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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; Chen, Hui
Biomedicine & pharmacotherapy, July 2020, 2020-Jul, 2020-07-00, 20200701, 2020-07-01, Letnik: 127Journal Article
•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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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