Maintenance of glucagon-promoted lipolysis in adipocytes by food restriction.

Life-prolonging food restriction is known to delay physiological changes that occur during senescence. The aim of the present study was to learn if this nutritional manipulation also can influence changes that occur during the developmental phase of life. Male, specific pathogen-free Fischer 344 rats were fed ad libitum (group A) or 60% of the ad libitum intake (group R) beginning at 6 weeks of age. The group R rats had a markedly increased median length of life. Starting at 6 months of age, rats were periodically killed, and free adipocytes were prepared from epididymal and perirenal depots. The free adipocytes were used for the in vitro study of the promotion of lipolysis by glucagon. At 6 months of age and all older ages, adipocytes from group A rats were not responsive to the lipolytic action of glucagon; this agrees with earlier studies showing a marked loss in responsiveness to glucagon between 4-15 weeks of age. However, adipocytes from group R rats were quite responsive to glucagon at 6 and 12 months of age. Although after 12 months of age there was a loss in responsiveness to glucagon, this response remained significant through 36 months of age in the group R rats. Thus, life-prolonging food restriction delays not only functional changes that take place late in life (senescent changes) but also those occurring during the developmental period of life. The value of these findings as a model for experimental gerontology is discussed.