Apigenin Ameliorates Insulin Resistance and Lipid Accumulation by Endoplasmic Reticulum Stress and SREBP-1c/SREBP-2 Pathway in Palmitate-Induced HepG2 Cells and High-Fat Diet–Fed Mice

Insulin resistance (IR) is the common basis of diabetes and cardiovascular diseases, its development closely associated with lipid metabolism disorder. Flavonoids have definite chemical defense effects, including anti-inflammatory anticancer antimutation effects. However, function mechanism apigenin (AP, a kind flavonoid) in IR are still unclear. In our study, intracellular fat accumulation model cells high-fat diet (HFD)–fed mice were established using palmitate (PA) HFD. Mechanistically, we first demonstrated that AP could notably downregulate sterol regulatory element-binding protein 1c (SREBP-1c), 2 (SREBP-2), fatty acid synthase, stearyl-CoA desaturase 1, 3-hydroxy-3-methyl-glutaryl-CoA reductase PA-induced hyperlipidemic mice. Functionally, verified markedly reduce decrease body weight, visceral IR, HFD-induced Besides, showed PA significantly endoplasmic reticulum stress (ERS)–related proteins inhibit ERS. Furthermore, proved blood lipids by inhibiting ERS cells. Meanwhile, 4-phenyl butyric (also called alleviator), like AP, alleviate HFD-fed Therefore, concluded substantially improve disorder metabolism, might be related to SREBP-1c, SREBP-2, downstream genes, inhibition ERS, reduction IR. Significance Statement Apigenin, nontoxic naturally sourced flavonoid, has antihyperlipidemic properties hepatocyte. This study highlights new proposes these hypolipidemic effects mitigation insulin diet-induced obesity. provide translational insight into prevention treatment hyperlipidemia-related diseases.