Introduction: Alms1 mutant (foz/foz) mice develop obesity due to defective appetite regulation. NOD.B10 foz/foz mice on 24 weeks of high fat (HF) diet develop diabetes, adipose tissue restriction and non-alcoholic steatohepatitis; whereas Balb/c foz/foz mice do not. The aim of this study is to determine the role of adipose tissue in the abnormal metabolic phenotype of NOD.B10 foz/foz mice.
Methods: FemaleNOD.B10 and Balb/c WT and foz/foz mice were fed chow or HF-diet from 4 weeks of age and body, liver and adipose weights, blood glucose, plasma insulin, adiponectin and alanine transferase (ALT) were measured after 2, 4, 6 and 8 weeks on diet. mRNA expression of markers for adipose differentiation and inflammation were analysed at 6 and 12 weeks of age and normalised to the geometric mean of 2 housekeeping genes: cyclophillin and GAPDH.
Results: At 12 weeks of age,HF-fedNOD.B10 foz/foz mice developed hyperglycaemia, hyperinsulinaemia and hepatomegaly with increased plasma ALT and hypoadiponectinaemia. These features were not evident in Balb/c foz/foz mice. However, no difference was observed in the adipose tissue depot weights and mRNA expression of differentiation and inflammation markers between both strains.
Conclusion: There was early evidence of diabetes and insulin resistance in HF-fed NOD.B10 foz/foz mice without concomitant adipose restriction and dedifferentiation, suggesting a secondary role for adipose tissue in the pathogenesis of NASH.