Objective: An increased understanding of the factors influencing interindividual variation in calorie restriction (CR)-induced weight loss is necessary to combat the current obesity epidemic. This study investigated the partitioning of the phenotypic variation in CR-induced wight loss. Methods: Two generations of male and female outbred MF1 mice raised by their biological mother or a foster mother were studied. Mice were exposed to 4 weeks of 30% CR when 6 months old. Results: Heritability was estimated at 0.43 6 0.12 for CR-induced changes in body mass and 0.24 6 0.10 for fat mass using mid-parent-offspring regressions. No significant relationships between weight loss in fathers or foster mothers and offspring were observed. Partitioning of phenotypic variance in weight loss using maximum likelihood modeling indicated 19 6 17% of the variation could be attributed to additive genetic effects, 8 6 14% to maternal effects during pregnancy, and <1% to maternal effects during lactation. A narrow-sense heritability around 0.50 was observed for ad libitum food intake and general activity. Conclusions: A large part of individual variation in CR-induced weight loss could be attributed to additive genetic and maternal effects during pregnancy, but not to maternal effects in lactation. Genetic differences in food intake and general activity may play a role in determining these effects.

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