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Eun Hee Koh, Yong Chen, David A Bader, Mark P Hamilton, Bin He, Brian York, Shingo Kajimura, Sean E McGuire, Sean M Hartig
The acquisition of beige adipocyte features by white fat cells corresponds to protection against obesity-induced metabolic diseases in humans and animal models of type 2 diabetes. In adipose tissue, expression of the E2-SUMO ligase Ubiquitin Carrier Protein 9 (Ubc9) is positively correlated with markers of insulin resistance and corresponds with impaired browning of human white adipocytes. However, the molecular regulation of Ubc9 expression in adipocytes and other cells remains unclear. In this study, we demonstrated the mRNA and protein expression of Ubc9 are regulated by the microRNA miRNA-30a (miR-30a) in human subcutaneous adipocytes...
October 10, 2016: Journal of Biological Chemistry
Sílvia Rocha-Rodrigues, Amaia Rodríguez, Alexandra M Gouveia, Inês O Gonçalves, Sara Becerril, Beatriz Ramírez, Jorge Beleza, Gema Frühbeck, António Ascensão, José Magalhães
AIMS: Exercise-stimulated myokine secretion into circulation may be related with browning in white adipose tissue (WAT), representing a positive metabolic effect on whole-body fat mass. However, limited information is yet available regarding the impact of exercise on myokine-related modulation of adipocyte phenotype in WAT from obese rats. MAIN METHODS: Sprague-Dawley rats (n=60) were divided into sedentary and voluntary physical activity (VPA) groups and fed with standard (35kcal% fat) or high-fat (HFD, 71kcal% fat)-isoenergetic diets...
September 27, 2016: Life Sciences
Kazuki Kodo, Sang-Ging Ong, Fereshteh Jahanbani, Vittavat Termglinchan, Keiichi Hirono, Kolsoum InanlooRahatloo, Antje D Ebert, Praveen Shukla, Oscar J Abilez, Jared M Churko, Ioannis Karakikes, Gwanghyun Jung, Fukiko Ichida, Sean M Wu, Michael P Snyder, Daniel Bernstein, Joseph C Wu
Left ventricular non-compaction (LVNC) is the third most prevalent cardiomyopathy in children and its pathogenesis has been associated with the developmental defect of the embryonic myocardium. We show that patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from LVNC patients carrying a mutation in the cardiac transcription factor TBX20 recapitulate a key aspect of the pathological phenotype at the single-cell level and this was associated with perturbed transforming growth factor beta (TGF-β) signalling...
October 2016: Nature Cell Biology
Qiyuan Yang, Xingwei Liang, Xiaofei Sun, Lupei Zhang, Xing Fu, Carl J Rogers, Anna Berim, Shuming Zhang, Songbo Wang, Bo Wang, Marc Foretz, Benoit Viollet, David R Gang, Buel D Rodgers, Mei-Jun Zhu, Min Du
Promoting brown adipose tissue (BAT) development is an attractive strategy for the treatment of obesity, as activated BAT dissipates energy through thermogenesis; however, the mechanisms controlling BAT formation are not fully understood. We hypothesized that as a master regulator of energy metabolism, AMP-activated protein kinase (AMPK) may play a direct role in the process and found that AMPKα1 (PRKAA1) ablation reduced Prdm16 expression and impaired BAT development. During early brown adipogenesis, the cellular levels of α-ketoglutarate (αKG), a key metabolite required for TET-mediated DNA demethylation, were profoundly increased and required for active DNA demethylation of the Prdm16 promoter...
October 11, 2016: Cell Metabolism
Jean Z Lin, Stephen R Farmer
In this issue of Genes & Development, Zeng and colleagues (pp. 1822-1836) identify lysine-specific demethylase 1 (LSD1) as a pivotal regulator of whole-body energy expenditure by controlling the oxidative and thermogenic activity of brown adipose tissue (BAT). They show that LSD1 interacts with PRDM16 to repress select white adipose tissue (WAT) genes but also represses hydroxysteroid 11-β-dehydrogenase 1 (HSD11B1) independently of PRDM16 to prevent production of glucocorticoids that impair BAT functions. Their study provides important insight into epigenetic mechanisms regulating the function of BAT...
August 15, 2016: Genes & Development
Sho Nishikawa, Hiroki Aoyama, Misa Kamiya, Jun Higuchi, Aiko Kato, Minoru Soga, Taeko Kawai, Kazuki Yoshimura, Shigenori Kumazawa, Takanori Tsuda
Induction of brown-like adipocytes (beige/brite cells) in white adipose tissue (WAT) suggests a new approach for preventing and treating obesity via induction of thermogenesis associated with uncoupling protein 1 (UCP1). However, whether diet-derived factors can directly induce browning of white adipocytes has not been well established. In addition, the underlying mechanism of induction of brown-like adipocytes by diet-derived factors has been unclear. Here, we demonstrate that artepillin C (ArtC), which is a typical Brazilian propolis-derived component, significantly induces brown-like adipocytes in murine C3H10T1/2 cells and primary inguinal WAT (iWAT)-derived adipocytes...
2016: PloS One
Shicheng Guo, Qi Zhu, Ting Jiang, Rongsheng Wang, Yi Shen, Xiao Zhu, Yan Wang, Fengmin Bai, Qin Ding, Xiaodong Zhou, Guangjie Chen, Dong Yi He
INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints. Recent evidence indicated the epigenetic changes may contribute to the pathogenesis of RA. METHOD: To understand the extent and nature of dysregulated DNA methylation in RA CD4T cells, we performed a genome-wide DNA methylation study in CD4 + T cells in 12 RA patients compared to 12 matched normal healthy controls. Cytosine methylation status was quantified with Illumina methylation 450K microarray...
September 1, 2016: Modern Rheumatology
Xing Zeng, Mark P Jedrychowski, Yi Chen, Sara Serag, Gareth G Lavery, Steve P Gygi, Bruce M Spiegelman
Brown adipocytes display phenotypic plasticity, as they can switch between the active states of fatty acid oxidation and energy dissipation versus a more dormant state. Cold exposure or β-adrenergic stimulation favors the active thermogenic state, whereas sympathetic denervation or glucocorticoid administration promotes more lipid accumulation. Our understanding of the molecular mechanisms underlying these switches is incomplete. Here we found that LSD1 (lysine-specific demethylase 1), a histone demethylase, regulates brown adipocyte metabolism in two ways...
August 15, 2016: Genes & Development
John R Shaffer, Ekaterina Orlova, Myoung Keun Lee, Elizabeth J Leslie, Zachary D Raffensperger, Carrie L Heike, Michael L Cunningham, Jacqueline T Hecht, Chung How Kau, Nichole L Nidey, Lina M Moreno, George L Wehby, Jeffrey C Murray, Cecelia A Laurie, Cathy C Laurie, Joanne Cole, Tracey Ferrara, Stephanie Santorico, Ophir Klein, Washington Mio, Eleanor Feingold, Benedikt Hallgrimsson, Richard A Spritz, Mary L Marazita, Seth M Weinberg
Numerous lines of evidence point to a genetic basis for facial morphology in humans, yet little is known about how specific genetic variants relate to the phenotypic expression of many common facial features. We conducted genome-wide association meta-analyses of 20 quantitative facial measurements derived from the 3D surface images of 3118 healthy individuals of European ancestry belonging to two US cohorts. Analyses were performed on just under one million genotyped SNPs (Illumina OmniExpress+Exome v1.2 array) imputed to the 1000 Genomes reference panel (Phase 3)...
August 2016: PLoS Genetics
Anne Drougard, Audren Fournel, Alysson Marlin, Etienne Meunier, Anne Abot, Tereza Bautzova, Thibaut Duparc, Katie Louche, Aurelie Batut, Alexandre Lucas, Sophie Le-Gonidec, Jean Lesage, Xavier Fioramonti, Cedric Moro, Philippe Valet, Patrice D Cani, Claude Knauf
Apelin is a bioactive peptide involved in the control of energy metabolism. In the hypothalamus, chronic exposure to high levels of apelin is associated with an increase in hepatic glucose production, and then contributes to the onset of type 2 diabetes. However, the molecular mechanisms behind deleterious effects of chronic apelin in the brain and consequences on energy expenditure and thermogenesis are currently unknown. We aimed to evaluate the effects of chronic intracerebroventricular (icv) infusion of apelin in normal mice on hypothalamic inflammatory gene expression, energy expenditure, thermogenesis and brown adipose tissue functions...
2016: Scientific Reports
Inmaculada Moreno-Santos, Luis Miguel Pérez-Belmonte, Manuel Macías-González, María José Mataró, Daniel Castellano, Miguel López-Garrido, Carlos Porras-Martín, Pedro L Sánchez-Fernández, Juan José Gómez-Doblas, Fernando Cardona, Eduardo de Teresa-Galván, Manuel Jiménez-Navarro
BACKGROUND: Although recent studies indicate that epicardial adipose tissue expresses brown fat-like genes, such as PGC1α, UCP1 and PRDM16, the association of these genes with type 2 diabetes mellitus (DM2) in coronary artery disease (CAD) remains unknown. METHODS: PGC1α, UCP1, and PRDM16 mRNAs expression levels were measured by real-time PCR in epicardial and thoracic subcutaneous adipose tissue from 44 CAD patients (22 with DM2 [CAD-DM2] and 22 without DM2 [CAD-NDM2]) and 23 non-CAD patients (NCAD)...
2016: Journal of Translational Medicine
Shaoxing Zhu, Yipeng Xu, Mei Song, Guiping Chen, Hua Wang, Yang Zhao, Zongping Wang, Fangyin Li
Histone methylation, which is regulated by histone methyltransferases (HMTs) and histone demethylases (HDMs), has been indicated to be involved in a variety of diseases, particularly in cancer, including androgen‑independent prostate cancer (PCa). However, the functions of HMTs and HDTs in cancer have largely remained elusive. The present study, utilized an RNA interference screening using a lentiviral small hairpin (sh)RNA library to systematically elucidate the function of HMTs and HDTs in PCa cell growth and viability...
October 2016: Molecular Medicine Reports
Suresh Ambati, Ping Yu, Elizabeth C McKinney, Muthugapatti K Kandasamy, Diane Hartzell, Clifton A Baile, Richard B Meagher
BACKGROUND: Obesity-related comorbidities are thought to result from the reprogramming of the epigenome in numerous tissues and cell types, and in particular, mature adipocytes within visceral and subcutaneous adipose tissue, VAT and SAT. The cell-type specific chromatin remodeling of mature adipocytes within VAT and SAT is poorly understood, in part, because of the difficulties of isolating and manipulating large fragile mature adipocyte cells from adipose tissues. METHODS: We constructed MA-INTACT (Mature Adipocyte-Isolation of Nuclei TAgged in specific Cell Types) mice using the adiponectin (ADIPOQ) promoter (ADNp) to tag the surface of mature adipocyte nuclei with a reporter protein...
2016: BMC Obesity
Shailendra P Singh, Joseph Schragenheim, Jian Cao, John R Falck, Nader G Abraham, Lars Bellner
BACKGROUND/OBJECTIVES: Obesity is a risk factor in the development of type 2 diabetes mellitus (DM2), which is associated with increased morbidity and mortality, predominantly as a result of cardiovascular complications. Increased adiposity is a systemic condition characterized by increased oxidative stress (ROS), increased inflammation, inhibition of anti-oxidant genes such as HO-1 and increased degradation of epoxyeicosatrienoic acids (EETs). We previously demonstrated that EETs attenuate mitochondrial ROS...
September 2016: Prostaglandins & Other Lipid Mediators
Alessandra Pasut, Natasha C Chang, Uxia Gurriaran Rodriguez, Sharlene Faulkes, Hang Yin, Melanie Lacaria, Hong Ming, Michael A Rudnicki
Pax7 is a nodal transcription factor that is essential for regulating the maintenance, expansion, and myogenic identity of satellite cells during both neonatal and adult myogenesis. Deletion of Pax7 results in loss of satellite cells and impaired muscle regeneration. Here, we show that ectopic expression of the constitutively active intracellular domain of Notch1 (NICD1) rescues the loss of Pax7-deficient satellite cells and restores their proliferative potential. Strikingly NICD1-expressing satellite cells do not undergo myogenic differentiation and instead acquire a brown adipogenic fate both in vivo and in vitro...
July 12, 2016: Cell Reports
Sandra Côté, Valérie Gagné-Ouellet, Simon-Pierre Guay, Catherine Allard, Andrée-Anne Houde, Patrice Perron, Jean-Patrice Baillargeon, Daniel Gaudet, Renée Guérin, Diane Brisson, Marie-France Hivert, Luigi Bouchard
BACKGROUND: Children exposed to gestational diabetes mellitus (GDM) are at a higher risk of developing obesity and type 2 diabetes. This susceptibility might involve brown adipose tissue (BAT), which is suspected to protect against obesity. The objective of this study is to assess whether fetal exposure to maternal hyperglycemia is associated with DNA methylation variations in genes involved in BAT genesis and activation. METHODS: DNA methylation levels at the PRDM16, BMP7, CTBP2, and PPARGC1α gene loci were measured in placenta samples using bisulfite pyrosequencing in E-21 (n = 133; 33 cases of GDM) and the HumanMethylation450 array in Gen3G (n = 172, all from non-diabetic women) birth cohorts...
2016: Clinical Epigenetics
Joseph F Pierre, Kristina B Martinez, Honggang Ye, Anuradha Nadimpalli, Timothy C Morton, Jinghui Yang, Qiang Wang, Noelle Patno, Eugene B Chang, Deng Ping Yin
The metabolic benefits induced by gastric bypass, currently the most effective treatment for morbid obesity, are associated with bile acid (BA) delivery to the distal intestine. However, mechanistic insights into BA signaling in the mediation of metabolic benefits remain an area of study. The bile diversion () mouse model, in which the gallbladder is anastomosed to the distal jejunum, was used to test the specific role of BA in the regulation of glucose and lipid homeostasis. Metabolic phenotype, including body weight and composition, glucose tolerance, energy expenditure, thermogenesis genes, total BA and BA composition in the circulation and portal vein, and gut microbiota were examined...
August 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Sujith Rajan, Kripa Shankar, Muheeb Beg, Salil Varshney, Abhishek Gupta, Ankita Srivastava, Durgesh Kumar, Raj K Mishra, Zakir Hussain, Jiaur R Gayen, Anil N Gaikwad
The growing pandemics of diabetes have become a real threat to world economy. Hyperinsulinemia and insulin resistance are closely associated with the pathophysiology of type 2 diabetes. In pretext of brown adipocytes being considered as the therapeutic strategy for the treatment of obesity and insulin resistance, we have tried to understand the effect of hyperinsulinemia on brown adipocyte function. We here with for the first time report that hyperinsulinemia-induced insulin resistance in brown adipocyte is also accompanied with reduced insulin sensitivity and brown adipocyte characteristics...
September 2016: Journal of Endocrinology
Omar Abdul-Rahman, Endre Kristóf, Quang-Minh Doan-Xuan, András Vida, Lilla Nagy, Ambrus Horváth, József Simon, Tamás Maros, István Szentkirályi, Lehel Palotás, Tamás Debreceni, Péter Csizmadia, Tamás Szerafin, Tamás Fodor, Magdolna Szántó, Attila Tóth, Borbála Kiss, Zsolt Bacsó, Péter Bai
Beige adipocytes are special cells situated in the white adipose tissue. Beige adipocytes, lacking thermogenic cues, morphologically look quite similar to regular white adipocytes, but with a markedly different response to adrenalin. White adipocytes respond to adrenergic stimuli by enhancing lipolysis, while in beige adipocytes adrenalin induces mitochondrial biogenesis too. A key step in the differentiation and function of beige adipocytes is the deacetylation of peroxisome proliferator-activated receptor (PPARγ) by SIRT1 and the consequent mitochondrial biogenesis...
2016: PloS One
Hanying Ding, Shasha Zheng, Daniel Garcia-Ruiz, Dongxia Hou, Zhe Wei, Zhicong Liao, Limin Li, Yujing Zhang, Xiao Han, Ke Zen, Chen-Yu Zhang, Jing Li, Xiaohong Jiang
Visceral adiposity is strongly associated with metabolic disease risk, whereas subcutaneous adiposity is comparatively benign. However, their relative physiological importance in energy homeostasis remains unclear. Here, we show that after 24-h fasting, the subcutaneous adipose tissue of mice acquires key properties of visceral fat. During this fast-induced 'visceralization', upregulation of miR-149-3p directly targets PR domain containing 16 (PRDM16), a key coregulatory protein required for the 'browning' of white fat...
2016: Nature Communications
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