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Brown adipose tissue epigenetics

J A Gill, Michele A La Merrill
Metabolic disease is a leading cause of death worldwide, and obesity, a central risk factor, is reaching epidemic proportions. Energy expenditure and brown adipose tissue (BAT) thermogenesis are implicated in metabolic disease, and it is becoming evident that impaired BAT activity is regulated by gene/environment interactions. Peroxisome proliferator-activated receptor γ coactivator 1α (Pgc-1α) is a critical regulator of BAT thermogenesis, which is highly inducible by environmental stimuli such as cold and diet...
May 2017: Environmental Epigenetics
Julia A Taylor, Keiko Shioda, Shino Mitsunaga, Shiomi Yawata, Brittany M Angle, Susan C Nagel, Frederick S Vom Saal, Toshi Shioda
Exposure of mammalian fetuses to endocrine disruptors can increase the risk of adult-onset diseases. We previously showed that exposure of mouse fetuses to bisphenol A (BPA) caused adult-onset obesity. To examine roles of epigenetic changes in this delayed toxicity, we determined the effects of fetal mouse exposure to BPA on genome-wide DNA methylation and messenger RNA (mRNA) expression in gonadal white adipose tissues (WATs) by deep sequencing, bisulfite pyrosequencing, and real-time quantitative polymerase chain reaction...
February 1, 2018: Endocrinology
Ariana Vargas-Castillo, Rebeca Fuentes-Romero, Leonardo A Rodriguez-Lopez, Nimbe Torres, Armando R Tovar
Obesity is characterized by an excess of white adipose tissue (WAT). Recent evidence has demonstrated that WAT can change its phenotype to a brown-like adipose tissue known as beige/brite adipose tissue. This transition is characterized by an increase in thermogenic capacity mediated by uncoupling protein 1 (UCP1). This browning process is a potential new target for treating obesity. The aim of this review is to integrate the different mechanisms by which beige/brite adipocytes are formed and to describe the physiological, pharmacological and nutritional inducers that can promote browning...
July 2017: Archives of Medical Research
Liangyou Rui
Brown and beige adipocytes arise from distinct developmental origins. Brown adipose tissue (BAT) develops embryonically from precursors that also give to skeletal muscle. Beige fat develops postnatally and is highly inducible. Beige fat recruitment is mediated by multiple mechanisms, including de novo beige adipogenesis and white-to-brown adipocyte transdifferentiaiton. Beige precursors reside around vasculatures, and proliferate and differentiate into beige adipocytes. PDGFRα+Ebf2+ precursors are restricted to beige lineage cells, while another PDGFRα+ subset gives rise to beige adipocytes, white adipocytes, or fibrogenic cells...
September 12, 2017: Comprehensive Physiology
Juliane Weiner, Kerstin Rohde, Kerstin Krause, Konstanze Zieger, Nora Klöting, Susan Kralisch, Peter Kovacs, Michael Stumvoll, Matthias Blüher, Yvonne Böttcher, John T Heiker
OBJECTIVE: Several studies have demonstrated anti-diabetic and anti-obesogenic properties of visceral adipose tissue-derived serine protease inhibitor (vaspin) and so evoked its potential use for treatment of obesity-related diseases. The aim of the study was to unravel physiological regulators of vaspin expression and secretion with a particular focus on its role in brown adipose tissue (BAT) biology. METHODS: We analyzed the effects of obesogenic diets and cold exposure on vaspin expression in liver and white and brown adipose tissue (AT) and plasma levels...
June 2017: Molecular Metabolism
Yun-Hee Lee, Sang-Nam Kim, Hyun-Jung Kwon, James G Granneman
Sustained β3 adrenergic receptor (ADRB3) activation simultaneously upregulates fatty acid synthesis and oxidation in mouse brown, beige, and white adipose tissues; however, the cellular basis of this dual regulation is not known. Treatment of mice with the ADRB3 agonist CL316,243 (CL) increased expression of fatty acid synthase (FASN) and medium chain acyl-CoA dehydrogenase (MCAD) protein within the same cells in classic brown and white adipose tissues. Surprisingly, in inguinal adipose tissue, CL-upregulated FASN and MCAD in distinct cell populations: high MCAD expression occurred in multilocular adipocytes that co-expressed UCP1+, whereas high FASN expression occurred in paucilocular adipocytes lacking detectable UCP1...
January 3, 2017: Scientific Reports
Saad Misfer Al-Qahtani, Galyna Bryzgalova, Ismael Valladolid-Acebes, Marion Korach-André, Karin Dahlman-Wright, Suad Efendić, Per-Olof Berggren, Neil Portwood
Both functional ovaries and estrogen replacement therapy (ERT) reduce the risk of type 2 diabetes (T2D). Understanding the mechanisms underlying the antidiabetic effects of 17β-estradiol (E2) may permit the development of a molecular targeting strategy for the treatment of metabolic disease. This study examines how the promotion of insulin sensitivity and weight loss by E2 treatment in high-fat-diet (HFD)-fed mice involve several anti-adipogenic processes in the visceral adipose tissue. Magnetic resonance imaging (MRI) revealed specific reductions in visceral adipose tissue volume in HFD+E2 mice, compared with HFD mice...
January 1, 2017: Hormone Molecular Biology and Clinical Investigation
A Ferrari, E Fiorino, R Longo, S Barilla, N Mitro, G Cermenati, M Giudici, D Caruso, A Mai, U Guerrini, E De Fabiani, M Crestani
BACKGROUND/OBJECTIVES: In the last decade, a strict link between epigenetics and metabolism has been demonstrated. Histone deacetylases (HDACs) have emerged as key epigenetic regulators involved in metabolic homeostasis in normal and pathologic conditions. Here we investigated the effect of the class I HDAC inhibitor MS-275 in a model of obesity induced by a high-fat diet (HFD). METHODS: C57BL6/J male mice were fed HFD for 17 weeks and then randomized in two groups, treated intraperitoneally with vehicle dimethylsulfoxide (DMSO) or with the class I selective HDAC inhibitor MS-275 every other day for 22 days...
February 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Audrey Sambeat, Olga Gulyaeva, Jon Dempersmier, Hei Sook Sul
In contrast to white adipose tissue (WAT), which stores energy in the form of triglycerides, brown adipose tissue (BAT) dissipates energy by producing heat to maintain body temperature by burning glucose and fatty acids in a process called adaptive thermogenesis. The presence of an inducible thermogenic adipose tissue, and its beneficial effects for maintaining body weight and glucose and lipid homeostasis, has raised intense interest in understanding the regulation of thermogenesis. Elucidating the regulatory mechanisms underlying the thermogenic adipose program may provide excellent targets for therapeutics against obesity and diabetes...
January 2017: Trends in Endocrinology and Metabolism: TEM
Yan Chen, Jeesun Kim, Ruipeng Zhang, Xiaoqin Yang, Yong Zhang, Jianwu Fang, Zhui Chen, Lin Teng, Xiaowei Chen, Hui Ge, Peter Atadja, En Li, Taiping Chen, Wei Qi
Adipose tissue plays important roles in animals. White fat stores energy in lipids, while brown fat is responsible for nonshivering thermogenesis through UCP1-mediated energy dissipation. Although epigenetic mechanisms modulate differentiation in multiple lineages, the epigenetic regulation of brown adipocyte differentiation is poorly understood. By screening a collection of epigenetic compounds, we found that Lysine-Specific Demethylase 1 (LSD1) inhibitors repress brown adipocyte differentiation. RNAi-mediated Lsd1 knockdown causes a similar effect, which can be rescued by expression of wild-type but not catalytic-inactive LSD1...
October 20, 2016: Cell Chemical 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
Olivier Goupille, Tipparat Penglong, Zahra Kadri, Marine Granger-Locatelli, Suthat Fucharoen, Leila Maouche-Chrétien, Stéphane Prost, Philippe Leboulch, Stany Chrétien
The bromodomain and extraterminal (BET) domain family proteins are epigenetic modulators involved in the reading of acetylated lysine residues. The first BET protein inhibitor to be identified, (+)-JQ1, a thienotriazolo-1, 4-diazapine, binds selectively to the acetyl lysine-binding pocket of BET proteins. We evaluated the impact on adipogenesis of this druggable targeting of chromatin epigenetic readers, by investigating the physiological consequences of epigenetic modifications through targeting proteins binding to chromatin...
April 15, 2016: Biochemical and Biophysical Research Communications
Matthew Van De Pette, Simon J Tunster, Grainne I McNamara, Tatyana Shelkovnikova, Steven Millership, Lindsay Benson, Stuart Peirson, Mark Christian, Antonio Vidal-Puig, Rosalind M John
The accurate diagnosis and clinical management of the growth restriction disorder Silver Russell Syndrome (SRS) has confounded researchers and clinicians for many years due to the myriad of genetic and epigenetic alterations reported in these patients and the lack of suitable animal models to test the contribution of specific gene alterations. Some genetic alterations suggest a role for increased dosage of the imprinted CYCLIN DEPENDENT KINASE INHIBITOR 1C (CDKN1C) gene, often mutated in IMAGe Syndrome and Beckwith-Wiedemann Syndrome (BWS)...
March 2016: PLoS Genetics
Dongning Pan, Lei Huang, Lihua J Zhu, Tie Zou, Jianhong Ou, William Zhou, Yong-Xu Wang
Progression from brown preadipocytes to adipocytes engages two transcriptional programs: the expression of adipogenic genes common to both brown fat (BAT) and white fat (WAT), and the expression of BAT-selective genes. However, the dynamics of chromatin states and epigenetic enzymes involved remain poorly understood. Here we show that BAT development is selectively marked and guided by repressive H3K27me3 and is executed by its demethylase Jmjd3. We find that a significant subset of BAT-selective genes, but not common fat genes or WAT-selective genes, are demarcated by H3K27me3 in both brown and white preadipocytes...
December 7, 2015: Developmental Cell
Thomas Tsiloulis, Matthew J Watt
Adipose tissue is a major regulator of metabolism in health and disease. The prominent roles of adipose tissue are to sequester fatty acids in times of energy excess and to release fatty acids via the process of lipolysis during times of high-energy demand, such as exercise. The fatty acids released during lipolysis are utilized by skeletal muscle to produce adenosine triphosphate to prevent fatigue during prolonged exercise. Lipolysis is controlled by a complex interplay between neuro-humoral regulators, intracellular signaling networks, phosphorylation events involving protein kinase A, translocation of proteins within the cell, and protein-protein interactions...
2015: Progress in Molecular Biology and Translational Science
Lin Zha, Fenfen Li, Rui Wu, Liana Artinian, Vincent Rehder, Liqing Yu, Houjie Liang, Bingzhong Xue, Hang Shi
Brown adipocytes function to dissipate energy as heat through adaptive thermogenesis. Understanding the molecular mechanisms underlying the brown fat thermogenic program may provide insights for the development of therapeutic approaches in the treatment of obesity. Most studies investigating the mechanisms underlying brown fat development focus on genetic mechanisms; little is known about the epigenetic mechanisms in this process. We have discovered that ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX), a histone demethylase for di- or tri-methylated histone 3 lysine 27 (H3K27me2/3), plays a potential role in regulating brown adipocyte thermogenic program...
October 9, 2015: Journal of Biological Chemistry
Xiao Li, Jinquan Wang, Zheng Jiang, Feng Guo, Paul D Soloway, Ruqian Zhao
The positive regulatory domain containing 16 (PRDM16) is commonly regarded as a "switch" controlling the transdifferentiation of myoblasts to brown adipocytes. The N-positive regulatory (PR) domain, which is highly homologous to SET domain, is a characteristic structure for the PRDM family. Many SET domain containing proteins and several PRDM members have been found to possess histone methyltransferase activity, yet the role of PRDM16 and its PR domain in the epigenetic regulation of myogenic and adipogenic genes during myoblasts/adipocytes transdifferentiation remains unexplored...
October 10, 2015: Gene
Jun Wu, Heejin Jun, Joseph R McDermott
Thermogenic fat cells that convert chemical energy into heat are present in both mice and humans. Recent years have witnessed great advances in our understanding of the regulation of these adipocytes and an increased appreciation of the potential these cells have to counteract obesity. We summarize recent efforts to understand the formation of these fat cells and critically review genetic models and other experimental tools currently available to further investigate the development and activation of both classical brown and inducible beige fat cells...
May 2015: Trends in Genetics: TIG
Yulia Biggar, Kenneth B Storey
Hibernation is crucial to winter survival for many small mammals and is characterized by prolonged periods of torpor during which strong global controls are applied to suppress energy-expensive cellular processes. We hypothesized that one strategy of energy conservation is a global reduction in gene transcription imparted by reversible modifications to DNA and to proteins involved in chromatin packing. Transcriptional regulation during hibernation was examined over euthermic control groups and five stages of the torpor/arousal cycle in brown adipose tissue of thirteen-lined ground squirrels (Ictidomys tridecemlineatus)...
October 2014: Cryobiology
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