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https://www.readbyqxmd.com/read/29763913/intraventricular-injection-of-lkb1-inhibits-the-formation-of-diet-induced-obesity-in-rats-by-activating-the-ampk-pomc-neurons-sympathetic-nervous-system-axis
#1
Pengjiao Xi, Jianying Du, Huimin Liang, Jie Han, Zhaoxia Wu, Haomin Wang, Lu He, Qiming Wang, Haize Ge, Yongmei Li, Jie Xue, Derun Tian
BACKGROUND/AIMS: Obesity is increasingly becoming a major public health problem worldwide. Peripheral LKB1 inhibits white fat generation, but the effect of central LKB1 on diet-induced obesity (DIO) is unknown. Therefore, we examined whether LKB1 over-expression in the hypothalamus can inhibit the development of obesity. METHODS: Adult male Sprague-Dawley rats were anesthetized and placed in a stereotaxic apparatus. LKB1-AAV-EGFP (2.0 × 108 or 2.0 × 1010 vector genomes) or Control-AAV-EGFP (2...
May 9, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29742429/diet-induced-growth-is-regulated-via-acquired-leptin-resistance-and-engages-a-pomc-somatostatin-growth-hormone-circuit
#2
Heiko Löhr, Simon Hess, Mafalda M A Pereira, Philip Reinoß, Sandra Leibold, Christel Schenkel, Claudia M Wunderlich, Peter Kloppenburg, Jens C Brüning, Matthias Hammerschmidt
Anorexigenic pro-opiomelanocortin (Pomc)/alpha-melanocyte stimulating hormone (αMSH) neurons of the hypothalamic melanocortin system function as key regulators of energy homeostasis, also controlling somatic growth across different species. However, the mechanisms of melanocortin-dependent growth control still remain ill-defined. Here, we reveal a thus-far-unrecognized structural and functional connection between Pomc neurons and the somatotropic hypothalamo-pituitary axis. Excessive feeding of larval zebrafish causes leptin resistance and reduced levels of the hypothalamic satiety mediator pomca...
May 8, 2018: Cell Reports
https://www.readbyqxmd.com/read/29736023/mc4r-agonism-promotes-durable-weight-loss-in-patients-with-leptin-receptor-deficiency
#3
Karine Clément, Heike Biebermann, I Sadaf Farooqi, Lex Van der Ploeg, Barbara Wolters, Christine Poitou, Lia Puder, Fred Fiedorek, Keith Gottesdiener, Gunnar Kleinau, Nicolas Heyder, Patrick Scheerer, Ulrike Blume-Peytavi, Irina Jahnke, Shubh Sharma, Jacek Mokrosinski, Susanna Wiegand, Anne Müller, Katja Weiß, Knut Mai, Joachim Spranger, Annette Grüters, Oliver Blankenstein, Heiko Krude, Peter Kühnen
Genetic defects underlying the melanocortin-4 receptor (MC4R) signaling pathway lead to severe obesity. Three severely obese LEPR-deficient individuals were administered the MC4R agonist setmelanotide, resulting in substantial and durable reductions in hyperphagia and body weight over an observation period of 45-61 weeks. Compared to formerly developed and tested MC4R agonists, setmelanotide has the unique capability of activating nuclear factor of activated T cell (NFAT) signaling and restoring function of this signaling pathway for selected MC4R variants...
May 7, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29726959/melanocortin-4-receptor-pathway-dysfunction-in-obesity-patient-stratification-aimed-at-mc4r-agonist-treatment
#4
Kristin L Ayers, Benjamin S Glicksberg, Alastair S Garfield, Simonne Longerich, Joseph A White, Pengwei Yang, Lei Du, Thomas W Chittenden, Jeffery R Gulcher, Sophie Roy, Fred Fiedorek, Keith Gottesdiener, Sarah Cohen, Kari E North, Eric E Schadt, Shuyu D Li, Rong Chen, Lex H T Van der Ploeg
Context: The hypothalamic melanocortin 4 receptor (MC4R)-pathway serves a critical role in regulating bodyweight. Loss of function (LoF) mutations in the MC4R pathway including mutations in the POMC (1), PCSK1, LEPR (2) or the MC4R genes (3) have been shown to be causative of early-onset severe obesity. Methods: Through a comprehensive epidemiological analysis of known and predicted LoF variants in the POMC, PCSK1 and LEPR genes, we sought to estimate the number of US individuals with bi-allelic MC4R pathway LoF variants...
May 2, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29717269/multiple-genetic-variations-confer-risks-for-obesity-and-type-2-diabetes-mellitus-in-arab-descendants-from-uae
#5
Wael Osman, Guan K Tay, Habiba Alsafar
BACKGROUND: The United Arab Emirates (UAE) is one of the countries most threatened with obesity. Here we investigated associations between hundreds of single-nucleotide polymorphisms (SNPs) and the following obesity indicators: body mass index (BMI), waist circumference (WC), and height. We also investigated the associations between obesity-related genes with type 2 diabetes mellitus (T2DM). METHODS: We tested 87, 58, and 586 SNPs in a previous genome-wide significance level for associations with BMI (n = 880), WC (n = 455), and height (n = 897), respectively...
March 12, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29704154/pharmacological-effect-of-human-melanocortin-2-receptor-accessory-protein-2-variants-on-hypothalamic-melanocortin-receptors
#6
Jinye Liang, Lei Li, Xuanxuan Jin, Bingxin Xu, Linyu Pi, Shangyun Liu, Wei Zhu, Cong Zhang, Bing Luan, Lulu Gong, Chao Zhang
PURPOSE: Melanocortin-3 receptor (MC3R), melanocortin-4 receptor (MC4R), and a recently identified melanocortin-2 receptor accessory protein 2 (MRAP2), are highly expressed in hypothalamus and coordinately regulate energy homeostasis, but the single cellular transcriptome of melanocortin system remains unknown. Several infrequent MRAP2 variants are reported from severe obese human patients but the mechanisms on how they affect melanocortin signaling are unclear. METHODS: First, we performed in silico analysis of mouse hypothalamus RNA sequencing datasets at single-cell resolution from two independent studies...
April 27, 2018: Endocrine
https://www.readbyqxmd.com/read/29696068/gene-polymorphisms-of-tnf-238g-a-tnf-308g-a-il10-1082g-a-tnfaip3-and-mc4r-and-comorbidity-occurrence-in-a-romanian-population-with-psoriasis
#7
Vlad Mihai Voiculescu, Iulia Solomon, Alexandra Popa, Carmen Cristina Draghici, Maria Dobre, Calin Giurcaneanu, Laura Maria Lucia Papagheorghe, Mihai Lupu
Rationale. Psoriasis is a prevalent chronic inflammatory disease with worldwide distribution affecting approximately 2% of the Caucasian population. There have been many population- and family-based studies that agree on the strong genetic component of this disease. Several studies have investigated the relationship between cytokine gene polymorphisms, psoriasis, and the occurrence of comorbidities but their data are conflicting. Objective. This study examines cytokine gene single-nucleotide polymorphisms (SNPs) in the context of psoriasis and metabolic syndrome, with a focus on the occurrence of comorbidities in psoriasis patients...
January 2018: Journal of Medicine and Life
https://www.readbyqxmd.com/read/29694503/neonatal-tobacco-smoke-reduces-thermogenesis-capacity-in-brown-adipose-tissue-in-adult-rats
#8
T C Peixoto, E G Moura, E Oliveira, V Younes-Rapozo, P N Soares, V S T Rodrigues, T R Santos, N Peixoto-Silva, J C Carvalho, C Calvino, E P S Conceição, D S Guarda, S Claudio-Neto, A C Manhães, P C Lisboa
Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT) hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower metabolic rate...
2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29691916/genomic-signatures-of-fine-scale-local-selection-in-atlantic-salmon-suggest-involvement-of-sexual-maturation-energy-homeostasis-and-immune-defence-related-genes
#9
Victoria L Pritchard, Hannu Mäkinen, Juha-Pekka Vähä, Jaakko Erkinaro, Panu Orell, Craig R Primmer
Elucidating the genetic basis of adaptation to the local environment can improve our understanding of how the diversity of life has evolved. In this study we used a dense SNP array to identify candidate loci potentially underlying fine-scale local adaptation within a large Atlantic salmon (Salmo salar) population. By combining outlier, gene-environment association, and haplotype homozygosity analyses, we identified multiple regions of the genome with strong evidence for diversifying selection. Several of these candidate regions had previously been identified in other studies, demonstrating that the same loci could be adaptively important in Atlantic salmon at sub-drainage, regional and continental scales...
April 25, 2018: Molecular Ecology
https://www.readbyqxmd.com/read/29686896/the-association-between-obesity-risk-genes-and-gestational-weight-gain-is-modified-by-dietary-intake-in-african-american-women
#10
Ying Meng, Susan W Groth, Dongmei Li
Obesity-risk genes have been associated with dietary intake, appetite regulation, and gestational weight gain (GWG). The purpose of this study was to examine whether dietary intake including total energy intake and macronutrients modify or mediate the association between obesity-risk genes and GWG. An observational study was conducted with 85 African American pregnant women. Sociodemographic, medical, and lifestyle factors and dietary recalls were collected during pregnancy. Seven obesity-risk genetic variants were genotyped...
2018: Journal of Nutrition and Metabolism
https://www.readbyqxmd.com/read/29679223/association-between-lepr-fto-mc4r-and-pparg-2-polymorphisms-with-obesity-traits-and-metabolic-phenotypes-in-school-aged-children
#11
Sílvia M Almeida, José M Furtado, Paulo Mascarenhas, Maria E Ferraz, José C Ferreira, Mariana P Monteiro, Manuel Vilanova, Fernando P Ferraz
PURPOSE: Evaluate the relationship of leptin receptor (LEPR) rs1137101, fat mass obesity-associated (FTO) receptors 9939609, melanocortin-4 receptors (MC4R) rs2229616 and rs17782313, and proliferator-activated receptor-gamma (PPARG) rs1801282 with clinical and metabolic phenotypes in prepubertal children. RESEARCH QUESTION: What is the effect of polymorphisms on clinical and metabolic phenotypes in prepubertal children? METHODS: A cross-sectional descriptive study was performed to evaluate anthropometric features, percentage body fat (%BF), biochemical parameters, and genotype in 773 prepubertal children...
April 20, 2018: Endocrine
https://www.readbyqxmd.com/read/29678289/pathophysiology-of-melanocortin-receptors-and-their-accessory-proteins
#12
REVIEW
T V Novoselova, L F Chan, A J L Clark
The melanocortin receptors (MCRs) and their accessory proteins (MRAPs) are involved in regulation of a diverse range of endocrine pathways. Genetic variants of these components result in phenotypic variation and disease. The MC1R is expressed in skin and variants in the MC1R gene are associated with ginger hair color. The MC2R mediates the action of ACTH in the adrenal gland to stimulate glucocorticoid production and MC2R mutations result in familial glucocorticoid deficiency (FGD). MC3R and MC4R are involved in metabolic regulation and their gene variants are associated with severe pediatric obesity, whereas the function of MC5R remains to be fully elucidated...
April 2018: Best Practice & Research. Clinical Endocrinology & Metabolism
https://www.readbyqxmd.com/read/29658457/-association-between-copy-number-variations-and-risk-of-overweight-obesity-among-han-uyghur-and-kazak-children
#13
Abidan Ainiwaer, Adalibieke Adalibieke, Bing-Xue Huang, Y E Yekejiergeli, Ya-Lan Dou, Jie Wu, Jiang-Hong Dai
OBJECTIVE: To study the association between the prevalence of overweight/obesity and copy number variations (CNVs) among Han, Uyghur, and Kazak children in Xinjiang, China. METHODS: The kindergartens in Ili, Altay, and Karamay in Xinjiang were selected as research sites, and stratified cluster sampling was used to select the children aged 3-7 years. Body height and body weight were measured, and exfoliated buccal mucosa cells were collected. CNVplex® was used to measure the CNVs of FTO_1, IRX3_1, IRX3_2, MC4R_1, and MC4R_2...
April 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/29642894/activation-of-melanocortin-receptor-4-with-ro27-3225-attenuates-neuroinflammation-through-ampk-jnk-p38-mapk-pathway-after-intracerebral-hemorrhage-in-mice
#14
Shengpan Chen, Lianhua Zhao, Prativa Sherchan, Yan Ding, Jing Yu, Derek Nowrangi, Jiping Tang, Ying Xia, John H Zhang
BACKGROUND: Neuroinflammation plays an important role in the pathogenesis of intracerebral hemorrhage (ICH)-induced secondary brain injury. Activation of melanocortin receptor 4 (MC4R) has been shown to elicit anti-inflammatory effects in many diseases. The objective of this study was to explore the role of MC4R activation on neuroinflammation in a mouse ICH model and to investigate the contribution of adenosine monophosphate-activated protein kinase (AMPK)/c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (p38 MAPK) pathway in MC4R-mediated protection...
April 11, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29623786/identification-of-two-additional-genomic-loci-responsible-for-experimentally-induced-testicular-teratoma-2-and-3-ett2-and-ett3
#15
Takehiro Miyazaki, Manami Fukui, Emi Inagaki, Kenji Miki, Shuji Takabayashi, Hideki Katoh, Yukio Ohira, Motoko Noguchi, Toshinobu Tokumoto
Experimental testicular teratomas (ETTs) can be induced in 129/Sv mouse by E12.5 fetal testes transplant into adult testes. Previously, we conducted linkage analysis to explore candidate genes possibly involved in ETT development using F2 intercross fetuses derived from F1[LTXBJ × 129/Sv- + /Ter (+ /+)] hybrids. By linkage analysis on Chr 18 and Chr 19, we identified the genomic locus for experimental testicular teratoma 1 (ett1) on Chr 18. In the present study, we conducted additional mapping and linkage analysis on teratoma susceptibility and genome composition on Chr 1-17...
April 2018: Zoological Science
https://www.readbyqxmd.com/read/29599718/re-evaluation-of-adrenocorticotropic-hormone-and-melanocyte-stimulating-hormone-activation-of-gpr139-in-vitro
#16
Diane Nepomuceno, Chester Kuei, Curt Dvorak, Timothy Lovenberg, Changlu Liu, Pascal Bonaventure
It is now well established that GPR139, a G-protein coupled receptor exclusively expressed in the brain and pituitary, is activated by the essential amino acids L-tryptophan (L-Trp) and L-phenylalanine (L-Phe) via Gαq -coupling. The in vitro affinity and potency values of L-Trp and L-Phe are within the physiological concentration ranges of L-Trp and L-Phe. A recent paper suggests that adrenocorticotropic hormone (ACTH), α and β melanocyte stimulating hormones (α-MSH and β-MSH) and derivatives α-MSH1-9 /α-MSH1-10 can also activate GPR139 in vitro ...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29598821/association-between-the-dna-methylations-of-pomc-mc4r-and-hnf4a-and-metabolic-profiles-in-the-blood-of-children-aged-7-9-years
#17
Eun Jin Kwon, Young-Ah You, Bohyun Park, Eun Hee Ha, Hae Soon Kim, Hyesook Park, Young Ju Kim
BACKGROUND: Proopiomelanocortin (POMC), melanocortin 4 receptor (MC4R), and hepatocyte nuclear factor 4 alpha (HNF4A) are closely associated with weight gain and metabolic traits. In a previous study, we demonstrated associations between the methylations of POMC, MC4R, and HNF4A and metabolic profiles at birth. However, little is known about these associations in obese children. To evaluate the clinical utility of epigenetic biomarkers, we investigated to determine whether an association exists between the methylations of POMC, MC4R, and HNF4A and metabolic profiles in blood of normal weight and overweight and obese children...
March 29, 2018: BMC Pediatrics
https://www.readbyqxmd.com/read/29568105/early-childhood-bmi-trajectories-in-monogenic-obesity-due-to-leptin-leptin-receptor-and-melanocortin-4-receptor-deficiency
#18
Katja Kohlsdorf, Adriana Nunziata, Jan-Bernd Funcke, Stephanie Brandt, Julia von Schnurbein, Heike Vollbach, Belinda Lennerz, Maria Fritsch, Susanne Greber-Platzer, Elke Fröhlich-Reiterer, Manuel Luedeke, Guntram Borck, Klaus-Michael Debatin, Pamela Fischer-Posovszky, Martin Wabitsch
OBJECTIVE: To evaluate whether early childhood body mass index (BMI) is an appropriate indicator for monogenic obesity. METHODS: A cohort of n = 21 children living in Germany or Austria with monogenic obesity due to congenital leptin deficiency (group LEP, n = 6), leptin receptor deficiency (group LEPR, n = 6) and primarily heterozygous MC4 receptor deficiency (group MC4R, n = 9) was analyzed. A control group (CTRL) was defined that consisted of n = 22 obese adolescents with no mutation in the above mentioned genes...
February 27, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29559925/agouti-signaling-protein-and-its-receptors-as-potential-molecular-markers-for-intramuscular-and-body-fat-deposition-in-cattle
#19
Yinuo Liu, Elke Albrecht, Lisa Schering, Christa Kuehn, Runjun Yang, Zhihui Zhao, Steffen Maak
Transcriptome analyses of bovine muscle tissue differing in intramuscular fat (IMF) content identified agouti signaling protein (ASIP) as a promising candidate gene for fat deposition. The protein is secreted from adipocytes and may serve as a signaling molecule in cross-talk between adipocytes and muscle fibers or other cells. Known receptors for ASIP are the melanocortin receptors (e.g., MC4R) and attractin (ATRN). The present study was conducted to determine relationships between the expression of ASIP and its receptors in different bovine tissues with fat deposition...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29545738/subdiaphragmatic-vagotomy-with-pyloroplasty-ameliorates-the-obesity-caused-by-genetic-deletion-of-the-melanocortin-4-receptor-in-the-mouse
#20
Ghazaul Dezfuli, Richard A Gillis, Jaclyn E Tatge, Kimbell R Duncan, Kenneth L Dretchen, Patrick G Jackson, Joseph G Verbalis, Niaz Sahibzada
Background/Objectives: We tested the hypothesis that abolishing vagal nerve activity will reverse the obesity phenotype of melanocortin 4 receptor knockout mice ( Mc4r -/- ). Subjects/Methods: In two separate studies, we examined the efficacy of bilateral subdiaphragmatic vagotomy (SDV) with pyloroplasty in the prevention and treatment of obesity in Mc4r -/- mice. Results: In the first study, SDV prevented >20% increase in body weight (BW) associated with this genotype. This was correlated with a transient reduction in overall food intake (FI) in the preventative arm of the study...
2018: Frontiers in Neuroscience
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