Lou/C obesity-resistant rat constitutes an original model to understand the phenomena of overweight and obesity. The aim of the present study was to identify metabolic causes for the outstanding leanness of Lou/C rat. To this end, the metabolic profiles (food intake, energy expenditure, and physical activity) and the cellular characteristics of white adipose tissue (lipogenesis, lipolysis, cellularity, and lipid composition) in 30-wk-old Lou/C rats were compared with age-matched Wistar rats. Lou/C rats exhibited a lower body weight (-45%), reduced adiposity (-80%), increased locomotor activity (+95%), and higher energy expenditure (+11%) than Wistar rats. Epididymal adipose tissue of Lou/C rat was twice lower than that of Wistar rat due to both a reduction in both adipocyte size (-25%) and number (three times). Basal lipolysis and sensitivity to noradrenaline were similar; however, the responsiveness to noradrenaline was lower in adipocytes from Lou/C compared with that from Wistar rats. Lipidomic analysis of plasma, adipose tissue, and liver revealed profound differences in lipid composition between the two strains. Of note, the desaturation indexes (ratio C16:1/C16:0 and C18:1/C18:0) were lower in Lou/C, indicating a blunted activity of delta-9-desaturase such as stearoyl-coenzyme A-desaturase-1. Increased physical activity, increased energy expenditure, and white adipose tissue cellularity are in good agreement with previous observations suggesting that a higher sympathetic tone in Lou/C could contribute to its lifelong leanness.