red Understanding the biological role of leptin in the human body has a great practical importance. This is the key to creating an adequate therapy for many pathologies connected to the hunger hormone and a biomarker of targets that need to be corrected. It is necessary to understand the affiliation of organs and tissues to leptin to improve molecular genetic technologies. It will help to reveal the mechanism of the hormone action and understand its potential for improving the treatment process, which concerns many pathologies.
This article will tell about the biological role of leptin in terms of genetics, the signaling pathway of the hormone, its regulation and the functions of the bioactive substance in pathology and normal health.
Contents:
- General data.
- Genetics and biology of the hormone.
- Mechanism of action.
- Regulation of the hormone formation.
- The biological role of the hormone.
- Leptin and newborns.
- Leptin and infancy and puberal growth stages.
General data
The word «Leptin» is translated from Greek as «thin, graceful». At its core, this is the secret of fat cells of a hormonal-peptide nature. The view of the scientific medical community on the functional capabilities of lipids has changed a lot from its discovery at the end of the 20th century. At first, it was called «ob protein», this is an abbreviation that means «obese» in English. The gene responsible for encoding the hormone was also called the «ob gene» (today there is another name — the «LEP gene»). This gene is localized in chromosome 7q31.31.
A fundamentally new concept of the functioning of fat in the body has emerged since the discovery of leptin. According to it, lipocytes act similarly to an active endocrine organ. Leptin consists of 167 amino acids, so this hypothesis is fully justified. The total concentration of the hormone in the body is equal to the total amount of human fat. At the same time, leptin is able to control the excess accumulation of fat mass, but an increase in its synthesis leads to greater food intake, and the accumulation of fat as a result.
The hormone is associated with the placenta and stomach. Representatives of the leptin in the brain are neural pathways through the hypothalamus that control energy homeostasis. Lack of the hormone leads to obesity, which explains its role in the amount of food consumed, energy expenditure, reproduction, participation in the functioning of the thyroid gland and immunity. Some researches suggest that leptin induces fat oxidation in obese people. Such a multi-vector nature required a detailed study of the hormone.
Genetics and biology of the hormone
The leptin gene is afiled with adipose tissue, stomach, placenta, and possibly the lactiferous gland. It comes from the family of cytokines, that are responsible for the development of inflammation. As a hormone, leptin has daily (circadian) fluctuations. They increase in the evening, and there is an impulse secretion in the morning. Since it is synthesized by lipocytes (adipocytes or fat cells), its main role is to control energy homeostasis. In a simple way, leptin is the tool for regulation of food intake in accordance with the energy expended without gaining excess body weight.
There are other important functions of leptin: balancing immunity, stopping inflammation, angiogenesis and tissue regeneration. In addition, its role in the development of hypertension against the background of obesity is great. Since the hormone is closely associated with adipose tissue, it is called the «weight loss hormone».
Mechanism of action
Leptin influences all processes in the body through the LEP-R or OB-R receptor. It is encoded by the LEPR gene. Receptors of the LEP-R type are found in many areas of the brain and in the endothelium of cerebral capillaries. These are cytokine receptors, which have several isoforms. They serve as a conductor of the hormone to various internal organs and tissues. Mutations in the LEPR gene are can cause an obesity. Once leptin binds to LEPR, it cascades to the brain, where it acts either directly or by activating specific centers in the central nervous system to minimize food intake and increase energy expenditure. In parallel, the hormone affects the metabolism of glucose and fats, changing the neuroendocrine function.
Regulation of the hormone formation
Leptin is controlled by a number of organs through their hormones, which increase or decrease leptin synthesis at the cellular level. For example, insulin activates the production of leptin, while adrenaline, norepinephrine, and dopamine reduce its synthesis. In addition, leptin also controls tumor necrosis factor-α, which also increases leptin secretion. Glucose and fatty acids act the same.
After synthesizing leptin and lipocytes, they bind to their receptors in the brain. Hormones change the direction of action of neuropeptides, which lead to reducing appetite, increasing energy consumption, changing sympathetic and parasympathetic tone, and neuroendocrine function. An increase in the level of the hormone activates the thyroid gland, growth hormone, and sex hormones. The hypophysis represented by adrenal glands minimize their activity. Leptin directly or indirectly affects hematopoiesis and immunity, improves carbohydrate, and fat metabolism.
The biological role of the hormone
According to the results of numerous clinical and experimental studies, leptin:
- regulates fat metabolism;
- balances energy homeostasis;
- controls neuroendocrine functions;
- plays an important role in newborns, children and adolescents;
- participates in the metabolism of the cardiovascular system, bone tissue, and immune responses.
Such a multi-vector nature of the hormone endows it with valuable properties and the ability to play the role of a biomarker in the early stages of the development of pathological conditions. Also, this biosubstance can be used as a drug.
Regulation of energy constants of the body
Leptin participates in energy metabolism and controls appetite. It activates a complex neuroloop made up of hunger-suppressing neurons. They release pro-opiomelanocortin (POMC). In addition, leptin also inhibits the neurons that stimulate appetite, which allows you to simultaneously regulate food intake. These neurons release neuropeptide Y (NPY). More recently, studies have shown that fasting is similar to a calorie-restricted diet in terms of leptin levels in the body. This suggests that a gene mutation at the level of leptin can lead to obesity due to hyperphagia. If someone determines the mutation in time and puts the injection of leptin into the human body, a feeling of satiety will be created, which will limit fat accumulation.
Regulation of neuroendocrine function
The level of leptin in blood automatically decreases if a person begins to starve. This does not depend on fat mass. Neuroendocrine corrections occur during this period. They include a decrease in the concentration of reproductive hormones. It leads to minimization of energy consumption during pregnancy. Also, it reduces the level of thyroid-stimulating hormones in the bloodstream, which slows down the metabolic rate, but increases the concentration of growth hormone involved in the expenditure of the body’s energy potential.
However, scientists warn that patients with leptin deficiency at birth may have habitual growth and normal development of the body. Their adrenal function also will be preserved. In other words, leptin cannot be a marker of pathology in this case.
Regulation of carbohydrate metabolism: insulin resistance, metabolic syndrome
The genetic low level of the hormone provokes the development of insulin resistance and some features of metabolic processes in the body. The administration of additional leptin in this case corrects hyperinsulinemia and hyperglycemia. The level of thyroid hormones, low-density cholesterol (LDL) decreases, and the level of high-density lipoproteins (HDL) increases in parallel. Leptin also causes inflammation in overweight women, which can trigger gestational diabetes mellitus (GDM).
Leptin is not only regulates the saturation of tissues with energy, but is also produced by the placenta, which guarantees the viability of the fetus, but increases the risk of developing GDM. In this case, the placenta increases in size, which gives an even greater amount of nutrients transported to the fetus, increasing the size of the fetus (macrosomia). Insulin resistance is associated with inflammation, therefore, for its correction, nutrients are used to stop this pathological process.
Obesity, which is developed on the background of insulin resistance, is associated with the development of polycystic ovaries with an increasing level of leptin. It allows us to speak of the hormone as a marker of pathology in its early stages.
Regulation of the cardiovascular system
This type of the hormone effect is not fully understood. Normally, the heart uses glucose and lipids as energy sources. However, glucose is preferential one. Fat oxidation increases, myocardial oxygen demand increases, and cardiac activity slows down in case, if there are some special conditions for the transition from glucose to fat.
Ultimately, this leads to systemic metabolic disorders: insulin resistance, leptin resistance, and metabolic dysfunction. High triglyceride levels and myocardial obesity provoke lipotoxicity. This violates the contractility of the myocardium.
The results of scientific studies regarding the association of leptin with coronary artery disease (CHD) and chronic heart failure (CHF) are contradictory. High levels of the hormone are associated with the risk of developing these diseases, and treatment that lowers leptin levels can prevent their development. This means that leptin can serve as a marker of the risk of stroke, atherosclerosis of the carotid and peripheral arteries. In addition, an increase of the leptin concentration in the blood indicates the growth of an aneurysm of the abdominal aorta. But there is still not enough data to make a final decision on leptin and its relationship with the pathology of the heart and blood vessels.
Role of leptin in bone metabolism and inflammation
Leptin plays an important role in rheumatic pathology, changes in the joints, osteoarthritis. Its level increases. There are data on the processes of cartilage catabolism under the influence of the hormone, moreover, the hormone acts as an anti-inflammatory factor and is considered as an inflammatory mediator in autoimmune and other inflammatory diseases. In contrast, chronic inflammation is resistant to leptin, which indirectly provokes obesity, which leads to inflammation again. This is such a vicious circle.
Role of leptin in immune responses
Leptin regulates both inborn and acquired immunity by increasing the strength of natural killer (NK) cells and activating granulocytes, macrophages, and dendritic cells. Leptin allows new T- and B-lymphocytes to multiply rapidly, minimizing the synthesis of T-suppressors with regard to acquired immunity. In other words, the hormone activates B-lymphocytes, which produce cytokines to control the maturation and functioning of immune system cells.
Leptin and newborns
The hormone is synthesized by the placenta during pregnancy, enters the navel cord blood and protects newborns. The total body weight and fat mass of the born baby depends on the concentration of leptin in the blood. Leptin correlates growth, activates hematopoiesis, and lymphopoiesis in infants in addition to energy homeostasis. The secretion of the hormone in milk suggests that its level in the blood of the mother affects the growth of newborns.
Hormone in children and puberty
In childhood and adolescence, leptin causes the brain to store fat, which regulates menstruation and other pubertal changes, and subsequently reproductive function. At the beginning of puberty, an increase in body fat mass occurs precisely due to the high concentration of leptin in the blood, which implies a qualitative transition of adolescents to the phase of puberty. If there is not enough leptin, or a gene mutation occurs, children become obese, experience irregular menstruation, remain as if in prepuberty and have problems with secondary sexual characteristics.
It turns out that leptin, or the ob protein, is a hormone produced by fat cells and reacts to any changes in the body through receptors that pave the signal path for it. Leptin signaling stimulates neuropeptides, resulting in either an absence or an increase in appetite. The level of the hormone indicates the overall energy reserve in the body, causes the central nervous system to regulate energy homeostasis.
Hormone deficiency can occur as a result of gene mutation or lipoatrophy, which leads to violations of many important functions: reproductive failure, obesity, insulin resistance, autoimmune pathologies. Therefore, the study of leptin is still going on today, and, of course, will take place in the near future to improve the early diagnosis of diseases, therapeutic measures for the correction of many nosologies.
Leptin and infancy and puberal growth stages
Leptin causes the brain to store fat, which regulates menstruation and other pubertal changes, and subsequently reproductive function in childhood and adolescence period. At the beginning of puberty, an increase in body fat mass occurs precisely due to the high concentration of leptin in the blood. It implies a qualitative transition of adolescents to the phase of puberty. Children become obese, experience irregular menstruation, remain as if in prepuberty and have problems with secondary sexual characteristics if there is not enough leptin in their blood, or if they have a gene mutation,
It turns out that leptin, or the ob protein, is a hormone produced by fat cells and reacts to any changes in the body through receptors that pave the signal path for it. Leptin signaling stimulates neuropeptides, resulting in either an absence or an increase in appetite. The level of the hormone indicates the overall energy reserve in the body, causes the central nervous system to regulate energy homeostasis.
Hormone deficiency can occur as a result of gene mutation or lipoatrophy, which leads to violations of many important functions: reproductive failure, obesity, insulin resistance, autoimmune pathologies. Therefore, the study of leptin is still going on today. It will take place in the near future to improve the early diagnosis of diseases, therapeutic measures for the correction of many nosologies.
