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.
Krief
S
S
Centre National de la Recherche Scientifique Unité Propre de Recherche 0415, Paris, France.
Fève
B
B
Baude
B
B
Zilberfarb
V
V
Strosberg
A D
AD
Pairault
J
J
Emorine
L J
LJ
D016475:3T3 Cells; D000067956:Adenylyl Cyclase Inhibitors; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000818:Animals; D001483:Base Sequence; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D017931:DNA Primers; D018076:DNA, Complementary / Q000096:biosynthesis; D004983:Ethanolamines / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011412:Propanolamines / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis* / Q000187:drug effects / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000096:biosynthesis* / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis* / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3; D014158:Transcription, Genetic / Q000187:drug effects
D000067956:Adenylyl Cyclase Inhibitors; D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D002087:Butyrates; D017931:DNA Primers; D018076:DNA, Complementary; D004983:Ethanolamines; D007093:Imidazoles; D016376:Oligonucleotides, Antisense; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; D020148:Butyric Acid; C026777:ICI 118551; C057368:BRL 37344; D020120:Iodocyanopindolol; D010869:Pindolol; C049763:CGP 20712A; D007545:Isoproterenol