Endocrine Abstracts

The increasing prevalence of obesity is paralleled by related metabolic disorders such as insulin resistance and type 2 diabetes mellitus (T2DM). Extensive 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 is in the focus of current research. Activated by moderate cold BAT utilises significant amounts of carbohydrates and fatty acids as substrates for heat production, thereby contributing to whole-body energy homeostasis. Beneficial metabolic effects of BAT activation lipid metabolism have been shown in mice and men. Here we assessed glucose homeostasis by Botnia clamping during cold-induced BAT activation in 15 healthy normal-weight men. Botnia clamp experiments combine an intravenous glucose tolerance test with a subsequent hyperinsulinaemic–euglycaemic clamp thereby allowing measurement of pancreatic β-cell capacity and peripheral insulin sensitivity within one session. BAT activation induced a highly significant 20% increase in glucose uptake due to improved insulin sensitivity while β-cell capacity remained unchanged as compared to thermo-neutral conditions. Interestingly, resting energy expenditure and pituitary–thyroid axis activity as possible pathways linking BAT activation and glucose homeostasis were not affected during BAT activation. Although, underlying molecular mechanisms remain to be established in follow-up studies, these findings clearly highlight the metabolic significance of BAT activation in men and therefore might be a promising target for novel treatment approaches in obesity and T2DM.

Disclosure: This work was supported by the DFG, German Research Foundation (GRK 1957).