Unique plasma metabolomic signatures of individuals with inherited disorders of long-chain fatty acid oxidation

Colin S. McCoin, Brian D. Piccolo, Trina A. Knotts, Dietrich Matern, Jerry Vockley, Melanie Gillingham, Sean H. Adams

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Blood and urine acylcarnitine profiles are commonly used to diagnose long-chain fatty acid oxidation disorders (FAOD: i.e., long-chain hydroxy-acyl-CoA dehydrogenase [LCHAD] and carnitine palmitoyltransferase 2 [CPT2] deficiency), but the global metabolic impact of long-chain FAOD has not been reported. We utilized untargeted metabolomics to characterize plasma metabolites in 12 overnight-fasted individuals with FAOD (10 LCHAD, two CPT2) and 11 healthy age-, sex-, and body mass index (BMI)-matched controls, with the caveat that individuals with FAOD consume a low-fat diet supplemented with medium-chain triglycerides (MCT) while matched controls consume a typical American diet. In plasma 832 metabolites were identified, and partial least squared-discriminant analysis (PLS-DA) identified 114 non-acylcarnitine variables that discriminated FAOD subjects and controls. FAOD individuals had significantly higher triglycerides and lower specific phosphatidylethanolamines, ceramides, and sphingomyelins. Differences in phosphatidylcholines were also found but the directionality differed by metabolite species. Further, there were few differences in non-lipid metabolites, indicating the metabolic impact of FAOD specifically on lipid pathways. This analysis provides evidence that LCHAD/CPT2 deficiency significantly alters complex lipid pathway flux. This metabolic signature may provide new clinical tools capable of confirming or diagnosing FAOD, even in subjects with a mild phenotype, and may provide clues regarding the biochemical and metabolic impact of FAOD that is relevant to the etiology of FAOD symptoms.

Original languageEnglish (US)
Pages (from-to)399-408
Number of pages10
JournalJournal of Inherited Metabolic Disease
Volume39
Issue number3
DOIs
StatePublished - May 1 2016

Fingerprint

Long-Chain Acyl-CoA Dehydrogenase
Metabolomics
Fatty Acids
Triglycerides
Phosphatidylethanolamines
Carnitine O-Palmitoyltransferase
Lipids
Fat-Restricted Diet
Sphingomyelins
Ceramides
Discriminant Analysis
Phosphatidylcholines
Body Mass Index
Urine
Diet
Phenotype
Carnitine palmitoyl transferase 2 deficiency

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Unique plasma metabolomic signatures of individuals with inherited disorders of long-chain fatty acid oxidation. / McCoin, Colin S.; Piccolo, Brian D.; Knotts, Trina A.; Matern, Dietrich; Vockley, Jerry; Gillingham, Melanie; Adams, Sean H.

In: Journal of Inherited Metabolic Disease, Vol. 39, No. 3, 01.05.2016, p. 399-408.

Research output: Contribution to journalArticle

McCoin, Colin S. ; Piccolo, Brian D. ; Knotts, Trina A. ; Matern, Dietrich ; Vockley, Jerry ; Gillingham, Melanie ; Adams, Sean H. / Unique plasma metabolomic signatures of individuals with inherited disorders of long-chain fatty acid oxidation. In: Journal of Inherited Metabolic Disease. 2016 ; Vol. 39, No. 3. pp. 399-408.
@article{d894ee6c3b7c464f9ba4f502efe7576a,
title = "Unique plasma metabolomic signatures of individuals with inherited disorders of long-chain fatty acid oxidation",
abstract = "Blood and urine acylcarnitine profiles are commonly used to diagnose long-chain fatty acid oxidation disorders (FAOD: i.e., long-chain hydroxy-acyl-CoA dehydrogenase [LCHAD] and carnitine palmitoyltransferase 2 [CPT2] deficiency), but the global metabolic impact of long-chain FAOD has not been reported. We utilized untargeted metabolomics to characterize plasma metabolites in 12 overnight-fasted individuals with FAOD (10 LCHAD, two CPT2) and 11 healthy age-, sex-, and body mass index (BMI)-matched controls, with the caveat that individuals with FAOD consume a low-fat diet supplemented with medium-chain triglycerides (MCT) while matched controls consume a typical American diet. In plasma 832 metabolites were identified, and partial least squared-discriminant analysis (PLS-DA) identified 114 non-acylcarnitine variables that discriminated FAOD subjects and controls. FAOD individuals had significantly higher triglycerides and lower specific phosphatidylethanolamines, ceramides, and sphingomyelins. Differences in phosphatidylcholines were also found but the directionality differed by metabolite species. Further, there were few differences in non-lipid metabolites, indicating the metabolic impact of FAOD specifically on lipid pathways. This analysis provides evidence that LCHAD/CPT2 deficiency significantly alters complex lipid pathway flux. This metabolic signature may provide new clinical tools capable of confirming or diagnosing FAOD, even in subjects with a mild phenotype, and may provide clues regarding the biochemical and metabolic impact of FAOD that is relevant to the etiology of FAOD symptoms.",
author = "McCoin, {Colin S.} and Piccolo, {Brian D.} and Knotts, {Trina A.} and Dietrich Matern and Jerry Vockley and Melanie Gillingham and Adams, {Sean H.}",
year = "2016",
month = "5",
day = "1",
doi = "10.1007/s10545-016-9915-3",
language = "English (US)",
volume = "39",
pages = "399--408",
journal = "Journal of Inherited Metabolic Disease",
issn = "0141-8955",
publisher = "Springer Netherlands",
number = "3",

}

TY - JOUR

T1 - Unique plasma metabolomic signatures of individuals with inherited disorders of long-chain fatty acid oxidation

AU - McCoin, Colin S.

AU - Piccolo, Brian D.

AU - Knotts, Trina A.

AU - Matern, Dietrich

AU - Vockley, Jerry

AU - Gillingham, Melanie

AU - Adams, Sean H.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Blood and urine acylcarnitine profiles are commonly used to diagnose long-chain fatty acid oxidation disorders (FAOD: i.e., long-chain hydroxy-acyl-CoA dehydrogenase [LCHAD] and carnitine palmitoyltransferase 2 [CPT2] deficiency), but the global metabolic impact of long-chain FAOD has not been reported. We utilized untargeted metabolomics to characterize plasma metabolites in 12 overnight-fasted individuals with FAOD (10 LCHAD, two CPT2) and 11 healthy age-, sex-, and body mass index (BMI)-matched controls, with the caveat that individuals with FAOD consume a low-fat diet supplemented with medium-chain triglycerides (MCT) while matched controls consume a typical American diet. In plasma 832 metabolites were identified, and partial least squared-discriminant analysis (PLS-DA) identified 114 non-acylcarnitine variables that discriminated FAOD subjects and controls. FAOD individuals had significantly higher triglycerides and lower specific phosphatidylethanolamines, ceramides, and sphingomyelins. Differences in phosphatidylcholines were also found but the directionality differed by metabolite species. Further, there were few differences in non-lipid metabolites, indicating the metabolic impact of FAOD specifically on lipid pathways. This analysis provides evidence that LCHAD/CPT2 deficiency significantly alters complex lipid pathway flux. This metabolic signature may provide new clinical tools capable of confirming or diagnosing FAOD, even in subjects with a mild phenotype, and may provide clues regarding the biochemical and metabolic impact of FAOD that is relevant to the etiology of FAOD symptoms.

AB - Blood and urine acylcarnitine profiles are commonly used to diagnose long-chain fatty acid oxidation disorders (FAOD: i.e., long-chain hydroxy-acyl-CoA dehydrogenase [LCHAD] and carnitine palmitoyltransferase 2 [CPT2] deficiency), but the global metabolic impact of long-chain FAOD has not been reported. We utilized untargeted metabolomics to characterize plasma metabolites in 12 overnight-fasted individuals with FAOD (10 LCHAD, two CPT2) and 11 healthy age-, sex-, and body mass index (BMI)-matched controls, with the caveat that individuals with FAOD consume a low-fat diet supplemented with medium-chain triglycerides (MCT) while matched controls consume a typical American diet. In plasma 832 metabolites were identified, and partial least squared-discriminant analysis (PLS-DA) identified 114 non-acylcarnitine variables that discriminated FAOD subjects and controls. FAOD individuals had significantly higher triglycerides and lower specific phosphatidylethanolamines, ceramides, and sphingomyelins. Differences in phosphatidylcholines were also found but the directionality differed by metabolite species. Further, there were few differences in non-lipid metabolites, indicating the metabolic impact of FAOD specifically on lipid pathways. This analysis provides evidence that LCHAD/CPT2 deficiency significantly alters complex lipid pathway flux. This metabolic signature may provide new clinical tools capable of confirming or diagnosing FAOD, even in subjects with a mild phenotype, and may provide clues regarding the biochemical and metabolic impact of FAOD that is relevant to the etiology of FAOD symptoms.

UR - http://www.scopus.com/inward/record.url?scp=84959152298&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959152298&partnerID=8YFLogxK

U2 - 10.1007/s10545-016-9915-3

DO - 10.1007/s10545-016-9915-3

M3 - Article

C2 - 26907176

AN - SCOPUS:84959152298

VL - 39

SP - 399

EP - 408

JO - Journal of Inherited Metabolic Disease

JF - Journal of Inherited Metabolic Disease

SN - 0141-8955

IS - 3

ER -