Caloric restriction results in decreased expression of peroxisome proliferator-activated receptor superfamily in muscle of normal and long-lived growth hormone receptor/binding protein knockout mice.
Resistance to growth hormone, reduced insulin-like growth factor 1 (IGF1) action, and enhanced insulin sensitivity are likely mediators of extended life span and delayed aging process in growth hormone receptor/binding protein knockout (GHR-KO) mice. Fat metabolism and genes involved in fatty acid oxidation are strongly involved in insulin action. Using real-time polymerase chain reaction and western blot we have examined expression of peroxisome proliferator-activated receptors (PPARs) and retinoid X receptor (RXR) genes in the skeletal muscle of normal and GHR-KO mice subjected to 30% caloric restriction. The results indicate that caloric restriction decreased the expression of PPARgamma, PPARalpha, and PPARbeta/delta which would lead to down-regulation of fat metabolism. This suggested metabolic change clearly does not affect whole-body insulin action. These findings suggest that whole-animal insulin sensitivity is not regulated through skeletal muscle insulin action.
Masternak
Michal M
MM
Department of Internal Medicine, Geriatrics Research, Southern Illnois University School of Medicine, Springfield, 62794-9628, USA. mmasternak@siumed.edu
Al-Regaiey
Khalid A
KA
Del Rosario Lim
Marc Michael
MM
Bonkowski
Michael S
MS
Panici
Jacob A
JA
Przybylski
Grzegorz K
GK
Bartke
Andrzej
A
D000818:Animals; D015153:Blotting, Western; D031204:Caloric Restriction; D002784:Cholesterol / Q000032:analysis; D005223:Fats / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000032:analysis; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000737:chemistry*; D047493:PPAR alpha / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics; D048068:PPAR-beta / Q000235:genetics; D047492:Peroxisome Proliferator-Activated Receptors / Q000032:analysis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011986:Receptors, Somatotropin / Q000235:genetics*; D047488:Retinoid X Receptors / Q000235:genetics; D014280:Triglycerides / Q000032:analysis
D005223:Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D047493:PPAR alpha; D047495:PPAR gamma; D048068:PPAR-beta; D047492:Peroxisome Proliferator-Activated Receptors; D011986:Receptors, Somatotropin; D047488:Retinoid X Receptors; D014280:Triglycerides; D002784:Cholesterol