Changes in responsiveness of appetite, leptin and hypothalamic IL-1β and TNF-α to lipopolysaccharide in developing rats

Abstract

In addition to its role as a regulator of energy homeostasis, leptin plays a pivotal role in some immune/inflammatory responses. Synthesis and secretion of leptin are increased under immune stress conditions, and increased leptin may participate in the development of anorexia and fever. These actions are partially mediated by up-regulation of hypothalamic IL-1β. Leptin also protects against immune stress-induced lethality. On the other hand, the response and roles of leptin to immune stress conditions in the neonatal period have scarcely been examined. We hypothesized that 1. the response of leptin to immune stress would be suppressed in the early neonatal period, 2. hyporesponse of leptin in the early neonatal period would attenuate the anorectic response and increase the lethal rate under immune stress conditions and 3. supplementation of leptin in the early neonatal period would increase the anorectic response, whereas it would decrease the lethal rate under immune stress conditions. To test these hypotheses, we first examined the developmental changes in the responses of leptin and hypothalamic proinflammatory cytokines, i.e., IL-1β and TNF-α, to LPS-induced immune stress in female rats. We also examined the developmental changes in the anorectic response and lethality rate under LPS-induced immune stress conditions. Five- and 15-day-old rats showed no leptin response and a weak hypothalamic IL-1β response to LPS when compared with 25- and 42-day-old rats. Fifteen-day-old rats showed low anorectic responses and high lethality rates when compared with 25- and 42-day-old rats under LPS-induced immune stress conditions. We then examined whether administration of leptin affected the response to the anorectic and lethal effects of LPS in 15-day-old rats. Administration of leptin further attenuated body weight after LPS injection, but not after saline injection. On the other hand, administration of leptin did not affect survival rate. In addition, hypothalamic IL-1β mRNA levels were not affected by leptin administration. In conclusion, the absence of a leptin response may act to prevent immune stress-induced anorexia during the early neonatal period.