Original episode & show notes | Raw transcript
A common misconception in exercise physiology is the simplistic view that fat is the “aerobic” fuel and carbohydrates are the “anaerobic” fuel. While it’s true that fat is a primary energy source during low-intensity activities and rest, its utilization during higher-intensity exercise is a complex and highly regulated process. The speed at which we can access and burn fat is a critical determinant of endurance performance. This document unpacks the intricate journey of a fat molecule from storage to energy production, revealing the multiple bottlenecks that limit its use.
Before fat can be used for energy, it must be liberated from its storage form, triglycerides (also called triacylglycerols), which are found in both adipose tissue (body fat) and within muscle cells (intramuscular triglycerides).
Lipolysis: This is the process of breaking the ester bonds that link three fatty acid chains to a glycerol backbone. It is a hydrolysis reaction, meaning it requires water.
Hormone-Sensitive Lipase (HSL): This is the key enzyme that catalyzes lipolysis. As its name suggests, its activity is controlled by hormones, creating a finely tuned balance between fat storage and fat release.
The activity of HSL, and thus the rate of fat mobilization, is dictated by a balance of opposing hormonal signals:
“Go” Signals (Stimulate Lipolysis):
Catecholamines (Epinephrine & Norepinephrine): These are the “fight-or-flight” hormones released in response to stress, including the stress of exercise. The sympathetic nervous system activates the adrenal glands (sympathoadrenal activity), flooding the system with these hormones. They signal to adipose tissue that the body has an urgent metabolic demand.
Glucagon: This hormone also stimulates lipolysis in adipose tissue, though it doesn’t directly affect muscle tissue.
“Stop” Signals (Inhibit Lipolysis):
Insulin: Released in response to elevated blood glucose (e.g., after eating carbohydrates), insulin’s primary role is to promote energy storage. In adipose tissue, it stimulates glucose uptake and fat storage (lipogenesis) while actively suppressing lipolysis.
Lactate: There is some evidence to suggest that lactate may also play a role in downregulating lipolysis.
This hormonal balance explains why it takes time to ramp up fat burning. When you start exercising, your body must shift from a resting (parasympathetic) state to a stressed (sympathetic) state to trigger the release of catecholamines and initiate significant fat mobilization. A single gel during a ride won’t slam the brakes on this process, as the powerful “go” signals from intense exercise will largely override the inhibitory signal from a small amount of insulin.
Once a fatty acid is freed from glycerol, its journey to the site of energy production—the mitochondria within the muscle cell—is long and fraught with barriers. This transport process is a major rate-limiting factor.
Exit Adipose Cell: Cross the adipose cell membrane.
Cross Interstitial Space: Traverse the fluid-filled space between cells.
Enter Capillary: Cross the capillary wall to enter the bloodstream.
Travel in Blood: Circulate through the body.
Exit Capillary: Cross the capillary wall near the working muscle.
Cross Interstitial Space Again: Traverse the space to reach the muscle cell.
Enter Muscle Cell: Cross the muscle cell membrane (sarcolemma).
Enter Mitochondria: Cross both the outer and inner mitochondrial membranes.
This multi-step transport is not a simple diffusion process for the most common long-chain fatty acids (like palmitate, with 16 carbons). They are too large and require specialized protein transporters.
The podcast highlights several key studies that illustrate how training status and exercise intensity interact to determine fat use.
Mobilization vs. Utilization: A key finding is that while trained and untrained individuals may mobilize fatty acids from adipose tissue at similar rates (as measured by glycerol release), the crucial difference lies in the muscle’s ability to take up and oxidize those fats.
Intensity-Dependent Fuel Mix: The contribution of different fuel sources changes dramatically with exercise intensity.
At 25% VO2 max (low intensity): Energy comes primarily from plasma fatty acids and intramuscular triglycerides. No muscle glycogen is used.
At 65% VO2 max (moderate/endurance intensity): Initially, there’s a significant reliance on muscle glycogen (~40% of energy). As the exercise continues, the body shifts to using more plasma fatty acids (increasing from ~30% to ~50% over 2 hours), thereby sparing muscle glycogen. This is a hallmark of a well-trained endurance athlete.
At 85% VO2 max (high intensity): Fat oxidation decreases from its peak at ~65% VO2 max. The body cannot meet the rapid energy demand through the slow process of fat metabolism and must rely more heavily on the faster-burning fuel: glycogen. However, highly trained athletes still derive a significant portion of their energy from fat even at these high intensities, primarily by tapping into their intramuscular triglyceride stores, which bypass the slow blood transport step.
The host proposes a compelling theory for why increasing mitochondrial mass is such a critical adaptation for endurance athletes.
The Surface Area Hypothesis: While we know that oxygen delivery (VO2 max) is the ultimate limiter of aerobic energy production, the question remains: why does the body bother building more mitochondria? The theory suggests that the primary benefit is not necessarily to increase the maximum oxidative rate of any single mitochondrion, but to vastly increase the total surface area available for fatty acid transport.
More Toll Booths: Mitochondria are elongated, snake-like organelles. By increasing their number and size, you create significantly more surface area on which to place fatty acid transporters (like CD36). This is analogous to adding more toll booths to a highway; it doesn’t increase the speed limit, but it dramatically increases the throughput of traffic (fatty acids).
The Evidence: There is a very strong correlation (r > 0.8 or 0.9) between an individual’s VO2 max and their muscle’s mitochondrial density and oxidative capacity. This suggests that as the body’s capacity to deliver oxygen increases, the muscles adapt by building the infrastructure needed to use that oxygen to burn fuel, particularly the slow-burning, sustainable fuel: fat.
The Importance of Volume and “Low-Intensity” Training: To improve fat utilization, you must provide the right stimulus. Long, steady endurance rides (at or below LT1) are the primary driver for increasing mitochondrial density and the expression of fatty acid transporters. This is the training that tells your body it has a high, sustained energy demand and must become better at using its most abundant fuel source.
Warm-ups are Crucial: Because the fat mobilization system is slow to activate, a proper warm-up is essential, even for long races. Jumping straight into a high intensity from a cold start forces the body to rely almost exclusively on its limited glycogen stores, digging a metabolic hole that is hard to escape.
Time to Exhaustion (TTE) as a Key Metric: An increase in how long you can hold your Functional Threshold Power (FTP) is a direct indicator of improved metabolic efficiency. It shows that at a high, sustainable intensity, your body is better able to contribute energy from fat oxidation, thereby sparing precious glycogen and extending your endurance.
The Body is Never in a Steady State: Metabolism is a dynamic and constantly shifting process. The interplay between fat and carbohydrate use is complex and co-regulated. Understanding these dynamics allows for smarter training and fueling strategies.