D-(-)-beta-hydroxybutyrate inhibits catecholamine-stimulated lipolysis and decreases beta-adrenoceptors' affinity in human fat cells but not in lymphomonocytes.
The effect of D-(-)-beta-hydroxybutyrate, at concentrations commonly achieved during ketoacidosis in humans (10 mmol/l), on human fat cell lipolysis in vitro was the aim of this study. The basal lipolysis was not modified and beta-hydroxybutyrate did not affect forskolin- or dibutyryl-cAMP-stimulated glycerol release, whereas it markedly inhibited isoproterenol-stimulated lipolysis. In membranes of intact adipocytes exposed to D-(-)-beta-hydroxybutyrate for 1 h, we found a decrease in beta-adrenoceptor affinity in saturation experiments and a shift to the right of the isoproterenol-mediated radioligand [( 125I]-cyanopindolol) displacement curve. These findings suggest that beta-hydroxybutyrate inhibits catecholamine-stimulated lipolysis by decreasing beta-adrenoceptor affinity. No effect of beta-hydroxybutyrate was found on beta-adrenoceptor binding of intact mononuclear cells of peripheral blood. In conclusion, the beta-adrenoceptor affinity lowering effect of beta-hydroxybutyrate is seemingly specific to human fat cells and might represent a feed-back mechanism that prevents an uncontrolled breakdown of triglycerides and indirectly regulates its own production rate.
De Pergola
G
G
Cattedra di Endocrinologia dell'Università di Bari, Italy.
Cignarelli
M
M
Corso
M
M
Garruti
G
G
Di Paolo
S
S
Giorgino
R
R
D020155:3-Hydroxybutyric Acid; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D003994:Bucladesine / Q000037:antagonists & inhibitors; D005576:Colforsin / Q000037:antagonists & inhibitors; D005246:Feedback; D006801:Humans; D006885:Hydroxybutyrates / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D007657:Ketone Bodies / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D006885:Hydroxybutyrates; D007657:Ketone Bodies; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D003994:Bucladesine; D007545:Isoproterenol; D020155:3-Hydroxybutyric Acid