K Alexander Iwen1, Jenny Backhaus1, Melanie Cassens1, Maren Waltl1, Oana C Hedesan2, Martin Merkel3, Joerg Heeren4, Christian Sina5, Leonie Rademacher1, Anne Windjäger1, Alexander R Haug6, Florian W Kiefer2, Hendrik Lehnert1,7, Sebastian M Schmid1,7. 1. Department of Internal Medicine I, Section of Endocrinology & Diabetes, University Hospital Schleswig-Holstein, 23538 Lübeck, Germany. 2. Clinical Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna, 1090 Vienna, Austria. 3. Endokrinologikum Hannover, 30161 Hannover, Germany. 4. Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. 5. Department of Internal Medicine I, Section of Nutritional Medicine and Institute of Nutritional Medicine, University Hospital Schleswig-Holstein, 23538 Lübeck, Germany. 6. Department of Biomedical Imaging and Image-Guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria. 7. German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany.
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.
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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