Xiaoyuan Zhao, Meixian Zhang, Jianxin Wu, Jie Mi
Purpose. Genome-wide association studies have found two obesity-related single-nucleotide polymorphisms (SNPs), rs17782313 near the melanocortin-4 receptor (MC4R) gene and rs6265 near the brain-derived neurotrophic factor (BDNF) gene, but the associations of both SNPs with other obesity-related traits are not fully described, especially in children. The aim of the present study is to investigate the associations between the SNPs and adiponectin that has a regulatory role in glucose and lipid metabolism. Methods...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28382155/preclinical-melanoma-imaging-with-68-ga-labeled-%C3%AE-melanocyte-stimulating-hormone-derivatives-using-pet
#15
Chengcheng Zhang, Zhengxing Zhang, Kuo-Shyan Lin, Jinhe Pan, Iulia Dude, Navjit Hundal-Jabal, Nadine Colpo, François Bénard
It is estimated that melanoma accounted for 76,380 new cases and 10,130 deaths in the United States in 2016. The melanocortin 1 receptor (MC1R) is highly expressed in the vast majority of melanomas, which makes it an attractive target for molecular imaging and radionuclide therapy. Lactam bridge-cyclized α-melanocyte-stimulating hormone (Ac-Nle(4)-cyclo[Asp(5)-His-D-Phe(7)-Arg-Trp-Lys(10)]-NH2, or Nle-CycMSHhex) analogues have been successfully developed and studied for MC1R-targeted imaging, predominantly with single-photon emission computed tomography (SPECT)...
2017: Theranostics
https://www.readbyqxmd.com/read/28356726/searching-for-the-relationship-between-the-parameters-of-metabolic-syndrome-and-the-rs17782313-t-c-polymorphism-of-the-mc4r-gene-in-postmenopausal-women
#16
Jacek Brodowski, Małgorzata Szkup, Anna Jurczak, Sylwia Wieder-Huszla, Agnieszka Brodowska, Maria Laszczyńska, Beata Karakiewicz, Katarzyna Kęcka, Elżbieta Grochans
Metabolic syndrome (MS) is widespread in the human population, and its incidence is continuously increasing, generating serious health problems. The purpose of this study was to find the relationship between the parameters of MS and the melanocortin type 4 receptor (MC4R) gene polymorphism in postmenopausal women. The study involved 344 healthy Polish women, who had their last menstrual cycle 1 year ago or earlier. The study included blood analysis, survey, and body measurements. The mean age was 58.5±6.6 years...
2017: Clinical Interventions in Aging
https://www.readbyqxmd.com/read/28333235/ovarian-hormones-and-obesity
#17
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
#18
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...
May 15, 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
#19
Tzlil Tabachnik, Tatiana Kisliouk, Asaf Marco, Noam Meiri, Aron Weller
Maternal obesity is a risk factor for offspring obesity. The melanocortin 4 receptor (Mc4r) is one of the mediators of food intake and energy balance. The present study examined the epigenetic mechanisms underlying altered Mc4r levels in the hypothalamic paraventricular nucleus in the offspring of high-fat diet (HFD)-induced obese dams and sought to elucidate the role of thyroid hormones in epigenetic regulation and tagging of their nucleosome at the Mc4r promoter. Female Wistar rats were fed an HFD or standard chow from weaning through gestation and lactation...
April 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28303974/antifibrotic-effect-of-pirfenidone-in-a-mouse-model-of-human-nonalcoholic-steatohepatitis
#20
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
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