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

Autor: Kooijman S; Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Room C7-Q44, Albinusdreef 2, PO Box 9600, 2300, RC, Leiden, the Netherlands. s.kooijman@lumc.nl.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands. s.kooijman@lumc.nl., Wang Y; Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Room C7-Q44, Albinusdreef 2, PO Box 9600, 2300, RC, Leiden, the Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands., Parlevliet ET; Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Room C7-Q44, Albinusdreef 2, PO Box 9600, 2300, RC, Leiden, the Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.; Department of Medicine, Academic Medical Center, Amsterdam, the Netherlands., Boon MR; Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Room C7-Q44, Albinusdreef 2, PO Box 9600, 2300, RC, Leiden, the Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands., Edelschaap D; Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Room C7-Q44, Albinusdreef 2, PO Box 9600, 2300, RC, Leiden, the Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands., Snaterse G; Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Room C7-Q44, Albinusdreef 2, PO Box 9600, 2300, RC, Leiden, the Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands., Pijl H; Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Room C7-Q44, Albinusdreef 2, PO Box 9600, 2300, RC, Leiden, the Netherlands., Romijn JA; Department of Medicine, Academic Medical Center, Amsterdam, the Netherlands., Rensen PC; Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Room C7-Q44, Albinusdreef 2, PO Box 9600, 2300, RC, Leiden, the Netherlands.; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
Jazyk: angličtina
Zdroj: Diabetologia [Diabetologia] 2015 Nov; Vol. 58 (11), pp. 2637-46. Date of Electronic Publication: 2015 Aug 09.
DOI: 10.1007/s00125-015-3727-0
Abstrakt: 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.
Databáze: MEDLINE
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