S. Krief et al., TRANSCRIPTIONAL MODULATION BY N-BUTYRIC ACID OF BETA-1-ADRENERGIC, BETA-2-ADRENERGIC, AND BETA-3-ADRENERGIC RECEPTOR BALANCE IN 3T3-P442A ADIPOCYTES, The Journal of biological chemistry, 269(9), 1994, pp. 6664-6670
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.