Leptin Resistance is Destroying Your Diet Success

Obese man

Most discussions on weight loss focus on what we eat and what we don’t eat.

That perspective tends to go hand-in-hand with ideas that overweight people simply need to exert greater self-control.

But, reality isn’t actually that simple.

One key factor is something called leptin resistance.

What is leptin resistance?

The term itself emerged towards the end of 1994, after the leptin hormone had been discovered. Following that discovery, the term has been used in thousands of different studies and references.

However, the term isn’t always used in the same way, and doesn’t have a single meaning.

In fact, leptin resistance may refer to a large number of different processes and mechanisms.

The range of definitions makes it difficult to compare studies to one another or to test leptin resistance in a quantitative manner.

Leptin itself is a molecule that helps promote specific responses when people eat too much or when they are obese. In particular, the hormone is critical for energy balance (you can find out more about leptin here).

It helps to reduce appetite in cases where no more food is needed.

So, it’s a really important hormone, particularly if you are trying to stay at a healthy weight.

But, when people are obese, things start to work a bit differently.

The body becomes less sensitive to the leptin, which means the body is less able to detect when it has had enough to eat (1).  So when a person is not as sensitive to leptin, their body isn’t able to detect satiety effectively.

This general issue is what is meant by the term leptin resistance.

Eating a burger

From a practical perspective, the issue means that when people are overweight it is hard for them to tell when they have had enough to eat.

That can make portion sizing very difficult and means that people who are overweight or obese will end up eating too much as a consequence.

Leptin resistance is still a field that is being very heavily researched, and for good reason too.

If we can understand the mechanics behind leptin resistance and work out ways to combat it, those answers may offer important insights into how to combat obesity.

So, in this post, we’re going to take a look at some of the science behind leptin resistance, including what we do know about leptin and leptin resistance, and also what the limits of our current knowledge are.

What is Leptin Resistance?

How Does It Work?

Leptin resistance is connected to the stored fat in the body.

In general, stored fat results in a range of biological effects and interactions. This is also one reason that obesity is connected to a wide range of potential health issues.

The hormone itself is actually derived from adipose tissue (fat tissue), which is one reason for the connection between stored fat and leptin.

Leptin has a receptor in the brain known as LRB. That receptor uses a range of pathways to communicate and to exert the outcomes of leptin (2). 

In general, high levels of leptin mean that a person feels satiated and does not feel hungry.

In contrast, low levels of the hormone result in high levels of hunger, which strongly contributes to obesity.

Leptin levels change as a person eats, and they respond strongest to decreases in food intake.

Girl with a scale, weight loss concept

So, people who are fasting or following a very low-calorie diet will dramatically decrease their leptin levels (3). That’s one reason why that approach to dieting is often hard to follow.

Research has shown that activity in the brain changes during diet-induced weight loss and these changes are leptin-related (4,5).  

Leptin levels also increase exponentially as people increase in their weight (6,7). 

In theory, this would suggest that obese people feel hungry less often and get full easier.

But, obesity is where leptin resistance comes into play.

So, people in this group might have higher levels of leptin, but they are less sensitive to that leptin.

This poses a major problem.

Changes in Behavior

Essentially, leptin is a hunger signal.

As such, it affects our behavior when it comes to food.

After all, hunger is a key reason why we eat.

Interestingly, there is also a second behavior that leptin affects, which is the desire to conserve energy. This means that low levels of leptin tend to make people less likely to be active.

There is also a physiological side of those impacts.

So, the end result is that people with low leptin will exercise less and eat more. Biologically that makes sense, because the body thinks it’s starving.

But, the same changes occur when people are leptin resistant, because their body thinks that they are starving (8,9,10,11). 

What Causes Leptin Resistance?

In general, the human body is a complex system, and there are a large number of different compounds that interact with and influence one another.

Because of this, there are many different factors that can affect the amount of leptin in the body and also the way that the body responds to that leptin.

Sleeping woman

Leptin levels also change over time.

In particular, the levels will increase overnight.

That pattern may play a key role in suppressing appetite as people sleep (12). 

There are a few key mechanisms that underlie leptin resistance.

Leptin Levels

The first mechanism is simply leptin levels themselves.

Simply having high levels of leptin can play a key role in the development of leptin resistance (13,14).

This makes a certain amount of sense from an evolutionary perspective, as the high levels of leptin we have today are unlikely to have been present in our ancestors.

It may simply be that our bodies do not have the mechanisms to handle such high levels of leptin, leading to issues in how the body responds to the leptin.

Leptin and Inflammation

Some research suggests that inflammation may also play a key role in the development of leptin resistance (15,16). 

Inflammation would help to explain how leptin resistance occurs with obesity, as inflammation is associated with obesity (17). 

In fact, overnutrition results in the development of a unique form of inflammation (18). 

Because of this connection, researchers have suggested the importance of future studies into the effects of lowering inflammation in patients. In theory, such approaches could potentially decrease leptin resistance and help people respond normally to leptin.

Free Fatty Acids

The third main factor in leptin resistance is free fatty acids (19,20). 

These have the potential to interfere with leptin signaling by increasing the fat metabolites that are present in the brain.

Thinking girl


Obesity itself isn’t a direct contributor to leptin resistance.

Instead, all three of those areas are common in people who are obese.

So, people in this situation tend to have high levels of leptin, inflammation and free fatty acids. All of that makes leptin resistance much more likely.

In turn, this creates a cycle, because leptin resistance makes overeating easier, which simply increases those factors.

Breaking free from that cycle can be extremely difficult, especially because people aren’t even aware of the processes that are occurring.

Limits of Current Research

Research into leptin has provided a much greater understanding of the processes of obesity and the way that obesity is developed and maintained (21). 

This research has highlighted the complexity of obesity and the presence of hormonal systems and feedback loops as part of the pathology of obesity.

Even though the hormone was discovered just over 20 years ago, there is still a lot that we don’t know about leptin.

That isn’t too surprising as it is a complex topic and isn’t particularly easy to study.

Challenges of Leptin Research

As I mentioned earlier, leptin resistance is a vague term, and it can apply to a number of different situations (22). 

This means that cases of leptin resistance could be quite different from one another, and could have different causes and outcomes.

This issue makes research challenging, as the outcomes of one research study are not necessarily relevant to another study.

Test tubes, research concept

At the same time, we don’t have good assays to look at the level of leptin responsiveness in humans (23).

Such tools are needed to strengthen research in the area and help us learn more about leptin and leptin resistance.

Additionally, reliable assays are needed to identify individuals who suffer from leptin resistance in order for the resistance to be combated.

These challenges mean that much more research is needed into the field of leptin resistance before leptin itself can have therapeutic value.

How to Reverse Leptin Resistance

So far, we’ve taken a good look at the answer to what is leptin resistance, but we haven’t really talked about what to do about the issue.

Certainly, leptin itself is not often used as a therapeutic tool and leptin itself may not be effective at combating leptin resistance anyway.

So, is there anything that can be done?

Inflammation and Leptin

The connection between leptin and inflammation is another area that can potentially be targeted for therapy.

In particular, reducing inflammation in the body does have the potential to decrease leptin resistance.

So, a diet focused on reducing inflammation could be a powerful tool for people struggling with obesity.

If such a diet did help to lower leptin resistance, then it could make it easier for obese people to watch their portions and decrease their overall energy consumption.

In the long-term, this could help promote weight loss.

Dieting and Leptin

Leptin resistance is a major issue with weight loss.

As a person loses weight, they will tend to decrease their leptin levels.

That’s particularly true if that person is following a very low-calorie diet or if they are skipping meals.

Decreasing leptin levels like this just reinforces the idea that the body is starving.

That’s an awful situation for dieting – because you are actively fighting your brain as you try to lose weight.

This may be a key reason for yo-yo dieting (24). 

That fight isn’t easy to win, and it is one reason why many people struggle to lose weight in the long term.

One proposed solution to this issue is leptin therapy. This is used to increase the amount of leptin as the person is losing weight.

This process can potentially be effective, because by increasing leptin the approach decreases the hunger that can typically come with dieting.

One study looked at the potential for leptin to be used in this way (25). 

The authors found that a subset of the participants in the study did respond to that treatment, although the rest of the participants did not.

This suggests that leptin has the potential to help people lose weight in some cases, but it is not a universal approach.

However, a second study found that leptin was not enough to predict whether or not people would regain weight (26). 

Girl eating salmon

A more general approach is for people to lose weight through diets that don’t dramatically drop leptin levels.

For example, leptin levels drop dramatically when people have very low-calorie diets.

Diets that are high in protein and involve regular meals could potentially be an effective way around this issue.

This type of diet helps you to feel satiated and can provide more energy.

This could help reduce the amount of leptin you lose, while also making the process of weight loss more bearable.

Leptin in the Media

Leptin is sometimes known as the ‘hunger hormone’, and it is easy to see the potential implications of this hormone in the treatment of obesity.

After all, hunger is a key issue with weight loss, and many people find it difficult to limit their food intake because of how hungry doing so can make them feel.

The potential of leptin has actually led to a number of popular books and even diets that focus on ways to improve the way the leptin hormone responds.

Some of these books tackle the question of what is leptin resistance, although some others don’t seem to focus on the topic very much.

Outside of the scientific community, understanding leptin is sometimes promoted as a weight loss miracle.

Often the emphasis is on diets that are supposed to help lower leptin resistance and/or help with leptin while a person is losing weight. For example, the site Wellness Resources talks about 5 rules of the leptin diet. Likewise, some authors (like The Paleo Diet) suggest that a paleo eating approach can help reduce leptin resistance. 

In some cases, these diets may be effective.

However, authors are also quick to promote the latest fad or idea, so many of the diets may be pretty limited.

Reversing Leptin Resistance

If people with obesity could reverse leptin resistance, it would be much easier for them to control their eating patterns and their weight.

However, we are still a long way from any solid answers about how to achieve this goal.

Confused man counting

The advice about anti-inflammatory foods and a high protein diet may be effective, but much more research is needed before we know effective ways to reverse leptin resistance.

Some research studies have also suggested other approaches, although in most of these cases more research is needed.

Nevertheless, the approaches tend to be beneficial for health in general, so they may be worth following.

The potential approaches are:

Decrease Triglycerides. Triglycerides in the blood may play a role in leptin resistance, making it harder for the leptin to cross the blood-brain barrier (27). Fish oil is one way to decrease triglycerides (27),  and a low carbohydrate diet is another approach (28).

Get Enough Sleep. Insufficient or poor quality sleep has been associated with a number of negative health outcomes, including leptin issues (29). 

Decrease Processed Food Intake. Processed foods have been linked to inflammation, which may, in turn, increase the risk of leptin resistance (30). 

At the End of the Day

Losing weight is a challenge that so many people face, and there aren’t any simple answers.

For many people, leptin resistance is certainly one part of the equation.

There is no simple answer for fighting leptin resistance, although answers may be found in time as research continues.

For the moment, simply being aware of leptin resistance offers valuable insight into obesity and into the challenges that people face.

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Have you ever heard of leptin resistance before? The term is becoming more popular, but a lot of people still don’t know about it. Please let me know what you think of the topic, I’d love to hear from you.

2 thoughts on “Leptin Resistance is Destroying Your Diet Success”

  1. It’s too bad with awareness we can’t do something more about it. The best way to reduce inflammation in the gut is to get off gluten. I have never heard of leptin resistance, thanks for bringing it to my attention.

    • Thanks for your comment. Leptin resistance is a fairly new area and I think a lot of people don’t know about it. I hope that as time goes on, more people do learn about leptin resistance. Even though there isn’t a lot we can do about it, being aware certainly helps. It would be nice if knowledge about this issue helped reduce some of the stigma that surrounds people who are overweight.


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