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Down‐regulation of micro RNA ‐375 regulates adipokines and inhibits inflammatory cytokines by targeting AdipoR2 in non‐alcoholic fatty liver disease
Author(s) -
Lei Lei,
Zhou Chao,
Yang Xue,
Li Liangping
Publication year - 2018
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12940
Subject(s) - adiponectin , adipokine , proinflammatory cytokine , endocrinology , tumor necrosis factor alpha , medicine , fatty liver , leptin , gene silencing , adipose tissue , inflammation , cancer research , biology , chemistry , disease , insulin resistance , gene , obesity , biochemistry
Summary Non‐alcoholic fatty liver disease ( NAFLD ) has been considered as a multi‐factorial metabolic syndrome. Micro RNA ‐375 (MiR‐375) was significantly up‐regulated in serum of NAFLD patients and the role of miR‐375 was addressed as a putative biomarker of NAFLD progression. However, the specific function of miR‐375 in the progression of NAFLD is still unclear and the molecular mechanisms underlying NAFLD have yet to be elucidated. Our study aimed at investigating the regulatory role of miR‐375 in the molecular mechanisms of the pathogenic progression of NAFLD and to find out whether miR‐375 regulates the expression level of adipokines and inflammatory cytokines in NAFLD . We found that miR‐375 expression was increased in the serum of high fat diet ( HFD )‐feeding mice comparing to that in healthy controls, whereas the expression of Adiponectin receptor 2 (AdipoR2) was decreased in mice fed with HFD . Moreover, inhibiton of miR‐375 up‐regulated the expression of Adiponectin, inhibited the lipid accumulation and down‐regulated both the level of Leptin and inflammatory cytokines including tumour necrosis factor ( TNF )‐α and interleukin ( IL )‐6 in palmiticacid ( PA )‐induced human hepatocellular carcinoma HepG2 cells. In addition, we also found that AdipoR2 was a target of miR‐375 by binding directly to the 3′ UTR of it. Of note, the reduced level of TNF ‐α, IL ‐6 as well as Leptin and the production of Adiponectin by miR‐375 inhibitors was significantly reversed by silencing of AdipoR2 in PA ‐induced HepG2 cells. Our findings bring new insight into understanding the complex mechanisms underlying the pathogenesis of NAFLD and provide evidence that miR‐375 might represent a novel therapeutic target for NAFLD .