TRANSCRIPTIONAL MODULATION BY N-BUTYRIC ACID OF BETA-1-ADRENERGIC, BETA-2-ADRENERGIC, AND BETA-3-ADRENERGIC RECEPTOR BALANCE IN 3T3-P442A 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%) popul ations, were used to investigate regulation by n-butyric acid of beta- AR subtype expression. Following butyrate treatment, EC(50), 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 (-)-[I-125]iodocyanopindo lol binding by selective beta 1- and beta 2-AR antagonists, CGP20712A and ICI118551, and by the beta 3-AR agonist, BRL37344, revealed that b oth beta 1- and beta 2-AR were increased in butyrate-treated adipocyte s, whereas beta 3-AR almost totally disappeared. In control adipocytes , beta 1-, beta 2-, and beta 3-AR transcripts (quantitated by a polyme rase 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 as says and accounted for 4.5% of beta-AR transcripts. Variations of beta -AR protein and mRNA levels were accompanied by parallel changes in th e transcription rates of the corresponding genes. The differential reg ulation of the three beta-ARs by n-butyric acid, a dietary factor prod uced from colonic fermentation, may have significant nutritional and e nergetic consequences.