PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism

G. Medina-Gomez, S.L. Gray, Laxman Yetukuri, K. Shimomura, M. Campbell, K. Curtis, S. Virtue, M. Jimenez-Linan, M. Blount, G.S.H. Yeo, M. Lopez, Tuulikki Seppänen-Laakso, F.M. Ashcroft, Matej Oresic, A. Vidal-Puig

Research output: Contribution to journalArticleScientificpeer-review

219 Citations (Scopus)

Abstract

Peroxisome proliferator activated receptor gamma 2 (PPARg2) is the nutritionally regulated isoform of PPARg.
Ablation of PPARg2 in the ob/ob background, PPARg2−/− Lepob/Lepob (POKO mouse), resulted in decreased fat mass, severe insulin resistance, β-cell failure, and dyslipidaemia.
Our results indicate that the PPARg2 isoform plays an important role, mediating adipose tissue expansion in response to positive energy balance. Lipidomic analyses suggest that PPARg2 plays an important antilipotoxic role when induced ectopically in liver and muscle by facilitating deposition of fat as relatively harmless triacylglycerol species and thus preventing accumulation of reactive lipid species.
Our data also indicate that PPARg2 may be required for the β-cell hypertrophic adaptive response to insulin resistance. In summary, the PPARg2 isoform prevents lipotoxicity by (a) promoting adipose tissue expansion, (b) increasing the lipid-buffering capacity of peripheral organs, and (c) facilitating the adaptive proliferative response of β-cells to insulin resistance.
Original languageEnglish
Article numbere64
Number of pages14
JournalPLoS Genetics
Volume3
Issue number4
DOIs
Publication statusPublished - 2007
MoE publication typeA1 Journal article-refereed

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PPAR gamma
Lipid Metabolism
lipid metabolism
adipose tissue
fat
Adipose Tissue
metabolism
lipid
buffering
ablation
energy balance
insulin resistance
muscle
Tissue Expansion
Insulin Resistance
Protein Isoforms
lipids
Fats
Lipids
buffering capacity

Cite this

Medina-Gomez, G., Gray, S. L., Yetukuri, L., Shimomura, K., Campbell, M., Curtis, K., ... Vidal-Puig, A. (2007). PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism. PLoS Genetics, 3(4), [e64]. https://doi.org/10.1371/journal.pgen.0030064
Medina-Gomez, G. ; Gray, S.L. ; Yetukuri, Laxman ; Shimomura, K. ; Campbell, M. ; Curtis, K. ; Virtue, S. ; Jimenez-Linan, M. ; Blount, M. ; Yeo, G.S.H. ; Lopez, M. ; Seppänen-Laakso, Tuulikki ; Ashcroft, F.M. ; Oresic, Matej ; Vidal-Puig, A. / PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism. In: PLoS Genetics. 2007 ; Vol. 3, No. 4.
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title = "PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism",
abstract = "Peroxisome proliferator activated receptor gamma 2 (PPARg2) is the nutritionally regulated isoform of PPARg. Ablation of PPARg2 in the ob/ob background, PPARg2−/− Lepob/Lepob (POKO mouse), resulted in decreased fat mass, severe insulin resistance, β-cell failure, and dyslipidaemia. Our results indicate that the PPARg2 isoform plays an important role, mediating adipose tissue expansion in response to positive energy balance. Lipidomic analyses suggest that PPARg2 plays an important antilipotoxic role when induced ectopically in liver and muscle by facilitating deposition of fat as relatively harmless triacylglycerol species and thus preventing accumulation of reactive lipid species. Our data also indicate that PPARg2 may be required for the β-cell hypertrophic adaptive response to insulin resistance. In summary, the PPARg2 isoform prevents lipotoxicity by (a) promoting adipose tissue expansion, (b) increasing the lipid-buffering capacity of peripheral organs, and (c) facilitating the adaptive proliferative response of β-cells to insulin resistance.",
author = "G. Medina-Gomez and S.L. Gray and Laxman Yetukuri and K. Shimomura and M. Campbell and K. Curtis and S. Virtue and M. Jimenez-Linan and M. Blount and G.S.H. Yeo and M. Lopez and Tuulikki Sepp{\"a}nen-Laakso and F.M. Ashcroft and Matej Oresic and A. Vidal-Puig",
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Medina-Gomez, G, Gray, SL, Yetukuri, L, Shimomura, K, Campbell, M, Curtis, K, Virtue, S, Jimenez-Linan, M, Blount, M, Yeo, GSH, Lopez, M, Seppänen-Laakso, T, Ashcroft, FM, Oresic, M & Vidal-Puig, A 2007, 'PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism', PLoS Genetics, vol. 3, no. 4, e64. https://doi.org/10.1371/journal.pgen.0030064

PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism. / Medina-Gomez, G.; Gray, S.L.; Yetukuri, Laxman; Shimomura, K.; Campbell, M.; Curtis, K.; Virtue, S.; Jimenez-Linan, M.; Blount, M.; Yeo, G.S.H.; Lopez, M.; Seppänen-Laakso, Tuulikki; Ashcroft, F.M.; Oresic, Matej; Vidal-Puig, A.

In: PLoS Genetics, Vol. 3, No. 4, e64, 2007.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism

AU - Medina-Gomez, G.

AU - Gray, S.L.

AU - Yetukuri, Laxman

AU - Shimomura, K.

AU - Campbell, M.

AU - Curtis, K.

AU - Virtue, S.

AU - Jimenez-Linan, M.

AU - Blount, M.

AU - Yeo, G.S.H.

AU - Lopez, M.

AU - Seppänen-Laakso, Tuulikki

AU - Ashcroft, F.M.

AU - Oresic, Matej

AU - Vidal-Puig, A.

PY - 2007

Y1 - 2007

N2 - Peroxisome proliferator activated receptor gamma 2 (PPARg2) is the nutritionally regulated isoform of PPARg. Ablation of PPARg2 in the ob/ob background, PPARg2−/− Lepob/Lepob (POKO mouse), resulted in decreased fat mass, severe insulin resistance, β-cell failure, and dyslipidaemia. Our results indicate that the PPARg2 isoform plays an important role, mediating adipose tissue expansion in response to positive energy balance. Lipidomic analyses suggest that PPARg2 plays an important antilipotoxic role when induced ectopically in liver and muscle by facilitating deposition of fat as relatively harmless triacylglycerol species and thus preventing accumulation of reactive lipid species. Our data also indicate that PPARg2 may be required for the β-cell hypertrophic adaptive response to insulin resistance. In summary, the PPARg2 isoform prevents lipotoxicity by (a) promoting adipose tissue expansion, (b) increasing the lipid-buffering capacity of peripheral organs, and (c) facilitating the adaptive proliferative response of β-cells to insulin resistance.

AB - Peroxisome proliferator activated receptor gamma 2 (PPARg2) is the nutritionally regulated isoform of PPARg. Ablation of PPARg2 in the ob/ob background, PPARg2−/− Lepob/Lepob (POKO mouse), resulted in decreased fat mass, severe insulin resistance, β-cell failure, and dyslipidaemia. Our results indicate that the PPARg2 isoform plays an important role, mediating adipose tissue expansion in response to positive energy balance. Lipidomic analyses suggest that PPARg2 plays an important antilipotoxic role when induced ectopically in liver and muscle by facilitating deposition of fat as relatively harmless triacylglycerol species and thus preventing accumulation of reactive lipid species. Our data also indicate that PPARg2 may be required for the β-cell hypertrophic adaptive response to insulin resistance. In summary, the PPARg2 isoform prevents lipotoxicity by (a) promoting adipose tissue expansion, (b) increasing the lipid-buffering capacity of peripheral organs, and (c) facilitating the adaptive proliferative response of β-cells to insulin resistance.

U2 - 10.1371/journal.pgen.0030064

DO - 10.1371/journal.pgen.0030064

M3 - Article

VL - 3

JO - PLoS Genetics

JF - PLoS Genetics

SN - 1553-7390

IS - 4

M1 - e64

ER -