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Anna V Motorina, Nadezhda V Palkina, Anna V Komina, Tatiana G Ruksha, Ivan P Artyukhov, Vasily V Kozlov
The melanocortin 1 receptor is a Gs protein-coupled receptor implicated in melanogenesis regulation. The receptor gene is highly polymorphic, which accounts for the association of several of its single-nucleotide polymorphisms (SNPs) with an increased risk of melanoma. The present study aimed to evaluate the distribution of melanocortin 1 receptor gene variants R151C, R160W, and D294H within the Russian population of Eastern Siberia and its association with melanoma development. Melanoma patients (n=95) admitted to Krasnoyarsk Territorial Oncological Center and healthy controls (n=334) were enrolled in the study...
October 13, 2016: European Journal of Cancer Prevention
Joon Kyungjoon Lim, Sandra Burke, Geoffrey Head
OBJECTIVE: Obesity during pregnancy is associated with a greater risk of developing hypertension in the offspring. Plasma leptin levels correlate strongly with blood pressure and renal sympathetic nerve activity (RSNA). The ventromedial hypothalamus (VMH) is a key centre of energy homeostasis, haemodynamic and sympathetic tone to renal vasculature. It is possible that exposure to over-nutrition during development change the activity of the neurons, amplifying sympathetic output leading to hypertension in the offspring...
September 2016: Journal of Hypertension
Sarah Abdullah, William Reginold, Courtney Kiss, Karen J Harrison, Jennifer J MacKenzie
Childhood obesity is a growing health concern, associated with significant physical and psychological morbidity. Childhood obesity is known to have a strong genetic component, with mutations in the melanocortin-4 receptor (MC4R) gene being the most common monogenetic cause of obesity. Over 166 different MC4R mutations have been identified in persons with hyperphagia, severe childhood obesity, and increased linear growth. However, it is unclear whether the MC4-R deficiency phenotype is due to haploinsufficiency or dominant-negative effects by the mutant receptor...
2016: Case Reports in Pediatrics
A M Obregón, K Oyarce, J L Santos, M Valladares, G Goldfield
Studies conducted in monozygotic and dizygotic twins have established a strong genetic component in eating behavior. Rare mutations and common variants of the melanocortin 4 receptor (MC4R) gene have been linked to obesity and eating behavior scores. However, few studies have assessed common variants in MC4R gene with the rewarding value of food in children. The objective of the study was to evaluate the association between the MC4R rs17782313 polymorphism with homeostatic and non-homeostatic eating behavior patterns in Chileans children...
October 11, 2016: Journal of Physiology and Biochemistry
Jennifer W Hill, Latrice D Faulkner
No abstract text is available yet for this article.
October 11, 2016: Neuroendocrinology
Minoru Kato, Yi-Ying Huang, Mina Matsuo, Yoko Takashina, Kazuyo Sasaki, Yasushi Horai, Aya Juni, Shin-Ichi Kamijo, Kaoru Saigo, Kumiko Ui-Tei, Hajime Tei
RNA interference (RNAi) is a powerful tool for the study of gene function in mammalian systems, including transgenic mice. Here, we report a gene knockdown system based on the human mir-187 precursor. We introduced small interfering RNA (siRNA) sequences against the mouse melanocortin-4 receptor (mMc4r) to alter the targeting of miR-187. The siRNA-expressing cassette was placed under the control of the cytomegalovirus (CMV) early enhancer/chicken β-actin promoter. In vitro, the construct efficiently knocked down the gene expression of a co-transfected mMc4r-expression vector in cultured mammalian cells...
September 30, 2016: Experimental Animals
Panpan You, Handan Hu, Yuting Chen, Yongliang Zhao, Yiqing Yang, Tongtong Wang, Roumei Xing, Yanjiao Shao, Wen Zhang, Dali Li, Huaqing Chen, Mingyao Liu
Melanocortin-3 and 4 receptors (MC3R and MC4R) can regulate energy homeostasis, but their respective roles especially the functions of MC3R need more exploration. Here Mc3r and Mc4r single and double knockout (DKO) rats were generated using CRISPR-Cas9 system. Metabolic phenotypes were examined and data were compared systematically. Mc3r KO rats displayed hypophagia and decreased body weight, while Mc4r KO and DKO exhibited hyperphagia and increased body weight. All three mutants showed increased white adipose tissue mass and adipocyte size...
October 7, 2016: Scientific Reports
B Paolini, P E Maltese, I Del Ciondolo, D Tavian, S Missaglia, C Ciuoli, M Zuntini, S Cecchin, M Bertelli, G Pompucci
Obesity is a major public health concern; despite evidence of high heritability, the genetic causes of obesity remain unclear. In this study, we assessed the presence of mutations in three genes involved in the hypothalamic leptin-melanocortin regulation pathway (leptin, LEP; leptin receptor, LEPR; and melanocortin-4 receptor, MC4R), which is important for energy homeostasis in the body, in a group of patients with severe obesity. For this study, we selected 77 patients who had undergone bariatric surgery and had a pre-operative body mass index (BMI) >35 kg/m(2), early onset and a family history of being overweight...
August 19, 2016: Genetics and Molecular Research: GMR
Agatha A van der Klaauw, Julia M Keogh, Elana Henning, Cheryl Stephenson, Sarah Kelway, Victoria M Trowse, Naresh Subramanian, Stephen O'Rahilly, Paul C Fletcher, I Sadaf Farooqi
Melanocortin-4-receptor (MC4R)-expressing neurons modulate food intake and preference in rodents but their role in human food preference is unknown. Here we show that compared with lean and weight-matched controls, MC4R deficient individuals exhibited a markedly increased preference for high fat, but a significantly reduced preference for high sucrose food. These effects mirror those in Mc4r null rodents and provide evidence for a central molecular circuit influencing human macronutrient preference.
October 4, 2016: Nature Communications
Davide Carta, Nicola Salvarese, Nicolò Morellato, Feng Gao, Wiebke Sihver, Hans Jurgen Pietzsch, Barbara Biondi, Paolo Ruzza, Fiorenzo Refosco, Debora Carpanese, Antonio Rosato, Cristina Bolzati
The purpose of this study was to evaluate the effect of cyclization on the biological profile of a [(99m)Tc(N)(PNP3)]-labeled α-melanocyte stimulating hormone peptide analog. A lactam bridge-cyclized H-Cys-Ahx-βAla(3)-c[Lys(4)-Glu-His-D-Phe-Arg-Trp-Glu(10)]-Arg(11)-Pro-Val-NH2 (NAP-NS2) and the corresponding linear H-Cys-Ahx-βAla-Nle-Asp-His-D-Phe-Arg-Trp-Gly-NH2 (NAP-NS1) peptide were synthetized, characterized by ESI-MS spectroscopy and their melanocortin-1 receptor (MC1R) binding affinity was determined in B16/F10 melanoma cells...
August 31, 2016: Nuclear Medicine and Biology
Jia Sun, Yong Gao, Ting Yao, Yiru Huang, Zhenyan He, Xingxing Kong, Kai-Jiang Yu, Rui-Tao Wang, Hongbo Guo, Jianqun Yan, Yongsheng Chang, Hong Chen, Philipp E Scherer, Tiemin Liu, Kevin W Williams
OBJECTIVE: Adiponectin receptors (AdipoRs) are located on neurons of the hypothalamus involved in metabolic regulation - including arcuate proopiomelanocortin (Pomc) and Neuropeptide Y/Agouti-related peptide (NPY/AgRP) neurons. AdipoRs play a critical role in regulating glucose and fatty acid metabolism by initiating several signaling cascades overlapping with Leptin receptors (LepRs). However, the mechanism by which adiponectin regulates cellular activity in the brain remains undefined...
October 2016: Molecular Metabolism
Maria Manfredi-Lozano, Juan Roa, Francisco Ruiz-Pino, Richard Piet, David Garcia-Galiano, Rafael Pineda, Aurora Zamora, Silvia Leon, Miguel A Sanchez-Garrido, Antonio Romero-Ruiz, Carlos Dieguez, Maria Jesus Vazquez, Allan E Herbison, Leonor Pinilla, Manuel Tena-Sempere
OBJECTIVE: Puberty is a key developmental phenomenon highly sensitive to metabolic modulation. Worrying trends of changes in the timing of puberty have been reported in humans. These might be linked to the escalating prevalence of childhood obesity and could have deleterious impacts on later (cardio-metabolic) health, but their underlying mechanisms remain unsolved. The neuropeptide α-MSH, made by POMC neurons, plays a key role in energy homeostasis by mediating the actions of leptin and likely participates in the control of reproduction...
October 2016: Molecular Metabolism
Pablo J Enriori, Weiyi Chen, Maria C Garcia-Rudaz, Bernadette E Grayson, Anne E Evans, Sarah M Comstock, Ursel Gebhardt, Hermann L Müller, Thomas Reinehr, Belinda A Henry, Russell D Brown, Clinton R Bruce, Stephanie E Simonds, Sara A Litwak, Sean L McGee, Serge Luquet, Sarah Martinez, Martin Jastroch, Matthias H Tschöp, Matthew J Watt, Iain J Clarke, Christian L Roth, Kevin L Grove, Michael A Cowley
OBJECTIVE: Central melanocortin pathways are well-established regulators of energy balance. However, scant data exist about the role of systemic melanocortin peptides. We set out to determine if peripheral α-melanocyte stimulating hormone (α-MSH) plays a role in glucose homeostasis and tested the hypothesis that the pituitary is able to sense a physiological increase in circulating glucose and responds by secreting α-MSH. METHODS: We established glucose-stimulated α-MSH secretion using humans, non-human primates, and mouse models...
October 2016: Molecular Metabolism
Qiong-Ying Tang, Li-Xia Shi, Fei Liu, Dan Yu, Huan-Zhang Liu
Fish of the superfamily Cobitoidea sensu stricto (namely loaches) exhibit extremely high diversity of color patterns, but so far little is known about their evolutionary mechanism. Melanocortin 1 receptor gene (MC1R) plays an important role during the synthesis of melanin and formation of animal body color patterns. In this study, we amplified and sequenced the partial MC1R gene for 44 loach individuals representing 31 species of four families. Phylogenetic analyses yielded a topology congruent with previous studies using multiple nuclear loci, showing that each of the four families was monophyletic with sister relationships of Botiidae+ (Cobitidae+(Balitoridae+Nemacheilidae))...
September 18, 2016: Dong Wu Xue Yan Jiu, Zoological Research
Betty R McConn, Justin Matias, Guoqing Wang, Mark A Cline, Elizabeth R Gilbert
OBJECTIVE: The objective was to determine the effects of high-protein and high-fat diets, and fasting and refeeding, on appetite regulation in chicks. METHODS: Day of hatch chicks were fed one of four diets: basal, high protein (25% crude protein), and 15 and 30% high fat (15 and 30% metabolizable energy derived from soybean oil, respectively), and assigned to one of three treatments at 4 days: (1) access to feed, (2) 3 hours of fasting, or (3) fasting followed by 1 hour of refeeding...
August 16, 2016: Nutritional Neuroscience
Stuart G Jarrett, Erin M Wolf Horrell, John A D'Orazio
Loss-of-function in melanocortin 1 receptor (MC1R), a GS protein-coupled receptor that regulates signal transduction through cAMP and protein kinase A (PKA) in melanocytes, is a major inherited melanoma risk factor. Herein, we report a novel cAMP-mediated response for sensing and responding to UV-induced DNA damage regulated by A-kinase-anchoring protein 12 (AKAP12). AKAP12 is identified as a necessary participant in PKA-mediated phosphorylation of ataxia telangiectasia mutated and Rad3-related (ATR) at S435, a post-translational event required for cAMP-enhanced nucleotide excision repair (NER)...
September 28, 2016: Nucleic Acids Research
Yuhuan Meng, Yujia Guan, Wenlu Zhang, Yu-E Wu, Huanhuan Jia, Yu Zhang, Xiuqing Zhang, Hongli Du, Xiaoning Wang
The Goto-Kakizaki (GK) rat is an animal model of non-obese type 2 diabetes (T2D). The GK rat was generated through the introduction of various genetic mutations from continuous inbreeding; these rats develop diabetes spontaneously. The mutated genes in GK rats may play key roles in the regulation of diabetes. The hypothalamus plays a central role in systematic energy homeostasis. Here, the hypothalamic transcriptomes in GK and Wistar rats at 4, 8 and 12 weeks were investigated by RNA-seq, and multiple variants and gene expression profiles were obtained...
September 28, 2016: Scientific Reports
N A Gustafson, B Gandolfi, L A Lyons
The Burmese is a breed of domestic cat that originated in Southeast Asia and was further developed in the United States. Variants in melanocortin 1 receptor (MC1R) causes common coat colour phenotypes in a variety of mammalian species but only limited colour variation in the domestic cat. Known as the extension (E) locus, melanocortin 1 receptor (MC1R) interacts with the agouti locus to produce the eumelanin and pheomelanin pigments. Recently, a novel reddish coloration, which is termed russet, was identified in the Burmese cat breed...
September 27, 2016: Animal Genetics
Luis M San-Jose, Anne-Lyse Ducrest, Valérie Ducret, Céline Simon, Hannes Richter, Kazumasa Wakamatsu, Alexandre Roulin
The melanocortin-1 receptor (MC1R) gene influences coloration by altering the expression of genes acting downstream in the melanin synthesis. MC1R belongs to the melanocortin system, a genetic network coding for the ligands that regulate MC1R and other melanocortin receptors controlling different physiological and behavioural traits. The impact of MC1R variants on these regulatory melanocortin genes was never considered, even though MC1R mutations could alter the influence of these genes on coloration (e.g...
September 24, 2016: Molecular Ecology
Stuart G Jarrett, John A D'Orazio
Melanoma is the deadliest form of skin cancer because of its propensity to spread beyond the primary site of disease and because it resists many forms of treatment. Incidence of melanoma has been increasing for decades. Though ultraviolet radiation (UV) has been identified as the most important environmental causative factor for melanoma development, UV-protective strategies have had limited efficacy in melanoma prevention. UV mutational burden correlates with melanoma development and tumor progression, underscoring the importance of UV in melanomagenesis...
September 19, 2016: Photochemistry and Photobiology
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