Introduction: Alms1 mutant (foz/foz) mice develop obesity due to defective appetite regulation. NOD.B10 foz/foz mice fed a high fat (HF) diet develop diabetes, ectopic lipid accumulation in non-adipose tissues and non-alcoholic steatohepatitis; whereas Balb/c foz/foz mice do not. The aim of this study is to determine if failure of adipose tissue expansion contributes to the abnormal metabolic phenotype of NOD.B10 foz/foz mice.
Methods: Female NOD.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 depot weights, blood glucose, plasma insulin, adiponectin and alanine transferase (ALT) were measured after 2, 4, 6 and 8 weeks on diet.
Results: After only 2 weeks of HF-feeding, NOD.B10 foz/foz mice showed evidence of hyperglycaemia, hyperinsulinaemia and hepatomegaly, which progressed with age. These features were not evident after 8 wks in Balb/c foz/foz mice. Plasma adiponectin fell in both NOD.B10 and Balb/c mice with HF-feeding. ALT increased in the NOD.B10 mice only. Adipose tissue depot weights were not different between strains after 8 weeks on HF-diet.
Conclusion: There was early evidence of an abnormal metabolic phenotype in HF-fed NOD.B10 foz/foz mice without concomitant failure of adipose tissue expansion.