Involvement of Insulin-Like Growth Factor-1 in the Effect of Caloric Restriction: Regulation of Plasma Adiponectin and Leptin

Abstract

Insulin-like growth factor (IGF)-1 signaling might partly mediate effects of caloric restriction (CR), an experimental intervention for increasing longevity in mammals. The present study evaluated effects of recombinant human (rh)IGF-1 infusion on adipokine levels in CR and transgenic (Tg) dwarf rats with the reduced growth hormone-IGF-1 axis, which shared similar body weight and food intake. At 9 months of age, each rat received a continuous infusion of rhIGF-1 for 14 days, and rats received an injection of glucose after overnight fasting. Infusion of rhIGF-1 had metabolic effects in all rat groups although it did not affect insulin sensitivity in any of the groups. In addition, plasma adiponectin was decreased to the control group levels and plasma leptin was further reduced in CR and Tg rats. The similarity of phenotypes and adipokine responses to rhIGF-1 between CR and Tg rats supports a role for reduced IGF-1 signaling in the CR effect.

Divergent regulation of adipose tissue metabolism by calorie restriction and inhibition of growth hormone signaling

“…Although our previous study reported an increment in the plasma adiponectin concentrations in Tg-AL rats (Yamaza et al 2007), the present study did not confirm an increase in adiponectin gene expression in WAT. Ames dwarf mice have also been reported to show similar characteristics with increased plasma adiponectin levels without increase of adiponectin mRNA levels in WAT (Wang et al 2006).…”

“…One such adipokine is adiponectin, which is reported to not only enhance insulin-stimulated glucose uptake in tissues, but can also act as an insulin-independent signal (Yamauchi et al 2002;Wu et al 2003). In our studies, the plasma adiponectin concentration was increased in CR and Tg rats (Yamaza et al 2007), whereas the leptin and resistin concentrations were decreased . Because overexpression of adiponectin is reported to extend the lifespan in mice (Otabe et al 2007), CR and reduced GH signaling might increase the lifespan by modulating energy metabolism and subsequently the secretion of adipokines from WAT.…”

“…The extracted RNA was reverse-transcribed using a Bio-Rad reverse transcriptase reagent kit (Hercules, USA) according to the manufacturers protocol, and real-time PCR was performed as previously described (Yamaza et al 2007) using primers and probes for acetyl-CoA carboxylase (ACC) 1, and -actin (Applied Biosystems, Tokyo, Japan). The sequences of the primers and TaqMan probes were as follows: ACC1: sense, For real-time PCR of Glut1, Glut4, PPAR, fatty acid synthase (FAS), adiponectin, and adiponectin R1 and R2, mixed TaqMan MGB probes and primers were used (Glut1, Rn01417099_m1; Glut4, Rn00562597_m1; PPAR, Rn00440940_m1; FAS, Rn00569117_m1; Adiponectin, Rn00595250_m1; Adiponectin R1, Rn01114954_g1; Adiponectin R2, Rn01463177_a1; PPAR, Rn00440940_m1 Applied Biosystems, Tokyo, Japan).…”

“…Our earlier study demonstrated that the lifespan of transgenic (Tg) rats, in which the GH-IGF-1 axis was moderately suppressed by over-expression of an antisense GH gene, was 10% longer than that of wild (W)-type rats (Shimokawa et al 2002). Tg rats, even those fed ad libitum (AL), shared some phenotypes with showed findings similar to those in CR rats, including food intake and body weight, and plasma parameters associated with insulin sensitivity, particularly the adipokines, adiponectin, leptin and resistin (Yamaza et al 2007;Chiba et al 2008). CR is known to suppress the GH-IGF-1 axis (Breeze et al, 1991;Shimokawa et al, 2003).…”

Calorie restriction minimizes activation of insulin signaling in response to glucose: Potential involvement of the growth hormone-insulin-like growth factor 1 axis

“…W-CR and Tg-AL rats also had normal or slightly improved glucose tolerance without a significant surge in the serum insulin concentration after glucose loading (Yamaza et al, 2004). Plasma adiponectin was increased in W-CR and Tg-AL rats, while plasma leptin was decreased (Yamaza et al, 2007). Elevation of adiponectin is involved in the sensitization of insulin action (Havel, 2004).…”