Melatonin Alleviates Lipopolysaccharide-induced Hepatic Lipid Accumulation In Mice

Objective In the mouse model of LPS-induced inflammation and infection, the role ofsterol regulatory element-binding protein (SREBP-1c) activation was investigated inlipopolysaccharide(LPS)-induced hepatic lipid accumulation. Furthermore, the effectsof melatonin on lipopolysaccharide-induced hepatic lipid accumulation were studyed inmice.Methods24male ICR mice were randomly divided into2groups. The saline-treatedmice served as control group, LPS groups were intraperitoneally injected with a singledose of LPS (2mg/kg). Body weight was assessed and mice were killed at24h afterLPS treatment. Blood samples were collected, and liver tissues were assessed. The levelof triglycerides（TG）and total cholesterol（TCH）were detected in serum and liver. HEstaining and oil red O staining was carried out to assess the change of hepatic histologyand lipid accumulation. The level of hepatic fatty acid synthase (FAS), acetylcoenzyme A carboxylase (ACC) and stearoyl coenzyme A desaturase-1(SCD-1) andfatty acid translocase（CD36）mRNA, which are key genes for de novo fatty acidsyntheses in liver, were determined using RT-PCR.The expressions of hepaticlipogenesis transcription factors carbohydrate response element binding protein(ChREBP) and sterol regulatory-binding protein (SREBP-1c) were determined usedwestern blotting.To observe the effects of melatonin on lipopolysaccharide-induced hepatic lipidaccumulation in mice,48mice were randomly divided into control group (CON),melatonin group (MT), LPS group (LPS), melatonin+LPS group (ML).Mice in control group were treated with saline. Mice in MT group were treated with melatonin (5mg/kg, i. p.). Mice in LPS group were treated with LPS (2mg/kg, i. p.).Mice inmelatonin+LPS group were treated with melatonin (5mg/kg, i. p.) and LPS (2mg/kg, i.p.). Mice in melatonin+LPS group mice were intraperitoneally injected with two dosesof melatonin (5mg/kg), one injected30min before LPS, and the second injected150min after LPS. Body weight was assessed and mice were killed at24h after LPStreatment. Blood samples were collected, and liver tissues were assessed. The level oftriglyceride（sTG）and total cholestero（lTCH）were detected in serum and liver. Oil redO staining was carried out to assess lipid accumulation. The level of FAS，ACC，SCD-1and CD36mRNA were determined using RT-PCR.The expressions of hepatic ChREBPand SREBP-1c were determined used western blotting.Results The absolute and relative liver weights were significantly increased inLPS-treated mice compared with the control group. The level of serum and hepatic TGwere significantly increased in LPS-treated mice. Hepatic histology showed a steatosisassociated with mild necrosis and inflammation. Oil red O staining showed an obvioushepatic lipid accumulation. Moreover, the level of hepatic FAS and ACC and CD36mRNA was significantly upregulated in LPS-treated mice. Western blotting showed thelevel of nuclear SREBP-1c was significantly increased.All mice in melatonin+LPS group were intraperitoneally injected with two dosesof melatonin (5mg/kg), one injected30min before LPS, and the second injected150min after LPS show melatonin interference significantly attenuated LPS-induced serumand hepatic TG increased;Oil red O staining showed melatonin attenuated LPS-inducedlipid accumulation;RT-PCR showed melatonin attenuated LPS-induced upregulation ofhepatic FAS and ACC and CD36mRNA; Western blotting showed LPS-inducedelevation of nuclear SREBP-1c was alleviated in mice interfered with melatonin. Conclussions ROS might be, at least partially, mediated in LPS-induced SREBP-1cactivation and hepatic lipid accumulation. Melatonin may be useful as pharmacologicalagents to protect against endotoxin-evoked nonalcoholic fatty liver disease (NAFLD).