Lyons Sulayman A, Lea Micah B S, Parikh Mihir, Guo Zhengzhang, Kagdi Samrin, Bisnauth Abigail R, Pitino Jonathan R, Ziai Sabrina, Mir Negar, Tyrrell Aidan D, Fu Yan, Chen Chuck T, Metherel Adam H, Bazinet Richard P, Yang Bin, Knerr Patrick J, Douros Jonathan D, Campbell Jonathan E, Beaudry Jacqueline L
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Novo Nordisk Research Center, Indianapolis, IN, USA.
EMBO Rep. 2025 Sep 22. doi: 10.1038/s44319-025-00582-7.
The contribution of glucose-dependent insulinotropic polypeptide receptor (GIPR) signalling in brown adipose tissue (BAT) remains underexplored. We studied the acute effects of exogenous acyl-GIP (1 nmol/kg) administration on whole-body lipid handling and fatty acid oxidation, using lipid tolerance tests (LTT) and indirect calorimetry, respectively. We demonstrate that in obese male mice, acute acyl-GIP administration improves lipid tolerance; however, pharmacological inhibition of GIPR, or genetic removal of GIPR globally or with the Myf5-Cre driver, completely abolishes GIP-mediated improvements in lipid tolerance, implicating GIPR in BAT. GIP-mediated improvements in lipid tolerance are associated with an increase in BAT lipid uptake, linked to increases in BAT lipoprotein lipase activity. Our data also reveal that BAT GIPR signalling is necessary for GIP-mediated increases in whole-body fatty acid oxidation, as Myf5-Cre: Gipr mice do not shift substrate oxidation upon GIP administration. Our findings suggest that BAT should be more closely considered in studies examining GIP's effects on whole-body metabolism in rodent models.
