During the last decades obesity has become on extremely wide spread occurrence with serious medicosocial after-effects. Besides the detriment to health, such as hypertension and heart disease, obese people are often stigmatized socially. But despite the fact that substantial advances have been made towards identifying the components of the physiological system that regulates body weight, we are still far from the full understanding of the pathogenesis of obesity. That the existing methods of treatment and other forms of control of obesity are insufficiently effective is indicated by the following fact: more than 90% of individuals who lose weight by dieting eventually return to their original weight [1]. Although much remains to be uncovered, there is growing optimism that the causes of susceptibility to a positive energy balance will be identified. The bulk of the ongoing research in this field focuses on the molecular mechanisms of appetite and satiety regulation, energy metabolism, nutrient partitioning, and adipose cell differentiation and enlargement. It is supposed that this is likely to provide geneticists with a whole new generation of candidate genes to explore for DNA sequence variation and relationships with body fat content and proneness to become obese with age [2].

Without contesting the importance of these studies, we have chosen a somewhat different approach to the search for biological markers predisposing to the development of obesity. It is based on studying the phenomenon of wide quantitative variability of chromosomal Q-HRs in the human genome in certain purely human pathologies [3]. The point is that quantitative Q-HRs variability only exists in man, though this type of constitutive heterochromatin is present in the genome of two other higher primates: Pan troglodytes and Gorilla gorilla [4-6].

The group studied consisted of Kyrgyz and Russian females of reproductive age who had an alimentary form of obesity without clinically pronounced neurohormonal defects. All of them were residents of Bishkek, the capital of Kyrgyzstan.

The choice of representative of only the female sex was mainly due to two reasons: 1) although variability in the amount of chromosomal Q-HRs in the genome of females and males is only determined by seven Q-polymorphic autosomes, males, however, have a Y chromosome with the largest Q-HR segment in the human karyotype, which is characterized by extremely high polymorphism [4,7]; 2) males, at least those living in our country, do not pay too much attention to their body mass, and, as was rightfully noted by [1] “…this view is very dependent on cultural context. In many cultures, obesity is considered to be a sign of affluence and prestige, particularly among those cultures where food is less available”, and this almost fully in keeping with the realities of the Kyrgyzstan of today.

Unfortunately, apart from the general medical examination and talks, we have not performed subtle laboratory and instrumental studies aimed at detecting latent forms of neuroendocrine disorders. Therefore, into our sample fell females with a weight that was 20% or higher than a normal one and was diagnosed from external clinical signs the alimentary form of obesity was diagnosed. The controls consisted of phenotypically healthy Kyrgyz and Russian females of reproductive age whose weight was normal.

Chromosomal preparations were made using short-term cultures of peripheral blood lymphocytes. The cultures were processed according to slightly modified [8] conventional methods [9]. The dye used was propyl quinacrine mustard. Calculation and registration of chromosomal Q-HR variability was performed using the criteria and methods described in detail elsewhere [10-14].

To describe Q-HR variability in our samples we used only three main quantitative characteristics of this cytogenetic phenomenon: (1) the distribution of Q-HRs in the populations studied, i.e., the distribution of individuals having different numbers of Q-HR in the karyotype regardless of the location (distribution of Q-HRs), which also reflected the range of Q-HR variability in the population genome; (2) the derivative of this distribution, an important population characteristic, is the mean number of Q-HR per individual; (3) the frequency of Q-HRs in seven Q-polymorphic autosomes in the population.

The χ² test was used to compare distributions of Q-HRs. The mean numbers of Q-HRs per individual were compared using the Student ttest.

Data on the distribution and mean number of Q-HRs per individual in the samples studied are presented in Table 1. As can be seen from this Table, females with obesity, regardless of their ethnic origin, are characterized by a consistently low value of the mean number and by narrow range of variability in the distribution of Q-HRs numbers in the samples as compared with controls. Their similarity in these two major quantitative characteristics of chromosomal Q-HRs variability allowed us to combine them into one group for subsequent comparative analyses.

Table 1: Distribution and mean number of Q-HR per individual in groups of obese females and in control samples.

Table 2 shows the values of absolute and relative Q-HRs frequencies on seven Q-polymorphic autosomes in studied and controls groups. Comparative analysis of our samples once again demonstrated our previous observations that on seven Q-polymorphic autosomes in the human genome the distribution of Q-HRs are not fortuitous. The greatest amount of Q-HRs, like in other previously examined populations, is located on autosomes 3 and 13 (more than half of all the Q-HRs), while the rest of the Q-HRs are more or less uniformly distributed on other Q-polymorphic autosomes, indicating, as we suppose, nonlocusspecificity of Q-HRs in the human genome [15-18]. Indeed, as can be seen from this Table, Q-HRs in obese individuals is encountered with an expected frequency on all the potentially Qpolymorphic autosomes [3].

Table 2: Q-HR frequencies in seven Q-polymorphic autosomes in obese females and in the control group.

* represents the Q-HR frequency from the number of chromosomes analyzed and ** represents the Q-HR frequency as percentage of the overall number of chromosomal Q-HR.

As was neatly noted by Friedman [1]: “…because eating is an activity in which we all partake, it is not surprising that almost everyone has an opinion about this subject.” Therefore, it is not surprising that the trends of fundamental studies devoted to obesity are extremely wide. The bulk of the ongoing research in this field focuses on the molecular mechanisms of appetite and satiety regulation, energy metabolism, nutrient portioning, and adipose cell differentiation and enlargement [2,19].

In contrast, little progress has been made during the same period of time with respect to the genetic basis of human obesity. Let us mention at once that a number of mendelian disorders are known to exist in humans, but no specific genes have yet been identified for them [20,21]. Although several single gene defects are known that produce obesity in animals and all of these have been cloned, providing a rich new base for understanding obesity [22-27].

From these studies the discovery of leptin has generated great excitement. It was shown, in particular, that mutations that result in leptin deficiency are associated with massive obesity in humans as well as rodent [28,29]. Leptin can also affect energy expenditure, which, in other context, is regulated independently of food intake [20,30]. Mutation in the leptin receptor is also associated with extreme obesity [31]. It has served as a major piece of evidence that obesity is a serious disease and can be produced by genetic and molecular abnormalities.

It should be kept in mind, however, that the effects of leptin deficiency are critically dependent on adrenal glucocorticoids. Adrenalectomy in the ob/ob mouse, the db/db mouses, and all the other animal models in rodents will stop the development of obesity. Moreover, this steroid is essential for the development of insulin resistance, for the alterations in muscle function, and for the alterations in bone growth and hyperphagia these animals manifest [2].

Why then are some individuals obese and others not? The answer of authors studying neuroendocrine and molecular aspects of obesity is that the intrinsic sensitivity to leptin is variable and that, in general, obese individuals are leptin-resistant [20,30]. The molecular basis for leptin resistance has been explained in some instances [32-35]. But nevertheless, the range of the latest studies is outlined by the system of leptin and body-weight regulation. Though it is admitted that there is plasticity of this system and such factors as diet, environment, age and perhaps exercise are also important in the pathogenesis of obesity [36]. Environmental factors have been shown to affect leptin sensitivity, as a high-fat diet leads to leptin resistance, although the basis for this poorly understood [20].

The point is that there are a number of circumstances that are directly or indirectly indicative of the scantiness of molecular approaches of studies, including the search for a hypothetical gene (or genes) involved in the development of obesity in man. Thus, for instance: 1) the results of numerous epidemiological studies carried out in many countries and regions have unequivocally shown that the frequency of obesity in females is two times higher than in males; 2) the global medico social problem of obesity only arised in the last decades; and we consider the functional derangements in the neuroendocrine and central nervous system in preserving energetic homeostasis in the contemporary man very doubtful just because of an improved diet and life conditions despite the fact that corresponding homeostatic systems act in nature have been acting for a long time. Moreover, our bodies are better adapted to combat weight loss than to combat weight gain, since for thousands of years our species evolved in circumstances where nutrients were in short supply; 3) in the evolution of the species Homo sapiens there never was such a period of “prosperity” as in the present economically developed countries to produce in its genome serious changes capable of causing the appearance of a specific structural gene of obesity, and therefore, the increasing rates of obesity cannot be explained exclusively by changes in the gene pool. In connection of the aforementioned facts we suppose that possibly exist other biological factors predisposing to obesity in man.

A remarkable feature of human chromosomal Q-heterochromatin regions (Q-HRs) is their wide quantitative variability characterized by the fact that individuals in a population differ in the number, location, size and intensity of fluorescence of these specific fluorescence areas [4,37]. The existence of population Q-HRs variability in twelve polymorphic loci of seven autosomes and on the distal portion of the long arm of chromosome Y is well-established fact [7,38-46].

By studying chromosomal Q-HRs variability in the human populations permanently living in various climatic-and-geographic conditions of Eurasia and Africa, in norm and pathology we have obtained the data indicating possible participation of chromosomal QHRs in cell thermoregulation (CT). We have checked this hypothesis on the level of human organism assuming that CT is the basis for heat conductivity of whole cell part of body [3,47].

In the present study we found that in individuals with obesity the amount of Q-HRs in their genome proved to be extremely low. We once again feel that the reason for this difference lies in the features of cell thermoregulation. Thus, in patients with alimentary obesity and therefore with a low BHC (even assuming that they use the same amount of calories as people with normal weight), we believe that a part of the calories accumulates in the body in the form of adipose deposits due to inadequate heat loss. The point is that alimentary obesity mainly occurs in people living in temperate, more often in northern but economically developed countries. Surplus heat is not completely removed from the body due to good heat insulation (comfortable habitation and life) and body insulation in the form of modern clothes that are warm but do not adequately contribute to heat loss. If we also take into account the use of high-caloric, easily assimilable food-stuffs, hypodynamia and, possibly, the use of power consuming beverages (alcohol), ineffective heat loss in alimentary obesity become evident.

And finally, the answer to the raised question: “Why are some individuals lean or some obese?” instead of the existing points of view that obesity is either the result of fundamental lack of discipline on the part of affected individuals or that the answer to this question will be found by the identification of genes that a responsible for human obesity, we would answer that obesity is not simply a personal failing or the result of abnormal functioning of some structural genes (here we mean only alimentary obesity). We suppose that in a human population there is a very great variety in the functioning of the system of energy homeostasis involved in the regulation of food intake, fat stores and energy expenditure related to the amount of Q-HRs in the genome. In individuals with a low BHC, even with a same consumption of food as in people with a normal weight, in comfortable conditions of life, more fat will be deposited than in individuals with a medium or high BHC, as their heat losses are lower due to a lesser BHC [48,49]. In any event the study factors implicated in weight gain and obesity is crucial for predictions about the future impact of the global epidemic of obesity, and provides a unique opportunity for the implementation of preventive actions [50].

We are grateful to all the women with obesity for their co-operation and understanding the importance of studying the problem of obesity.