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

Peroxisome proliferator activated receptor gamma 2 (PPARg2) is the nutritionally regulated isoform of PPARg. Ablation of PPARg2 in the ob/ob background, PPARg2(-/-) Lep(ob)/Lep(ob) (POKO mouse), resulted in decreased fat mass, severe insulin resistance, beta-cell failure, and dyslipidaemia. Our resu...

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Bibliographic Details
Published in:PLoS genetics 2007-04, Vol.3 (4), p.e64
Main Authors: Medina-Gomez, Gema, Gray, Sarah L, Yetukuri, Laxman, Shimomura, Kenju, Virtue, Sam, Campbell, Mark, Curtis, R Keira, Jimenez-Linan, Mercedes, Blount, Margaret, Yeo, Giles S H, Lopez, Miguel, Seppänen-Laakso, Tuulikki, Ashcroft, Frances M, Oresic, Matej, Vidal-Puig, Antonio
Format: Article
Language:English
Subjects:
Adipose Tissue - growth & development
Adipose tissues
Animals
Biochemistry
Body fat
Body Weight - physiology
Diabetes
Diabetes and Endocrinology
Energy Metabolism - physiology
Female
Health aspects
Hyperglycemia - genetics
Hyperglycemia - pathology
Insulin
Insulin - blood
Insulin resistance
Insulin Resistance - genetics
Insulin-Secreting Cells - pathology
Lipid metabolism
Lipid Metabolism - genetics
Lipids - adverse effects
Lipids - chemistry
Male
Metabolism
Metabolites
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Obese
Models, Biological
Molecular Biology
Mus (Mouse)
Nutrition
Obesity
Peroxisomes
PPAR gamma - genetics
PPAR gamma - physiology
Risk factors
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Summary:Peroxisome proliferator activated receptor gamma 2 (PPARg2) is the nutritionally regulated isoform of PPARg. Ablation of PPARg2 in the ob/ob background, PPARg2(-/-) Lep(ob)/Lep(ob) (POKO mouse), resulted in decreased fat mass, severe insulin resistance, beta-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 beta-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 beta-cells to insulin resistance.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.0030064