[HTML][HTML] Central GLP-1 receptor signalling accelerates plasma clearance of triacylglycerol and glucose by activating brown adipose tissue in mice

S Kooijman, Y Wang, ET Parlevliet, MR Boon… - Diabetologia, 2015 - Springer
S Kooijman, Y Wang, ET Parlevliet, MR Boon, D Edelschaap, G Snaterse, H Pijl, JA Romijn
Diabetologia, 2015Springer
Aims/hypothesis Glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonism, used in the
treatment of type 2 diabetes, has recently been shown to increase thermogenesis via the
brain. As brown adipose tissue (BAT) produces heat by burning triacylglycerol (TG) and
takes up glucose for de novo lipogenesis, the aim of this study was to evaluate the potential
of chronic central GLP-1R activation by exendin-4 to facilitate clearance of lipids and
glucose from the circulation by activating BAT. Methods Lean and diet-induced obese (DIO) …
Aims/hypothesis
Glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonism, used in the treatment of type 2 diabetes, has recently been shown to increase thermogenesis via the brain. As brown adipose tissue (BAT) produces heat by burning triacylglycerol (TG) and takes up glucose for de novo lipogenesis, the aim of this study was to evaluate the potential of chronic central GLP-1R activation by exendin-4 to facilitate clearance of lipids and glucose from the circulation by activating BAT.
Methods
Lean and diet-induced obese (DIO) C57Bl/6J mice were used to explore the effect of a 5 day intracerebroventricular infusion of the GLP-1 analogue exendin-4 or vehicle on lipid and glucose uptake by BAT in both insulin-sensitive and insulin-resistant conditions.
Results
Central administration of exendin-4 in lean mice increased sympathetic outflow towards BAT and white adipose tissue (WAT), resulting in increased thermogenesis as evidenced by increased uncoupling protein 1 (UCP-1) protein levels and decreased lipid content, while the uptake of TG-derived fatty acids was increased in both BAT and WAT. Interestingly, in DIO mice, the effects on WAT were blunted, while exendin-4 still increased sympathetic outflow towards BAT and increased the uptake of plasma TG-derived fatty acids and glucose by BAT. These effects were accompanied by increased fat oxidation, lower plasma TG and glucose concentrations, and reduced body weight.
Conclusions/interpretation
Collectively, our results suggest that BAT activation may be a major contributor to the glucose- and TG-lowering effects of GLP-1R agonism.
Springer