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 female "viable yellow" Avy/A (BALB/cStCrlfC3Hf/Nctr x VY/WffC3Hf/Nctr-Avy) F1 hybrid mice. In adult yellow Avy/A mice, caloric restriction eliminated the increased metabolic efficiency associated with the presence of agouti protein in ectopic sites. At 4 weeks of age, the yellow Avy/A mice were approximately 14% heavier and by 12 weeks of age, when caloric restriction began, they were approximately 24% heavier than the congenic agouti A/a mice. Between 4 and 12 weeks, the yellow mice gained approximately 63% in body weight, whereas the agouti mice gained only approximately 44%. While the comparable AL Avy/A mice gained approximately 128% and the AL A/a mice gained approximately 41% between 12 and 51 weeks of age, the CR Avy/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 libitum-fed (AL) groups; however, CR Avy/A mice had slightly, but significantly (P < 0.0001), higher brain weights than CR A/a mice. The larger mean brain weight and retention, during caloric restriction, of the somewhat greater prerestriction Avy/A mean body weight compared with prerestriction A/a mice were consonant with the hypothesis that ectopic agouti protein affects somatic growth directly or indirectly. This may be related to altered developmental/metabolic programming in yellow mice, indicated by greater metabolic efficiency and by an early transient increase in circulating IGF-1 levels. The specific cellular processes modulated by the agouti protein in ectopic sites remain to be identified.
Wolff
G L
GL
Division of Biochemical Toxicology, National Center for Toxicological Research/Food and Drug Administration, Jefferson, Arkansas 72079, USA. GWOLFF@NCTR.FDA.GOV
Kodell
R L
RL
Kaput
J A
JA
Visek
W J
WJ
D000367:Age Factors; D054366:Agouti Signaling Protein; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D001921:Brain / Q000378:metabolism; D002149:Energy Intake; D005260:Female; D006824:Hybridization, Genetic; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000378:metabolism*
D054366:Agouti Signaling Protein; D001786:Blood Glucose; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; C515183:a protein, mouse; D007334:Insulin-Like Growth Factor I