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J Biol Chem. 2018 Mar 16;293(11):3981-3988. doi: 10.1074/jbc.RA117.000885. Epub 2018 Feb 5.

Maresin 1 attenuates NAFLD by suppression of endoplasmic reticulum stress via AMPK-SERCA2b pathway.

Author information

1
From the Research Administration Team, Seoul National University Bundang Hospital, 13620 Gyeonggi, Republic of Korea.
2
the Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, 24341 Chunchon, Republic of Korea.
3
the Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, 12211-Giza, Egypt, and.
4
the Department of Pharmacology, College of Medicine, Chung-Ang University, 06974 Seoul, Republic of Korea jhjeong3@cau.ac.kr.

Abstract

Maresin 1 (MAR1), which is derived from docosahexaenoic acid biosynthesized by macrophages, has been reported to improve insulin resistance. Recently, it has been documented that MAR1 could ameliorate inflammation and insulin resistance in obese mice. These findings led us to investigate the effects of MAR1 on hepatic lipid metabolism. We found that MAR1 could stimulate AMP-activated protein kinase (AMPK), thereby augmenting sarcoendoplasmic reticulum Ca2+-ATPase 2b (SERCA2b) expression. This stimulation suppressed lipid accumulation by attenuating the endoplasmic reticulum (ER) stress in hepatocytes under hyperlipidemic conditions. Attenuation was mitigated by knockdown of AMPK or thapsigargin, a SERCA2b inhibitor. We also demonstrated that MAR1 administration resulted in increased hepatic AMPK phosphorylation and Serca2b mRNA expression, whereas hepatic ER stress was reduced in high-fat diet (HFD)-fed mice. Moreover, MAR1 treatment suppressed hepatic lipid synthesis, thereby attenuating hepatic steatosis in HFD-fed mice. In conclusion, our results suggest that MAR1 ameliorates hepatic steatosis via AMPK/SERCA2b-mediated suppression of ER stress. Therefore, MAR1 may be an effective therapeutic strategy for treating non-alcoholic fatty liver disease (NAFLD) via regulation of ER stress-induced hepatic lipogenesis.

KEYWORDS:

AMP-activated kinase (AMPK); Maresin 1; adiponectin; autophagy; endoplasmic reticulum stress (ER stress); fatty acid metabolism; non-alcoholic fatty liver disease; sarco-endoplasmic reticulum (ER) Ca2+-ATPase 2b

PMID:
29414781
PMCID:
PMC5857988
DOI:
10.1074/jbc.RA117.000885
[Indexed for MEDLINE]
Free PMC Article

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