Dietary fat and sex modify heterozygote effects of the rat fatty (fa) allele

Rats carrying one copy of the obesity gene fa may exhibit intermediate phenotypes between lean (+/+) and homozygous mutants (fa/fa). Previous data suggested to us that fa heterozygotes may be more sensitive than wild-type rats to high fat diets. To test this hypothesis, we generated +/+ and fa/+ rats and fed them diets containing 12% or 48% energy as fat for 7 wk. Energy efficiency was significantly greater in males than in females and in high fat-fed vs. low fat-fed rats. Perirenal fat pad weights were significantly greater in males than in females, in high fat-vs. low fat-fed rats and in fa/+ vs. +/+ rats. Adipose and soleus plasma membrane calcium-ATPase concentrations were significantly lower in rats fed the high fat diet. This protein was also lower in soleus of fa/+ rats compared with +/+ rats. There were significant diet x genotype interactions such that the high fat diet had the greatest effect on fat pads and calcium-ATPase in fa/+ rats. The results of the present study show heterozygote effects of the fa allele and suggest that these effects may be modulated by both sex-related factors and dietary manipulation.