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

Autor: Yu Fu, Hui Chen, Junying Song, Zhenqiang Zhang, Yuan Yong, Xie Zhishen, Gao Gai, Wang Hui, Xu Jiangyan, Wang Pan, Christian Hölscher, Huahui Zeng, Er-Wen Li
Rok vydání: 2020
Předmět:
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
Zdroj: Biomedicine & Pharmacotherapy, Vol 127, Iss, Pp 110155-(2020)
ISSN: 1950-6007
Popis: 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.
Databáze: OpenAIRE
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