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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 the MAPK-JNK/P38 signaling pathway. Western blot analysis for total and phosphorylated c-Jun N-terminal kinases (JNK) 1/2 and P38, n‚ÄČ=‚ÄČ6/group. a relative JNK(1/2 )/GAPDH intensity of ¬†four groups; b¬†relative p-JNK(1/2 )/GAPDH intensity of ¬†four groups; c¬†relative P38/GAPDH intensity of ¬†four groups; d¬†relative p-P38/GAPDH intensity of four groups; GAPDH: glyceraldehyde 3-phosphate dehydrogenase.¬†*P‚ÄČ<‚ÄČ0.05 for group A vs group B; #P‚ÄČ<‚ÄČ0.05 for group B vs group D
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Fig5: Effect of melatonin on the MAPK-JNK/P38 signaling pathway. Western blot analysis for total and phosphorylated c-Jun N-terminal kinases (JNK) 1/2 and P38, n‚ÄČ=‚ÄČ6/group. a relative JNK(1/2 )/GAPDH intensity of ¬†four groups; b¬†relative p-JNK(1/2 )/GAPDH intensity of ¬†four groups; c¬†relative P38/GAPDH intensity of ¬†four groups; d¬†relative p-P38/GAPDH intensity of four groups; GAPDH: glyceraldehyde 3-phosphate dehydrogenase.¬†*P‚ÄČ<‚ÄČ0.05 for group A vs group B; #P‚ÄČ<‚ÄČ0.05 for group B vs group D

Mentions: Furthermore, we evaluated the expression of P38 and c-Jun N-terminal kinases (JNK) 1/2 in liver by Western blotting (Fig. 5). HFD increased phosphorylated levels of P38 and JNK1/2, which was reversed by treatment with melatonin.Fig. 5


Melatonin improves non-alcoholic fatty liver disease via MAPK-JNK/P38 signaling in high-fat-diet-induced obese mice
Effect of melatonin on the MAPK-JNK/P38 signaling pathway. Western blot analysis for total and phosphorylated c-Jun N-terminal kinases (JNK) 1/2 and P38, n‚ÄČ=‚ÄČ6/group. a relative JNK(1/2 )/GAPDH intensity of ¬†four groups; b¬†relative p-JNK(1/2 )/GAPDH intensity of ¬†four groups; c¬†relative P38/GAPDH intensity of ¬†four groups; d¬†relative p-P38/GAPDH intensity of four groups; GAPDH: glyceraldehyde 3-phosphate dehydrogenase.¬†*P‚ÄČ<‚ÄČ0.05 for group A vs group B; #P‚ÄČ<‚ÄČ0.05 for group B vs group D
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Related In: Results  -  Collection

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Fig5: Effect of melatonin on the MAPK-JNK/P38 signaling pathway. Western blot analysis for total and phosphorylated c-Jun N-terminal kinases (JNK) 1/2 and P38, n‚ÄČ=‚ÄČ6/group. a relative JNK(1/2 )/GAPDH intensity of ¬†four groups; b¬†relative p-JNK(1/2 )/GAPDH intensity of ¬†four groups; c¬†relative P38/GAPDH intensity of ¬†four groups; d¬†relative p-P38/GAPDH intensity of four groups; GAPDH: glyceraldehyde 3-phosphate dehydrogenase.¬†*P‚ÄČ<‚ÄČ0.05 for group A vs group B; #P‚ÄČ<‚ÄČ0.05 for group B vs group D
Mentions: Furthermore, we evaluated the expression of P38 and c-Jun N-terminal kinases (JNK) 1/2 in liver by Western blotting (Fig. 5). HFD increased phosphorylated levels of P38 and JNK1/2, which was reversed by treatment with melatonin.Fig. 5

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