Leptin and Leptin Resistance 


Many people believe that weight gain and loss is all about calories and willpower.

However, modern obesity research disagrees. Scientists increasingly say that a hormone called leptin is involved.

Leptin resistance, in which your body does not respond to this hormone, is now believed to be the leading driver of fat gain in humans.

This article explains everything you need to know about leptin and how it is implicated in obesity.

Meet Leptin — A Hormone That Regulates Body Weight

Leptin is a hormone that is produced by your body’s fat cells.

It is often referred to as the “satiety hormone” or the “starvation hormone.”

Leptin’s primary target is in the brain — particularly an area called the hypothalamus.

Leptin is supposed to tell your brain that — when you have enough fat stored — you don’t need to eat and can burn calories at a normal rate.

It also has many other functions related to fertility, immunity and brain function.

However, leptin’s main role is long-term regulation of energy, including the number of calories you eat and expend, as well as how much fat you store in your body.

The leptin system evolved to keep humans from starving or overeating, both of which would have made you less likely to survive in the natural environment.

Today, leptin is very effective at keeping us from starving. But something is broken in the mechanism that is supposed to prevent us from overeating.


Leptin is a hormone produced by the fat cells in your body. Its main role is to regulate fat storage and how many calories you eat and burn.

Impact on Your Brain

Leptin is produced by your body’s fat cells. The more body fat they carry, the more leptin they produce.

Leptin is carried by the bloodstream into your brain, where it sends a signal to the hypothalamus — the part that controls when and how much you eat.

The fat cells use leptin to tell your brain how much body fat they carry. High levels of leptin tell your brain that you have plenty of fat stored, while low levels tell your brain that fat stores are low and that you need to eat.

When you eat, your body fat goes up, leading your leptin levels to go up. Thus, you eat less and burn more.

Conversely, when you don’t eat, your body fat goes down, leading your leptin levels to drop. At that point, you eat more and burn less.

This kind of system is known as a negative feedback loop and similar to the control mechanisms for many different physiological functions, such as breathing, body temperature and blood pressure.


The main function of leptin is to send a signal telling your brain how much fat is stored in your body’s fat cells.

What Is Leptin Resistance?

People who are obese have a lot of body fat in their fat cells.

Because fat cells produce leptin in proportion to their size, people who are obese also have very high levels of leptin.

Given the way leptin is supposed to work, many obese people should naturally limit their food intake. In other words, their brains should know that they have plenty of energy stored.

However, their leptin signaling may not work. While copious leptin may be present, the brain doesn’t see it.

This condition — known as leptin resistance — is now believed to be one of the main biological contributors to obesity.

When your brain doesn’t receive the leptin signal, it erroneously thinks that your body is starving — even though it has more than enough energy stored.

This makes your brain change its behavior in order to regain body fat.

Your brain then encourages:

Eating more: Your brain thinks that you must eat in order to prevent starvation.Reduced energy expenditure: In an effort to conserve energy, your brain decreases you energy levels and makes you burn fewer calories at rest.

Thus, eating more and exercising less is not the underlying cause of weight gain but rather a possible consequence of leptin resistance, a hormonal defect .

For most people who struggle with leptin resistance, willing yourself to overcome the leptin-driven starvation signal is next to impossible.


People who are obese have high levels of leptin, but the leptin signal isn’t working due to a condition known as leptin resistance. Leptin resistance can cause hunger and reduced the number of calories you burn.

Impact on Dieting

Leptin resistance may be one reason that many diets fail to promote long-term weight loss.

If you’re leptin-resistant, losing weight still reduces fat mass, which leads to a significant reduction in leptin levels — but your brain doesn’t necessarily reverse its leptin resistance.

When leptin goes down, this leads to hunger, increased appetite, reduced motivation to exercise and a decreased number of calories burned at rest.

Your brain then thinks that you are starving and initiates various powerful mechanisms to regain that lost body fat.

This could be a main reason why so many people yo-yo diet — losing a significant amount of weight only to gain it back shortly thereafter.


When people lose fat, leptin levels decrease significantly. Your brain interprets this as a starvation signal, changing your biology and behavior to make you regain the lost fat.

What Causes Leptin Resistance?

Several potential mechanisms behind leptin resistance have been identified.

Inflammation: Inflammatory signaling in your hypothalamus is likely an important cause of leptin resistance in both animals and humans.

Free fatty acids: Having elevated free fatty acids in your bloodstream may increase fat metabolites in your brain and interfere with leptin signaling.

Having high leptin: Having elevated levels of leptin in the first place seems to cause leptin resistance.

Most of these factors are amplified by obesity, meaning that you could get trapped in a vicious cycle of gaining weight and becoming increasingly leptin resistant over time.


Potential causes of leptin resistance include inflammation, elevated free fatty acids and high leptin levels. All three are elevated with obesity.

Can Leptin Resistance Be Reversed?

The best way to know if you are leptin resistant is to look in the mirror.

If you have a lot of body fat, especially in the belly area, then you are almost certainly leptin resistant.

It is not entirely clear how leptin resistance can be reversed, though theories abound.

Some researchers believe that reducing diet-induced inflammation may help reverse leptin resistance. Focusing on an overall healthy lifestyle is also likely to be an effective strategy.

There are several things you can do:

Avoid processed food: Highly processed foods may compromise the integrity of your gut and drive inflammation.

Eat soluble fiber: Eating soluble fiber can help improve your gut health and may protect against obesity.

Exercise: Physical activity may help reverse leptin resistance.

Sleep: Poor sleep is implicated in problems with leptin.

Lower your triglycerides: Having high triglycerides can prevent the transport of leptin from your blood to your brain. The best way to lower triglycerides is to reduce your carb intake.

Eat protein: Eating plenty of proteincan cause automatic weight loss, which may result from an improvement in leptin sensitivity.

Though there is no simple way to eliminate leptin resistance, you can make long-term lifestyle changes that may improve your quality of life.


Though leptin resistance does seem reversible, it involves significant diet and lifestyle changes.

The Bottom Line

Leptin resistance may be one of the main reasons people gain weight and have such a hard time losing it.

Thus, obesity is usually not caused by greed, laziness or a lack of willpower.

Rather, there are strong biochemical and social forces at play as well. The Western diet in particular may be a leading driver of obesity.

If you’re concerned you may be resistant to leptin, there are several steps you can take to live a healthier lifestyle — and possibly improve or reverse your resistance.

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