Bromelain activates the AMP-activated protein kinase-autophagy pathway to alleviate hepatic lipid accumulation

Po-An Hu, Graduate Institute and Department of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan
Man-Chen Hsu, Graduate Institute and Department of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan
Szu-Han Chen, Chien Kuo Senior High School, Taipei, Taiwan
Chia-Hui Chen, Graduate Institute and Department of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan
Yu Ru Kou, Department of Physiology, National Yang Ming Chiao Tung University, Taipei, Taiwan
Jenq-Wen Huang, Nephrology division, Department of Internal Medicine, National Taiwan University Hospital YunLin Branch, YunLin, Taiwan
Tzong-Shyuan Lee, Graduate Institute and Department of Physiology, College of Medicine, National Taiwan University, Taipei, TaiwanFollow

Keywords

AMPK; Autophagy; Bromelain; NAFLD

Abstract

Bromelain, 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 lysosome-associated membrane protein 2 (LAMP2), and the decreased levels of p62 in the liver of HFD-fed mice. In human hepatoma Huh7 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.

Abstract Image

Recommended Citation

Hu, Po-An; Hsu, Man-Chen; Chen, Szu-Han; Chen, Chia-Hui; Kou, Yu Ru; Huang, Jenq-Wen; and Lee, Tzong-Shyuan (2022) "Bromelain activates the AMP-activated protein kinase-autophagy pathway to alleviate hepatic lipid accumulation," Journal of Food and Drug Analysis: Vol. 30 : Iss. 3 , Article 3.
Available at: https://doi.org/10.38212/2224-6614.3416