PPARalpha does not suppress muscle-associated gene expression in brown adipocytes but does influence expression of factors that fingerprint the brown adipocyte

Abstract

Brown adipocytes and myocytes develop from a common adipomyocyte precursor. PPARalpha is a nuclear receptor important for lipid and glucose metabolism. It has been suggested that in brown adipose tissue, PPARalpha represses the expression of muscle-associated genes, in this way potentially acting to determine cell fate in brown adipocytes. To further understand the possible role of PPARalpha in these processes, we measured expression of muscle-associated genes in brown adipose tissue and brown adipocytes from PPARalpha-ablated mice, including structural genes (Mylpf, Tpm2, Myl3 and MyHC), regulatory genes (myogenin, Myf5 and MyoD) and a myomir (miR-206). However, in our hands, the expression of these genes was not influenced by the presence or absence of PPARalpha, nor by the PPARalpha activator Wy-14,643. Similarly, the expression of genes common for mature brown adipocyte and myocytes (Tbx15, Meox2) were not affected. However, the brown adipocyte-specific regulatory genes Zic1, Lhx8 and Prdm16 were affected by PPARalpha. Thus, it would not seem that PPARalpha represses muscle-associated genes, but PPARalpha may still play a role in the regulation of the bifurcation of the adipomyocyte precursor into a brown adipocyte or myocyte phenotype.