Saturday, April 13, 2013

How Leptin Resistance can Cause Obesity



Recently, That Paleo Guy posted a great rant about the weaknesses found in the popular concept of calories in vs calories out. Essentially, while a person may eat enough calories to support their everyday activities, disease and dysfunction in the body may make some of these calories unavailable for use, trapping them in fat cells. Ultimately, he argued that calories in vs. calories out should be changed to calories available vs. calories expended.

While I completely agree with his overall argument, he seems to be under the impression that calories are not tracked by the brain:
And this is again the problem with the whole calories deal.  We can’t accurately count them outside of our body, our bodies don’t count them at all, and a whole raft of hormonal and neurological factors determines where the ‘calories’ go and whether they are actually available for biological functions.
I don’t know why The Paleo Guy thinks that calories aren't tracked by the brain. Calorie intake relates directly to your bodyweight. (1,2) If calories were not tracked, then your bodyweight would be highly unstable, changing radically with whatever calorie intake and level of physical activity you experience on a given day.

Elite athletes, who can burn thousands of calories a day during training, (3) would be most affected by this laissez-faire management of calories: If their calories are not tracked and controlled, then they could actually exercise themselves into such low bodyweights that they would die from starvation. Obviously, this doesn't actually happen. (4)

Although bodyweight may be higher for some, and lower for others, the brain's use of feedback controls ensures that a person's calorie intake adjusts to maintain a fairly stable bodyweight. However, if these feedback controls aren't working correctly, then a person's brain will maintain an abnormally high bodyweight, which necessitates increased calorie intake. But this isn't the whole story.

I believe that these malfunctioning feedback controls not only cause someone to be overweight, but also cause their brain to actively defend this abnormally heavy bodyweight, producing the familiar yo-yo like effect on bodyweight if they try to consciously restrict their calories (either through eating fewer calories, trying to "burn" off extra stored calories, or both). This could prevent someone from losing weight even if they are technically starving themselves. Let me explain what I mean.

Calorie Consumption, Bodyweight, and Feedback Controls
Your brain and body work hard to maintain balance and order. This is known as homeostasis. (5)

A good example of homeostasis is regulating core body temperature, which is controlled by the hypothalamus and uses feedback controls to maintain core body temperature. (6)
  • As core body temperature increases above normal (about 98.6 degrees), blood circulation and sweating increases to cool down the body.
  • As core body temperature drops below normal, blood vessels constrict, sweating stops, shivering starts, and adrenaline is secreted to heat up the body.

This feedback control allows the brain to maintain a stable core body temperature despite small changes in the surrounding environment.

When it comes to calories and bodyweight, the brain uses various feedback controls to constantly meet daily energy requirements while also maintaining a stable bodyweight. For instance, most of those who participated in various starvation studies in the 1950s almost always gained back the weight they lost, automatically stabilizing at their starting weight (no matter how much weight a person lost due to calorie restriction). (7,8)

Also, many women in the West African country of Mauritania practice overeating as a way of attracting a husband. The process of becoming and staying overweight is so difficult that some families will send their daughters to fattening experts who will literally force them to be inactive and eat thousands of calories every day. While these girls do gain a lot of weight, this extra weight is usually lost over time, despite their best efforts to remain heavy. (9)

This shows that as long as you are healthy, getting just enough to eat and maintaining a stable bodyweight is automatic and shouldn't require conscious calorie counting because your brain does the counting for you.

Normalizing Bodyweight
Before a person’s bodyweight can be regulated, the brain (specifically the hypothalamus (10)) has to determine a specific healthy bodyweight. This is known as a bodyweight set point. (11,12) Exactly how the hypothalamus establishes a given set point isn't clear, but healthy individuals tend to have a bodyweight that equates to a body mass index (BMI) between 19 and 25. Those above and below that BMI range tend to be progressively less healthy. (13)

Simplified Bodyweight Regulation (Leptin Sensitive). This graphic illustrates how the brain of someone who is leptin sensitive will automatically maintain their established bodyweight set point. If this person’s bodyweight moves above or below this setpoint then hunger, appetite, and metabolism can all be adjusted to add or remove fat weight.

Once a bodyweight set point is established, the hypothalamus can regulate this set point to make sure that a person is not too heavy or light. This is largely accomplished by figuring out how many calories are required to support everyday operations (keeping the heart pumping, maintaining body temperature, fueling physical activities, and so on) and adjusting calorie intake (via hunger and appetite) and metabolism when bodyweight goes above or below this set point. (14,15Body fat (as opposed to lean mass) is usually adjusted to maintain bodyweight. (12)

But this simplistic description describes how your brain regulates bodyweight when you are healthy. What if you are overweight?

When Feedback Controls Break
If a person is not completely healthy, then feedback controls can break, leading to dysfunction. When it comes to calories and bodyweight, the brain’s insensitivity to the hormone leptin (known as leptin resistance) can lead to obesity. (16)

A person’s bodyweight is mostly the combination of lean and fat masses, both of which are tracked by the hypothalamus. Lean mass (I believe) is detected by nerves, while fat mass is determined by measuring how much leptin is circulating in the blood. (17)

Because the level of leptin in the blood represents a specific amount of body fat, the hypothalamus can use the level of leptin to determine the weight of its fat mass. (18The hypothalamus can then adjust hunger, appetite, and metabolism to increase or decrease a person’s fat mass to compensate for changes in bodyweight. This allows bodyweight to remain stable despite changes to a person’s lean mass or level of physical activity. (There are limits and exceptions to a lot of this, which I won’t go into right now.)

However, if the hypothalamus becomes resistant to leptin, then it will underestimate a person’s fat mass. If a person’s lean mass doesn't change, but their fat mass appears to be reduced, the hypothalamus will underestimate their bodyweight, giving it the impression that this person is underweight and starving. This now broken feedback control can then cause a person to become overweight as the hypothalamus creates an energy surplus that is then stored in body fat to counteract leptin resistance (because more fat produces more leptin).

And this energy surplus isn't always produced when this person takes in more calories than they expend. The hypothalamus can generate a calorie surplus by maintaining calorie intake while dropping metabolism, allowing this person to gain weight without eating a single extra calorie and having neutral calorie balance on paper. This is why calories in vs. calories out is such a terrible way of describing how someone maintains their bodyweight.

How Leptin Resistance Works
Let’s say that a person’s brain determines that their bodyweight set point should be 150 pounds. If this person has 121.5 pounds as lean mass (which is largely determined by their physical activity and protein intake), then their body fat will have to weigh 28.5 pounds if their bodyweight is to equal 150 pounds. Without having to count a single calorie, their hypothalamus will adjust calorie intake and metabolism to make sure that this person’s body fat equals 28.5 pounds.

Simplified Bodyweight Regulation (Becoming Leptin Resistant). This graphic illustrates how the brain’s insensitivity to leptin can simulate a lower bodyweight. This triggers a starvation response, even if a person’s body weight is actually at the established set point.

However, when this person becomes leptin resistant, their body could be telling their brain that it has 28.5 pounds of fat, but their brain only senses that there are 23.5 pounds. So even though a person has all the fat they need to maintain their healthy weight, their brain actually thinks that this person is five pounds underweight. This causes a starvation response—complete with an increase in hunger and appetite, as well as a decrease in metabolism—to build up fat stores.

Simplified Bodyweight Regulation (Leptin Resistant by five pounds). In this graphic, the brain has reacted to the perceived starvation by adding the five pounds of fat that it thought it was missing. While its feedback controls tell it that a person’s weight is at the established set point, their bodyweight is actually five pounds above this set point, making them overweight. The brain will now defend this heavier weight.

Because the brain is leptin resistant by five pounds, the body has to actually have 33.5 pounds of body fat to make sure that the hypothalamus senses the 28.5 pounds required to make a person’s bodyweight 150 pounds. Although the brain believes that its bodyweight is exactly 150 pounds, this person’s weight is actually 155 pounds.

Simplified Bodyweight Regulation (Leptin Resistant by 75 pounds). As a person becomes more and more leptin resistant, their brain will continue to think that their weight is at the established set point.

As a person becomes more and more leptin resistant, their body will have to build up more and more body fat to make sure that their hypothalamus always senses 28.5 pounds (even if a person actually has hundreds of pounds of fat weight). Even though a person may become more and more overweight according to a scale, their brain will believe that they are actually at their established set point.

Simplified Progression of Obesity with increasing leptin resistance. For those who are leptin resistant, no matter how heavy a person is on the scale, their brain will always believe that it is at or close to its established bodyweight set point. As leptin resistance gets worse, so too does the increase in bodyweight. The only way to reverse this problem is to eliminate the diet, lifestyle, and environmental factors that cause leptin resistance.

Unfortunately, a person will always remain overweight as long as they are leptin resistant. And if a person is overweight, they will feel inclined to eat more calories because it takes more energy to move the extra bodyweight.

Conclusion
Without a doubt, the brain tracks calorie intake and expenditure to regulate bodyweight. After establishing a person's bodyweight set point, the hypothalamus uses feedback controls to maintain this set point by adjusting calorie intake and energy expenditure, increasing or decreasing body fat mass as necessary. However, if this person is leptin resistant, these feedback controls under-report their bodyweight, causing the brain to add extra body fat. This causes a person to become overweight. As this leptin resistance get worse, their bodyweight and calorie intake also increases.

But this can also work in reverse. If someone corrects their leptin resistance with a clean diet (e.g., Paleo, ancestral, or traditional), they will likely experience effortless and consistent reductions in hunger, appetite, body fat, and bodyweight until a they reach their actual bodyweight set point. (19,20) Essentially, the reduction or elimination of leptin resistance allows the hypothalamus to suddenly sense that a person is overweight, causing it to decrease hunger and appetite and raise metabolism to get rid of the excess bodyweight.

And while calories in vs. calories out is not a helpful way of understanding a person's actual calorie balance, it can be used as a troubleshooting tool to determine if your body fat detection feedback controls are working correctly:
  • If you are at a healthy weight (that is, not starving yourself to maintain your healthy weight), then your feedback controls are likely working properly, allowing your brain to get a very good understanding of how heavy you are and what your calorie requirements are. 
  • However, if you are overweight, then it is likely that your body fat detection feedback systems are malfunctioning (although there are some other dysfunctions other than leptin resistance that can also cause you to become overweight). 
So, to start permanently losing your extra body fat, you should first look into trying to eliminate leptin resistance. If you try to lose your extra body fat while still leptin resistant, then your brain will fight your weight loss efforts (and win), ultimately guaranteeing that you will remain overweight.

Because obesity is such a complex subject, I think I’ll stop here since this post is already too long. I’ll talk about the things that can cause leptin resistance (and causing you to gain lots of fat weight) in another post.

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