Downregulation of plasma insulin levels and hepatic PPARgamma expression during the first week of caloric restriction in mice.
Calorie restriction extends lifespan by decreasing the rate of tumor formation, an effect occurring within 8 weeks of initiating a restricted diet. Our goal was to define how the first weeks of a calorie restricted diet (60% of ad libitum calories) affects putative mediators of the calorie restriction phenotype, focusing on regulators of fatty acid biosynthesis. In C57Bl/6 mice, insulin decreased over 50% (p<0.05) during the first week of calorie restriction whereas IGF-1 was unaffected. In the liver, PPARgamma mRNA fell to 13% of baseline after 1 week of calorie restriction (p<0.05), whereas hepatic SREBP-1c and SIRT1 mRNA levels were unaffected. No changes in abdominal or subcutaneous adipose tissue were observed until after 4 weeks of caloric restriction. We conclude that calorie restriction-induced decreases in insulin and hepatic PPARgamma are rapid enough to support a role for these molecules in triggering the initial phase of the calorie restriction phenotype.
Department of Medicine, University of Wisconsin, 1630 Medical Sciences Center, Madison, WI 53706, USA.
Jacob D
JD
Mulligan
Annette M
AM
Stewart
Kurt W
KW
Saupe
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D031204:Caloric Restriction; D015536:Down-Regulation; D007328:Insulin / Q000096:biosynthesis / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D056564:Sirtuin 1; D037761:Sirtuins / Q000096:biosynthesis / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000096:biosynthesis / Q000235:genetics; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D047495:PPAR gamma; D012333:RNA, Messenger; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D007334:Insulin-Like Growth Factor I; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D037761:Sirtuins