Pro12Ala substitution in peroxisome proliferator-activated receptorγ2 is associated with low adiponectin concentrations in young Japanese men

Abstract Peroxisome proliferator-activated receptor gamma (PPARγ) has been shown to play an important role in adipocyte differentiation. A Pro12Ala substitution in PPARγ2 has been reported to decrease receptor activity in vitro and to be associated with a decreased risk of type 2 diabetes in the general population. Recently, a PPAR response element (PPRE) was identified in the adiponectin promoter, suggesting that decreased PPARγ activity may lead to lower adiponectin levels. In the present study, serum adiponectin concentrations and the PPARγ Pro12Ala polymorphism were analyzed to determine whether this polymorphism is associated with lower serum adiponectin concentrations in young healthy Japanese subjects. Serum adiponectin concentrations were significantly lower in men with than in those without the Ala12 allele, whereas body mass index (BMI), homeostasis model assessment (HOMA)-β, HOMA-IR, the insulin sensitivity index during oral glucose tolerance test (ISI [composite]), and serum leptin did not differ significantly between subjects with and without the Ala12 allele. Stepwise regression demonstrated BMI and the Ala12 allele to be independent predictors of serum adiponectin concentrations in men. In conclusion, the Pro12Ala substitution in PPARγ2 may reduce serum adiponectin concentrations in young Japanese men.