Leptin selectively reduces white adipose tissue in mice via a UCP1-dependent mechanism in brown adipose tissue

We tested the hypothesis that leptin, in addition to reducing body fat by r estraining food intake, reduces body fat through a peripheral mechanism req uiring uncoupling protein 1 (UCP1). Leptin was administered to wild-type (W T) mice and mice with a targeted disruption of the UCP1 gene (UCP1 deficien t), while vehicle-injected control animals of each genotype were pair-fed t o each leptin-treated group. Leptin reduced the size of white adipose tissu e (WAT) depots in WT mice but not in UCP1-deficient animals. This was accom panied by a threefold increase in the amount of UCP1 protein and mRNA in th e brown adipose tissue (BAT) of WT mice. Leptin also increased UCP2 mRNA in WAT of both WT and UCP1-deficient mice but increased UCP2 and UCP3 mRNA on ly in BAT from UCP1-deficient mice. These results indicate that leptin redu ces WAT through a peripheral mechanism requiring the presence of UCP1, with little or no involvement of UCP2 or UCP3.