PPARgamma plays a key role in the regulation of adipocyte differentiation and energy balance. The polymorphism in human PPARG gene resulting in the substitution of Pro12 to Ala in the PPARgamma2 isoform has been established as conferring anti-diabetic and anti-obesity effects, especially in the conditions such as westernized lifestyle with high levels of endogenous ligands for PPARgamma. Thus this is a good example of gene-environment interaction in human diseases. Since this polymorphism is predicted to generate a less active transcription factor, several different phases for metabolism in vivo with regard to PPARgamma activities are assumed.