Understanding how skeletal muscle adapts to carbohydrates and fats, why mitochondrial health matters, and how individualized exercise training supports metabolic regulation, endurance, and long-term physical health.
What allows a well-trained athlete to sustain prolonged physical activity while also producing bursts of high-intensity effort?
Why can some individuals transition efficiently between using carbohydrates and fats for energy, while others demonstrate impaired metabolic regulation?
And why does regular exercise produce physiological benefits that cannot necessarily be replicated by changing dietary composition alone?
These questions point toward one of the most important concepts in contemporary exercise physiology: metabolic flexibility.
Metabolic flexibility describes the capacity to adjust fuel utilization according to changing energy availability and physiological demands.
During rest and lower-intensity physical activity, skeletal muscle may obtain a substantial proportion of its energy from fatty acid oxidation.
As exercise intensity increases, carbohydrate metabolism generally becomes increasingly important because it can support higher rates of ATP production.
Following a meal, insulin and nutrient availability influence how tissues use and store energy.
During fasting, exercise, and recovery, these processes change again.
A metabolically adaptable body can respond to these transitions through coordinated adjustments in fuel transport, cellular metabolism, hormonal signaling, and mitochondrial activity.
However, metabolic flexibility is not simply the ability to burn more fat.
It is the ability to use the appropriate energy sources, in appropriate proportions, when physiological circumstances change.
In 2020, researchers Andreas Mæchel Fritzen, Anne-Marie Lundsgaard, and Bente Kiens published Tuning Fatty Acid Oxidation in Skeletal Muscle With Dietary Fat and Exercise in Nature Reviews Endocrinology.
Their review examined how dietary fat and exercise influence the proteins and pathways responsible for fatty acid metabolism within human skeletal muscle.
The authors identified an important finding.
Both high dietary fat availability and aerobic exercise can stimulate certain adaptations in skeletal muscle's ability to handle fatty acids.
However, exercise provides an additional and particularly important stimulus: the substantial increase in cellular energy turnover necessary to produce muscular work.
This helps explain why aerobic training consistently improves mitochondrial capacity, whereas simply consuming more dietary fat does not reliably produce equivalent adaptations.
More recent research published in Nature Metabolism, Nature Communications, and Nature Reviews Molecular Cell Biology has expanded our understanding of these mechanisms.
Together, these discoveries reinforce a fundamental principle of movement health:
Exercise does not merely consume energy. It trains the biological systems responsible for producing, distributing, and using energy.
1. Skeletal Muscle: One of the Body's Most Important Metabolic Tissues
Skeletal muscle is commonly associated with strength, movement, and athletic performance.
However, it also plays an essential role in whole-body metabolism.
Muscle contributes substantially to glucose disposal following meals.
It stores glycogen that can be used during physical activity.
It contains mitochondria responsible for producing ATP through oxidative metabolism.
And it continuously adjusts how it handles carbohydrates, fatty acids, and other metabolic substrates.
During muscular contraction, ATP is consumed to support several processes.
These include interactions between actin and myosin, calcium handling, and the maintenance of cellular electrochemical gradients.
Because ATP stores within muscle are limited, the body must continually regenerate ATP.
This requires the coordinated activity of multiple metabolic pathways.
Importantly, the relative contribution of these pathways changes according to exercise intensity, duration, training status, and substrate availability.
The metabolic flexibility of skeletal muscle is therefore fundamental to exercise performance and everyday physical function.
2. How Muscles Produce Energy
Skeletal muscle produces ATP through several interconnected energy systems.
These pathways operate simultaneously, although their relative contributions vary.
The Phosphagen System
The phosphagen system uses stored phosphocreatine to rapidly regenerate ATP.
It is particularly important during brief, high-intensity efforts such as sprint starts, jumping, and heavy lifting. However, its capacity is limited.
Glycolysis
Glycolysis breaks down glucose or glycogen-derived substrates to support ATP production.
It contributes during both lower- and higher-intensity activities, with its importance generally increasing as energy demands rise.
Glycolysis can support rapid ATP production without requiring mitochondrial oxygen consumption at the point of ATP generation.
Its products may subsequently enter mitochondrial metabolism.
Oxidative Phosphorylation
Oxidative metabolism uses mitochondria to produce ATP from substrates derived from carbohydrates, fats, and other fuels.
It is essential for sustaining prolonged activity.
These systems should not be understood as separate switches.
A person does not exclusively use one pathway before suddenly activating another.
Instead, the body continually adjusts the relative contribution of overlapping processes.
A 2020 review in Nature Metabolism, Skeletal Muscle Energy Metabolism During Exercise, provides a comprehensive explanation of these interactions.
The authors emphasize that exercise performance depends on maintaining ATP availability across changing energy demands.
3. What Is Fatty Acid Oxidation?
Fatty acid oxidation is the process through which fatty acids are broken down to contribute to cellular energy production.
Fatty acids can originate from several sources.
These include circulating fatty acids released from adipose tissue, fatty acids derived from circulating triglyceride-containing lipoproteins, and lipids stored within skeletal muscle.
Once fatty acids become available to muscle cells, they can be transported and metabolized through several coordinated steps.
Long-chain fatty acids must be activated and appropriately transported into mitochondria.
Within mitochondria, beta-oxidation progressively breaks fatty acids into acetyl-CoA molecules.
Acetyl-CoA can enter the tricarboxylic acid cycle, while reducing equivalents contribute to oxidative phosphorylation.
These processes support ATP production.
However, the ability to oxidize fatty acids depends on more than having fatty acids available.
Muscle must possess the cellular machinery necessary to transport, activate, and metabolize them.
This machinery adapts in response to exercise training and other physiological influences.
4. How Exercise Changes the Muscle's Fat-Metabolism Machinery
The 2020 Fritzen, Lundsgaard, and Kiens review identifies several proteins involved in skeletal muscle fatty acid metabolism.
One is CD36, a protein that contributes to fatty acid transport.
Others include fatty acid transport proteins and fatty acid-binding proteins.
Once fatty acids enter muscle cells, enzymes participate in their activation and subsequent handling.
Carnitine palmitoyltransferase 1, or CPT1, helps regulate the mitochondrial import of long-chain fatty acids.
Additional enzymes, including beta-hydroxy-acyl-CoA dehydrogenase, participate in beta-oxidation.
Aerobic exercise training can increase the abundance or activity of several of these proteins.
The resulting adaptations help muscle handle greater energetic demands and improve its capacity to use fatty acids during appropriate conditions.
However, these changes are not identical across every exercise program.
Their magnitude depends on training intensity, duration, frequency, prior fitness, and the metabolic characteristics of the individual.
Some adaptations may occur relatively quickly, while others develop through repeated training over weeks or months.
This is one reason exercise programming must consider both the individual workout and the cumulative training stimulus.
5. Why Burning More Fat Is Not the Same as Being Metabolically Healthy
A common misconception is that a higher rate of fat oxidation always indicates better metabolic health.
However, the relationship is more complicated.
The proportion of energy derived from carbohydrates or fats changes according to the circumstances.
For example, carbohydrate oxidation appropriately increases following carbohydrate consumption and during sufficiently demanding exercise.
A healthy, trained individual may therefore demonstrate substantial carbohydrate utilization during high-intensity physical activity.
That does not indicate poor metabolic flexibility.
Instead, the ability to increase carbohydrate use when it is needed is an important component of flexibility.
Similarly, consuming a high-fat diet can increase the proportion of energy derived from fat without necessarily improving mitochondrial capacity, insulin sensitivity, or cardiovascular health.
The key consideration is not whether the body preferentially uses fat at every moment.
It is whether metabolic processes respond appropriately to fuel availability and energy demand.
A metabolically flexible body is not permanently in fat-burning mode. It is capable of changing modes when circumstances require it.
6. Dietary Fat and Exercise Can Produce Some Similar Molecular Changes
One of the most interesting findings from the 2020 Nature Reviews Endocrinology article is that dietary fat and exercise can stimulate overlapping adaptations in muscle.
When dietary fat intake increases, the availability of fatty acids also changes.
These fatty acids can serve as metabolic substrates.
They may also participate in cellular signaling.
Certain fatty acids interact with receptors involved in regulating genes associated with lipid metabolism.
As a result, high-fat dietary interventions can increase the abundance or activity of selected proteins involved in fatty acid uptake and handling.
Aerobic exercise can produce some similar adaptations.
However, the underlying physiological circumstances differ.
Dietary interventions primarily change nutrient availability and associated metabolic signals.
Exercise changes nutrient availability while also generating muscular contractions, calcium signaling, ATP turnover, altered cellular energy states, and numerous additional physiological stimuli.
Consequently, the adaptations are not interchangeable.
This distinction is important when interpreting claims that a high-fat or ketogenic dietary strategy can reproduce the metabolic benefits of exercise.
Diet may influence substrate utilization.
But it does not necessarily reproduce the broader adaptations induced by repeated muscular work.
7. Why Exercise Is a More Potent Stimulus for Mitochondrial Adaptation
Mitochondria are organelles responsible for numerous aspects of cellular metabolism, including oxidative ATP production.
Their function is particularly important in skeletal muscle because physical activity can substantially increase ATP demand.
Repeated aerobic exercise stimulates adaptations involving mitochondrial proteins, oxidative enzyme activity, and mitochondrial structure.
The 2020 review emphasizes that these adaptations are more consistently produced by exercise training than by high dietary fat intake alone.
For example, aerobic exercise training increases the activity of citrate synthase, an enzyme commonly used as a marker of mitochondrial oxidative capacity.
Exercise also stimulates adaptations in the mitochondrial respiratory machinery.
In contrast, human high-fat feeding studies have generally not demonstrated comparable increases in mitochondrial volume or respiratory capacity.
This finding helps explain why improved fat oxidation following dietary fat adaptation should not automatically be described as improved mitochondrial fitness.
A muscle can alter its relative fuel preference without developing the same oxidative capacity obtained through exercise training.
8. Mitochondrial Biogenesis: Building Greater Oxidative Capacity
Mitochondrial biogenesis refers to processes contributing to the development and maintenance of the mitochondrial network.
Exercise-related mitochondrial adaptation involves multiple interacting pathways.
These include signaling related to cellular energy demand, calcium regulation, and changes in redox state.
One important regulatory protein is PGC-1α, which participates in coordinating transcriptional programs associated with oxidative metabolism.
However, mitochondrial adaptation cannot be reduced to one molecular switch.
The response involves numerous proteins, transcription factors, enzymes, and post-translational modifications.
A 2023 review in Nature Reviews Molecular Cell Biology, Exercise Metabolism and Adaptation in Skeletal Muscle, describes the functional plasticity of skeletal muscle in response to exercise.
The authors discuss how changes in training demands influence both metabolic pathways and cellular architecture.
Their work reinforces that mitochondrial adaptation is a dynamic process involving the structure and function of muscle fibers.
These adaptations help explain why aerobic training can improve exercise tolerance even when body weight changes very little.
9. The Role of PPARs in Fatty Acid Metabolism
Peroxisome proliferator-activated receptors, commonly abbreviated PPARs, are nuclear receptors involved in regulating metabolic gene expression.
They participate in lipid metabolism, energy regulation, and other biological processes.
Some fatty acids can act as ligands for PPARs.
This provides one potential mechanism through which nutrient availability influences metabolic adaptations.
The 2020 review discusses the possibility that elevated fatty acid availability stimulates PPAR-related signaling in skeletal muscle.
These pathways may contribute to changes in proteins involved in fatty acid transport and oxidation.
However, the precise contribution of PPAR signaling varies according to tissue, receptor subtype, and experimental conditions.
The findings should not be interpreted as evidence that simply increasing dietary fat will optimize PPAR activity or improve whole-body metabolic health.
The physiological consequences of a diet depend on more than one nuclear receptor pathway.
10. AMPK: A Cellular Energy-Sensing System
AMP-activated protein kinase, or AMPK, is an important regulator of cellular energy homeostasis.
Its activity is influenced by changes in cellular energy conditions.
During muscular exercise, ATP consumption increases.
This can stimulate signaling that helps coordinate cellular responses to increased energy demand.
AMPK participates in pathways involving glucose transport, lipid metabolism, and other adaptive processes.
The 2020 review discusses evidence that fatty acid availability may also influence AMPK signaling.
However, the exact mechanisms remain incompletely characterized in humans.
An important distinction is that activating AMPK through one experimental pathway does not necessarily reproduce the physiological benefits of exercise.
Exercise produces numerous interacting signals.
No single molecule explains all its effects.
11. SIRT1, NAD+, and Metabolic Regulation
Sirtuin 1, or SIRT1, is a protein involved in regulating several cellular processes through NAD+-dependent enzymatic activity.
NAD+ is an essential cofactor involved in numerous metabolic reactions.
The 2020 review proposes that changes in fatty acid oxidation may influence NAD+-related signaling and SIRT1 activity.
These processes could contribute to regulating genes involved in lipid metabolism.
However, the authors present several of these mechanisms as proposed pathways rather than fully established explanations.
This distinction matters because molecular signaling research is sometimes used to justify nutritional supplements or interventions without adequate clinical evidence.
For example, identifying an association between SIRT1 and metabolic adaptation does not establish that increasing NAD+ through supplementation will improve exercise performance or insulin sensitivity.
Clinical recommendations require evidence that the intervention improves meaningful outcomes in humans.
12. Lactate: More Than a Metabolic Byproduct
Lactate was historically portrayed primarily as a waste product associated with intense exercise.
However, contemporary physiology recognizes it as an important metabolic substrate and signaling molecule.
Lactate can be transported between tissues and used in energy metabolism.
Researchers are also investigating its role in regulating exercise-related cellular adaptations.
The 2020 review discusses evidence that lactate may contribute to changes in lipid-metabolism pathways.
A particularly interesting possibility is that lactate participates in signaling associated with mitochondrial adaptation.
However, the specific molecular mechanisms and their relative importance in humans remain under investigation.
This illustrates a broader lesson.
Molecules produced during exercise often have multiple biological roles.
Their presence should not automatically be interpreted as evidence of metabolic dysfunction.
13. What Is Metabolic Inflexibility?
Metabolic inflexibility describes an impaired ability to appropriately adjust substrate utilization when physiological conditions change.
For example, some individuals with insulin resistance demonstrate a reduced ability to increase carbohydrate oxidation in response to insulin.
Others may show altered fatty acid oxidation in response to changing nutrient availability.
However, metabolic inflexibility is not a single uniform defect.
Different studies measure it through different physiological challenges.
Some examine changes in respiratory exchange ratio during insulin stimulation.
Others investigate fasting-to-fed transitions or changes in fuel oxidation during exercise.
Consequently, a person cannot be accurately classified as metabolically inflexible based solely on one resting measurement.
The concept must be interpreted according to the specific metabolic response being investigated.
14. Why Obesity and Insulin Resistance Can Affect Fuel Utilization
The 2020 Fritzen, Lundsgaard, and Kiens review describes findings involving impaired skeletal muscle fatty acid oxidation capacity in some populations with obesity.
Researchers have observed differences in mitochondrial fatty acid handling and the ability to respond to increased dietary fat availability.
However, obesity is heterogeneous.
Individuals with similar body mass indexes can differ substantially in metabolic health, fitness, muscle composition, and insulin sensitivity.
Some people with obesity maintain relatively preserved metabolic function.
Others demonstrate clinically significant insulin resistance or additional metabolic abnormalities.
The underlying mechanisms are also complex.
They may involve physical inactivity, ectopic lipid accumulation, altered mitochondrial processes, inflammation, genetics, medications, and other factors.
It would therefore be inaccurate to assume that every person with obesity has impaired mitochondrial function.
Likewise, the presence of intramuscular lipids does not automatically indicate disease.
The significance depends partly on how lipids are stored, metabolized, and regulated.
15. The Athlete's Paradox: Why Muscle Fat Is Not Always Harmful
One particularly useful example is the athlete's paradox.
Endurance-trained individuals may possess substantial amounts of intramuscular triglyceride.
However, they often demonstrate excellent insulin sensitivity and oxidative capacity.
By contrast, some individuals with insulin resistance also demonstrate increased intramuscular lipid content.
This apparent contradiction illustrates why the quantity of stored muscle fat cannot explain metabolic health by itself.
The capacity to mobilize, transport, and oxidize fatty acids also matters.
So do lipid intermediates, cellular signaling, mitochondrial function, and the organization of lipid droplets.
For trained athletes, intramuscular triglyceride can serve as a useful energy reserve during prolonged activity.
This reinforces the importance of understanding metabolic function rather than interpreting one anatomical or biochemical finding in isolation.
16. Can Exercise Improve Metabolic Flexibility Without Significant Weight Loss?
One of the most encouraging findings in the uploaded review concerns the effects of exercise among individuals with obesity.
The authors describe studies demonstrating improvements in skeletal muscle fatty acid oxidation capacity following aerobic training.
Importantly, several of these improvements occurred under conditions of body-weight maintenance.
This suggests that changes in muscle metabolism can develop independently of substantial weight loss.
Exercise can improve the capacity of muscle to handle metabolic substrates even when the number on the scale changes little.
This is clinically important.
Weight loss may be an appropriate goal for selected individuals.
However, body weight alone does not capture changes in cardiorespiratory fitness, muscular function, mitochondrial capacity, or insulin sensitivity.
A program focused exclusively on weight reduction may overlook meaningful improvements in physiological health.
For Move Well, this distinction is particularly valuable:
Exercise should not be evaluated only according to how much weight someone loses. Its benefits also include changes in what the body becomes capable of doing.
17. A 2025 Discovery: PanK4 and Metabolic Flexibility
A January 2025 Nature Communications study, Pantothenate Kinase 4 Controls Skeletal Muscle Substrate Metabolism, identified a molecular regulator associated with skeletal muscle metabolic flexibility.
The researchers investigated PanK4, a protein involved in metabolic regulation.
Using experimental models, they found that muscle-specific deletion of PanK4 impaired fatty acid oxidation and altered intracellular acetyl-CoA and malonyl-CoA concentrations.
These changes were associated with impaired glucose regulation and reduced glucose uptake in selected circumstances.
The findings suggest that PanK4 contributes to mechanisms coordinating carbohydrate and lipid metabolism.
However, much of the causal evidence came from experimental models.
The study does not establish PanK4 testing or targeted treatment as an established clinical strategy for metabolic disease.
Its importance lies in identifying another potential mechanism governing the muscle's ability to adjust fuel utilization.
18. Epigenetic Regulation and Metabolic Adaptation
A second 2025 Nature Metabolism study, Kdm2a Inhibition in Skeletal Muscle Improves Metabolic Flexibility in Obesity, investigated how changes in gene regulation influence muscular metabolism.
Researchers studied KDM2A, an enzyme involved in epigenetic regulation.
In mouse models, disrupting Kdm2a activity altered skeletal muscle characteristics and increased the proportion of mitochondria-rich slow-twitch fibers.
These changes were associated with improved metabolic responses under selected experimental conditions.
The findings suggest that epigenetic processes can influence muscle fiber characteristics and metabolic function.
However, this research does not establish that KDM2A inhibition is an approved treatment for obesity or metabolic dysfunction.
Nor does it mean that exercise benefits can be fully replicated through one molecular intervention.
The broader lesson is that skeletal muscle demonstrates considerable biological plasticity.
Its structure and function can change according to physiological demands and regulatory signals.
19. What New Human Research Reveals About Exercise and Mitochondria
A recent Nature Communications study, Miro1 Mediates Skeletal Muscle Insulin Resistance in Type 2 Diabetes, investigated the relationship between mitochondrial organization and insulin resistance.
The researchers identified alterations involving the mitochondrial-associated protein Miro1 in skeletal muscle.
They also conducted a randomized exercise-training investigation involving individuals with obesity and type 2 diabetes.
Participants completed a 12-week aerobic training program or continued standard care.
The exercise intervention improved several measures of physical fitness and muscle function.
Researchers also identified changes in mitochondrial morphology and respiratory capacity.
These findings provide additional evidence that exercise can influence mitochondrial characteristics in human skeletal muscle.
However, the trial was relatively small, and the detailed mechanisms require further validation.
The research does not mean that Miro1 measurement is currently necessary for exercise prescription.
Its value lies in demonstrating that exercise training can influence cellular organization and metabolic function in individuals with established metabolic disease.
20. Aerobic and Resistance Exercise Produce Complementary Adaptations
Different exercise modalities stimulate different physiological demands.
Aerobic training generally emphasizes sustained energy production and cardiorespiratory function.
Resistance training emphasizes force generation and neuromuscular adaptation.
However, the distinction is not absolute.
Both forms of exercise influence metabolism.
A July 2025 Nature Communications study, Aerobic and Resistance Exercise-Regulated Phosphoproteome and Acetylproteome Modifications in Human Skeletal Muscle, investigated molecular responses to these training modalities.
After 12 weeks, high-intensity aerobic training produced prominent changes involving mitochondrial proteins and energetic regulation.
Resistance training produced changes involving contractile and cytoskeletal machinery consistent with strength adaptation.
The study demonstrates that different exercise modalities can produce distinct molecular signatures.
This supports the value of individualized programming.
Someone primarily seeking improved aerobic endurance may require a different training emphasis from someone recovering muscular strength following injury.
Many individuals benefit from combining exercise modalities to address multiple dimensions of physical capacity.
21. Why Exercise Intensity Matters
Exercise intensity influences the relative contribution of different energy pathways.
At lower intensities, fatty acid oxidation may provide a substantial proportion of energy.
As intensity rises, carbohydrate metabolism becomes increasingly important.
However, the exact relationship depends on fitness, training status, nutritional state, and individual physiology.
Endurance training can alter the intensity at which different fuels contribute to energy production.
A trained individual may sustain a higher absolute workload while oxidizing substantial amounts of fat compared with their previous untrained condition.
Nevertheless, this does not mean that every exercise session should target maximal fat oxidation.
Higher-intensity training can provide important benefits for cardiorespiratory fitness and performance.
Resistance training contributes to strength and physical capacity.
Lower-intensity activity can support sustainable movement participation and recovery.
The appropriate intensity depends on the intended adaptation.
22. Exercise Volume, Frequency, and Recovery
The body's response to exercise depends on more than intensity.
Training frequency, duration, volume, and recovery also influence adaptation.
For example, brief exercise sessions may provide meaningful health benefits but may not generate the same mitochondrial adaptations as appropriately structured programs with greater aerobic training volume.
The uploaded review describes differences among training interventions in their ability to improve lipid oxidation.
Some studies involving very low-volume training produced limited changes in selected metabolic measures.
Other interventions demonstrated improvements following repeated moderate-intensity or interval-based training.
These differences illustrate why exercise prescriptions should account for the specific desired outcome.
Recovery is also necessary.
Sleep, nutrition, training history, and overall physiological demands influence the capacity to adapt.
The goal is not simply to accumulate more exercise.
It is to provide a sustainable stimulus that produces meaningful improvement over time.
23. Why Fat-Burning Zones Should Not Define an Entire Exercise Program
Many exercise programs emphasize a particular heart-rate range described as the fat-burning zone.
This terminology usually refers to intensities at which fat contributes a relatively high proportion of energy.
However, the percentage of energy derived from fat is not equivalent to total energy expenditure.
Nor does it establish that an exercise intensity is optimal for long-term fat loss, cardiovascular health, or metabolic flexibility.
A higher-intensity session may derive a smaller percentage of energy from fat while still producing significant physiological adaptations.
Likewise, resistance exercise may support metabolic health even though it is not primarily designed to maximize fat oxidation during the activity itself.
A comprehensive program should therefore consider multiple outcomes.
These include fitness, strength, exercise tolerance, body composition when relevant, and functional capacity.
The best exercise prescription is not necessarily the one that produces the highest percentage of fat oxidation during a single workout.
24. How Do We Measure Metabolic Flexibility?
Researchers and clinicians use several approaches to evaluate metabolic function.
Indirect calorimetry measures oxygen consumption and carbon dioxide production, allowing estimates of substrate oxidation under appropriate conditions.
The respiratory exchange ratio provides information about the relative contribution of carbohydrate and fat oxidation.
However, interpretation becomes more complicated during high-intensity exercise because of changes in carbon dioxide production and acid–base regulation.
Researchers may also use insulin-stimulation protocols, metabolic chambers, muscle biopsies, and other specialized techniques.
These methods provide different types of information.
For routine fitness evaluation, cardiorespiratory testing may help characterize aerobic capacity and exercise responses.
Selected laboratories also estimate substrate oxidation across exercise intensities.
However, these estimates do not fully describe every aspect of metabolic flexibility.
For example, measuring fat oxidation during cycling does not necessarily reveal how effectively skeletal muscle responds to insulin following a meal.
The clinical significance of a measurement depends on the question it is intended to answer.
25. Why Individualized Exercise Prescription Matters
Two individuals with similar body weights may demonstrate very different levels of physical capacity.
One may possess substantial muscular strength but limited aerobic conditioning.
Another may have excellent endurance but reduced strength or mobility.
A third may experience chronic pain or medical limitations that restrict their exercise options.
Consequently, a universal exercise prescription is unlikely to produce optimal results for everyone.
Individualized programming considers several dimensions of physical function.
These may include strength, cardiovascular fitness, balance, movement capacity, exercise experience, medical history, and personal goals.
For some individuals, the starting point may involve restoring tolerance to basic physical activities.
For others, the emphasis may involve progressively increasing aerobic workload or resistance-training demands.
The objective is to identify the training stimulus most appropriate for the individual.
26. How This Research Informs Move Well
We recognize that movement is essential not only for musculoskeletal function but also for metabolic regulation.
The research on skeletal muscle metabolic flexibility provides an important scientific foundation for understanding why exercise can influence health independently of body weight.
Our Move Well philosophy emphasizes individualized movement assessment, exercise prescription, and progressive development of physical capacity.
Depending on the individual's presentation, this may involve functional movement screening, chiropractic care, physiotherapy, corrective exercise, strength and conditioning, or aerobic fitness training.
We recognize that some individuals first need to address pain, movement limitations, deconditioning, or other barriers before participating in more demanding exercise.
Others may benefit from a structured program designed to improve endurance, muscular strength, or athletic performance.
Where appropriate, fitness testing can help guide training intensity and monitor progress.
However, we do not assume that every functional movement limitation causes metabolic dysfunction.
Nor do we claim that a particular screening score directly measures mitochondrial function or metabolic flexibility.
Instead, movement assessment helps inform practical exercise decisions.
Our objective is to help individuals participate in an appropriate amount and type of physical activity while progressing according to their capabilities.
We also recognize the importance of collaboration when patients have medical conditions that influence exercise tolerance or metabolic regulation.
Conclusion: Metabolic Health Depends on the Capacity to Adapt
Skeletal muscle is one of the body's most important metabolic tissues.
It must continuously adjust how it uses carbohydrates, fatty acids, and other energy substrates as physiological demands change.
This adaptive capacity is essential for movement, exercise performance, and metabolic regulation.
The 2020 Nature Reviews Endocrinology review demonstrates that dietary composition and exercise can influence overlapping pathways involved in muscle lipid metabolism.
However, exercise provides a distinct stimulus through increased muscular energy demand.
This helps explain why aerobic training can produce substantial mitochondrial adaptations that are not reliably reproduced through high dietary fat intake alone.
More recent research has expanded our understanding of the proteins, signaling pathways, and cellular structures involved in metabolic flexibility.
These discoveries also reinforce the importance of appropriate exercise training for individuals experiencing metabolic dysfunction.
Yet the ultimate goal is not to maximize fat oxidation or optimize one molecular pathway.
It is to develop a body capable of meeting changing demands.
Metabolic flexibility is not simply about which fuel your body prefers. It is about having the capacity to use the fuels available, respond to the demands placed upon you, and adapt through appropriate training.
We believe this perspective strengthens the case for comprehensive movement care. Movement is not merely a way to expend calories; it’s a powerful stimulus through which the body develops greater physiological capacity.
And the benefits of exercise should be evaluated not only by changes in weight or appearance, but also by improvements in physical function, metabolic health, and the freedom to participate in meaningful activities throughout life.
Research References
Fritzen AM, Lundsgaard AM, Kiens B. Tuning fatty acid oxidation in skeletal muscle with dietary fat and exercise. Nature Reviews Endocrinology. 2020;16:683–696. https://doi.org/10.1038/s41574-020-0405-1
Hargreaves M, Spriet LL. Skeletal muscle energy metabolism during exercise. Nature Metabolism. 2020;2:817–828. https://doi.org/10.1038/s42255-020-0251-4
Smith JAB, Murach KA, Dyar KA, Zierath JR. Exercise metabolism and adaptation in skeletal muscle. Nature Reviews Molecular Cell Biology. 2023;24:607–632. https://doi.org/10.1038/s41580-023-00606-x
Pantothenate kinase 4 controls skeletal muscle substrate metabolism. Nature Communications. Published January 2, 2025. https://doi.org/10.1038/s41467-024-55036-w
Wang Y, Xie H, Liu Q, et al. Kdm2a inhibition in skeletal muscle improves metabolic flexibility in obesity. Nature Metabolism. 2025. https://doi.org/10.1038/s42255-024-01210-9
Epigenetic modification increases skeletal muscle resilience to metabolic stress. Nature Metabolism. 2025;7:251–252. https://doi.org/10.1038/s42255-024-01211-8
Aerobic and resistance exercise-regulated phosphoproteome and acetylproteome modifications in human skeletal muscle. Nature Communications. Published July 1, 2025. https://doi.org/10.1038/s41467-025-60049-0
Miro1 mediates skeletal muscle insulin resistance in type 2 diabetes. Nature Communications. Published October 2026. https://doi.org/10.1038/s41467-026-77278-6