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Insulin Resistance and Fat Loss

The topic of insulin resistance/insulin sensitivity  and body fat is one that is still rife with confusion and misinformation.  Specifically, it’s usually stated that insulin resistance causes fat gain or that insulin sensitivity improves fat loss.  However, in at least one of my books (The Ultimate Diet 2.0) I stated that insulin resistance is superior for fat loss, which seems to run against both common thought and common sense.  So let me address the topic again.

How Hormones Work

A hormone is any substance in the body that causes something to happen elsewhere. Technically you can divide up neurotransmitters (which work locally) and hormones (which work elsewhere/all over the body) but this is unnecessary detail.  So a hormone is released from some gland or another (i.e. thyroid from the thyroid gland, insulin from the pancreas), binds to a receptor somewhere and makes stuff happen (a technical term).

The almost universal analogy for how hormones work is the lock and key analogy.  The hormone is the key and its specific receptor is the lock.  So the lock fits into the key and makes stuff happen (still a technical term).  Every hormone has its own specific receptor (just as a key fits into one lock) but there can be something called cross-reactivity where one hormone kind of fits into a different hormone.  Don’t worry about this.

So insulin has an insulin receptor.  When insulin binds to that receptor, stuff happens (see a trend here).  And that insulin receptor is found all over the body, in the brain, in skeletal muscle, in the liver, and in fat cells.  The last three are the key things to worry about here.

Now, a number of factors determine how well a hormone works (i.e. how much stuff happens). The three main ones are the amount of that hormone (more generally means more stuff happens), how sensitive the receptor is (how well it responds to the hormone) and something called affinity.  Don’t worry about this either; I include it for completeness only.

So if there is a lot of a hormone, it tends to send more of a signal than when there is less and vice versa.  More testosterone builds more muscle than less for example.   But this isn’t always true and that’s where receptor sensitivity (or resistance) comes into play.  This represents how well or poorly a given receptor responds to a hormone.  So if a receptor is sensitive, a little bit of hormone makes a lot of stuff happen; if a receptor is resistant, even a lot of hormone may not make much happen.

NB: Technically there can be something called receptor insensitivity and resistance which are slightly different things but, practically speaking, they don’t matter much here.

What Does Insulin Do?

There are a lot of silly ideas about insulin floating around (get it, hormones float around?) but just think of insulin as a storage hormone.  Released in response to eating carbohydrate and protein (but not in response to fat, which can impact on insulin resistance in other ways) insulin puts the body in an energy storage mode.  But don’t think this means that dietary fat can’t make you fat.

In skeletal muscle, insulin stimulates the storage and/or burning of carbohydrate for fuel.  In the liver, it shuts down glucose production.  In fat cells, it both stimulates the storage of calories and inhibits the release of fat (it inhibits lipolysis).  This is where insulin has gotten it’s evil reputation.

Oh yeah, insulin is also one of the signals in the brain that should decrease hunger although it clearly doesn’t work that well.  There is also evidence that men respond more to insulin than women (who respond more to leptin).   Women also tend to be more insulin resistant than men although even that varies throughout the menstrual cycle.

What Does Insulin Resistance Mean?

By mean here I mean what are the consequences of insulin resistance physiologically.  In skeletal muscle, insulin resistance means that insulin can’t store carbohydrate as glycogen or stimulate the burning of glucose.  In the liver, insulin resistance means that the increase in insulin can’t inhibit hepatic glucose oxidation.  In the brain, insulin resistance means that insulin doesn’t do its job of decreasing hunger.

But when a fat cell becomes insulin resistant, that means that insulin not only doesn’t store calories but that insulin can’t inhibit fatty acid release as well.  Please read that sentence until it makes sense since that’s the key to this.

As well, when the body starts to become insulin resistance and insulin is working more poorly, the body tends to release more insulin to compensate.  This is a general truism in the body, if a receptor is resistant, the body will crank out more in an attempt to make itself function properly.  But it doesn’t always work.  As well, a chronic elevation of a hormone tends to cause receptor resistance itself.  So it becomes a bit of a vicious circle.

What Causes Insulin Resistance?

Well, a lot of things.  Genetics are a big player of course but we can’t control that so ignore it.  Inactivity decreases insulin sensitivity and regular activity increases it (I won’t get into the reasons).  When a cell becomes full of nutrients, such as when a muscle is full of glycogen or intramuscular triglyceride (IMTG, a type of fat stored inside skeletal muscle) it becomes insulin resistant.  Think of this as when your gas tank is full, trying to put more gas into it just makes it spill over; there’s no room.

Diet impacts on this with high intakes of refined carbohydrates and fat causing insulin resistance.  In the long-term, a high saturated fat intake may change the structure of the cell membrane and that causes problems.  Excessive fructose (key word excessive) may cause insulin resistance.

I mentioned above that a chronic elevation of a hormone can cause receptor resistance.  So someone is inactive, consuming an excess of carbohydrates and fats, etc. will keep insulin elevated and that causes resistance.  Basically a majority of people in the modern world.

Carrying too much body fat is also associated with insulin resistance. This isn’t universal, you can find lean people who are insulin resistance and overfat people who are insulin sensitive. But there is a pretty good correlation.

Now a key factor to understand is that the body becomes insulin resistant in stages.   The liver is first and insulin resistance causes the liver to no longer inhibit glucose production.  So blood glucose tends to stay constantly high.  Skeletal muscle is next.  At this point insulin can no longer store nutrients such as carbohydrate, fat or protein there.

That only leaves the fat cells.  As they fill up and become insulin resistant, insulin can no longer store calories there.  When that occurs, what you tend to see is a lot of fatty acids floating around in the bloodstream (hypertrglyceridemia), a lot of cholesterol, a lot of glucose, etc.  Incoming nutrients have nowhere to go.  Can’t be stored in muscle, can’t be stored in the liver, can’t be stored in fat cells.

This causes a bunch of other problems.  One of those is what is called ectopic fat deposition.  Basically fat starts getting stored in places it shouldn’t be such as the pancreas.  Over time this causes damage and the body loses the ability to release insulin.

The Impact of Insulin Resistance on Body Fat

Which finally brings me to the original question.  Insulin resistance is usually thought of as causing fat to be gained while I asserted that it helps with fat loss. And both are sort of true.  Some people, in the first place, release excessive insulin in response to food intake.  If you couple this with genetic or lifestyle related insulin resistance in skeletal muscle calories can’t be stored in muscle so they spill over into fat cells (where insulin may still be working).  Aha, insulin resistance causes fat gain.

But consider what happens when the body becomes completely insulin resistant.  Or a theoretical situation where you could make fat cells only insulin resistant.  Now insulin can’t store calories in the fat cells and can’t inhibit fat mobilization.  From a fat loss perspective this is would have to be a good thing.  If you can’t store fat in fat cells when you eat and it’s easier to get fatty acids, that means that fat is easier to lose.

It almost looks as if the body is trying to push fat away from fat cells (which also get full) to prevent a further increase in body fat.  And that’s basically exactly what it’s trying to do; there are a ton of adaptations as people get fat that should inhibit further fat gain and this is one of them.  They just don’t work very well.

And consider some of the following factoids.  There is a class of drugs called thiazolidinedione or glitazones that are often used to improve insulin sensitivity in obesity or the metabolic syndrome.  Chronically elevated blood glucose and fatty acids cause damage to the body and doctors want to get that down.  But those drugs work by increasing fat cell insulin sensitivity.  And fat is gained.

There is also some data (but not all) finding that insulin sensitivity predicts weight gain and insulin resistance fat loss.  This would also explain why insulin resistant but lean people are resistant to weight gain: calories can’t be stored in fat cells.

If you think about this it actually makes a weird sort of sense.

Consider that the easiest time to regain weight is at the end of a diet, when insulin sensitivity is high.  And the easiest time to lose fat is when someone is carrying a lot of fat, and are typically insulin resistant.  I think you get the idea.

Consider that when the obese start training, especially weight training (which depletes muscle glycogen and enhances specific skeletal muscle insulin sensitivity) and especially if they moderate dietary carbohydrates, they seem to see this amazing situation where they lose fat and gain muscle.

Consider that two of the most powerful partitioning drugs, clenbuterol and growth hormone induce insulin resistance.  But when people are weight training, it keeps that specific tissue insulin sensitive.  Muscle sucks up calories that can’t be stored elsewhere (for the most part).

It’s as if the body is shifting calories from fat cells into muscle.  And I think this is exactly what is happening.  Activity, skeletal muscle glycogen depletion both raise muscle insulin sensitivity.  So long as the fat cells are still insulin resistance, calories get partitioned into muscle and away from fat cells.

The Reality of Insulin Resistance

Unfortunately, outside of this one situation in the obese (or when using drugs), insulin resistance tends to improve in the opposite direction that it develops.  As people lose fat, fat cells become more insulin sensitive (part of why it’s more difficult to mobilize further fat), then liver (or muscle), then muscle.

Training can reverse this, of course; it’s honestly the single most powerful factor we have to improve specific tissue insulin sensitivity.  And until fat cells become insulin sensitive (again which they do as fat as lost), there can be at least some partitioning effect away from fat cells towards skeletal muscle.

And hopefully that answers what the statement in my Ultimate Diet 2.0 was getting at.

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6 thoughts on “Insulin Resistance and Fat Loss

  1. Thanks Lyle – wow this is definitely confusing – you always hear that being insulin resistant is bad – are you saying that being insulin resistant is just an artifact of obese people and not the cause of obesity?

  2. thank u lyle for this article but im just curious.. we know that i sulin sensitivity high at morning and low at night .. is insulin resistant at night will cause less fat gain fromeating carbs(at night) at least thats the premise of cbl

  3. o my god. i just typed up my whole confused understanding of insulin resistance brought on by low carbing/ketogenic dieting, and it all disappeared. could you explain that kind of resistance?

    also, is it true that in the presence of inflammation, fat becomes more insulin sensitive and muscle less so? isn’t talking about insulin resistance or sensitivity vacuous unless you specify what kind of tissue you are talking about?

    i remember this student i had from haiti. she would eat crap school cafeteria food and not put on any belly fat. instead she was well-muscled. it seemed like it didn’t matter that she wasn’t getting a lot of nutritious food, she could still use the calories from wherever and build muscle!

  4. Hey Lyle. I love your articles, but feel that the lack of editing really hurts their readability and thus their quality. If you want/need any assistance, please send me an E-mail as I’d be happy to help.


  5. Lyle,

    I over-secrete insulin, while having high sensitivity. If I consume a gel early in a long ride I’ll bonk hard about hour 2, but if I fast 4 to 5 hours of same effort is very doable, with a much more controllable sugar crash towards the end.

    This of course limits my ability to train and race longer events such as 100 mile mountain bike races. What is the best way to address this problem? Is there a feeding pattern/macro profile that prevents insulin spikes while still adding sufficient glucose into the bloodstream? Could I raise insulin resistance somehow to make the response to the insulin more appropriate? A CKD might be one way to do that, if the insulin resistance lasts through the refeed. I’ve also had some success on rice cakes with ground meat for very controlled long rides, but I doubt that would be digestible in a race.


  6. From the article “Calorie Partitioning: Part 2”:

    “Another problem with many cyclical dieting approaches is that they don’t coordinate training with the diet.”

    Dunno if you’ve written about this before, but I’d be interested to read your take on different ways to coordinate/periodize training around the diet, with the generic goal of hypertrophy and fat loss.

    Kind of like UD 2.0., but for less experienced trainees with more average body composition.

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