Linking temperature to metabolism – The role of brown adipose tissue in humans

Abstract

Insulin resistance is a metabolic disorder evident in most obese patients and characterized by reduced insulin-mediated glucose utilization of peripheral tissues as well as elevated plasma glucose concentrations. Increasing obesity prevalence is paralleled by related metabolic disorders such as insulin resistance and Typ 2 Diabetes mellitus (T2DM). Extensive research efforts across disciplines are made to reveal underlying mechanisms and develop effective therapies against obesity and its comorbidities. Since PET-CT studies provided evidence for functional brown adipose tissue (BAT) in adult humans, this specialized thermogenic compartment of adipocytes again attracted the attention of a large body of research. Activated by moderate cold BAT burns large amounts of carbohydrates and fatty acids as substrates for heat production, thereby significantly contributing to whole-body energy homeostasis. Beneficial metabolic effects of cold-activated BAT, e.g. improved peripheral glucose uptake and increased fatty acid clearance, have been shown in mice and men. To test our hypothesis that BAT enhances insulin sensitivity but not ß-cell-capacity we induced BAT activity by moderate cold assessed human glucose homeostasis by Botnia clamp, which allows measurement of insulin sensitivity and pancreatic ß-cell function within one session. Preliminary data of this pilot study in normal-weight men (n = 15) showed a highly significant 20% increase in glucose uptake due to improved insulin sensitivity during BAT-activation as compared to thermo-neutral conditions. Interestingly, resting energy expenditure as well as pituitary-thyroid axis activity as possible mediators linking BAT activation to glucose homeostasis were unchanged. Although underlying molecular mechanisms remain to be established in follow-up studies, these findings clearly highlight the metabolic significance of BAT activation in men. Therefore, BAT activation might be a promising target for novel treatment approaches in obesity and T2DM.