What Is Leptin Resistance? [5 Causes And Strategies To Reverse It]

We hear a lot about insulin resistance, but what is leptin resistance? Just as cells can become resistant to the effects of insulin, they can also stop responding to leptin, a hormone associated with satiety and hunger. Interestingly, leptin resistance can be caused by insulin resistance. In this post, I’ll be discussing facts about leptin resistance, how it correlates to weight gain, inflammation, osteoporosis, fatty liver, diabetes, cardiovascular disease, and potentially cancer because of its impact on immune function.

What Is Leptin Resistance - Ghrelin And Leptin Graphic

When Leptin Levels Aren’t Balanced

Just as chronically high levels of insulin cause insulin resistance, high levels of leptin, along with reduced sensitivity to the hormone in the brain, cause leptin resistance. Leptin resistance is one of the fundamental causes of weight gain and obesity. When leptin levels are balanced, the body responds appropriately to signals of hunger and feelings of fullness because the brain gets the message that it time to stop eating.

Here’s a scenario of how it should work: you eat a meal, fat cells release leptin, you get the signal that you’ve had enough to eat, and you stop eating. This is normal. This process goes south when you become resistant to the effects of leptin. Instead of getting the signal that you’re full, you keep eating because your body thinks it’s starving, a result of faulty leptin signaling.

Leptin is a hormone and hormones are extremely powerful. This is one mechanism in which weight gain can eventually progress to obesity. Leptin works in conjunction with ghrelin, the hunger hormone, to regulate energy balance in the body.

Inflammation and Leptin

Chronic inflammation, hypothyroidism, and metabolic syndrome can all be the result of imbalanced leptin levels. A syndrome is a cluster of conditions and symptoms that occur together. Metabolic syndrome is characterized by high blood sugar, high blood pressure, abdominal body fat, high triglycerides, and abnormal ratios of cholesterol.

Hypothyroidism causes weight gain, low body temperature, and reduced metabolic rate. It can also lead to insulin resistance, imbalanced cortisol levels, and disruptions in ovarian hormones. Inflammation is a precursor to all chronic disease, and happens when the inflammatory response continues unabated, without turning off.

Chronic inflammation can be silent and linger for years, with no apparent symptoms, yet with dangerous implications. It can cause alterations in affected tissues, imbalance hormones, and cause intestinal permeability, which can lead to nutritional deficiencies, while negatively impacting immune function.

Low-grade inflammation can be caused by high-glycemic diets, insulin resistance, smoking, stress, lack of sleep, and the excess body fat caused by leptin resistance. You can get a peek into how much inflammation you have by getting your CRP levels checked. Levels should be under 0.7 mg/dl and ideally below 0.2 mg/dl.

Check your thyroid levels here (TSH should be < 2)

Check CRP here

What Is Leptin Resistance And What Causes It?

Leptin resistance is caused by lifestyle factors, which is actually good news because you have control over how you live your life, in terms of what you eat, how much your sleep, and your activity level:

  • Excessive fructose consumption
  • High-carb diets
  • Too little sleep
  • Lack of movement
  • High triglycerides
  • Insulin Resistance

1. Eating Too Much Fructose

Eating too much fructose, the sugar in fruit, can cause cells to become resistant to leptin. This is because fructose is metabolized differently than glucose. Whereas, glucose is metabolized directly into the bloodstream, fructose is metabolized in the liver. This is significant because the liver regulates appetite, and is the main fat-burning organ in the body. Isn’t fruit healthy to eat? Yes, fruit can be healthy, the problem lies in the overconsumption of it, especially fruit juice, which can be easy to over indulge in.

Ideally, you don’t want to consume more than 20-25 grams of fructose per day. To put this in perspective, a glass of orange juice, made from approximately six oranges, equals close to 18 grams of fructose. Fruit that contains more than four grams of fructose per serving is considered high-fructose. Fruit juice and dried fruit should be eaten sparingly due to their fructose content.

High-fructose fruit includes dates, prunes, raisins, grapes, plums, kiwi, mangos, and cherries. Lemons, limes, and berries, are the best choices if you are trying to lose weight or are insulin resistant because they’re low in fructose. Another common source of fructose is high-fructose corn syrup (HFCS). It’s pervasive in the American food supply, and is in virtually all processed foods. HFCS contains 50% fructose, whereas, fruit contains roughly a third as it also contains glucose and sucrose.

HFCS is genetically-modified and very cheap to produce, hence why it’s used in processed foods. Steer clear of anything that is boxed or packaged to prevent impairments in leptin signaling. Eating too much fructose can lead to non-alcoholic fatty liver disease, insulin resistance and leptin resistance.

beautiful platter of assorted fruit

2. High Carbohydrate Diets and Insulin Resistance

Insulin resistance, caused by high-carb diets, is a precursor to diabetes, and can take years to develop.

As cells become resistant, insulin and blood sugar remain elevated long after a meal is eaten. This burdens the insulin-producing cells in the pancreas.

As the condition progresses, insulin is no longer produced and glucose can’t enter cells, eventually resulting in diabetes.

Insulin resistance is epidemic in the United States, with many people having no idea they have it, until they are diagnosed with fatty liver, diabetes, PCOS, metabolic syndrome, or heart disease.

It can take years for cells to become insulin resistant. The condition progressively worsens over time, as the person continues to gain weight in the abdominal area, without realizing the damage that’s occurring in their body. This is because weight gain and other symptoms can easily be blamed on other factors.

Insulin not only regulates glucose levels, but also regulates fat storage. When insulin levels are high, fat cells are stimulated to take up glucose and turn it into fat, via a process called lipogenesis, initiating a vicious cycle. It’s not possible to lose weight unless insulin levels are low, this is why obesity is epidemic. Fat keeps you fat.

Insulin and Leptin Resistance

Both insulin and leptin resistance are to blame for unnatural hunger, intense cravings, and overeating. Leptin is released from fat cells after a meal. It sends the signal: “Stop eating, you’ve had enough!” The inverse is also true, when leptin levels are low, hunger is stimulated.

This illustrates the fact that chronic overeating is not merely a function of willpower. Just as high-carb diets cause insulin resistance, overeating causes leptin resistance and obesity. Cravings and weight gain are the result of cells becoming resistant to insulin, which exacerbates leptin resistance. It’s clear that leptin and insulin are team players.

Add thyroid resistance to the mix and you’ve got a triple hitter in terms of weight gain, and the inability to lose the excess pounds. To make matters worse, thyroid labs can appear normal with leptin resistance in the mix. This is due to leptin’s effect on Reverse T3, an inactive thyroid hormone that blocks the active form of thyroid (T3), at the receptor site. As leptin levels rise, so do levels of RT3 and T3, which can mimic normal thyroid levels, when in reality, levels are low.

Check your leptin levels here


Triglycerides are a type of fat in the blood that correlate with obesity, leptin and insulin resistance, type II diabetes, and cardiovascular disease. In regard to leptin resistance, elevated triglycerides can hinder the messages leptin sends to the brain.

Since leptin regulates appetite, failure of the brain to receive messages, can lead to cravings, overeating, and weight gain. Resistance to leptin arises from impaired leptin transport across the blood-brain barrier, along with defects in receptor signaling.

Triglycerides should be lower than 100 mg/dL on a blood chemistry panel, and ideally under 50 mg/dL, particularly if you’re overweight, have high blood sugar, or are insulin resistant.

Check your triglycerides here

3. Lack Of Sleep

Lack of sleep is a known contributor to increased blood sugar and insulin, as well as the release of stress hormones. Sleep is an important regulator of leptin.

Disruptions in circadian rhythm and sleep disorders impact the concentrations of leptin in the blood. In fact, patients with narcolepsy were found to have a reduction in leptin levels.

Sleep deprivation (5 hours of sleep per night or less) significantly increased obesity risk by stimulating appetite.

Going to bed an hour earlier every night may help you lose weight. Exercise, reducing the amount of caffeine you consume, and eliminating sugar can all increase the quality of your sleep.

Implement a consistent sleep schedule and practice good sleep hygiene, such as turning down the lights an hour or two before you go to bed, sleeping in a cool environment, and making time for relaxation so you can unwind before bed.

Ways To Reverse Leptin Resistance

It is possible to reverse leptin resistance, although it won’t happen overnight, and you’ll need to be diligent and patient.

  • Reduce fructose consumption to under 20 grams a day
  • Eat a low-glycemic diet (will reduce triglycerides and insulin)
  • Get plenty of sleep
  • Drink less alcohol
  • Implement an intermittent fasting routine into your schedule
  • Do high-intensity exercises three times a week

Intermittent fasting is a time-tested tool to reverse both leptin and insulin resistance. It helps you shift from burning sugar for energy to burning fat as your main fuel source. This aids in weight loss and appetite-regulation. Intermittent fasting is not as hard as you think, especially once you’ve made the transition to becoming a fat-burner.

Plus, you’ll save money on food, while saving time on meal prep and clean up. I follow the 16/8 method of fasting, meaning I eat during an eight-hour window, and fast for 16 hours. Essentially, I just skip breakfast and don’t eat after dinner.

High-intensity exercise (HIIT), also called interval training, is a strategic way to exercise because it doesn’t take much time, decreases insulin levels, and releases human growth hormone. Human growth hormone is a powerful fat burner, combine this with reductions in insulin, and you have a highly beneficial strategy for losing weight and increasing leptin sensitivity.

Strenuous exercise, on the other hand, can worsen leptin resistance. HIIT sessions can be performed in a variety of ways, including weight lifting, speed walking, cycling, body-weight exercises, and jumping rope.

[Read More: High Intensity Interval Training Workouts – Lose Weight and Keep It Off]

What Is Leptin Resistance- FDN Banner

Key Points

Leptin is a key play when it comes to the regulation of body fat. It is a primary driver of weight gain, obesity, and inflammation. To keep leptin working properly, monitor closely how much fructose and sugar you eat, get at least eight hours of sleep per night, especially if you’re a woman.

Implement an intermittent fasting and high-intensity interval training routine into your schedule. These strategies will not only help you lose weight, but will keep your leptin levels humming along as they should.

Have you heard of leptin resistance? Let me now in the comments:)


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(1) SugarScience: How The Body Metabolized Sugar

(2) HaleGenic: List of High Fructose Fruits

(3) Mercola: Clinical Scientist Sets the Record Straight on Hazards of Sugar

(4) Mayo Clinic: Metabolic Syndrome

(5) NCBI: Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding

(6) PubMed: The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review.

(7) PubMed: Triglycerides induce leptin resistance at the blood-brain barrier

(8) Harvard T.H. Chan: Carbohydrates and Blood Sugar

(9) Diet Doctor: What is insulin resistance

(10) AOSIS Publishing: How much variance in insulin resistance is explained by obesity?

(11) Wellmark: The hidden dangers of inflammation

(12) healthline: Leptin and Leptin Resistance: Everything You Need to Know

(13) NCBI: Leptin: A biomarker for sleep disorders?


Disclaimer: “I am not a medical doctor, and therefore, cannot diagnose or treat any medical condition, nor do I claim in any way to cure disease. Please be diligent and always do your own research in regard to any material I present on this site. I claim no responsibility for any distress, whether it be physical or emotional, that may occur as a result of the information you obtain from my blog.”

18 thoughts on “What Is Leptin Resistance? [5 Causes And Strategies To Reverse It]”

  1. Glad I came across this blog, it was an interesting read. For the last year I have had weight gain. I used to be really skinny and didn’t have to watch my weight.

    Sometimes I think it is my thyroid but don’t really know. Never heard of leptin before and I enjoyed learning about it. I do have a high carb diet, too little sleep, lack of movement. So it gets me thinking about taking a trip to the doctor.

    And I never thought people could eat too much fruit to the point it becomes bad for the body. That’s surprising! So good job, I don’t like fruit then:)

    • Hi Jenny,

      I’m glad you came across my blog too. Leptin resistance can be tied into thyroid function, and is definitely associated with fructose, high-carb diets, and lack of sleep. Maybe try cutting out fruit and lower your carb intake to see what happens. It also wouldn’t hurt to get your thyroid levels accessed. Thanks for commenting:)

  2. I had heard of insulin resistance, but never leptin resistance, so this article has definitely helped me understand why hunger can occur in myself, as I always try to exercise, but I definitely have too much fructose and my sleep could also improve. Maybe this is why my exercise is not having the intended effects. 

    • You’re in the majority of people, most have heard of insulin resistance, but have little awareness about leptin resistance and how it can affect appetite and weight. Try reducing the amount of fruit you eat, and sleep an extra hour every night. I think you’ll be pleasantly surprised at the results. Best of luck to you. Thanks so much for reading my post:)

  3. Hi! I’m glad I found your post. It has clarified several points for me. First of all, I didn’t know that excessive fructose consumption could cause leptin resistance. But now that I have read it, it makes perfect sense. 

    And the most important point I gathered from your article is the importance of sleep in all this. This speaks directly to me! Thank you very much!

    • Hi Ann, 

      Yes, isn’t that interesting that fructose consumption is directly associated with leptin resistance and weight gain? Sleep is so important. I’m one who literally does not function unless I get enough sleep. I’m glad you learned something you didn’t know. Thanks so much for reading:)

  4. Thanks a lot for such an amazing review about Leptin and explanations are given.

    We have to be careful about what we eat and how much we eat. We can eat anything in reasonable quantities. Leptin is a hormone that plays an important role in our diet. A very good article about leptin, the best I have been able to find.

    Thanks again and keep in touch!

  5. Great info about leptin. It seems that living a healthy lifestyle and keeping tabs on the types of fruit, as well as the amount of fruit you eat is key to keeping leptin in check. We all know how important sleep is, but I still didn’t realize just how important it was in regards to leptin. 

    • Hi Nate,

      Thank you. So many imbalances in the body could be prevented by living a healthy lifestyle. Fruit is healthy in moderation, especially fruit that is low in fructose. I’m confident that if people understood the role that sleep played in regard to weight management, they would make it more of a priority. I appreciate your comment:)

  6. I believe there are important points to be taken from this. From the moment I saw the headline, I was sure it was  going to be an interesting read. Now leptin resistance is clearly not a good thing. In fact, prior to going through this post, I had no idea the degree of it could cause weight gain. 

    So the part that caught my attention is the analogy you used to explain how leptin works. No wonder that had me wondering, is it possible (and safe) to intentionally ignore the signals of the leptin hormones when I’m already full, say, if I was trying to put on extra weight. 

    Thanks for sharing and kindly reply when you get this!

    • Hi Rhain, 

      Thank you. I think leptin resistance is an important topic, considering such a high percentage of the population is overweight. Many people don’t understand the association between leptin resistance and obesity. I’m assuming you’re thin if you’re trying to put on weight, if so, your leptin levels are normal. I hope I understood your question correctly.

      Having sad that, it’s highly likely that many people ignore the messages they get from their brains that they’re full, because after all, food tastes good and eating is an enjoyable experience. We all need to be better in tune with our bodies, a little self-awareness goes a long way in weight management. Thanks you much for taking the time to leave your thoughtful comment:)

  7. Extraordinary post! I thank you very much for the knowledge that you provide here. I personally, have never heard of this hormone, Leptin. However, based on what you wrote, I became more aware about Leptin which turned out to have a very significant effect on the body. As far as I know, diabetes occurs because of high glucose levels in the blood and insulin resistance. However, because of your writing, I have come to understand that insulin resistance can cause leptin resistance and that resistance can worsen the condition.
    By the way, speaking of leptin resistance,  I have several questions:

    – Is there any medical test that can be done? Such as insulin resistance tests using HbA1C.
    – Is leptin produced in all fatty cells in the body? Or is there a certain place?
    – And is it possible, leptin resistance can occur without insulin resistance?

    Once again, thanks for your valuable information. I have bookmarked your website and subscribed to it.

    • Hi Kylie,

      Thanks so much for commenting and for subscribing. Many people haven’t heard of leptin, but most are familiar with insulin and the role it plays in diabetes. You can get your leptin levels tested. There is a link in my post if you’re interested. 

      Leptin is released from the fat cells throughout the body after a meal is consumed. Insulin resistance is an underlying factor in leptin resistance. They typically occur together. Thank you so much for reading my article:)

  8. With regard to the obesity cases, researchers have discovered that even mild sleep deprivation can disturb the hormones ghrelin and leptin that control appetite. Sleep deprivation may also develop substances in the blood that indicate prolonged inflammation which is linked with diseases like colon cancer, breast cancer, heart disease and diabetes.

    • Very interesting. It seems that more and more research is coming to light in regard to health and sleep. Those who don’t get enough sleep almost wear it like a badge of honor, not realizing what they’re doing to their health. I’m not surprised that lack of sleep correlates with inflammation. Thank you for your input:)

  9. A few years ago I tried another really good diet, I believe it was called the “Slow-Carb diet” from a book called, “The 4-Hour Body” by Tim Ferris. This diet was known to decrease leptin resistance. I felt great, lost my sugar cravings, and lost a full 60 lbs within 3 months of implementing the first few chapters of the book. Great tips!

    • Hi Elaine,

      Wow, that’s awesome that you were able to lose 60 pounds. It’s all about the carbs when you’re trying to lose weight. Thanks for reading and commenting:)


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