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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

¹ Departments of Internal Medicine and Physiology, Geriatrics Research, Southern Illinois University School of Medicine, Springfield.
² Complutense University School of Medicine, Department of Biochemistry & Molecular Biology II, Madrid, Spain.
³ Edison Biotechnology Institute, Department of Biomedical Sciences, Ohio University, Athens.
⁴ Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

Address correspondence to Michal M. Masternak, PhD, 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. E-mail: mmasternak{at}siumed.edu

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 PPAR and PPAR 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.