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Open AccessJournal ArticleDOI

Thermogenic Fat: Development, Physiological Function, and Therapeutic Potential

TLDR
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 is provided.
Abstract
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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The evolving view of thermogenic fat and its implications in cancer and metabolic diseases

TL;DR: Current knowledge about the significant advances made in the origin and physiological functions of thermogenic fat is enumerated and imaging technologies for identifying thermogenic adipose tissue and pharmacologic agents via modulating thermogenesis in preclinical experiments and clinical trials are summarized.
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The Stress Axis in Obesity and Diabetes Mellitus: An Update

TL;DR: The evidence supporting hypothalamic–pituitary–adrenal axis dysregulation as an important biological link between stress, obesity, inflammation and type 2 diabetes mellitus is reviewed and summarized.
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Flattening of circadian glucocorticoid oscillations drives acute hyperinsulinemia and adipocyte hypertrophy.

TL;DR: In this paper , the authors flatten glucocorticoid oscillations in mice to prevent hyperinsulinemia and adipocyte hypertrophy, which leads to a more than 2-fold increase in brown and white adipose tissue mass within 3 weeks.
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Crosstalk between adipose tissue and the microbiota-gut-brain axis in metabolic diseases

TL;DR: It is proposed that exploring the interaction among peripheral organs and the MGBA could verify the dominant role of the latter in the onset of metabolic diseases and promote the clinical application of research outcomes.
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Sodium butyrate attenuated diet-induced obesity, insulin resistance and inflammation partly by promoting fat thermogenesis via intro-adipose sympathetic innervation

TL;DR: A potential pharmacological target for NaB is revealed to combat obesity and metabolic disorders by blocking the β3-adrenergic signaling pathway by 6-hydroxydopamine abolished NaB-induced thermogenesis.
References
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Journal ArticleDOI

Positional cloning of the mouse obese gene and its human homologue

TL;DR: The ob gene product may function as part of a signalling pathway from adipose tissue that acts to regulate the size of the body fat depot.
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Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance

TL;DR: A role for TNF-alpha in obesity and particularly in the insulin resistance and diabetes that often accompany obesity is indicated.
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Identification and Importance of Brown Adipose Tissue in Adult Humans

TL;DR: Defined regions of functionally active brown adipose tissue are present in adult humans, are more frequent in women than in men, and may be quantified noninvasively with the use of (18)F-FDG PET-CT.
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Mechanisms Controlling Mitochondrial Biogenesis and Respiration through the Thermogenic Coactivator PGC-1

TL;DR: PGC-1, a cold-inducible coactivator of nuclear receptors, stimulates mitochondrial biogenesis and respiration in muscle cells through an induction of uncoupling protein 2 (UCP-2) and through regulation of the nuclear respiratory factors (NRFs).
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Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha.

TL;DR: RSV's effects were associated with an induction of genes for oxidative phosphorylation and mitochondrial biogenesis and were largely explained by an RSV-mediated decrease in P GC-1alpha acetylation and an increase in PGC-1 alpha activity.
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