45 Thus, insulin is likely to contribute to a large number of the regulations observed following BPA exposure. However, although the expression of some genes (e.g., Pnpla3) parallels plasma insulin levels, many other gene expression patterns do not strictly follow the insulin profile. Moreover, the up-regulation of genes involved in neoglucogenesis (G6pc and Pck1, Fig. 3C) is unexpected in the context of high insulin levels. We cannot rule out that other mechanisms, independent of insulin and possibly involving direct effects of BPA on the liver, may contribute to the transcriptional impacts of

low BPA doses reported here. We have shown an accumulation of liver Tanespimycin triglycerides and cholesteryl esters together with associated changes in hepatic FA composition in the animals exposed to low BPA doses. Among the mechanisms potentially involved in these effects (increased FA uptake, impaired secretion, increased lipogenesis, or reduced oxidation), our results point to an activation of lipogenesis and cholesterol

biosynthesis as the major mechanism involved, potentially associated Selleck EGFR inhibitor with an inhibition of FA oxidation. Simple hepatic lipid accumulation is generally considered a benign and reversible process that does not invariably progress to a more serious condition. However, inappropriate regulation of hepatic de novo lipogenesis is now believed to facilitate the generation of lipotoxic lipid intermediates that could contribute to the pathogenesis of NASH.46 NAFLD is strongly linked to overnutrition, underactivity,

and insulin resistance,47 but many other factors initiating hepatic steatosis or supporting the progression of NAFLD to NASH have been proposed.48 These include biologic or synthetic hepatotoxins, bacterial endotoxins, second and exposure to industrial petrochemicals. Because hepatic steatosis may lead to more severe pathologies such as NASH and fibrosis, the effects of environmental pollutants on liver functions should be carefully examined. We thank Colette Bétoulières, Raymond Gazel and Florence Blas Y Estrada for animal care and technical assistance for animal experiments and Joëlle Laffitte for help in setting up protein analyses. We thank Dr. Gilles Mithieux (INSERM U855) for the generous gift of the G6PASE antibody. We thank the staff members of the following GenoToul core facilities for technical assistance: MetaToul/Lipidomic, Genome & Transcriptome, Anexplo/Histopathology and Phenotyping. Additional Supporting Information may be found in the online version of this article. “
“Background and Aim:  The incidence of colorectal cancer (CC) is increasing in many Asian countries, but decreasing in western countries. The present study examined the local incidence of CC in the past few decades. Methods:  A population based study, using data from Hong Kong (HK) Cancer Registry, was carried out to examine the trends of CC in different age groups in HK.