CIRCADIAN NEUROENDOCRINE ROLE IN AGE-RELATED-CHANGES IN BODY-FAT STORES AND INSULIN SENSITIVITY OF THE MALE SPRAGUE-DAWLEY RAT

A role for circadian neuroendocrine rhythms in the age-related develop ment of obesity and insulin resistance was investigated in the male Sp rague-Dawley rat. The phases and amplitudes of the plasma rhythms of s everal metabolic hormones (i.e., corticosterone, prolactin, insulin, a nd triiodothyronine) differed in lean, insulin-sensitive (3-week-old r ats), insulin-resistant (8-week-old rats) and obese, insulin-resistant (44-week-old rats) animals. Simulation of the daily rhythms of endoge nous corticosterone and prolactin by daily injections of the hormones at times corresponding to the peak levels found in 3-week-old rats rev ersed age-related increases in insulin resistance and body fat in olde r (5-6-month-old) rats. Ten such daily injections of corticosterone an d prolactin in 12-14-week-old rats produced long-term reductions in bo dy fat stores (30%), plasma insulin concentration (40%), and insulin r esistance (60%) (determined by a glucose tolerance test) measured 11-1 4 weeks after the treatment. Alterations in circadian neuroendocrine r hythms may account for age-related changes in carbohydrate and lipid m etabolism in the male Sprague-Dawley rat, and resetting of these rhyth ms by appropriately timed daily injections of corticosterone and prola ctin may help maintain metabolism characteristic of younger animals.