• Open Access

Aging alters PPARγ in rodent and human adipose tissue by modulating the balance in steroid receptor coactivator-1


Frédéric Picard, Laval Hospital Research Center, Y3106 Pavillon Marguerite-d’Youville, Hôpital Laval, 2725 Chemin Ste-Foy, Québec, QC G1V 4G5, Canada. Tel.: (418) 656 8711 ext 3737; fax: (418) 656 4942; e-mail: frederic.picard@crhl.ulaval.ca


Age is an important risk factor for the development of metabolic diseases (e.g. obesity, diabetes and atherosclerosis). Yet, little is known about the molecular mechanisms occurring upon aging that affect energy metabolism. Although visceral white adipose tissue (vWAT) is known for its key impact on metabolism, recent studies have indicated it could also be a key regulator of lifespan, suggesting that it can serve as a node for age-associated fat accretion. Here we show that aging triggers changes in the transcriptional milieu of the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) in vWAT, which leads to a modified potential for transactivation of target genes upon ligand treatment. We found that in vWAT of mice, rats and men, aging induced a specific decrease in the expression of steroid receptor coactivator-1 (SRC-1), whose recruitment to PPARγ is associated with improved insulin sensitivity and low adipogenic activity. In contrast, aging and oxidative stress did not impact on PPARγ expression and PPARγ ligand production. Age-induced loss of PPARγ/SRC-1 interactions increased the binding of PPARγ to the promoter of the adipogenic gene aP2. These findings suggest that strategies aimed at increasing SRC-1 expression and recruitment to PPARγ upon aging might help improve age-associated metabolic disorders.