Abstract Background/Aims: Liver fatty acid–binding protein (FABP1) is a key regulator of hepatic lipid metabolism. Fundamentals of computer pdf download. MicroRNAs (miRNAs) are thought to be involved in nonalcoholic fatty liver disease (NAFLD), and the underlying mechanism is largely unclear. We investigated whether miRNAs influence hepatocyte steatosis by regulating the FABP1 gene. Methods: Candidate FABP1-targeting miRNAs were evaluated using luciferase reporter assay. FABP1 expression was measured using western blotting and quantitative reverse transcription–PCR. These are described in more detail in this linked article. Serial mandala siluman sungai ular terengganu. In valve repair, the diseased valve is fixed by making adjustments to the existing valve. Heart valve repair and replacement is conventionally performed with the use of the heart lung machine. Dec 14, 2017 - Surgically resected adjacent normal liver tissues were obtained. II Microplate Luminometer, Berthold Detection Systems, Pforzheim, Germany). Oil Red O staining was performed using standard procedures as previously described [30]. Starley BQ, Calcagno CJ, Harrison SA: Nonalcoholic fatty liver. The most extensively characterized action is the prejunctionally mediated inhibition of the release of neurotransmitters from many peripheral and central neurons. Α 2-adrenoceptors are also present at postjunctional sites, where they mediate actions such as smooth muscle contraction, platelet aggregation and inhibition of insulin secretion. Intracellular lipid accumulation was measured based on Oil Red O staining and intracellular triglyceride content. Hepatocyte injury was evaluated based on culture supernatant levels of alanine aminotransferase, aspartate aminotransferase, and intracellular adenosine triphosphate, and mitochondrial membrane potential. Results: Dicer1 knockdown significantly elevated FABP1 expression. In total, 68 miRNAs potentially targeting FABP1 were selected; of these, miR-3941, miR-4517, and miR-4672 directly targeted the FABP1 3ʹ untranslated region. Mimics of the three miRNAs substantially repressed FABP1 expression at translational level and led to HepG2 cell resistance to steatosis and cell injury induced by free fatty acids mixture, which rescue of FABP1 overexpression reversed. Conclusion: Our findings identify a novel mechanism by which miRNAs protect against hepatocyte steatosis and injury by downregulating FABP1 expression. © 2017 The Author(s). Published by S. Karger AG, Basel Introduction Non-alcoholic fatty liver disease (NAFLD) is deemed the hepatic manifestation of metabolic syndrome, the characteristics of which include insulin resistance, dyslipidemia, hypertension, and type 2 diabetes [, ]. The occurrence of NAFLD is mainly attributed to the accumulation of fat in the liver, and cirrhosis can follow; it is irreversible and may eventually develop into hepatocellular carcinoma [, ]. However, many factors are involved in the complex process of liver steatosis; its pathogenesis is largely unknown. Flexisign pro 10 crack only windows 7. Recent cell studies and genetically modified mouse models have demonstrated that hepatic lipid metabolism and steatosis are crucially affected by peroxisome proliferators–activated receptor (PPAR)-c coactivator 1α and 1β [, ], receptor-interacting protein 140 [], and liver fatty acid–binding protein [] (FABP1 or L-FABP). FABP1 belongs to a multi-gene FABP family of 14–15-kDa cytoplasmic proteins involved in the uptake, transport, and metabolism of cellular long-chain fatty acids and other lipid ligands []. The human FABP1 gene is localized in the p11.2 region of chromosome 2 []. FABP1 is abundant in the cytosol of liver parenchymal cells [, ] and represents approximately 0.2% of the total cytosolic proteins in the human hepatoblastoma cell line HepG2 []. ![]() Similar to its family members, FABP1 plays a central role in intracellular fatty acid transport and utilization [] and is also involved in modulating mitosis [], cell growth, and differentiation []. In vitro cell models and in vivo mouse models have indicated that FABP1 plays an important role in regulating hepatic lipid metabolism. HepG2 cell studies have indicated that FABP1 overexpression markedly increased the rate of fatty acid uptake. ![]() In contrast, FABP1 antisense RNA expression decreased fatty acid uptake significantly []. FABP1 -/- mice fed a high–saturated fat, high-cholesterol “Western” diet were protected against diet-induced obesity and hepatic steatosis, reflecting an alteration in the kinetics of saturated fatty acid utilization [, ]. MicroRNAs (miRNAs) are single-stranded, 19–25-nucleotide long, non-coding RNAs that are involved in the regulation of numerous biological processes by base-pairing, usually imperfectly, to the 3’ untranslated region (UTR) of a target mRNA, inhibiting it post-transcriptionally and occasionally leading to mRNA degradation [, ]. MiRNAs can regulate the metabolism-related genes potentially involved in NAFLD pathogenesis. For example, the most highly expressed hepatic miRNA is miR-122, a regulator of cholesterol and fatty acid metabolism [,, ]; miR-10b regulates cellular steatosis levels through PPARα [].
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