Lactate increases hepatic secretion of VLDL-triglycerides in humans

• Published in: Atherosclerosis Vol. 228; no. 2; pp. 443 - 450
• Main Authors: Sondermeijer, Brigitte M., Battjes, Suzanne, van Dijk, Theo H., Ackermans, Mariëtte T., Serlie, Mireille J., Nieuwdorp, Max, Groen, Albert K., Dallinga-Thie, Geesje M., Stroes, Erik S.G.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.06.2013
• Subjects: administration & dosage; Adult; atherosclerosis; blood; Cardiovascular; central nervous system; drug effects; excretion; Fatty Acids, Monounsaturated; Fatty Acids, Monounsaturated - blood; glycerol; Glycerol - administration & dosage; Homeostasis; Humans; hypertriglyceridemia; Infusions, Intravenous; Injections, Intravenous; Lactate; Lactic Acid; Lactic Acid - administration & dosage; lipid metabolism; Lipoproteins, VLDL; Lipoproteins, VLDL - blood; Lipoproteins, VLDL - secretion; Liver; Liver - drug effects; Liver - secretion; Male; men; metabolism; Models, Biological; nerve tissue; Netherlands; palmitic acid; Palmitic Acid - blood; palmitoleic acid; pathophysiology; rodents; SCD1; secretion; Stearoyl-CoA Desaturase; Stearoyl-CoA Desaturase - metabolism; Time Factors; triacylglycerols; Triglycerides; Triglycerides - blood; Triglycerides - secretion; Up-Regulation; very low density lipoprotein; VLDL; Young Adult; Netherlands; FFA; Apo; Lactate; FTR; Liver; Triglycerides; HDL; TG; LDL; SCD; VLDL; NPY; SCD1; BMI; low density lipoprotein; apolipoprotein; body mass index; neuropeptide Y; fractional transfer rate; free fatty acid; very low density lipoprotein; high density lipoprotein; stearyl-CoA desaturase
• ISSN: 0021-9150; 1879-1484; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2013.02.040

The pathophysiology of hypertriglyceridemia is complex hampering effective therapeutic strategies. Increased central parasympathetic nerve activity was shown to inhibit hepatic triglyceride (TG) excretion via modulation of liver stearyl-CoA desaturase (SCD)-1 activity in rodents. We evaluated the impact of 7-h lactate clamping on VLDL-TG homeostasis in humans. Eight normolipidemic, male subjects were subjected to a continuous infusion of l-lactate (target concentration 3 mmol/L) or saline for 7 h in random order on two separate occasions. TG kinetics in very low density lipoproteins (VLDL1 and 2) were measured after a bolus injection of [1,1,2,3,3]-2H5-glycerol. Palmitic acid (16:0) and palmitoleic acid (16:1) in VLDL1 and VLDL2 were measured as a reflection of liver SCD1 activity. Plasma TG levels changed by 0.16 ± 0.09 mmol/L during lactate vs −0.15 ± 0.08 mmol/L during saline (P < 0.05). VLDL1 16:1/16:0 ratio increased to 1.2 ± 0.7 during lactate versus a decrease during saline by −1.5 ± 0.6 (p = 0.01). During lactate VLDL1-TG excretion was higher compared to saline (1604 [827–2870] versus 1285 [505–2155] μmol glycerol; p < 0.05), trending toward higher VLDL1-TG pool sizes during lactate (28%; p = 0.07 versus saline). In normolipidemic men, 7-h l-lactate clamp increases, rather than decreases SCD1 activity and hepatic TG secretion leading to elevated plasma TG levels. These conflicting data between human and rodents on central regulation of hepatic TG excretion illustrate that experimental findings on the role of the central nervous system in lipid metabolism should be interpreted with caution. ► A 7-h lactate clamp leads to an increase in TG secretion mainly in VLDL1. ► A small increase in SCD1 activity coincides with an increase in TG in VLDL1. ► These conflicting data between humans and rodents on regulation of hepatic TG excretion illustrate that experimental findings on regulation of TG metabolism should be interpreted with caution.