Inhibition of adipocyte differentiation by RORα

Here we show that gene expression of the nuclear receptor ROR alpha is induced during adipogenesis, with ROR alpha 4 being the most abundantly expressed isoform in human and murine adipose tissue. Over-expression of ROR alpha 4 in 3T3-L1 cells impairs adipogenesis as shown by the decreased expression of adipogenic markers and lipid accumulation, accompanied by decreased free fatty acid and glucose uptake. By contrast, mouse embryonic fibroblasts from staggerer mice, which carry a mutation in the ROR alpha gene, differentiate more efficiently into mature adipocytes compared to wild-type cells, a phenotype which is reversed by ectopic ROR alpha 4 restoration. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.