Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Atherosclerosis. 2013 Jun;228(2):443-50. doi: 10.1016/j.atherosclerosis.2013.02.040. Epub 2013 Mar 14.
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]-(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.
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.
高甘油三酯血症的病理生理学十分复杂，这给有效的治疗策略带来了阻碍。研究表明，在啮齿动物中，增加中枢副交感神经活动可以通过调节肝脏硬脂酰辅酶 A 去饱和酶（SCD）-1 的活性来抑制肝内甘油三酯（TG）的排泄。我们评估了 7 小时乳酸钳夹对人体 VLDL-TG 稳态的影响。
8 名血脂正常的男性受试者分别在两次单独的试验中，随机接受持续 7 小时的 l-乳酸（目标浓度 3mmol/L）或生理盐水输注。在静脉注射[1,1,2,3,3]-(2)H5-甘油后，测量极低密度脂蛋白（VLDL1 和 2）中的甘油三酯动力学。VLDL1 和 VLDL2 中的棕榈酸（16:0）和棕榈油酸（16:1）被测量作为反映肝脏 SCD1 活性的指标。
与生理盐水相比，乳酸期间血浆 TG 水平变化 0.16±0.09mmol/L，而生理盐水期间变化-0.15±0.08mmol/L（P<0.05）。与生理盐水相比，乳酸期间 VLDL1 16:1/16:0 比值增加 1.2±0.7，而生理盐水降低-1.5±0.6（p=0.01）。与生理盐水相比，乳酸期间 VLDL1-TG 排泄量更高（1604[827-2870]与 1285[505-2155]μmol 甘油；p<0.05），乳酸时 VLDL1-TG 池大小也呈增加趋势（28%；p=0.07 与生理盐水相比）。
在血脂正常的男性中，7 小时 l-乳酸钳夹增加而不是降低 SCD1 活性和肝内 TG 分泌，导致血浆 TG 水平升高。这些关于中枢调节肝内 TG 排泄的人类与啮齿动物之间的矛盾数据表明，中枢神经系统在脂质代谢中的作用的实验发现应谨慎解释。
