Female glucagon receptor knockout mice are prone to steatosis but resistant to weight gain when fed a MASH-promoting GAN diet and a high-fat diet.

IF 2.2 Q3 PHYSIOLOGY
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
{"title":"Female glucagon receptor knockout mice are prone to steatosis but resistant to weight gain when fed a MASH-promoting GAN diet and a high-fat diet.","authors":"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","doi":"10.14814/phy2.70235","DOIUrl":null,"url":null,"abstract":"<p><p>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<sup>-/-</sup> mice). To investigate whether Gcgr<sup>-/-</sup> mice tolerated a diet promoting metabolic dysfunction-associated steatohepatitis (MASH) and steatosis, we fed female Gcgr<sup>-/-</sup> mice the Gubra Amylin Nonalcoholic steatohepatitis (GAN) diet and high-fat diet (HFD), respectively. We found that non-fasted Gcgr<sup>-/-</sup> mice fed standard chow showed hypercholesterolemia and increased liver fat (borderline significant in non-fasted male Gcgr<sup>-/-</sup> 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<sup>-/-</sup> 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.</p>","PeriodicalId":20083,"journal":{"name":"Physiological Reports","volume":"13 4","pages":"e70235"},"PeriodicalIF":2.2000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845321/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Physiological Reports","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.14814/phy2.70235","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
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.

求助全文
约1分钟内获得全文 求助全文
来源期刊
Physiological Reports
Physiological Reports PHYSIOLOGY-
CiteScore
4.20
自引率
4.00%
发文量
374
审稿时长
9 weeks
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.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信