Short chain fatty acids increase fat oxidation and promote browning through β3-adrenergic receptor/AMP-activated protein kinase α signaling pathway in 3T3-L1 adipocytes
Wenkai Zhang, Li Kong, Zhen Zhong, Lezhen Lin, Jingen Li, Guodong Zheng
Abstract
To investigate the molecular mechanism of short chain fatty acids (SCFAs) on promoting fatty acid β-oxidation and browning in 3T3-L1 adipocytes. SCFAs significantly reduced lipid accumulation in 3T3-L1 adipocytes. In addition, via increasing the expression of Tfam and Nrf1, SCFAs enhanced mitochondrial biogenesis. According to the results of qPCR analysis, the expression levels of fatty acid β-oxidation genes (PPARα, CPT1α, ACOX1) were up-regulated by SCFAs. Moreover, SCFAs treatment increased the genes and proteins expression of brown adipocyte-specific factors such as PRDM16, PGC-1α, and UCP-1, as well as up-regulated the genes expression of beige adipocytes markers (Tmem26, Tbx1, CD137, and Cited1). Furthermore, the effects of β3-AR and AMPK antagonist were reversed by SCFAs. In conclusion, SCFAs promote fat β-oxidation and browning of adipocytes through β3-AR/AMPKα signaling pathway, thereby reducing fat accumulation in 3T3-L1 adipocytes. Therefore, SCFAs may be a helpful supplement to combat obesity.