Circulating adiponectin levels increase in rats on caloric restriction: the potential for insulin sensitization.
Caloric restriction (CR) has a well-known insulin sensitizing effect in vivo. Although this effect has been confirmed in rodents and primates for many years, its precise molecular mechanisms remain unknown. Here we show a significant increase in plasma adiponectin and a decrease in blood glucose, plasma triglyceride and insulin levels in rats maintained on CR diet for 2, 10, 15, and 20 months. Long-term CR rats exhibited significantly higher insulin-stimulated insulin receptor tyrosine phosphorylation and lower PTP-1B activity both in liver and skeletal muscle than those observed in rats fed ad libitum (AL). In addition, the triglyceride levels in these tissues were significantly lower in long-term CR animals. Interestingly, concentrations of plasma adiponectin in long-term CR rats were associated with increased expression of the transcription factor mRNAs for the peroxisome proliferator-activated receptor (PPAR)alpha, gamma and delta, but decreased expression for SREBP-1c, resulting in a concerted modulation in the expression of key transcription target genes involved in fatty acid oxidation and energy combustion in liver. Taken together, our findings suggest an important role for adiponectin in the beneficial effects of long-term CR.
Zhu
Min
M
Laboratory of Experimental Gerontology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA.
Miura
Junnosuke
J
Lu
Lucy X
LX
Bernier
Michel
M
DeCabo
Rafael
R
Lane
Mark A
MA
Roth
George S
GS
Ingram
Donald K
DK
D052242:Adiponectin; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D031204:Caloric Restriction; D005786:Gene Expression Regulation / Q000502:physiology; D007328:Insulin / Q000097:blood*; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D010766:Phosphorylation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction / Q000502:physiology; D014280:Triglycerides / Q000097:blood; D014443:Tyrosine / Q000378:metabolism
D052242:Adiponectin; D001786:Blood Glucose; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D014280:Triglycerides; D014443:Tyrosine; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C516610:Ptpn1 protein, rat