The investigators also compared responses in normal mice to mice that lack a functional PPARalpha to determine if PPARalpha was directly involved in any of the responses that are induced by calorie restriction. They found that the PPARalpha-mutant mice lack many of the characteristics of calorie restriction, including changes in genes that may play important roles in heart disease and cancer. Calorie restriction is also known to protect animals from chemical exposure, and the investigators found that the protection afforded by calorie restriction in normal mice was lost in PPARalpha-mutant mice.

"PPARalpha may be one of a handful of receptors that play important roles in mediating the beneficial effects of calorie restriction. Our findings could be used to take a rational approach to designing drugs that mimic beneficial aspects of calorie restriction," said Harihara M. Mehendale, PhD, senior author and professor and Kitty DeGree Endowed Chair in Toxicology at the University of Louisiana at Monroe.

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Contact: Kenna L. Lowe
paffairs@jhsph.edu
410-955-6878
Johns Hopkins University Bloomberg School of Public Health
10-Aug-2004