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Melatonin improves non-alcoholic fatty liver disease via MAPK-JNK/P38 signaling in high-fat-diet-induced obese mice

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus

Effect of melatonin on body weight and liver mass. (A) Body weight (g) of HFD with melatonin, HFD, RD with melatonin and RD during 36 weeks, n = 6 mice/group. (B) Liver mass of HFD with melatonin, HFD, RD with melatonin and RD at the end of treatment, n = 6 mice/group. *P < 0.05 for group A vs group B; #P < 0.05 for group B vs group D
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Fig1: Effect of melatonin on body weight and liver mass. (A) Body weight (g) of HFD with melatonin, HFD, RD with melatonin and RD during 36 weeks, n = 6 mice/group. (B) Liver mass of HFD with melatonin, HFD, RD with melatonin and RD at the end of treatment, n = 6 mice/group. *P < 0.05 for group A vs group B; #P < 0.05 for group B vs group D

Mentions: As shown in Fig. 1A, HFD increased body weight and liver mass compared with RD. [at 24w: (A) 53.11 ± 0.72 vs (B) 53.30 ± 0.60 vs (C) 37.25 ± 0.40 vs (D) 37.50 ± 0.39 g]. The average body weight of high fat diet fed mice is ~42.4% more than the regular diet fed mice. Administration of melatonin significantly reduced both body weight by ~30.2% less than the HFD mice [at36w: (A) 39.48 ± 0.74 vs (B) 56.56 ± 0.62 vs (C) 38.18 ± 0.45 vs (D) 38.01 ± 0.44 g]. Livers were removed upon sacrifice and liver mass was measured. As shown in Fig. 1B, the liver mass of melatonin treated mice is ~ 33.9% less than the HFD mice [(A) 1.93 ± 0.09 vs (B) 2.92 ± 0.19 vs (C) 1.48 ± 0.09 vs (D) 1.49 ± 0.10 g] (p < 0.01 between A and B).Fig. 1


Melatonin improves non-alcoholic fatty liver disease via MAPK-JNK/P38 signaling in high-fat-diet-induced obese mice
Effect of melatonin on body weight and liver mass. (A) Body weight (g) of HFD with melatonin, HFD, RD with melatonin and RD during 36 weeks, n = 6 mice/group. (B) Liver mass of HFD with melatonin, HFD, RD with melatonin and RD at the end of treatment, n = 6 mice/group. *P < 0.05 for group A vs group B; #P < 0.05 for group B vs group D
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Fig1: Effect of melatonin on body weight and liver mass. (A) Body weight (g) of HFD with melatonin, HFD, RD with melatonin and RD during 36 weeks, n = 6 mice/group. (B) Liver mass of HFD with melatonin, HFD, RD with melatonin and RD at the end of treatment, n = 6 mice/group. *P < 0.05 for group A vs group B; #P < 0.05 for group B vs group D
Mentions: As shown in Fig. 1A, HFD increased body weight and liver mass compared with RD. [at 24w: (A) 53.11 ± 0.72 vs (B) 53.30 ± 0.60 vs (C) 37.25 ± 0.40 vs (D) 37.50 ± 0.39 g]. The average body weight of high fat diet fed mice is ~42.4% more than the regular diet fed mice. Administration of melatonin significantly reduced both body weight by ~30.2% less than the HFD mice [at36w: (A) 39.48 ± 0.74 vs (B) 56.56 ± 0.62 vs (C) 38.18 ± 0.45 vs (D) 38.01 ± 0.44 g]. Livers were removed upon sacrifice and liver mass was measured. As shown in Fig. 1B, the liver mass of melatonin treated mice is ~ 33.9% less than the HFD mice [(A) 1.93 ± 0.09 vs (B) 2.92 ± 0.19 vs (C) 1.48 ± 0.09 vs (D) 1.49 ± 0.10 g] (p < 0.01 between A and B).Fig. 1

View Article: PubMed Central - PubMed

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&nbsp;weeks while groups C and D were fed with a regular diet (RD). During the last 12&nbsp;weeks, Groups A and C were treated with 10&nbsp;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&nbsp;weeks of treatment with melatonin, body weights (Group A: before 53.11&thinsp;&plusmn;&thinsp;0.72 vs after 12w treatment 39.48&thinsp;&plusmn;&thinsp;0.74) and liver weights (A 1.93&thinsp;&plusmn;&thinsp;0.09&nbsp;g vs B 2.92&thinsp;&plusmn;&thinsp;0.19&nbsp;g vs C 1.48&thinsp;&plusmn;&thinsp;0.09&nbsp;g vs D 1.49&thinsp;&plusmn;&thinsp;0.10&nbsp;g), fasting plasma glucose, alanine transaminase (A 24.33&thinsp;&plusmn;&thinsp;11.90&nbsp;IU/L vs B 60.80&thinsp;&plusmn;&thinsp;10.18&nbsp;IU/L vs C 13.01&thinsp;&plusmn;&thinsp;3.49&nbsp;IU/L vs D 16.62&thinsp;&plusmn;&thinsp;2.00&nbsp;IU/L), and low-density cholesterol (A 0.24&thinsp;&plusmn;&thinsp;0.06&nbsp;mmol/L vs B 1.57&thinsp;&plusmn;&thinsp;0.10&nbsp;mmol/L vs C 0.28&thinsp;&plusmn;&thinsp;0.06&nbsp;mmol/L vs D 0.29&thinsp;&plusmn;&thinsp;0.03&nbsp;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-&alpha;, IL-1&beta;, 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.

No MeSH data available.


Related in: MedlinePlus