High‐fat diet‐induced increases in glucocorticoids contribute to the development of non‐alcoholic fatty liver disease in mice. Issue 1 (27th December 2021)

• Record Type: Journal Article
• Authors: Tsai, Sheng‐Feng; Hung, Hao‐Chang; Shih, Monica Meng‐Chun; Chang, Fu‐Chuan; Chung, Bon‐chu; Wang, Chia‐Yih; Lin, Yu‐Ling; Kuo, Yu‐Min
• Is Part Of: FASEB journal. Volume 36:Issue 1(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-27
• Subjects: CD36 -- corticosterone -- hepatic steatosis -- lipid metabolism -- triglycerides; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.202101570R
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract: This study aimed to investigate the causal relationship between chronic ingestion of a high‐fat diet (HFD)‐induced secretion of glucocorticoids (GCs) and the development of non‐alcoholic fatty liver disease (NAFLD). We have produced a strain of transgenic mice (termed L/L mice) that have normal levels of circulating corticosterone (CORT), the major type of GCs in rodents, but unlike wild‐type (WT) mice, their circulating CORT was not affected by HFD. Compared to WT mice, 12‐week HFD‐induced fatty liver was less pronounced with higher plasma levels of triglycerides in L/L mice. These changes were reversed by CORT supplement to L/L mice. By analyzing a sort of lipid metabolism‐related proteins, we found that expressions of the hepatic cluster of differentiation 36 (CD36) were upregulated by HFD‐induced CORT and involved in CORT‐mediated fatty liver. Dexamethasone, an agonist of the glucocorticoid receptor (GR), upregulated expressions of CD36 in HepG2 hepatocytes and facilitated lipid accumulation in the cells. In conclusion, the fat ingestion‐induced release of CORT contributes to NAFLD. This study highlights the pathogenic role of CORT‐mediated upregulation of hepatic CD 36 in diet‐induced NAFLD.