Journal of Pineal Research Volume 51, Issue 4 pages 416–425, November 2011
Abstract: A link between endotoxemia and nonalcoholic fatty liver
disease (NAFLD) has been demonstrated in human and rodent animals. Nevertheless,
the molecular mechanisms of endotoxin-evoked NAFLD remain poorly understood. We
hypothesize that reactive oxygen species (ROS) mediate lipopolysaccharide
(LPS)-evoked hepatic lipid accumulation. Melatonin is an antioxidant. In the
present study, we investigated the effects of melatonin on LPS-induced hepatic
lipid accumulation. We showed that a single dose of LPS significantly increased
hepatic triglyceride (TG) contents and caused hepatic lipid accumulation in
mice. Further analysis found that hepatic sterol regulatory element-binding
protein (SREBP)-1c was activated in LPS-treated mice. In agreement with hepatic
SREBP-1c activation, fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC),
two SREBP-1c target genes, were significantly upregulated in liver of mice
injected with LPS. Melatonin significantly attenuated LPS-induced SREBP-1c
activation and the expression of SREBP-1c target genes. In addition, melatonin
reduced serum and hepatic triglyceride (TG) content and prevented LPS-induced
hepatic lipid accumulation. Taken together, these results suggest that ROS might
be, at least partially, mediated in LPS-induced SREBP-1c activation and hepatic
lipid accumulation. Melatonin may be useful as pharmacological agents to protect
against endotoxin-evoked NAFLD.
