Factors predicting individual variability in diet-induced weight loss in MF1 mice

The effectiveness of caloric restriction (CR) as a treatment for obesity varies considerably between individuals. Reasons for this interindividual variation in weight loss in response to CR may lie in pre-existing individual differences and/or individual differences in compensatory responses. Here we studied the responses of 127 MF1 mice to 30% CR over four weeks, and investigated whether pre-existing differences or compensatory changes in body temperature, resting metabolic rate (RMR) and behavior explained the variation observed in body mass (BM) and fat mass (FM) changes. Mice showed considerable variation in BM loss (36-1%), and in the type of tissue lost (FM or fat free mass, FFM). About 50% of the variation in BM and FM loss could be predicted by pre-existing differences in food intake, RMR, and general activity, where BM loss was greater when food intake was lower and activity and RMR were higher. Compensatory changes in activity and body temperature together explained ~50% of the variation in BM and FM loss in both sexes. In models incorporating baseline variables and compensatory changes, food intake, and activity were the strongest predictors of weight loss in both sexes; i.e., lower baseline food intake and increased changes in activity resulted in greater BM and FM loss. Interestingly, increased baseline activity was a significant predictor of weight loss independent of compensatory changes in activity. Identifying factors involved in individual variability in weight loss may give insights into the mechanisms that underlie this variability, and is important to develop individually tailored weight-management strategies.