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https://www.readbyqxmd.com/read/27911598/type-3-deiodinase-role-on-central-thyroid-hormone-action-affects-the-leptin-melanocortin-system-and-circadian-activity
#1
Zhaofei Wu, M Elena Martinez, Donald L St Germain, Arturo Hernandez
The role of thyroid hormones (TH) in the central regulation of energy balance is increasingly appreciated. Mice lacking the type 3 deiodinase (DIO3), which inactivates TH, have decreased circulating TH levels relative to control mice due to defects in the hypothalamic-pituitary-thyroid axis. However, we have shown that the TH status of the adult Dio3(-/-) brain is opposite that of the serum, exhibiting enhanced levels of TH action. Since the brain, specially the hypothalamus, harbors important circuitries that regulate metabolism, we aimed to examine the energy balance phenotype of Dio3(-/-) mice and determine whether it is associated with hypothalamic abnormalities...
December 2, 2016: Endocrinology
https://www.readbyqxmd.com/read/27890744/gene-expression-of-pro-opiomelanocortin-and-melanocortin-receptors-is-regulated-in-the-hypothalamus-and-mesocorticolimbic-system-following-nicotine-administration
#2
Damla E Tapinc, Rabia Ilgin, Egemen Kaya, Oguz Gozen, Muzeyyen Ugur, Ersin O Koylu, Lutfiye Kanit, Aysegul Keser, Burcu Balkan
Pro-opiomelanocortin (POMC)-derived peptides and their receptors have been shown to play important roles in natural and drug-induced reward and reinforcement. Reward process may involve the regulation of POMC gene expression and the gene expression of POMC-derived peptide receptors. The present study investigated the alterations observed in the transcript levels of POMC, melanocortin 3 (MC3R), melanocortin 4 (MC4R) and mu-opioid receptors (MOR) in the hypothalamus and mesocorticolimbic system during nicotine exposure...
November 24, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27886210/physical-activity-energy-expenditure-and-defense-of-body-weight-in-melanocortin-4-receptor-deficient-male-rats
#3
Tariq I Almundarij, Mark E Smyers, Addison Spriggs, Lydia A Heemstra, Lisa Beltz, Eric Dyne, Caitlyn Ridenour, Colleen M Novak
Melanocortin 4 receptor (MC4R) variants contribute to human obesity, and rats lacking functional MC4R (Mc4r(K314X/K314X)) are obese. We investigated the hypothesis that low energy expenditure (EE) and physical activity contribute to this obese phenotype in male rats, and determined whether lack of functional MC4R conferred protection from weight loss during 50% calorie restriction. Though Mc4r(K314X/K314X) rats showed low brown adipose Ucp1 expression and were less physically active than rats heterozygous for the mutation (Mc4r(+/K314X)) or wild-type (Mc4r(+/+)) rats, we found no evidence of lowered EE in Mc4r(K314X/K314X) rats once body weight was taken into account using covariance...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27869800/a-rapidly-acting-glutamatergic-arc%C3%A2-pvh-satiety-circuit-postsynaptically-regulated-by-%C3%AE-msh
#4
Henning Fenselau, John N Campbell, Anne M J Verstegen, Joseph C Madara, Jie Xu, Bhavik P Shah, Jon M Resch, Zongfang Yang, Yael Mandelblat-Cerf, Yoav Livneh, Bradford B Lowell
Arcuate nucleus (ARC) neurons sense the fed or fasted state and regulate hunger. Agouti-related protein (AgRP) neurons in the ARC (ARC(AgRP) neurons) are stimulated by fasting and, once activated, they rapidly (within minutes) drive hunger. Pro-opiomelanocortin (ARC(POMC)) neurons are viewed as the counterpoint to ARC(AgRP) neurons. They are regulated in an opposite fashion and decrease hunger. However, unlike ARC(AgRP) neurons, ARC(POMC) neurons are extremely slow in affecting hunger (many hours). Thus, a temporally analogous, rapid ARC satiety pathway does not exist or is presently unidentified...
November 21, 2016: Nature Neuroscience
https://www.readbyqxmd.com/read/27849360/robust-reductions-of-excess-weight-and-hyperphagia-by-beloranib-in-rat-models-of-genetic-and-hypothalamic-obesity
#5
Clinton T Elfers, Christian L Roth
Hypothalamic lesions or deficient melanocortin (MC) signaling via MC4 receptor (MC4r) mutations often lead to hyperphagia and severe treatment resistant obesity. We tested the methionine amino peptidase 2-inhibitor beloranib (ZGN-440) in two male rat models of obesity, one modeling hypothalamic obesity (HO) with combined medial hypothalamic lesions (CMHL), and the other modeling a monogenic form of obesity with MC4r mutations (MC4rKO). In CMHL rats (age 3 months), post-surgery excess weight gain was significantly inhibited (ZGN-440 0...
November 16, 2016: Endocrinology
https://www.readbyqxmd.com/read/27833052/dietary-calcium-supplementation-in-adult-rats-reverts-brown-adipose-tissue-dysfunction-programmed-by-postnatal-early-overfeeding
#6
Ellen Paula Santos Conceição, Egberto Gaspar Moura, Elaine Oliveira, Deysla Sabino Guarda, Mariana Sarto Figueiredo, Fernanda Torres Quitete, Camila Calvino, Rosiane Aparecida Miranda, Paulo Cezar Freitas Mathias, Alex Christian Manhães, Patricia Cristina Lisboa
Brown adipose tissue (BAT) dysfunction is associated with obesity and its comorbidities, such as hypertension, and the improvement of BAT function seems important for obesity management. Here we investigated the effects of dietary calcium supplementation on BAT autonomic nerve activity, sympathoadrenal function and cardiovascular parameters in adult obese rats that were raised in small litters (SL group). Three days after birth, SL litters were adjusted to three pups to induce early overfeeding. The control group remained with 10 pups/litter until weaning (NL group)...
January 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27829468/fat-mass-obesity-associated-fto-rs9939609-and-melanocortin-4-receptor-mc4r-rs17782313-snp-are-positively-associated-with-obesity-and-blood-pressure-in-mexican-school-aged-children
#7
Pablo García-Solís, Marissa Reyes-Bastidas, Karla Flores, Olga P García, Jorge L Rosado, Lorena Méndez-Villa, Carlota Garcia-G, David García-Gutiérrez, Aarón Kuri-García, Hebert L Hernández-Montiel, Ofelia Soriano-Leon, Maria Elena Villagrán-Herrera, Juan C Solis-Sainz
Childhood overweight and obesity are worldwide public health problems and risk factors for chronic diseases. The presence of SNP in several genes has been associated with the presence of obesity. A total of 580 children (8-13 years old) from Queretaro, Mexico, participated in this cross-sectional study, which evaluated the associations of rs9939609 (fat mass obesity-associated (FTO)), rs17782313 (melanocortin 4 receptor (MC4R)) and rs6548238 (transmembrane protein 18 (TMEM18)) SNP with obesity and metabolic risk factors...
November 10, 2016: British Journal of Nutrition
https://www.readbyqxmd.com/read/27829153/stimulation-of-the-hippocampal-pomc-mc4r-circuit-alleviates-synaptic-plasticity-impairment-in-an-alzheimer-s-disease-model
#8
Yang Shen, Min Tian, Yuqiong Zheng, Fei Gong, Amy K Y Fu, Nancy Y Ip
Hippocampal synaptic plasticity is modulated by neuropeptides, the disruption of which might contribute to cognitive deficits observed in Alzheimer's disease (AD). Although pro-opiomelanocortin (POMC)-derived neuropeptides and melanocortin 4 receptor (MC4R) are implicated in hippocampus-dependent synaptic plasticity, how the POMC/MC4R system functions in the hippocampus and its role in synaptic dysfunction in AD are largely unknown. Here, we mapped a functional POMC circuit in the mouse hippocampus, wherein POMC neurons in the cornu ammonis 3 (CA3) activate MC4R in the CA1...
November 8, 2016: Cell Reports
https://www.readbyqxmd.com/read/27791019/central-role-for-melanocortin-4-receptors-in-offspring-hypertension-arising-from-maternal-obesity
#9
Anne-Maj S Samuelsson, Amandine Mullier, Nuria Maicas, Nynke R Oosterhuis, Sung Eun Bae, Tatiana V Novoselova, Li F Chan, Joaquim M Pombo, Paul D Taylor, Jaap A Joles, Clive W Coen, Nina Balthasar, Lucilla Poston
Melanocortin-4 receptor (Mc4r)-expressing neurons in the autonomic nervous system, particularly in the paraventricular nucleus of the hypothalamus (PVH), play an essential role in blood pressure (BP) control. Mc4r-deficient (Mc4rKO) mice are severely obese but lack obesity-related hypertension; they also show a reduced pressor response to salt loading. We have previously reported that lean juvenile offspring born to diet-induced obese rats (OffOb) exhibit sympathetic-mediated hypertension, and we proposed a role for postnatally raised leptin in its etiology...
October 25, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27773974/pparg-lyplal1-multi-allelic-combination-associated-with-obesity-and-overweight-in-mexican-adolescent-females
#10
Esther Alhelí Hernández-Tobías, Luisa Torres-Sánchez, Gino Noris, Carla Santana, María Reyna Samano, José Arellano-Galindo, María de la Luz Arenas-Sordo, Daniel Brooks, Ana Lilia Rodríguez-Ventura, Marco Antonio Meraz-Ríos, Rocío Gómez
OBJECTIVE: We studied multi-loci variants to identify the contribution of six candidate genes (ADIPOQ, CDH13, LYPLAL1, MC4R, PPARG and PGC1A) in the development of obesity and overweight. DESIGN: We genotyped 404 chromosomes with eleven SNPs in Mexican female adolescents, who were subdivided into two groups (obesity-overweight and normal-weight) using the World Health Organization parameters. Genomic (800 chromosomes) and ancestral (208 chromosomes) controls were included to reduce the population bias...
October 20, 2016: Ethnicity & Disease
https://www.readbyqxmd.com/read/27738543/melanocortin-4-receptor-deficiency-phenotype-with-an-interstitial-18q-deletion-a-case-report-of-severe-childhood-obesity-and-tall-stature
#11
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
https://www.readbyqxmd.com/read/27730429/association-of-the-melanocortin-4-receptor-gene-rs17782313-polymorphism-with-rewarding-value-of-food-and-eating-behavior-in-chilean-children
#12
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
https://www.readbyqxmd.com/read/27713523/effects-of-melanocortin-3-and-4-receptor-deficiency-on-energy-homeostasis-in-rats
#13
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
https://www.readbyqxmd.com/read/27706562/prevalence-of-mutations-in-lep-lepr-and-mc4r-genes-in-individuals-with-severe-obesity
#14
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
https://www.readbyqxmd.com/read/27701398/divergent-effects-of-central-melanocortin-signalling-on-fat-and-sucrose-preference-in-humans
#15
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
https://www.readbyqxmd.com/read/27701175/evaluation-of-the-obesity-genes-fto-and-mc4r-for-contribution-to-the-risk-of-large-artery-atherosclerotic-stroke-in-a-chinese-population
#16
Zhi Song, Lingling Qiu, Zhongyang Hu, Jia Liu, Ding Liu, Deren Hou
BACKGROUND: Obesity is a well-established risk factor for large artery atherosclerotic (LAA) stroke. The aim of the study was to explore whether obesity genes, such as MC4R and FTO, contribute to LAA stroke risk in the Chinese Han population. METHODS: 322 LAA stroke patients and 473 controls were recruited. Gene polymorphism of MC4R (rs17782313) and FTO (rs8050136 and rs9939609) were genotyped. RESULTS: No differences were observed in genotype frequencies of variants of FTO (rs8050136 and rs9939609) or MC4R (rs17782313) between LAA stroke patients and control subjects...
October 5, 2016: Obesity Facts
https://www.readbyqxmd.com/read/27634552/effects-of-mc4r-fto-and-nmb-gene-variants-to-obesity-physical-activity-and-eating-behavior-phenotypes
#17
Deniz Kirac, Ozgur Kasimay Cakir, Tuba Avcilar, Oguzhan Deyneli, Hizir Kurtel, Dilek Yazici, Elif Cigdem Kaspar, Nurgul Celik, Ahmet Ilter Guney
Obesity is a major contributory factor of morbidity and mortality. It has been suggested that biological systems may be involved in the tendency to be and to remain physically inactive also behaviors such as food and beverage preferences and nutrient intake may at least partially genetically determined. Consequently, besides environment, genetic factors may also contribute to the level of physical activity and eating behaviors thus effect obesity. Therefore the aim of this study is to investigate the effect of various gene mutations on obesity, physical activity levels and eating behavior phenotypes...
October 2016: IUBMB Life
https://www.readbyqxmd.com/read/27626491/delineation-of-the-central-melanocortin-circuitry-controlling-the-kidneys-by-a-virally-mediated-transsynaptic-tracing-study-in-transgenic-mouse-model
#18
Tao Tao Liu, Bao Wen Liu, Zhi Gang He, Li Feng, San Guang Liu, Hong Bing Xiang
To examine if brain neurons involved in the efferent control of the kidneys possess melanocortin-4 receptor (MC4-R) and/or tryptophan hydroxylase (TPH). Retrograde tracing pseudorabies virus (PRV)-614 was injected into the kidneys in adult male MC4R-green fluorescent protein (GFP) transgenic mice. After a survival time of 3-7 days, spinal cord and brain were removed and sectioned, and processed for PRV-614 visualization. The neurochemical phenotype of PRV-614-positive neurons was identified using double or triple immunocytochemical labeling against PRV-614, MC4R, or TPH...
September 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27612207/exchange-factors-directly-activated-by-camp-mediate-melanocortin-4-receptor-induced-gene-expression
#19
Evi Glas, Harald Mückter, Thomas Gudermann, Andreas Breit
Gs protein-coupled receptors regulate many vital body functions by activation of cAMP response elements (CRE) via cAMP-dependent kinase A (PKA)-mediated phosphorylation of the CRE binding protein (CREB). Melanocortin 4 receptors (MC4R) are prototypical Gs-coupled receptors that orchestrate the hypothalamic control of food-intake and metabolism. Remarkably, the significance of PKA for MC4R-induced CRE-dependent transcription in hypothalamic cells has not been rigorously interrogated yet. In two hypothalamic cell lines, we observed that blocking PKA activity had only weak or no effects on reporter gene expression...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27606321/genetics-of-common-antipsychotic-induced-adverse-effects
#20
REVIEW
Raymond R MacNeil, Daniel J Müller
The effectiveness of antipsychotic drugs is limited due to accompanying adverse effects which can pose considerable health risks and lead to patient noncompliance. Pharmacogenetics (PGx) offers a means to identify genetic biomarkers that can predict individual susceptibility to antipsychotic-induced adverse effects (AAEs), thereby improving clinical outcomes. We reviewed the literature on the PGx of common AAEs from 2010 to 2015, placing emphasis on findings that have been independently replicated and which have additionally been listed to be of interest by PGx expert panels...
July 2016: Molecular Neuropsychiatry
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