The link between nutritional status and insulin sensitivity is dependent on the adipocyte-specific peroxisome proliferator-activated receptor-γ2 isoform

G. Medina-Gomez, S. Virtue, C. Lelliott, R. Boiani, M. Campbell, C. Christodoulides, C. Perrin, M. Jimenez-Linan, M. Blount, J. Dixon, D. Zahn, R. R. Thresher, S. Aparicio, M. Carlton, W. H. Colledge, M. I. Kettunen, Tuulikki Seppänen-Laakso, J. K. Sethi, S. O'Rahilly, K. BrindleS. Cinti, Matej Oresic, R. Burcelin, A. Vidal-Puig

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Abstract

The nuclear receptor peroxisome proliferator–activated receptor-γ (PPARγ) is critically required for adipogenesis. PPARγ exists as two isoforms, γ1 and γ2. PPARγ2 is the more potent adipogenic isoform in vitro and is normally restricted to adipose tissues, where it is regulated more by nutritional state than PPARγ1. To elucidate the relevance of the PPARγ2 in vivo, we generated a mouse model in which the PPARγ2 isoform was specifically disrupted. Despite similar weight, body composition, food intake, energy expenditure, and adipose tissue morphology, male mice lacking the γ2 isoform were more insulin resistant than wild-type animals when fed a regular diet. These results indicate that insulin resistance associated with ablation of PPARγ2 is not the result of lipodystrophy and suggests a specific role for PPARγ2 in maintaining insulin sensitivity independently of its effects on adipogenesis. Furthermore, PPARγ2 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 PPARγ2 is required for the maintenance of normal insulin sensitivity in mice but also raises the intriguing notion that PPARγ2 may be necessary for the adverse effects of a high-fat diet on carbohydrate metabolism.
Original languageEnglish
Pages (from-to)1706 - 1716
Number of pages11
JournalDiabetes
Volume54
Issue number6
DOIs
Publication statusPublished - 2005
MoE publication typeA1 Journal article-refereed

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Medina-Gomez, G., Virtue, S., Lelliott, C., Boiani, R., Campbell, M., Christodoulides, C., Perrin, C., Jimenez-Linan, M., Blount, M., Dixon, J., Zahn, D., Thresher, R. R., Aparicio, S., Carlton, M., Colledge, W. H., Kettunen, M. I., Seppänen-Laakso, T., Sethi, J. K., O'Rahilly, S., ... Vidal-Puig, A. (2005). The link between nutritional status and insulin sensitivity is dependent on the adipocyte-specific peroxisome proliferator-activated receptor-γ2 isoform. Diabetes, 54(6), 1706 - 1716. https://doi.org/10.2337/diabetes.54.6.1706