title: Ectopic UCP1 Overexpression in White Adipose Tissue Improves Insulin Sensitivity in Lou/C Rats, a Model of Obesity Resistance.
abstract: Brown adipose tissue (BAT), characterized by the presence of uncoupling protein 1 (UCP1), has been described as metabolically active in humans. Lou/C rats, originating from the Wistar strain, are resistant to obesity. We previously demonstrated that Lou/C animals express UCP1 in beige adipocytes in inguinal white adipose tissue (iWAT), suggesting a role of this protein in processes such as the control of body weight and the observed improved insulin sensitivity. A β3 adrenergic agonist was administered for 2 weeks in Wistar and Lou/C rats to activate UCP1 and delineate its metabolic impact. The treatment brought about decreases in fat mass and improvements in insulin sensitivity in both groups. In BAT, UCP1 expression increased similarly in response to the treatment in the two groups. However, the intervention induced the appearance of beige cells in iWAT, associated with a marked increase in UCP1 expression, in Lou/C rats only. This increase was correlated with a markedly enhanced glucose uptake measured during euglycemic-hyperinsulinemic clamps, suggesting a role of beige cells in this process. Activation of UCP1 in ectopic tissues, such as beige cells in iWAT, may be an interesting therapeutic approach to prevent body weight gain, decrease fat mass, and improve insulin sensitivity.
authors.affiliation: Laboratory of Metabolism, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland anne-laure.poher@unige.ch.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Poher
authors.affiliation: Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Christelle
authors.initials: C
authors.lastname: Veyrat-Durebex
authors.affiliation: Laboratory of Metabolism, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Jordi
authors.initials: J
authors.lastname: Altirriba
authors.affiliation: Division of Radiology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Xavier
authors.initials: X
authors.lastname: Montet
authors.affiliation: MicroPET/SPECT/CT Imaging Laboratory, Centre for BioMedical Imaging, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Didier J
authors.initials: DJ
authors.lastname: Colin
authors.affiliation: Laboratory of Metabolism, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Caillon
authors.affiliation: Laboratory of Metabolism, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Lyautey
authors.affiliation: Laboratory of Metabolism, Division of Endocrinology, Diabetology, Hypertension and Nutrition, Department of Internal Medicine Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Françoise
authors.initials: F
authors.lastname: Rohner-Jeanrenaud
mesh_terms: D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism*; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D001823:Body Composition / Q000187:drug effects / Q000502:physiology; D004149:Dioxoles / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D022722:Thermogenesis / Q000187:drug effects / Q000502:physiology; D000071256:Uncoupling Protein 1
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D004149:Dioxoles; D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604371:UCP1 protein, human; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate