Transcriptional modulation by n-butyric acid of beta 1-, beta 2-, and beta 3-adrenergic receptor balance in 3T3-F442A adipocytes.

3T3-F442A adipocytes, which express major beta 3-adrenergic receptors (beta 3-AR) (90%) and minor beta 1-AR (< 10%) and beta 2-AR (< 1%) populations, were used to investigate regulation by n-butyric acid of beta-AR subtype expression. Following butyrate treatment, EC50 values of beta 1- and beta 2-selective agonists, dobutamine and fenoterol, were decreased, whereas that of the beta 3-selective agonist BRL37344 was increased. Direct binding and competition of (-)-[125I]iodocyanopindolol binding by selective beta 1- and beta 2-AR antagonists, CGP20712A and ICI118551, and by the beta 3-AR agonist, BRL37344, revealed that both beta 1- and beta 2-AR were increased in butyrate-treated adipocytes, whereas beta 3-AR almost totally disappeared. In control adipocytes, beta 1-, beta 2-, and beta 3-AR transcripts (quantitated by a polymerase chain reaction assay) represented 6.5, 0.5, and 93% of total beta-AR mRNA, respectively. In butyrate-exposed cells, proportions of beta-AR proteins and mRNAs were, respectively, 87 and 94% for beta 1 and 9 and 1% for beta 2-AR. beta 3-ARs were barely detectable in binding assays and accounted for 4.5% of beta-AR transcripts. Variations of beta-AR protein and mRNA levels were accompanied by parallel changes in the transcription rates of the corresponding genes. The differential regulation of the three beta-ARs by n-butyric acid, a dietary factor produced from colonic fermentation, may have significant nutritional and energetic consequences.