Male 11β-HSD1 knockout mice fed trans-fats and fructose are not protected from metabolic syndrome or non-alcoholic fatty liver disease

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External organisations

  • University of Oxford
  • University of Leeds


Non-alcoholic fatty liver disease (NAFLD) defines a spectrum of conditions from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis, and is regarded as the hepatic manifestation of the metabolic syndrome (MetS). Glucocorticoids (GCs) can promote steatosis by stimulating lipolysis within adipose tissue, FFA delivery to liver and hepatic de novo lipogenesis. GCs can be reactivated in liver through 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme activity. Inhibition of 11β-HSD1 has been suggested as a potential treatment for NAFLD. To test this, male mice with global (11β-HSD1KO) and liver-specific (LKO) 11β-HSD1 loss-of-function were fed the American Lifestyle Induced Obesity Syndrome (ALIOS) diet, known to recapitulate the spectrum of NAFLD, and metabolic and liver phenotypes assessed. Body weight, muscle and adipose tissue masses, and parameters of glucose homeostasis showed that 11β-HSD1KO and LKO mice were not protected from systemic metabolic disease. Evaluation of hepatic histology, triglyceride content and blinded NAS assessment indicated that levels of steatosis were similar between 11β-HSD1KO, LKO and control mice. Unexpectedly, histological analysis revealed significantly increased levels of immune foci present in livers of 11β-HSD1KO but not LKO or control mice, suggestive of a transition to NASH. This was endorsed by elevated hepatic expression of key immune cell and inflammatory markers. These data indicate that 11β-HSD1 deficient mice are not protected from metabolic disease or hepatosteatosis in the face of a NAFLD inducing diet. However, global deficiency of 11β-HSD1 did increase markers of hepatic inflammation and suggests a critical role for 11β-HSD1 in restraining the transition to NASH. - See more at:


Original languageEnglish
Issue number9
Early online date6 Jul 2016
Publication statusPublished - Sep 2016

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