Brown adipose tissue activity controls triglyceride clearance

Abstract

Brown adipose tissue (BAT) burns fatty acids for heat production to defend the body against cold and has recently been shown to be present in humans. Triglyceride-rich lipoproteins (TRLs) transport lipids in the bloodstream, where the fatty acid moieties are liberated by the action of lipoprotein lipase (LPL). Peripheral organs such as muscle and adipose tissue take up the fatty acids, whereas the remaining cholesterol-rich remnant particles are cleared by the liver. Elevated plasma triglyceride concentrations and prolonged circulation of cholesterol-rich remnants, especially in diabetic dyslipidemia, are risk factors for cardiovascular disease. However, the precise biological role of BAT for TRL clearance remains unclear. Here we show that increased BAT activity induced by short-term cold exposure controls TRL metabolism in mice. Cold exposure drastically accelerated plasma clearance of triglycerides as a result of increased uptake into BAT, a process crucially dependent on local LPL activity and transmembrane receptor CD36. In pathophysiological settings, cold exposure corrected hyperlipidemia and improved deleterious effects of insulin resistance. In conclusion, BAT activity controls vascular lipoprotein homeostasis by inducing a metabolic program that boosts TRL turnover and channels lipids into BAT. Activation of BAT might be a therapeutic approach to reduce elevated triglyceride concentrations and combat obesity in humans.

Metabolic cycles in a circannual hibernator

“…This early rise of glycerol and FFAs during spontaneous natural arousal in 13-lined ground squirrels matches results obtained in an artificially induced arousal of arctic ground squirrels (16) and is consistent with systemic use of medium and long chain FFAs as fuel for hibernation. The energy stored in FFAs may be recovered by ␤-oxidation to generate ATP or to be converted to heat via nonshivering thermogenesis in brown adipose tissue; the latter process is important for rewarming from torpor and is also now recognized as having therapeutic implications for human obesity (6). In addition, two-carbon acetyl group derivatives of these FFAs are the building blocks for hepatic ketogenesis (10,11), which provides ketone bodies for use in target tissues including heart and brain (1,25).…”

High-fat diet induces emergence of brown-like adipocytes in white adipose tissue of spontaneously hypertensive rats

“…26 In addition, SHR are characterized by a deletion mutation of Cd36, 47,48 which is a fatty acid transporter that mediates fatty acids uptake by adipocytes (and other cells) and is involved in cold-induced brown fat thermogenesis. 49 Because of the deletion mutation, Cd36 is undetectable in SHR adipocyte plasma membrane. 47,48 Whether this genetic alteration has a role in the observed HFD-induced brown-fat emergence in WAT requires further studies, however.…”

Surgical injury induces local and distant adipose tissue browning

“…4,27 In mice, both activation and transplantation of BAT were shown to improve whole body metabolism and insulin sensitivity. 1,29 Furthermore, human white adipocytes can be manipulated in vitro to develop "brown" characteristics (UCP1 expression) by forced adenoviral overexpression of PGC1a. 30,31 As a result, promotion of BAT (through an increase in BAT mass or turning WAT into BAT) is increasingly acknowledged as a potential therapeutic strategy for obesity and obesity related diseases.…”

“…[1][2][3] While WAT is the primary site of energy storage and of release of hormones and cytokines, 4 brown adipose tissue (BAT) is composed of multilocular brown adipocytes with high mitochondrial content and Uncoupling Protein-(UCP-)1, contributing to heat production in small mammals and humans in response to cold exposure. 1,[5][6][7] In prevailing models of browning, the central nervous system triggers pathways such as sympathetic discharge, resulting in the release of norepinephrine (NE) and b-adrenergic receptor activation in WAT and BAT.…”

“…[1][2][3] While WAT is the primary site of energy storage and of release of hormones and cytokines, 4 brown adipose tissue (BAT) is composed of multilocular brown adipocytes with high mitochondrial content and Uncoupling Protein-(UCP-)1, contributing to heat production in small mammals and humans in response to cold exposure. 1,[5][6][7] In prevailing models of browning, the central nervous system triggers pathways such as sympathetic discharge, resulting in the release of norepinephrine (NE) and b-adrenergic receptor activation in WAT and BAT. 8 Beige adipocytes arise from both de novo adipogenesis of a subgroup of precursor cells expressing plateletderived growth factor receptor a (PDGFRa), CD34, and Sca-1 7,9,10,11,12 and pre-existing adipocytes (transdifferentiation), 13,14 depending on depot, diet and temperature.…”