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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Yu Fu, Hui Chen, Junying Song, Zhenqiang Zhang, Yuan Yong, Xie Zhishen, Gao Gai, Wang Hui, Xu Jiangyan, Wang Pan, Christian Hölscher, Huahui Zeng, and Er-Wen Li
- Subjects
0301 basic medicine ,Agonist ,Male ,medicine.medical_specialty ,Hepatic steatosis ,PPARs ,medicine.drug_class ,Peroxisome proliferator-activated receptor ,RM1-950 ,Diet, High-Fat ,Partial agonist ,Cell Line ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Insulin resistance ,Oxygen Consumption ,In vivo ,Internal medicine ,3T3-L1 Cells ,medicine ,Animals ,Humans ,PPAR alpha ,Oncology & Carcinogenesis ,Pharmacology ,Liver injury ,chemistry.chemical_classification ,Lipid metabolism ,General Medicine ,medicine.disease ,Lipid Metabolism ,Dehydroabietic acid ,Mitochondria ,Fatty Liver ,Mice, Inbred C57BL ,PPAR gamma ,030104 developmental biology ,Endocrinology ,Hyperlipidemia ,chemistry ,030220 oncology & carcinogenesis ,Abietanes ,lipids (amino acids, peptides, and proteins) ,Therapeutics. Pharmacology ,Steatosis ,1115 Pharmacology and Pharmaceutical Sciences ,Insulin Resistance - 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.
- Published
- 2020