Aged Wistar rats are characterized by leptin and insulin resistance. The expression of SOCS-3 in hypothalamus increases with ageing. Food restriction during 3 months decreases obesity Lee index in aged rats with respect to their ad libitum aged-mates and brings serum leptin concentrations to values close to those of young rats. Food restriction partially reverts the increases in SOCS-3 mRNA levels associated with ageing. These results suggest that SOCS-3 may be a mediator of hypothalamic leptin resistance in the aged Wistar rat and that the hyperleptinemia associated with ageing is. at least in part, responsible for the increase of SOCS-3 expression in hypothalamus. (C) 2002 Elsevier Science (USA), All rights reserved.