title: The Lou/C rat: a model of spontaneous food restriction associated with improved insulin sensitivity and decreased lipid storage in adipose tissue.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Centre Médical Universitaire, 1211 Geneva 4, Switzerland. christelle.veyrat-durebex@unige.ch
authors.forename: Christelle
authors.initials: C
authors.lastname: Veyrat-Durebex
authors.forename: Xavier
authors.initials: X
authors.lastname: Montet
authors.forename: Manlio
authors.initials: M
authors.lastname: Vinciguerra
authors.forename: Asllan
authors.initials: A
authors.lastname: Gjinovci
authors.forename: Paolo
authors.initials: P
authors.lastname: Meda
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Foti
authors.forename: Françoise
authors.initials: F
authors.lastname: Rohner-Jeanrenaud
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D031204:Caloric Restriction; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism; D005951:Glucose Tolerance Test; D007333:Insulin Resistance / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D014280:Triglycerides / Q000097:blood / Q000378:metabolism; D000071256:Uncoupling Protein 1
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D014280:Triglycerides; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt