Influence of Lactate on Isoproterenol-Induced Lipolysis and β-Adrenoceptors Distribution in Human Fat Cells

Abstract

The influence of lactate on human adipocytes lipolysis and the possible relationship between lactate-induced metabolic effects and beta-adrenoceptor binding sites were investigated. beta-sites were identified in membranes with (125I)-cyanopindolol and in intact cells with (125I)-cyanopindolol and (3H)-CGP 12177. Lactate reduced isoproterenol-induced lipolysis in a dose-response fashion and such inhibition became significant only at 16 mmol/l lactate. Exposure of human fat cells to 16 mmol/l lactate significantly reduced beta-adrenoceptors density on crude membranes. When the binding assay was performed on intact cells using (125I)-cyanopindolol at 37 degrees C, the radioligand identified the same number of receptors, regardless of the presence of lactate in the preincubation medium. When (3H)-CGP 12177 was used, it bound to about 35% less receptors in lactate pre-treated cells than in control. Seemingly, at 37 degrees C, because of its lipophilicity, (125I)-cyanopindolol can cross the plasma membrane and bind to intracellular sites whereas, (3H)-CGP 1277, due to its hydrophilicity, identifies surface receptors only. Thus, the present in vitro study provides evidence that high levels of lactate, similar to the concentrations usually achieved in overt lactic acidosis, are able per se to inhibit human lipolysis and to redistribute beta-adrenoceptors from cell surface to a domain not accessible to hydrophilic ligands.

Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs.

“…For example, growth hormone is suppressed with somatostatin (18) and is known to have a lipolytic effect (23,24). Also, lactate increased in the present study and this may have contributed to the suppression of lipolysis (25). In any case, the role of glucagon in maintaining basal HGO may need to be reevaluated in a study in which FFA levels are carefully controlled.…”

Lactate Inhibits Lipolysis in Fat Cells through Activation of an Orphan G-protein-coupled Receptor, GPR81

“…Both of these studies used concentrations of lactate at the lower end of the dose-response curve that we have observed for recombinant GPR81. De Pergola et al (29) reported in 1989 that lactate could suppress stimulated but not basal lipolysis and that this effect was only significant when lactate reached 16 mM. Lower exposure was not described in the paper.…”

Inflammation inhibits GPR81 expression in adipose tissue

“…It has been recognized for many years that lactate inhibits lipolysis both in vivo and in vitro [22][23][24][25]. One can speculate that the decrease in GPR81 expression in adipose tissue could reduce the ability of lactate to inhibit lipolysis and thereby facilitate adipose tissue lipolysis.…”