Katrine D Galsgaard, Emilie Elmelund, Jenna E Hunt, Mark M Smits, Trisha J Grevengoed, Christina Christoffersen, Nils J Færgeman, Jesper Havelund, Nicolai J Wewer Albrechtsen, Jens J Holst
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引用次数: 0
Abstract
Glucagon is secreted from the pancreatic alpha cells and regulates not only hepatic glucose production, but also hepatic lipid and amino acid metabolism. Thus, glucagon provides a switch from hepatic glucose and lipid storage towards lipid and amino acid breakdown fueling glucose production during fasting. However, the effects of genetic deletion of the glucagon receptor on lipid metabolism are unclear. We therefore assessed parameters of lipid metabolism in fasted and non-fasted male and female mice with permanent whole-body deletion of the glucagon receptor (Gcgr-/- mice). To investigate whether Gcgr-/- mice tolerated a diet promoting metabolic dysfunction-associated steatohepatitis (MASH) and steatosis, we fed female Gcgr-/- mice the Gubra Amylin Nonalcoholic steatohepatitis (GAN) diet and high-fat diet (HFD), respectively. We found that non-fasted Gcgr-/- mice fed standard chow showed hypercholesterolemia and increased liver fat (borderline significant in non-fasted male Gcgr-/- mice, but significant in the remaining groups). In the fasted state these changes were insignificant due to fasting-induced steatosis. When challenged with a GAN diet and HFD, female Gcgr-/- mice were prone to steatosis and dyslipidemia but resistant to weight gain. Taken together, our data highlight glucagon as an important physiological regulator of not just glucose, but also hepatic lipid metabolism.
期刊介绍:
Physiological Reports is an online only, open access journal that will publish peer reviewed research across all areas of basic, translational, and clinical physiology and allied disciplines. Physiological Reports is a collaboration between The Physiological Society and the American Physiological Society, and is therefore in a unique position to serve the international physiology community through quick time to publication while upholding a quality standard of sound research that constitutes a useful contribution to the field.