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Dehydroabietic acid alleviates high fat diet-induced insulin resistance and hepatic steatosis through dual activation of PPAR-γ and PPAR-α.
- Source :
-
Biomedicine & Pharmacotherapy . Jul2020, Vol. 127, pN.PAG-N.PAG. 1p. - Publication Year :
- 2020
-
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]
Details
- Language :
- English
- ISSN :
- 07533322
- Volume :
- 127
- Database :
- Academic Search Index
- Journal :
- Biomedicine & Pharmacotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 143496634
- Full Text :
- https://doi.org/10.1016/j.biopha.2020.110155