Decreased leptin uptake in hypothalamic nuclei with ageing in Wistar rats

Leptin interacts with specific receptors in hypothalamic nuclei and modulat es energy balance. Growing evidence has shown the association of obesity an d hyperleptinaemia with non-insulin-dependent diabetes mellitus and insulin resistance. The aged Wistar rat shows peripheral insulin resistance in the absence of obesity and alterations of glucose homeostasis. However, it is not known whether, in these animals, the leptin action is altered. Here we studied the effect of ageing on plasma leptin concentration and the ability of hypothalamic nuclei to capture i.c.v.-injected digoxigenin-labelled lep tin. Our data indicate that 24-month-old animals are hyperleptinaemic. Howe ver, daily food intake was greater in old animals, suggesting that they are leptin resistant. Leptin uptake in the hypothalamus was reduced in old rat s. This uptake was a receptor-mediated process as demonstrated by displacem ent. Leptin accumulation in hypothalamic nuclei was partially colocalized w ith neuropeptide Y fibres. Immunohistochemical and western blot analyses sh owed a lower amount of the long form of leptin receptors in the hypothalamu s of aged rats. Analysis by R-T-PCR also demonstrated a decreased expressio n of leptin receptor mRNA in old animals. We conclude that the lower leptin uptake may be explained, at least in part, by a decreased amount of recept ors in hypothalamic neurones of the aged rats.