Effects of caloric restriction and growth hormone resistance on the expression level of peroxisome proliferator-activated receptors superfamily in liver of normal and long-lived growth hormone receptor/binding protein knockout mice.
Growth hormone receptor/binding protein knockout (GHR-KO) mice live approximately 40% longer than their normal siblings do. These mice have dramatically reduced plasma levels of insulin-like growth factor 1 (IGF1) and enhanced insulin sensitivity. We examined the expression level of peroxisome proliferator-activated receptors (PPARs) and retinoid X receptors family genes in the livers of normal and GHR-KO mice fed ad libitum or subjected to long-term 30% caloric restriction (CR). The levels of PPARgamma and PPARalpha messenger RNA and proteins and the levels of retinoid X receptors messenger RNA were elevated in long-lived GHR-KO mice as compared to normal mice with no major effect of CR in either genotype. These findings suggest that enhanced insulin sensitivity of GHR-KO mice may be related to the altered actions of PPARs family members in the liver. The results also indicate that CR may increase insulin sensitivity through a different mechanism.
Masternak
Michal M
MM
Southern Illinois University, School of Medicine, Geriatrics Research, Department of Internal Medicine, 801 N. Rutledge St., Room 4389, P.O. Box 19628, Springfield, IL 62794-9628, USA. mmasternak@siumed.edu
Al-Regaiey
Khalid A
KA
Del Rosario Lim
Marc Michael
MM
Jimenez-Ortega
Vanesa
V
Panici
Jacob A
JA
Bonkowski
Michael S
MS
Kopchick
John J
JJ
Bartke
Andrzej
A
D000818:Animals; D015153:Blotting, Western; D031204:Caloric Restriction; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011986:Receptors, Somatotropin / Q000235:genetics / Q000502:physiology*; D047488:Retinoid X Receptors / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D047492:Peroxisome Proliferator-Activated Receptors; D011986:Receptors, Somatotropin; D047488:Retinoid X Receptors