title: Melatonin alleviates lipopolysaccharide-induced hepatic SREBP-1c activation and lipid accumulation in mice.
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.
authors.affiliation: First Affiliated Hospital, Anhui Medical University, Hefei, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.forename: Chang-E
authors.initials: CE
authors.lastname: Shi
authors.forename: Ren-Min
authors.initials: RM
authors.lastname: Zhu
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Jia-Bin
authors.initials: JB
authors.lastname: Li
authors.forename: De-Xiang
authors.initials: DX
authors.lastname: Xu
mesh_terms: D000818:Animals; D050356:Lipid Metabolism / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D051379:Mice; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D051780:Sterol Regulatory Element Binding Protein 1; D008550:Melatonin