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Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor
Open accessAbstract
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.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Increasing palmitate concentration in vitro produced an increase in 14 CO 2 and ASP production (r = 0.998; P < 0.0001; Figure 1B).”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Relationship between metabolic flexibility and IS in vivo.
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In the paper
“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.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Relationship between metabolic flexibility and IS in vivo.
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In the paper
“Metabolic flexibility, defined as the change in RQ during a clamp [∆RQ (clamp)], was negatively correlated with percent body fat and fasting FFA levels”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Relationship between metabolic flexibility and IS in vivo.
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In the paper
“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).”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Relationship between metabolic flexibility and IS in vivo.
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In the paper
“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).”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Relationship between metabolic flexibility and IS in vivo.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“An inverse relationship was observed between basal FOx (at 1 µCi/ml 14 C-palmitate with 0 µM cold palmitate) and the fold increase in FOx (r = -0.51;P = 0.025).”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Relationship between metabolic flexibility and IS in vivo.
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In the paper
“A positive relationship was observed between percent suppression of 14 CO 2 by glucose (% suppression = [1 -(FOx at 5 mM glucose / FOx at 0 mM glucose)] × 100) and percent suppression of total palmitate oxidation (TOx) by glucose (TOx = 14 CO 2 + 14 C-ASPs) (r = 0.51; P = 0.03).”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Relationship between metabolic flexibility and IS in vivo.
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In the paper
“For fold change of TOx, no significant relationship was found between the results of the 2 assays.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Relationship between metabolic flexibility and IS in vivo.
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In the paper
“However, these in vitro-in vivo relationships were only observed for CO 2 , not for total FOx (P = 0.5 for percent body fat; P = 0.1 for FFA levels)”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Glucose suppressibility of FOx is an intrinsic characteristic of muscle cells.
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In the paper
“No significant relationship was observed between fold increase in 14 CO 2 (in the in vitro adaptability assay) and percent suppression of 14 CO 2 (in the in vitro suppressibility assay), when all 16 subjects were used for the analysis.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Relationship between metabolic flexibility and IS in vivo.
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In the paper
“A negative relationship was observed between body fat (r = -0.62;P = 0.01, Figure 3D) and a proxy of abdominal fatness, waist circumference (r = -0.4;P = 0.01).”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Metabolic adaptability is an intrinsic characteristic of muscle cells.
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In the paper
“The relationships between fold increase in TOx and waist circumference or fasting insulin level were statistically significant (r = -0.34,P = 0.02 and r = -0.55,P = 0.027, respectively).”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Metabolic adaptability is an intrinsic characteristic of muscle cells.
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In the paper
“It was inversely correlated with in vivo metabolic flexibility [as indicated by ∆RQ (clamp)] (r = -0.61;P = 0.007) and IS (as measured by clamp) (r = -0.60;P = 0.007)”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Glucose suppressibility of FOx is an intrinsic characteristic of muscle cells.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The inverse correlation between suppressibility and IS remained significant after IS was adjusted for fat mass (r = -0.47;P = 0.04).”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Glucose suppressibility of FOx is an intrinsic characteristic of muscle cells.
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In the paper
“Weaker relationships were found between the fold increase in TOx in vitro and level of body fat (r = -0.37;P = 0.1).”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Metabolic adaptability is an intrinsic characteristic of muscle cells.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For both assays, 14 CO 2 represented 10-30% of the total FOx”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Relationship between metabolic flexibility and IS in vivo.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the relationship between adaptability and IS was blunted after IS was adjusted for body fat (P = 0.58).”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Metabolic adaptability is an intrinsic characteristic of muscle cells.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A highly significant correlation was observed between the fold increase in 14 CO 2 in vitro and fasting insulin in vivo (r = -0.81;P = 0.0002; Figure 3E).”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Metabolic adaptability is an intrinsic characteristic of muscle cells.
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In the paper
“However, a significant correlation was present after 1 subject was eliminated with a value greater than 3 SDs away from the mean of the remaining subjects (r = -0.46;P = 0.048; n = 15).”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Relationship between metabolic flexibility and IS in vivo.
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In the paper
“Importantly, we found substantial interindividual differences in the magnitude of glucose suppression of FOx in vitro.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Discussion
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In the paper
“Maximal 14 CO2 | 0.57 ± 0.43 | 0.15-1.96”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Statistical analysis.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“r = 0.12 r = -0.61 A r = -0.05 | r = -0.60 A r = 0.11 | r = 0.56 A r = -0.44 r = 0.58 A | r = 0.35”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Statistical analysis.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The in vitro suppressibility assay in insulin-free medium measures the same process as in vivo insulin responsiveness.
- Rests on an assumption: The in vitro adaptability assay measures the capacity of myotubes to increase fat oxidation in a way that reflects in vivo adaptability.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“r = -0.25 r = 0.53 A r = -0.30 | r = 0.60 A r = -0.39 A r = -0.62 A r = 0.70 B r = -0.41 r = -0.81 B”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Statistical analysis.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The in vitro suppressibility assay in insulin-free medium measures the same process as in vivo insulin responsiveness.
- Rests on an assumption: The in vitro adaptability assay measures the capacity of myotubes to increase fat oxidation in a way that reflects in vivo adaptability.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Parameters of metabolic switching in vitro correlate with clinical phenotypes of subjects”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Statistical analysis.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The in vitro suppressibility assay in insulin-free medium measures the same process as in vivo insulin responsiveness.
- Rests on an assumption: The in vitro adaptability assay measures the capacity of myotubes to increase fat oxidation in a way that reflects in vivo adaptability.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“r = 0.12 r = -0.61 A r = -0.05 | r = -0.60 A r = 0.11 | r = 0.56 A r = -0.44 r = 0.58 A | r = 0.35”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Statistical analysis.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The in vitro suppressibility assay in insulin-free medium measures the same process as in vivo insulin responsiveness.
- Rests on an assumption: The in vitro adaptability assay measures the capacity of myotubes to increase fat oxidation in a way that reflects in vivo adaptability.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“According to our studies, in vivo insulin responsiveness increases with increasing in vitro adaptability, which indicates a greater capacity to increase FOx in subjects with higher IS.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Figure 4
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The in vitro adaptability assay measures the capacity of myotubes to increase fat oxidation in a way that reflects in vivo adaptability.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Dose response of FOx (measured by14 CO2 production) to an increasing palmitate concentration (adaptability).”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Statistical analysis.
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“r = 0.12 r = -0.61 A r = -0.05 | r = -0.60 A r = 0.11 | r = 0.56 A r = -0.44 r = 0.58 A | r = 0.35”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Statistical analysis.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The in vitro suppressibility assay in insulin-free medium measures the same process as in vivo insulin responsiveness.
- Rests on an assumption: The in vitro adaptability assay measures the capacity of myotubes to increase fat oxidation in a way that reflects in vivo adaptability.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“r = 0.12 r = -0.61 A r = -0.05 | r = -0.60 A r = 0.11 | r = 0.56 A r = -0.44 r = 0.58 A | r = 0.35”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Statistical analysis.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The in vitro suppressibility assay in insulin-free medium measures the same process as in vivo insulin responsiveness.
- Rests on an assumption: The in vitro adaptability assay measures the capacity of myotubes to increase fat oxidation in a way that reflects in vivo adaptability.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“r = -0.25 r = 0.53 A r = -0.30 | r = 0.60 A r = -0.39 A r = -0.62 A r = 0.70 B r = -0.41 r = -0.81 B”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Statistical analysis.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The in vitro suppressibility assay in insulin-free medium measures the same process as in vivo insulin responsiveness.
- Rests on an assumption: The in vitro adaptability assay measures the capacity of myotubes to increase fat oxidation in a way that reflects in vivo adaptability.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Dose response of FOx (measured by14 CO2 production) to an increasing glucose concentration (suppressibility).”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Statistical analysis.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Suppressed 14 CO2 | 0.24 ± 0.18 | 0.07-0.82”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Statistical analysis.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“r = -0.25 r = 0.53 A r = -0.30 | r = 0.60 A r = -0.39 A r = -0.62 A r = 0.70 B r = -0.41 r = -0.81 B”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Statistical analysis.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The in vitro suppressibility assay in insulin-free medium measures the same process as in vivo insulin responsiveness.
- Rests on an assumption: The in vitro adaptability assay measures the capacity of myotubes to increase fat oxidation in a way that reflects in vivo adaptability.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“% Suppression of 14 CO2 | 58.72 ± 10.18 40.0-81.37”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Statistical analysis.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“r = -0.25 r = 0.53 A r = -0.30 | r = 0.60 A r = -0.39 A r = -0.62 A r = 0.70 B r = -0.41 r = -0.81 B”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Statistical analysis.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The in vitro suppressibility assay in insulin-free medium measures the same process as in vivo insulin responsiveness.
- Rests on an assumption: The in vitro adaptability assay measures the capacity of myotubes to increase fat oxidation in a way that reflects in vivo adaptability.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Figure 4
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The in vitro suppressibility assay in insulin-free medium measures the same process as in vivo insulin responsiveness.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Fold increase in 14 CO2 | 3.19 ± 0.76 | 2.99-4.87”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Statistical analysis.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“14 CO2 at 100 µM palmitate | 1.27 ± 0.7 | 0.67-3.37”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Statistical analysis.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“which suggests that defects in metabolic switching might be one of the primary events in the development of obesity and insulin resistance.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Figure 2
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: In vitro intrinsic defects in metabolic switching reflect processes that contribute to obesity and insulin resistance in vivo.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“our results from cells incubated in an insulin-free medium demonstrate that insulin is not needed for the expression of the metabolic switching phenotype in muscle cells.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Figure 2
Load-bearingStrength:boosted· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“which indicates that the majority of palmitate was processed through β-oxidation to intermediate metabolites (ASPs).”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Relationship between metabolic flexibility and IS in vivo.
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our in vitro results demonstrate that glucose suppresses FOx in the absence of insulin.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Moreover, the change in CO 2 production correlates better with clinical phenotypes than does the change in production of intermediate metabolites of FOx.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Figure 2
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Myotubes retained the characteristics of the donor.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Figure 2
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The donor's metabolic phenotype is stable and captured well enough by the measured in vivo traits.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“which supports the hypothesis that metabolic switching is an intrinsic property of skeletal muscle.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Abstract
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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.
None of the sources cited for this claim have been checked yet.
In the paper
“Zurlo (8) and others (9)(10)(11) showed that decreased fat oxidation (FOx) (represented by a higher respiratory quotient [RQ], the ratio of CO 2 produced to O 2 consumed) is a predictor of weight gain”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Introduction
What the sources say
- Not checked yetcites Zurlo (8) Zurlo, 1990, Am. J. Physiol.
- Not checked yetcites (9)(10)(11)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesWhat the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Both FOx assays were performed on 2 different occasions, in a random subset of the whole population (n = 7 or 8).Results for both parameters of metabolic switching, suppressibility and adaptability, were highly reproducible”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Relationship between metabolic flexibility and IS in vivo.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The interindividual variability in metabolic phenotypes was preserved in human myotubes separated from their neuroendocrine environment”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our results suggest that differences in the dynamics of FOx in young, healthy individuals mirror the metabolic characteristics of the donor.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Figure 2
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The donor's metabolic phenotype is stable and captured well enough by the measured in vivo traits.
None of the sources cited for this claim have been checked yet.
In the paper
“Muscle cells from insulin-resistant individuals remain insulin resistant in vitro (39-42)”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Introduction
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“According to our observations, skeletal muscle does not appear to be an innocent bystander but rather an active participant in the pathogenesis of obesity and insulin resistance.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Figure 2
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: In vitro intrinsic defects in metabolic switching reflect processes that contribute to obesity and insulin resistance in vivo.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This indicates that metabolic switching is, at least to a certain extent, an intrinsic characteristic of skeletal muscle”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Figure 2
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The principal finding from this study is that metabolic switching, represented by dynamic changes in FOx in muscle cells, reflects the metabolic characteristics of the cells' donor.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- 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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Metabolic adaptability: Adaptable cells possess a higher capacity to increase FOx when exposed to a high palmitate concentration compared with nonadaptable cells.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Figure 4
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Arrows indicate a dynamic change in FOx, representing an in vitro correlate to the clinical phenotype.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Statistical analysis.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“According to our studies, in vivo insulin responsiveness increases with increasing in vitro adaptability, which indicates a greater capacity to increase FOx in subjects with higher IS.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Figure 4
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Glucose suppressibility: In insulinfree medium, adaptable cells are able to maintain a relatively high rate of FOx in the presence of glucose compared with nonadaptable cells.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Figure 4
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 13
- Probably not a substantial claim. 7
- The quote only partly states this claim. 3
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“On the other hand, ∆RQ (clamp) correlated positively with IS and VO 2 max”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Relationship between metabolic flexibility and IS in vivo.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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)”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Relationship between metabolic flexibility and IS in vivo.
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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).”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Relationship between metabolic flexibility and IS in vivo.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Glucose suppressibility of FOx is an intrinsic characteristic of muscle cells.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Glucose suppressibility of FOx is an intrinsic characteristic of muscle cells.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Metabolic adaptability is an intrinsic characteristic of muscle cells.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“14 CO2 at basal palmitate | 0.33 ± 0.25 | 0.15-0.71”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Statistical analysis.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Metabolic adaptability is an intrinsic characteristic of muscle cells.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe quote only partly states this claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- 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.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Figure 4
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“RQ were adjusted for energy balance as described previously (71).”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Body composition.
What the sources say
- Not checked yetcites [71] Nguyen, 2003, Med. Biol. Eng. Comput. source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Glucose disposal rate, a parameter of IS, was adjusted for kilograms of LBM.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Figure 3
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All assays were performed in duplicate, and data were normalized to protein content.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Figure 4
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one. The quote only partly states this claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Body composition.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“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).”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Introduction
What the sources say
- Not checked yetcites [1] Colberg, 1995, J. Clin. Invest. source
- Not checked yetcites [5] Kelley, 1999, Am. J. Physiol. source
- Not checked yetcites [12] Bruce, 2003, J. Clin. Endocrinol. Metab. source
- Not checked yetcites [13] Storlien, 2004, Proc. Nutr. Soc. source
- Not checked yetcites [14] Kelley, 2000, Diabetes. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Coefficients of variation for total daily energy expenditure and RQ are 2% and 16%, respectively.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Body composition.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one. The quote only partly states this claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor > Statistical analysis.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
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.”
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?
In the citing paper
“Accordingly, MetFlex-lip of human myotubes in vitro correlates directly with the donor's insulin sensitivity in vivo (29).”
From Metabolic flexibility to lipid availability during exercise is enhanced in individuals with high insulin sensitivity (2018) · cites this paper as [29]
In the citing paper
“cross-sectional studies showing that isolated muscle strips, tissue homogenates or cultured myocytes from severely obese and/or diabetic humans exhibit diminished rates of fat oxidation when compared to specimens derived from healthy control subjects [9,41,46,87].”
From Intramuscular triacylglycerol and insulin resistance: guilty as charged or wrongly accused? (2010) · cites this paper as [87]
In the citing paper
“This characteristic appears to be intrinsic to skeletal muscle because primary muscle cell cultures from insulin-resistant subjects retain abnormal patterns of whole-body fuel use (1).”
In the citing paper
“The relationship between fasting RQ and insulin sensitivity, however, has not always been observed.”
From Metabolic flexibility and insulin resistance (2008) · cites this paper as [61]
In the citing paper
“Metabolic inflexibility to glucose and impaired glucose storage during a hyperinsulinemic clamp is consistently reported in insulin-resistant subjects.”
From Metabolic flexibility and insulin resistance (2008) · cites this paper as [61]
In the citing paper
“Contrary to expectations, in vitro suppressibility of fat oxidation was lower in subjects with higher whole body insulin sensitivity and higher metabolic flexibility to glucose.”
From Metabolic flexibility and insulin resistance (2008) · cites this paper as [61]
In the citing paper
“In fact, a direct relationship between metabolic flexibility to glucose and glucose disposal rate is described ([14](#r14), [24](#r24), [61](#r61), [62](#r62)) ([Fig. 3*B*](#f3)).”
From Metabolic flexibility and insulin resistance (2008) · cites this paper as [61]
In the citing paper
“Such muscle mitochondrial dysfunction was suggested to be an intrinsic characteristic of muscle cells, since fat oxidation in response to palmitate was lower in myotubes from insulin-resistant vs. insulin-sensitive individuals ([16](#r16), [61](#r61)).”
From Metabolic flexibility and insulin resistance (2008) · cites this paper as [61]
In the citing paper
“Such observations are most likely attributed to testosterone-induced changes in lipid metabolism and/or altered postreceptor insulin signaling in muscle (54) and also improved insulin sensitivity enhancing muscle lipid uptake (55).”
From Onset of effects of testosterone treatment and time span until maximum effects are achieved (2011) · cites this paper as [55]
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
MinorFor 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.
“| In vitro adaptability | Fold increase in 14 CO2 | 3.19 ± 0.76 | 2.99-4.87 |”
“Muscle cells from 16 individuals were grown and differentiated into myotubes in 24-well plates.”
Biopsy-method citation points to a different reference
MinorThe 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.
“Samples of vastus lateralis, weighing 60-100 mg, were obtained by muscle biopsy using the Bergstrom technique (73).”
“73. Ravussin, E., Lillioja, S., Anderson, T.E., Christin, L., and Bogardus, C. 1986. Determinants of 24- hour energy expenditure in man. Methods and results using a respiratory chamber. J. Clin. Invest. 78:1568-1578.”
Citations
Cites
Glucose clamp technique: a method for quantifying insulin secretion and resistance.
DeFronzo, R. A., Tobin, J. D., & Andres, R. (1979) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1979.237.3.e214 · Cited by 7,425
Yamauchi, T., Kamon, J., Waki, H., Terauchi, Y., Kubota, N., Hara, K., Mori, Y., Ide, T., Murakami, K., Tsuboyama-Kasaoka, N., et al. (2001) · Nature Medicine · doi:10.1038/90984 · Cited by 4,915
Age-predicted maximal heart rate revisited
Tanaka, H., Monahan, K. D., & Seals, D. R. (2001) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(00)01054-8 · Cited by 3,775 · cited 2×
“VO2max was determined by a progressive treadmill test to exhaustion in accordance with the recommendations described by the American College of Sports Medicine (69).”
MethodWeyer, C., Funahashi, T., Tanaka, S., Hotta, K., Matsuzawa, Y., Pratley, R. E., & Tataranni, P. A. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.5.7463 · Cited by 3,541
Cellular mechanisms of insulin resistance
Shulman, G. I. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10583 · Cited by 2,714
Dysfunction of Mitochondria in Human Skeletal Muscle in Type 2 Diabetes
Kelley, D. E., He, J., Menshikova, E. V., & Ritov, V. B. (2002) · Diabetes · doi:10.2337/diabetes.51.10.2944 · Cited by 2,321
Mechanism of free fatty acid-induced insulin resistance in humans.
Roden, M., Price, T. B., Perseghin, G., Petersen, K. F., Rothman, D. L., Cline, G. W., & Shulman, G. I. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118742 · Cited by 1,539
Percutaneous Needle Biopsy of Skeletal Muscle in Physiological and Clinical Research
Bergström, J. P. (1975) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.3109/00365517509095787 · Cited by 1,173
Determinants of 24-hour energy expenditure in man. Methods and results using a respiratory chamber.
Ravussin, E., Lillioja, S., Anderson, T. E., Christin, L., & Bogardus, C. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112749 · Cited by 1,166
Kelley, D. E., Goodpaster, B., Wing, R. R., & Simoneau, J.-A. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.277.6.e1130 · Cited by 1,096
Flagged first, then by citations
Research works printed but not linked: 12
- Raben, 1998, Am. J. Physiol., 275, E487
- Ranneries, 1998, Am. J. Physiol., 274, E155
- Zurlo, 1990, Am. J. Physiol., 259, E650
- Ravussin, 1993, Int. J. Obes. Relat. Metab. Disord., 17(Suppl. 3), S28
- Astrup, 1994, Am. J. Physiol., 266, E592
- Mandarino, 1996, Am. J. Physiol., 270, E463
- Sidossis, 1996, Am. J. Physiol., 270, E733
- Kleiber, 1992, Diabete. Metab., 18, 84
- Oakes, 2002, J. R. Soc. Med., 95(Suppl. 42), 33
- Kirkwood, 1991, Am. J. Physiol., 260, E89
- DeFronzo, 1979, Am. J. Physiol., 237, E214
- Acheson, 1984, Am. J. Physiol., 246, E62
Cited by
Sorted by citations
Metabolic Flexibility in Health and Disease
Goodpaster, B. H., & Sparks, L. M. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.04.015 · Cited by 995
Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans
Civitarese, A. E., Carling, S., Heilbronn, L. K., Hulver, M. H., Ukropcova, B., Deutsch, W. A., Smith, S. R., & Ravussin, E. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040076 · Cited by 790
Self-citationReduced Adipose Tissue Oxygenation in Human Obesity
Pasarica, M., Sereda, O. R., Redman, L. M., Albarado, D. C., Hymel, D. T., Roan, L. E., Rood, J. C., Burk, D. H., & Smith, S. R. (2009) · Diabetes · doi:10.2337/db08-1098 · Cited by 786
Self-citationAdams, S. H., Hoppel, C. L., Lok, K. H., Zhao, L., Wong, S. W., Minkler, P. E., Hwang, D. H., Newman, J. W., & Garvey, W. T. (2009) · The Journal of Nutrition · doi:10.3945/jn.108.103754 · Cited by 598
Metabolic flexibility and insulin resistance
Galgani, J. E., Moro, C., & Ravussin, E. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90558.2008 · Cited by 532
Metadata
- 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.
- Venue
- Journal of Clinical Investigation
- Published
- 2005-07-01
- Volume
- 115
- Issue
- 7
- Pages
- 1934-1941
- ISSN
- 0021-9738 (ISSN-L)
- 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
- bronze
- doi.org
- 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 (medical) › 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
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