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Clinical Trial
. 2017 Nov 1;102(11):4226-4234.
doi: 10.1210/jc.2017-01250.

Cold-Induced Brown Adipose Tissue Activity Alters Plasma Fatty Acids and Improves Glucose Metabolism in Men

K Alexander Iwen  1 , Jenny Backhaus  1 , Melanie Cassens  1 , Maren Waltl  1 , Oana C Hedesan  2 , Martin Merkel  3 , Joerg Heeren  4 , Christian Sina  5 , Leonie Rademacher  1 , Anne Windjäger  1 , Alexander R Haug  6 , Florian W Kiefer  2 , Hendrik Lehnert  1   7 , Sebastian M Schmid  1   7
Affiliations
Clinical Trial

Cold-Induced Brown Adipose Tissue Activity Alters Plasma Fatty Acids and Improves Glucose Metabolism in Men

K Alexander Iwen et al. J Clin Endocrinol Metab. .

Abstract

Context: Mounting evidence suggests beneficial effects of brown adipose tissue (BAT) activation on glucose and lipid metabolism in humans. It is unclear whether cold-induced BAT activation affects not only insulin sensitivity but also insulin secretion. Likewise, the role in clearing circulating fatty acids (FAs) has not been fully explored.

Objective: Exploring the effects of cold-induced BAT activation on insulin sensitivity and secretion, as well as on plasma FA profiles.

Design: Fifteen healthy men participated in a cross-balanced repeated within-subject study with two experimental conditions. Subjects were exposed to thermoneutrality (22°C) and to moderate cold (18.06°C, shivering excluded) by use of a water-perfused whole body suit. Cold-induced BAT activation was quantified by [18F]-fluorodeoxyglucose positron emission tomography-computed tomography in a subset of volunteers. A Botnia clamp procedure was applied to determine pancreatic first phase insulin response (FPIR) and insulin sensitivity. Hormones and metabolites, including 26 specific plasma FAs, were sampled throughout the experiment.

Results: Cold exposure induced BAT activity. Plasma noradrenaline and dopamine concentrations increased in response to cold. Peripheral glucose uptake and insulin sensitivity significantly improved by ∼20%, whereas FPIR remained stable. Lignoceric acid (C24:0) concentrations increased, whereas levels of eicosanoic acid (C20:1n9), nervonic acid (C24:1n9), and behenic acid (C22:0) decreased.

Conclusions: Cold-exposure induces sympathetic nervous system activity and BAT metabolism in humans, resulting in improved glucose metabolism without affecting pancreatic insulin secretion. In addition, BAT activation is associated with altered circulating concentrations of distinct FAs. These data support the concept that human BAT metabolism significantly contributes to whole body glucose and lipid utilization in a coordinated manner.

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