Leptin and Obesity: Key Things to Know about Leptin Resistance

Medical Reviewer: Florencia Halperin, MD
Published on: April 13, 2023
Updated on: March 5, 2024

Learn more about how FORM pairs patients with a doctor and dietitian to achieve their weight loss goals.

Gherlin and Leptin


The common assumption about weight loss is that all a person needs to do is “eat less and move more,” but in reality it’s not that simple. Various factors can affect body weight balance and many of these are not under a person’s control. For example, fat cells produce hormones, also known as adipokines, that can affect our regulation of appetite. Leptin is one of these hormones that we’ll discuss and highlight the link between leptin resistance and obesity.

What is Leptin and Why is it Important? 

Leptin is a hormone produced by fat cells that normally signals to our brain to make us feel full.  Leptin production is linked to our body fat stores, so with more body fat we make more leptin and with less body fat there is less leptin. Normally, when there is more leptin (more fat stores) it signals to the brain that we are full and food intake decreases, eventually leading to a decrease in weight. On the other hand, as we lose weight (less fat stores) we have a decrease in leptin, so now the brain is not getting those signals for fullness and as a result appetite increases eventually leading to weight gain. Simply put, if we lose weight we have a biological drive to eat more. This is an important evolutionary adaptation that allowed our ancestors to survive starvation and is also thought to play a role in why weight regain is common after weight loss

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Leptin Resistance and Obesity

When the leptin hormone was first discovered, it was thought that it would be a major game changer in treatment of obesity. Perhaps the reason why someone is not able to lose weight is that they are not making enough leptin? While there are rare genetic conditions where inadequate leptin production leads to severe obesity, for the majority of people with obesity that is not the underlying cause. In fact, what researchers have found is that people with obesity can have high levels of leptin, yet there is not the expected decrease in appetite and subsequent weight loss.  

So why is leptin high in obesity? Well, it goes back to the understanding that leptin production occurs when there is more body fat. The real question is why is there obesity despite high leptin levels? This is explained by something known as leptin resistance where the brain no longer listens to the leptin signal- it becomes resistant or unresponsive- even though the body is fully capable of making the leptin signal. In the case of obesity, if there is leptin resistance despite having an excess of body fat and making leptin, we have strong feelings of hunger which ultimately leads to increased food consumption with worsening weight gain. It also turns out that leptin plays a role in dampening the “feel good” feelings we get from food. So another driver of weight gain in leptin resistance is the continued stimulation of the reward system in our brain by food. It is also important to point out that leptin does not just regulate appetite. In fact, it can affect weight balance through its impact on energy expenditure, glucose and cholesterol metabolism, insulin resistance, and fat deposition.

How Can You Tell If You Have Leptin Resistance?

If you have excess weight and struggle with losing weight and feeling hungry, it’s possible that you may have underlying leptin resistance. However, testing for leptin resistance is typically done in clinical research settings. Ultimately, addressing leptin resistance in the context of obesity is through treatment of obesity itself.

Evidence-Based Treatment of Obesity

Lifestyle Changes

Studies have identified key foundational lifestyle changes for weight loss: Nutrition, physical activity and mindset shifts.  Nutrition for successful weight loss focuses on decreasing calorie intake in a manner that is sustainable. Increased physical activity in combination with a low-calorie diet has been shown to be an important component of weight loss and long-term weight loss maintenance. Additionally, adjusting our environment and our mindset to better support our healthy habits is essential. At FORM, our approach to helping patients with their weight loss goals involves understanding the unique challenges in your life and helping you find a personalized path to your weight loss success that addresses these key foundational lifestyle factors.


Those who have struggled to lose weight or to maintain weight that was lost with just nutrition and physical activity may be candidates for weight loss medications. The current FDA-approved medications for weight loss include phentermine, orlistat, Qsymia®, Contrave®, Wegovy® and Saxenda®. 

How do these medications work?

These medications work in different ways to ultimately decrease appetite and cravings resulting in a lower calorie intake. Orlistat is the exception, it works by blocking fat absorption such that the calories from fat in a meal are not processed by the body.  

How much weight can I expect to lose with these medications?  

On average, patients lose 5-10% of their body weight when taking most of the current FDA-approved medications for weight loss, when used in combination with a reduced-calorie diet and increased physical activity. A notable exception to this is Wegovy which demonstrated on average ~15% body weight loss at one year in subjects taking the highest dose (2.4 mg) in combination with diet and exercise.  

Am I a candidate for weight loss medication?

For adults who have struggled to lose weight or maintain weight that was lost with lifestyle changes (low-calorie diet, increased physical activity) alone, medications may be considered so long as the person meets the following body mass index (BMI) criteria:

  • BMI 30 kg/m2 or more
  • BMI 27 kg/m2 or more with a weight-related medical condition such as high blood pressure, diabetes, high cholesterol, sleep apnea, etc.

There are specific contraindications to weight loss medications and considerations based on your medical history, so it is important that you discuss this with your doctor.

Let FORM Help You Reach Your Weight Loss Goals

Losing weight can be challenging for many different reasons, but FORM is here to help.  At FORM, you are paired with a medical doctor who is board-certified in Obesity Medicine and a Registered Dietitian who utilize their expertise in weight management to develop a personalized weight loss plan tailored to your needs. They address nutrition, physical activity, and mindset shifts to help you be successful, and, if appropriate, may prescribe FDA-approved weight loss medications.

FORM is here to help you successfully achieve your weight loss and health goals. Visit FORM online for more information on weight loss medications or send a message with additional questions. Ready to get started? Take our quiz to see if FORM is right for you.

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