The effect of calorie restriction on insulin signaling in skeletal muscle and adipose tissue of Ames dwarf mice

Long-living Ames dwarf (df/df) mice are homozygous for a mutation of the Prop1(df) gene. As a result, mice are deficient in growth hormone (GH), prolactin (PRL) and thyrotropin (TSH). In spite of the hormonal deficiencies, df/df mice live significantly longer and healthier lives compared to their wild type siblings. We studied the effects of calorie restriction (CR) on the expression of insulin signaling genes in skeletal muscle and adipose tissue of normal and df/df mice. The analysis of genes expression showed that CR differentially affects the insulin signaling pathway in these insulin target organs. Moreover, results obtained in both normal and Ames dwarf mice indicate more direct effects of CR on insulin signaling genes in adipose tissue than in skeletal muscle. Interestingly, CR reduced the protein levels of adiponectin in the epididymal adipose tissue of normal and Ames dwarf mice, while elevating adiponectin levels in skeletal muscle and plasma of normal mice only. In conclusion, our findings suggest that both skeletal muscle and adipose tissue are important mediators of insulin effects on longevity. Additionally, the results revealed divergent effects of CR on expression of genes in the insulin signaling pathway of normal and Ames dwarf mice.