The Pro12Ala PPARγ2 Variant Determines Metabolism at the Gene-Environment Interface
The metabolic impact of the common peroxisome proliferator-activated receptor gamma isoform 2 (PPARγ2) 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 plas...
Saved in:
Published in | Cell metabolism Vol. 9; no. 1; pp. 88 - 98 |
---|---|
Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Elsevier Inc
01.01.2009
Elsevier |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | The metabolic impact of the common peroxisome proliferator-activated receptor gamma isoform 2 (PPARγ2) 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 Pparγ2 as an important modulator in metabolic control that strongly depends on the metabolic context. |
---|---|
ISSN: | 1550-4131 1932-7420 |
DOI: | 10.1016/j.cmet.2008.11.007 |