Modulation of Resistin Expression by Retinoic Acid and Vitamin A Status

Abstract

This work identifies retinoic acid (RA), the acid form of vitamin A, as a signal that inhibits the expression of resistin, an adipocyte-secreted protein previously proposed to act as an inhibitor of adipocyte differentiation and as a systemic insulin resistance factor. Both 9-cis and all-trans RA reduced resistin mRNA levels in white and brown adipocyte cell model systems; the effect was time- and dose-dependent, was followed by a reduced secretion of resistin, and was reproduced by selective agonists of both RA receptors and rexinoid receptors. Association of CCAAT/enhancer-binding protein α (a positive regulator of the resistin gene) and its coactivators p300, cAMP response element-binding protein binding protein, and retinoblastoma protein with the resistin gene promoter was reduced in RA-treated adipocytes. RA administration to normal mice resulted in reduced resistin mRNA levels in brown and white adipose tissues, reduced circulating resistin levels, reduced body weight, and improved glucose tolerance. Resistin expression was also downregulated after dietary vitamin A supplementation in mice. The results raise the possibility that vitamin A status may contribute to modulate systemic functions through effects on the production of adipocyte-derived protein signals.