Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390; Department of Clinical Nutrition, University of Texas Southwestern Medical Center, Dallas, TX 75390.
J Lipid Res. 2018 Sep;59(9):1685-1694. doi: 10.1194/jlr.M086405. Epub 2018 Jul 27.
It is a challenge to assess metabolic dysregulation in fatty liver of human patients prior to clinical manifestations. Here, we recruited obese, but otherwise healthy, subjects to examine biochemical processes in the liver with simple triglyceride accumulation using stable isotopes and NMR analysis of metabolic products in blood. Intrahepatic triglycerides were measured using H magnetic resonance spectroscopy, and volunteers received HO and [U-C]glycerol orally, followed by a series of blood draws. NMR analysis of plasma triglycerides and glucose provided detailed information about metabolic pathways in patients with simple hepatic steatosis. Compared with subjects with low hepatic fat, patients with hepatic steatosis were characterized by the following: lower C enrichments in the glycerol backbones of triglycerides (i.e., TG-[C]glycerol), higher [U-C]glycerol metabolism through the tricarboxylic acid (TCA) cycle, delayed gluconeogenesis from [U-C]glycerol, and less flexibility in adjusting supporting fluxes of glucose production upon an oral load of glycerol. In summary, simple hepatic steatosis was associated with enhanced [U-C]glycerol metabolism through pathways that intersect the TCA cycle and delayed gluconeogenesis from glycerol.
在临床表现之前评估人类患者脂肪肝中的代谢失调是一项挑战。在这里，我们招募了肥胖但其他方面健康的受试者，使用稳定同位素和血液代谢产物的 NMR 分析来检查肝脏中简单甘油三酯积累的生化过程。使用 H 磁共振光谱法测量肝内甘油三酯，志愿者口服 HO 和 [U-C]甘油，然后进行一系列血液采集。对血浆甘油三酯和葡萄糖的 NMR 分析提供了患有单纯性肝脂肪变性患者代谢途径的详细信息。与肝脂肪含量低的受试者相比，患有肝脂肪变性的患者具有以下特征：甘油三酯（即 TG-[C]甘油）甘油骨架中的 C 丰度降低，通过三羧酸 (TCA) 循环的 [U-C]甘油代谢增加，从 [U-C]甘油生成的糖异生延迟，以及在口服甘油负荷时调节葡萄糖生成支持通量的灵活性降低。总之，单纯性肝脂肪变性与通过与 TCA 循环相交的途径增强 [U-C]甘油代谢和从甘油生成糖异生延迟有关。
