The Pro12Ala PPARgamma2 variant determines metabolism at the gene-environment interface. - Archive ouverte HAL Access content directly
Journal Articles Cell Metab Year : 2009

The Pro12Ala PPARgamma2 variant determines metabolism at the gene-environment interface.

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Abstract

The metabolic impact of the common peroxisome proliferator-activated receptor gamma isoform 2 (PPARgamma2) variant Pro12Ala in human populations has been widely debated. We demonstrate, using a Pro12Ala knockin model, that on chow diet, Ala/Ala mice are leaner, have improved insulin sensitivity and plasma lipid profiles, and have longer lifespans. Gene-environment interactions played a key role as high-fat feeding eliminated the beneficial effects of the Pro12Ala variant on adiposity, plasma lipids, and insulin sensitivity. The underlying molecular mechanisms involve changes in cofactor interaction and adiponectin signaling. Altogether, our results establish the Pro12Ala variant of Ppargamma2 as an important modulator in metabolic control that strongly depends on the metabolic context.

Dates and versions

inserm-00357415 , version 1 (30-01-2009)

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Cite

Sami Heikkinen, Carmen A Argmann, Jérôme N. Feige, Hana Koutnikova, Marie-France Champy, et al.. The Pro12Ala PPARgamma2 variant determines metabolism at the gene-environment interface.. Cell Metab, 2009, 9 (1), pp.88-98. ⟨10.1016/j.cmet.2008.11.007⟩. ⟨inserm-00357415⟩
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