scholarly journals Epigenetic interaction between UTX and DNMT1 regulates diet-induced myogenic remodeling in brown fat

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Fenfen Li ◽  
Jia Jing ◽  
Miranda Movahed ◽  
Xin Cui ◽  
Qiang Cao ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Dna Methyltransferase ◽  
Promoter Hypermethylation ◽  
Histone Demethylase ◽  
Brown Fat ◽  
Brown Adipocyte ◽  
High Fat ◽  
Brown Adipocytes ◽  
Repressive Mark ◽  
Diet Induced Thermogenesis

AbstractBrown adipocytes share the same developmental origin with skeletal muscle. Here we find that a brown adipocyte-to-myocyte remodeling also exists in mature brown adipocytes, and is induced by prolonged high fat diet (HFD) feeding, leading to brown fat dysfunction. This process is regulated by the interaction of epigenetic pathways involving histone and DNA methylation. In mature brown adipocytes, the histone demethylase UTX maintains persistent demethylation of the repressive mark H3K27me3 at Prdm16 promoter, leading to high Prdm16 expression. PRDM16 then recruits DNA methyltransferase DNMT1 to Myod1 promoter, causing Myod1 promoter hypermethylation and suppressing its expression. The interaction between PRDM16 and DNMT1 coordinately serves to maintain brown adipocyte identity while repressing myogenic remodeling in mature brown adipocytes, thus promoting their active brown adipocyte thermogenic function. Suppressing this interaction by HFD feeding induces brown adipocyte-to-myocyte remodeling, which limits brown adipocyte thermogenic capacity and compromises diet-induced thermogenesis, leading to the development of obesity.

scholarly journals Epigenetic Interaction between UTX and DNMT1 Regulates Diet-Induced Myogenic Remodeling in Brown Fat

2020 ◽  
Author(s):  
Fenfen Li ◽  
Jia Jing ◽  
Miranda Movahed ◽  
Xin Cui ◽  
Qiang Cao ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Dna Methyltransferase ◽  
Promoter Hypermethylation ◽  
Histone Demethylase ◽  
Brown Fat ◽  
Brown Adipocyte ◽  
High Fat ◽  
Brown Adipocytes ◽  
Repressive Mark ◽  
Diet Induced Thermogenesis

SummaryBrown adipocytes share the same developmental origin with skeletal muscle. Here we find that a brown adipocyte-to-myocyte remodeling also exists in mature brown adipocytes, and is induced by prolonged high fat diet (HFD) feeding, leading to brown fat dysfunction. This process is regulated by the interaction of epigenetic pathways involving histone and DNA methylation. In mature brown adipocytes, the histone demethylase UTX maintains persistent demethylation of the repressive mark H3K27me3 at Prdm16 promoter, leading to high Prdm16 expression. PRDM16 then recruits DNA methyltransferase DNMT1 to Myod1 promoter, causing Myod1 promoter hypermethylation and suppressing its expression. The interaction between PRDM16 and DNMT1 coordinately serves to maintain brown adipocyte identity while repressing myogenic remodeling in mature brown adipocytes, thus promoting their active brown adipocyte thermogenic function. Suppressing this interaction by HFD feeding induces brown adipocyte-to-myocyte remodeling, which limits brown adipocyte thermogenic capacity and compromises diet-induced thermogenesis, leading to the development of obesity.

Dietary fat interacts with QTLs controlling induction of Pgc-1α and Ucp1 during conversion of white to brown fat

2003 ◽  
Vol 14 (2) ◽  
pp. 139-147 ◽  
Author(s):  
Ann Allen Coulter ◽  
Christie M. Bearden ◽  
Xiaotuan Liu ◽  
Robert A. Koza ◽  
Leslie P. Kozak
Keyword(s):  
Energy Metabolism ◽  
Dietary Fat ◽  
High Fat Diet ◽  
Brown Fat ◽  
Brown Adipocyte ◽  
Chromosome 3 ◽  
Mrna Levels ◽  
High Fat ◽  
Chromosome 5 ◽  
White Fat

To identify novel regulatory factors controlling induction of the brown adipocyte-specific mitochondrial uncoupling protein ( Ucp1) mRNA in the retroperitoneal white fat depot, we previously mapped quantitative trait loci (QTLs) that control this trait to chromosomes 2, 3, 8, and 19. Since the peroxisome proliferator activator receptor-γ coactivator-1α (PGC-1α) regulates Ucp1 and other genes of energy metabolism, we have evaluated whether the QTLs controlling Ucp1 mRNA levels also modulate Pgc-1α mRNA levels by analysis of backcross progeny from the A/J and C57BL/6J strains of mice. The results indicate that a locus on chromosome 3 orchestrates expression of Pgc-1α and Ucp1 in retroperitoneal fat of mice fed a low-fat diet; however, the effect of this locus on Pgc-1α is lost, and a significant correlation between Ucp1 and Pgc-1α is severely reduced in mice fed a high-fat diet. An additional QTL located on chromosome 5 has also been identified for the selective regulation of Ucp1 mRNA levels. Similar to the effects of a high-fat diet on the chromosome 3 QTL, linkage of the chromosome 5 QTL is also lost in mice on a high-fat diet. Thus dietary fat has a profound influence on PGC-1α-regulated pathways controlling energy metabolism in white fat. The allelic variation observed in the regulation of Ucp1 and Pgc-1α expression in brown adipocytes of white fat but not interscapular brown fat suggests that fundamentally different regulatory mechanisms exist to control the thermogenic capacities of these tissues.

miRNA-22 deletion limits white adipose expansion and activates brown fat to attenuate high-fat diet-induced fat mass accumulation

Metabolism ◽  
2021 ◽  
Vol 117 ◽  
pp. 154723
Author(s):  
Vanessa M. Lima ◽  
Jianming Liu ◽  
Bruna B. Brandão ◽  
Caroline A. Lino ◽  
Camila S. Balbino Silva ◽  
...  
Keyword(s):  
Fat Mass ◽  
High Fat Diet ◽  
Brown Fat ◽  
High Fat ◽  
Mass Accumulation

scholarly journals NT-PGC-1α Activation Attenuates High-Fat Diet–Induced Obesity by Enhancing Brown Fat Thermogenesis and Adipose Tissue Oxidative Metabolism

Diabetes ◽  
2014 ◽  
Vol 63 (11) ◽  
pp. 3615-3625 ◽  
Author(s):  
Hee-Jin Jun ◽  
Yagini Joshi ◽  
Yuvraj Patil ◽  
Robert C. Noland ◽  
Ji Suk Chang
Keyword(s):  
Adipose Tissue ◽  
Oxidative Metabolism ◽  
High Fat Diet ◽  
Brown Fat ◽  
High Fat ◽  
Diet Induced Obesity

scholarly journals PPARγ in Vagal Neurons Regulates High-Fat Diet Induced Thermogenesis

2014 ◽  
Vol 19 (4) ◽  
pp. 722-730 ◽  
Author(s):  
Chen Liu ◽  
Angie L. Bookout ◽  
Syann Lee ◽  
Kai Sun ◽  
Lin Jia ◽  
...  
Keyword(s):  
High Fat Diet ◽  
High Fat ◽  
Diet Induced Thermogenesis

Anti-obesity effect of taurine through inhibition of adipogenesis in white fat tissue but not in brown fat tissue in a high-fat diet-induced obese mouse model

Amino Acids ◽  
2018 ◽  
Vol 51 (2) ◽  
pp. 245-254 ◽  
Author(s):  
Kyoung Soo Kim ◽  
Min Ju Jang ◽  
Sungsoon Fang ◽  
Seul Gi Yoon ◽  
Il Yong Kim ◽  
...  
Keyword(s):  
Mouse Model ◽  
High Fat Diet ◽  
Brown Fat ◽  
Obese Mouse ◽  
Fat Tissue ◽  
High Fat ◽  
White Fat

scholarly journals CXCL12-CXCR4 pathway activates brown adipocytes and induces insulin resistance in CXCR4-deficient mice under high-fat diet

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kenichi Kurita ◽  
Ko Ishikawa ◽  
Kenji Takeda ◽  
Masanori Fujimoto ◽  
Hiraku Ono ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
High Fat ◽  
Brown Adipocytes ◽  
Deficient Mice

Diet, lighting, and food intake affect norepinephrine turnover in dietary obesity

1987 ◽  
Vol 252 (2) ◽  
pp. R402-R408 ◽  
Author(s):  
T. Yoshida ◽  
J. S. Fisler ◽  
M. Fukushima ◽  
G. A. Bray ◽  
R. A. Schemmel
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
High Fat Diet ◽  
Brown Fat ◽  
Light Cycle ◽  
High Fat ◽  
Interscapular Brown Adipose Tissue ◽  
Norepinephrine Turnover ◽  
Brown Adipose ◽  
Dietary Obesity

The effects of dietary fat content, lighting cycle, and feeding time on norepinephrine turnover in interscapular brown adipose tissue, heart, and pancreas, and on blood 3-hydroxybutyrate, serum glucose, insulin, and corticosterone have been studied in two strains of rats that differ in their susceptibility to dietary obesity. S 5B/Pl rats, which are resistant to dietary obesity, have a more rapid turnover of norepinephrine in interscapular brown adipose tissue and heart and a greater increase in the concentration of norepinephrine in brown fat when eating a high-fat diet than do Osborne-Mendel rats, which are sensitive to fat-induced obesity. Light cycle and feeding schedule are important modulators of sympathetic activity in heart and pancreas but not in brown fat. Rats of the resistant strain also have higher blood 3-hydroxybutyrate concentrations and lower insulin and corticosterone levels than do rats of the susceptible strain. A high-fat diet increases 3-hydroxybutyrate concentrations and reduces insulin levels in both strains. These studies show, in rats eating a high-fat diet, that differences in norepinephrine turnover, particularly in brown adipose tissue, may play an important role in whether dietary obesity develops and in the manifestations of resistance to this phenomenon observed in the S 5B/Pl rat.

Effects of P2 purinergic receptor stimulation in brown adipocytes

1997 ◽  
Vol 273 (2) ◽  
pp. C679-C686 ◽  
Author(s):  
S. C. Lee ◽  
P. A. Pappone
Keyword(s):  
Heat Production ◽  
Purinergic Receptor ◽  
Cytosolic Calcium ◽  
Extracellular Atp ◽  
Brown Fat ◽  
Brown Adipocyte ◽  
Fat Cells ◽  
Sympathetic Stimulation ◽  
Adrenergic Stimulation ◽  
Brown Adipocytes

Sympathetic stimulation of brown adipocytes plays a major role in body energy homeostasis by activating energy-wasting pathways. Sympathetic neuronal input initiates a variety of metabolic, developmental, and membrane responses in brown fat cells. Many of these actions are mediated by adrenergic pathways mobilized by released norepinephrine. However, since sympathetic stimulation may also release vesicular ATP, we tested brown fat cells for ATP responses. Micromolar concentrations of extracellular ATP had a number of effects on brown adipocytes. We have shown previously that ATP elicits substantial (average of approximately 30%) increases in cell membrane capacitance (P. A. Pappone and S. C. Lee, J. Gen. Physiol. 108: 393-404, 1996). Here, we show that cytosolic calcium levels were increased by ATP, both through release from intracellular stores and through influx, as assessed by fura 2 imaging. In addition, ATP indirectly activated a nonselective cation conductance that was independent of cytosolic calcium levels in patch voltage-clamped brown fat cells. Similar calcium, conductance, and capacitance responses could be activated by 2-methylthio-ATP and ADP, consistent with mediation by a P2 type purinergic receptor. Calorimetric measurements from cell suspensions showed that ATP increased basal heat production of isolated brown fat cells by approximately 40% but had no effect on the greater than fivefold increase in heat production seen with maximal adrenergic stimulation. These myriad responses to extracellular ATP suggest that P2 receptor-mediated signaling is important in brown adipocyte physiology and that sympathetic stimulation may normally activate purinergic as well as adrenergic pathways in brown fat.

scholarly journals Emergence during development of the white-adipocyte cell phenotype is independent of the brown-adipocyte cell phenotype

2001 ◽  
Vol 356 (2) ◽  
pp. 659-664 ◽  
Author(s):  
Karine MOULIN ◽  
Nathalie TRUEL ◽  
Mireille ANDRÉ ◽  
Emmanuelle ARNAULD ◽  
Maryse NIBBELINK ◽  
...  
Keyword(s):  
Brown Fat ◽  
Late Gestation ◽  
Brown Adipocyte ◽  
Cell Phenotype ◽  
Lacz Gene ◽  
Experimental Proof ◽  
Brown Adipocytes ◽  
White Adipocytes ◽  
Adipocyte Cell ◽  
White Fat

In mammals, two types of adipose tissue are present, brown and white. They develop sequentially, as brown fat occurs during late gestation whereas white fat grows mainly after birth. However, both tissues have been shown to have great plasticity. Thus an apparent transformation of brown fat into white fat takes place during post-natal development. This observation raises questions about a possible conversion of brown into white adipocytes during development, although indirect data argue against this hypothesis. To investigate such questions in vivo, we generated two types of transgenic line. The first carried a transgene expressing Cre recombinase specifically in brown adipocytes under the control of the rat UCP1 promoter. The second corresponded to an inactive lacZ gene under the control of the human cytomegalovirus promoter. This dormant gene is inducible by Cre because it contains a Stop sequence between two loxP sequences, separating the promoter from the coding sequence. Adipose tissues of progeny derived by crossing independent lines established from both constructs were investigated. LacZ mRNA corresponding to the activated reporter gene was easily detected in brown fat and not typically in white fat, even by reverse transcriptase PCR experiments. These data represent the first direct experimental proof that, during normal development, most white adipocytes do not derive from brown adipocytes.

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