1. Hormones of the adipose tissue
Hormones of the adipose tissue
Due to its large quantity, adipose tissue represents an important, but often neglected endocrine organ.
Its cells (adipocytes) form an extensive amount of peptide hormones known as adipokines (or adipocytokines). In general, they mainly regulate the energy metabolism and their effect on appetite and feeding behaviour influences a long-term regulation of the body weight. Apart from affecting the metabolism they also modulate immune functions and the course of the inflammatory processes. Among the most important and well-known hormones are leptin, adiponectin and resistin.
In addition to the direct production of its own hormones the adipose tissue influences hormones secreted by other endocrine organs. For example, an excessive amount of adipose tissue can significantly contribute to the formation of insulin resistance, type 2 diabetes or atherosclerosis.
There are several hypotheses explaining the mechanism by which the adipokines work. The so-called lipostatic hypothesis claims that the adipose tissue produces, proportionally to its amount in the body, signaling molecules affecting hypothalamus and leading to an increase in energy expenditure and decrease in food intake. The first uncovered mediator of this kind was leptin.
Structure and synthesis
Leptin is a 167 amino acid hormone, a product of the ob gene (“ob” derived from the word obesity). Its receptor is coded by a db gene, which exists in several alternative splicing forms. Different forms of this receptor can be found in different parts of the body – e.g. in brain (hypothalamus mainly) or in peripheral tissues.
Leptin is synthesized mainly by adipocytes of the white adipose tissue and the synthesized amount correlates with the quantity of the adipose tissue in the body. Obese people therefore produce more leptin than people with normal body weight. Apart from white adipose tissue, leptin is synthesized at lesser extent by other tissues as well (e.g. brown adipose tissue, skeletal muscles, stomach, liver or placenta).
Function and pathology
Leptin extensively regulates the energy intake and expenditure by its influence over feeding behaviour, appetite, hunger and energy metabolism. Because its amount in bloodstream corresponds to the amount of adipose tissue, it provides the brain with feedback information about the status of energy reserves.
Leptin passes through the hematoencephalic barrier and has an anorexigenic effect on hypothalamus, suppressing appetite and increasing the energy expenditure. In periphery it influences the sensitivity towards insulin. It thus acts against the orexigenic effect of neuropeptide Y, which, on the contrary, increases appetite and stimulates the secretion of insulin. Leptin activates an enzyme AMP-kinase (AMPK) located in myocytes, which causes an increase in TAG oxidation in muscles.
There exist rare cases of mutations damaging the leptin receptor or the leptin itself. They present themselves as often morbidly extensive obesity occurring at low age and dyslipidemia, which results from an uncontrolled hunger and gluttony. An increased production of insulin in this patients leads to the development of the insulin resistance.
In contrast, most of the obese patients do not have a leptin deficiency. On the contrary, because the leptin is formed proportionally to the amount of adipose tissue in the body, obese people usually have rather hyperleptinemia and leptin resistance. Therapeutic administration of leptin, which was at first considered a universal cure for obesity, thus helps only a fraction of patients (those with a mutation affecting the leptin or its receptor).
Structure and synthesis
Adiponectin is a protein hormone produced mainly by adipocytes of the adipose tissue. Its concentration in blood is quite high (several orders higher compared to leptin).
Another difference from leptin is the correlation between the amount of body fat and the synthesis of the hormones. In the case of adiponectin it is negative and that is why obese patients have plasma concentrations lower than patients with normal BMI.
There exist several polymeric isoforms of adiponectin in blood plasma (trimers, hexamers or higher polymer structures), each having different effect on body.
Adiponectin is a hormone mainly influencing the metabolism of saccharides and lipids, increasing the sensitivity of tissues to insulin. Its effect leads to an increased transport and utilization of glucose and free fatty acids in muscles, liver and adipose cells and inhibits gluconeogenesis in liver.
Adiponectin, at the same time prevents the development of atherosclerosis, especially at early stages of its formation. It inhibits the transformation of macrophages to foam cells and decreases the expression of the surface adhesive receptors.
Similar to other adipokines, resistin belongs to the group of proteins synthesized by adipocytes. It can also be formed by cells of the immune system and its expression is regulated mainly by a presence of proinflammatory cytokines IL-6 and TNFα.
Animal experiments have shown that the administration of resistin reduces the glucose tolerance and insulin sensitivity. It is therefore probable that the increased concentration is involved in the development of insulin resistance. The association of resistin with obesity and diabetes is still unclear, the results of experimental studies on humans were contradictory. It is thought that its importance in humans lies rather in the regulation of inflammatory processes.
Subchapter Authors: Petra Lavríková and Josef Fontana