Excess Fat Accumulation – Part 1 An Introduction

Welcome to the first installment of the excess fat accumulation series. In the next four articles (parts two, three, and four), we will be walking through another pathway of metabolic dysfunction – the pathway involving fat build-up in excess in adipose tissue. Along the way, we will see how and why this problem arises, how we can think about addressing the problem overall, and of course, specific actions we can take to address it in our own lives, today. 

When it comes to teaching about different dysfunctional metabolic pathways that regularly plague our modern society, none is more challenging than that of excess fat accumulation. The challenge comes not from the level of technical difficulty of the pathway, but rather, from its great oversimplification in how it has been taught to the public. The challenge then becomes shifting an individual’s perspective away from the overly simplified message that is calorie balance (all you need to do to lose weight is eat less and exercise more!), and towards a more complex framework that involves signals, mechanisms, and overall, an energy balance.

With this series, my hope is to help you gain a more accurate understanding of this pathway of excess fat accumulation so that you will be better equipped with information regarding how your actions may lead down this pathway, or away from it and towards a life of good health.

Now, let me be clear on what I mean when I use the word “problem” in relation to excess fat accumulation. Because here’s the thing – currently in our society, there are a whole host of feelings and beliefs surrounding the idea of being overweight, and if we want to be able to produce results, we need to stay clear of emotionally charged beliefs and get clear on why the situation is worth labeling as a problem.

With this series, our attention goes directly to the problem that is the negative health implications that accompany excess fat mass. As we will see, this includes the connection between excess fat accumulation and system-wide dysfunction including insulin resistance, chronic inflammation, hyperlipidemia, and hyperglycemia.

To get started now, let’s head to the body’s primary site of fat storage: adipose tissue.

From there, we will examine the pathways of fat accumulation, including the dysregulation of energy balance that is driving the excess accumulation of fat, along with the downstream implications for the health of the body, overall.

Along the way, my intention is to help you reframe the problem of excess fat accumulation, and with it, to help you gain a better idea of decisions you can make to help live your life in a body with a healthy balance of fat mass.

Some Background on Adipose Tissue

The primary role of adipose tissue is to store energy in the form of fat. When energy is elevated in the bloodstream (after a meal, for example), adipose tissue will take in this energy and store it. When energy is low in the bloodstream, the adipose tissue will release its stored fat in the form of fatty acids.

A couple background items to note:

Lipids are stored as triglycerides – 3 fatty acids bound together by a glycerol backbone – in adipose tissue; for the rest of this series, I will refer to stored lipid in adipose tissue simply as fat. When this energy is released back into circulation, most of it is released in the form of free fatty acids. Because lipids that enter into adipose tissue may come in different forms (free fatty acids or triglycerides), I will refer to these simply as lipids.

The movement of energy into and out of adipose tissue is controlled by signaling molecules. The primary signaling molecule of interest in this pathway is insulin, the body’s pro-energy storage hormone. Note that another signaling molecule, glucagon, does the opposite – it serves as a signal to release energy from storage; however, for simplicity sake, we will focus on insulin in this series.

Adipose tissue also has a key regulatory signal of its own: leptin. Leptin is a hormone that can be released from adipose tissue to signal its capacity. When leptin is elevated, the body hears the signal that fat stores are full. When leptin is low the body hears the signal that fat stores are low.

In response, tissues throughout the body will respond in their own way to correct for the energy imbalance. For example, the brain will hear the elevated leptin signal and decrease hunger leading to the consumption of fewer calories. Also, the mitochondria-containing tissues (muscle, for example) will hear the same elevated leptin signal and increase their rate of fatty acid oxidize to essentially burn more fats as a fuel source.

Because the body is working together as a whole system, energy balance is carefully orchestrated such that, over time, a balance of fat is maintained within adipose tissue.

Let’s walk through this balance to get a clear picture of how fat balance is achieved within the body.

Fat Balance is Maintained Over Time in Adipose Tissue

To walk through fat balance in adipose tissue, I will use a simple model that includes adipose tissue (fat storage site), blood vessels (circulation of signals and lipids), and mitochondria (site of fatty acid oxidation). Keep in mind that this is only a piece of the greater system that includes extra components (liver, muscle, etc.) along with additional forms of energy (sugars).  I will not be including glucose in this model for simplicity sake, but you can keep in mind that when insulin is present, this means that blood sugar is elevated.

Beginning with the main idea that is overall lipid balance:

Let’s break this long term balance out into what is experienced over several hours of time.

When we consume a food, energy enters into circulation along with the insulin signal that blood sugar is elevated. In response, adipose tissue takes in this energy and stores it as fat.

Later on, once the body has processed the energy from this meal and blood sugar has decreased back down to baseline, then adipose tissue is free to release this stored fat. This fat gets released into circulation in the form of free fatty acids. Once in the bloodstream, this energy can make its way to the mitochondria to be oxidized.

In this way, an overall balance is maintained.

To be more technical, a dynamic state of equilibrium is achieved within the adipose tissue. This means that the level of fat contained within will continuously increase or decrease, and yet will never veer too far from a healthy set point (a healthy mean). The body is able to achieve this thanks to feedback mechanisms that steer the system in the direction that it needs to go to stay close to this  healthy mean.

Now that we have a basic understanding of fat balance within adipose tissue, let’s ask the more interesting question of what happens when this system does not function in this way.

What happens when this system is dysfunctional?

In order to maintain this dynamic state of equilibrium, the system must have functional feedback mechanisms in place to course-correct. Recall the two primary mechanisms in place in this particular sub-system, insulin and leptin.

You can think of insulin more as a short-lived signal that varies in response to each meal. When insulin is elevated, the adipose tissue understands that it needs to store, not release, energy. In this way, throughout the day, the functioning of adipose tissue is changing dependent on insulin levels.

You can think of leptin as more of a long-term signal. It is released by the adipose tissue when adipose tissue expands, serving as the body’s primary means of signaling its long-term energy stores. If these stores start filling up, leptin is released, resulting in a lowered appetite, release of fatty acids from storage, and greater energy oxidation.

So, what happens if these signals become dysregulated? That is, what if adipose tissue loses its ability to effectively listen to these signals, and in turn, to communicate with its own signals?

We know the short answer: the build-up of excess fat.

Let’s walk through this dysregulated pathway, beginning where we left off:

This is the normal, healthy step that we saw above. Now, let’s ask a few important questions:

What happens if this temporary accumulation of fat is no longer temporary?

The answer to this is simple: if energy keeps getting diverted into adipose tissue for storage, then that adipose tissue will continue to accumulate more fat.

Another question: is this really a problem?

Better question: At what point does this become a problem? That is, at what point does the accumulation of excess fat in adipose tissue become a problem, and what exactly is that problem?

The answer is summarized as follows:

If adipose tissue is forced to keep taking in energy and storing it as fat, there is a certain point at which the adipocyte will understand that this accumulation is in excess. In turn, it will signal for help.

If you recall from our last series on metabolic flexibility, the “help” signal for the build-up of excess fat in a tissue occurs via a biochemical cascade of pro-inflammatory, pro-oxidative compounds, resulting in insulin resistance.

This is all to say, as adipose tissue keeps taking in more and more energy to store as fat, it will reach a certain point at which time it will become resistant to the insulin signal.

One more point to note here: if adipose tissue is not listening to the insulin signal to take in energy and store it as fat, then that energy must go somewehere. For now, note that it is forced to remain in circulation, which is a significant problem.

Let’s check in at this point with our knowledge of the different forms of dysregulation and dysfunction of this system:

First and foremost, we see dysregulation of the insulin signal (insulin resistance). When adipose tissue stops responding to the insulin signal, it will no longer take in energy from the bloodstream, which itself will lead to elevated blood sugar and elevated blood lipids. Moreover, adipose tissue will actually release some of its stored energy as lipid into the bloodstream because it does not understand that energy is already elevated.

The result of insulin-resistance adipose tissue is elevated blood sugar and elevated blood lipid (hyperglycemia and hyperlipidemia)

Second, if the body continues to receive energy even though adipose tissue is at capacity, this means that there must be dysregulation of hunger signaling. This includes (but is not limited to) leptin. Remember, as adipose tissue fills up with fat, it releases leptin as a signal to the brain to decrease appetite so that less energy enters the body. If adipose tissue is at capacity and yet food is still being regularly consumed, then there must be a disruption in leptin signaling and thus we can add leptin resistance to the picture.

At this point, we have achieved a state of metabolic dysfunction: adipose tissue in the form of the build-up of excess fat.

Let’s see where it takes us if we continue down this pathway.

Before we do though, if you are interested, click on the image below to follow the link to check out an important question that I touched upon: the question of how much adipose tissue expansion is too much.

How much fat is too much fat?

Downstream Implications of Adipose Tissue Dysfunction

We left off with insulin resistance arising in adipose tissue as it reaches capacity. We know that this means that:

1. Adipose tissue is not taking in energy from circulation
2. Adipose tissue is releasing lipids into a system in which energy is already elevated
3. Adipose tissue is also releasing pro-inflammatoy help signals via cytokines and lipokines.

All-in-all, we have a system composed of systemic inflammation, hyperlipidemia, hyperglycemia, elevated insulin, and insulin-resistant adipose tissue.

Now let’s add one more piece before wrapping up.

Given what we know about the body from our previous series, what happens when blood sugar continues to rise?

The answer – the pancreas releases even more insulin, which means that we can add to this dysfunctional system one more variable:

Once the pancreas is releasing extra insulin to overcome a system that is already dysfunctional, the body is in a dangerous state. The extra insulin may temporarily allow the body to overcome the hyperlipidemia and hyperglycemia (the extra insulin will force the adipose tissue to take up this excess energy). However, this will only put the adipose tissue in an even unhealthier state – as it crams in more fat, it will produce a stronger help signal in the form of more inflammation, a stronger pro-oxidative state, and ultimately, greater resistance to insulin.

Which means that the pancreas will be forced to release even more insulin to overcome this heightened resistance to insulin.

And the vicious cycle continues from their until the pancreas burns out, stops producing insulin, and the individual becomes diabetic.

To summarize, we have the following metabolic dysfunction of the entire body:

Excess Fat Accumulation Pathway Wrap-Up

We began this pathway with the excess accumulation of fat in adipose tissue, driven by the dysregulation of insulin and leptin.

We ended up with system wide metabolic dysfunction, consisting of:

1. Hyperlipidemia
2. Hyperinsulinemia & Hyperglycemia
3. Systemic Insulin Resistance
4. Pro-inflammatory state

We also ended up with a system progressing towards two obvious modern disease diagnoses:

1. As this pathway progresses, the pancreas will continue to pump out insulin until it can no longer sustain the load, at which point it will burn out, stop producing insulin, and diabetes will set in.
2. As this pathway progresses, the adipose tissue will continue to fill up with fat as obesity sets in.

Note that we also have a system progressing towards other disease diagnoses. I’ll give you an idea of two of them here:

1. The progression of atherosclerosis and cardiovascular disease is one driven by hyperlipidemia, hyperglycemia, and chronic inflammation. When the bloodstream is overly concentrated with energy and is also burdened by pro-inflammatory and pro-oxidative compounds, it is subject to damage to the arterial wall. As this damage progresses, lipids accumulate in the wall, leading to blocked passages.
2. The progression of neurological disorders also arises when the bloodstream is overly concentrated with glucose and is also burdened by pro-inflammatory and pro-oxidative compounds.

Now that we have an idea of this particular pathophysiological pathway, I am betting you have a few questions. Here are a couple of my own:

• What exactly causes the dysregulation of insulin and leptin, leading to the excess accumulation of fat in adipose tissue?
• What actions can we take to avoid (or even reverse) the progression of this pathophysiological pathway?

In the next three articles, we will continue to work through this pathway while ansering these two questions. As we do, we will dive deeper into:

1. Mechanisms underlying the progression of this pathway
2. Deeper dives into how our actions tie into this pathway
3. Discussion on how this pathway fits into the overall framework for healthy-decision making.

To wrap up for today, let’s focus our attention on what we can do, right now, to avoid this pathophysiological pathway and create a body with better health, overall.

What actions can you take right now?

Get started with the 3 Key Principles and Practices

1. Eat Real, Whole Foods
2. Move your body regularly and dynamically
3. Practice a balance of stress and rest