How hormones affect weight loss: leptin and leptin resistance

How leptin metabolism works and its effect on the brain

Leptin is a protein that acts as a hormone in the human body. It is made in many places in the human body, the most important of which are white adipose tissue, specifically cells called adipocytes (cells of the adipose tissue) and enterocytes (cells of the small intestine).

Leptin binds to receptors in the hypothalamus and endometrium (the lining of the uterus). This hormone is commonly known as the satiety hormone or the starvation hormone.

Its main function is to regulate energy homeostasis, mainly by suppressing hunger. Respectively, through the hypothalamus, it acts on adipocyte tissue and influences hunger, food energy utilization, physical exercise and energy balance.

Leptin acts on receptors in the hypothalamus by suppressing the effect of neuropeptide Y and Anandamide, potent promoters of hunger. It also stimulates the synthesis of α-MSH, a hunger-suppressing hormone.

Low leptin levels, on the other hand, induce hunger and are commonly a sign of starvation or eating disorders such as anorexia or bulimia. It is naturally present in higher amounts in women, regardless of weight.

In obesity, a state of hyperleptinemia occurs, which causes leptin resistance. Leptin further interacts with other hormones and energy regulators. It serves as an indirect mediator of the action of insulin, glucagon, growth hormone and others.

What is leptin resistance?

In a healthy individual, leptin serves as a messenger that tells the brain if it has enough body fat stores. When there is excessive fat, large amounts of leptin are secreted.

In this situation, leptin acts as a satiation hormone and at the same time the body starts burning more energy. Otherwise, leptin levels are low, which sends a signal to the brain that it is time to eat and conserve energy.

In obese people, this system does not work. Increased levels of the hormone do not regulate hunger and does not help weight loss. This leads to so-called leptin resistance, similar to insulin resistance in type 2 diabetes.

This could be due to high levels of triglycerides in the blood, which prevent leptin from crossing the blood-brain barrier (which separates the vascular system and the brain) and thus preventing it from acting on receptors in the hypothalamus.

The effect of leptin on weight loss

Leptin resistance is probably one of the reasons why many diets do not have long-term effects. Even a short fast or reduction in food intake results in a rapid reduction in blood leptin levels. This phenomenon leads to decreased energy – fatigue, and hunger. This could probably be the reason why most diets fail within the 2nd week.

In addition, leptin levels seem to respond more to starvation than satiety. The body tries to be in balance (homeostasis) all the time, so it does not respond to high leptin levels in obese people or women with polycystic ovary syndrome.

This is despite the fact that leptin production rises exponentially, not linearly, in proportion to the fat cell supply.

Thus, it is very easy to get into a state of leptin resistance while having low leptin levels that induce hunger even in overweight individuals.

What causes leptin resistance and can it be reversed?

There are three main mechanisms that can potentially influence and cause leptin resistance:

  • Inflammation of the body: Inflammatory processes negatively affect the hypothalamus and thus may influence leptin resistance in animals and humans
  • Free fatty acids: Elevated levels of free fatty acids in the blood counteract leptin’s satiety signaling
  • High leptin levels: Elevated levels of the hormone appear to be a major cause of leptin resistance

Most of the factors are more pronounced due to obesity. It is very easy to develop leptin resistance, for example on so-called cheat days.

Especially at the beginning of a diet, there is a rapid drop in leptin levels and thus an induced feeling of hunger. The body then demands more food and reduces energy consumption. Moreover, leptin resistance has a certain inertia and it takes time for the body to adapt to a permanent reduction in blood levels of the hormone.

Thebest way to reverse resistance is to limit foods that cause inflammation in the body, especially junk foods containing refined sugars. Try to eat a balanced diet overall and do not follow crash diets. It is better to gradually change your diet, reduce the number of calories and start exercising so that the body gradually gets used to it.

How to reverse leptin resistance?

Unfortunately, there is no miracle cure for this problem. Experiments have been conducted where obese people have been given leptin itself in the form of a supplement. This was effective, but not in all individuals.

The main difference between subjects was leptin resistance, which is a result of large amounts of the hormone in the blood. Therefore, increasing it did not achieve the desired goal.

Another substance that is used to treat obesity is amylin. Amylin is pectin, a hormone secreted by the beta-cells of the pancreas along with insulin. Its main function is to regulate blood glucose levels, acting synergistically with insulin and leptin.

In obese individuals suffering from leptin resistance, it helps to reduce body weight. Amylin seems to be able to suppress hunger and control energy expenditure even in the case of leptin resistance.

Another effective strategy is to limit consumption of foods that cause inflammation. A gradual change in diet and a healthy lifestyle is most effective in the long term to reverse the effect of leptin resistance.

  • Avoid processed foods: Highly processed food can disrupt the gut wall, causing inflammation
  • Eat plenty of soluble fibre: Water-soluble fibre, such as pectin (found in fruit skins and legumes), psyllium or soya milk, reduces the reabsorption of bile from the small intestine and thus lowers blood cholesterol levels.
  • Exercise: Physical activity is needed to reverse leptin resistance. Start with short stretches and walks and gradually progress to higher loads.
  • Sleep: Adequate amounts of quality sleep are highly effective. This is because leptin levels are highest during the night and early morning hours. So enjoy it to the fullest.
  • Reduce free fatty acids: Free fatty acids, specifically triglycerides, inhibit the transport of leptin from the blood to the brain. You can most effectively reduce triglyceride levels by limiting your intake of carbohydrates, especially refined sugars.
  • Increase protein intake: Although modern humans eat seemingly large amounts of meat, lack of protein in the diet is still a problem, especially for women. It is the ratio of macronutrients in the diet, which often contains too many carbohydrates. By increasing protein intake, it helps to reduce body weight and prolong the feeling of satiety.

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