title: Lactate increases hepatic secretion of VLDL-triglycerides in humans.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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]-(2)H5-glycerol. Palmitic acid (16:0) and palmitoleic acid (16:1) in VLDL1 and VLDL2 were measured as a reflection of liver SCD1 activity.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Brigitte M
authors.initials: BM
authors.lastname: Sondermeijer
authors.forename: Suzanne
authors.initials: S
authors.lastname: Battjes
authors.forename: Theo H
authors.initials: TH
authors.lastname: van Dijk
authors.forename: Mariëtte T
authors.initials: MT
authors.lastname: Ackermans
authors.forename: Mireille J
authors.initials: MJ
authors.lastname: Serlie
authors.forename: Max
authors.initials: M
authors.lastname: Nieuwdorp
authors.forename: Albert K
authors.initials: AK
authors.lastname: Groen
authors.forename: Geesje M
authors.initials: GM
authors.lastname: Dallinga-Thie
authors.forename: Erik S G
authors.initials: ES
authors.lastname: Stroes
mesh_terms: D000328:Adult; D005229:Fatty Acids, Monounsaturated / Q000097:blood; D005990:Glycerol / Q000008:administration & dosage; D006706:Homeostasis; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D019344:Lactic Acid / Q000008:administration & dosage*; D008079:Lipoproteins, VLDL / Q000097:blood* / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009426:Netherlands; D019308:Palmitic Acid / Q000097:blood; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism; D013997:Time Factors; D014280:Triglycerides / Q000097:blood* / Q000378:metabolism; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D005229:Fatty Acids, Monounsaturated; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; C008757:palmitoleic acid; D019308:Palmitic Acid; D019344:Lactic Acid; C523776:SCD1 protein, human; D013230:Stearoyl-CoA Desaturase; D005990:Glycerol