TY - JOUR
T1 - High-fat diet-induced increases in glucocorticoids contribute to the development of non-alcoholic fatty liver disease in mice
AU - Tsai, Sheng Feng
AU - Hung, Hao Chang
AU - Shih, Monica Meng Chun
AU - Chang, Fu Chuan
AU - Chung, Bon chu
AU - Wang, Chia Yih
AU - Lin, Yu Ling
AU - Kuo, Yu Min
N1 - Funding Information:
We are grateful for the supports from (1) Laboratory Animal Center, Medical College, National Cheng Kung University, (2) Bioimaging Core Facility of the National Core Facility for Biopharmaceuticals, Ministry of Science and Technology, Taiwan, (3) National Laboratory Animal Center, NARLabs, Taiwan. This study was supported by grants: MOST 109‐2320‐B‐006‐043‐MY3 (Ministry of Science and Technology, Taiwan), MOST 109‐2811‐B‐006‐520 (Ministry of Science and Technology, Taiwan), MOST 107‐2320‐B‐006‐054‐MY3 (Ministry of Science and Technology, Taiwan), MOST 107‐2321‐B‐001‐034 (Ministry of Science and Technology, Taiwan), and DAROC2017YPI‐0001 (The Diabetes Association of the Republic of China, Taiwan).
Funding Information:
We are grateful for the supports from (1) Laboratory Animal Center, Medical College, National Cheng Kung University, (2) Bioimaging Core Facility of the National Core Facility for Biopharmaceuticals, Ministry of Science and Technology, Taiwan, (3) National Laboratory Animal Center, NARLabs, Taiwan. This study was supported by grants: MOST 109-2320-B-006-043-MY3 (Ministry of Science and Technology, Taiwan), MOST 109-2811-B-006-520 (Ministry of Science and Technology, Taiwan), MOST 107-2320-B-006-054-MY3 (Ministry of Science and Technology, Taiwan), MOST 107-2321-B-001-034 (Ministry of Science and Technology, Taiwan), and DAROC2017YPI-0001 (The Diabetes Association of the Republic of China, Taiwan).
Publisher Copyright:
© 2021 Federation of American Societies for Experimental Biology
PY - 2022/1
Y1 - 2022/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85122039419&partnerID=8YFLogxK
U2 - 10.1096/fj.202101570R
DO - 10.1096/fj.202101570R
M3 - Article
C2 - 34959259
AN - SCOPUS:85122039419
SN - 0892-6638
VL - 36
JO - FASEB Journal
JF - FASEB Journal
IS - 1
M1 - e22130
ER -