In itself, the participation of genetic factors in the development of obesity can be considered firmly proven, according to the Internet publication for girls and women from 14 to 35 years old Pannochka. net We are convinced of this by the existence of lines of laboratory animals with a high incidence of obesity, and the existence of families in which the incidence of obesity is much higher than the average, and the presence of populations (for example, the Pima Indians) with a very high frequency of obesity.

In the hereditary nature of obesity in humans, we are also convinced by the twin method of analysis..

The incidence of obesity in pairs of homozygous twins is significantly higher than in pairs of heterozygous twins (Hakala P. et al. , 1999).

Differences in the propensity for obesity among representatives of different races should also be attributed to hereditary in nature (Chitwood L.. et al. , 1996; Albu J. et al. , 1999). Chitwood L. et al (1996) investigated this issue and found that black women, compared with white women, have a reduced ability to oxidize fats, more carbohydrate participation in oxidative processes, and higher insulin levels.. This, according to the authors, makes black women more likely to develop obesity..

The likelihood of hereditary obesity.

According to modern concepts, a person can be considered hereditarily inclined to be overweight if one of his parents is overweight.. Indeed, the probability of being obese in this case approaches 70-80%, while in the general population it does not exceed 25-30% (Hakala P. et al. , 1999).

Undoubtedly, the involvement of genetic factors in the development of obesity in some lines of laboratory animals. And it seems that recent studies are bringing us closer to understanding the nature and intimate mechanisms of their participation in the pathogenesis of weight gain.. Thus, in particular, it was found that obesity in ob/ob mice is determined by a mutation in the ob gene.

Normally, this gene encodes the protein leptin, consisting of 167 amino acid residues, which is produced by adipocytes (Pankov Yu. , 1996). It turned out that leptin in a certain way affects the stores of fat in the body (Brunner L. , LevensN. , 1998).

In any case, in ob/ob mice with obesity, its content in the blood is reduced compared to normal animals, and when leptin is administered to mice of this line, the latter lose weight.. By the way, leptin got its name from the Greek word " , 1996; Brunner L. , LevensN. , 1998).

Leptin has been shown to influence the feeding behavior of animals. When it is introduced into the body of mice of the ob/ob line, food intake decreases and it is precisely because of this that the animals lose weight (Schwartz M. et al. , 1996; Brunner L. , LevensN. , 1998). It is believed that the regulatory effect of this protein is realized at the level of the food centers of the hypothalamus.. This allows us to consider leptin as a specific hormone that regulates energy reserves in the body (Casanueva F. , Dieguez C. , 1999).

Naturally, the study of leptin content was also undertaken in other lines of animals with a high frequency of obesity.. And here a situation was found that is fundamentally different from that in ob/ob mice.. It turned out that in mice of the db / db line and in rats of the fa / fa line, the content of leptin in the blood is not less, but significantly higher than in normal animals (Hardie L.. et al. , 1996).

Additional administration of this protein to sick animals did not affect their eating behavior and did not lead to a decrease in body weight (Schwartz M. et al. , 1996). Then it was suggested that obesity in this case develops due to a decrease in sensitivity to leptin (Hardie L.. et al. , 1996).

Protein similar to mouse leptin found in humans. However, its exact role in the development of obesity in humans has not yet been established.. As follows from a large number of studies, the concentration of leptin in the blood of overweight patients is 2-7 times higher than normal..

This applies to both adults (Segal K. et al. , 1996; McGregor G. et al. 1996 Liu J. et al. , 1999) and children (Hassink S. et al. , 1996). The concentration of leptin in humans directly and significantly correlates with the severity of obesity and fat mass.. In special studies, it was shown that an increase in the content of this protein in the blood of patients with obesity is associated precisely with an increase in its production, and not with a possible slowdown in elimination from the blood (Klein S. et al. , 1996; Liu J. et al. , 1999).

Here, the hypothesis turned out to be absolutely logical that obese patients, due to some as yet unexplained reasons, lose sensitivity to the action of leptin.. So, in particular J. Holst (1996) proposed a lipostatic hypothesis of body weight control, the main provisions of which can be reduced to the following.

Normally, fat cells produce leptin, which has the properties of a protein hormone, the main purpose of which is to signal to special centers of the hypothalamus about the state of fat stores in the body..

This signal is perceived with the help of the corresponding receptors and is realized through the system of regulation of appetite and food intake.. Obesity can develop if there is at least one of two mutations - either a mutation that disrupts the synthesis of leptin, or a mutation that disrupts the synthesis of receptors for it.

The fact that leptin affects the neurochemical processes in the hypothalamus is also indicated by the data of Glaum S.. et al. (1996). Moreover, the authors found that leptin enhances synaptic transmission of impulses in the arcuate nucleus of the hypothalamus in Zuker rats with normal body weight, but does not affect these processes in obese rats.. This, according to the authors, is associated with a mutation in the leptin receptor gene in the latter..

Attempts have also been made to detect mutations in the hypothalamic leptin receptors in obese people.. For example, in the Considine R study. et al. (1995) compared leptin receptors isolated from the hypothalamus of obese and normal weight subjects..

However, the authors were unable to find any differences. In receptors isolated from obese humans, it was not possible to detect mutations characteristic of those in receptors in db/db mice or fa/fa rats.. In this regard, the authors suggested that resistance to the action of leptin, if present, is not realized at the level of the hypothalamic receptor..

According to Caro J. et al. (1996) although the concentration of leptin in plasma in obese individuals is indeed several times higher, the content of this protein in the cerebrospinal fluid is only 30% higher..

The ratio of leptin concentrations in cerebrospinal fluid and in plasma in lean people was 4 times higher than that in obese patients.. According to the authors, in obese individuals, as a result of the mutation, the production of the leptin transporter across the blood-brain barrier is disrupted and, as a result, the sensitivity to its regulatory action is reduced..

The brain is not the only place where leptin receptors are found.. Receptors for this protein have also been found in pancreatic ?-cells (Kieffer T. et al. , 1996). In this regard, it has been suggested that leptin somehow affects the production of insulin..

Based on the inhibitory effect of leptin on the development of obesity (lipogenesis), it is believed that normally, in response to an increase in insulin concentration, the production of leptin also increases, which, according to the principle of negative feedback, inhibits further production and release of insulin..

The fact that insulin stimulates the production of leptin in cultures of adipocytes was also demonstrated in a study by Nolan J.. et al. (1996). Moreover, this effect is observed only during long-term, but not short-term incubation of cultures with an increased concentration of insulin in the culture medium..

Summing up our brief review on leptin, we point out that everything related to this protein is, at the very least, very interesting.. However, all this is still very far from final clarity..

It seems that leptin is involved in maintaining normal body weight and protects the body from weight gain..

But why does this protection not work in almost every second adult

Perhaps in the future we will have either a leptin drug or a leptin receptor drug or a drug that specifically improves the binding of leptin to the receptor or acts in some other way, but protects the body from the development of obesity or causes weight loss (Heymsfield S. et al, 1999). In the meantime, we have a new area of \u200b\u200bresearch and it is premature to talk about the possible practical use of the results of these studies..

Ginzburg M.

medbe. en.