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Week 1 – Lipid Overflow

Given societal norms of the past several decades, most of us have come to view fat from a negative perspective. When consumed as a source of food, we tend to try to minimize it. When seen on our body, we tend to want to get rid of it.

This is unfortunate, as consuming fatty foods provides the body with energy while also delivering important nutrients – both of which the body needs to function properly. Moreover, the body stores energy as fat so that it can function at any time of day, regardless of whether food has recently been consumed, and thus fat serves an important role as a long term source of energy.

And yet, this prejudice against fat doesn’t stem from nothing. It arose due to the link between carrying excess fat and experiencing health problems and the link between consuming fatty foods and experiencing health problems.

The bottom line is that fat provides an efficient form of energy for the body to take in, ship around, store, and utilize. However, somewhere along the line – whether it be in the form we eat it or the internal state of the body – fat can become problematic.

Clearly, there is something at work that leads from fat playing the role of the hero to playing the role of the villain. What exactly these factors are needs to be clarified so that we are equipped to make the healthiest decisions possible.

With this post, I will aim to address the following: What exactly are the factors that change fat from a healthy, necessary part of the body’s functioning, to an unhealthy, dangerous burden on the body, and what actions can we take to do something about it?

Moreover, I aim to help each of us understand how our beliefs surrounding fat play a role in the decisions we make, and to reconsider whether the actions we have been making are aligned with healthy pathways, or are leading us down a road of dysregulation, dysfunction, and potentially even disease.

To answer these questions of what is disrupting healthy fat metabolism, and more importantly, to understand the actions we can take to deal with it, we will dig into fat regulation and homeostasis. This includes some of the mechanisms and pathways by which fats are managed, including how these pathways can go from being healthy to unhealthy.

Before we continue, I want to clarify the language used for a specific term. So far, I have been using the term “fat,” as this will be the term most familiar to you. However, there are better ways to classify the relevant molecules that will become important as we walk through this pathway.

A better term to use is “lipid,” which describes an entire class of biomolecules. “Fat” as a term is useful to describe the way in which lipids are consumed or stored on the body. When discussing the flow of lipids in the body, “fat” becomes less accurate, and “lipids” is more appropriate. We can get more specific as to the type of lipids, however, for the purpose of today’s article, I will stick with “lipid,” and as “fat” as the form in which lipids are consumed and stored.

While we are on the topic of terminology, I will make one more important distinction: lipids are one primary form of energy-containing molecule, and sugars are another. Sugars and carbohydrate are interchangeable terms and come in simple and complex forms. The primary simple sugars that we consume are glucose and fructose, although for the purposes of today’s article, we can consider all sugars as having the same property relevant to the discussion below.*

Lipid homeostasis

The ability to effectively regulate energy is a key characteristic of a healthy body. When the body receives incoming energy (as is the case when the individual consumes food), that energy must get to where it is needed most, with any excess stored for later use. If the body is incapable of performing this function, then it is at risk – either from systems that are unable to receive the energy they need or from systems receiving too much energy (which can become acutely toxic).

Figure 1: As food makes its way through the digestive tract and into the bloodstream, it is broken down into two primary classes of energy-containing biomolecules: lipids and sugars. From the bloodstream, both forms of energy can be stored, utilized as a fuel source, or converted from one form to another. Energy can be stored as fat in the adipose tissue or as glycogen in the muscle or liver. The mitochondria can use either source of energy to synthesize ATP (the body’s useable form og energy); however, it can only use one form of energy at a time, and will use sugars first before using lipids.

Figure 1 is a simplified diagram of this energy regulation. When food enters the bloodstream via the digestive tract, this energy can go directly to:

1. The mitochondria to be used as a fuel source for oxidation

2. To storage as glycogen in the muscle or liver

3. To storage as fat in the adipose tissue

Alternatively, this energy may be converted to a different form, from which it can be stored or utilized. For example, ingested sugars or protein may be converted to fat for storage, or alternatively, ingested fat or protein may be converted to sugars.

What the body does with each meal depends entirely on a complex system of signals, which are in turn dependent on the state of the body.

Keep in mind that our goal is to determine what it is that turns fat from being a healthy part of a well-functioning body to an unhealthy part of a poorly functioning body on its way to a modern disease diagnosis. To answer this question, we need to first understand how a healthy body functions in regard to lipid homeostasis.

As we move forward, I will be simplifying the diagram to focus on lipid homeostasis. As we go through these, remember that lipids are not the only source of energy that the body is managing at the same time. Sugars are still present and still play an important role, but for now we’ll put our focus on lipids, tying in sugar later on.

Under normal physiologic conditions, lipids are free to be sent into storage, released from storage, or oxidized by the mitochondria. This flow is going to be driven primarily by energetic supply and demand throughout the body.

Figure 2: At baseline, lipids are free to be released into circulation and oxidized as an energy source in the mitochondria

When this system receives a very special signal (insulin), lipids are ushered from the bloodstream into storage, they are no longer released from storage, and they are no longer oxidized by the mitochondria.

Figure 3: The elevation of insulin puts the body into fat storage mode, wherein fat is tucked away into storage in adipose tissue, and fat oxidation is halted in the mitochondria

Finally, when the insulin signal returns to baseline, those stored lipids can be released into circulation and oxidized by the mitochondria as a fuel source.

Figure 4: As insulin levels return to baseline, the fat that had been stored is free to be released into circulation and to be oxidized as a fuel source in the mitochondria

In this way, an overall balance is achieved, as fat that had been stored during times of feeding is able to be released and utilized.

I want you to note a few key ideas away from this very simple walkthrough of lipid homeostasis:

First, fat storage is an incredibly important part of this healthy, balanced system. Without the ability to store fat, the body would have to continuously take in food. Now, I love eating as much as everyone else, but to eat all day every day – well, I’m thankful that we adapted this system so that I could spend part of my day doing other activities (sleeping, for one).

Second, the insulin signal not only shuttles fat into storage, but it also halts the release and oxidation of fat. This means that, when insulin is elevated, the body can’t be burning fat as a fuel source.**

I also want you to bring to your attention, once again, the simplification of this process that I have performed. Remember, the actual system involves a number of components, and the energy available to the system is not only in the form of lipids. So, keep in mind that the system looks closer to the following, although even this expanded figure is greatly simplified.

Figure 5: When food is consumed, glucose and lipids enter circulation. This results in elevated blood sugar, which signals to the pancreas to release insulin. When insulin is elevated, energy (both lipids and sugars) are stored as fat in adipose tissue; glucose is utilized as a fuel source in the mitochondria; lipids are not oxidized as a fuel source in the mitochondria; sugars are stored as glycogen in muscle and liver; and the liver packages all forms of energy (both lipids and sugars) as lipids to be sent back into circulation.

We will move forward using the simplified version of the model to help understand this one specific pathway, keeping in mind the part it plays in a complex system.

Lipid Dysregulation

Now that we understand a simple walkthrough of lipid homeostasis, we can move on to undertsanding our primary question: What is it that takes this healthy system and changes it to one that is unhealthy – that is, one that has become dysregulated, becomes dysfunctional, and is on the path to modern disease.

To get to the answer, I will pose a simple question: What happens if that insulin signal does not turn off? More precisely, what happens if insulin is secreted too much and too often?

Figure 6: The elevation of insulin puts the body into fat storage mode, wherein fat is tucked away into storage in adipose tissue, and fat oxidation is halted in the mitochondria.

Remember, the elevation of insulin and the storage of fat shown in Figure 6 is healthy. However, what happens if, instead of turning off and allowing fat to be released and oxidized, that insulin signal stays on? Moreover, what if this insulin signal is stronger than the body has been designed to manage?

Figure 7: If the signal to keep storing energy as fat gets louder, and if it does not turn off, then energy is going to keep getting forced into storage, it is not going to be able to be released, and it is not going to be oxidized as a fuel source.

The result is that fat is going to continue to build up in adipose tissue. Then, at some point, the adipose tissue is going to reach capacity, at which point it is going to stop taking in energy and it is going to begin releasing energy.

There is a mechanism by which the adipose does this, and it is, quite simply, to the diminished ability to listen to the insulin signal: insulin resistance.

Figure 8: As adipose tissue reaches capacity, the ability to respond to the insulin signal will diminish. This allows the adipose tissue to stop taking in energy and to begin to release some stored energy.

Note something important here – becoming insulin resistant is a protective mechanism for the adipose tissue. As an adipocyte (an individual cell in the adipose tissue) fills up, this cell is in danger. Adipocytes are only designed to be able to store so much fat, and at some point it has to be able to do something to help itself. The answer that nature has provided*** is the ability to stop listening to insulin so that it can stop taking in more lipid and release some of its load.

However, this becomes a problem for the body as a whole. If lipids aren’t being stored away safely in the adipose tissue, then where does this excess energy have to go?

The anwser – that excess lipid will go out into the bloodstream, resulting in hyperlipidemia (elevated lipid in the bloodstream). Since the body understands*** that hyperlipidemia is dangerous, it responds by dealing with that lipid the only way that it can – by having other orgparts of the body take in that excess lipid.

Unfortunately, these other areas of the body (e.g. the liver and muscle) were not designed to take in this heavy load of lipid. Moreover, these parts of the body, themselves, are already under a heavy burden, as they too are having to deal with the hyperinsulinemia (the elevated insulin signal).

So, what do they do? As we saw with adipose tissue, the answer that nature delivered is insulin resistance:

Figure 9: In the presence of hyperinsulinemia, which can arise as a result of insulin resistant adipose tissue, this excess load of lipid gets placed on other areas of the body including the liver, pancreas, and muscle. In the presence of the insulin signal, the response of these tissues is to become insulin-resistant themselves. In this way, systemic insulin resistance arises via lipid overflow.

In this way, excessive isulin secretion leads to lipid overflow and hyperlipidemia, and ultimately, systemic insulin resistance.

Figure 10: The excessive secretion of insulin leads to the excessive accumulation of fat. As this energy dysregulation occurs over time, the accumulated fat spills over into the bloodstream. Note that this is accompanied by a pro-inflammatory signal. The result is a systemic state of inflammation and hyperlipidemia, which together drive metabolic dysfunction.

This is one primary pathway by which tissues throughout the body become insulin resistant. By elevating insulin too much too often, the body is sent down a path to inflammation, hyperlipidemia, hyperinsulinemia, and systemic insulin resistance.

This state is considered metabolic dysfunction, as the ability to maintain a metabolic balance has been lost. From here, the body is primed for the progression to a modern disease diagnosis, as the inability to regulate energy levels in systems throughout the body results in these systems receiving both high and low levels of sugar and lipids. For example, in the bloodstream, elevated sugar and lipids present a danger of causing damage to the arterial wall, the build-up of plaque in that damaged wall, and the unstable plaque formation – that is, in the bloodstream, elevated sugar and lipids drive atherosclerosis and the progression of cardiovascular disease. If we look at the brain, pancreas, or other organs, we can follow similar pathways to Alzheimer’s disease and dementia, Diabetes, and cancer.

I want you to sit with this idea for a moment, combined with this startling publication:

https://jamanetwork.com/journals/jama/fullarticle/2434682

In a 2011-2012 population, the prevalence of pre-diabetes (systemic insulin resistance) was found to be 38.0% (95% CI, 34.7%-41.3%). Estimates for today (8 years later) have been calculated to be closer to 50%.

That means that nearly 35-50% of the population are dealing with insulin resistance, which is well-established to be the first step on the way to cardiovascular disease, diabetes, Alzheimers disease, some cancers, and other modern diseases.

Fortunately, this lipid overflow pathway is completely preventable by taking the time to make some simple changes to your life.

Room for Intervention

Now that we understand a primary pathway by which hyperlipidemia and systemic insulin resistance arises, we can begin to ask ourselves what we can do about it.

As we now understand that the excessive secretion of insulin drives this entire pathway internally (in the body), we can begin forming an intervention with a basic question: What drives the elevation of insulin externally (from outside of the body)?

Stated slightly differently, now that we understand a primary driver of energy dysregulation inside the body, we can look to how our decions may drive this pathway.

Figure 11: The Reprogrammed Systems Model helps us frame how our decisions (environmental inputs) drive pathways inside the body that can progress towards metabolic dysfunction and, ultimately, manifest as a modern disease diagnosis. Focusing in on how these inputs tie directly into energy dysregulation and metabolic dysfunction, we can envision how we may best make decisions for optimal health.

Fortunately, anwering this question is easy.

If the excessive secretion of insulin is the primary internal driver of energy dysregulation and downstream dysfunction, then the primary external driver of this pathway would be whatever causes the body to release insulin in this unhealthy fashion.

Since insulin is elevated in response to elevated blood sugar, then the answer is anything that excessively elevates blood sugar drives this pathway.

So, what results in the digestice tract dumping sugar into the bloodstream? Again, the answer is simple: the consumption of industrially processed carbohydrates.

Re-evaluating beliefs

At this point in the walkthrough, it is simple to see how we have the ability to intervene in our lives so that we can make decisions that do not lead us down this unhealthy path of lipid overflow.

However, I’m going to take this one step further, because if we are going to take anything away from this pathway and put it to good use, we need to go deeper than just a conceptual understanding.

Look, we’ve all been told for years that we should avoid refined foods. We all know that whole foods are better for us and that we should stay away from the processed junk. And yet, we don’t.

Although we are told over and over again to avoid refined foods in the name of whole foods, we don’t. Although we are told over and over again to avoid processed sugars and high glycemic foods, this problem has never been more prevalent in the population.

My question is why? Why can we not get ourselves, as a population, to make the decision to stop eating insustrial not-so-foods that dump sugar into the bloodstream, all day every day, causing a chronic “on” signal for insulin, and driving the pathway discussed above?

Now, we don’t have time to get to the bottom of this question today, but we do have a few moments to look inward and ask some simple questions.

First, based on our conceptual understanding of this pathway, what can we do to aim for good health over this dysfunction?

Quite simply, we can avoid industrial not-so-foods and instead base our diets on real, whole foods.

Digging deeper, we can ask ourselves why we haven’t been doing this all along, because, let’s be honest, it’s the advice that I’ve been hearing my entire life, and I’m sure you’ve been hearing much of the same.

So, why have we gone through life allowing ourselves to consume refined foods?

Let me take a guess at two of the common answers:

1. There has been a misunderstanding of what it means to consume unhealthy (industrially refined not-so-) foods

This answer is understandable, and honestly, is the primary reason I spent the time to take you through this pathway. The common guidelines for consuming healthy foods are often misleading, resulting in the consumption of insulin-spiking foods, even when we believe we are making the healthy choice.

Can you think of any of these? I’ll name a few:

  • Foods labeled with “whole grain” – even though that carbohydrate has been refined down into easily digestible sugars that are quickly released into the bloodstream
  • Foods labeled as “heart healthy” – which really is just a way of saying low-fat high-carb, and very often are primarily made of refined carbohydrates and/or refined protein, both of which spike insulin
  • Foods labeled as low-fat, aiming to elicit a fear of high cholesterol – but really, are just refined forms of carbohydrate and refined protein

To those who fall under the category of aiming to eat healthy, and yet failing becuase of misguided information, I ask you to look internally with this question:

What nutritional beliefs have been guiding you to choose insulin-spiking foods in the name of being healthy? Is it a fear of fatty foods? Or maybe a mis-understood belief in what “whole foods” are?

If this (or similar answers) are the case, I ask you to consider what we went through with the lipid overflow pathway – and to re-evaluate what it really is that makes fat unhealthy.

Is it really the ingestion of fat?

Is it really the temporary storage of fat?

Or is it seemingly unrelated properties of food that lead downstream to lipids playing a dangerous role?

If this is you, I hope that this walkthrough has given you some greater insight into what it means to make the healthy decision.

For more on this topic, check out this article on healthy decision-making, and I hope you continue along in the following weeks as we go through additional pathways.

2. You are holding onto beliefs that allow you to rationalize the consumption of refined foods, even though you know that there are healthier options:

  • I am too busy to regularly prepare meals, so it’s okay if I pick up fast food on the way home, microwave meals.
  • I like the taste of these foods, and I ___ so I deserve to enjoy them
  • I’m young / I have a healthy metabolism, so I can get away with eating these foods
  • I know these foods are bad for me, but I’m never going to actually develop  (fill in the blank); besides, if I do, I’ll just go to the doctor and he/she will fix me.

If this is you, I’m not here to tell you that these beliefs – these stories – are wrong and that you aren’t justified in continuing to make the choices you do. It’s your life, and if you’re working two jobs and shuttling kids around and you feel like you have to skip the real, whole foods, then that’s your decision.

But what I can tell you is this:

Metabolic dysfunction is now the norm in today’s society. The common path through life is to lose the ability to regulate and balance energy levels, suffer from metabolic dysfunction, and eventually to receive multiple modern disease diagnoses and begin playing the game of the modern healthcare system.

I can also tell you that it is the consumption of refined foods that drive this progression. More specifically:

  • It is the consumption of refined carbohydrate that spikes insulin, driving energy into fat storage
  • It is the consumption of concentrated forms of fat that have been added to this food that add an extra burden of lipid into a storage-directed system
  • It is the regular consumption of industrial not-so-foods that turns the temporary storage of energy into a chronic “on” signal for fat storage, leading to lipid overflow and the downstream dysfunction

And, I can also tell you that, given all of this, you have the ability to avoid these foods, if only you make it a priority in your life.

It’s your choice, and I can only hope that you choose wisely.

 

Notes:

*Although different simple sugars have different properties, the sugars that we most often consume all have a glucose component, and therefore all stimulate the secretion of insulin.

** In the name of being completely accurate, I should clarify this point as it is not necessarily true. There are exceptions to the rule – the mitochondria can oxidize lipids as a fuel source in the presence of glucose/insulin; however, for the relevance to this discussion – that being the ability to efficiently oxidize the volume of lipids necessary to maintain a balance throughout the day – the mitochondria cannot maintain its normal oxidation of lipids when glucose/insulin is present. When glucose is present, it gets priority from the mitochondria, which means that lipids cannot be effectively oxidized.

*** The body has been designed to respond in specific ways (via specific mechanisms) in response to specific conditions. For example, when blood sugar elevates, the body understands that insulin must be released. A second example – when both sugar and fat are elevated, the mitochondria understands that it oxidized sugar first and does not oxidize fatty acids. How does the body understand what to do? Because selective pressures of the past led to the passing on of genes that manifested as mechanisms that made the body act in this way

References:

Click here for more on adipose tissue and insulin resistance from the literature.

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