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

Abstract
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.
AuthorsG L Wolff, R L Kodell, J A Kaput, W J Visek
JournalProceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) (Proc Soc Exp Biol Med) Vol. 221 Issue 2 Pg. 99-104 (Jun 1999) ISSN: 0037-9727 [Print] United States
PMID10352119 (Publication Type: Journal Article)
Chemical References
  • Agouti Signaling Protein
  • Blood Glucose
  • Intercellular Signaling Peptides and Proteins
  • Proteins
  • a protein, mouse
  • Insulin-Like Growth Factor I
Topics
  • Age Factors
  • Agouti Signaling Protein
  • Animals
  • Blood Glucose (analysis)
  • Body Weight
  • Brain (metabolism)
  • Energy Intake
  • Female
  • Hybridization, Genetic
  • Insulin-Like Growth Factor I (analysis)
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Organ Size
  • Phenotype
  • Proteins (genetics, metabolism)

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