Calorie restriction counteracts the impairment of adipocyte insulin-stimulated lipogenesis in aging rats, but not that induced by dexamethasone treatment.

In order to detect metabolic derangements that could be implicated in the pathogenesis of age-related insulin resistance, insulin-stimulated lipogenesis was investigated in isolated adipocytes from 24-month-old Sprague-Dawley rats, and the protective influence of caloric restriction was assessed. For comparison, the effects of glucocorticoid administration, used as a pharmacological tool to alter insulin sensitivity, were also studied. Caloric restriction consisted in a 40% reduction of the daily food intake of controls starting at 3 months of age. Dexamethasone (0.13 mg/kg/day) was administered for 14 days prior to sacrifice to both ad libitum-fed and dietary-restricted aging rats. Three-month-old animals, treated or untreated with dexamethasone, served as young controls. The results showed a significant age-related decrease of insulin-stimulated lipogenesis, which was fully prevented by a lifelong regimen of dietary restriction. Dexamethasone treatment markedly reduced insulin-stimulated lipogenesis in adipocytes isolated from all groups of rats, including those submitted to calorie restriction. In conclusion, our data indicate that the mechanism by which aging alters adipose tissue insulin-induced lipogenesis is reversed by dietary intervention and appears to be different from that triggered by dexamethasone. This particular defect might contribute to an imbalance of fat distribution among tissues that could induce or aggravate peripheral insulin resistance in old age.