D-(-)-BETA-HYDROXYBUTYRATE INHIBITS CATECHOLAMINE-STIMULATED LIPOLYSIS AND DECREASES BETA-ADRENOCEPTORS AFFINITY IN HUMAN FAT-CELLS BUT NOT IN LYMPHOMONOCYTES

The effect of D-(-)-β-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 β-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-(-)-β-hydroxybutyrate for 1 h, we found a decrease in β-adrenoceptor affinity in saturation experiments and a shift to the right of the isoproterenol-mediated radioligand ([125I]-cyanopindolol) displacement curve. These findings suggest that β-hydroxybutyrate inhibits catecholamine-stimulated lipolysis by decreasing β-adrenoceptor affinity. No effect of β-hydroxybutyrate was found on β-adrenoceptor binding of intact mononuclear cells of peripheral blood. In conclusion, the β-adrenoceptor affinity lowering effect of β-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.