Evidence map›Paper›PMID 37121548›Full record

ArticleThe Journal of biological chemistry2023

CYP4F2 is a human-specific determinant of circulating N-acyl amino acid levels.

Julia T Tanzo, Veronica L Li, Amanda L Wiggenhorn, Maria Dolores Moya-Garzon, Wei Wei, Xuchao Lyu, Wentao Dong, Usman A Tahir, Zsu-Zsu Chen, Daniel E Cruz and 10 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.1field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 5 institutions in 1 country.

Julia T TanzoDepartment of Pathology, Stanford University School of Medicine, Stanford, California, USA; Stanford ChEM-H, Stanford University, Stanford, California, USA; Stanford Diabetes Research Center, Stanford University, Stanford, California, USA.
Veronica L LiDepartment of Pathology, Stanford University School of Medicine, Stanford, California, USA; Stanford ChEM-H, Stanford University, Stanford, California, USA; Department of Chemistry, Stanford University, Stanford, California, USA; Wu Tsai Human Performance Alliance, Stanford University, California, USA.
Amanda L WiggenhornDepartment of Pathology, Stanford University School of Medicine, Stanford, California, USA; Stanford ChEM-H, Stanford University, Stanford, California, USA; Department of Chemistry, Stanford University, Stanford, California, USA.
Maria Dolores Moya-GarzonDepartment of Pathology, Stanford University School of Medicine, Stanford, California, USA; Stanford ChEM-H, Stanford University, Stanford, California, USA.
Wei WeiDepartment of Pathology, Stanford University School of Medicine, Stanford, California, USA; Stanford ChEM-H, Stanford University, Stanford, California, USA; Department of Biology, Stanford University, Stanford, California, USA.
Xuchao LyuDepartment of Pathology, Stanford University School of Medicine, Stanford, California, USA; Stanford ChEM-H, Stanford University, Stanford, California, USA; Wu Tsai Human Performance Alliance, Stanford University, California, USA.
Wentao DongStanford ChEM-H, Stanford University, Stanford, California, USA; Department of Chemical Engineering, Stanford University, Stanford, California, USA.
Usman A TahirDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Zsu-Zsu ChenDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Daniel E CruzDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Shuliang DengDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Xu ShiDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Shuning ZhengDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Yan GuoUniv of Mississippi Medical Center, Jackson, Mississippi, USA.
Mario SimsUniv of Mississippi Medical Center, Jackson, Mississippi, USA.
Monther Abu-RemailehStanford ChEM-H, Stanford University, Stanford, California, USA; Department of Chemical Engineering, Stanford University, Stanford, California, USA.
James G WilsonDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Robert E GersztenDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA; Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
Jonathan Z LongDepartment of Pathology, Stanford University School of Medicine, Stanford, California, USA; Stanford ChEM-H, Stanford University, Stanford, California, USA; Stanford Diabetes Research Center, Stanford University, Stanford, California, USA; Wu Tsai Human Performance Alliance, Stanford University, California, USA. Electronic address: jzlong@stanford.edu.
Mark D BensonDivision of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: mbenson@bidmc.harvard.edu.
Beth Israel Deaconess Medical Center · USStanford Medicine · USStanford University · USJackson Memorial Hospital · USBroad Institute · US

Funding

Metabolomic predictors of insulin resistance and diabetesR01DK081572 · NIDDK · VANDERBILT UNIVERSITY · PI CLISH, CLARY B, GERSZTEN, ROBERT E · 2008 to 2025
$9.3M
Proteomics of Cardiometabolic and Renal Traits in African AmericansR01HL133870 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI ROBERT E GERSZTEN · 2017 to 2026
$6.7M
Biochemical profiling to identify cardiometabolic responsiveness to an endurance exercise interventionR01NR019628 · NINR · BETH ISRAEL DEACONESS MEDICAL CENTER · PI GERSZTEN, ROBERT E, SARZYNSKI, MARK ANDREW · 2021 to 2025
$2.7M
Chemical control of energy metabolism by N-acyl amino acidsR01DK124265 · NIDDK · STANFORD UNIVERSITY · PI LONG, JONATHAN Z · 2020 to 2024
$2.0M
Molecular Pharmacology Training GrantT32GM113854 · NIGMS · STANFORD UNIVERSITY · PI MOCHLY-ROSEN, DARIA · 2015 to 2019
$1.1M
The Role of PPM1G in Apolipoprotein E Biology and Atherosclerotic Cardiovascular DiseaseK08HL145095 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI BENSON, MARK DANIEL · 2019 to 2023
$836k
The Role of SECTM1 in Monocyte Biology and AtherosclerosisK08HL161445 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Usman A. Tahir · 2022 to 2026
$822k
NHLBI NIH HHS HHSN268201800010INHLBI NIH HHS HHSN268201800011CNHLBI NIH HHS HHSN268201800011INHLBI NIH HHS HHSN268201800012CNHLBI NIH HHS HHSN268201800012INHLBI NIH HHS HHSN268201800014CNHLBI NIH HHS HHSN268201800014INHLBI NIH HHS HHSN268201800015INHLBI NIH HHS K08 HL145095NHLBI NIH HHS K08 HL161445NHLBI NIH HHS R01 HL133870NIDDK NIH HHS R01 DK081572NIDDK NIH HHS R01 DK124265NIGMS NIH HHS T32 GM113854NIMHD NIH HHS HHSN268201800013ININR NIH HHS R01 NR019628
6 · The paper itself

Abstract

N-acyl amino acids are a large family of circulating lipid metabolites that modulate energy expenditure and fat mass in rodents. However, little is known about the regulation and potential cardiometabolic functions of N-acyl amino acids in humans. Here, we analyze the cardiometabolic phenotype associations and genomic associations of four plasma N-acyl amino acids (N-oleoyl-leucine, N-oleoyl-phenylalanine, N-oleoyl-serine, and N-oleoyl-glycine) in 2351 individuals from the Jackson Heart Study. We find that plasma levels of specific N-acyl amino acids are associated with cardiometabolic disease endpoints independent of free amino acid plasma levels and in patterns according to the amino acid head group. By integrating whole genome sequencing data with N-acyl amino acid levels, we identify that the genetic determinants of N-acyl amino acid levels also cluster according to the amino acid head group. Furthermore, we identify the CYP4F2 locus as a genetic determinant of plasma N-oleoyl-leucine and N-oleoyl-phenylalanine levels in human plasma. In experimental studies, we demonstrate that CYP4F2-mediated hydroxylation of N-oleoyl-leucine and N-oleoyl-phenylalanine results in metabolic diversification and production of many previously unknown lipid metabolites with varying characteristics of the fatty acid tail group, including several that structurally resemble fatty acid hydroxy fatty acids. These studies provide a structural framework for understanding the regulation and disease associations of N-acyl amino acids in humans and identify that the diversity of this lipid signaling family can be significantly expanded through CYP4F-mediated ω-hydroxylation.

Indexed as

Amino AcidsCytochrome P450 Family 4Oleic AcidsCardiovascular DiseasesFatty AcidsGlycineHumansLeucinePhenylalanineAmino AcidsCYP4F2 protein, humanCytochrome P450 Family 4Fatty AcidsGlycineLeucineN-oleoylglycineOleic AcidsPhenylalanineCYP4F2fatty acidfatty acid hydroxy fatty acidsfunctional genomicsmetabolomicsN-acyl amino acid

Identifiers

PMID37121548
PMCPMC10318452
OpenAlexW4367311328

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.