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). Previou s data suggested to us that fa heterozygotes may be more sensitive tha n wild-type rats to high fat diets. To test this hypothesis, we genera ted +/+ 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 fa t 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 so leus plasma membrane calcium-ATPase concentrations were significantly lower in rats fed the high fat diet. This protein was also lower in so leus of fa/+ rats compared with +/+ rats. There were significant diet x genotype interactions such that the high fat diet had the greatest e ffect on fat pads and calcium-ATPase in fa/+ rats. The results of the present study show heterozygote effects of the fa allele and suggest t hat these effects may be modulated by both sex-related factors and die tary manipulation.