Caloric restriction abolishes enhanced metabolic efficiency induced by ectopic agouti protein in yellow mice

Caloric restriction (CR), from approximately 3 months of age, at 70% of the ad libitum (AL) caloric intake prevented development of overt obesity in f emale "viable yellow" A(vy)/A (BALB/cStCrlfC3Hf/Nctr x VY/WffC3Hf/Nctr-A(vy )) F-1 hybrid mice, In adult yellow A(vy)/A mice, caloric restriction elimi nated the increased metabolic efficiency associated with the presence of ag outi protein in ectopic sites, At 4 weeks of age, the yellow A(vy)/A mice w ere approximate to 14% heavier and by 12 weeks of age, when caloric restric tion began, they were approximate to 24% heavier than the congenic agouti A /a mice. Between 4 and 12 weeks, the yellow mice gained approximate to 63% in body weight, whereas the agouti mice gained only approximate to 44%, Whi le the comparable AL A(vy)/A mice gained approximate to 128% and the AL A/a mice gained approximate to 41% between 12 and 51 weeks of age, the CR A(vy )/A and A/a mice gained only 16% and 15%, respectively. Mean brain weights of CR mice of both genotypes were lower than those of the comparable ad lib itum-fed (AL) groups; however, CR A(vy)/A mice had slightly, but significan tly (P < 0.0001), higher brain weights than CR A/a mice. The larger mean br ain weight and retention, during caloric restriction, of the somewhat great er prerestriction A(vy)/A mean body weight compared with prerestriction A/a mice were consonant with the hypothesis that ectopic agouti protein affect s somatic growth directly or indirectly. This may be related to altered dev elopmental/metabolic programming in yellow mice, indicated by greater metab olic efficiency and by an early transient increase in circulating IGF-1 lev els. The specific cellular processes modulated by the agouti protein in ect opic sites remain to be identified.