Note: The following is an edited and updated article based on “Energy Out,” a piece of the original series Building The Reprogrammed Systems Model. This article is part of my current (as of April 2021) project to update these models and to make them more approachable to understand and use as tools to make healthy decisions. For more on this project, check out the main page.
A healthy body is one that can properly store, release, convert, and utilize energy sources. When all these tasks are effectively orchestrated by the complex systems supporting the body, overall energy balance within the many sub-systems supporting the human body is achieved.
However, when fat accumulates in excess, as is the case for the vast majority of modern human beings, we need to be able to think critically about how to release fat from storage and to utilize it as a fuel source. Even better, we need to ensure that this thinking encompasses solutions that effectively address the underlying problems.
Before we do, it’s important to note why we care about fat accumulation. The problem is not necessarily that fat is building up (as this can be a normal and healthy situation). The problem is that energy imbalance in the form of fat build-up within various bodily sub-systems is often a key feature of poor metabolic health. As fat builds up in excess within different sub-systems (e.g. subcutaneous adipose tissue, within specific organs, around organs) it plays a significant part in driving pathophysiologic pathways.
The figure above shows just one pathophysiological pathway in which excess fat accumulation plays a significant role in driving the progression of poor metabolic health and chronic disease. What we will be thinking about in this post is how we address this excess accumulation of fat, no matter where that fat may be building up.
This means that we will be focusing on one particular pathway: lipolysis and the oxidation of fatty acids. In other words, we will focus on how we get our bodies to utilize fats as a fuel source such that the body is releasing stored fat and utilizing it as a fuel source.
Because as we know from energy balance, energy can accumulate in excess as a surplus of energy enters in the system or as too little energy leaves the system. Here, we focus on the latter by asking ourselves how to enhance the oxidation of fatty acids.
Or, more colloquially, how do we get our bodies to burn more fat?
Framing the problem: Calling upon two models of energy balance
To maintain metabolic homeostasis and good health, the body communicates via innumerable signaling mechanisms and pathways, and with this complex network, the body does a great job of taking care of its needs. Unfortunately, this signaling network has the tendency to become dysfunctional as a result of living in the modern, industrialized world.
Modern disease is, to a large extent, the product of dysregulated metabolic signaling pathways (i.e. energy dysregulation). One manifestation of this dysfunction is that excess accumulation of fat that we are focused on.
That statement is worth picking apart:
- “Modern disease is, to a large extent, the product of dysregulated metabolic signaling pathways (i.e. energy dysregulation).” That is, dysregulated metabolic signaling pathways play a key role driving the progression of poor metabolic health and modern disease.
- “One manifestation of this dysfunction is that excess accumulation of fat that we are focused on.” One example of this poor health and metabolic disease has to do with the accumulation of excess fat. Sometimes that accumulation of fat is obvious and becomes a direct problem for the individual (as is the case in obesity). Other times, though, the accumulation of fat may go unnoticed (as is the case with fatty liver) until it begins to cause other problems.
To summarize these ideas, I developed The Energy Dysregulation and Metabolic Dysfunction Model. To summarize the model: when energy follows along specific pathophysiologic pathways (e.g. excess fat accumulation and/or irregular fat storage), the body can find itself in a state of metabolic dysfunction (characterized by insulin resistance, hyperinsulinemia, hyperlipidemia, systemic inflammation) which is a strong internal signal that dysfunction is arising and that the body must take drastic action to attempt to fight off this danger. Unhealthy decisions drive these pathways of energy dysregulation and metabolic dysfunction. The goal becomes understanding these pathways so that we can avoid this behavior, and in turn, avoid these pathways of poor health and disease.
The Reprogrammed Systems Model Meets Energy Balance
The above model describes the progression of poor health and disease from an energy signaling perspective. This perspective focuses on the mechanisms of action within the body that drive pathways of health vs. disease. For example, when we consume carbohydrates, blood sugar is elevated which leads to the secretion of insulin, driving the bulk flow of energy into storage. Moreover, as fat builds up in excess, the body may become desensitized to leptin – the body’s sensor indicating how much energy has been stored away. This may lead to an inability to recognize that a surplus of fat has been stored and the continuation of eating patterns that lead to further fat storage.
This model is useful for understanding specific pathways and causal drivers of energy accumulation. It is also useful for understanding underlying problems and that which may be most useful for targeting with interventions.
To better understand the entirety of the problem, including overall energy balance within and across the human body, it is useful to pull in an extra piece of information – The First Law of Thermodynamics:
Energy Balance:
Energy In – Energy Out = Change in Internal Energy
This equation is useful to help us understand energy imbalance in the body. However, it isn’t useful on its own to tell us what needs to happen to actually address problems of energy imbalance.
However, when combined with the previous model describing causal mechanisms and pathways of energy dysregulation of metabolic dysfunction, we get a powerful model that helps us better understand the full picture.
Combining energy balance with The Reprogrammed Systems Models, we get the following, in which we can view energy balance across the entire body while still understanding that energy is tightly regulated within the body:
By examining the Reprogrammed Systems Model from an energy balance perspective, we can easily notice a few things. First, the energy that enters the system can go down three primary pathways: storage, oxidation, or conversion. (Note one other path we could consider has to do more with the structural formation of the body. For example, proteins can form muscle or various lipids can form the cell membrane; however, to keep things simpler, let’s focus on what’s most relevant to energy storage and utilization with this model).
- Storage: When we consume a meal, much of that energy is stored. Energy storage can be largely understood by understanding insulin, the body’s pro-energy storage hormone (among other functions). (Glucagon and Leptin are other useful hormones to understand)
- Conversions: Energy sources are readily modified by different organs (e.g. the liver) to shift from one energy source to another (e.g. sugars are converted into fat).
- Oxidation: The utilization of energy as a fuel source is done by breaking that molecule down and using the energy contained within it to create useable energy (ATP).
Addressing the problem:
With this expanded perspective, we gain a more thorough understanding of what really needs to happen to fully address the problem that is energy dysregulation driving an energy imbalance. What needs to happen is a shift of energy away from excess storage and instead towards oxidation. This could include:
- less energy being converted to and stored as fat
- fat being released from storage
- fat being oxidized as a fuel source (instead of glucose and other sugars)
Here, let’s focus our attention on the latter two points, including the release and oxidation of fat as a fuel source (making sure that we don’t completely ignore the first point).
One final note before diving into this pathway:
Some may argue that all we need to reach this conclusion is to think about the simple model that is energy balance. After all, fat oxidation is really just “energy out” right?
To an extent, yes, but the key here is that we must not forget the rest of the model. Energy is always flowing through these other pathways, and all these pathways are regulated by various complex systems (including the brain, the liver, other organs, and the many nerves and biomolecules that connect them all) and if we simplify the problem down to just “energy in” and “energy out” then we are bound to overlook other important pathways at play.
For example, we could make the disastrous mistake to recommend a low-fat diet to lower calorie intake while recommending that individuals simply exercise more to burn more calories without taking care to consider the details of that plan. This may lead individuals to eat far too little and exercise far too much, which could lead to temporary fat loss but is most often unhealthy for the body as a whole (plus, the weight almost always piles back on when this method is used) (see references #9).
This advice could also lead to individuals consuming a bunch of refined carbohydrate and exercising intensely for long periods of time, as is the case for far too many individuals who took this old advice from the government and food industry.
The result of these behaviors can lead to:
- blood sugar spiking, blood sugar depletion –> rapid blood sugar spiking
- chronic patterns of elevated blood sugar –> a chronic elevated insulin signal (which means a chronic pro-energy storage signal)
Neither of these is going to leave the individual feeling healthy nor help them achieve the goal that is losing weight.
This is why it is so important to keep energy signaling in mind while we also pull in energy balance.
Both models have their uses, and when tied together we can make much more powerful decisions.
Fatty acid oxidation as part of a healthy body
Now that we understand that we can’t just focus on simply burning more calories to burn more fat, let’s take a closer look at this fatty oxidation mechanism and the pathways involved.
To get started, let’s draw our attention to the fact that there are multiple pathways involved in fatty acid oxidation. That is, utilizing energy is more than just exercise. Energy is required for all functioning, including:
- Sleep
- Movement
- Cognitive Processes
- Metabolic Processes
Also, keep in mind that when we want to burn energy to address the excess energy accumulation problem, what we really mean is that we want to burn fat. Being more technical here, this means we want to oxidize fatty acids: it is the oxidation of fatty acids that results in fat leaving the body.
When the mitochondria oxidize fuel for energy production, the molecule that is formed for use as energy by the body is ATP. A number of metabolites are also formed in the process, which will become relevant soon.
The bulk of ATP synthesis, particularly speaking of fat oxidation, occurs at the site of the mitochondria.
As always, remember that this is not a simple, passive process. There are an incredible number of regulatory mechanisms involved fatty acid metabolism, including the process of getting fatty acids into a cell, processed, and then sent into the mitochondria.
Remember back to a particularly useful diagram – when energy enters the body it can go in any number of directions.
If we want to lose weight by burning a large amount of fat, then we need to ensure that this system is programmed for these particular pathways:
- Fat storage –> oxidation
- Stored fat must be released, sent to mitochondria, and oxidized
- Proper glucose <–> glycogen conversion and usage
- glucose (the free form) and glycogen (the stored form) must be converted and used wisely. This form of energy is important for the body, but its overuse is the very thing we are aiming to avoid.
This means that it is not necessarily true that we need to burn off a whole bunch of energy (the calorie centered approach). Rather it means that we need to get the body programmed to send stored fat towards oxidation, while sparing energy from other forms (e.g. glycogen, muscle, and other tissues).
How is this done? How do we get the body to direct the food we consume to avoid fat storage, and also to allow the fat stored in the body to go towards oxidation?
Step 1: Think About Energy Signaling
Note, the rest of this article addresses fatty acid oxidation advice from an energy signaling perspective. It comes from the original piece that was my initial thoughts on addressing this challenge. I’ve left it here for you if you care to keep reading. The updated and simplified version lives within the membership program. If you do continue reading, please note that this is just one piece of an overall weight-loss strategy that you could consider thinking about as you make your own health-conscious decisions.
First, we need to keep in mind key signals that drive the bulk flow of energy within the body. You may remember that there is one particular signal that halts the flow of energy (more specifically, of fat) from going into the cell and into the mitochondria to be oxidized.
That signal is none other than insulin. When insulin is elevated, the cell becomes unable to burn fat for fuel. This means that, if an individual is trying to burn fat (as any healthy individual needs to do), then they will have a much more difficult time doing so when there is a strong insulin signal.
I cannot stress enough the role that insulin has to play in energy dysregulation and metabolic dysfunction. As the body’s primary energy storage hormone, its excess and irregular secretion, brought on by an industrial foods based diet, is arguably the most significant factor driving modern disease.
However, insulin is not the only important signal involved in this system. To get an even better understanding of how the body handles energy storage and oxidation, let me bring in the new hormone signal: glucagon.
You can think of glucagon, quite simply, as your energy release hormone. While insulin signals to cells to store energy, glucagon signals to cells to release energy into circulation so that it can be utilized for ATP synthesis. As the goal is to release large amounts of fat from storage, we need to make sure that glucagon is on our side.
We already know how to avoid the excessive and irregular release of insulin: Refined foods and high carbohydrate meals spike blood sugar, resulting in a spike in insulin. By avoiding these foods and instead consuming real, whole foods – foods that are high in fat and contain adequate amounts of protein – we can minimize the release of insulin.
The good news is that the same guidelines can, for the most part, be followed for glucagon secretion. Remember, if we want to release lots of fat for oxidation, glucagon needs to be elevated. This means that chronic inhibition of glucagon should be avoided.
To keep things simple, you can think about how your diet influences glucagon as macronutrient-based: Diets high in carbohydrate tend to result in inhibited glucagon secretion, while diets higher in fat and protein tend to elevate glucagon levels.
Overall, quite simply, you can think about the lowering of glucagon and elevation of insulin as driven by high carbohydrate meals. If you consume a high carbohydrate meal, insulin becomes elevated while glucagon release is inhibited, resulting in a high insulin to glucagon ratio, putting the body in fat storage mode. By consuming a lower amount of carbohydrate while consuming more fat and protein, the resulting low insulin-to-glucagon ratio allows for fat burning.
Be careful though, as it is not just the type of macronutrient that matters – quality is just as important. Consuming a load of plant-based foods that are high in fiber, polyphenols, and other nutrients will likely end up contributing to a better ratio. Consuming refined foods, even refined protein, is a sure way to send these hormones in the wrong direction, sending you down the road to fat storage and halted fat oxidation.
Although this is not so relevant to insulin and glucagon, the avoidance of refined fats, particularly refined polyunsaturated fat (i.e. vegetable oils), is also of utmost importance, albeit for different reasons. I bring this up here because it is common for people to hear the message to avoid processed carbohydrate, and to fill that void with refined fat. This is not a healthy way to do this. Consuming large quantities of refined vegetable oils may not set off insulin, but it will send you down other pathways towards poor health, which is missing the entire point.
Note – glucagon is incredibly interesting and relevant, but it doesn’t get the attention it deserves. I recommend checking out Dr. Ben Bikman, particularly his lectures on the topic of insulin:glucagon ratios.
The Finishing Touch: Signaling in the Mitochondria
To finish things up, we have one more concept to understand. We now know how the foods we consume can lead to halted fat oxidation through the direct flow of energy, but now we have to understand how things are operating from a functional point of view. To do so, we need to understand signaling at the site of fat oxidation.
To take energy as we know it (as carbohydrate, fat, or protein), and then to convert it into ATP, the body has to go through many steps. That energy must be digested, sent around the body, potentially stored or converted to other forms, and then finally sent to the cell for oxidation. The final step in this process is completed with the help of an incredible biological machine: the mitochondria.
The mitochondrion is no simple machine. It continuously senses the energetic state of the cell, using this information to decide what to do with the energy it receives. That energy can come in a number of forms and is dealt with in a different manner depending on the form of energy, the energetic state, and the state of the machinery itself.
To put things into perspective, I want us to first think about the scale of the system we are discussing. There are hundreds of trillions of mitochondria in each human body. A cell can contain thousands of these little machines, which are continuously processing ATP. For reference, a common statistic tossed around is that the body produces its own weight in ATP every day.
In terms of what the mitochondria is actually processing – it is taking molecules consisting of several atoms and stripping away individual atoms (e.g. the removal /addition of hydrogen). Thus, when I speak of micro signals here, we are literally discussing atomic, or even subatomic processes.
Be careful here though – don’t be fooled by the microscopic size of this system, as its dysfunction has consequences that accumulate, feedforward, and emerge as dysfunction at the macroscopic, life-altering level.
Getting into these signals now, let us focus on what is arguably the most significant signal in this system: ROS, which stands for reactive oxidative species. As the mitochondria processes energy for ATP synthesis, electrons are passed down a chain of complexes embedded in the mitochondrial membrane (i.e. the electron transport chain). Each of these electrons is, ideally, destined for an oxygen molecule(which produces water). Of course, this process is not always perfect, which means that sometimes this process is incomplete, leaving an oxygen radical free to leave the complex with the potential to become a reactive oxygen species.
Mitochondria work as a balanced system. As they oxidize energy, oxygen species are naturally created. This isn’t inherently a bad thing because, as nature is designed, there are systems in place to balance the formation of these oxygen species. It is the job of antioxidants to gather up these free radicals before they can go on to cause trouble.
However, when a shift in this balance occurs (i.e. too many oxygen species and too few antioxidants), then the system becomes overloaded with oxygen species, putting the cell in a dangerous situation.
ROS tend to get a bad rep, as their presence tends to result in damage and/or dysfunction. For example, ROS are present at the scene of the crime for most pathophysiologic metabolic conditions (e.g. insulin resistance). However, I don’t like to judge ROS as an inherently bad thing – something that needs to be minimized as much as possible. Instead, I see ROS simply as a signaling mechanism – a signal that alerts the body that a potential problem has arisen and that it needs to respond. For example, the elevation of ROS can alert the cell that a mitochondrion is losing its ability to properly function and that it should be killed off (mitophagy) so that a new, healthy mitochondrion can take its place.
Overall, I will argue that ROS production is a beneficial signal because it alerts the cell that a response is needed to help the distressed mitochondria. Unfortunately, as is the case with many signals arising from a body living in an industrialized world, this signal is dealt with in a manner that can lead to further damage.
The elevation of ROS is a signal that the mitochondrion is in distress, and that the cell needs to do something. The responses to this misbalance are far and wide, but most significantly for this discussion is the resulting insulin resistance. ROS can form because too much glucose is being pushed through the mitochondria. The body responds, logically, by becoming insulin resistant, thus disallowing glucose to enter the mitochondria.
As we all know, insulin resistance is a primary condition driving metabolic dysfunction and modern disease. When cells lose the ability to respond to glucose, yet the body continues to receive large amounts of glucose, the system is on a clear path toward disease.
Also, note that this is a major site of cancer-based research – the inability to properly oxidize energy is tightly linked to cancer overall – see metabolic theory of cancer. Dr. Thomas Seyfried is a great source.
To counteract this dangerous phenomenon, it is not that ROS production needs to be shut down. Shutting down ROS production may help mitigate problems downstream, but it does not necessarily address the larger issue – that issue being the cell’s mitochondria in distress. Rather, the system needs to be put back into a healthy balance, as a healthy balance is a sign that the machinery is working properly and dealing with a healthy load of energy.
Based off of this logic, let us move forward with the Reprogrammed approach by focusing on simple, practical options that you have to better program your body for optimal mitochondrial functioning.
Reprogram your Body for Optimal Mitochondrial Functioning
Overall, it helps to think about the mitochondria found in the typical modern day body as under an incredible load. They work all day every day to handle the absurd load put on them by the incredible amount of energy sent through their ATP production lines. On top of this, these mitochondria are withdrawn from the proper resources they need, including the antioxidants naturally found in real food. Finally, to make matters worse, they are regularly exposed to dangerous toxins – foreign molecules that interfere with their ability to properly function.
To address the burden and distress the mitochondria, I suggest starting with the following:
- Stop consuming refined foods, particularly in the form of refined carbohydrates
- A high carbohydrate or refined foods based meal sends an overload of energy to the cell, putting the mitochondria in overdrive. Give the mitochondria a break by consuming real, whole foods – foods that release energy in a controlled fashion, a manner in which cells are designed to oxidize fuels.
- Give the mitochondria a break by eating less frequently
- Remember that point I made about ROS being a signal that the mitochondria need help. Remember the additional point I made about this signal becoming detrimental in today’s industrial food-based society. Here’s a problem: Mitochondria become overstressed due to the load put on them by an industrial foods based diet. However, when they try to signal for help (via ROS production), the cell is unable to help them out because the cell is under a constant load of incoming energy.
Instead of overloading your cells and mitochondria with a load of energy all day every day, allow them some time to take care of themselves by stopping the constant inflow of food.
Reprogramming your mitochondria for optimal fat oxidation begins with eating real, whole food – food consumed in 2 or 3 substantial meals. Preferably, these meals are consumed in a window of 10-12 hours or less. By consuming your food in 2-3 meals all within a 10-12 hour window, you give your cells and the mitochondria contained within the downtime they need to assess and respond to their own needs (note: see autophagy or mitophagy for more on this concept).