PPARalpha does not suppress muscle-associated gene expression in brown adipocytes but does influence expression of factors that fingerprint the brown adipocyte.
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.
Waldén
Tomas B
TB
The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, SE-106 91 Stockholm, Sweden.
Petrovic
Natasa
N
Nedergaard
Jan
J
D052437:Adipocytes, Brown / Q000378:metabolism*; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D005819:Genetic Markers / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D007473:Ion Channels / Q000235:genetics; D060850:LIM-Homeodomain Proteins; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D024101:Mitochondrial Proteins / Q000235:genetics; D024510:Muscle Development / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics; D000071256:Uncoupling Protein 1
D004268:DNA-Binding Proteins; D005819:Genetic Markers; D018398:Homeodomain Proteins; D007473:Ion Channels; C112960:LIM homeobox protein 8; D060850:LIM-Homeodomain Proteins; D024101:Mitochondrial Proteins; D047493:PPAR alpha; C521133:Prdm16 protein, mouse; D014157:Transcription Factors; D000071256:Uncoupling Protein 1; C492122:Zic1 protein, mouse