The Pro12Ala PPARγ2 Variant Determines Metabolism at the Gene-Environment Interface

被引：64

作者：

Heikkinen, Sami ^{[1
,2
]}

Argmann, Carmen ^{[1
]}

Feige, Jerome N. ^{[1
]}

Koutnikova, Hana ^{[1
,3
]}

Champy, Marie-France ^{[3
]}

Dali-Youcef, Nassim ^{[4
]}

Schadt, Eric E. ^{[5
]}

Laakso, Markku ^{[6
]}

Auwerx, Johan ^{[1
,3
,4
,7
]}

机构：

[1] Univ Strasbourg 1, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France

[2] Univ Kuopio, AI Virtanen Inst Mol Sci, FIN-70211 Kuopio, Finland

[3] Inst Clin Souris, F-67404 Illkirch Graffenstaden, France

[4] Hop Univ Strasbourg, Lab Biochim Gen & Specialisee, F-67000 Strasbourg, France

[5] Rosetta Inpharmat LLC, Seattle, WA 98109 USA

[6] Univ Kuopio, Dept Med, Kuopio 70211, Finland

[7] Ecole Polytech Fed Lausanne, CH-1015 Lausanne, Switzerland

来源：

CELL METABOLISM | 2009年 / 9卷 / 01期

基金：

芬兰科学院;

关键词：

ACTIVATED-RECEPTOR-GAMMA; GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; PPAR-GAMMA; INSULIN-RESISTANCE; RISK LOCI; ADIPOGENESIS; MICE; POLYMORPHISM; EXPRESSION;

D O I：

10.1016/j.cmet.2008.11.007

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The metabolic impact of the common peroxisome proliferator-activated receptor gamma isoform 2 (PPAR gamma 2) 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 Ppar gamma 2 as an important modulator in metabolic control that strongly depends on the metabolic context.

引用

页码：88 / 98

页数：11

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