The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index; 6 of the 73 sources its claims cite were checked for support.
Metabolic flexibility and insulin resistance
Open accessAbstract
Metabolic flexibility is the capacity for the organism to adapt fuel oxidation to fuel availability. The inability to modify fuel oxidation in response to changes in nutrient availability has been implicated in the accumulation of intramyocellular lipid and insulin resistance. The metabolic flexibility assessed by the ability to switch from fat to carbohydrate oxidation is usually impaired during a hyperinsulinemic clamp in insulin-resistant subjects; however, this “metabolic inflexibility” is mostly the consequence of impaired cellular glucose uptake. Indeed, after controlling for insulin-stimulated glucose disposal rate (amount of glucose available for oxidation), metabolic flexibility is not altered in obesity regardless of the presence of type 2 diabetes. To understand how intramyocellular lipids accumulate and cause insulin resistance, the assessment of metabolic flexibility to high-fat diets is more relevant than metabolic flexibility during a hyperinsulinemic clamp. An impaired capacity to upregulate muscle lipid oxidation in the face of high lipid supply may lead to increased muscle fat accumulation and insulin resistance. Surprisingly, very few studies have investigated the response to high-fat diets. In this review, we discuss the role of glucose disposal rate, adipose tissue lipid storage, and mitochondrial function on metabolic flexibility. Additionally, we emphasize the bias of using the change in respiratory quotient to calculate metabolic flexibility and propose novel approaches to assess metabolic flexibility. On the basis of current evidence, one cannot conclude that impaired metabolic flexibility is responsible for the accumulation of intramyocellular lipid and insulin resistance. We propose to study metabolic flexibility in response to high-fat diets in individuals having contrasting degree of insulin sensitivity and/or mitochondrial characteristics.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review argues that impaired metabolic flexibility during a hyperinsulinemic clamp in insulin-resistant subjects is largely a consequence of reduced insulin-stimulated glucose disposal, not a primary defect in fuel switching. It concludes that evidence linking impaired metabolic flexibility to intramyocellular lipid accumulation and insulin resistance is inconclusive, and calls for studies of metabolic flexibility to high-fat diets in individuals with contrasting insulin sensitivity and mitochondrial characteristics.
Key findings
- During a hyperinsulinemic clamp, the commonly reported metabolic inflexibility in insulin-resistant subjects is mostly explained by lower cellular glucose uptake: insulin-stimulated glucose disposal rate explained ∼50% of the variance in the change in respiratory quotient (ΔRQ). In quartile analysis, the insulin-sensitive group (n = 25) had about a fourfold higher glucose disposal rate, nonoxidative glucose disposal rate, and steady-state RQ than the insulin-resistant group (n = 25), but after adjustment for glucose disposal rate there was no longer any difference in nonoxidative glucose disposal rate or steady-state RQ (P > 0.44).
- The paper reports that after controlling for insulin-stimulated glucose disposal rate, metabolic flexibility is not altered in obesity regardless of type 2 diabetes, and no improvement in metabolic flexibility was observed after weight loss in type 2 diabetic individuals after controlling for glucose disposal rate.
- Evidence does not support the hypothesis that impaired mitochondrial function leads to lower metabolic flexibility to lipid; mitochondrial dysfunction may coexist with high fuel oxidation and enhanced insulin sensitivity. In one cited study, subjects with a family history of type 2 diabetes had on average 22% less mitochondrial DNA copy number, related to a higher decrease in sleeping RQ after a 3-day isoenergetic high-fat diet, but not to the change in 24-h RQ.
- The authors emphasize that using ΔRQ to calculate metabolic flexibility is biased by baseline RQ: in an illustrative example, two well-matched subjects both matched 24-h RQ to food quotient, yet one was classified as flexible (ΔRQ = −0.17) and the other as inflexible (ΔRQ = −0.07). They propose assessing the time to reach 50% of the expected change in RQ (ΔRQ50%) and studying responses to high-fat diets; based on RQ profiles, metabolically inflexible individuals could accumulate ∼200 g more fat than flexible subjects after 1 wk of a high-fat diet (60% of total energy).
Methods
- Narrative review; no primary experimental data are reported. The paper synthesizes human whole-body, skeletal muscle, and cultured myotube studies on metabolic flexibility, insulin resistance, obesity, type 2 diabetes, and family history of type 2 diabetes.
- It discusses assessment paradigms including fasting RQ, euglycemic-hyperinsulinemic clamp, high-carbohydrate and high-fat meals/diets, and in vitro myotube substrate switching.
- Main analysis is qualitative synthesis, with illustrative calculations and tables, including a table comparing steady-state RQ between subjects with high and low insulin-stimulated glucose disposal rate.
Limitations
- Stated in paper: few studies have investigated metabolic flexibility to high-fat diets, and no studies have evaluated metabolic flexibility to lipid in subjects with contrasting degrees of insulin resistance; most studies used fasting RQ, which is not a reliable indicator of lipid oxidation capacity because it is strongly influenced by energy balance and dietary macronutrient composition.
- Stated in paper: the causal link between mitochondrial abnormalities and metabolic inflexibility/insulin resistance remains to be established, and evidence indicating mitochondrial defects as a driving factor is far from conclusive or even unavailable.
- Evident from text: as a narrative review, no systematic search or meta-analysis is described; conclusions depend on selected literature, and the paper notes that some cited comparisons failed to match groups for physical fitness, which could confound mitochondrial findings.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
46 Not checked yet · 30 Own interpretation · 5 No basis given · 3 Partly supported · 1 Supported so far · 1 Own result · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, after adjustment for differences in glucose disposal rates, there was no longer any difference in nonoxidative glucose disposal rate and steady-state RQ between groups (Ref. [14](#r14); [Table 2](#t2)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Partly supportedcites [14] sourceExperimental — accuracy not yet measured
The Results report that nonoxidative glucose disposal no longer differed after adjustment for glucose disposal rate (P = 0.87), and that the difference in ΔRQ was abolished (P = 0.19). The paper defines ΔRQ as the change from fasting to steady-state RQ, but does not report the adjusted comparison as a difference in steady-state RQ itself. Its groups were participants with type 2 diabetes and obesity-matched participants without diabetes, rather than groups defined solely by insulin sensitivity. (LLM, conf=0.83)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Further support for these findings comes from studies in which glucose disposal rates were matched by increasing the glucose or insulin infusion rates ([27](#r27), [66](#r66)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Supportedcites [27] source
The Introduction describes studies that used hyperglycemia to match glucose disposal in people with NIDDM and controls. The Discussion says this paper likewise achieved comparable systemic glucose uptake by studying participants with NIDDM at their fasting hyperglycemia while controls remained euglycemic. This supports the glucose-based example; the sentence also cites another study for the insulin-based alternative. (LLM, conf=0.89)
- Not checked yetcites [66] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the 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)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Partly supportedcites [16] sourceExperimental — accuracy not yet measured
The Fatty acid oxidation results report 26% lower palmitate-derived CO₂ production in myotubes from people with type 2 diabetes than in control myotubes. The paper compared diabetic and control donors, not groups classified as insulin-resistant and insulin-sensitive, and it found no significant decrease in total palmitate oxidation. (LLM, conf=0.86)
- Supportedcites [61] source
The section “Metabolic adaptability is an intrinsic characteristic of muscle cells” reports that the increase in myotube fat oxidation after palmitate exposure was positively correlated with donors’ insulin sensitivity. Figure 4 interprets this as greater capacity to increase fat oxidation in subjects with higher insulin sensitivity. The evidence is a correlation across donors, rather than a categorical comparison of two groups; it supports the claim’s direction. (LLM, conf=0.88)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
In the paper
“As a consequence, data corrected for glucose disposal rate, a mechanism proximal to glucose oxidation, indicates no difference in metabolic flexibility and nonoxidative glucose disposal rate between subjects with or without type 2 diabetes and matched for body mass index, sex, and race.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [14] source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“For instance, patients with lipodystrophy (partial or total absence of subcutaneous adipose tissue) have similar fat oxidation than control individuals when fed a eucaloric, mixed diet ([51](#r51)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [51] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“However, in response to excess energy as fat, lipodystrophic subjects have higher fat oxidation compared with control individuals ([51](#r51)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [51] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Furthermore, after controlling for glucose disposal rate, no improvement in metabolic flexibility is observed after weight loss in type 2 diabetic individuals subjected to a 1-yr intensive lifestyle intervention including energy restriction and increased physical activity ([14](#r14)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [14] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 fact, fasting RQ is inversely related to metabolic flexibility to carbohydrate during a clamp ([Fig. 3*A*](#f3)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“On the basis of the RQ profile for metabolically flexible and inflexible subjects shown in [Fig. 2*D*](#f2), and considering an energy intake of 2,500 kcal/day (protein intake 20% of total energy), the metabolically inflexible individuals would accumulate ∼200 g more fat than flexible subjects after 1 wk of a high-fat diet (60% of total energy).”
§ Metabolic flexibility and insulin resistance > Abstract > Conclusions
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In addition, we observed that metabolic flexibility to glucose was directly related to plasma adiponectin concentration.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [14] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 16
- Probably not a substantial claim. 2
- The quote only partly states this claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Metabolic inflexibility to glucose and impaired glucose storage during a hyperinsulinemic clamp is consistently reported in insulin-resistant subjects.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Supportedcites [14] source
The CONCLUSIONS section says insulin-resistant subjects have shown a blunted respiratory-quotient response during a hyperinsulinemic clamp. The RESULTS and DISCUSSION sections report lower insulin-stimulated nonoxidative glucose disposal—a measure that includes glucose storage—in the type 2 diabetes group. The paper also notes that both differences disappear after adjustment for glucose disposal rate; the claim describes the reported unadjusted findings. (LLM, conf=0.91)
- Not checked yetcites [24] source
- Partly supportedcites [61] sourceExperimental — accuracy not yet measured
The Introduction says insulin-resistant muscle does not switch to carbohydrate oxidation in response to insulin, and the results section reports that metabolic flexibility during a hyperinsulinemic clamp correlates with insulin sensitivity. The cited paper does not report impaired glucose storage during the clamp; its clamp measures glucose disposal and fuel switching, not storage. Page numbers are unavailable in our copy. (LLM, conf=0.87)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
In the paper
“We ([14](#r14)) recently described that insulin-stimulated glucose disposal rate is the main determinant of the change in RQ during a clamp, explaining ∼50% of its variance.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [14] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Using the ΔRQ as an index of metabolic flexibility, *subject A* will be characterized as flexible (ΔRQ = −0.17) and *subject B* as inflexible (ΔRQ = −0.07).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
plainn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“However, in response to a high-carbohydrate meal (1,000 kcal, 76% energy from carbohydrate), individuals with a family history of diabetes had a higher plasma insulin concentration and a similar increase in RQ compared with control subjects.”
§ Metabolic flexibility and insulin resistance > Abstract > Metabolic Flexibility in Individuals with Insulin Resistance, Obesity or Family History of Type 2 Diabetes
What the sources say
- Not checked yetcites [20] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“If skeletal muscle cannot match fat oxidation to lipid uptake, fat accumulation will ensue, which in turn will cause insulin resistance.”
§ Metabolic flexibility and insulin resistance > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In addition, in vitro adaptability was positively related to aerobic capacity, suggesting that myotubes established from lean, fit, insulin-sensitive subjects are more metabolically flexible in response to palmitate exposure in vitro.”
§ Metabolic flexibility and insulin resistance > Abstract > Metabolic Flexibility in Individuals with Insulin Resistance, Obesity or Family History of Type 2 Diabetes
What the sources say
- Not checked yetcites [15] source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“On the other hand, such impaired mitochondrial lipid oxidation could simply be the result of reduced energy demand and not necessarily due to impaired substrate switching.”
§ Metabolic flexibility and insulin resistance > Abstract > Metabolic Flexibility in Individuals with Insulin Resistance, Obesity or Family History of Type 2 Diabetes
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
“Using the ΔRQ as an index of metabolic flexibility, *subject A* will be characterized as flexible (ΔRQ = −0.17) and *subject B* as inflexible (ΔRQ = −0.07).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“Consequently, the assessment of metabolic flexibility should take into account the differences in baseline RQ and the timing required to match 24-h RQ to FQ.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“During postabsorptive conditions, diabetic individuals had higher RQ throughout the 6 h following the high-fat meal compared with nondiabetic subjects.”
§ Metabolic flexibility and insulin resistance > Abstract > Metabolic Flexibility in Individuals with Insulin Resistance, Obesity or Family History of Type 2 Diabetes
What the sources say
- Not checked yetcites [28] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Additionally, high plasma FFA concentration impairs insulin-stimulated glucose disposal rate and decreases intracellular glucose, which in turn reduces glucose oxidation and consequently enhances lipid oxidation ([2](#r2), [8](#r8)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“However, metabolic flexibility also depends on the rate at which nutrients are available to the cells, the ability of adipose tissue to handle fatty acids and even the method used for its calculation (i.e., ΔRQ).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“Accordingly, impaired metabolic flexibility may result from both a lower stimulated RQ and/or an elevated baseline RQ.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“However, comparisons among obese, diabetic, and lean individuals have failed to appropriately match the groups for physical fitness, opening up the possibility that mitochondrial dysfunction may be related to lower physical activity in metabolically inflexible subjects ([45](#r45)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [45] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This is in line with the finding that high-fat diets increase mitochondrial biogenesis and fat oxidation in parallel with a decrease in insulin sensitivity ([18](#r18)), possibly as a consequence of increased partially oxidized lipid intermediates.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [18] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Similarly, mice with muscle-specific PGC1α (PPARγ coactivator-1α) deletion have defective mitochondrial function (e.g., lower staining for cytochrome *c* oxidase and succinate dehydrogenase); however, they have increased metabolic rate, lower RQ, and improved insulin-stimulated glucose uptake in skeletal muscle compared with wild-type animals ([19](#r19)).”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
What the sources say
- Not checked yetcites [19] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“Individuals able to increase fat oxidation quickly in response to day-to-day changes in fat intake will eventually have lower muscle fat accumulation and be less prone to insulin resistance compared with slower adapters.”
§ Metabolic flexibility and insulin resistance > Abstract > Conclusions
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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 answer is yes, since the speed of the adaptation will probably impact the amount of lipid accumulation in the muscle and therefore impact insulin sensitivity.”
§ Metabolic flexibility and insulin resistance > Abstract > Conclusions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Since vo2max has been shown to be directly related to muscle mitochondrial density ([62](#r62), [63](#r63)), one could expect an improved metabolic flexibility in young vs. elderly individuals.”
§ Metabolic flexibility and insulin resistance > Abstract > Determinant Factors of Metabolic Flexibility
hedgedconditional- Asserted: fails — The authors may not put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The authors may not put it forward as true.
The paper relies on this without support.
The switch in fuel oxidation depends on the type and amount of nutrient available for oxidation at the cellular level.
“The switch in fuel oxidation will depend on the type and amount of nutrient available for oxidation at the cellular level.”
The paper relies on this without support.
Increased availability of carbohydrate rapidly increases carbohydrate oxidation and suppresses lipid oxidation.
“Increased availability of carbohydrate results in a rapid increase in carbohydrate oxidation associated with concomitant suppression of lipid oxidation.”
The paper relies on this without support.
When dietary fat intake increases, lipid oxidation increases slowly and progressively while carbohydrate oxidation is suppressed.
“However, when dietary fat intake increases, one observes a much slower progressive increase in lipid oxidation paralleled by suppression of carbohydrate oxidation.”
The paper relies on this without support.
After 7–10 days, all individuals will be in equilibrium between 24-h RQ and FQ.
“since after 7–10 days it is generally expected that all individuals will be in equilibrium between 24-h RQ and FQ.”
The paper relies on this without support.
The ΔRQ50% is in the range of 1–2 days in response to high-carbohydrate diets and in the range of 3–5 days in response to high-fat diets.
“Such a ΔRQ50% may be in the range of 1–2 days in response to high-carbohydrate diets and in the range of 3–5 days in response to high-fat diets.”
The paper relies on this without support.
The adaptation of fat oxidation to high fat intake cannot take much more time than that required to deplete glycogen stores, i.e., a few days to a week.
“However, this adaptation cannot take much more time than that required to deplete the glycogen stores, i.e., a few days to a week.”
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
“As such, metabolic inflexibility is at the core of the pathophysiology of insulin resistance (146).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [146]
In the citing paper
“In turn, metabolically inflexible individuals fail to adapt their fuel preference to changes in carbohydrate or lipid supplies (Galgani et al, 2008).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Galgani et al, 2008
In the citing paper
“Metabolic inflexibility is defined as an impaired capacity to switch between different energy substrates and is a hallmark of insulin resistance and type 2 diabetes mellitus (T2DM).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Galgani et al, 2008
In the citing paper
“Diverse mitochondrial parameters vary between insulin-resistant and insulin-sensitive subjects, such as mitochondrial number, structure, and function.”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Galgani et al, 2008
In the citing paper
“This suggests that mitochondrial dysfunction might contribute to metabolic inflexibility and insulin resistance (Galgani et al, 2008).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Galgani et al, 2008
Citations
Cites
Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197
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
Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes
Petersen, K. F., Dufour, S., Befroy, D., Garcia, R., & Shulman, G. I. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa031314 · Cited by 2,193
Koves, T. R., Ussher, J. R., Noland, R. C., Slentz, D., Mosedale, M., Ilkayeva, O., Bain, J., Stevens, R., Dyck, J. R. B., Newgard, C. B., et al. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.10.013 · Cited by 1,990
Patti, M. E., Butte, A. J., Crunkhorn, S., Cusi, K., Berria, R., Kashyap, S., Miyazaki, Y., Kohane, I., Costello, M., Saccone, R., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1032913100 · Cited by 1,952
Dresner, A., Laurent, D., Marcucci, M., Griffin, M. E., Dufour, S., Cline, G. W., Slezak, L. A., Andersen, D. K., Hundal, R. S., Rothman, D. L., et al. (1999) · Journal of Clinical Investigation · doi:10.1172/jci5001 · Cited by 1,311
Krssak, M., Falk Petersen, K., Dresner, A., DiPietro, L., Vogel, S. M., Rothman, D. L., Shulman, G. I., & Roden, M. (1999) · Diabetologia · doi:10.1007/s001250051123 · Cited by 1,264
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
Fuel selection in human skeletal muscle in insulin resistance: a reexamination.
Kelley, D. E., & Mandarino, L. J. (2000) · Diabetes · doi:10.2337/diabetes.49.5.677 · Cited by 1,017
Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes
Ritov, V. B., Menshikova, E. V., He, J., Ferrell, R. E., Goodpaster, B. H., & Kelley, D. E. (2005) · Diabetes · doi:10.2337/diabetes.54.1.8 · Cited by 887
Cited by
Sorted by citations
Items 301–400 of 528
Pathak, K., Soares, M. J., Zhao, Y., James, A. P., Sherriff, J. L., & Newsholme, P. (2016) · Nutrition · doi:10.1016/j.nut.2016.12.007 · Cited by 11
Metabolism and Whole-Body Fat Oxidation Following Postexercise Carbohydrate or Protein Intake
Andersson-Hall, U. K., Pettersson, S., Edin, F., Pedersen, A., Malmodin, D., & Madsen, K. (2017) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.2017-0129 · Cited by 12
“From a health perspective, metabolic flexibility, i.e. the ability to switch between different fuels, is linked to insulin resistance (Galgani et al., 2008).”
BackgroundKibret, K. T., Peeters, A., Tegegne, T. K., Mesfin, Y. M., & Nichols, M. S. (2025) · Current Nutrition Reports · doi:10.1007/s13668-025-00684-7 · Cited by 11
Hummel, J., Fritsche, L., Vosseler, A., Dannecker, C., Hoene, M., Kantartzis, K., Häring, H., Stefan, N., Machann, J., Birkenfeld, A. L., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-95750-9 · Cited by 10
Daussin, F., Cuillerier, A., Touron, J., Bensaid, S., Melo, B. P., Al-Rewashdy, A., Vasam, G., Menzies, K. J., Harper, M., Heyman, E., et al. (2021) · Nutrients · doi:10.3390/nu13103466 · Cited by 11
“However, besides mitochondrial function, the basal respiratory quotient, glucose disposal rate, adipose tissue lipid storage capacity, and plasma free fatty acid concentration were also identified as determinant factors of metabolic flexibility and should be considered [40].”
BackgroundDrosophila mitotypes determine developmental time in a diet and temperature dependent manner
Towarnicki, S. G., & Ballard, J. W. O. (2017) · Journal of Insect Physiology · doi:10.1016/j.jinsphys.2017.06.002 · Cited by 12
Chien, H., Greenhaff, P. L., & Constantin‐Teodosiu, D. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165942 · Cited by 10
“Obesity and chronically elevated levels of circulating free fatty acids (FFA) are recognised as factors contributing to the development of metabolic inflexibility (MI; defined as the inability to switch from lipid to glucose oxidation during the fasting-to-fed transition), insulin resistance (IR), and type 2 diabetes…”
BackgroundDassonvalle, J., Díaz‐Castro, F., Donoso-Barraza, C., Sepúlveda, C., la Fuente, F. P.-D., Pino, P., Espinosa, A., Chiong, M., Llanos, M. N., & Troncoso, R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207582 · Cited by 10
Wang, W., Huang, Z., Huang, L., Gao, L., Cui, L., Cowley, M. A., Guo, L., & Chen, C. (2021) · Neuroendocrinology · doi:10.1159/000515960 · Cited by 10
Casanova, E., Baselga‐Escudero, L., Ribas‐Latre, A., Arola‐Arnal, A., Bladé, C., Arola, L., & Salvadó, M. J. (2013) · BioFactors · doi:10.1002/biof.1129 · Cited by 10
Isacco, L., Thivel, D., Duclos, M., Aucouturier, J., & Boisseau, N. (2014) · Diabetes & Metabolism · doi:10.1016/j.diabet.2014.02.006 · Cited by 10
Role of Dgat2 in Glucose Uptake and Fatty Acid Metabolism in C2C12 Skeletal Myotubes
Bu, S. (2023) · Journal of Microbiology and Biotechnology · doi:10.4014/jmb.2307.07018 · Cited by 10
Prifti, K. K., McCarthy, R., Ma, X., Finck, B. N., England, S. K., & Frolova, A. I. (2024) · Biology of Reproduction · doi:10.1093/biolre/ioae086 · Cited by 8
“In contrast, skeletal muscle is unable to do so and even has a corresponding decrease in mitochondrial respiration, suggesting energetic deficiency [61].”
Ryan, A. S., & Ortmeyer, H. K. (2018) · International Journal of Obesity · doi:10.1038/s41366-018-0068-3 · Cited by 10
“Insulin resistance and mitochodrial dysfunction lead to the inability to modify fuel utilization [8].”
Cominetti, O., Hosking, J., Jeffery, A., Pinkney, J. H., & Martin, F. (2020) · Frontiers in Nutrition · doi:10.3389/fnut.2020.00139 · Cited by 9
“Higher fasting respiratory exchange ratio values in adults (29) and in adolescents (30) may be linked to reduced metabolic flexibility (i.”
BackgroundTippairote, T., Bjørklund, G., & Yaovapak, A. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1907299 · Cited by 8
“…reported the positive correlations between the adipocyte size and the critical NCD triggers and mediators, i.e., insulin resistance (IR), inflammation, and increased lipolysis (Galic, Oakhill, and Steinberg 2010; Kosteli et al. 2010; Lundgren et al. 2007; Stern et al. 1972; Weyer et al. 2000).”
BackgroundCamargo, A., Meneses, M. E. P. D., Rangel-Zúñiga, O. A., Pérez‐Martínez, P., Marı́n, C., Delgado‐Lista, J., Paniagua, J. A., Tinahones, F. J., Roche, H. M., Malagón, M. M., et al. (2013) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201300036 · Cited by 8
“In this sense, “metabolic flexibility” is defined as the capacity for the organism to adapt fuel oxidation to fuel availability [47].”
BackgroundByun, K.-A., Oh, S., Son, M., Oh, S. E., Park, C.-H., Son, K. H., & Byun, K. (2021) · Nutrients · doi:10.3390/nu13093160 · Cited by 8
“Intramyocellular lipid (IMCL), which refers to the accumulation of toxic lipids in the myocytes, arises from the increasing uptake of fatty acids (FA) and decreasing removal of FA by decreasing FA oxidation [1].”
BackgroundBuch, A., Yeshurun, S., Cramer, T., Baumann, A., Sencelsky, Y., Sagi, S. Z., Serebro, M., Greenman, Y., Mor, M., & Eldor, R. (2022) · Obesity Facts · doi:10.1159/000527227 · Cited by 8
Li, X.-T., Kuang, H., & Zhao, J. (2015) · InTech eBooks · doi:10.5772/60675 · Cited by 8
“This suggests that mitochondrial dysfunction might contribute to metabolic inflexibility and insulin resistance [113].”
BackgroundMulliniks, J. T., Cope, E. R., McFarlane, Z. D., Hobbs, J. D., & Waterman, R. C. (2016) · Journal of Animal Science · doi:10.2527/jas.2015-0711 · Cited by 8
Metabolic flexibility and resting autonomic function in active menopausal women
Monferrer-Marín, J., Roldán, A., Helge, J. W., & Blasco-Lafarga, C. (2024) · European Journal of Applied Physiology · doi:10.1007/s00421-024-05568-2 · Cited by 9
“Similarly, major interest has been focused on metabolic flexibility, or rather its dysfunction, the metabolic inflex-ibility (Frandsen et al. 2021), the latter being an impaired ability to switch energy substrates in response to physiological demands (Galgani et al. 2008).”
Cowan, S., Gibson, S., Sinclair, A. J., Truby, H., & Dordevic, A. L. (2022) · Nutrients · doi:10.3390/nu14071470 · Cited by 10
Weight gain and insulin sensitivity: a role for the glycaemic index and dietary fibre?
Sleeth, M., Psichas, A., & Frost, G. S. (2012) · British Journal Of Nutrition · doi:10.1017/s0007114512005016 · Cited by 7
“Metabolic flexibility enables an efficient transition from lipid oxidation and high rates of fatty acid uptake during the fasted state, to suppression of lipid oxidation and increased glucose uptake and utilisation in response to insulin stimulation((20)).”
BackgroundWang, W., Huang, Z., Huang, L., Tan, C., Chen, W., Roelfsema, F., Chen, C., & Guo, L. (2021) · Neuroendocrinology · doi:10.1159/000518338 · Cited by 8
“Insulin resistance was a crucial factor to influence metabolic flexibility in obesity[22,23].”
BackgroundXue, Q., Li, X., Ma, H., Zhou, T., Heianza, Y., Rood, J. C., Bray, G. A., Sacks, F. M., & Qi, L. (2022) · Diabetes Obesity and Metabolism · doi:10.1111/dom.14662 · Cited by 8
Dutt, C., Salles, J. E. N., Joshi, S., Nair, T., Chowdhury, S., Mithal, A., Mohan, V., Kasliwal, R. R., Sharma, S., Tijssen, J. G. P., et al. (2022) · DOAJ (DOAJ: Directory of Open Access Journals) · Cited by 7
Nguo, K., McGowan, M., Cowan, S., Davidson, Z. E., Pirotta, S., Dordevic, A. L., Teede, H. J., Hajishafiee, M., Carmichael, M. A., & Moran, L. (2023) · Nutrition Reviews · doi:10.1093/nutrit/nuad169 · Cited by 12
Sánchez‐Delgado, G., Martínez‐Téllez, B., García‐Rivero, Y., Alcántara, J. M. A., Acosta, F. M., Amaro‐Gahete, F. J., Elvira, J. M. L., & Ruiz, J. R. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01577 · Cited by 7
Pathophysiological hallmarks in type 2 diabetes heterogeneity (review)
Datta, D., Kundu, R., Basu, R., & Chakrabarti, P. (2024) · Diabetology International · doi:10.1007/s13340-024-00783-w · Cited by 9
“Metabolic inflexibilities are largely responsible for genesis of T2DM heterogeneity through a number of ways-by activation of insulin resistance, enhancement in ectopic lipid accumulations and impairment in metabolic coordination between different organs [82, 83].”
Santiago-Arriaza, P., Corral‐Pérez, J., Velázquez‐Díaz, D., Pérez‐Bey, A., Rebollo‐Ramos, M., Marín-Galindo, A., Montes‐de‐Oca‐García, A., Rosety, M. Á., Casals, C., & Ponce‐González, J. G. (2025) · Nutrients · doi:10.3390/nu17111901 · Cited by 8
“MFO in particular has been proposed as a functional marker of metabolic flexibility [4–6], and lower fat oxidation rates during physical activity have been associated with greater cardiometabolic risk, including insulin resistance and excessive weight gain [4,7].”
Barrea, L., Verde, L., Camajani, E., Annunziata, G., Mollica, M. P., Minnetti, M., Trinchese, G., Losignore, P., Colao, A., Ferlin, A., et al. (2026) · Current Nutrition Reports · doi:10.1007/s13668-026-00731-x · Cited by 8
“During the post-absorptive or fasting state, fat oxidation predominates and the respiratory quotient declines [119].”
Shanahan, C. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1532961 · Cited by 7
“This is a common finding in people with insulin resistance and type two diabetes, as measured by respiratory quotient (124, 125).”
Pomar, C. A., Castro, H., Picó, C., Palou, A., & Sánchez, J. (2019) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201900504 · Cited by 7
Springer, C., Binsch, C., Weide, D., Toska, L., Cremer, A. L., Backes, H., Scheel, A. K., Espelage, L., Kotzka, J., Sill, S., et al. (2024) · Diabetes · doi:10.2337/db23-0463 · Cited by 6
Validity and reliability of a novel metabolic flexibility test in children with obesity
Chu, L., Morrison, K. M., Riddell, M. C., Raha, S., & Timmons, B. W. (2017) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00093.2017 · Cited by 4
“Prior studies have combined a hyperinsulinemic-euglycemic clamp with indirect calorimetry to study MetFlex under resting conditions (2, 15, 22).”
BackgroundMethodInfluentialBaugh, M. E., Bowser, S. M., McMillan, R. P., Davy, B. M., Essenmacher, L. A., Neilson, A. P., Hulver, M. W., & Davy, K. P. (2020) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00576.2019 · Cited by 6
Variance in respiratory quotient among daily activities and its association with obesity status
Júdice, P. B., Sardinha, L. B., & Silva, A. M. (2021) · International Journal of Obesity · doi:10.1038/s41366-020-0591-x · Cited by 6
“carbohydrates as the main source of energy [14, 15].”
BackgroundFernando Carrasco, N., & Galgani, J. E. (2012) · Revista Médica Clínica Las Condes · doi:10.1016/s0716-8640(12)70289-4 · Cited by 11
Association Between Exercise and Treatment with Liraglutide in Obese Rats by Cafeteria Diet
Didek, D., Cordeiro, M. M., Xavier, J. L. D. P., Ribeiro, P. R., Rentz, T., Franco, G. C. N., Kanunfre, C. C., Emilio, H. R. D. O., & Scomparin, D. X. (2019) · Brazilian Archives of Biology and Technology · doi:10.1590/1678-4324-2019180563 · Cited by 6
ACAD10 and ACAD11 enable mammalian 4-hydroxy acid lipid catabolism
Rashan, E. H., Bartlett, A. K., Khana, D. B., Zhang, J., Jain, R., Wade, G., Abriata, L. A., Smith, A. J., Baker, Z. N., Cook, T., et al. (2025) · Nature Structural & Molecular Biology · doi:10.1038/s41594-025-01596-4 · Cited by 14
Foppiani, A., Sileo, F., Menichetti, F., Pozzi, G., Gallosti, S., Amicis, R. S. D., Leone, A., Bertoli, S., & Battezzati, A. (2025) · Journal of the Endocrine Society · doi:10.1210/jendso/bvaf047 · Cited by 4
“Indeed, metabolic inflexibility and insulin resistance are tightly related [2].”
Yang, M., Zhou, F., Wang, C., sun, T., zhao, W., Liu, L., Meng, Y., & tian, L. (2026) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00473.2025 · Cited by 5
Hong, S. L., Longo, K. A., Gosney, E. S., et al. (2013) · The Journals of Gerontology Series A · doi:10.1093/gerona/glt090 · Cited by 5
Metabolic Flexibility during Exercise in Children with Obesity and Matched Controls
Chu, L., Morrison, K. M., Riddell, M. C., Raha, S., & Timmons, B. W. (2020) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000002428 · Cited by 4
“A P Metabolic flexibility (MetFlex) refers to the ability of a system to efficiently adapt substrate metabolism to substrate availability based on demand and supply (1,2).”
BackgroundLumor, L., Bock, C., Mark, F. C., Ponsuksili, S., & Sokolova, I. M. (2025) · Journal of Experimental Biology · doi:10.1242/jeb.249870 · Cited by 4
Bjørklund, G., Tippairote, T., Dadar, M., Lizcano, F., Aaseth, J., & Borisova, O. (2020) · Current Medicinal Chemistry · doi:10.2174/0929867327666200505090449 · Cited by 5
Mantha, O. L., Huneau, J., Mathé, V., Hermier, D., Khodorova, N., Mariotti, F., & Fouillet, H. (2020) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00061.2020 · Cited by 5
The neurometabolic axis: A novel therapeutic target in heart failure
Chakraborty, P., Po, S. S., Scherlag, B. J., & Dasari, T. W. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.122122 · Cited by 5
Chu, L., Morrison, K. M., Riddell, M. C., Raha, S., & Timmons, B. W. (2018) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2017-0358 · Cited by 5
Cyber-Physical System for Management and Self-Management of Cardiometabolic Health
Őri, Z. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.84262 · Cited by 5
“Another definition of metabolic flexibility is the capacity for the organism to adept fuel oxidation to fuel availability [31].”
BackgroundMethodInfluentialChu, L., Morrison, K. M., Riddell, M. C., Raha, S., & Timmons, B. W. (2016) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00419.2016 · Cited by 5
Complementary Therapies for the Body, Mind and Soul
Saad, M. (2015) · InTech eBooks · doi:10.5772/59418 · Cited by 5
Dörner, R., Hägele, F. A., O’Donovan, S. D., Miles-Chan, J. L., Müller, M. J., & Bosy‐Westphal, A. (2025) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00102.2025 · Cited by 4
Aktaş, H., ATAKAN, M. M., Aktitiz, S., Ergün, Z., Koşar, Ş. N., Astorino, T. A., & Turnagöl, H. H. (2025) · Clinical Nutrition · doi:10.1016/j.clnu.2025.04.022 · Cited by 5
Cao, Y., Xu, R., & Zhang, J. (2026) · Frontiers in Pediatrics · doi:10.3389/fped.2026.1679527 · Cited by 5
Resting and exercise metabolic characteristics in obese children with insulin resistance
Cao, Y., Lin, Z., Chen, Z., & Xie, W. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.1049560 · Cited by 4
“, impaired energy substrate conversion), which is central to the pathophysiology associated with IR (Galgani et al., 2008).”
BackgroundGodfrey, H., Shoveller, A. K. K., Kelly, J., Kostiuk, D., Blades, J. S., & Verbrugghe, A. (2025) · Journal of Animal Science · doi:10.1093/jas/skaf081 · Cited by 4
“In the immediate postprandial state, RQ in obesity or type II diabetes appears conflicting, though studies have used a variety of dietary treatments (Galgani et al., 2008).”
Tofogliflozin ameliorates cardiotoxin induced skeletal muscle injury and fibrosis in obesity
Bilal, M., Phuong, N. Q., Kado, T., Liu, J., Anh, L. D., Khalid, S., Aslam, M. R., Memoona, M., Nishimura, A., Igarashi, Y., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-12734-9 · Cited by 4
“Another report showed that an overloaded supply of FA and a limited rate of β-oxidation 33 and leads the FAPs towards fibro-genic or adipo-genic fate after skeletal muscle injury 34 .”
McCue, A., Munten, S., Herzig, K., & Gagnon, D. D. (2021) · Journal of Thermal Biology · doi:10.1016/j.jtherbio.2021.102912 · Cited by 4
WBSCR16 is essential for mitochondrial 16S rRNA processing in mammals
Zhang, S., Dong, Z., Yang, F., Guo, W., Zhang, C., Shi, Y., Zhao, Z., Wang, J., Ning, G., & Huang, G. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkae1325 · Cited by 4
“For instance, adipocytes were shown to passively take more advantage of fatty acids rather than glucose as fuels under metabolic dysfunctions such as insulin resistance ( 29 ,30 ).”
Anthropometric Trajectories and Dietary Compliance During a Personalized Ketogenic Program
García-Gorrita, C., Soriano, J. M., Merino-Torres, J. F., & Onofre, N. S. (2025) · Nutrients · doi:10.3390/nu17091475 · Cited by 4
Derno, M., Langhammer, M., Renne, U., et al. (2012) · Archives animal breeding/Archiv für Tierzucht · doi:10.5194/aab-55-633-2012 · Cited by 4
“…(3) Carbohydrate oxidation = 4.57 × VCO2–3.23 × VO2 Metabolic flexibility, which is defined as the ability of a system to adjust fuel oxidation to fuel availability (Galgani et al. 2008), was analysed by the Percentage Relative Cumulative Frequency (PRCF) method as described (Riachi et al. 2004).”
MethodInfluentialLee, J. Y., Kim, A.-R., Jung, Y.-H., & Bu, S. Y. (2018) · Biotechnology and Bioprocess Engineering · doi:10.1007/s12257-018-0261-1 · Cited by 4
Arad, A. D., DiMenna, F. J., Kittrell, H. D., Kissileff, H. R., & Albu, J. (2022) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00042.2022 · Cited by 4
Astragaloside IV ameliorates metabolic disorder in db/db obese mice as a PPARγ antagonist
Wu, H., Wang, G., Wang, X., et al. (2022) · Journal of Asian Natural Products Research · doi:10.1080/10286020.2022.2098726 · Cited by 4
Alcántara, J. M. A., & Galgani, J. E. (2023) · European Journal of Clinical Nutrition · doi:10.1038/s41430-023-01373-w · Cited by 3
Self-citationAberrant PDK4 Promoter Methylation Preceding Hyperglycemia in a Mouse Model
Putra, S. E. D., Singajaya, S., Thesman, F., Pranoto, D. A., Sanjaya, R. B., Vianney, Y. M., & Artadana, I. B. M. (2019) · Applied Biochemistry and Biotechnology · doi:10.1007/s12010-019-03143-6 · Cited by 4
Őri, Z. (2020) · IntechOpen eBooks · doi:10.5772/intechopen.94232 · Cited by 4
McDougal, D. H., Sánchez‐Delgado, G., Flanagan, E. W., Marlatt, K. L., Sparks, J. R., Yang, S., Redman, L. M., & Ravussin, É. (2025) · Obesity · doi:10.1002/oby.24245 · Cited by 3
“Metabolic flexibility (MetFlex) refers to the ability of an organism to match macronutrient use to overall energy demands [1,2], often by rapidly adjusting macronutrient oxidation to its availability [3].”
Self-citationSambashivaiah, S., Bhadra, R., Bhattacharya, S., & Kurpad, A. (2023) · Journal of the Indian Institute of Science · doi:10.1007/s41745-022-00349-2 · Cited by 3
Biyikoglu, H., Robertson, M. D., & Collins, A. L. (2025) · European Journal of Nutrition · doi:10.1007/s00394-025-03646-5 · Cited by 3
“The enhancement in fat oxidation from a one-day low-carbohydrate diet, irrespective of energy content, and the response to reintroduced carbohydrates can be seen as demonstrative of metabolic flexibility [ 53].”
Are Individuals With Type 2 Diabetes Metabolically Inflexible? A Systematic Review and Meta‐Analysis
Hansen, M., Lange, K. K., Stausholm, M. B., & Dela, F. (2025) · Endocrinology Diabetes & Metabolism · doi:10.1002/edm2.70044 · Cited by 8
“Diet, energy balance, and fasting duration may affect basal RER [71], which is important for the magnitude of the RER increase during insulin stimulation.”
Resilience of the mitochondrial reticulum in aging
Leija, R. G., Vázquez‐Medina, J. P., & Brooks, G. A. (2025) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00110.2025 · Cited by 4
RELAÇÃO ENTRE POLIMORFISMOS GENÉTICOS, LIPÓLISE, METABOLISMO DE LIPÍDEOS E EXERCÍCIOS AERÓBIOS
de Jesus, Í. C., Alle, L. F., Percegona, C. G., Purim, K. S. M., & Leite, N. (2016) · Pensar a Prática · doi:10.5216/rpp.v19i2.37232 · Cited by 3
Chinese Medical Therapies for Diabetes, Infertility, Silicosis and the Theoretical Basis
Li, X.-T. (2017) · InTech eBooks · doi:10.5772/63167 · Cited by 3
Maternal Complications of Pregnancy that Affect Fetal Development
Longo, L. D. (2018) · Springer eBooks · doi:10.1007/978-1-4939-7483-2_11 · Cited by 3
Chien, H., Constantin, D., Greenhaff, P. L., & Constantin‐Teodosiu, D. (2021) · Biology · doi:10.3390/biology10111098 · Cited by 3
García-Roche, M., Talmón, D., Cañibe, G., Astessiano, A. L., Mendoza, A. R., Quijano, C., Cassina, A., & Carriquiry, M. (2022) · Journal of Dairy Science · doi:10.3168/jds.2021-21358 · Cited by 3
Olenick, A., Pearson, R. C., Shaker, N., Blankenship, M. M., Tinius, R. A., Winchester, L. J., Oregon, E., & Maples, J. M. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph191912913 · Cited by 3
“The impaired ability to upregulate lipid oxidation in the face of lipid oversupply may increase fat accumulation and contribute to insulin resistance [25].”
BackgroundArtificially-Intelligent Fascicle-Selective Bidirectional Peripheral Nerve Interfaces
Xu, J., Filho, J. D. S., Hwang, E., Nag, S., Long, L., Kanchwala, M., Abdolrazzaghi, M., Huang, Y. T., Zariffa, J., & Genov, R. (2023) · IEEE Biomedical Circuits and Systems Conference (BioCAS) · doi:10.1109/biocas58349.2023.10388693 · Cited by 3
“Furthermore, such PNS interface technologies have been leveraged in the development of implantable closed-loop therapeutic devices, which mark a significant break-through in the management of chronic medical conditions linked to autoimmune or metabolic disorders [1].”
BackgroundMeasuring PGC-1α and Its Acetylation Status in Mouse Primary Myotubes
Gomes, A. P., & Sinclair, D. A. (2014) · Methods in molecular biology · doi:10.1007/978-1-4939-1875-1_5 · Cited by 3
Sinha, N., Diez, M. S., Hooiveld, G. J. E. J., Keijer, J., dos Santos, V. A. P. M., & van Schothorst, E. M. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00749 · Cited by 3
“Increasing dietary fat intake causes a gradual increase in wholebody fat oxidation, a process called metabolic adaptation (Galgani et al., 2008; Hall and Guo, 2017).”
BackgroundCarbohydrate, Fat and Protein Metabolism in Obesity
Galgani, J. E., Cortés, V., & Fernando Carrasco, N. (2015) · Springer eBooks · doi:10.1007/978-3-319-12125-3_21-1 · Cited by 4
Self-citationIdentificación del fenotipo ahorrador para la personalización del manejo del sobrepeso y la obesidad
Fernando Carrasco, N., & Navarro, G. N. C. (2022) · Revista Médica Clínica Las Condes · doi:10.1016/j.rmclc.2022.03.006 · Cited by 6
Ellett, M. D., Daniels, K. M., Hanigan, M. D., Corl, B. A., Pérez-Hernández, G., Parsons, C. L. M., Melvin, J. A., Fausnacht, D. W., McMillan, R. P., Baumgard, L. H., et al. (2024) · JDS Communications · doi:10.3168/jdsc.2024-0631 · Cited by 2
“In humans, reduced Met Flex is linked to diabetes (Galgani et al., 2008) and cancer (Dart, 2016).”
Using Metabolic Testing to Personalize Behavioral Obesity Treatment
Epstein, L. H., Apolzan, J. W., Moore, M., Neuwald, N. V., & Faith, M. S. (2025) · Obesity Science & Practice · doi:10.1002/osp4.70065 · Cited by 2
Liu, X., Zhao, W., Bao, Y., Gu, Y., Tao, S., Monroig, Ó., Navarro, J. C., Zhu, T., Sun, P., Zhou, Q., et al. (2025) · Aquaculture · doi:10.1016/j.aquaculture.2025.743456 · Cited by 3
Liu, J., Fan, J., & Zhou, B. (2026) · Physiology International · doi:10.1556/2060.2026.00780 · Cited by 3
Metabolic flexibility during late pregnancy is associated with neonatal adiposity
Tinius, R. A., Blankenship, M. M., Furgal, K. E., Cade, W. T., Duchette, C., Pearson, K. J., & Maples, J. M. (2021) · Applied Physiology Nutrition and Metabolism · doi:10.1139/apnm-2020-1005 · Cited by 2
Regulation of Fatty Acid Oxidation in Skeletal Muscle During Exercise: Effect of Obesity
Fritzen, A. M., Broskey, N. T., Lundsgaard, A., Dohm, G. L., Houmard, J. A., & Kiens, B. (2022) · Physiology in health and disease · doi:10.1007/978-3-030-94305-9_8 · Cited by 3
Yeshurun, S., Cramer, T., Souroujon, D., & Mor, M. (2024) · JMIR mhealth and uhealth · doi:10.2196/56083 · Cited by 2
“In addition, it reveals metabolic inflexibility in individuals with obesity as they show a reduced %CO 2 response compared with healthy individuals, which again is in accordance with the literature on metabolic flexibility [8,9,26].”
Xing, B., Wang, R., Kou, T., Liu, W., & Zhu, Z. (2025) · Advanced Science · doi:10.1002/advs.202503662 · Cited by 3
Insulin and the Physiology of Carbohydrate Metabolism
Pereira, S., & Giacca, A. (2011) · Energy balance and cancer · doi:10.1007/978-1-4419-9911-5_1 · Cited by 3
Effect ofSardina pilchardusoil on alloxan-induced diabetic rats
Belhadj, S., Hentati, O., Baccouch, N., Salah, H. B., Boudaouara, T., Hadj, A. B., Allouch, N., & Feki, A. E. (2015) · Archives of Physiology and Biochemistry · doi:10.3109/13813455.2015.1118128 · Cited by 2
Alsaif, M., Triador, L., Colin-Ramírez, E., Elliott, S. A., Mackenzie, M. L., Field, C. J., Prado, C. M. M., & Haqq, A. M. (2021) · Current Developments in Nutrition · doi:10.1093/cdn/nzab016 · Cited by 2
Jannah, F. N., Anggraini, P. D., Gofur, A., & Lestari, S. R. (2021) · AIP conference proceedings · doi:10.1063/5.0052672 · Cited by 2
Günaştı, Ö., Özdemir, Ç., Özgünen, K., Yılmaz, M. B., Öksüz, H., Zorludemir, S., & Kurdak, S. S. (2021) · General Physiology and Biophysics · doi:10.4149/gpb_2021019 · Cited by 2
“Fatty acid accumulation in skeletal muscle may impair mitochondrial dynamics (Chen et al. 2018), which disrupt fuel homeostasis together with beta-oxidation (Galgani et al. 2008; Koves et al. 2008; Heo et al. 2017).”
Salari, B., Samankan, S., & Porhomayon, J. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-800093-9.00002-8 · Cited by 3
Metadata
- Authors
- Galgani, J. E., Moro, C., & Ravussin, E.
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2008-11
- Volume
- 295
- Issue
- 5
- Pages
- E1009-E1017
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- PMC
- PMC2584808
- OpenAlex
- W2168445785
- Cited by
- 532
- References
- 68
- Citations by year
- 2026: 36 · 2025: 40 · 2024: 17 · 2023: 22 · 2022: 38 · 2021: 36 · 2020: 46 · 2019: 34 · 2018: 32 · 2017: 38 · 2016: 21 · 2015: 28 · 2014: 39 · 2013: 40 · 2012: 17
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Universidad de Chile (submittedVersion)
- Funders
- National Institute on Aging (U01AG020478)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK060412, R01-DK-60412)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- metabolic flexibility, insulin resistance, intramyocellular lipid, glucose disposal rate, hyperinsulinemic-euglycemic clamp, respiratory quotient, high-fat diet, mitochondrial function, fuel oxidation, type 2 diabetes, obesity
- MeSH terms
- Animals, Diabetes Mellitus, Type 2, Energy Metabolism, Humans, Insulin Resistance, Mitochondria, Obesity, Muscle, Skeletal, Carbohydrate Metabolism, Lipid Metabolism
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.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
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
