Response to Dupuis, Petersen, and Weydt

The points raised by Dupuis, Petersen, and Weydt (Dupuis et al., 2012) regarding our findings (Matsubara et al., 2012) are intriguing. We found that PGRN-deficient mice exhibit decreased body weight, increased insulin sensitivity, and decreased respiratory quotient compared to wild-type mice only when they are exposed to high-fat diet (HFD); there are no differences in these metabolic parameters between wild-type mice and PGRN-deficient mice under normal chow conditions. This suggests that ablation of PGRN suppresses HFD-induced obesity by consuming lipids more preferentially than carbohydrates.