High-fat diet-induced increase in glucocorticoids contributes to adipogenesis in obese mice

Sheng-Feng Tsai; Pei-Ling Hsu; Mei-Chen Yeh; Hao-Chang Hung; Monica Meng-Chun Shih; Bon-Chu Chung; Chia-Yih Wang; Chih-Jen Chang; Yu-Min Kuo

doi:10.1016/j.bj.2024.100772

High-fat diet-induced increase in glucocorticoids contributes to adipogenesis in obese mice

Biomed J. 2024 Jul 22:100772. doi: 10.1016/j.bj.2024.100772. Online ahead of print.

Authors

Sheng-Feng Tsai¹, Pei-Ling Hsu², Mei-Chen Yeh³, Hao-Chang Hung³, Monica Meng-Chun Shih⁴, Bon-Chu Chung⁵, Chia-Yih Wang¹, Chih-Jen Chang⁶, Yu-Min Kuo⁷

Affiliations

¹ Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, 701401, Taiwan; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, 701401, Taiwan.
² Department of Anatomy, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807378, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 807378, Taiwan; Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 807378, Taiwan.
³ Division of Endocrinology and Metabolism, Department of Internal Medicine, Chi Mei Medical Center, Tainan, 710402, Taiwan.
⁴ National Laboratory Animal Center, National Applied Research Laboratories, Taipei, 115021, Taiwan.
⁵ National Laboratory Animal Center, National Applied Research Laboratories, Taipei, 115021, Taiwan; Graduate Institute of Biomedical Sciences, Neuroscience and Brain Disease Center, China Medical University, Taichung, 404328, Taiwan.
⁶ Department of Family Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, 600566, Taiwan. Electronic address: [email protected].
⁷ Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan, 701401, Taiwan; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, 701401, Taiwan. Electronic address: [email protected].

PMID: 39048079
DOI: 10.1016/j.bj.2024.100772

Abstract

Background: This study was designed to examine how glucocorticoids (GCs) induced by a long-term ingestion of high-fat diet (HFD) mediate the HFD-induced adipose expansion and obesity.

Material and methods: To address this goal, we used a unique L/L mouse model that fails to induce its corticosterone (CORT) level, a major type of GCs in rodents, after prolonged exposure to an HFD.

Results: We found that, after receiving a 12-week HFD feeding, the L/L mice show less weight gain, milder adipose expansion, and higher plasma levels of triglycerides than the wild-type mice. These changes were reversed by replenishing CORT to L/L mice. When examining the expression levels of various molecules linked to lipid uptake and de novo lipogenesis in CORT-induced adipose expansion, we observed a reduction in the expression of adipose preadipocyte factor 1 (Pref-1), a key regulator in adipogenesis. In 3T3-L1 preadipocyte-like cells, dexamethasone, an agonist of the glucocorticoid receptor, also reduced expressions of Pref-1 and facilitated intracellular accumulation of lipids.

Conclusions: Our results suggest that fat ingestion-induced release of CORT contributes to adipose expansion and development of obesity and highlight the pathogenic role of CORT-mediated downregulation of adipose Pref-1 in diet-induced obesity.

Keywords: Pref-1; adipogenesis; adipose expansion; corticosterone; diet-induced obesity; obesity.