Long non-coding RNA (lncRNA) H19 induces hepatic steatosis through activating MLXIPL and mTORC1 networks in hepatocytes.

Long non-coding RNA (lncRNA) H19 induces hepatic steatosis through activating MLXIPL and mTORC1 networks in hepatocytes. J Cell Mol Med. 2019 Dec 06;: Authors: Wang H, Cao Y, Shu L, Zhu Y, Peng Q, Ran L, Wu J, Luo Y, Zuo G, Luo J, Zhou L, Shi Q, Weng Y, Huang A, He TC, Fan J Abstract Liver plays an essential role in regulating lipid metabolism, and chronically disturbed hepatic metabolism may cause obesity and metabolic syndrome, which may lead to non-alcoholic fatty liver disease (NAFLD). Increasing evidence indicates long non-coding RNAs (lncRNAs) play an important role in energy metabolism. Here, we investigated the role of lncRNA H19 in hepatic lipid metabolism and its potential association with NAFLD. We found that H19 was up-regulated in oleic acid-induced steatosis and during the development of high-fat diet (HFD)-induced NAFLD. Exogenous overexpression of H19 in hepatocytes induced lipid accumulation and up-regulated the expression of numerous genes involved in lipid synthesis, storage and breakdown, while silencing endogenous H19 led to a decreased lipid accumulation in hepatocytes. Mechanistically, H19 was shown to promote hepatic steatosis by up-regulating lipogenic transcription factor MLXIPL. Silencing Mlxipl diminished H19-induced lipid accumulation in hepatocytes. Furthermore, H19-induced lipid accumulation was effectively inhibited by PI3K/mTOR inhibitor PF-04691502. Accordingly, H19 overexpression in hepatocytes up-regulated most compone...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research

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In conclusion, all above mechanisms appear to intervene synergistically and may act as modifiable risk factors for infant and mother NAFLD. PMID: 31969089 [PubMed - as supplied by publisher]
Source: Current Pharmaceutical Design - Category: Drugs & Pharmacology Authors: Tags: Curr Pharm Des Source Type: research
Obesity is a chronic disease with rising worldwide prevalence and largely associated with several other comorbidities, such as cancer, non-alcoholic fatty liver disease (NAFLD), and metabolic syndrome. Hepatic steatosis, a hallmark of NAFLD, is strongly correlated with obesity and has been correlated with changes in the gut microbiota, which can promote its development through the production of short-chain fatty acids (SCFAs) that regulate insulin resistance, bile acid, choline metabolism, and inflammation. Recent studies have suggested a controversial role for the inflammasome/caspase-1 in the development of obesity and n...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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Non-alcoholic fatty liver disease (NAFLD) figures prominently into the clinical hepatology landscape. NAFLD represents a disease spectrum comprising simple steatosis, steatosis with elevated liver enzymes, and non-alcoholic steatohepatitis (NASH), the entity with clear potential for fibrosis progression. Risk factors associated with fibrosis progression in NASH include histologic findings of lobular inflammation and any fibrosis as well as clinical comorbidities that include type 2 diabetes, obesity, and metabolic syndrome. Liver biopsy remains the gold standard in evaluating NASH; however, noninvasive methods are accumula...
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Source: Arquivos de Gastroenterologia - Category: Gastroenterology Source Type: research
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