Insulin resistance isn’t just about sugar anymore.
New research suggests that how cells handle fat—or fail to—may be just as critical to metabolic health as glucose management.
Popular health and fitness educator Thomas DeLauer recently unpacked emerging science pointing to an unexpected culprit: impaired fat oxidation, particularly when certain fats are consumed alongside carbohydrates.
What he reveals could change how people approach meal composition, especially those already struggling with metabolic issues.
Jump to:
- When Fat Oxidation Stops, Cells Suffer
- Trans Fats: A Unique Metabolic Threat
- Metabolic Gridlock: Why Cells Can’t Handle Both Fuels at Once
- Worst-Case Scenario: Trans Fats Plus Carbs in Caloric Surplus
- Protein: A Surprising Solution for Fat Oxidation
- Evolutionary Context: What Nature Intended
- Context Matters: Individual Metabolic Flexibility
- Long-Term Cellular Damage From Chronic Energy Overload
- Practical Takeaways for Better Metabolic Health
When Fat Oxidation Stops, Cells Suffer
DeLauer references a study published in PNAS that highlights a critical hypothesis: when cells stop burning fat efficiently, toxic lipid byproducts accumulate and interfere with insulin signaling.
The correlations between intramyocellular lipids, decreased fatty acid oxidation, and insulin resistance have led to the hypothesis that impaired fatty acid oxidation causes accumulation of lipotoxic intermediates that inhibit muscle insulin signaling.
Translation? Problems arise not just from poor glucose utilization, but from stalled fat breakdown inside muscle cells.
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This mechanism creates a feedback loop: impaired fat oxidation worsens insulin resistance, which further hampers nutrient processing.
Trans Fats: A Unique Metabolic Threat
DeLauer dives into rodent model research published in Biological Chemistry that compared how different fats behave inside cells.
Scientists examined oleic acid (a healthy monounsaturated fat), stearic acid (a beneficial saturated fat), and nine trans octadecenoic acid (a trans fat).
The first step in fat breakdown requires an enzyme called long-chain acetyl-CoA dehydrogenase (LCAD). Natural fats like oleic and stearic acid broke down smoothly. Trans fats did not.
Instead, they accumulated in cell membranes, triggering oxidative stress and disrupting insulin signaling pathways.
It led to accumulation of components of that fat in the cell membrane, leading to oxidative stress in the cell membrane, therefore leading to impaired insulin signaling.
For people already dealing with insulin resistance, trans fats create additional cellular gridlock—making existing metabolic dysfunction even worse.
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- Comfortable grip that makes high-rep workouts easier to handle
Metabolic Gridlock: Why Cells Can’t Handle Both Fuels at Once
DeLauer explains research from Cell describing reciprocal fuel regulation: cells preferentially burn either fats or carbohydrates at any given moment, not both simultaneously.
Healthy individuals switch between fuel sources efficiently. Metabolically compromised individuals struggle.
When high amounts of fats and carbs enter cells together, enzymatic pathways clash. Neither fuel gets processed properly, leading to energy accumulation and cellular toxicity.
The biggest issue with insulin resistance and metabolic disease today is not sugar, this, that, and the other. It is about too much energy, energy abundance.
This phenomenon—dubbed metabolic gridlock—occurs meal by meal when cells face more energy than they can utilize.
Healthy people may tolerate mixed macronutrient meals without issue. Those with insulin resistance cannot.
Worst-Case Scenario: Trans Fats Plus Carbs in Caloric Surplus
Combining trans fats with refined carbohydrates creates a perfect storm, especially during caloric surplus.
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- Full-body training with one weight using swings, squats, and presses
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- Comfortable grip that makes high-rep workouts easier to handle
Trans fats resist breakdown, carbs flood cells with glucose, and excess calories overwhelm mitochondrial capacity.
For people in caloric deficit—already experiencing reduced metabolic rate—this combination becomes particularly damaging.
Your metabolic rate slows down as you decrease your caloric intake, and then wham bam, you have a bunch of calories, already a problem, but you also have a bunch of fats, possibly trans fats, and carbs combined, and the cells say, “Wait a minute, we don’t know what to do with this.”
Common cheat meals—pizza, burgers with fries, pastries—often hit this trifecta: hyperpalatable, high in both fats and carbs, frequently containing trans fats.
Protein: A Surprising Solution for Fat Oxidation
Research published in Journal of Clinical Endocrinology and Metabolism offers practical intervention: replacing carbohydrates with protein increases fatty acid oxidation after meals.
Simply swapping some carbs for protein at one meal enhanced fat burning throughout the remainder of that day.
DeLauer’s recommendation: add protein shakes to meals or increase protein portions while reducing carbohydrate intake.
If you want something simple that actually works, this is one of the most effective tools I’ve used to build strength, conditioning, and endurance without needing a full gym setup.
- Full-body training with one weight using swings, squats, and presses
- Solid cast iron build that feels stable and lasts for years
- Comfortable grip that makes high-rep workouts easier to handle
Add that protein shake, add the protein along with your lunch, and that’s a huge game-changer.
Protein doesn’t create the same metabolic gridlock because it doesn’t compete with fat oxidation pathways the way carbohydrates do.
Evolutionary Context: What Nature Intended
DeLauer draws from evolutionary biology to contextualize modern eating patterns.
Ancestral humans consumed either protein-fat combinations (from animal foods) or carbohydrates independently (from wild plants, occasional honey).
Large quantities of fats combined with high carbohydrates rarely occurred naturally.
When do we ever have fats and carbohydrates really combined in nature? It’s pretty seldom.
Modern sedentary lifestyles compound this mismatch. Athletes with high energy demands may handle mixed macronutrient meals better than inactive individuals whose cellular machinery operates at lower capacity.
Context Matters: Individual Metabolic Flexibility
DeLauer emphasizes that blanket rules don’t apply universally.
If you want something simple that actually works, this is one of the most effective tools I’ve used to build strength, conditioning, and endurance without needing a full gym setup.
- Full-body training with one weight using swings, squats, and presses
- Solid cast iron build that feels stable and lasts for years
- Comfortable grip that makes high-rep workouts easier to handle
- Metabolically healthy, active individuals likely tolerate mixed meals containing both fats and carbohydrates
- Sedentary or insulin-resistant people benefit from separating fat and carbohydrate intake
- Athletes with high energy expenditure create demand that justifies mixed macronutrient consumption
The key differentiator? Metabolic flexibility—how efficiently cells switch between fuel sources.
Long-Term Cellular Damage From Chronic Energy Overload
Repeated exposure to metabolic gridlock creates cumulative damage beyond immediate fat storage.
Chronic consequences include:
- Impaired insulin signaling pathways
- Increased oxidative stress within cells
- Accumulation of toxic lipid intermediates
- Progressive decline in metabolic flexibility
There’s a long term damage that can be done if you are combining these things in high amounts consistently over time, over time, over time.
These effects compound, potentially creating self-reinforcing cycles of metabolic dysfunction.
Practical Takeaways for Better Metabolic Health
DeLauer acknowledges that most established research defaults to calories in versus calories out—scientifically sound but incomplete.
Emerging evidence suggests meal composition matters, particularly for vulnerable populations.
If you want something simple that actually works, this is one of the most effective tools I’ve used to build strength, conditioning, and endurance without needing a full gym setup.
- Full-body training with one weight using swings, squats, and presses
- Solid cast iron build that feels stable and lasts for years
- Comfortable grip that makes high-rep workouts easier to handle
Evidence-based strategies include:
- Eliminate trans fats completely, especially when insulin resistant
- Avoid combining large amounts of fats with high carbohydrates in single meals
- Increase protein intake to displace carbohydrates and enhance fat oxidation
- Consider separating fat-based meals from carbohydrate-based meals
- Prioritize natural, whole foods over hyperpalatable processed combinations
- Match macronutrient intake to activity level and metabolic health status
For those already dealing with insulin resistance, these adjustments may provide meaningful improvement beyond simple caloric restriction.
While definitive proof requires further research, current evidence suggests cellular fuel management extends beyond total energy intake—how nutrients arrive matters as much as how much.
