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https://www.readbyqxmd.com/read/28537674/correlations-of-mc4r-and-msh2-expression-with-obesity-in-colon-cancer-patients
#1
Y-Z Liu, K-Q Wang, D-H Ji, L-C Zhang, M Bi, B-Y Shi
OBJECTIVE: To investigate the correlations of MC4R and MSH2 with adult obesity, a total of 46 patients with early-stage colon cancer were treated in our hospital between February 2008 and February 2009 and were enrolled. PATIENTS AND METHODS: Venous blood was regularly drawn from subjects of the observation group and 48 healthy subjects for 6 years. Expression levels of MC4R and MSH2 genes were tested using quantitative polymerase chain reaction analyses, and the ensuing proteins were determined using enzyme-linked immunosorbent assays and Western blotting and immunohistochemical analyses...
May 2017: European Review for Medical and Pharmacological Sciences
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
#2
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
#3
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/28507313/chronic-intrahypothalamic-rather-than-subcutaneous-liraglutide-treatment-reduces-body-weight-gain-and-stimulates-the-melanocortin-receptor-system
#4
K Kaineder, T Birngruber, G Rauter, B Obermüller, J Eichler, J Münzker, W Al-Zoughbi, S I Mautner, S S Torekov, B Hartmann, P Kotzbeck, T R Pieber
BACKGROUND: The GLP-1 receptor agonist liraglutide is marketed for obesity treatment where it induces body weight reduction possibly via the hypothalamus, which regulates energy homeostasis. In animal studies, acute liraglutide treatment triggers satiety, weight loss and activates thermogenesis in adipose tissue. However, the precise mechanisms how liraglutide affects in particular chronic weight loss are still under investigation. OBJECTIVES: We aimed to evaluate whether chronic hypothalamic or chronic subcutaneous administration of liraglutide induces sustained weight loss through altered adipose tissue function and to what extent hypothalamic neuronal appetite regulators are involved in the liraglutide-induced weight loss in healthy lean rats on a normal diet...
April 25, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28500249/maternal-high-fat-diet-induces-metabolic-stress-response-disorders-in-offspring-hypothalamus
#5
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
#6
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/28472148/genetic-analysis-of-single-minded-1-gene-in-early-onset-severely-obese-children-and-adolescents
#7
Daniela Stanikova, Marek Buzga, Patrik Krumpolec, Martina Skopkova, Martina Surova, Barbara Ukropcova, Lubica Ticha, Miroslava Petrasova, Dominika Gabcova, Miroslava Huckova, Lucie Piskorova, Jan Bozensky, Marian Mokan, Jozef Ukropec, Ivona Zavacka, Iwar Klimes, Juraj Stanik, Daniela Gasperikova
BACKGROUND: Inactivating mutations of the hypothalamic transcription factor singleminded1 (SIM1) have been shown as a cause of early-onset severe obesity. However, to date, the contribution of SIM1 mutations to the obesity phenotype has only been studied in a few populations. In this study, we screened the functional regions of SIM1 in severely obese children of Slovak and Moravian descent to determine if genetic variants within SIM1 may influence the development of obesity in these populations...
2017: PloS One
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
#8
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/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/28424580/the-role-of-microrna-in-the-modulation-of-the-melanocortinergic-system
#12
REVIEW
Adel Derghal, Mehdi Djelloul, Jérôme Trouslard, Lourdes Mounien
The central control of energy balance involves a highly regulated neuronal network within the hypothalamus and the dorsal vagal complex. In these structures, pro-opiomelanocortin (POMC) neurons are known to reduce meal size and to increase energy expenditure. In addition, leptin, a peripheral signal that relays information regarding body fat content, modulates the activity of melanocortin pathway neurons including POMC-, Agouti-related peptide (AgRP)/Neuropeptide Y (NPY)-, melanocortin receptors (MC3R and MC4R)-expressing neurons...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28409883/melanocortin-4-receptor-activation-attenuates-mitochondrial-dysfunction-in-skeletal-muscle-of-diabetic-rats
#13
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
#14
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
#15
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/28384342/assessing-gene-environment-interaction-effects-of-fto-mc4r-and-lifestyle-factors-on-obesity-using-an-extreme-phenotype-sampling-design-results-from-the-hunt-study
#16
Thea Bjørnland, Mette Langaas, Valdemar Grill, Ingrid Løvold Mostad
BACKGROUND: Our aim was to assess the influence of age, gender and lifestyle factors on the effect of the obesity-promoting alleles of FTO and MCR4. METHODS: The HUNT study comprises health information on the population of Nord-Trøndelag county, Norway. Extreme phenotype participants (gender-wise lower and upper quartiles of waist-hip-ratio and BMI ≥ 35 kg/m2) in the third survey, HUNT3 (2006-08), were genotyped for the single-nucleotide polymorphisms rs9939609 (FTO) and rs17782313 (MC4R); 25686 participants were successfully genotyped...
2017: PloS One
https://www.readbyqxmd.com/read/28378841/%C3%AE-msh-and-melanocortin-receptors-at-early-ontogeny-in-european-sea-bass-dicentrarchus-labrax-l
#17
A Tsalafouta, M Gorissen, T N M Pelgrim, N Papandroulakis, G Flik, M Pavlidis
Temporal patterns of whole-body α-MSH concentrations and of transcripts of melanocortin receptors during early development as well as the endocrine response (α-MSH, cortisol, MCR mRNAs) to stress at the end of the larval period were characterized in Dicentrarchus labrax. Immunohistochemistry showed α-MSH positive cells in the pituitary pars intermedia in all stages examined. As development proceeds, α-MSH content gradually increases; mRNA levels of mc2r and mc4r remain low until first feeding where peak values are observed...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28377240/next-generation-sequencing-of-the-monogenic-obesity-genes-lep-lepr-mc4r-pcsk1-and-pomc-in-a-norwegian-cohort-of-patients-with-morbid-obesity-and-normal-weight-controls
#18
Gry B N Nordang, Øyvind L Busk, Kristian Tveten, Hans Ivar Hanevik, Anne Kristin M Fell, Jøran Hjelmesæth, Øystein L Holla, Jens K Hertel
BACKGROUND: Rare sequence variants in at least five genes are known to cause monogenic obesity. In this study we aimed to investigate the prevalence of, and characterize, rare coding and splice site variants in LEP, LEPR, MC4R, PCSK1 and POMC in patients with morbid obesity and normal weight controls. METHOD: Targeted next-generation sequencing of all exons in LEP, LEPR, MC4R, PCSK1 and POMC was performed in 485 patients with morbid obesity and 327 normal weight population-based controls from Norway...
March 29, 2017: Molecular Genetics and Metabolism
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
#19
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/28351432/-genetic-obesity-new-diagnostic-options
#20
T I de Vries, S I M Alsters, L Kleinendorst, G van Haaften, B van der Zwaag, M M Van Haelst
- Obesity is an important risk factor for morbidity and premature death, as well as a contributing factor to psychosocial problems. The incidence of obesity has increased dramatically over the last few decades.- Obesity is considered to be a multifactorial condition in which both environmental factors and genetic factors play a part.- In approximately 5% of patients with morbid obesity, a monogenic cause can be identified. Mutations in the MC4R gene are the most frequently occurring monogenic cause of obesity...
2017: Nederlands Tijdschrift Voor Geneeskunde
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