The yellow agouti mutation alters some but not all responses to diet and exercise.
OBJECTIVE
Effects of ectopic expression of the agouti signaling protein were studied on responses to diet restriction and exercise in C57BL/6J (B6) mice and obese B6 mice congenic for the yellow agouti mutation [B6.Cg-Ay (Ay)].


METHODS
Adult male Ay mice were either kept sedentary or exercised on a running wheel and fed ad libitum or diet restricted until weight matched to ad libitum-fed B6 control mice. Body composition, plasma lipids, leptin, and adiponectin were measured. mRNA levels for leptin, adiponectin, lipoprotein lipase, and pyruvate dehydrogenase kinase 4 were measured in a visceral (epididymal) and a subcutaneous (femoral) fat depot by real-time polymerase chain reaction.


RESULTS
Correlations among traits exhibited one of three patterns: similar lines for B6 and Ay mice, different slopes for B6 and Ay mice, and/or different intercepts for B6 and Ay mice. Correlations involving plasma leptin, mesenteric and epididymal adipose weights, or low-density lipoprotein-cholesterol were most likely to have different slopes and/or intercepts in B6 and Ay mice. mRNA levels for leptin, Acrp30, pyruvate dehydrogenase kinase 4, and lipoprotein lipase in epididymal adipose tissue were not correlated with corresponding levels in femoral adipose tissue.


CONCLUSIONS
The agouti protein interferes with leptin signaling at melanocortin receptors in the hypothalamus of Ay mice. Our results are consistent with the hypothesis that the melanocortin portion of the leptin-signaling pathway mediates effects primarily on certain fat depots and on some, but not all, components of cholesterol homeostasis.
Chiu
Sally
S
Rowe Program in Genetics, University of California, Davis, Davis, CA 95616, USA.
Fisler
Janis S
JS
Espinal
Glenda M
GM
Havel
Peter J
PJ
Stern
Judith S
JS
Warden
Craig H
CH
D052242:Adiponectin; D000273:Adipose Tissue / Q000033:anatomy & histology / Q000737:chemistry; D054366:Agouti Signaling Protein; D000818:Animals; D001823:Body Composition; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D004032:Diet; D004435:Eating; D005508:Food Deprivation; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000502:physiology; D020738:Leptin / Q000097:blood / Q000235:genetics; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009765:Obesity / Q000235:genetics; D009929:Organ Size; D005082:Physical Exertion; D011494:Protein Kinases / Q000235:genetics; D011506:Proteins / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction
D052242:Adiponectin; D054366:Agouti Signaling Protein; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D008055:Lipids; D011506:Proteins; D012333:RNA, Messenger; C515183:a protein, mouse; D002784:Cholesterol; D011494:Protein Kinases; C403287:pyruvate dehydrogenase kinase 4; D008071:Lipoprotein Lipase