The fat cell hormone leptin is elevated: what does this mean and is there any cause for concern. Leptin is a satiety hormone. How to restore sensitivity to it? Excess leptin

Calories enter the body, calories are consumed by the body - to put it very simply. If you really want to curb desire and control your appetite, you need to increase your leptin levels in your body. Leptin is a hormone that tells your body that it is full. If your leptin levels are too low, you can eat and eat and eat and still feel hungry. With the help of things like diet and lifestyle, it is possible to raise leptin levels in your body (assuming it is functioning properly). To get started see Step 1 below.

Steps

Part 1

Limit your fructose intake. In scientific terms, fructose suppresses your leptin receptors. . There are no alternatives. You may have enough leptin in your body, but if your body isn't able to recognize and harvest it, it won't do you any good. Therefore, you should stop taking fructose - high fructose corn syrup. Let your body take care of itself.

• The main culprit here is processed foods. Fructose is often used as the cheapest sugar substitute in sodas, cookies and other sugary snacks that clutter many kitchen cabinets. Therefore, the best way to avoid them is to be sure that whatever foods you eat, they should not be related to the packaging industry.

1. Say no to simple carbohydrates. It's time to get used to this idea, isn't it? The fact is that simple carbohydrates (refined, sugary, and generally white) reduce insulin levels in the body. This in turn leads to resistance and imbalance in leptin production. Therefore, eating white bread, white rice and all those delicious baked goods that tempt you should be completely avoided.

   • If you have carbohydrates in your diet, they should be good quality: whole oats, quinoa and whole pasta. The darker the color, the better - this means that they were not bleached during processing and did not lose nutrients.

2. Avoid strict calorie restriction. Some people may advise you to stop eating carbohydrates almost completely. You can do this, but you must be sure that your body does not think that you are starving. If your body does not receive enough nutrients, it will stop working and hormonal imbalance will occur. To complete such a diet you will need enormous willpower, as you will have a strong feeling of hunger. This is not a good system for success.

   • Of course, weight loss has a positive effect on leptin production. When you are at a healthy weight, your hormone levels normalize (in a normal situation, of course). If you are overweight or obese, it would be good to follow a diet. At the same time, the diet should be healthy and balanced. You should also be able to stick to this diet for a long time.

3. If you adhere to a low-carbohydrate diet, then give your body loading days. If you decide to follow diets such as the Atkins diet, raw diet or paleo diet, arrange loading days. Your body needs carbohydrates to refuel, rebuild, and jump-start your metabolism. During the loading day, your goal is to eat 100-150% more carbohydrate-containing foods than usual. After this, you should continue to follow the diet.

   • It's also good for motivation. It's very difficult to stop eating pizza for the rest of your life. But when you know you can eat it on Saturday, it's easier to avoid it on Wednesday. That's why some people call such a day "cheating."

4. Don't yo-yo diet. Seriously. Don't use it. It will lead to both metabolic failure and hormonal imbalance in your body. This will not pass without a trace for you. As a result, you will not only return to your weight again, but even gain it. Therefore, you need to choose a healthy and sustainable diet. Many researchers agree that a diet should not force you or break you in any way. Your body cannot afford to first starve and then suddenly consume large amounts of harmful foods. The body will not be able to work with such changes.

   • While you are on this diet, do not break it. This will help you lose weight (at least initially, of course). But such a diet will not help normalize leptin levels. First you will get rid of toxins. But when you stop drinking only lemonade and spicy sauces, you will pay for it.

Part 3

1. Relieve stress. When we are anxious and stressed, our body increases the production of cortisol, which in turn disrupts hormonal balance, including leptin balance. If you have heard about the phenomenon of stress eating, then the connection will become clear to you. Therefore, if you don’t remember how to relax, you need to learn how to do it. Your leptin levels depend on this.

   • If this is still not a mandatory procedure during the day, then try yoga or meditation. Both options lead to relaxation. Therefore, your sleep will improve and your cortisol levels will decrease. Don't dismiss these relaxation options until you try them!

2. Get a good night's sleep. This will lead directly to the goal, as sleep regulates leptin and ghrelin levels (ghrelin is the hormone that tells your body that it is hungry). When you don't get enough sleep, your body starts producing ghrelin and stops producing leptin. Therefore, go to bed on time so that you get about 8 hours of sleep each day.

   • To make this easier, stop using electronics a few hours before bed. Light tells our brain to stay awake. Thus we feel anxious. Turn off the lights early and your brain will know it's time to sleep.

3. Don't overexert yourself. Madness. Never thought you'd hear something like this? There is such a thing as heart failure when it comes to leptin. Too much stress on the cardiovascular system (endurance, longevity) leads to increased cortisol levels, increased oxidative damage, systemic damage, suppressed immune system and slowed metabolism. There is nothing good about this. So you can consider this as an excuse when you skip going to the gym one day. If there is too much useful stuff, it can end badly.

   • It is worth noting that moderate exercise is beneficial for strengthening the cardiovascular system. High-intensity interval training, or exercises with intervals in general, are very beneficial for your body. Our ancestors didn't need to run for hours without stopping and we don't need to either. If you are looking for a place to work out, then play sports and have fun. There is no need to stress about this.

4. ...But be sure to do at least a little exercise. On the other hand, a sedentary lifestyle is leading. It's also not very good for you. Therefore, when you get to the gym, stick to interval training (for example, you can run for about a minute, and then walk for about a minute. This exercise can be repeated about 10 times) and some pull-ups. You want to be viable and relatively healthy, and not a skinny couch potato?

   • Make an active lifestyle come naturally to you. Instead of forcing yourself to go to the gym, you can go for a hike, go to the pool, or play basketball with friends. After all, exercise doesn't have to be done as an "exercise"? In any case, it doesn’t have to be perceived that way!

5. Let's look at medications. There are currently two drugs on the market that can affect leptin levels. This is Simlin and Baeta.

Leptin (from the Greek λεπτός leptos, “thin”) is the “satiety hormone” and is composed of adipose cells that help regulate energy balance by suppressing appetite. The action of leptin is opposite to the action of another “satiety hormone” -. Both of these hormones act on receptors in the arcuate nucleus of the hypothalamus and affect appetite, which promotes energy homeostasis. In obesity, there is a decrease in sensitivity to leptin, which makes it difficult to control satiety, despite the energy already accumulated in significant quantities in the body. Although leptin's main function is to control fat storage, it is also involved in other physiological processes, as evidenced by the multiple pathways of leptin synthesis (not just through fat cells) and the different types of cells (not just hypothalamic) that leptin receptors possess. Many of these processes and functions of leptin have not yet been identified.

Gene identification

In 1950, the Jackson Laboratory studied a colony of non-obese mice and found that the offspring of some of the mice were already obese, indicating the presence of a mutation in the hormone responsible for regulating hunger and energy consumption. Mice homozygous for the so-called ob mutation (ob/ob) had excessive appetite and, as a result, increased body weight. In the 1960s, Douglas Coleman of the Jackson Laboratory identified another type of mutation that causes obesity and a similar phenotype, which he called diabetes because it made ob/ob and db/db mice obese. In 1990, Rudolf Leibel and Jeffrey Friedman reported mapping of the ob gene (obesity gene). According to the hypotheses of Coleman and Leibl, as well as studies by Leibl, Friedman and other research groups, it was confirmed that the obesity gene encodes an unknown hormone circulating in the blood and is responsible for suppressing appetite and weight in wild mice and ob mice, which, however, is not observed in db mice. In 1994, Friedman's laboratory announced the identification of the gene. In 1995, José Caro's laboratory presented evidence that mutation of the mouse obesity gene is impossible in the human body. Moreover, due to the prevalence of the obesity gene in obese people, the above finding suggested leptin immunity. On the recommendation of Roger Guillemin, Friedman named the new hormone leptin (translated from Greek as thin). Leptin was the first hormone to originate from the fat cell. Subsequent studies in 1995 confirmed that the db gene encodes the leptin receptor and is expressed in the hypothalamus, an area responsible for hunger and also regulating body weight.

Recognition of scientific progress

Coleman and Friedman have received numerous awards for their contributions to the discovery of leptin, including the Gardner International Prize (2005), the Shao Prize (2009), the Lasker Prize, an international award given by the BBVA Foundation in conjunction with the Supreme Council of Scientific Research, and King Faisal International Prize. Label did not receive as much public recognition as Friedman, since the latter did not mention co-authorship with Label in the scientific work dedicated to the discovery of the gene. This fact, along with others like it, is described in several works, including the book “The Hungry Gene” by Ellen Ruppel Schell. The discovery of leptin is also covered in books such as Fat: Fighting the Obesity Epidemic by Robert Poole, The Hungry Gene by Ellen Ruppel Schell, and Rethinking Thin: The New Science of Weight Loss, the Myths and Realities of Dieting by Gina Kolata. Books by Robert Poole and Gina Kolata describe the progress and subsequent cloning of the obesity gene in Friedman's laboratory, while Ellen Ruppel Schell's book pays close attention to Label's contributions to the field.

Gene location and hormone structure

The obesity gene and leptin in humans are located on chromosome 7. Human leptin is a protein (16 kDa) consisting of 167 amino acids.

Mutations

The leptin mutation in the human body was first described in 1997, and later 6 other types of mutations appeared. All of them were found in eastern countries and with these mutations leptin arose, which could not be detected using standard immunoreactive techniques, therefore the level of leptin with these mutations was assessed as low or even zero. The most recent case of a new, eighth type of mutation was identified in January 2015, this mutation developed in a child whose parents were Turkish, and, surprisingly, it was detected using standard immunoreactive techniques and leptin levels were characterized as elevated; however, leptin did not activate the leptin receptor and therefore the patient actually had decreased leptin levels. This eighth type of mutation leads to the development of obesity at an early age, as well as hyperphragia.

Nonsense mutation

A nonsense mutation in the leptin gene, which causes a stop codon and deficiency in leptin production, was first identified in a mouse study in 1950. In the mouse gene, arginine 105 is encoded by CGA and only a single nucleotide change is required to create the TGA stop codon. The corresponding amino acid in the human body is encoded by the CGG sequence and to produce a stop codon requires a change in two nucleotides, which is much less likely.

Phase shift mutation

A recessive phase-shift mutation resulting in decreased leptin was observed in two consanguineous children who suffered from adolescent obesity.

Polymorphism

A detailed review of the human genome in 2004 was aimed at investigating the interaction between genetic mutations affecting leptin regulation and obesity. Polymorphism in the leptin gene (A19G; frequency – 0.46), three types of mutations in the leptin receptor gene (Q223R, K109R and K656N) and two types of mutations in the PPARG gene (P12A and C161T) were examined. No relationship was found between obesity and any of the polymorphisms. A 2006 study in Taiwanese aborigines found an association between the LEP-4548 G/A phenotype and morbid obesity, which, however, was not confirmed by a 20154 meta-analysis; this polymorphism was observed in people suffering from weight gain due to antipsychotic use. The LEP-2548 G/A polymorphism increases the risk of prostate cancer, gestational diabetes and osteoporosis. Other types of polymorphism have also been identified, but their involvement in obesity has not been proven.

Transversion

In January 2015, a single case of homozygous transversion of the gene encoding leptin was identified. This transversion led to a decrease in the total level of leptin and to its increase in the bloodstream. The transversion (c.298G → T) resulted in the emergence of a tyrosine from aspartic acid at position 100 (p.D100Y). In vitro, mutated leptin was unable to bind to or activate the leptin receptor, and in vivo in leptin-deficient mice. The transversion was discovered in a two-year-old boy suffering from severe obesity and recurrent infections of the ears and lungs. The use of metreleptin contributed to changes in food intake (decreased appetite), a decrease in the body's daily energy consumption and, as a result, significant weight loss.

Synthesis methods

Leptin is produced primarily in adipocytes of white adipose tissue. Also produced through brown adipose tissue, placenta (syncytiotrophoblasts), ovaries, skeletal muscle, stomach (lower fundic glands), mammary epithelial cells, bone marrow and P/D1 cells.

Blood level

Leptin circulates in free form in the bloodstream and binds to proteins.

Physiological change in blood leptin levels

Leptin levels in relation to fat mass do not change linearly, but exponentially. Leptin levels in the blood are higher during the night and early morning because it suppresses appetite at night. The daily rhythm of leptin levels in the blood can change depending on the time of food intake.

Factors affecting leptin levels

In many cases, leptin in the human body does not perform its direct function - establishing nutritional status between the body and the brain and, as a result, does not affect fat mass:

Mutated leptin

All but one known leptin mutation makes it difficult to detect leptin levels in the blood using immunoreactive techniques. The exception is a type of leptin mutation that was identified in January 2105 using standard immunoreactive methods. This type of mutation was found in a 2-year-old boy with high levels of leptin in the bloodstream, which, however, did not affect leptin receptors and therefore a general leptin deficiency was observed.

Impacts

To the central part (hypothalamic)

It is important to distinguish that the terms central, main and direct are not synonymous: a distinction is made between the effects of leptin on the central (hypothalamic) and peripheral (non-hypothalamic) parts; The principle of leptin’s action itself is divided into direct (without an intermediary) and indirect (with an intermediary); and also distinguish between the function of leptin - primary and secondary. The action of leptin in the lateral part of the hypothalamus suppresses the feeling of hunger, and in the middle part of the hypothalamus it causes a feeling of satiety.

In the lateral hypothalamus, lieptin suppresses hunger by neutralizing the effects of neuropeptide Y, a substance secreted by the genitourinary tract and hypothalamus that causes hunger. It also neutralizes the effects of anandamine, which binds to the same receptors as THC and promotes hunger.

In the medial hypothalamus, leptin promotes satiety by promoting the synthesis of α-MSH, which suppresses hunger.

In this regard, damage to the anterior hypothalamus can cause anorexia (because there are not enough hunger signals), and damage to the middle hypothalamus contributes to feelings of excessive hunger (because there are not enough satiety signals). This appetite suppressant property is long lasting compared to the fast hunger suppressant cholecystokinin and the slower hunger suppressant produced after eating. The absence of leptin (or its receptor) contributes to the occurrence of uncontrollable feelings of hunger, which leads to obesity. Fasting and a low-calorie diet can lower leptin levels. Leptin levels change more markedly with decreasing food intake than with increasing food intake. Changes in leptin levels depend on energy balance and are associated primarily with appetite and the amount of food consumed rather than with already accumulated fat.

In the mediobasal hypothalamus, leptin, by acting on its receptors, controls the amount of food taken and energy expenditure.

By binding to neuropeptide Y neurons in the arcuate nucleus, leptin reduces the activity of these neurons. Leptin sends signals to the hypothalamus about the state of satiety. Moreover, leptin signals make it easier to avoid high-calorie foods. Activation of leptin receptors inhibits neuropeptide Y and agouti-related peptide, and activates α-melanocyte-stimulating hormone. Neuropeptide Y neurons are a key element in regulating hunger; When low doses of these neurons were introduced into the brains of experimental animals, an improvement in appetite was observed, and selective destruction of these neurons in mice contributed to the development of anorexia. On the other hand, α-melanocyte-stimulating hormone is an important mediator of satiety, and differences in genes for the receptor for this hormone contribute to the development of obesity in humans. Leptin interacts with six types of receptors (Ob-Ra–Ob-Rf, or LepRa-LepRf), which, in turn, are encoded by one LEPR gene. Ob-Rb is the only receptor that transmits signals intracellularly through the Jak-Stat and MAPK signaling pathways and is located in the hypothalamic nucleus. Leptin is thought to enter the brain through the choroid plexus, where the transport mechanism may be a distinct form of the leptin receptor molecule. When leptin binds to the Ob-Rb receptor, it activates stat3, which is phosphorylated and enters the nucleus, causing changes in gene expression - reducing the expression of endocannabinoids responsible for increasing hunger. In response to the action of leptin, receptor neurons modify the number and types of synapses affecting them. Increasing melatonin levels leads to a decrease in the amount of leptin, but melatonin together with insulin can increase leptin levels, thereby reducing hunger during sleep. Partial sleep deprivation can also lead to a decrease in leptin levels. Mice treated with leptin or a combination of leptin and insulin had better metabolism than those treated with insulin alone: ​​blood sugar levels were more stable, cholesterol levels were reduced, and body fat gain was reduced.

Effect on the peripheral (non-hypothalamic) part

Non-hypothalamic targets of leptin are called peripheral, in comparison: hypothalamic targets are called central. Leptin receptors are found in various types of cells. The effects on the peripheral and central parts vary depending on the physiological conditions and species of living beings. In the peripheral part, leptin is a modulator of energy expenditure, a modulator of maternal and fetal metabolism, is responsible for maturity, is an activator of immune cells, an activator of beta insular cells, and is also responsible for growth. Moreover, leptin interacts with other hormones and energy expenditure regulators: insulin, glucagon, growth hormone, glucocorticoids, cytokines and metabolites.

Circulatory system

Experiments with mice have shown that leptin or its receptors play a role in modulating the activity of T cells in the immune system. Leptin/its receptors modulate the immune system response to atherosclerosis, which can be caused by obesity. Exogenous leptin may promote tissue regeneration by improving vascular endothelial growth factor. Infusion- or adenovirus-induced hyperleptinemia in mice results in decreased blood pressure.

Mature lungs

In mature lungs, leptin is involved in the formation of lipofibroblasts, since with the gradual stretching of tissues under the influence of the alviolar epithelium, PTHrP is released. Leptin from the mesoderm, in turn, acts on the leptin receptor contained in the second type of alveolar epithelial pneumocytes and causes surface expression, which is one of the main functions of these pneumocytes.

Reproductive system

Ovulatory cycle

In mice, and to a lesser extent in humans, leptin affects reproductive function in both sexes. In the female sex, the ovulatory cycle is related to energy balance (positive or negative depending on weight gain or loss) and energy flow (how much energy is absorbed and expended) and much less related to energy status (body fat levels). When the energy balance is negative (when the woman is hungry) or when the energy flow is too high (when the woman exercises and simultaneously consumes enough calories), the ovulatory cycle stops along with menstruation. Only when a woman's body fat content is extremely low can her energy status stop menstruation. Leptin levels outside the normal range can negatively affect egg quality and in vitro fertilization. Leptin is involved in reproduction by stimulating the hormone responsible for the release of gonadotropin from the hypothalamus.

Pregnancy

The placenta produces leptin. Leptin levels increase throughout pregnancy and decrease after childbirth. Leptin is also present in mature uterine membranes and tissues. Leptin inhibits uterine contractions. Leptin plays a role in hyperemesis of pregnancy (severe morning sickness), polycystic ovary disease, and hypothalamic leptin is involved in bone growth in mice.

Lactation period

The immunoreactive leptin is found in human breast milk. Leptin, found in breast milk, has also been found in the blood of nursing babies of various animals.

Puberty

Together with kisseptin, leptin influences the onset of puberty. High levels of leptin, observed mainly in obese females, can trigger early menarche, which in turn can lead to cessation of growth, since estrogen secretion begins at menarche, which causes early formation of the pineal gland.

Bones

Leptin's ability to regulate bone mass was first identified in 2000. Leptin is able to influence bone metabolism through direct signaling through the brain. Leptin reduces cancellous bone content but increases cortical bone. This feature of leptin helps to increase bone size, as well as their strength (along with an increase in overall body weight). Bone metabolism can be regulated through sympathetic outflow because sympathetic pathways innervate bone tissue. Several molecules associated with brain signals (neuropeptides and neurotransmitters) have been found in bone, including epinephrine, norepinephrine, serotonin, vasoactive peptide intestinal peptide and neuropeptide Y. Leptin binds to its receptors in the hypothalamus, where it regulates bone metabolism through the sympathetic nervous system. Leptin may also influence bone metabolism by maintaining a balance between the body's energy intake and the IGF-I pathway. The use of leptin to combat diseases associated with bone growth, such as poor healing of fractures, looks promising.

Brain

Leptin receptors are located not only in the hypothalamus - also in other parts of the brain, partly in the hippocampus. Therefore, it was decided to classify leptin receptors in the brain according to their location - central (hypothalamic) and peripheral (non-hypothalamic).

The immune system

The decrease in leptin levels is influenced mainly by the same factors that cause inflammatory processes - testosterone, sleep, stress, lack of calories and body fat. Since leptin is well known to be involved in the immune system response, it has been suggested that leptin could be used to detect cytokine-induced inflammatory processes. From both a structural and functional point of view, leptin resembles IL-6 and is a member of the cytokine superfamily. Leptin circulation affects the hypothalamic-pituitary-adrenal axis, which suggests that leptin is involved in stress. High leptin levels increase white blood cell counts in both men and women. As with chronic inflammation, chronically elevated leptin levels lead to obesity, overeating, and inflammatory diseases, including hypertension, metabolic syndrome, and cardiovascular disease. Although leptin is associated with fat mass, interestingly, exercise does not affect fat cell size or overeating, meaning leptin is not released (in comparison, IL-6 is released in response to muscle contraction, which is achieved through exercise). Therefore, there is some debate that leptin only responds to inflammation caused by fat. Leptin is a proangiogenic, proinflammatory and mitogenic factor, the effectiveness of which is enhanced only by its membership in the family of cytokines in cancer cells. Essentially, increasing leptin levels (with caloric intake) acts as a pro-inflammatory response mechanism and prevents the excessive cellular stress that causes overeating. When the growth of fat cells or their number does not keep pace with the amount of calories consumed, stress occurs, leading to inflammatory processes at the cellular level and ectopic fat, that is, harmful accumulation of fat occurs in all internal organs, arteries and muscles. An increase in insulin with excessive calorie consumption provokes the release of leptin. This insulin-leptin interaction is also observed with increased IL-6 gene expression and secretion from preadipocytes. Moreover, the concentration of leptin in the blood serum increases significantly when taking Acipimox (used to break down fats). This finding may help reverse harmful fat accumulation and also explains the link between chronically elevated leptin and ectopic fat accumulation in obese people.

The role of leptin in obesity and weight loss

Obesity

Although leptin reduces appetite, the concentration of leptin in the blood of obese people (due to the percentage of fat/non-fat tissue) is significantly higher than in healthy people. This results in leptin resistance, which is similar to insulin resistance in people with type 2 diabetes, and increasing leptin even more does not help control weight and, as a result, does not promote weight loss. Several options have been proposed to solve this problem. For example, changes in leptin receptor signaling in the arcuate nucleus. Along with this, changes in the way leptin crosses the blood-brain barrier. Studies of leptin levels in the cerebrospinal fluid have shown that leptin concentrations decrease when it crosses the blood-brain barrier and reaches the hypothalamus in obese individuals. Leptin levels in the cerebrospinal fluid compared to blood levels in obese people have been found to be lower than in people of normal weight. This may be due to elevated triglyceride levels, which influence leptin when crossing the blood-brain barrier. Although a deficiency in the supply of leptin from plasma to the cerebrospinal fluid is observed in obese people, their cerebrospinal fluid leptin levels are 30% higher than in lean people. This high content does not prevent obesity, since the number and quality of leptin receptors in the hypothalamus in obese people is within normal limits and leptin resistance is noted. When leptin binds to the leptin receptor, it activates a number of pathways. Leptin resistance may be caused by defects in one step of this process, in particular defects in the JAK/STAT pathway. Mice with a mutation in the leptin receptor gene, which prevents STAT3 activation, suffer from obesity and hyperphragia. The PI3K pathway may also influence leptin resistance, as demonstrated by studies in mice by artificially blocking PI3K signaling. The PI3K pathways are also activated by the insulin receptor and are therefore an important site of leptin-insulin interaction as part of energy homeostasis. The insulin-PI3K pathway may render POMC neurons insensitive to leptin through hyperpolarization. Consumption of foods containing high levels of leptin from early childhood reduces leptin levels and reduces leptin receptor mRNA expression in rats. Long-term consumption of fructose in rats increased triglyceride levels and contributed to the development of insulin and leptin resistance. However, another study found that leptin resistance was produced only when the diet was high in fructose and high in fat. Another study found that high fructose levels in rats fed a high-fat diet helped alleviate leptin resistance. These conflicting results indicate that what exactly causes insulin resistance is not yet fully understood. Leptin is known to interact with amylin, a hormone involved in gastric emptying and creating a feeling of fullness. When both leptin and amylin were given to leptin-resistant obese rats, a significant reduction in body weight was observed. Due to amylin's ability to reverse leptin resistance, it is often recommended for obese people. Essentially, leptin's job is to signal that there is not enough fat in the orgasm and encourage it to be restored for survival, rather than serve as a signal to prevent overeating. The level of leptin in animals alerts them to a sufficient amount of stored energy and encourages them to waste it rather than obtain even more food. It is possible that leptin resistance is natural in mammals and has some survival significance. Leptin resistance (along with insulin resistance and weight gain) is observed in rats that are given unlimited access to palatable, rich foods. This effect reverses its direction when the food is replaced with a less saturated one. This fact also carries evolutionary significance: the ability to store excessive amounts of energy with short-term access to rich food may help to survive, since the opportunity to “overeat” may no longer present itself.

Weight loss response

People on a diet, and especially those who have excess fat cells, experience a decrease in circulating levels of leptin. This feature helps to reduce thyroid activity, tone the sympathetic nervous system, energy consumption in skeletal muscle, as well as increase muscle efficiency and tone of the parasympathetic nervous system. As a result, a person who has lost more weight than his natural weight has a lower basal metabolic rate than people who have not lost weight and have a natural body weight. Decreased circulating levels of leptin also lead to changes in brain activity in areas responsible for regulation, control of emotions and thoughts about appetite, which, however, are restored when leptin is taken.

Therapeutic Use

Leptin

In the US, leptin is used for leptin deficiency and general lipodystrophy.

Metreleptin analogue

It is generally accepted that fat people are weak-willed, lazy, weak, and unable to pull themselves together. Although the causes of obesity are complex and varied, modern research shows that it is not so much a matter of willpower as it is a matter of the body's biochemistry, with particular attention paid to the hormone leptin, which was discovered only recently

LEPTIN

It is generally accepted that fat people are weak-willed, lazy, weak, and unable to pull themselves together. Although the causes of obesity are complex and varied, modern research shows that it is less about willpower and more about the biochemistry of the body, with particular attention paid to the hormone leptin, which was discovered only recently.

What is leptin?

Leptin is a hormone produced by fat cells. The more fat there is in the body, the more leptin is produced. With its help, fat cells “communicate” with the brain.

Leptin tells you how much energy is stored in the body. When there is a lot of it, the brain understands that there is enough fat (energy) in the body. As a result, there is no severe hunger, and the metabolic rate is at a good level.

When leptin is low, it is a signal that fat reserves (energy) are low, which means hunger and possible death. As a result, metabolism decreases and hunger increases.

Thus, leptin's main role is long-term control of energy balance. It helps support the body during times of hunger by signaling the brain to turn on the appetite and reduce metabolism. It also protects against overeating, “turning off” hunger.

Leptin resistance

Obese people have high levels of leptin. Logically, the brain should know that there is more than enough energy stored in the body, but sometimes the brain’s sensitivity to leptin is impaired. This condition is called leptin resistance and is now considered the main biological cause of obesity.

When the brain loses sensitivity to leptin, the control of energy balance is disrupted. There are a lot of fat reserves in the body, a lot of leptin is also produced, but the brain does not see it.

Leptin resistance is when your body thinks you're starving (even though you're not) and adjusts your eating behavior and metabolism accordingly:

A person may feel hungry all the time; food does not satisfy him, which is why he eats much more than normal.

Activity decreases, calorie expenditure at rest decreases, and metabolism decreases.

A person eats too much, moves little, becomes lethargic, his metabolism and the activity of the thyroid gland are reduced, excess weight up to obesity is the result.

It's a vicious circle:

He eats more and stores more fat.

More body fat means more leptin is released.

High levels of leptin cause the brain to reduce the sensitivity of its receptors to it.

The brain stops receiving leptin and thinks that hunger has come and forces you to eat more and spend less.

You eat more, spend less and accumulate even more fat.

What Causes Leptin Resistance?

1. Inflammatory processes

Inflammation in the body can be asymptomatic. In obese people, similar processes can occur in the subcutaneous fat tissue with severe overcrowding of fat cells or in the intestines due to a passion for the “Western” diet, rich in refined, processed foods.

Immune cells called macrophages arrive at the site of inflammation and release inflammatory substances, some of which interfere with leptin's function.

What to do:

Increase omega-3 acids in food (fatty fish, flax, fish oil supplements).

Bioflavonoids and carotenoids also show anti-inflammatory properties. They are rich in ginger, cherries, blueberries, currants, chokeberries and other dark berries, pomegranates.

Reduced insulin levels (more on that below).

2. Fast food

Fast food and a Western diet with a lot of processed foods can also cause leptin resistance.

It is assumed that the main culprit for this is fructose a, which is widely distributed in the form of additives in food products and as one of the components of sugar.

What to do:

Avoid processed foods.

Eat soluble fiber.

3. Chronic stress

Chronically elevated stress hormone cortisol reduces the sensitivity of brain receptors to leptin.

4. Insulin Insensitivity

When a lot of carbohydrates enter the body, a lot of insulin is released to remove glucose from the blood. If there is chronically too much insulin, cells lose sensitivity to it. Under these conditions, unused glucose is converted into fatty acids, what interferes with the transport of leptin to the brain.

What to do:

Strength training helps restore insulin sensitivity.

Limit simple carbohydrates in your diet.

5. Overweight and obesity

The more fat you have in your body, the more leptin is produced. If there is too much leptin, the brain reduces the number of leptin receptors and its sensitivity to it decreases.

So it's a vicious circle: more fat = more leptin = more leptin resistance = more body fat.

What to do:

• Lose weight through proper nutrition and physical activity.

6. Genetics

Sometimes there is a genetically impaired sensitivity of the brain receptors to leptin or mutations in the structure of leptin itself, which prevent the brain from seeing it. It is believed that up to 20% of obese people have these problems.

What to do?

The best way to know if you have leptin resistance is to know your body fat percentage. If you have a high percentage of fat, which indicates obesity, if you have a lot of excess weight especially in the abdominal area, there is a possibility.

It is also used for the primary diagnosis of obesity. body mass index (BMI).

BMI = body weight in kg: (height in sq.m.)

Example: 90 kg: (1.64 x 1.64) = 33.4

The good news is that leptin resistance is reversible in most cases.

The bad news is that there is no easy way to do this yet, and there is no drug yet that can improve leptin sensitivity.

While in the arsenal of those losing weight, everyone knows tips on changing their lifestyle - healthy diet, calorie control, strength training and increased daily household activity. published .

Irina Brecht

Any questions left - ask them

P.S. And remember, just by changing your consciousness, we are changing the world together! © econet

1. Mechanism of action and function 2. Leptin levels 3. How to improve the function of the hormone?

Why do many people feel hungry all the time? It is not they who are to blame for this, but the hormone leptin. It is this substance that controls the rate of metabolism and energy consumption or expenditure.

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Leptin is a protein produced by fat cells (adipocytes) in adipose tissue. It belongs to adipokines - the collective name given to substances produced by fat cells - and is the first compound of this type to be discovered. Was investigated in 1994.

Leptin is a hormone that regulates energy absorption and expenditure (including appetite) and metabolism. This is the most important hormone that can explain why a person sometimes feels full and sometimes hungry. If the hormone is at a high level in the body, it sends signals to the brain that a person is full and it’s time to stop eating. On the other hand, low levels of the hormone lead to uncontrolled hunger and excessive calorie (energy) consumption. The binding of leptin to hypothalamic receptors promotes the release of hormones that suppress appetite.

This protein consists of 167 amino acids. Its structure is very rich - it is formed by 4 antiparallel alpha helices, which are held together by 2 long and 1 short connection. Like every protein, the hormone is encoded by DNA - its gene is localized on chromosome 7 at position 7q31.3.

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Leptin is produced not only in white adipose tissue, but also in other parts of the body. It is present, for example, in brown adipose tissue, placenta, oocytes, granulosa cells of the preovulatory follicle, gastric mucosa, hypothalamus, pituitary gland or skeletal muscle.

The hormone circulating in the human body directly corresponds to the total amount of fat in the body. Accordingly, its level depends on body weight. This means that during rapid weight loss through liposuction or restrictive diets that cause accelerated fat loss, there is an equally dramatic decrease in leptin levels.

A person feels hungry, thyroid function and metabolism decrease. The body reacts by increasing anabolic reactions (conserving reserves) and a feeling of hunger. Based on this, it can be explained why crash diets for weight loss do not work: even despite much less food consumption, there is a feeling of fatigue and a slower metabolism.

Leptin is much more sensitive to fasting than to overeating. In the first case, during fat burning, the values ​​of this hormone drop sharply, while in the second, its rise is limited. The indicator also increases due to an increase in insulin levels, for example after eating.

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In order for a hormone to act, that is, to mediate its physiological functions, it must bind to the Ob receptor. There are 6 leptin receptor isoforms in the body:

• Ob-R;
• Ob-Rb;
• Ob-Rc;
• Ob-Rd;
• Ob-Re;
• Ob-Rf.

However, only the Ob-Rb form contains the intracellular structures necessary to activate cellular signals. This isoform is found in the hypothalamus and endometrium, others are involved in hormone transport in the body.

Leptin has numerous functions in the human body. Its main task is to adapt the body to fasting. It promotes the following processes:

• maintaining energy homeostasis;
• decreased food consumption;
• increased energy consumption;
• signal about the amount of fat in the body and food reserves;
• direct inhibition of intracellular lipid concentrations;
• increased glucose uptake and gluconeogenesis in the liver.

The hormone plays a role in reproduction, regulation of puberty (the molecule is of great importance for the maturation of the reproductive axes) and in eating disorders. It is involved in the regulation of cardiovascular (sympathetic activation, increased blood pressure, induction of angiogenesis) and immune functions, and control of ontogenesis.

Leptin indirectly affects bone metabolism, the extent of which depends on the nutritional state of the body and the onset of menstruation. Low levels and poor nutritional status or late menstruation are risk factors for the subsequent development of osteoporosis.

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Plasma leptin levels correlate with body fat stores. These rates are generally higher in women than in men, regardless of body weight, fat volume or age. Leptin is present in small quantities only in people with eating disorders (anorexia, bulimia).

Typically, high concentrations are found in obese individuals, which is considered a state of leptin resistance. High levels of this hormone are also associated with the presence of polycystic ovary syndrome. Plasma levels of the substance exhibit circadian rhythms, with levels of the hormone being highest around midnight and in the early morning hours.

In February 2012, a note was published in the journal Nature, in which, citing growing evidence, it was indicated that the agent that inhibits leptin levels may be sugar, in particular fructose, which is widely used in the food industry. Leptin is able to provoke the desire to move and control what foods are attractive to a person. Therefore, for some people, leptin tablet is considered an ideal substance for treating obesity.

The problem is that the body is constantly trying to regulate basal levels of the hormone. If its level periodically increases, as happens in overweight people, the brain loses sensitivity and responds to leptin in a limited way. In such individuals, fat tissue produces high levels of the hormone, but the brain does not respond to it sufficiently. They need more of this substance to feel full.

Therefore, in order to lose weight, it is necessary to give the body enough time so that it can adapt to new, lower levels of leptin, that is, so that the body losing fat perceives the reduced levels of the hormone as normal and receives a signal of satiety at the right time.

In addition to obesity, a diet high in fructose leads to leptin resistance. This sweet product reduces the hormone's ability to cross the blood-brain barrier and reach the hypothalamus. Thus, even at high levels, leptin in the blood does not necessarily reach the necessary signal of satiety.

5 How to improve hormone function?

Improving hormone function depends on a person’s lifestyle. Following some rules and basics of a healthy diet can help with this:

1. Quality sleep. The body craves rest, so leptin levels rise during sleep. A sleepy person suffers more from hunger.
2. Limit your intake of sugar and concentrated fructose, meaning the use of sweets, carbonated drinks, juices or fructose concentrates. Likewise, sweet processed foods should be avoided. Today, fructose is present almost everywhere. Therefore, it is advisable to give preference to natural fruits. They also contain fructose, but not in concentrated form. In addition, they contain many vitamins, minerals and nutrients that slow down the absorption of fructose in the blood.
3. Reduce your carbohydrate intake. Large and regular amounts of these compounds cause a sudden secretion of insulin, which is reflected by an increase in leptin levels. The biggest enemy in this case is represented by carbohydrates with a high glycemic index, which are consumed at the wrong time (during low physical activity or late in the evening).
4. Forget about radical diets and fasting. These methods disrupt metabolism and, due to low leptin levels, will immediately have the opposite effect. Forget about restrictions, pay attention to proper and healthy nutrition.
5. Consume Omega-3 fatty acids. Eat fish, nuts, healthy natural oils - anything that contains these substances. They activate leptin sensitivity.

Leptin is a hormone that regulates energy metabolism and suppresses appetite, produced by adipose tissue and affects the brain.

Its reduced concentration leads to obesity, since a person constantly experiences an unsuppressed feeling of hunger and incessantly eats.

Where elevated levels of the hormone are diagnosed, they speak of a lack of appetite, a decrease in body weight to critical levels, as happens with anorexia.

One way or another, the hormone leptin affects all processes in the body. Where is leptin found and what products should be preferred for excellent health and a good figure.

Such a necessary and important hormone leptin:

• produced by the human body;
• found in food;
• synthesized artificially and is part of weight loss products;
• is the basis of medications (in particular, for weight loss) for people with a congenital deficiency in the synthesis of this hormone.

Women have higher leptin levels than men. But during a diet, its level decreases significantly.

Do you know what diabetes insipidus is? You can read more about this disease.

Foods containing leptin

By consuming foods containing leptin, you can influence its amount in the body.

Products with a high percentage of fat content are good for lowering hormone levels:

• milk;
• sour cream;
• yoghurts;
• and other high-calorie foods.

• skim cheese;
• low-calorie milk yoghurts;
• cereals, soybeans, peas, beans;
• lamb, turkey meat.

It follows that all weight loss diets make sense only if a person’s leptin levels are fine.

Food restrictions and physical activity will not help you lose weight if there is not enough leptin: a person will constantly feel hungry, which means they will eat, steadily gaining weight.

Proper nutrition

To maintain a sufficient level of the “hunger hormone” you need to eat right.

1. Control the amount of fructose you consume, since it has a detrimental effect on the receptors that regulate the production of leptin. Under the influence of fructose, the body loses the ability to identify and concentrate the hormone, and, accordingly, cannot estimate its amount and use it correctly. Fructose is found in soda, cookies and other sweets, the consumption of which is best avoided.
2. Eliminate simple carbohydrates. They reduce the production of insulin, and this affects the production of leptin. Unfortunately, delicious white bread, pearly light rice and other foods with simple carbohydrates are not healthy at all. They can be replaced with quality pasta and whole oats.

By giving up carbohydrates, you cannot completely deprive your body of “fuel”.

It is carbohydrates that help accumulate energy and start metabolism.

To do this, from time to time it is advisable to arrange “loading days”, eating carbohydrate-containing “goodies” 2-2.5 times more than usual.

Then the diet must be continued. Days like these provide excellent motivation for dietary restrictions in exchange for the opportunity to occasionally “vent your soul.”

1. More fish and seafood. Omega-3 acids increase the body's sensitivity to leptin, have a beneficial effect on the functioning of the cardiovascular system and reduce cholesterol. Beneficial acids are also contained in the meat of animals fed on fresh grass. But it is better to avoid products with Omega-6. We are talking about vegetable oils and regular meat. This type of food lowers leptin levels.
2. Down with snacks and sugar substitutes. Artificial flavors and sugar substitutes do nothing good for the body. As for snacking, they interfere with normal cleansing of the body. If you can't do without snacks, you can sometimes chew nuts or fruits. This will temporarily quench your appetite without harm to your health.
3. More foods that are rich in zinc. Zinc deficiency and leptin deficiency go hand in hand. People who have such problems are overweight.

Getting rid of excess weight is a useful thing. The main thing is that the diet is optimal in composition and balanced so that a person can stick to it for a long time without harm to health.

Some tips for maintaining optimal leptin levels.

1. It is better to eat little by little, but more often, while controlling the amount of food.
2. High levels of leptin in the body help you lose weight. This must be taken into account when planning your diet.
3. A person weighing more than 130 kg should visit a doctor to be examined for possible leptin resistance.
4. When choosing a diet or a set of physical exercises, it would be useful to consult a doctor to insure yourself against possible undesirable consequences.
5. The easiest and fastest way to increase leptin levels is to eat 250 grams of mango. You can do this every day, it's useful.

It is important to know that a strict and unambiguous refusal of high-calorie foods can lead to nutritional deficiencies and, as a result, initiate hormonal imbalance.

Right way of life

A balanced diet is certainly important to maintain normal leptin levels in the blood. But no less important for this is the ability to properly organize your lifestyle.

1. Stress needs to be relieved. The body in a state of increased nervous or physical stress is exposed to cortisol, which disrupts the normal balance of hormones, including leptin. A person begins to “eat up” stress, and this is not the best way out of the situation. It is preferable to do yoga or meditate a little. This will help you relax and set yourself up for a restful sleep.
2. You need to sleep enough to get enough sleep. The body, which is in a state of chronic sleep deprivation, stops producing leptin. To prevent this from happening, you need to sleep at least 8 hours a day. Before going to bed, you should not watch TV or scroll through gadgets.
3. Overexertion is harmful. This is fraught with cardiovascular exhaustion. Heavy loads increase cortisol levels, have a depressing effect on the immune system and slow down metabolism. Sports training is certainly useful, but only if it does not lead to exhaustion.
4. Physical inactivity is dangerous. A lack of movement, just like excessive loads, does not bring anything good. But living by the principle “from the couch to the gym” is also wrong. An active lifestyle should become an urgent need and a natural pastime.

But in life, an ideal set of circumstances is extremely rare.

In order to achieve what you want, you have to try.

If you suspect a health problem, you should make time to visit a doctor.

In particular, if there are assumptions about problems with the level of leptin in the body, you should contact an endocrinologist. After the examination, the situation will become clear, and if treatment is required, the doctor will prescribe it.

To correct the level of the hormone leptin, there is a considerable range of drugs, but only a doctor will tell you exactly what and in what dosage should be taken. Self-medication with hormonal medications is life-threatening!

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