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Dietary Fat and Sex Modify Heterozygote Effects of the Rat Fatty (fa) Allele¹

Physiology Program and Department of Nutrition, University of Tennessee, Knoxville, TN 37996-1900 ^* Pennington Biomedical Research Center, Baton Rouge, LA 70808-4124

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.

KEY WORDS: • Zucker rats • heterozygote effects • high fat diet • genetics • obesity

¹ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

² To whom correspondence should be addressed.

Manuscript received 20 February 1996. Revision accepted 2 July 1996.

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