Apigenin ameliorates hepatic lipid accumulation by activating the autopha-gy-mitochondria pathway
Man-Chen Hsu, Bei-Chia Guo, Chia-Hui Chen, Po-An Hu, Tzong-Shyuan Lee*
Graduate Institute and Department of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan
Apigenin, a flavonoid isolated from plants, provides protection against non-alcoholic fatty liver disease. However, the mechanism by which apigenin decreases lipid accumulation in the liver is unclear. In this study, we investigated the molecular mechanism underlying the beneficial effect of apigenin on the hepatic deregulation of lipid metabolism. Oleic acid (OA)-induced lipid accumulation in human hepatoma cells (Huh7 cells) was used as an in vitro model. Western blot analysis was used for evaluating protein expression. Oil red O staining, Nile red staining, and conventional assay kits were used to assess the level of lipids. Immunocytochemistry was performed to observe mitochondrial morphology. Seahorse XF analyzer was used to measure mitochondrial bioenergetics. Treatment with OA induced lipid accumulation in Huh7 cells, which was attenuated by apigenin. Mechanistically, treatment with apigenin increased the expression of autophagy-related proteins including Beclin1, autophagy related gene 5 (ATG5), ATG7, and LC3II, and the formation of autophagolysosomes, leading to an increase in intracellular levels of fatty acids. Inhibition of autophagy by bafilomycin A1 or chloroquine abolished the protection of apigenin in OA-induced lipid accumulation. Apigenin up-regulated the protein expression related to the b-oxidation pathway including acyl-CoA synthetase long chain family member 1, carnitine palmitoyltransferase 1a, acyl-CoA oxidase 1, peroxisome proliferator activated receptor (PPAR) a, and PPARg coactivator 1-a. Moreover, apigenin increased the mitochondrial network structure and mitochondrial function by increasing the protein expression related to the process of mitochondria fusion and mitochondrial function. Collectively, our findings suggest that apigenin ameliorates hepatic lipid accumulation by activating the autophagy-mitochondrial pathway.
Keywords: Apigenin, Autophagy, Hepatic lipid metabolism, Mitochondria
https://doi.org/10.38212/2224-6614.3269
(https://www.jfda-online.com/journal/vol29/iss2/4)