Hu, PAPAHuHsu, MCMCHsuChen, SHSHChenCHERYL CHIA-HUI CHENKou, YRYRKouJENQ-WEN HUANGTZONG-SHYUAN LEE2022-12-292022-12-2920221021-9498https://scholars.lib.ntu.edu.tw/handle/123456789/626791Bromelain, a cysteine protease found in pineapple, is known to exert protective effects against non-alcoholic fatty liver disease (NAFLD); however, the underlying mechanism is unclear. In this study, we aimed to investigate the molecular mechanisms underlying the beneficial effects of bromelain using in vivo and in vitro models. C57BL/6 mice were fed a high-fat diet (HFD) with or without bromelain (20 mg/kg/day) for 12 weeks. We found that treatment with bromelain alleviated hepatic lipid accumulation accompanied by the activation of AMP-activated protein kinase (AMPK) and autophagy flux, as evidenced by the elevated levels of phosphorylated AMPK, ATG5, ATG7, LC3-II, and lysosomeassociated membrane protein 2 (LAMP2), and the decreased levels of p62 in the liver of HFD-fed mice. In human hepatoma Huh 7 cells, bromelain prevented oleic acid (OA)-induced lipid accumulation and increased the levels of phosphorylated AMPK, ATG5, ATG7, LC3-II, and LAMP2 but decreased the levels of p62. Inhibition of AMPK and autophagy flux by specific inhibitors or small interfering RNAs suppressed bromelain-mediated protective effect on lipid accumulation. Moreover, inhibition of AMPK activity abolished the activation of autophagy flux in OA-treated hepatocytes. Collectively, these findings suggest a new molecular mechanism involving the AMPK-autophagy pathway through which bromelain confers protection against the deregulation of lipid metabolism in the liver.AMPK; Autophagy; Bromelain; NAFLD; NONALCOHOLIC FATTY LIVER; METABOLIC SYNDROME; DISEASE; THERAPIES[SDGs]SDG3journal article10.38212/2224-6614.34162-s2.0-85139470226WOS:000863217100004https://api.elsevier.com/content/abstract/scopus_id/85139470226