Thermogenesis and cellular senescence of diabetic adipocytes in response toβ-agonists and 18-carbon fatty acids
10.4163/jnh.2024.57.4.376
- Author:
Seonjeong PARK
1
;
Seung A OCK
;
Yun Jeong PARK
;
Sung Nim HAN
;
Sunhye SHIN
Author Information
1. Department of Food and Nutrition, Seoul Women’s University, Seoul 01797, Republic of Korea
- Publication Type:Research Article
- From:Journal of Nutrition and Health
2024;57(4):376-388
- CountryRepublic of Korea
- Language:English
-
Abstract:
Purpose:Adipocyte dysfunction has been reported in diabetes, and stimulating thermogenesis and suppressing senescence in adipocytes potentially alleviates metabolic dysregulation. This study aimed to investigate thermogenesis and cellular senescence in diabetic adipocytes under basal conditions and in response to stimuli.
Methods:White and brown primary adipocytes derived from control (CON) and db/db(DB) mice were treated with β-agonists, such as norepinephrine (NE) and CL316,243, and 18-carbon fatty acids, including stearic acid, oleic acid (OLA), linoleic acid (LNA), and α-linolenic acid, and the expression of the genes related to thermogenesis and cellular senescence was measured.
Results:Although no difference in the thermogenic and cellular senescence gene expression in white adipose tissue (WAT) was noted between the CON and DB mice, brown adipose tissue (BAT) from the DB mice exhibited lower uncoupling protein 1 (Ucp1) expression and higher cyclin-dependent kinase inhibitor (Cdkn)1a and Cdkn2a expression levels compared to that from the CON mice. Stromal vascular cells isolated from the BAT of the DB mice displayed higher peroxisome proliferator-activated receptor gamma (Pparg), CCAAT/ enhancer-binding protein alpha (Cebpa), Cdkn1a, and Cdkn2a expression levels. White adipocytes from the DB mice exhibited lower Ucp1, peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (Pgc1a), and PR domain containing 16 (Prdm16) expression levels regardless of β-agonist treatment. NE upregulated Pgc1a in both white and brown adipocytes from the CON mice, but not in those from the DB mice. Although none of the fatty acids were observed to downregulate the cellular senescence genes in fully differentiated adipocytes, the OLA-treated brown adipocytes derived from DB mice exhibited lower Cdkn1a and Cdkn2b expression levels than the LNA-treated cells.
Conclusion:These results indicate that the lower thermogenic capacity of diabetic adipocytes may be related to their cellular senescence, and different fatty acids potentially exert divergent effects on the expression of cellular senescence genes.
