Responses of lean and obese Zucker rats to centrally administered leptin

Obese (Lepr(fa)/Lepr(fa)) Zucker rats have a missense mutation in the lepti n receptor gene. One amino acid substitution in the extracellular domain co mmon to all known leptin receptor proteins results from this mutation. Obes e Zucker rats are unable to respond behaviorally to leptin which is periphe rally administered. However, conflicting reports exist on whether obese Zuc ker rats can respond to centrally administered leptin. The purpose of this study was to determine whether obese Zucker rats responded behaviorally and metabolically to intracerebroventricularly (i.c.v.) administered leptin an d to compare the responses of lean and obese Zucker rats. We found that bot h lean and obese Zucker rats had similar body weight and food intake respon ses when administered a single i.c.v. leptin injection in a range of doses (1.25, 2.5,5, and 10 mu g), as well as daily i.c.v. administered leptin for five consecutive days. Both single and daily leptin administration also de creased respiratory quotient (RQ) similarly in lean and obese Zucker rats, indicating mobilization of fat as an energy source for leptin-treated rats. After withdrawal of daily leptin treatment, lean and obese Zucker rats exh ibited different recovery responses, It is concluded that obese Zucker rats can respond to exogenous leptin when leptin is delivered into the brain ve ntricles. (C) 1998 Elsevier Science Inc.