Etomoxir suppresses the expression of PPARgamma2 and inhibits the thermogenic gene induction of brown adipocytes through pathways other than β-oxidation inhibition

• Published in: Journal of biochemistry (Tokyo) 2024-12
• Main Authors: Shimura, Hiroki, Yamamoto, Sota, Shiiba, Isshin, Oikawa, Mami, Uchinomiya, Shohei, Ojida, Akio, Yanagi, Shigeru, Kadowaki, Hisae, Nishitoh, Hideki, Fukuda, Toshifumi, Nagashima, Shun, Yamaguchi, Tomoyuki
• Format: Article
• Language: English
• ISSN: 1756-2651; 1756-2651
• DOI: 10.1093/jb/mvae092

Brown adipocytes are characterized by a high abundance of mitochondria, allowing them to consume fatty acids for heat production. Increasing the number of brown adipocytes is considered a promising strategy for combating obesity. However, the molecular mechanisms underlying their differentiation remain poorly understood. In this study, we demonstrate that etomoxir, an inhibitor of Carnitine Palmitoyltransferase 1 (CPT1), inhibits their differentiation through mechanisms independent of β-oxidation inhibition. In the presence of etomoxir during brown adipocyte differentiation, reduced expression of the thermogenic gene UCP1 and decreased lipid droplets formation were observed. Furthermore, a transient reduction in the expression of PPARγ2, a critical factor in adipocyte differentiation, was also observed in the presence of etomoxir. These findings suggest the presence of a regulatory mechanism that specifically enhances PPARγ2 expression during brown adipocyte differentiation, thereby modulating thermogenic gene expression.