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Lou/C Obesity-resistant Rat Exhibits Hyperactivity, Hypermetabolism, Alterations in White Adipose Tissue Cellularity, and Lipid Tissue Profiles

Université de Lyon 1, Lyon F-69003, France; Institut National de la Santé et de la Recherche Médicale, Unité 870, Institut Fédératif de Recherche 62, Hospices Civils de Lyon, and Institut National de la Recherche Agronomique, Unité Mixte de Recherche 1235, Lyon F-69008, France; and Institut National des Sciences Appliquées-Lyon, Régulations Métaboliques Nutrition et Diabètes, Villeurbanne F-6921, France

Address all correspondence and requests for reprints to: Dr. Christophe Soulage, U-870 Institut National de la Santé et de la Recherche Médicale, Unité 1235 Institut National de la Recherche Agronomique, Institut National des Sciences Appliquées-Lyon, Université Claude Bernard Lyon, Hospices Civils de Lyon, Régulations Métaboliques, Nutrition et Diabètes, Building Louis Pasteur (406), F-69621 Villeurbanne cedex, France. E-mail: Christophe.Soulage{at}insa-lyon.fr.

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 -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.