Dexamethasone treatment induces long-lasting hyperleptinemia and anorexia in old rats

Aging brings poor adaptation to stress, the causes of which remain unclear. We previously reported impairment of nitrogen metabolism in glucocorticoid-treated old rats due to profound anorexia. Here we investigated whether leptin, a satiety hormone, was implicated in impaired adaptation to stress. Plasma glucose and insulin levels, which are known to modulate leptin secretion, were also studied. Adult (3 months, n = 18) and aged (24 months, n = 18) rats were treated with dexamethasone (DEX) (1.5 mg/kg/d, intraperitoneal [IP] injection) for 3, 5, and 7 days. Results were compared with ad libitum (n = 12) and pair-fed groups, receiving intraperitoneal saline injection, for each age (n = 6 per group). Transitory anorexia was observed in adult rats (day 3 to day 5), whereas anorexia persisted in aged rats until day 7. This anorexia was associated (r = -.65, P <.05) with an elevated constant hyperleptinemia. In contrast, hyperleptinemia was moderate and reverted rapidly to basal values by day 5 in adult rats. The time course of plasma insulin and glucose levels was similar in old and adult rats, except for marked hyperglycemia noted in aged animals. In old stressed rats, DEX treatment induces an anorexia, which is concomitant to an increase in serum leptin levels. Thus, leptin may be implicated in the poor adaptation to stress of aged compared with adult rats.