Jin Eunsook S, Lee Min H, Malloy Craig R
Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Department of Internal Medicine, University of Texas Southwestern Medical Center, USA.
Metabol Open. 2021 Feb 26;9:100086. doi: 10.1016/j.metop.2021.100086. eCollection 2021 Mar.
In our recent study using [U-C]glycerol, a small subset of hamsters showed an unusual profile of glycerol metabolism: negligible gluconeogenesis from glycerol plus conversion of glycerol to 1,3-propanediol (1,3PDO) and 3-hydroxypropionate (3HP) which were detected in the liver and blood. The purpose of the current study is to evaluate the association of these unusual glycerol products with other biochemical processes in the liver.
Fasted hamsters received acetaminophen (400 mg/kg; n = 16) or saline (n = 10) intraperitoneally. After waiting 2 h, all the animals received [U-C]glycerol intraperitoneally. Liver and blood were harvested 1 h after the glycerol injection for NMR analysis and gene expression assays.
1,3PDO and 3HP derived from [U-C]glycerol were detected in the liver and plasma of eight hamsters (two controls and six hamsters with acetaminophen treatment). Glycerol metabolism in the liver of these animals differed substantially from conventional metabolic pathways. [U-C]glycerol was metabolized to acetyl-CoA as evidenced with downstream products detected in glutamate and β-hydroxybutyrate, yet C labeling in pyruvate and glucose was minimal (p < 0.001, C labeling difference in each metabolite). Expression of aldehyde dehydrogenases was enhanced in hamster livers with 1,3PDO and 3HP (p < 0.05).
Detection of 1,3PDO and 3HP in the hamster liver was associated with unorthodox metabolism of glycerol characterized by conversion of 3HP to acetyl-CoA followed by ketogenesis and oxidative metabolism through the TCA cycle. Additional mechanistic studies are needed to determine the causes of unusual glycerol metabolism in a subset of these hamsters.
在我们最近使用[U-C]甘油的研究中，一小部分仓鼠呈现出异常的甘油代谢特征：甘油的糖异生作用可忽略不计，同时甘油可转化为1,3-丙二醇（1,3PDO）和3-羟基丙酸（3HP），这些物质在肝脏和血液中被检测到。本研究的目的是评估这些异常甘油产物与肝脏中其他生化过程的关联。
禁食的仓鼠腹腔注射对乙酰氨基酚（400mg/kg；n = 16）或生理盐水（n = 10）。等待2小时后，所有动物腹腔注射[U-C]甘油。甘油注射1小时后采集肝脏和血液用于核磁共振分析和基因表达检测。
在8只仓鼠（2只对照仓鼠和6只接受对乙酰氨基酚治疗的仓鼠）的肝脏和血浆中检测到了源自[U-C]甘油的1,3PDO和3HP。这些动物肝脏中的甘油代谢与传统代谢途径有很大不同。[U-C]甘油代谢生成了乙酰辅酶A，这在谷氨酸和β-羟基丁酸中检测到的下游产物中得到了证实，但丙酮酸和葡萄糖中的碳标记极少（p < 0.001，各代谢物的碳标记差异）。在有1,3PDO和3HP的仓鼠肝脏中，醛脱氢酶的表达增强（p < 0.05）。
仓鼠肝脏中1,3PDO和3HP的检测与甘油的非常规代谢有关，其特征是3HP转化为乙酰辅酶A，随后通过三羧酸循环进行生酮和氧化代谢。需要进一步的机制研究来确定这些仓鼠中一部分出现异常甘油代谢的原因。
