title: The link between nutritional status and insulin sensitivity is dependent on the adipocyte-specific peroxisome proliferator-activated receptor-gamma2 isoform.
abstract: The nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) is critically required for adipogenesis. PPARgamma exists as two isoforms, gamma1 and gamma2. PPARgamma2 is the more potent adipogenic isoform in vitro and is normally restricted to adipose tissues, where it is regulated more by nutritional state than PPARgamma1. To elucidate the relevance of the PPARgamma2 in vivo, we generated a mouse model in which the PPARgamma2 isoform was specifically disrupted. Despite similar weight, body composition, food intake, energy expenditure, and adipose tissue morphology, male mice lacking the gamma2 isoform were more insulin resistant than wild-type animals when fed a regular diet. These results indicate that insulin resistance associated with ablation of PPARgamma2 is not the result of lipodystrophy and suggests a specific role for PPARgamma2 in maintaining insulin sensitivity independently of its effects on adipogenesis. Furthermore, PPARgamma2 knockout mice fed a high-fat diet did not become more insulin resistant than those on a normal diet, despite a marked increase in their mean adipocyte cell size. These findings suggest that PPARgamma2 is required for the maintenance of normal insulin sensitivity in mice but also raises the intriguing notion that PPARgamma2 may be necessary for the adverse effects of a high-fat diet on carbohydrate metabolism.
authors.affiliation: Department of Clinical Biochemistry, University of Cambridge/Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QR, UK.
authors.forename: Gema
authors.initials: G
authors.lastname: Medina-Gomez
authors.forename: Sam
authors.initials: S
authors.lastname: Virtue
authors.forename: Christopher
authors.initials: C
authors.lastname: Lelliott
authors.forename: Romina
authors.initials: R
authors.lastname: Boiani
authors.forename: Mark
authors.initials: M
authors.lastname: Campbell
authors.forename: Constantinos
authors.initials: C
authors.lastname: Christodoulides
authors.forename: Christophe
authors.initials: C
authors.lastname: Perrin
authors.forename: Mercedes
authors.initials: M
authors.lastname: Jimenez-Linan
authors.forename: Margaret
authors.initials: M
authors.lastname: Blount
authors.forename: John
authors.initials: J
authors.lastname: Dixon
authors.forename: Dirk
authors.initials: D
authors.lastname: Zahn
authors.forename: Rosemary R
authors.initials: RR
authors.lastname: Thresher
authors.forename: Sam
authors.initials: S
authors.lastname: Aparicio
authors.forename: Mark
authors.initials: M
authors.lastname: Carlton
authors.forename: William H
authors.initials: WH
authors.lastname: Colledge
authors.forename: Mikko I
authors.initials: MI
authors.lastname: Kettunen
authors.forename: Tuulikki
authors.initials: T
authors.lastname: Seppänen-Laakso
authors.forename: Jaswinder K
authors.initials: JK
authors.lastname: Sethi
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Rahilly
authors.forename: Kevin
authors.initials: K
authors.lastname: Brindle
authors.forename: Saverio
authors.initials: S
authors.lastname: Cinti
authors.forename: Matej
authors.initials: M
authors.lastname: Oresic
authors.forename: Remy
authors.initials: R
authors.lastname: Burcelin
authors.forename: Antonio
authors.initials: A
authors.lastname: Vidal-Puig
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D001823:Body Composition; D004041:Dietary Fats / Q000378:metabolism*; D002149:Energy Intake; D004734:Energy Metabolism; D005247:Feeding Behavior; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D047495:PPAR gamma / Q000235:genetics / Q000502:physiology*; D020033:Protein Isoforms
chemical_list: D004041:Dietary Fats; D007328:Insulin; D047495:PPAR gamma; D020033:Protein Isoforms