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

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

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..

Medienart:	E-Artikel

Erscheinungsjahr:	2015
Erschienen:	2015

Enthalten in:	Zur Gesamtaufnahme - volume:58
Enthalten in:	Diabetologia - 58(2015), 11 vom: 09. Aug., Seite 2637-2646

Sprache:	Englisch

Beteiligte Personen:	Kooijman, Sander [VerfasserIn] Wang, Yanan [VerfasserIn] Parlevliet, Edwin T. [VerfasserIn] Boon, Mariëtte R. [VerfasserIn] Edelschaap, David [VerfasserIn] Snaterse, Gido [VerfasserIn] Pijl, Hanno [VerfasserIn] Romijn, Johannes A. [VerfasserIn] Rensen, Patrick C. N. [VerfasserIn]

Links:	Volltext [kostenfrei]

Themen:	Brown adipose tissue Exendin-4 GLP-1 Mice Triacylglycerol

RVK:	RVK Klassifikation ELIB24

Anmerkungen:	© The Author(s) 2015

doi:	10.1007/s00125-015-3727-0

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	OLC2096728754

Internformat


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520			\|a 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.
650		4	\|a Brown adipose tissue
650		4	\|a Exendin-4
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700	1		\|a Wang, Yanan \|4 aut
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700	1		\|a Edelschaap, David \|4 aut
700	1		\|a Snaterse, Gido \|4 aut
700	1		\|a Pijl, Hanno \|4 aut
700	1		\|a Romijn, Johannes A. \|4 aut
700	1		\|a Rensen, Patrick C. N. \|4 aut
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Central GLP-1 receptor signalling accelerates plasma clearance of triacylglycerol and glucose by activating brown adipose tissue in mice

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