Leptin Resistance: What it Means, Symptoms, Causes, Treatment

Fernando Mariz

Medically reviewed by

Fernando Mariz

Fernando Mariz

About

Dr. Fernando Mariz is a Manhattan-based doctor focused on contemporary medicine. He trained in gynecology and is a specialist in preventative care, pelvic pain, abnormal uterine bleeding, and sonography. His philosophy is to establish a partnership with his patients with their goals in mind, to achieve the best possible outcomes. Dr. Mariz completed his undergraduate studies with a Bachelor of Science in Biology and Chemistry at the Florida State University, followed by his Medical Degree at the Poznan University of Medical Sciences. He went on to do a residency in Obstetrics and Gynecology at the University of Toledo Medical Center. In residency, Dr. Mariz took special interest in minimally invasive surgery and sonography. He taught co-residents and medical students, was awarded 'Teacher of the Year', and even honorarily inducted into the American Association for Gynecologic Laparoscopists.

Credentials

Medical Advisory Board Member At:

• Nu Image Medical

Written by our editorial team.

Last Edited 1 year ago · 8 min read

Hormones are chemicals that manage different body functions by carrying messages through the bloodstream to the tissues, organs, and muscles, telling them what to do, and when. Over the years, scientists have discovered  50 hormones in our body that all work harmoniously to keep us functioning at our peak. 

However, peak functioning can be thrown off, causing imbalances and resistances due to illness or lifestyle. Leptin is one of the lesser-known hormones that can cause quite a stir when its presence or function is disrupted. 

Below we uncover more about leptin resistance, its symptoms, causes, and possible treatment options: 

What is Leptin?

Leptin, also known as the starvation or satiety hormone, is responsible for feelings of satiety (fullness) and regulating hunger, making it a key player in long-term weight maintenance. The hormone is produced and released by the adipose tissue (body fat), which means adipose tissue is the main regulator of the hormone. 

Leptin levels often fluctuate from person to person depending on an individual's current weight and body fat percentage. Although leptin was discovered in 1994, there is still a lot about the hormone that scientists are yet to discover, but presently, research shows that its significant effect on the stomach starts in the brain and ends with the thyroid gland. 

According to studies, leptin acts within the hypothalamus  (a part of the brain) to suppress food intake and decrease body fat. It also notifies the brain when energy levels or calorie intakes are sufficient or when intake needs to increase. Several factors can influence the presence and functionality of leptin, some of which include:

• Stress

• Exercise

• Meal timing 

• Calorie intake

• Light exposure

• Sleep/wake schedule and sleep duration (circadian rhythm)

Although its primary function lies with intake and weight management, leptin also influences immunity and inflammation while creating a balance in several other systems.  

What is Leptin Resistance? 

To properly understand the concept of leptin resistance, we must first acknowledge how the leptin hormone works. Leptin is also mainly  created and released by fat tissues. Its primary function is to regulate appetites and metabolisms by sending signals to receptors in the brain. 

Once these signals reach the brain, it's broken down and interpreted as feelings of fullness (also known as satiety). These feelings stop the body from consuming more food and consuming calories unnecessarily. It also sends the body into a state of fat-burning when we are active, converting excess fat into energy. 

People with leptin resistance often experience a disconnect between the brain and body. Fat tissue releases leptin, but the brain doesn't respond to the feelings of fullness or the signals to burn calories or excess fat when needed. Instead, the hormone remains dormant, and individuals continue to feel hungry despite eating a full meal. 

Leptin resistance makes it difficult for the body to understand signals which tell it to:

• Convert unnecessary fat into energy

• Increase metabolism rates to burn excess calories 

• Control or stop eating because the body has enough food or energy supply

This results in excessive food/calorie consumption, causing weight gain and the growth of fat cells (adipocytes). Those fat cells produce more leptin, typically causing high leptin levels (hyperleptinemia). The uneven consumption of calories also causes an energy imbalance which, in retrospect, affects our overall functionality.

Leptin Resistance Symptoms

In essence, leptin resistance results in the decreased response to the leptin hormone. So whether leptin is present in high or low amounts, it is completely unable to carry out its main function to suppress appetites or appropriately trigger metabolisms or energy use. Because of this, the main signs/symptoms of leptin resistance are constant hunger and increased food consumption despite having already consumed adequate amounts of calories.

Leptin resistance can also present other symptoms, which are quite noticeable. Let's look at some of them below:

• Obesity, continuous weight gain, or excessive amount of body fat

This is the most common sign of leptin resistance and typically has quite a rapid onset. It primarily happens because the feeling of fullness is not experienced, and the body is not burning excess calories. 

Evidence shows that this symptom can show quite early-childhood or early puberty with weight gain driven by improper conversion of fat to energy, interference with accelerating metabolism rates at ideal times, and illogical responses to food and food consumption. 

• Belly fat

Similar to obesity or excessive weight gain, belly fat formation is very prominent and can be noticed and formed very fast. It primarily happens in the case of leptin resistance due to lowered or inconsistent metabolisms and is supported by overeating.

According to studies, leptin resistance plays a role in metabolic decline, causing the uneven distribution of fat and the formation of belly fat (also called abdominal fat). Visceral fat negatively affects overall health and increases risks for diseases like diabetes and heart disease.

• Fatigue

Fatigue is the constant feeling of tiredness and lack of energy. As we mentioned earlier, leptin resistance causes an energy imbalance because food is not being consumed when needed, and fat is not properly converted into energy. 

A PubMed study supplies evidence of the correlation between leptin resistance and chronic fatigue, confirming that the resistance causes low energy levels because the brain doesn't respond to the signals telling it to burn calories. Leptin-resistant individuals may also be less physically active due to a lack of energy, which makes this another symptom of the condition. 

• Pain disorders

Those with leptin resistance often have large volumes of the hormone flowing through the body, making them more sensitive to pain and more prone to developing chronic pain disorders such as fibromyalgia. 

Studies show that the link between pain and leptin comes from leptin-mediated inflammation. Leptin basically tells the body when to induce inflammation, so too much of the hormone causes the body to receive the wrong signals, becoming inflamed for no reason, leading to pain sensitivity/disorders. 

• "Junk food" cravings

Leptin resistance can support excessive and unexplained cravings because the brain doesn't receive the correct information about calorie intakes, feelings of fullness, stored energy levels, or metabolic boosts. This cause the body to be in constant search mode, looking for something to fulfill hunger and supply energy fast—junk food, unhealthy food, high sugar/fat food. 

The hunger and cravings also send metabolisms into idle mode, making it hard to control weight. A PubMed study shows that excessive cravings in leptin-resistant individuals cause larger hip circumferences and altered body compositions.

Causes of Leptin Resistance 

Most medical illnesses, diseases, deficiencies, and conditions can be traced back to a cause that is often divided into several categories to better understand and plot a way forward for treatment. However, not all conditions are easy to dissect, and finding a definitive cause behind a condition like leptin resistance can be hard.

So research is still ongoing for a specific cause, though some theorize contributing factors may be involved. Researchers have found that leptin resistance usually develops over an extended period, and may occur because of 3 potential factors: 

1. Limited sleep 

When we sleep, leptin levels increase and let our brains know we have plenty of energy, so there's no need to trigger hunger or burn calories for energy because we are essentially in a resting phase. According to studies, limited amounts of sleep and decreased sleep quality or duration cause leptin levels to drop, making the body think we have too little energy for our needs. 

This triggers feelings of hunger and unnecessary eating, which results in slow metabolisms and weight gain because we are essentially not active during this period. The constant miscommunication between the brain, leptin, and the body results in leptin resistance. 

1. High cortisol levels—too much stress 

When we stress too much, cortisol levels peak over and above normal levels, leaving us reaching for comfort food. This is not only because we want to feel better but also because leptin functionality is being affected. 

Research shows that high cortisol levels often cause leptin levels to drop, eventually encouraging unnecessary food consumption, energy deficits, and metabolism issues. The complex relationship between cortisol and leptin may fuel insufficient amounts of leptin production or end organ target resistance. 

1. Overeating or high consumption of unhealthy or wrong foods 

Unhealthy eating is a common contributing factor to most illnesses, and leptin resistance is no exception. Studies show that excessive or late-night snacking can cause a build-up of triglycerides (a type of blood fat).

This results in a never-ending cycle of hunger, inadequate energy supply, increased weight gain, and prolonged leptin exposure potentially contributing to leptin resistance.

Other factors that may contribute to the development of leptin resistance may include:

• High insulin levels

• High triglyceride levels

• Too little or too much exercise

• Too little sun or time spent outdoors

• Abnormal brain response to leptin signals

• Too much sugar, especially high-fructose corn syrup

• Inconsistent dieting (alternating starvation with binge eating)

The contributing factors or causes mentioned above often cause damage to metabolic functions and the endocrine system worsening the symptoms of leptin resistance. It also supports the development of other conditions like disordered eating. All these conditions almost play off each other, creating a vicious cycle. 

Diagnosis of Leptin Resistance 

Similar to its causes which are still being researched, leptin resistance does not have criteria for diagnosis as the details are still being ironed out. At the moment, leptin resistance is more often seen as an underlying condition that contributes to obesity rather than a distinct illness that requires diagnosis on its own.

Nevertheless, healthcare professionals use the leptin resistance symptom list we explained earlier and the below to confirm the presence of the condition:

• Unstable leptin levels 

• High levels of inflammation

• Inability to lose weight, no matter how hard you try

In addition to the above, professionals also do a standard blood test to check for other associated abnormalities, but this is more of an additional measure that goes along with checking off experienced symptoms. After the presence of leptin resistance is confirmed, the course of treatment often revolves around the other health issues paired with leptin resistance. However, effective treatment options are available if users decide to take an individual approach. 

Leptin Resistance Treatment 

Most of them are diet-related because the key to reversing resistance is weight loss, and while that may seem a bit too conservative for the issue at hand, it does indeed work.

Research shows that an improved diet can help leptin work for you instead of against you, which is very beneficial in the long run. Since the resistance is active and present when you may be seeking treatment, and the symptoms of leptin resistance are overeating and cravings, it might be hard to get a grip on healthy eating.

This is why the first step to treatment is controlling the types of food eaten rather than the amount. Once you zero in on consuming the ideal food types, food portioning can come in, and the road to leptin resistance recovery is paved. A nutrient-dense diet with very little processed food should be paired with exercise, sleep, and stress management. 

When leptin resistance is paired with weight-related conditions/disordered eating—obesity and its associated conditions. The diet, exercise, and improve lifestyle approach have been used in combination with several drugs, based on concurrent medical conditions, to aid in condition management such as:

• Saxenda

• Victoza

• Byetta

• Bydureon

• Trulicity

• Ozempic

These drugs belong to a class of medication called GLP-agonists, which was created to treat diabetes. However, research shows that they have a positive effect on both leptin sensitivity, insulin sensitivity and even help with weight loss, 3 effects that may improve leptin resistance. 

The Bottom Line

Leptin plays quite an influential and interesting role in the body. It acts on the brain to regulate various functions, including hunger and energy, two of the most important aspects that keep us running like well-oiled machines. Leptin resistance can drastically affect our health, so it's definitely important to keep leptin functionality in check and reverse leptin resistance as soon as we notice the signs and symptoms creeping up.

10 Sources

Nu Image Medical has strict sourcing guidelines to ensure our content is accurate and current. We rely on peer-reviewed studies, academic research institutions, and medical associations. We strive to use primary sources and refrain from using tertiary references.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2670357/

https://pubmed.ncbi.nlm.nih.gov/16932334/

https://pubmed.ncbi.nlm.nih.gov/12023258/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637529/#B10

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829991/.

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC535701/

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https://pubmed.ncbi.nlm.nih.gov/30472395/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651558/

This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your physician about the risks and benefits of any treatment. Nu Image Medical may not offer the medications or services mentioned in this article.