SFEBES2014 Poster Presentations Steroids (39 abstracts)
Enhanced expression of hepatic inflammatory markers in 11β-hydroxysteroid dehydrogenase type 1 knockout mice fed a steatogenic diet
Dean Larner 1 , Stuart Morgan 1 , Laura Gathercole 1 , Maryam Nasiri 1 , Philip Guest 1 , Matthew Chapman 1 , Jeremy Tomlinson 1 , Paul Stewart 2 & Gareth Lavery 1
1University of Birmingham, Birmingham, UK; 2University of Leeds, Leeds, UK.
Non-alcoholic fatty liver disease (NAFLD) is characterised by intra-hepatocyte lipid accumulation. Simple steatosis, which is a reversible condition, can progress to non-alcoholic steatohepatitis (NASH), cirrhosis and eventually hepatocellular carcinoma. The aetiology of NAFLD is not fully understood and it is suggested that glucocorticoid reactivation through the activity of the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme may promote hepatic lipid accumulation and contribute to the potential to develop steatosis. To test this, 11β-HSD1KO and C57BL/6 control mice (n=11–13) were fed the American life style induced obesity syndrome (ALIOS) diet, known to induce NAFLD, for 16 weeks. Mice were weighed weekly and glucose and insulin tolerance tests (GTT and ITT respectively) performed. We found that there were no differences between bodyweights or fasting blood-glucose concentrations, with GTTs and ITTs showing no differences between 11β-HSD1KO and controls. There was no difference between liver weights of WT and KOs. To assess hepatic histopathology, H&E stained sections were blind scored for the degree of steatosis (0–3, zero being absent, three being severe). In control livers, an average score of 1.8 was seen, which was elevated to 2.3 in 11β-HSD1KO livers. Finally, we have expression profiled our cohorts and did not observe any changes in the expression of genes associated with metabolic processes or reactive oxygen species defence. However, as the ALIOS diet can induce hepatic inflammation, we assessed the expression of a series of inflammatory markers and had highly significant increases in the mRNA of Tnfa (P<0.001), Col1a1 (P<0.01) and Fsp (P<0.001) in 11β-HSD1KO mice compared to controls. While the ablation of 11β-HSD1 does not ameliorate steatosis in mice, it does evoke increased expression of inflammatory response genes that could exacerbate the progression of simple steatosis to NASH. These data highlight the important role 11β-HSD1 may play in restricting inflammation associated with the steatotic liver.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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