1. Dehydroabietic acid alleviates high fat diet-induced insulin resistance and hepatic steatosis through dual activation of PPAR-γ and PPAR-α.
- Author
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Xie, Zhishen, Gao, Gai, Wang, Hui, Li, Erwen, Yuan, Yong, Xu, Jiangyan, Zhang, Zhenqiang, Wang, Pan, Fu, Yu, Zeng, Huahui, Song, Junying, Hölscher, Christian, and Chen, Hui
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INSULIN resistance , *FATTY degeneration , *GLUCOSE intolerance , *LIPID metabolism , *OXYGEN consumption - Abstract
• DA is a dual-PPAR-α/γ and PPAR-γ partial agonist. • DA alleviates HFD-induced insulin resistance via PPAR-γ. • DA alleviates HFD-induced hepatic steatosis via PPAR-α. Dual-PPAR-α/γ agonist has the dual potentials to improve insulin resistance (IR) and hepatic steatosis associated with obesity. This study aimed to investigate whether dehydroabietic acid (DA), a naturally occurred compound, can bind to and activate both PPAR-γ and PPAR-α to ameliorate IR and hepatic steatosis in high-fat diet (HFD)-fed mice.. We found that DA formed stable hydrogen bonds with the ligand-binding domains of PPAR-γ and PPAR-α. DA treatment also promoted 3T3-L1 differentiation via PPAR-γ activation, and mitochondrial oxygen consumption in HL7702 cells via PPAR-α activation. In HFD-fed mice, DA treatment alleviated glucose intolerance and IR, and reduced hepatic steatosis, liver injury markers (ALT, AST), and lipid accumulation, and promoted mRNA expression of PPAR-γ and PPAR-α signaling elements involved in IR and lipid metabolism in vivo and in vitro , and inhibited mRNA expression of pro-inflammatory factors. Therefore, DA is a dual-PPAR-α/γ and PPAR-γ partial agonist, which can attenuate IR and hepatic steatosis induced by HFD-consumption in mice. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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