1660-P: Lactate Inhibits Lipolysis in Healthy Males—A Randomized Crossover Trial

Abstract

Background: The intermediary metabolite lactate has signaling capacities through the lactate specific receptor GPR81/HCA1. Ex-vivo, lactate inhibits lipolysis through GPR81, but in-vivo human data are scarce. Lactate-mediated inhibition of lipolysis could improve insulin sensitivity. The aim of the study was to investigate if hyperlactatemia at physiological concentrations inhibits palmitate lipolysis and affects glucose metabolism in healthy males. Methods: In a randomized cross-over design, eight healthy men were studied after an overnight fast on two occasions 1) during a sodium-lactate infusion (LAC) and 2) during a NaCl infusion (CTL). Both study days comprised a 3-hour basal period followed by a 3-hour hyperinsulinemic euglycemic clamp (HEC) period. Lipolysis rate and endogenous glucose production (EGP) were evaluated using [9,10-3H]-palmitate and [3H]-glucose tracers. Average glucose infusion rate (mg/kg/min) during the last 30 min of the HEC (M-value) was used as a measure of insulin sensitivity. Data are mean±SD Results: Plasma lactate increased to 2.6 ±0.6 mmol/L during LAC vs. 0.8 ±0.3 mmol/L during CTL (p<0.001). At the end of the basal period, palmitate flux was 30% lower during LAC compared with CTL (84 ±32 μmol/min vs. 120 ±35 μmol/min, p=0.003). At the end of the HEC, palmitate flux was similarly suppressed during both interventions (p=0.7). Plasma FFA were lower during LAC compared with CTL (0.2 ±0.1 mmol/L vs. 0.3 ±0.1 mmol/L, p=0.03) at the end of the basal period and equally suppressed during both interventions at the end of the HEC (p=0.7). EGP was unaffected by LAC compared with CTL at the end of the basal period (p=1.0) and suppressed at the end of the HEC during both interventions (p=1.0). M-value was unaffected by LAC compared with CTL (p=0.8). Conclusion: Lactate inhibits palmitate lipolysis by 30 %, an effect which per se may improve insulin sensitivity. Hyperlactatemia did not affect EGP or insulin sensitivity, possibly because lactate intrinsically may induce insulin resistance. Disclosure M.G.B.Pedersen: None. N.Rittig: Research Support; ARLA. E.Søndergaard: None. L.C.Gormsen: None. N.Møller: Other Relationship; Aarhus University/Ketlace.