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Melatonin alleviates lipopolysaccharide‐induced hepatic SREBP‐1c activation and lipid accumulation in mice
Author(s) -
Chen Xi,
Zhang Cheng,
Zhao Mei,
Shi ChangE.,
Zhu RenMin,
Wang Hua,
Zhao Hui,
Wei Wei,
Li JiaBin,
Xu DeXiang
Publication year - 2011
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2011.00905.x
Subject(s) - melatonin , medicine , endocrinology , sterol regulatory element binding protein , lipopolysaccharide , nonalcoholic fatty liver disease , triglyceride , lipid metabolism , fatty liver , lipogenesis , biology , chemistry , sterol , cholesterol , disease
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.