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  2. Dehydroabietic acid alleviates high fat diet-induced insulin resistance and hepatic steatosis through dual activation of PPAR-γ and PPAR-α

Dehydroabietic acid alleviates high fat diet-induced insulin resistance and hepatic steatosis through dual activation of PPAR-γ and PPAR-α

  • Biomed Pharmacother. 2020 Jul;127:110155. doi: 10.1016/j.biopha.2020.110155.
Zhishen Xie 1 Gai Gao 1 Hui Wang 1 Erwen Li 1 Yong Yuan 1 Jiangyan Xu 2 Zhenqiang Zhang 3 Pan Wang 1 Yu Fu 1 Huahui Zeng 1 Junying Song 1 Christian Hölscher 1 Hui Chen 4
Affiliations

Affiliations

  • 1 Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, China.
  • 2 Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, China. Electronic address: xujiangyan2008@163.com.
  • 3 Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, China. Electronic address: zhang_zhenqiang@126.com.
  • 4 School of Life Sciences, Faculty of Science, University of Technology Sydney, PO Box 123, Broadway, NSW, 2007, Australia.
Abstract

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.

Keywords

Dehydroabietic acid; Hepatic steatosis; Hyperlipidemia; Insulin resistance; PPARs.

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