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Am J Physiol Endocrinol Metab 296: E1120-E1132, 2009. First published February 10, 2009; doi:10.1152/ajpendo.90592.2008
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The Lou/C rat: a model of spontaneous food restriction associated with improved insulin sensitivity and decreased lipid storage in adipose tissue

Christelle Veyrat-Durebex,1 Xavier Montet,2 Manlio Vinciguerra,3 Asllan Gjinovci,3 Paolo Meda,3 Michelangelo Foti,3 and Françoise Rohner-Jeanrenaud1

1Laboratory of Metabolism, Department of Internal Medicine, 2Laboratory of Molecular Imaging, Department of Radiology, and 3Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland

Submitted 14 July 2008 ; accepted in final form 8 February 2009

The inbred Lou/C rat, originating from the Wistar strain, has been described as a model of resistance to diet-induced obesity, but little is known about its metabolism. Since this knowledge could provide some clues about the etiology of obesity/insulin resistance, this study aimed at characterizing glucose and lipid metabolism in Lou/C vs. Wistar rats. This was achieved by performing glucose and insulin tolerance tests, euglycemic hyperinsulinemic clamps, and characterization of intracellular insulin signaling in skeletal muscle. Substrate-induced insulin secretion was evaluated using perfused pancreas and isolated islets. Finally, body fat composition and the expression of various factors involved in lipid metabolism were determined. Body weight and caloric intake were lower in Lou/C than in Wistar rats, whereas food efficiency was similar. Improved glucose tolerance of Lou/C rats was not related to increased insulin output but was related to improved insulin sensitivity/responsiveness in the liver and in skeletal muscles. In the latter tissue, this was accompanied by improved insulin signaling, as suggested by higher activation of the insulin receptor and of the Akt/protein kinase B pathway. Fat deposition was markedly lower in Lou/C than in Wistar rats, especially in visceral adipose tissue. In the inguinal adipose depot, expression of uncoupling protein-1 was detected in Lou/C but not in Wistar rats, in keeping with a higher expression of peroxisome proliferator-activated receptor-{gamma} coactivator-1 in these animals. The Lou/C rat is a valuable model of spontaneous food restriction with associated improved insulin sensitivity. Independently from its reduced caloric intake, it also exhibits a preferential channeling of nutrients toward utilization rather than storage.

metabolism; obesity; animal model


Address for reprint requests and other correspondence: C. Veyrat-Durebex, Laboratory of Metabolism, Dept. of Internal Medicine, Centre Médical Universitaire, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland (e-mail: christelle.veyrat-durebex{at}unige.ch)






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