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Evidence Level: 1 Technical Efficacy Stage: 3 [ABSTRACT FROM AUTHOR]

Dysregulated hepatic de novo lipogenesis contributes to the pathogenesis of nonalcoholic fatty liver disease in both humans and rodents. Clinical evidence suggests fatty liver to have a positive correlation with serum lead (Pb2+) levels. However, an exact mechanism of Pb2+‐induced fatty liver progression is still unknown. Here, we show that exposure to Pb2+ regulates ChREBP‐dependent hepatic lipogenesis. Presence of Pb2+ ions within the hepatocytes reduces transcript and protein levels of sorcin, a cytosolic adaptor partner of ChREBP. Adenovirus‐mediated overexpression of sorcin in Pb2+ exposed hepatocytes and an in vivo mouse model ameliorates liver steatosis and hepatotoxicity. Hereby, we present Pb2+ exposure to be a lethal disruptor of lipid metabolism in hepatocytes and highlight sorcin as a novel therapeutic target against Pb2+‐induced hepatic dyslipidemia. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease ( NAFLD) and associated advanced liver diseases have become prevalent conditions in many countries and are associated with increased mortality. Gene expression profiles in NAFLD have been examined recently but changes in expression elicited by chemical compound treatments have not been investigated. Since (-)-Epigallocatechin-3-gallate ( EGCG) and atorvastatin ( ATST) exhibit similar efficacy in NAFLD models, we reasoned that some common key genes might alter after treatment of EGCG and ATST. Accordingly, we applied integrated bioinformatics analyses of RNA microarray data from EGCG and ATST treatment groups compared to controls in a NAFLD phenotypic mouse model. Using differential expression ( DE) analysis, Kyoto Encyclopaedia of Genes and Genomes ( KEGG) pathway analysis, Gene Set Enrichment Analysis ( GSEA) and Clue GO enrichment, shared EGCG and ATST down-regulated pathways were identified which included extracellular matrix ( ECM)-receptor interaction and protein processing in endoplasmic reticulum ( ER). To refine key genes associated with liver fibrosis, a human NAFLD signature derived from patients of different fibrosis stages was analyzed. The results showed that fibrosis-related genes Col1a1, Col1a2, Col3a1 and Col6a3 were significantly down-regulated. These four genes were further validated as down-regulated in an independent mouse NAFLD dataset. We conclude that EGCG and ATST treatment results in the significant down-regulation of genes related to liver fibrosis. [ABSTRACT FROM AUTHOR]

Ciliary neurotrophic factor ( CNTF) analogues were reported to ameliorate fatty liver in db/db or high-fat diet-fed mice. It is generally thought that CNTF exerts its actions centrally. The aim of this study was to investigate whether peripheral effects of CNTF analogues are involved in the therapeutic effect on high fat-induced hepatic steatosis. The rat model of fatty liver was induced by a high-fat diet ( HFD) for 12 weeks. In the next 2 weeks, rats were fed the HFD along with subcutaneous injection of vehicle or mutant recombinant human CNTF (rhm CNTF 0.05-0.2 mg/kg per day). Steatotic HepG2 cells were induced by 50% fetal bovine serum ( FBS) for 48 hours, and then treated with rhm CNTF for 24 hours. The results showed that after rhm CNTF treatment, hepatic triglyceride ( TG) accumulation was attenuated both in vivo and in vitro. Rhm CNTF increased protein expression of CPT-1 and PPARα, and decreased SREBP-1c, FAS and SCD-1 in steatotic HepG2 cells. But the production of nitric oxide and 8-iso PGF2α in steatotic HepG2 cells was not affected by rhm CNTF. These results suggest that rhm CNTF has a peripheral effect that alleviates fat-induced hepatic steatosis. [ABSTRACT FROM AUTHOR]

Objective Streptococcus mutans, a major dental caries pathogen, has shown to be associated with the aggravation of cerebral hemorrhage and inflammatory bowel diseases. In this study, we evaluated the effects of S. mutans on the development of non-alcoholic steatohepatitis ( NASH) in a mouse model. Materials and methods Streptococcus mutans oral strain MT8148 (serotype c) and a blood isolate TW871 ( k) were used. C57BL/6J mice (6 weeks old) were fed a high-fat diet for 4 weeks; the test strains or phosphate-buffered saline was then intravenously administered. Mice were euthanized after 8 or 12 weeks. Whole body, extirpated liver, and visceral fat weights were determined, and histopathological evaluations of the liver specimens were performed. Results Mice infected with TW871 showed significantly greater body and liver weights than those administered MT8148 or phosphate-buffered saline. Histopathological analyses revealed prominent infiltration of inflammatory cells and adipocellular deposition in livers extirpated 8 weeks after an infection with TW871; fibrosis was also observed in livers extirpated after 12 weeks. Conclusion These results suggest that a specific strain of S. mutans could induce NASH. [ABSTRACT FROM AUTHOR]