title: Melatonin improves non-alcoholic fatty liver disease via MAPK-JNK/P38 signaling in high-fat-diet-induced obese mice.
abstract: BACKGROUND
  Melatonin can regulate lipid metabolism, increase insulin sensitivity, regulate glucose metabolism and reduce body weight. This study is aimed to determine the effects and mechanism of action of melatonin on non-alcoholic fatty liver disease (NAFLD) in high-fat-diet (HFD) induced obese mice.
  
  
  METHODS
  NAFLD was induced by HFD in C57BL/6 mice. A total of 24 mice were randomly assigned to 4 groups. Groups A and B were fed with HFD for 36 weeks while groups C and D were fed with a regular diet (RD). During the last 12 weeks, Groups A and C were treated with 10 mg/kg melatonin while Groups B and D were treated with water in the same volume by intragastric administration. Body and liver weight, blood glucose, serum transaminases and lipid levels, and markers of hepatic inflammation were measured. Histological analyses were also performed on liver tissue.
  
  
  RESULTS
  After 12 weeks of treatment with melatonin, body weights (Group A: before 53.11 ± 0.72 vs after 12w treatment 39.48 ± 0.74) and liver weights (A 1.93 ± 0.09 g vs B 2.92 ± 0.19 g vs C 1.48 ± 0.09 g vs D 1.49 ± 0.10 g), fasting plasma glucose, alanine transaminase (A 24.33 ± 11.90 IU/L vs B 60.80 ± 10.18 IU/L vs C 13.01 ± 3.49 IU/L vs D 16.62 ± 2.00 IU/L), and low-density cholesterol (A 0.24 ± 0.06 mmol/L vs B 1.57 ± 0.10 mmol/L vs C 0.28 ± 0.06 mmol/L vs D 0.29 ± 0.03 mmol/L) were significantly decreased in HFD mice. HFD fed mice treated with melatonin showed significantly less liver steatosis. Treatment of HFD fed mice with melatonin led to a significant decrease in the expression of TNF-α, IL-1β, and IL-6 measured using quantitative real-time polymerase chain reaction (qRT-PCR). HFD fed mice demonstrated increased phosphorylation of P38 and JNK1/2, which was reduced by melatonin treatment.
  
  
  CONCLUSIONS
  The study concluded that melatonin could improve NAFLD by decreasing body weight and reduce inflammation in HFD induced obese mice by modulating the MAPK-JNK/P38 signaling pathway.
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
authors.forename: Xingchun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
authors.forename: Kexiu
authors.initials: K
authors.lastname: Song
authors.affiliation: Department of Neurology, Weill Cornell Medical College, New York, NY, 10065, USA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Gusdon
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
authors.forename: Le
authors.initials: L
authors.lastname: Bu
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China. qushencn@hotmail.com.
authors.forename: Shen
authors.initials: S
authors.lastname: Qu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D016207:Cytokines / Q000187:drug effects / Q000235:genetics; D059305:Diet, High-Fat; D015536:Down-Regulation; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D016207:Cytokines; D008550:Melatonin
keywords: Inflammation; MAPK; Melatonin; NAFLD; Obesity