Down-regulation of peroxisome proliferator-activated receptor-gamma gene expression by sphingomyelins

We recently demonstrated that the sphingomyelin (SM) content of adipocyte membranes was negatively correlated with the expression of peroxisome proliferator-activated receptor-gamma (PPARgamma) in the subcutaneous adipose tissue of obese women with variable degrees of insulin resistance. We have now investigated whether SM really does have an impact on the expression of PPARgamma in 3T3-F442A adipocytes. Adding SM to the culture medium for 24 h caused a significant increase in SM content of adipocyte membranes and an acyl chain length-dependent decrease in the levels of PPARgamma mRNA and protein. The longer the acyl chain of the fatty acid of SM, the greater was the decrease in PPARgamma. These data suggest that the nature of the fatty acid is important in the regulation of PPARgamma by the SM pathway.