Brown Adipose Tissue Activation Is Linked to Distinct Systemic Effects on Lipid Metabolism in Humans

Chondronikola, Maria; Volpi, Elena; Børsheim, Elisabet; Porter, Craig; Saraf, Manish Kumar; Annamalai, Palam; Yfanti, Christina; Chao, Tony; Wong, Daniel; Shinoda, Kosaku; Labbé, Sébastien M.; Hurren, Nicholas M.; Cesani, Fernardo; Kajimura, Shingo; Sidossis, Labros S.

doi:10.1016/j.cmet.2016.04.029

Cited by 276 publications

(240 citation statements)

References 33 publications

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“…This binding results in activation of cAMP/protein kinase A (PKA) pathway which induces lipolysis and thermogenic genes expression and substantially activates brown and beige adipocytes (Cao et al 2004b. In adult humans, BAT activation by prolonged cold exposure appears to increase lipid mobilization from other fat depots to BAT and promotes lipid burning through heat production in mitochondria (Chondronikola et al 2016). Brown and beige fat not only maintains energy balance through non-shivering thermogenesis but also promotes glucose uptake and TGs clearance from the circulation (Bartelt et al 2011).…”

Section: Thermogenic Function Of Brown and Beige Adipose Tissuementioning

confidence: 99%

“…Given that adiposity-induced mobilization of fatty acids from adipose tissue to other organs is a main cause of insulin resistance, inhibition of lipolysis has been considered for the treatment of insulin resistance (Guilherme et al 2008). However, lipolysis is also closely linked to thermogenesis and energy expenditure by supplying fatty acids for β-oxidation (Haemmerle et al 2006, Chondronikola et al 2016. On the other hand, inhibiting adipose lipogenesis by fatty acid synthase deficiency promotes energy expenditure and protects from diet-induced obesity and insulin resistance (Lodhi et al 2012).…”

Section: :3mentioning

confidence: 99%

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Adipose tissue in control of metabolism

Luo

Liu

2016

Journal of Endocrinology

479

331

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Adipose tissue plays a central role in regulating whole-body energy and glucose homeostasis through its subtle functions at both organ and systemic levels. On one hand, adipose tissue stores energy in the form of lipid and controls the lipid mobilization and distribution in the body. On the other hand, adipose tissue acts as an endocrine organ and produces numerous bioactive factors such as adipokines that communicate with other organs and modulate a range of metabolic pathways. Moreover, brown and beige adipose tissue burn lipid by dissipating energy in the form of heat to maintain euthermia, and have been considered as a new way to counteract obesity. Therefore, adipose tissue dysfunction plays a prominent role in the development of obesity and its related disorders such as insulin resistance, cardiovascular disease, diabetes, depression and cancer. In this review, we will summarize the recent findings of adipose tissue in the control of metabolism, focusing on its endocrine and thermogenic function.

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Section: Thermogenic Function Of Brown and Beige Adipose Tissuementioning

confidence: 99%

Section: :3mentioning

confidence: 99%

Adipose tissue in control of metabolism

Luo

Liu

2016

Journal of Endocrinology

479

331

View full text Add to dashboard Cite

show abstract

“…Although increasing the activity of BAT or expansion of brownlike adipocytes has been proposed as a treatment for obesity, the overall contribution of BAT and brownlike adipocytes to whole body metabolism is still being debated (Chondronikola et al 2016, Labbe et al 2016. BAT-specific insulin receptor knockout in mice results in the loss of fat-burning BAT tissue, illustrating an important role for insulin in this tissue (Guerra et al 2001).…”

Section: :3mentioning

confidence: 99%

A causal role for hyperinsulinemia in obesity

Templeman

Skovsø

Page

et al. 2017

Journal of Endocrinology

133

116

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Insulin modulates the biochemical pathways controlling lipid uptake, lipolysis and lipogenesis at multiple levels. Elevated insulin levels are associated with obesity, and conversely, dietary and pharmacological manipulations that reduce insulin have occasionally been reported to cause weight loss. However, the causal role of insulin hypersecretion in the development of mammalian obesity remained controversial in the absence of direct loss-of-function experiments. Here, we discuss theoretical considerations around the causal role of excess insulin for obesity, as well as recent studies employing mice that are genetically incapable of the rapid and sustained hyperinsulinemia that normally accompanies a high-fat diet. We also discuss new evidence demonstrating that modest reductions in circulating insulin prevent weight gain, with sustained effects that can persist after insulin levels normalize. Importantly, evidence from long-term studies reveals that a modest reduction in circulating insulin is not associated with impaired glucose homeostasis, meaning that body weight and lipid homeostasis are actually more sensitive to small changes in circulating insulin than glucose homeostasis in these models. Collectively, the evidence from new studies on genetic loss-of-function models forces a re-evaluation of current paradigms related to obesity, insulin resistance and diabetes. The potential for translation of these findings to humans is briefly discussed.

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“…The recent recognition of these depots in adult humans has reignited interest in utilizing the metabolic properties of BAT to regulate energy and glucose homeostasis in humans. Most recently, studies have revealed the physiological contributions of human scBAT to whole body energy and glucose homeostasis and identified biomarkers that are specific to human scBAT (19,(23)(24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%