Quantifying ceramide kinetics in vivo using stable isotope tracers and LC-MS/MS

被引：9

作者：

Chen, Ying ^{[1
]}

Berejnaia, Olga ^{[1
]}

Liu, Jinqi ^{[1
]}

Wang, Sheng-Ping ^{[1
]}

Daurio, Natalie A. ^{[1
]}

Yin, Wu ^{[1
]}

Mayoral, Rafael ^{[1
]}

Petrov, Aleksandr ^{[1
]}

Kasumov, Takhar ^{[2
]}

Zhang, Guo-Fang ^{[3
,4
]}

Previs, Stephen F. ^{[1
]}

Kelley, David E. ^{[1
]}

McLaren, David G. ^{[1
]}

机构：

[1] Merck & Co Inc, MRL, Kenilworth, NJ USA

[2] Northeast Ohio Med Univ, Dept Pharmaceut Sci, Rootstown, OH USA

[3] Duke Univ, Duke Mol Physiol Inst, Div Endocrinol Metab & Nutr, Durham, NC USA

[4] Duke Univ, Dept Med, Durham, NC USA

来源：

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 2018年 / 315卷 / 03期

关键词：

dyslipidemia; insulin resistance; kinetics; lipid turnover; mass spectrometry; INDUCED INSULIN-RESISTANCE; TANDEM MASS-SPECTROMETRY; AMINO-ACIDS; CHOLESTEROL-SYNTHESIS; DEUTERATED WATER; FATTY-ACIDS; DEUTERIUM INCORPORATION; TRIGLYCERIDE SYNTHESIS; PLASMA CERAMIDES; BIOSYNTHESIS;

D O I：

10.1152/ajpendo.00457.2017

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Numerous studies have implicated dyslipidemia as a key factor in mediating insulin resistance. Ceramides have received special attention since their levels are inversely associated with normal insulin signaling and positively associated with factors that are involved in cardiometabolic disease. Despite the growing literature surrounding ceramide biology, there are limited data regarding the activity of ceramide synthesis and turnover in vivo. Herein, we demonstrate the ability to measure ceramide kinetics by coupling the administration of [H-2] water with LC-MS/MS analyses. As a "proof-of-concept" we determined the effect of a diet-induced alteration on ceramide flux; studies also examined the effect of myriocin (a known inhibitor of serine palmitoyltransferase, the first step in sphingosine biosynthesis). Our data suggest that one can estimate ceramide synthesis and draw conclusions regarding the source of fatty acids; we discuss caveats in regards to method development in this area.

引用

页码：E416 / E424

页数：9

共 60 条

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