The link between nutritional status and insulin sensitivity is dependent on the adipocyte-specific peroxisome proliferator-activated receptor-gamma2 isoform.
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.
Medina-Gomez
Gema
G
Department of Clinical Biochemistry, University of Cambridge/Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QR, UK.
Virtue
Sam
S
Lelliott
Christopher
C
Boiani
Romina
R
Campbell
Mark
M
Christodoulides
Constantinos
C
Perrin
Christophe
C
Jimenez-Linan
Mercedes
M
Blount
Margaret
M
Dixon
John
J
Zahn
Dirk
D
Thresher
Rosemary R
RR
Aparicio
Sam
S
Carlton
Mark
M
Colledge
William H
WH
Kettunen
Mikko I
MI
Seppänen-Laakso
Tuulikki
T
Sethi
Jaswinder K
JK
O'Rahilly
Stephen
S
Brindle
Kevin
K
Cinti
Saverio
S
Oresic
Matej
M
Burcelin
Remy
R
Vidal-Puig
Antonio
A
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
D004041:Dietary Fats; D007328:Insulin; D047495:PPAR gamma; D020033:Protein Isoforms