Extracts of Vine Tea Improve Diet-Induced Non-Alcoholic Steatohepatitis Through AMPK-LXRα Signaling

Chinese vine tea can improve glucose and lipid metabolic disorders. However, its protective effects in non-alcoholic steatohepatitis (NASH) and its underlying molecular mechanisms remain unclear. Liver X receptor alpha (LXR alpha) inhibition and adenosine monophosphate-(AMP)-activated protein kinase (AMPK) activation can enhance control of NASH. AMPK activators have also been shown to inactivate LXR alpha. Here, the anti-NASH effects of vine tea extract (VTE) dosed at 1 g.100 g(-1) diet were investigated using NASH mice challenged with a methionine and choline-deficient l-amino acid diet (MCDD) and a high-fat diet (HFD). Pharmacological mechanisms of VTE were explored using TUNEL staining, AMPK inhibition, Western blot, reporter assays, qRT-PCR analyses, and immunofluorescence. VTE treatment improved fatty liver in HFD-induced mice, while it alleviated the progression of NASH including protecting against liver lipid accumulation, steatosis, endoplasmic reticulum stress, apoptosis, inflammation, and functional injury in MCDD-fed mice. VTE reduced the action of hepatic lipogenic genes, F4/80, pro-inflammatory cytokines, CHOP, and cleaved Caspase-3 expression, while promoting expression of fatty acid oxidation genes CPT1 alpha, ss. VTE also enhanced AMPK and blocked LXR alpha signaling in mouse livers. In vitro results indicated that VTE increased AMPK phosphorylation and reduced LXR alpha activity in HepG2 cells. Conversely, the antagonistic effect of VTE on LXR alpha was decreased through AMPK inhibition. Our data suggests that VTE may improve diet-induced NASH, which involves the pharmacological modulation of the AMPK-LXR alpha signaling pathway.