Abstract
ABSTRACT MiR-455 has been verified a key regulator of brown adipose tissue and adipose tissue-specific overexpression of miR-455 (ap2-miR-455) mice could combat high-fat-diet-induced obesity. This study is to verify overexpression of miR-455 could ameliorate the lipid accumulation and metabolism in the liver of db/db diabetic mice and explore the potential mechanisms. Diabetic mice (db/db) and control mice (db/m) were randomly divided into four groups. After overexpression of miR-455 in the liver of db/db mice, the triglycerides level in both serum and liver decreased, the lipid deposit in liver was improved, the expression of fatty acid synthase, stearoyl-CoA desaturase 1, sterol regulatory element binding protein 1c (SREBP-1c) and acetyl-CoA carboxylase (ACCα) was also significantly down-regulated. TargetScan indicated that suppressor of cytokine signalling 3 (SOCS3) is predicated to target miR-455 and the protein of SOCS3 in the liver of db/db mice after intervention was significantly decreased. The dual luciferase reporter assay showed that SOCS3 was target gene of miR-455. In vitro, in Palmitate (PA)-stimulated human normal liver (LO2) cells, transfected miR-455 mimic could significantly inhibit the expression of SOCS3, while transfected miR-455 inhibitor could up-regulate the expression of SOCS3. Transfecting LO2 cells with siRNA of SOCS3 could significantly down-regulate the protein expression of SREBP-1c and ACCα. Our study showed that overexpression of miR-455 in the liver could improve lipid metabolism in diabetic mice by down-regulating its target gene SOCS3.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is closely related to diabetes
Our study showed that overexpression of miR-455 in the liver could improve lipid metabolism in diabetic mice by down-regulating its target gene suppressor of cytokine signalling 3 (SOCS3)
We found that miR-455 could improve the liver metabolism by inhibiting suppressor of cytokine signalling 3 (SOCS3), as a member of SOCS family, negatively regulates the transduction of cytokine signalling [12]
Summary
Non-alcoholic fatty liver disease (NAFLD) is closely related to diabetes. Recent clinical researches have revealed that diabetes plays an important role in the progression of NAFLD [2,3] and has become a strong predictor of non-alcoholic steatohepatitis (NASH) and liver fibrosis [4]. MicroRNA (miRNA) is a non-coding single-stranded RNA molecule of approximately 20–24 nucleotides in length, regulates gene expression at the posttranscriptional level by binding to the mRNA of the target gene [6]. MiRNAs have been used as the clinical diagnostic markers for NAFLD/NASH, and even the potential predictors of primary liver cancer [8]. Recent studies indicate that miR-455 could improve the progression of different cancers [10,11], while there is still lack of the research focused on the regulation of miR-455 on liver metabolism
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