In contrast to the Wistar rat, the Lou/C rat does not develop obesity with age. To determine the role of sympathetic output and brain monoamines in the different energy balance of Lou/C rats, the monoamine contents and activity of rate-limiting enzymes in catecholamine and serotonin biosynthesis were assessed in brain structures involved in energy balance regulation, i.e., brainstem noradrenergic (A6, A5, A2) and serotonergic cell groups (dorsal raphe, and median raphe), and two hypothalamic nuclei (ventromedial nucleus and paraventricular nucleus). In vivo tyrosine hydroxylase activity and noradrenaline content were measured in sympathetic target organs storing fuel substrates, the liver, white adipose and brown adipose tissues in the Lou/C rat and compared to the Wistar rat. In Lou/C rats, indirect calorimetric measurements showed a higher energy expenditure despite a reduced food intake. The Lou/C rat displayed selective monoamine features. The catecholaminergic activity was higher in the white adipose tissue and interscapular brown adipose tissue but lower in the liver and adrenal gland of Lou/C rats. The noradrenergic activity in A2, A6 and ventromedial nucleus, and the serotonergic pattern in A6, dorsal raphe and median raphe were lower in Lou/C. The metabolic particularities of Lou/C rats are associated with (i) a selectively enhanced sympathetic activity restricted to the white adipose tissue and brown adipose tissue, (ii) a reduced noradrenergic activity in selective brainstem and hypothalamic areas, which control the energy expenditure and food intake.