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

Research output: Contribution to journalArticleScientificpeer-review

127 Citations (Scopus)

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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Peroxisome Proliferator-Activated Receptors
Nutritional Status
Adipocytes
Insulin Resistance
Protein Isoforms
Adipogenesis
Peroxisomes
High Fat Diet
Adipose Tissue
Insulin
Diet
Lipodystrophy
Wild Animals
Carbohydrate Metabolism
Cytoplasmic and Nuclear Receptors
Body Composition
Cell Size
Knockout Mice
Energy Metabolism
Eating

Cite this

Medina-Gomez, G., Virtue, S., Lelliott, C., Boiani, R., Campbell, M., Christodoulides, C., ... 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
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, Tuulikki ; Sethi, J. K. ; O'Rahilly, S. ; Brindle, K. ; Cinti, S. ; Oresic, Matej ; Burcelin, R. ; Vidal-Puig, A. / The link between nutritional status and insulin sensitivity is dependent on the adipocyte-specific peroxisome proliferator-activated receptor-γ2 isoform. In: Diabetes. 2005 ; Vol. 54, No. 6. pp. 1706 - 1716.
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title = "The link between nutritional status and insulin sensitivity is dependent on the adipocyte-specific peroxisome proliferator-activated receptor-γ2 isoform",
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.",
author = "G. Medina-Gomez and S. Virtue and C. Lelliott and R. Boiani and M. Campbell and C. Christodoulides and C. Perrin and M. Jimenez-Linan and M. Blount and J. Dixon and D. Zahn and Thresher, {R. R.} and S. Aparicio and M. Carlton and Colledge, {W. H.} and Kettunen, {M. I.} and Tuulikki Sepp{\"a}nen-Laakso and Sethi, {J. K.} and S. O'Rahilly and K. Brindle and S. Cinti and Matej Oresic and R. Burcelin and A. Vidal-Puig",
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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, RR, Aparicio, S, Carlton, M, Colledge, WH, Kettunen, MI, Seppänen-Laakso, T, Sethi, JK, O'Rahilly, S, Brindle, K, Cinti, S, Oresic, M, Burcelin, R & 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, vol. 54, no. 6, pp. 1706 - 1716. https://doi.org/10.2337/diabetes.54.6.1706

The link between nutritional status and insulin sensitivity is dependent on the adipocyte-specific peroxisome proliferator-activated receptor-γ2 isoform. / 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, Tuulikki; Sethi, J. K.; O'Rahilly, S.; Brindle, K.; Cinti, S.; Oresic, Matej; Burcelin, R.; Vidal-Puig, A. (Corresponding Author).

In: Diabetes, Vol. 54, No. 6, 2005, p. 1706 - 1716.

Research output: Contribution to journalArticleScientificpeer-review

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T1 - The link between nutritional status and insulin sensitivity is dependent on the adipocyte-specific peroxisome proliferator-activated receptor-γ2 isoform

AU - Medina-Gomez, G.

AU - Virtue, S.

AU - Lelliott, C.

AU - Boiani, R.

AU - Campbell, M.

AU - Christodoulides, C.

AU - Perrin, C.

AU - Jimenez-Linan, M.

AU - Blount, M.

AU - Dixon, J.

AU - Zahn, D.

AU - Thresher, R. R.

AU - Aparicio, S.

AU - Carlton, M.

AU - Colledge, W. H.

AU - Kettunen, M. I.

AU - Seppänen-Laakso, Tuulikki

AU - Sethi, J. K.

AU - O'Rahilly, S.

AU - Brindle, K.

AU - Cinti, S.

AU - Oresic, Matej

AU - Burcelin, R.

AU - Vidal-Puig, A.

PY - 2005

Y1 - 2005

N2 - 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.

AB - 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.

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DO - 10.2337/diabetes.54.6.1706

M3 - Article

VL - 54

SP - 1706

EP - 1716

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 6

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