CoChat
Sign Up
Cited by 213Metabolism, Diabetes, and CancerAdipose Tissue and MetabolismMuscle Physiology and Disorders

Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor

Open access
Ukropcova, Barbara, McNeil, Michele, Sereda, Olga, de Jonge, Lilian, Xie, Hui, Bray, George A., Smith, Steven R.·2005·Journal of Clinical Investigation
DOI 10.1172/jci24332PMC PMC1159139
Open this paper in CoChat — free accountOpen PDF

Abstract

Metabolic flexibility of skeletal muscle, that is, the preference for fat oxidation (FOx) during fasting and for carbohydrate oxidation in response to insulin, is decreased during insulin resistance. The aim of this study was to test the hypothesis that the capacity of myotubes to oxidize fat in vitro reflects the donor's metabolic characteristics. Insulin sensitivity (IS) and metabolic flexibility of 16 healthy, young male subjects was determined by euglycemic hyperinsulinemic clamp. Muscle samples were obtained from vastus lateralis, cultured, and differentiated into myotubes. In human myotubes in vitro, we measured suppressibility (glucose suppression of FOx) and adaptability (an increase in FOx in the presence of high palmitate concentration). We termed these dynamic changes in FOx metabolic switching. In vivo, metabolic flexibility was positively correlated with IS and maximal oxygen uptake and inversely correlated with percent body fat. In vitro suppressibility was inversely correlated with IS and metabolic flexibility and positively correlated with body fat and fasting FFA levels. Adaptability was negatively associated with percent body fat and fasting insulin and positively correlated with IS and metabolic flexibility. The interindividual variability in metabolic phenotypes was preserved in human myotubes separated from their neuroendocrine environment, which supports the hypothesis that metabolic switching is an intrinsic property of skeletal muscle.

Integrity signals

Registry

Crossref · 10.1172/jci24332

Cites

79 of 79 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 12 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    In vitro, increasing palmitate concentration increases 14CO2 and ASP production.

    “Increasing palmitate concentration in vitro produced an increase in 14 CO 2 and ASP production (r = 0.998; P < 0.0001; Figure 1B).”
    Quote in the paperSubstantial claim
  • Findingown data

    In some subjects, maximal fat oxidation rate reflected by ASP production plateaus at 100 μM palmitate.

    “However, in some subjects, the maximal rate of FOx (reflected by ASP production) flattened out at 100 µM palmitate, which suggests an inability to further oxidize fatty acids.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Metabolic flexibility, the insulin-stimulated change in RQ during clamp, is inversely related to percent body fat and fasting FFA levels.

    “Metabolic flexibility, defined as the change in RQ during a clamp [∆RQ (clamp)], was negatively correlated with percent body fat and fasting FFA levels”
    Quote in the paperSubstantial claim
  • Findingown data

    In vitro, increasing extracellular glucose decreases fat oxidation as measured by 14CO2 and acid-soluble products.

    “An increase in the extracellular glucose concentration in vitro resulted in a decrease of FOx as indicated by levels of both 14 CO 2 and 14 C-intermediate metabolites of FOx (acidsoluble products [ASPs]) (r = -0.96,P < 0.0001 for 14 CO 2 ; r = -0.95,P < 0.0001 for ASPs; data not shown).”
    Quote in the paperSubstantial claim
  • Findingown data

    In these subjects, insulin sensitivity is negatively correlated with fasting insulin and fasting FFA levels.

    “A negative correlation was observed between IS and fasting levels of both insulin (r = -0.65;P = 0.0003) and FFAs (r = -0.81;P < 0.0001).”
    Quote in the paperNot a substantial claim
  • May combine two claims. 13
  • Classified as probably not a substantial claim. 7
  • The quote only partly states this claim. 3

  • May combine two claims.

    Findingown data

    Metabolic flexibility (∆RQ clamp) is positively correlated with insulin sensitivity and VO2max.

    “On the other hand, ∆RQ (clamp) correlated positively with IS and VO 2 max”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In healthy young men, insulin sensitivity measured by euglycemic hyperinsulinemic clamp is negatively correlated with percent body fat and positively correlated with maximal oxygen uptake.

    “As expected, IS, measured by euglycemic hyperinsulinemic clamp (clamp), correlated negatively with percentage body fat (r = -0.60;P = 0.008) and positively with maximal oxygen uptake (VO 2 max) (r = 0.59; P = 0.015)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Fasting RQ during the clamp is not related to insulin sensitivity or percent body fat.

    “Fasting RQ during the clamp, a parameter of fasting fuel partitioning, was related neither to IS (P = 0.80) nor to anthropometric characteristics of subjects (percent body fat; P = 0.60).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Neither percent suppression of 14CO2 nor percent suppression of total palmitate oxidation correlated with fasting RQ or 24-hour RQ in vivo.

    “Neither percentage suppression of 14 CO 2 nor percentage suppression of TOx correlated with fasting RQ (measured by clamp) or 24hour RQ (measured by indirect calorimetry) in vivo.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Brief palmitate exposure raised myotube fat oxidation by roughly three- to fivefold, and the size of that rise tracked donor clinical phenotype.

    “In our model, short-term exposure of myotubes to increased palmitate levels enhanced FOx 3-to 5-fold, the magnitude of response correlating with clinical phenotype.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In vitro suppressibility (percent suppression of 14CO2) is positively correlated with percent body fat and fasting FFA levels.

    “Similarly, we found a correlation between the suppressibility of FOx by glucose (percent suppression of 14 CO 2 ) in vitro and percent body fat (r = 0.56; P = 0.02) and fasting FFA levels (r = 0.58; P = 0.01; Figure 2, C and D) in vivo.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In vitro adaptability (fold increase in 14CO2) is positively correlated with in vivo metabolic flexibility (∆RQ clamp), insulin sensitivity, and aerobic capacity (VO2max).

    “Fold increase in 14 CO 2 was positively correlated with in vivo metabolic flexibility [as indicated by ∆RQ (clamp)] (r = 0.53; P = 0.035; Figure 3A), IS (as measured by clamp) (r = 0.60; P = 0.015; Figure 3B) and aerobic capacity (VO 2 max) (r = 0.70; P = 0.002; Figure 3C), respectively.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The 14CO2 fat oxidation rate at basal palmitate was 0.33 ± 0.25 nmol per 3 hours per mg protein.

    “14 CO2 at basal palmitate | 0.33 ± 0.25 | 0.15-0.71”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Interpretationown data

    In both assays, CO2 output tracked clinical phenotypes more closely than ASP output did.

    “As was the case with the in vitro glucose suppressibility assay, CO 2 production appeared to be a better correlate with the clinical phenotypes than was ASP production.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The data show an association between donor clinical traits and dynamic fat-oxidation changes in cultured myotubes, which backs the idea that metabolic switching is partly intrinsic to skeletal muscle.

    “analysis clearly demonstrate the relationship between clinical phenotypes and dynamic changes in FOx in cultured myotubes, which supports the hypothesis that metabolic switching is, at least to a certain extent, an intrinsic characteristic of skeletal muscle.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Growing human myotubes in a standardized insulin-free medium strips away whole-body neuroendocrine and environmental effects, so the in vitro readouts reveal intrinsic muscle-cell properties.
    • Rests on an assumption: The donor's metabolic phenotype is stable and captured well enough by the measured in vivo traits.

  • May combine two claims.

    Interpretationown data

    Greater glucose suppression of fat oxidation indicates insulin resistance and metabolic inflexibility.

    “According to our studies, in vivo insulin responsiveness decreases with increasing in vitro suppressibility, which indicates greater glucose suppression of FOx in insulin resistance and metabolic inflexibility.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Respiratory quotient was adjusted for energy balance.

    “RQ were adjusted for energy balance as described previously (71).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [71] Nguyen, 2003, Med. Biol. Eng. Comput. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Insulin sensitivity, measured as glucose disposal rate, was adjusted for kilograms of lean body mass.

    “Glucose disposal rate, a parameter of IS, was adjusted for kilograms of LBM.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims. The quote only partly states this claim.

    Study design and conductown data

    The in vitro suppressibility and adaptability assays were run in duplicate, and results were normalized to protein content.

    “All assays were performed in duplicate, and data were normalized to protein content.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Body composition measurements had coefficients of variation of 0.8% for lean body mass, 1.6% for fat mass, and 1.7% for body fat percentage.

    “Coefficients of variation for the measurement of the LBM, fat mass, and percentage of body fat were 0.8%, 1.6%, and 1.7%, respectively.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Skeletal muscle oxidative and fat-metabolism defects track closely with insulin sensitivity and are thought to help cause insulin resistance.

    “Defects in skeletal muscle oxidative capacity and fat metabolism are highly correlated with insulin sensitivity (IS) (1,5,12) and are believed to contribute to the pathogenesis of insulin resistance (13,14).”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [1] Colberg, 1995, J. Clin. Invest. source

      Not checked in the free run.

    • cites [5] Kelley, 1999, Am. J. Physiol. source

      Not checked in the free run.

    • cites [12] Bruce, 2003, J. Clin. Endocrinol. Metab. source

      Not checked in the free run.

    • cites [13] Storlien, 2004, Proc. Nutr. Soc. source

      Not checked in the free run.

    • cites [14] Kelley, 2000, Diabetes. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims. The quote only partly states this claim.

    Study design and conductown data

    Total daily energy expenditure and respiratory quotient measured in the respiratory chamber had coefficients of variation of 2% and 16%, respectively.

    “Coefficients of variation for total daily energy expenditure and RQ are 2% and 16%, respectively.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    A semi-partial correlation was used to relate fold increase in fat oxidation to clinical characteristics while holding basal fat oxidation constant.

    “To account for the effect of basal FOx on the fold increase in FOx, the semi-partial correlation was computed to examine the relations between fold increase FOx and clinical characteristics (BMI, VO2max, fasting insulin, etc.), while basal FOx production was held as a constant.”
    Quote in the paperSubstantial claim
18 of 18

  • The paper relies on this without support.

    Growing human myotubes in a standardized insulin-free medium strips away whole-body neuroendocrine and environmental effects, so the in vitro readouts reveal intrinsic muscle-cell properties.

    “We cultured muscle satellite cells from individuals with differing clinical characteristics in a standardized, insulin-free medium”
    “This model is ideal for studying interindividual differences of metabolism intrinsic to the skeletal muscle, i.e., independent of the influences of the whole-body environment”

  • The paper relies on this without support.

    The donor's metabolic phenotype is stable and captured well enough by the measured in vivo traits.

    “We related these responses of myotubes in vitro to the clinical phenotypes of their donors.”

  • The paper relies on this without support.

    In vitro intrinsic defects in metabolic switching reflect processes that contribute to obesity and insulin resistance in vivo.

    “Intrinsic defects in metabolic switching of skeletal muscle might participate in the generation of a “lipotoxic milieu” in the muscle cell (13, 14) that acts in concert with environmental factors, such as a HFD, to favor the accumulation of lipids and lipid intermediates implicated in insulin resistance (34)(35)(36)(37).”

  • The paper relies on this without support.

    The in vitro suppressibility assay in insulin-free medium measures the same process as in vivo insulin responsiveness.

    “The in vitro suppressibility assay was designed to measure the ability of myotubes to maintain FOx in the presence of glucose, in insulin-free medium (that is, fuel preference of metabolic switching).”

  • The paper relies on this without support.

    The in vitro adaptability assay measures the capacity of myotubes to increase fat oxidation in a way that reflects in vivo adaptability.

    “The in vitro adaptability assay focused on the capacity of myotubes to increase FOx in response to an acute exposure to a high palmitate concentration.”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Adaptability SD is incompatible with its mean and range

    Minor

    For 16 observations with a mean of 3.19 and a range of 2.99-4.87, the sample SD cannot exceed about 0.60. The reported SD of 0.76 is therefore incompatible with the other reported values.

  • Biopsy-method citation points to a different reference

    Minor

    The text cites reference 73 for the Bergstrom biopsy technique, but reference 73 is about energy expenditure. The Bergstrom biopsy paper is listed as reference 74.

2 of 2

Cites

Flagged first, then by citations

Research works printed but not linked: 12

  1. Raben, 1998, Am. J. Physiol., 275, E487
  2. Ranneries, 1998, Am. J. Physiol., 274, E155
  3. Zurlo, 1990, Am. J. Physiol., 259, E650
  4. Ravussin, 1993, Int. J. Obes. Relat. Metab. Disord., 17(Suppl. 3), S28
  5. Astrup, 1994, Am. J. Physiol., 266, E592
  6. Mandarino, 1996, Am. J. Physiol., 270, E463
  7. Sidossis, 1996, Am. J. Physiol., 270, E733
  8. Kleiber, 1992, Diabete. Metab., 18, 84
  9. Oakes, 2002, J. R. Soc. Med., 95(Suppl. 42), 33
  10. Kirkwood, 1991, Am. J. Physiol., 260, E89
  11. DeFronzo, 1979, Am. J. Physiol., 237, E214
  12. Acheson, 1984, Am. J. Physiol., 246, E62

Cited by

Sorted by citations

Related

Authors
Ukropcova, B., McNeil, M., Sereda, O., de Jonge, L., Xie, H., Bray, G. A., & Smith, S. R.
Affiliations
Pennington Biomedical Research Center (US)
Corresponding author
Smith, Steven R.
ORCID
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
2005-07-01
Volume
115
Issue
7
Pages
1934-1941
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci24332
PMC
PMC1159139
OpenAlex
W2098384661
Semantic Scholar
f721ac6c8e8feb8139e5dd7e128cb8df2dd30680
Cited by
213
References
79
Citations by year
2026: 2 · 2025: 7 · 2024: 4 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 10 · 2019: 4 · 2018: 7 · 2017: 9 · 2016: 10 · 2015: 11 · 2014: 12 · 2013: 21 · 2012: 11
FWCI
5.52
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
U.S. Department of Agriculture
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords
fat oxidation, insulin sensitivity, myotubes, metabolic switch, insulin resistance, palmitate, fat mass, VO2max, interindividual variability, vastus lateralis
MeSH terms
Adolescent, Adult, Dietary Fats, Glucose, Humans, Insulin Resistance, Male, Models, Biological, Oxidation-Reduction, Phenotype, Glucose Clamp Technique, Muscle Fibers, Skeletal, Palmitic Acid, In Vitro Techniques

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-05.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-05.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review