Suppression of miR-30a-3p Attenuates Hepatic Steatosis in Non-alcoholic Fatty Liver Disease
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Suppression of miR‑30a‑3p Attenuates Hepatic Steatosis in Non‑alcoholic Fatty Liver Disease De‑Run Wang, et al. [full author details at the end of the article] Received: 25 October 2019 / Accepted: 4 May 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Non-alcoholic fatty liver disease (NAFLD) have a high prevalence in humans in the past two decades. Here, we elucidated the functions of miR-30a-3p in the development of NAFLD and identified its potential targets. HepG-2 cells and NAFLD patients’ blood samples were used in our study. Bioinformatics analysis as well as luciferase reporter assays were employed to distinguish peroxisome proliferator-activated receptor alpha (PPAR-α) as a target gene. Western blotting showed the expressions of lipid metabolic proteins and the target gene PPAR-α. Oil red O staining and triglyceride activity tested the fatty deposits after treatment with miR-30a-3p. miR30a-3p was substantially up-regulated in NAFLD. Bioinformatics analyses showed that PPAR-α was a possible target of miR-30a-3p, linked with signaling pathways in NAFLD. PPAR-α as a novel target of miR-30a-3p, and suppression of its levels. The lipid metabolic-related proteins ACC, p-GSK-3β and FASN were up-regulated after transfecting with miR-30a-3p mimic, but the proteins CPT1, p-AMPK and UCP2 were down-regulated. miR-30a-3p inhibitor could diminish the protein manifestation of ACC, p-GSK-3β and FASN; and augment the protein manifestation of CPT1, p-AMPK and UCP2. On the contrary, overexpression of miR-30a-3p had adverse impacts on the performance of hepatocellular lipid accumulation and Triglyceride (TG) activity. Co-treatment with miR-30a-3p mimic and overexpression PPAR-α could revise the hepatic steatosis and the TG level induced by fat milk. Our findings suggest that miR-30a-3p/PPAR-α may be developed as a potential agent in NAFLD, which is enough to attenuate triglyceride accumulation and hepatic steatosis. Keywords microRNAs · PPAR-α · Hepatic steatosis · Non-alcoholic fatty liver disease
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1052 8-020-09971-0) contains supplementary material, which is available to authorized users.
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Biochemical Genetics
Introduction NAFLD is a multifactorial, global chronic liver disorder, especially in adult humans (Fukui et al. 2017). Approximately 15–30% of the general adult population suffer from NAFLD (Firneisz 2014; Long et al. 2018). Existing reports suggest that many diseases are related with the advancement of NAFLD, such as type two diabetes mellitus and dyslipidemia (David et al. 2017; Szabo and Csak 2016; Wong et al. 2017) and NAFLD can further develop into non-alcoholic steatohepatitis and then develop into hepatic steatosis, liver fibrosis, and ultimately lead to cirrhosis and liver cancer (He et al. 2016; Otsuka et al. 2017; Spahis et al. 2017). However, the diagnostic markers or effective drugs or underlying mechanisms for non-alcoholic fatty liver disease are
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