Leptin is a hormone produced primarily by fat cells in the body. It regulates appetite, energy expenditure, and other functions related to metabolism. Leptin plays an essential role in regulating body weight and blood glucose levels. However, there are rare cases where the body does not produce enough leptin. These individuals have been known as “leptin resistant” or “obese without obesity.”
The exact cause of leptin resistance is unknown, but it may result from genetic factors or environmental influences. There are several theories about how leptin works.
The leptin-deficient patient has high levels of circulating leptin, but leptin is either unable to bind to its receptor or the receptor can no longer respond to the binding.
The leptin receptor itself is not working properly.
The hypothalamus no longer responds to leptin.
Some studies suggest that a combination of these factors may be at play.
Since the exact cause of leptin resistance is unknown, there is no known cure. Some studies have shown that leptin injections can reduce food intake and body weight in leptin-resistant mice.
One theory about how leptin resistance develops suggests that it is a protective response to excess leptin, rather than a problem with the leptin receptor itself. The body may develop resistance as a way of defending against too much leptin.
This may occur when there is too much leptin in the blood for the receptor to handle.
The body’s defense mechanism is similar to the way the body defends itself from allergens by developing histamine intolerance.
Excess leptin in the blood may also cause inflammation of the brain’s hypothalamus, which may be responsible for causing leptin resistance. A leptin-resistant brain may also trigger hunger, lower the body’s metabolic rate, and cause weight gain.
In rare cases, congenital leptin deficiency may be caused by mutations in the leptin gene. Congenital leptin deficiency can be diagnosed by a blood test that measures leptin levels.
Treatment for congenital leptin deficiency involves regulating diet and exercise in order to maintain or gain weight. Specialists may also prescribe a combination of leptin and a low-calorie diet.
In obese people, obesity is a more common cause of leptin resistance.
Obesity is a risk factor for several diseases, including heart disease, stroke, and type 2 diabetes. Excess weight can make it more difficult for the body to control its blood sugar levels, putting users at risk for diabetes.
It can also cause life-threatening health conditions such as hypertension and heart disease.
The exact link between leptin resistance and obesity is not yet known. However, it is clear that obese people are more likely to become leptin resistant.
Obesity has a major effect on leptin levels and the body’s response to leptin.
Many obese people experience a drop in leptin levels as their fat cells begin to produce less of the hormone. Since the body becomes used to the normal level of leptin in the blood, it becomes increasingly difficult to lose weight.
The brain may also develop leptin resistance as a result of high leptin levels caused by obesity.
Since leptin is primarily transported by blood, a lack of exercise can also lead to leptin resistance. The transport of leptin from the blood into the brain is not well understood.
Some studies have shown that leptin may cross the blood-brain barrier directly. During exercise, capillaries in the muscles expand to transport more blood and nutrients to those muscles.
This may allow greater transport of leptin into the brain, which could explain why exercise helps some people to maintain normal levels of leptin.
As a rule, obese people do not exercise regularly. This lack of exercise leads to reduced transport of leptin and a greater risk of leptin resistance.
There is some evidence that stress can lead to leptin resistance. When people are under stress, the body may respond by raising the levels of the hormone cortisol.
Cortisol has been found to block leptin from reaching the brain. This may be part of the body’s natural defense against starvation during times of stress.
Unfortunately, this mechanism can also lead to leptin resistance.
Stress can also cause the body to store fat in unhealthy ways. For instance, stress may cause the body to store fat around the abdomen.
This abdominal fat has been associated with several diseases and disorders.
Stress is often caused by work, family, and other life events. When people are under stress, they are less likely to exercise or otherwise take care of themselves.
Stress can also cause people to eat more comfort foods, often high-calorie and high-fat snacks.
Environmental toxins such as pesticides may also contribute to leptin resistance. Certain pesticides have been found to affect the brain’s response to leptin, making it harder for a person to lose weight.
Even sleep has an effect on leptin. People who don’t get enough sleep tend to have higher levels of leptin and a reduced response to the hormone.
Obese people tend to have a chronically reduced amount of sleep.
As more studies are done on leptin, we may find other factors that cause leptin resistance. Obesity is clearly one of the major causes, but it isn’t the only one.
How Is Leptin Resistance Diagnosed?
There is no specific test to measure leptin resistance. A diagnosis is usually made by a medical professional after discussing symptoms with the patient. They may also perform some tests to ensure that the patient doesn’t have other conditions such as thyroid problems or eating disorders.
The best way to diagnose leptin resistance is to track weight and diet. The patient must first go on a diet that reduces calories to between 1,200 and 1,500 per day.
After two weeks of dieting, the patient should notice a reduction in weight. If the patient doesn’t lose any weight, this may be a sign of leptin resistance.
How Is Leptin Resistance Treated?
There is currently no cure for leptin resistance. However, the effects of leptin resistance can be treated and reduced with diet and exercise.
The diet required is very strict for the first two weeks. A patient needs to consume only between 1,200 and 1,500 calories per day.
Carbohydrates should be restricted to only those found in vegetables. Fruits are allowed, but only if they are not overly ripe. Proteins should also be restricted. Dairy products and most fats are not allowed.
After two weeks of this restrictive diet, the patient should lose weight. At this point, the patient can slowly add more healthy foods back in their diet.
However, they should continue to eat healthily and exercise regularly to maintain their weight loss.
It is also very important that the patient keep exercising while dieting. This is often the hardest part for people.
People who have lost weight tend to be very tired and do not feel like exercising. However, an exercise program must be followed in order to keep excess weight off.
While it may be difficult in the beginning, the patient should find that exercising does get easier as their weight goes down. It’s also important to remember that weight loss is not a quick process.
It can take several months to reach one’s goal weight.
People who have lost weight and kept it off become “metabolically flexible.” This means that they become more responsive to the hormone leptin.
This makes it easier to diet and exercise when needed.
Recent studies on leptin have also shown that a low calorie diet can increase leptin levels and make a person more sensitive to the hormone.
In certain extreme cases of leptin resistance, bariatric surgery may be necessary. Weight loss surgeries are used in cases of obesity where other methods have failed.
These procedures can cause as much as a 30 percent weight loss in one month. This can drastically increase a person’s sensitivity to leptin and make dieting easier.
One increasingly popular method of weight loss is a procedure called the duodenal switch. This surgery causes weight loss by making the stomach smaller and making the digestive system process food in a different way.
This can cause dramatic weight loss in certain patients and make it much easier to lose weight in the future.
In the next section, we’ll look at a few patient case studies that highlight some of the symptoms and treatment options for leptin resistance.
Sources & references used in this article:
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- Mutations in ligands and receptors of the leptin–melanocortin pathway that lead to obesity (IS Farooqi, S O’rahilly – Nature Clinical Practice Endocrinology & …, 2008 – nature.com)
- Leptin promoter mutations affect leptin levels and performance traits in dairy cows1 (SC Liefers, RF Veerkamp, MFW Te Pas… – Animal …, 2005 – Wiley Online Library)
- Leptin deficiency and leptin gene mutations in obese children from Pakistan (W Fatima, A Shahid, M Imran, J Manzoor… – … journal of pediatric …, 2011 – Taylor & Francis)
- Human leptin receptor gene in obese Japanese subjects: evidence against either obesity-causing mutations or association of sequence variants with obesity (N Matsuoka, Y Ogawa, K Hosoda, J Matsuda… – Diabetologia, 1997 – Springer)
- Mapping of the leptin binding sites and design of a leptin antagonist (F Peelman, K Van Beneden, L Zabeau… – Journal of Biological …, 2004 – ASBMB)