From Hibernation to Obesity: The Seed Oil Connection

Is there a hidden link between PUFAs, hibernation, and the alarming obesity rates?

Prepare to be astounded as we uncover a fascinating connection that sheds light on why our bodies might be chronically preparing for a period of starvation that never arrives.

In this post, we’ll go over my thesis, that if true should cause a complete paradigm shift in the way we view obesity and how we should tackle the obesity epidemic.

While preparing for hibernation mammals become obese and insulin resistant.

During hibernation, they lose weight and once again become insulin sensitive.

In obese humans, it seems as if we a chronically stuck preparing for a period of starvation (hibernation) that never comes.

So, why haven’t we looked at hibernating mammals when trying to solve our weight issues?

Today is the day.

We’ll take a look at how increased consumption of PUFAs (seed oils) drives:

1. Decreased metabolism (calories going out)

2. Increased appetite (calories coming in)

3. Fat storage (where the calories go)

Mammalian hibernation & human obesity

Across mammals, many species undergo hibernation even some primates. The mechanism for triggering hibernation might thus be conserved in all mammals, including humans.

During the preparatory phase, mammals become obese and insulin resistant.

In hibernating mammals, the weight gain is way faster than in humans.

A grizzly bear will double its body weight in just a couple of months, gaining up to 1,5 kg per day.

What allows this to happen, physiologically, might not be so different from what is seen in obese humans.

But, the function of this in hibernating mammals is clear, it is to survive periods of starvation.

In humans, the function of obesity remains unknown.

Let’s look at the similarities.

Both humans and hibernating mammals:

• Overeat

• Has increased fat storage

• Has lowered metabolism

• Has impaired insulin function

• Develop systemic insulin resistance

  • In mammals, it reverses during hibernation

  • In humans, it remains chronic

What is the link between the two models?

The common denominator is increased dietary consumption of polyunsaturated fatty acids (PUFAs).

In every single hibernating mammalian species ever studied, they increase their consumption of PUFAs during the preparatory phase.

It seems to be important for entering hibernation and the length of hibernation.

In the US, from 1959 to 2008 the percentage of linoleic acid (LA), an omega-6 PUFA, in fat tissue increased from 9.1% to 21.5%.

While comparing overweight, obese and morbidly obese Korean women Choi & Jim (2017) found that the ratio between omega-6 to omega-3 fatty acids increases for every categorical increase in BMI.

This suggests PUFAs, and particularly omega-6 LA, could be important in inducing obesity.

Insulin, fat tissue & obesity

Before we dive in we need an understanding of what insulin is and how it links to obesity.

We also need to understand the basics of fat tissue and insulin resistance more broadly.

Insulin is a hormone involved in:

• Glucose regulation

• Increasing glucose uptake & glycogen synthesis (the storage form of glucose)

• Fat metabolism

• Inhibiting the breakdown of fat

Fat tissue is a fuel storage tissue and an endocrine (hormone) organ important in metabolism.

More specifically, it regulates fat metabolism, sugar metabolism, and appetite.

Insulin resistance is a whole-body desensitization to insulin.

• It negatively affects metabolism

• And is implicated in multiple disease states

Obesity-induced insulin resistance is a theory which suggests that insulin resistance begins in the fat tissue.

It goes something like this.

Chronic fat storage causes fat cells to become overfull.

Once this happens the fat cell has reached its storage capacity or fat threshold.

This then causes the fat cell to become dysfunctional driving insulin resistance in the entire body (more on that later).

We have three key takeaways so far.

1. The physiology in both hibernating mammals and obese humans is very similar.

2. Consumption of PUFAs is increased in both hibernating mammals and obese humans.

3. Hibernating mammals and obese humans develop systemic insulin resistance that seems to start at the level of fat tissue.

The question to answer becomes:

Is the increase in PUFAs in the Western diet one of the driving factors behind obesity through a similar mechanism seen in hibernating mammals?

The main idea – how PUFAs drive obesity

Increased PUFA consumption disrupts normal physiology at three main levels.

1. Insulin signalling

2. Metabolism

3. Appetite

Taking this one step further,

1. PUFAs dysregulate insulin signalling driving fat gain.

2. PUFAs lower metabolism driving fat gain.

3. PUFAs increase appetite driving fat gain.

This is what I want you to understand when we are done today.

PUFAs – calories in and calories out

Now let’s look at how this happens, starting with appetite and metabolism.

The main aspect of obesity we are all aware of is fat gain.

Looking at the calorie equation we know that fat gain is the same as a calorie surplus.

This can happen by:

• Either an increase in calories coming in

• A decrease in calories going out

• Or both, simultaneously

Remember, overeating is seen in both models.

Looking at this graph and you’ll realize that physiology is quite complex.

I won’t bore you with the details but will give you an overview I think you can understand.

PUFAs directly affect the fat tissue master regulator (PPAR-Y).

It regulates fat storage and glucose metabolism and has multiple downstream effects.

The fat tissue master regulator has two main downstream effects that drive increased appetite.

• It increases the activity of the endocannabinoid system driving an increase in appetite. (This is the same system that causes the munchies when smoking weed.)

• It also inhibits a hormone that decreases appetite. (This causes a decrease in appetite suppression = increased appetite).

The downstream effects also affect energy production, the calories out part of the equation (Look at the grey part of the graph).

PUFAs indirectly cause a decrease in metabolism.

Looking back at the calorie equation, we have now created a perfect metabolic state to allow fat gain to take place.

PUFAs downstream effects increase calories coming in, and calories going out – shifting the balance toward a calorie surplus.

Now over to insulin’s role in all of this.

Pathological Insulin Resistance vs. Physiological Insulin Resistance

This is the fun part. Where most researchers and scientists get it wrong (in my humble opinion).

Insulin sensitivity and insulin resistance are not fixed states as most people assume.

You can think of insulin signalling as a cell’s way of telling the body that it is hungry or full.

1. If it has less fuel than it needs, it becomes insulin sensitive to bring in more fuel.

2. If it has enough fuel, it becomes insulin resistant so that the fuel can go to cells that need it more.

This insulin resistance is different from the insulin resistance we see in type-2 diabetes.

• When the insulin resistance is flexible and shifts depending on energy need we call it physiological insulin resistance.

• When the insulin resistance gets stuck and does not shift, we call it pathological insulin resistance.

Once we understand this simple fact it gets really interesting when looking at fat tissue.

Let’s see if you are following along. Answer this question and see if you were correct.

For fat cells to grow in size do they need to remain insulin sensitive or insulin resistant?

Chronically Hungry Fat Cells

Insulin acts on cells by bringing in fuel and inhibiting the breakdown of fuel inside the cells.

It seems as if fat cells need to get stuck in the insulin-sensitive state to chronically grow in size.

The way insulin signalling works is beautifully designed.

The fat cells need a way to gauge how much fuel they have stored.

It does this by monitoring how much fuel is being burnt.

When the cell burns fuel it produces reactive oxygen species (ROS).

The more ROS produced the more fuel it has.

ROS is thus a proxy of how much fuel the fat cell has.

The fat cell uses this information to become insulin resistant or insulin sensitive.

ROS production seems to be the signal for cellular satiety.

High ROS production is the cell’s way of saying “I’m full, give the food to someone else.”

The amount of ROS produced is not just dependent on the amount of fuel being burnt but also the type.

Because of the differing amounts of double bonds in the fatty acids, they produce different amounts of ROS when burnt.

The more double bonds, the less ROS is produced.

So, if the concentration of PUFAs in fat cells reaches a certain threshold this signalling becomes disrupted.

Even if the fat cell has enough fuel it cannot signal this to the surface (look at the graph).

It becomes stuck in an insulin-sensitive state (the left side).

This causes the cell to become chronically hungry which causes fuel to be chronically brought in.

A chronic state of fat accumulation.

The key takeaway here is that it seems as if fat tissue needs to remain chronically insulin sensitive to reach its fat threshold.

This might be the most important point of this post.

Why?

Because almost everyone interested in obesity views it as a problem of insulin resistance.

Because of this, we think that insulin sensitivity is good regardless of context.

So, don’t we want to be insulin sensitive?

No, we want to be insulin flexible, not pathologically insulin sensitive nor pathologically insulin resistant.

The logic goes, PUFAs are insulin-sensitizing so PUFAs must be good.

1. If we assume this to be true then small, healthy, insulin-sensitive fat cells should be higher in PUFAs.

2. And large, insulin resistant, fat cells should be lower in PUFAs

The opposite is what we find.

Roberts et al. 2009 found that insulin sensitivity was inversely correlated with the size of fat cells.

Meaning that the larger the cell, the less insulin sensitive it was.

They also found that the more insulin sensitive a fat cell was, the more saturated the fat in the cell was.

And, so it seems that pathological insulin resistance is not driven by saturated fats but instead by size.

So, what drives size? (The answer to this is the same as the answer to the last question)

Large fat cells & pathological insulin resistance

We now have two assumptions we can make:

1. Insulin resistance seems to be driven by size.

2. For a fat cell to grow, it needs to bring in lots of fuel.

To bring in fuel the cell needs to be insulin sensitive.

If the cell gets stuck in an insulin-sensitive state it will grow indefinitely (if fuel is available).

Well, not forever.

Fat cells can only hold a certain amount of fuel, we call this the storage capacity.

Once the storage capacity is reached the fat cell becomes insulin resistant and dysfunctional (or we could call it broken).

These broken fat cells then start leaking out free fatty acids and inflammatory mediators.

These then travel throughout the bloodstream and get into other cells around the body.

The free fatty acids and the inflammatory mediators drive inflammation and have been shown to interfere with insulin signalling causing pathological insulin resistance.

Preparing For Starvation That Never Comes

In the preparatory phase, hibernation mammals shift their diet to one higher in PUFAs.

This causes a metabolic shift that increases appetite and fat storage while also decreasing metabolism.

A perfect metabolic state to allow massive amounts of fat to be put on in a short period of time.

We have now looked at how this could potentially be similar in humans that develop obesity.

We’ve looked at how PUFAs disrupt normal physiology at three levels.

1. Insulin signalling

2. Metabolism

3. Appetite

Fat gain requires a calorie surplus.

This can be done by:

• increasing calories coming in (appetite)

• decreasing calories going out (metabolism)

• or both simultaneously.

In both hibernating mammals and obese humans there seems to be a perfectly orchestrated metabolic shift to maximally allow fat gain to take place.

PUFAs downstream effects:

1. Increases appetite (calories coming in).

2. Lowers metabolism (calories going out).

We now have a metabolic state in which more fuel is coming in and less fuel is being burnt.

Where should all this extra fuel be stored?

In the fat cells.

PUFAs also drive chronic insulin sensitivity in fat cells which causes fat to be accumulated until the fat cells reach their storage capacity.

Once this occurs, fat cells become insulin resistant.

They also start leaking free fatty acids and inflammatory mediators both implicated in systemic insulin resistance.

Increased dietary consumption of PUFAs seems to cause mammals to shift into a metabolic state in preparation for a period of starvation.

A period of starvation that in humans never comes.

If you want to read the actual thesis you can email me at jenkinson.max@gmail.com 

Hope this gave you some insight into how, and why we are so obese.

And, until next week, do what makes your future self proud.