The Lou/C rat is presented both as an obesity-resistant rat with a low fat accumulation and as a model of healthy ageing. To characterise the mechanisms underlying obesity resistance in this strain, we measured adiposity, food intake and energy expenditure by indirect calorimetry at 1, 6, 12, 18, and 24 months of age in comparison with Wistar rat. The role of brain monoamines in the different energy balance of Lou/C rats was evaluated by assessing the monoamine contents and the activity of rate-limiting enzymes in monoamine biosynthesis, in brainstem noradrenergic and serotonergic cell groups and in two hypothalamic nuclei. The sympathetic nerve activity was measured in target organs storing fuel substrates or implicated in energy expenditure. Moreover, plasma insulin and leptin concentrations two hormones providing rewards of energy stores to brain were determined throughout life span in Wistar and Lou/C rats. At each age, compared to Wistar rats, Lou/C rats presented a lesser food intake and exhibited higher energy expenditure at 6 and 12 months of age. The Lou/C rats exhibit an enhanced sympathetic outflow restricted to the white and brown adipose tissue, associated with a reduced noradrenergic pattern in brainstem and hypothalamic areas involved in energy balance regulation. From the age of 6 months, the plasma leptin concentrations in Wistar rats were higher than in Lou/C rats of the same age. Plasma insulin concentration increased markedly in elderly Wistar rats, but in contrast remained stable during ageing in Lou/C rats. Lou/C rats did not develop insulin resistance as confirmed by the hyperinsulinemic-euglycemic clamp. The sympathetic nervous system and the brain monoamines seem to be involved in the particular energy balance exhibited by the Lou/C rat. Lou/C rats display a healthy ageing considering fat accretion, leptin and insulin resistance.
