Inhibition of SREBP-1c-mediated hepatic steatosis and oxidative stress by sauchinone, an AMPK-activating lignan in Saururus chinensis

Abstract

Sauchinone, as an AMP-activated kinase (AMPK)-activating lignan in Saururus chinensis. has been shown to prevent iron-induced oxidative stress and liver Injury Sterol regulatory element binding protein-1c (SREBP-1c) plays a key role in hepatic steatosis, which promotes oxidative stress in obese subjects Previously, we identified the role of AMPK in liver X receptor-alpha (LXR alpha)-mediated SREBP-1c-dependent lipogenesis Because sauchinone as an antioxidant has the ability to activate AMPK, this study investigated its effects on SREBP-1c-dependent lipogenesis in hepatocytes and in high-fat diet (HFD)-induced hepatic steatosis and oxidative injury. Sauchinone prevented the ability of an LXR alpha agonist (T0901317) to activate SREBP-1c. repressing transcription of the fatty acid synthase, acetyl-CoA carboxylase, stearoyl-CoA desaturase-1, ATP-binding cassette transporter A1, and LXRa genes. Consistent with this, an HFD in mice caused fat accumulation in the liver with SREBP-1c induction, which was attenuated by sauchinone treatment Also, sauchinone had the ability to inhibit oxidative stress its shown by decreases in thiobarbituric acid-reactive substance formation, nitrotyrosinylation, and 4-hydroxynonenal production. Moreover. it prevented not only the liver Injury, but also the AMPK inhibition elicited by HFD feeding These results demonstrate that sauchinone has the capability to inhibit LXR alpha-mediated SREBP-is induction and SREBP-1c-dependent hepatic steatosis, thereby protecting hepatocytes from oxidative stress induced by fat accumulation. (C) 2009 Elseviei Inc All rights reserved.