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J Gerontol A Biol Sci Med Sci. 2005 Oct;60(10):1238-45.

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.

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Department of Internal Medicine, Geriatrics Research, Southern Illnois University School of Medicine, Springfield, 62794-9628, USA.


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.

[Indexed for MEDLINE]

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