Epigenetic Regulators of White Adipocyte Browning

Nanduri, Ravikanth

doi:10.3390/epigenomes5010003

Cited by 14 publications

(10 citation statements)

References 166 publications

(189 reference statements)

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“…These changes were accompanied by reduced visceral lipogenic gene expression, improved fatty acid utilization, which reversed diet-induced visceral obesity and glucose intolerance ( 39 ). Moreover, activation of both ERα ( 70 ) and ERβ ( 123 ) has been shown by others to activate WAT browning ( 124 ). Taken together, ERα may promote thermogenesis by relieving repressive methylation marks on key positive regulators of beiging and mitochondrial uncoupling.…”

Section: Estrogen-mediated Epigenetic Regulation In Adipocytesmentioning

confidence: 96%

Metabolic and Epigenetic Regulation by Estrogen in Adipocytes

et al. 2022

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Sex hormones contribute to differences between males and females in body fat distribution and associated disease risk. Higher concentrations of estrogens are associated with a more gynoid body shape and with more fat storage on hips and thighs rather than in visceral depots. Estrogen-mediated protection against visceral adiposity is shown in post-menopausal women with lower levels of estrogens and the reduction in central body fat observed after treatment with hormone-replacement therapy. Estrogen exerts its physiological effects via the estrogen receptors (ERα, ERβ and GPR30) in target cells, including adipocytes. Studies in mice indicate that estrogen protects against adipose inflammation and fibrosis also before the onset of obesity. The mechanisms involved in estrogen-dependent body fat distribution are incompletely understood, but involve, e.g., increased mTOR signaling and suppression of autophagy and adipogenesis/lipid storage. Estrogen plays a key role in epigenetic regulation of adipogenic genes by interacting with enzymes that remodel DNA methylation and histone tail post-translational modifications. However, more studies are needed to map the differential epigenetic effects of ER in different adipocyte subtypes, including those in subcutaneous and visceral adipose tissues. We here review recent discoveries of ER-mediated transcriptional and epigenetic regulation in adipocytes, which may explain sexual dimorphisms in body fat distribution and obesity-related disease risk.

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Section: Estrogen-mediated Epigenetic Regulation In Adipocytesmentioning

confidence: 96%

Metabolic and Epigenetic Regulation by Estrogen in Adipocytes

et al. 2022

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“…Histone covalent modifiers are enzymes that chemically modify positively-charged amino acids (mainly lysine) present in these proteins. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) catalyze the removal or insertion of acetyl group, respectively, influencing histone acetylation pattern [ 303 ]. Acetylation decreases histones’ positive charge, leading to histone-DNA looser interaction, chromatin decompaction and gene activation.…”

Section: Introductionmentioning

confidence: 99%

Browning of the white adipose tissue regulation: new insights into nutritional and metabolic relevance in health and diseases

Machado

Pasquarelli-do-Nascimento

Silva

et al. 2022

Nutr Metab (Lond)

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Adipose tissues are dynamic tissues that play crucial physiological roles in maintaining health and homeostasis. Although white adipose tissue and brown adipose tissue are currently considered key endocrine organs, they differ functionally and morphologically. The existence of the beige or brite adipocytes, cells displaying intermediary characteristics between white and brown adipocytes, illustrates the plastic nature of the adipose tissue. These cells are generated through white adipose tissue browning, a process associated with augmented non-shivering thermogenesis and metabolic capacity. This process involves the upregulation of the uncoupling protein 1, a molecule that uncouples the respiratory chain from Adenosine triphosphate synthesis, producing heat. β-3 adrenergic receptor system is one important mediator of white adipose tissue browning, during cold exposure. Surprisingly, hyperthermia may also induce beige activation and white adipose tissue beiging. Physical exercising copes with increased levels of specific molecules, including Beta-Aminoisobutyric acid, irisin, and Fibroblast growth factor 21 (FGF21), which induce adipose tissue browning. FGF21 is a stress-responsive hormone that interacts with beta-klotho. The central roles played by hormones in the browning process highlight the relevance of the individual lifestyle, including circadian rhythm and diet. Circadian rhythm involves the sleep–wake cycle and is regulated by melatonin, a hormone associated with UCP1 level upregulation. In contrast to the pro-inflammatory and adipose tissue disrupting effects of the western diet, specific food items, including capsaicin and n-3 polyunsaturated fatty acids, and dietary interventions such as calorie restriction and intermittent fasting, favor white adipose tissue browning and metabolic efficiency. The intestinal microbiome has also been pictured as a key factor in regulating white tissue browning, as it modulates bile acid levels, important molecules for the thermogenic program activation. During embryogenesis, in which adipose tissue formation is affected by Bone morphogenetic proteins that regulate gene expression, the stimuli herein discussed influence an orchestra of gene expression regulators, including a plethora of transcription factors, and chromatin remodeling enzymes, and non-coding RNAs. Considering the detrimental effects of adipose tissue browning and the disparities between adipose tissue characteristics in mice and humans, further efforts will benefit a better understanding of adipose tissue plasticity biology and its applicability to managing the overwhelming burden of several chronic diseases.

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“…Histone deacetylase 3 (Hdac3) activates estrogen-related receptor α (Errα) in BAT, which itself is governed by deacetylation of Pgc1α and is essential for the transcription of Ucp1, Pgc1α, and OXPHOS genes which are engaged and necessary for thermogenic programming [ 158 ]. Kmt5c methyltransferase regulates the expression of thermogenic genes by increasing the H4K20me3 repressive mark in the vicinity of enhanced transformation-related protein 53 (Trp53) promoters [ 159 ].…”

Section: Molecular Circuits Regulating Brown and Beige Adipose Tissue Development And Functionmentioning

confidence: 99%

Thermogenic Fat: Development, Physiological Function, and Therapeutic Potential

Brandão

Poojari

Rabiee

2021

IJMS

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The concerning worldwide increase of obesity and chronic metabolic diseases, such as T2D, dyslipidemia, and cardiovascular disease, motivates further investigations into preventive and alternative therapeutic approaches. Over the past decade, there has been growing evidence that the formation and activation of thermogenic adipocytes (brown and beige) may serve as therapy to treat obesity and its associated diseases owing to its capacity to increase energy expenditure and to modulate circulating lipids and glucose levels. Thus, understanding the molecular mechanism of brown and beige adipocytes formation and activation will facilitate the development of strategies to combat metabolic disorders. Here, we provide a comprehensive overview of pathways and players involved in the development of brown and beige fat, as well as the role of thermogenic adipocytes in energy homeostasis and metabolism. Furthermore, we discuss the alterations in brown and beige adipose tissue function during obesity and explore the therapeutic potential of thermogenic activation to treat metabolic syndrome.

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Epigenetic Regulators of White Adipocyte Browning

Cited by 14 publications

References 166 publications

Metabolic and Epigenetic Regulation by Estrogen in Adipocytes

Metabolic and Epigenetic Regulation by Estrogen in Adipocytes

Browning of the white adipose tissue regulation: new insights into nutritional and metabolic relevance in health and diseases

Thermogenic Fat: Development, Physiological Function, and Therapeutic Potential

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