Evidence map›Paper›PMID 20352092›Full record

ArticlePloS one2010

Long-chain fatty acid combustion rate is associated with unique metabolite profiles in skeletal muscle mitochondria.

Erin L Seifert, Oliver Fiehn, Véronic Bezaire, David R Bickel, Gert Wohlgemuth, Sean H Adams, Mary-Ellen Harper

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.6field-weighted citation impact, top 11% 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

14 citing papers in PubMed, 28 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Article
  5. Article
  6. A novel amino acid and metabolomics signature in mice overexpressing muscle uncoupling protein 3.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017
    Article
  7. Review
  8. Article
  9. Muscle uncoupling protein 3 overexpression mimics endurance training and reduces circulating biomarkers of incomplete β-oxidation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2013
    Article
  10. Review
  11. Role of intramyocelluar lipids in human health.Trends in endocrinology and metabolism: TEM · 2012
    Review
  12. Article
  13. Article
  14. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Erin L SeifertDepartment of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
Oliver Fiehn
Véronic Bezaire
David R Bickel
Gert Wohlgemuth
Sean H Adams
Mary-Ellen Harper
University of Ottawa · CAUniversity of California, Davis · USWestern Human Nutrition Research Center · US

Funding

Identification of Muscle-Specific Biomarkers of Fatty Acid beta-OxidationR01DK078328 · NIDDK · U.S. AGRICULTURAL RESEARCH SERVICE · PI ADAMS, SEAN HARRISON · 2008 to 2012
$1.8M
CIHR 57810NIDDK NIH HHS R01 DK078328NIDDK NIH HHS R01DK078328
6 · The paper itself

Abstract

BACKGROUND/

aimIncomplete or limited long-chain fatty acid (LCFA) combustion in skeletal muscle has been associated with insulin resistance. Signals that are responsive to shifts in LCFA beta-oxidation rate or degree of intramitochondrial catabolism are hypothesized to regulate second messenger systems downstream of the insulin receptor. Recent evidence supports a causal link between mitochondrial LCFA combustion in skeletal muscle and insulin resistance. We have used unbiased metabolite profiling of mouse muscle mitochondria with the aim of identifying candidate metabolites within or effluxed from mitochondria and that are shifted with LCFA combustion rate. METHODOLOGY/PRINCIPAL

findingsLarge-scale unbiased metabolomics analysis was performed using GC/TOF-MS on buffer and mitochondrial matrix fractions obtained prior to and after 20 min of palmitate catabolism (n = 7 mice/condition). Three palmitate concentrations (2, 9 and 19 microM; corresponding to low, intermediate and high oxidation rates) and 9 microM palmitate plus tricarboxylic acid (TCA) cycle and electron transport chain inhibitors were each tested and compared to zero palmitate control incubations. Paired comparisons of the 0 and 20 min samples were made by Student's t-test. False discovery rate were estimated and Type I error rates assigned. Major metabolite groups were organic acids, amines and amino acids, free fatty acids and sugar phosphates. Palmitate oxidation was associated with unique profiles of metabolites, a subset of which correlated to palmitate oxidation rate. In particular, palmitate oxidation rate was associated with distinct changes in the levels of TCA cycle intermediates within and effluxed from mitochondria. CONCLUSIONS/SIGNIFICANCE: This proof-of-principle study establishes that large-scale metabolomics methods can be applied to organelle-level models to discover metabolite patterns reflective of LCFA combustion, which may lead to identification of molecules linking muscle fat metabolism and insulin signaling. Our results suggest that future studies should focus on the fate of effluxed TCA cycle intermediates and on mechanisms ensuring their replenishment during LCFA metabolism in skeletal muscle.

Indexed as

3-Hydroxybutyric AcidAnimalsChromatography, GasFatty AcidsFemaleInsulin ResistanceKetonesMass SpectrometryMetabolomicsMiceMice, Inbred C57BLMitochondriaMitochondria, MuscleMuscle, SkeletalOxygen3-Hydroxybutyric AcidFatty AcidsKetonesOxygen

Identifiers

PMID20352092
PMCPMC2844415
OpenAlexW2080270129

What OpenQuestion holds

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LicenceCC0
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Registered trials

None linked

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.