The Presence of Active Brown Adipose Tissue Determines Cold-Induced Energy Expenditure and Oxylipin Profiles in Humans

Abstract

Background Accumulating evidence links brown adipose tissue (BAT) to increased cold-induced energy expenditure (CIEE) and regulation of lipid metabolism in humans. BAT has also been proposed as a novel source for biologically active lipid mediators including polyunsaturated fatty acids (PUFAs) and oxylipins. However, little is known about cold-mediated differences in energy expenditure and various lipid species between individuals with detectable BAT positive (BATpos) and those without BAT negative (BATneg). Methods Here we investigated a unique cohort of matched BATpos and BATneg individuals identified by 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography ([18F]-FDG PET/CT). BAT function, CIEE, and circulating oxylipins, were analyzed before and after short-term cold exposure using [18F]-FDG PET/CT, indirect calorimetry, and high-resolution mass spectrometry, respectively. Results We found that active BAT is the major determinant of CIEE since only BATpos individuals experienced significantly increased energy expenditure in response to cold. A single bout of moderate cold exposure resulted in the dissipation of an additional 20 kcal excess energy in BATpos but not in BATneg individuals. The presence of BAT was associated with a unique systemic PUFA and oxylipin profile characterized by increased levels of anti-inflammatory omega-3 fatty acids as well as cytochrome P450 products but decreased concentrations of some proinflammatory hydroxyeicosatetraenoic acids when compared with BATneg individuals. Notably, cold exposure raised circulating levels of various lipids, including the recently identified BAT-derived circulating factors (BATokines) DiHOME and 12-HEPE, only in BATpos individuals. Conclusions In summary, our data emphasize that BAT in humans is a major contributor toward cold-mediated energy dissipation and a critical organ in the regulation of the systemic lipid pool.

Mitochondrial Lipid Signaling and Adaptive Thermogenesis

“…Brown adipocytes increase the production and secretion of 12,13-diHOME with cold exposure in both mice and humans [ 39 , 40 ]. Activation of β 3 AR leads to the increased production of sHE transcripts and subsequent increases in 12,13-diHOME levels.…”

Intact vitamin A transport is critical for cold-mediated adipose tissue browning and thermogenesis

“…Next, we tested whether cold-induced alterations in vitamin A metabolism were also present in humans. Thirty healthy lean subjects (baseline characteristics Table S1 ) were exposed to moderate cold (14–17 °C) for 2.5 h using water-perfused cooling vests under a protocol which has been used successfully to activate BAT in humans [ [28] , [29] , [30] ]. Notably, only 2.5 h of moderate cold exposure increased circulating retinol and RBP concentrations significantly in these lean subjects ( Figure 1 C,D).…”

“…Moderate cold exposure (14°C–17 °C) for 2 h is usually sufficient to activate human BAT [ [28] , [29] , [30] ]. We applied this protocol in 30 young healthy lean subjects (age: 20–45 years, BMI: 18.5–24.9 kg/m 2 ), which was approved by the ethics committee of the Medical University of Vienna (EK-No.…”

Energy Metabolism and Aging

“…This indicates that BAT concentrated in that region effectively induced non-shivering thermogenesis to produce heat, thereby increasing energy expenditure. It was recently reported that presence of active BAT determines cold-induced increase in energy expenditure in humans [64]. Cold exposure has also been proven to induce white fat beiging [65].…”