A Basis of New Way Therapy of Obesity

From the received own data on biochemical impairment of the carbohydrate metabolism in patients with obesity and features of functioning of a genetic control system the organism and literary data it is possible to offer the following scheme of restoration the metabolism of carbohydrates.

1. To normalize structure of carbohydrates in nutrition of patients up to norm according to the theory of the balanced foodstuffs, which is up to parity: 4 parts of carbohydrates, 2 parts of fats and 1 part proteins.

2.Foods should be safe, should not contain pathogenic microorganisms and not promoting occurrence of allergic reactions(peanut, egg, milk, gluten, tree nuts, soya, fish, crustacea, sesame).

3. To enter in nutrition of the patients with obesity of a food with the contents of mannose, fucose or polysaccharides on their basis up to 50 - 100 g into day.

4. For normalization of metabolic processes to support such level of carbohydrates in nutrition during a long period before the following genetic transition. During the next genetic transition necessitate to supervise the contents of mannose in blood of the patient with obesity and fucose in structure mucopolysaccharides of a saliva.

5. For normalisation of biochemical processes in intestinal tract be necessary entered the bifidobacteria 1-2 time in week for 30 min before reception of foods.

6. With the following genetic transition, at the expense of normalization of biochemical processes to translate of energy reserve in organism from a adipose tissue to cell's glycogen.

BIOCHEMICAL IMPAIRMENT of CARBOHYDRATES METABOLISM at OBESITY

Ivan P. Chepurnoy

Stavropol Cooperative Institute BUCC

SUMMARY

In the patients with obesity was revealed biochemical impairment of carbohydrates metabolism. In blood of the patients after introduction they of glucose increased it level is marked and the reduction of a level begins after 60 minutes. Simultaneously in urine of the patients was detected the significant contents of an pyruvic acid (0,35 - 0,85 mg/mL), that indicated an overload of a metabolic way of translation of glucose in fatty acids. In blood of the patients with obesity was detected the lowered contents of mannose (1,25 - 2,36 mmol/L) and absence of fucose. Simultaneously was established the lowered contents of fucose in structure of a carbohydrate fraction of mucopolysaccharides in a saliva. It specifies impairment of synthesis glycoproteins in organism of the patients with obesity with a lack of mannose in blood, that promotes infringement of reception of a insulin in cells of muscles, liver and other cells. Us was revealed the age's features of formation for obesity and close interrelation of occurrence the obesity with genetic transitions in human life. Us was offered the specific recommendations for elimination of biochemical impairments of carbohydrates metabolism at the patients with obesity.

Etiology of the obesity connect with genetics, nervous system impairment, endocrine, metabolic influence and influence of a nutrition[1]. However established connections between these factors and obesity were explained from a position of existing concepts the caloric content of a nutrition. It promoted search of genetic infringements in thermoregulatory of organism [2,3] at incomprehension the elementary biochemical processes proceeded in human organism at the diseases of obesity. In the article was investigated biochemical processes a regulation of glucose in organism of healthy persons and in human obesity under operation of glycoproteins and glycolipids. Glucose (instead of mythic calorie) is basic energetically substance used the human organism for the synthesis of fatty, replaceable amino acid, organic acids, glycoproteins and glycolipids, and also other saccharums (mannose, fucose, sialic acid, galactose, arabinose, xylose, ribose, desoxyribose and others) and others compound. Therefore content in human blood the glucose is to sustain on standard independent from the age. Both increased, and lowered content in human blood of the glucose promotes to development to diseases, and then to lethal outcome [4]. The control the contents in the human blood of glucose is especially necessary for the patients with diabetes mellitus. Both hyperglycaemia, and hypoglycaemia result in irreversible changes in organism of the diabetic. The obesity results in occurrence in elderly age also frequently insulin-independent diabetes. At the obesity also it is recommended to inject of insulin for regulation of a level glucose in blood. Thus, at the obesity in organism of the patient there is an impairment of carbohydrate metabolism, particularly of a glucose.

IMPAIRMENT OF GLUCOSE METABOLISM at OBESITY

For study of features the glucose metabolism in blood of the patients with obesity were carried out the researches by a method of loads. Introduction of glucose 7 healthy and 9 patients with obesity of 1 degree carried out at the rate of 1 a glucose on 1 kg of weight of a body and within 2 hours. Through each 30 minutes, were made definitions of glucose in blood by a colorimetric's method. On figure 1 are given glycemic responses constructed by results of average meanings of the contents glucose in blood for healthy and the patients with obesity.

FIGURE 1 Comparison of mean incremental blood glucose responses in healthy and patients with obesity. The increase of quantity glucose in blood of the patients with obesity in comparison with healthy and longer in time is caused by increase of a metabolic way on translation of glucose in fatty acids. (Black - healthy, Fuchsia - patients with obesity).

As it is visible from fig.1, postprandial glycemic responses of the patients with obesity differ from the healthy people. At the healthy person through 20 - 30 minutes in blood begin to be increased a level of glucose with reception a nutrition that contain of carbohydrates. It promotes its increase of glucose metabolism in organism, including and synthesis of mannose. The increase of concentration of mannose in blood promotes secretion of insulin from basophile cells of the pancreas [4]. The insulin transferred with blood to cells of a liver, a muscular, enters interaction with the receptors of cells (glycoproteins).

In cells of the liver, muscular the insulin participates in translation of glucose in glycogen (polysaccharides), therefore to 60 minutes, as we see on fig.1, the level of glucose in blood is reduced up to norm. Thus, at the healthy person the increased contents of the glucose in blood after reception of nutrition results in secretion from beta cells of insulin, and it promotes synthesis from glucose of glycogen, that results in decrease of a level of glucose up to norm. With starvation, during the further decrease of glucose in blood is lower than a level, is secretion from acidophile cells of the pancreas of glucagon. Already with the help others cells reception he is entered in cells of a liver and muscles and promotes the hydrolysis of glycogen up to glucose and increase in blood of glucose.

Thus is adjusted the contents of glucose in blood of the healthy persons. It proves to be true also by other scientists [5].

After reception a nutrition content carbohydrate in obesity through 20 - 30 minutes in blood of the patient also begin to be increased the level of glucose, that results in it increased the metabolism in organism, including and synthesis of mannose. The increase of concentration mannose in blood promotes secretion of insulin from basophile cells of a pancreas. Insulin is transferred with blood to cells of the liver, the muscular, but to enter interaction with incorrectly constructed reception of cells of the liver, a muscular he cannot. As a result of its the surplus of glucose in blood cannot transform in the glycogen.

Therefore increase of the contents of glucose in blood for obesity, to 60 minutes, as we see on fig.1, it reaches already 9,4 mmol/L. In this case the organism is compelled metabolize of glucose in fatty acids with the subsequent synthesis of fat and deposit its in cells of the patient.

Basic metabolic ways of glucose in healthy organism and at the patients with obesity are submitted in the fig. 2 and 3.

FIGURE 2 The basics of the metabolic ways of use glucose at the healthy person. Glucose in blood is supported at the expense of nutrition containing of glucose, fructose, saccharose, lactose and others oligosaccharides and polysaccharides. It is constantly used for functioning of a cerebrum brain, of muscle cells, synthesis of fatty acids and replaceable amino acids. The increased contents of glucose in blood after reception of food is to translate in the cell's glycogen.

FIGURE 3 The basics of the metabolic ways of use glucose at the patients with obesity. The glucose in blood of the patients with obesity is supported not only at the expense of nutrition containing carbohydrates, but also for the account metabolism of fatty acids and replaceable amino acids on a way glyconeogenesis. The glucose is used also for functioning a cerebral brain, of muscle cells. With increase of a level of glucose in blood after a nutrition with a carbohydrate-containing is to translate glucose in fatty acids.

It is known, that in blood at the patients with obesity is marked the increased contents lactic, pyruvic acids [6]. Pyruvic acid is an intermediate link in metabolism of glucose in fatty acids and increased her contents not only in blood, but also in urea can specify only an overload given metabolic way. We carried out research at the contents pyruvic acid in urea healthy and patients with obesity with the help of gas liquid chromatography on glass capillary columns on a known technique [7].

In Table 1 are given the results of the carried out researches. In healthy person the contents of pyruvic acid in urine is in vestige quantities. In patients with obesity a quantity of pyruvic acid in urine makes 0,85 - 0,35 mg/mL, that in tens times as large, than in healthy person. Thus, we see, that increased the levels of glucose in blood of the patients with obesity conduce a translation of glucose in free fatty acid, and further to formation fatty deposits in adipose cells. This metabolic way function in organism of the patient with obesity under a large overload, that results in increase of the contents pyruvic acid in blood, and the part its is secrete in urine.

Table 1 Structure of organic acids in urine healthy and the patients with obesity (mg/mL)

The note: Here and in table 2: The sign " X" stands for non-identified fractions of acids; blank - stuff is not detected.

Impairment of reception of insulin by cells

The deposits of fat in adipose cells is the compelled energetic reserve of glucose with impairment a reception of insulin in human organism. The impairment of reception of insulin in muscular cells and cells of liver results in development of hyperinsulinism.

On fig.4 are shown the systems of reception and endocytosis of insulin in liver cell healthy and patient with obesity. At the approach of insulin to the liver cell will be formed on a surface of the cell the layer of receptors, consisten from glycoproteins [8]. The insulin contacts with receptors, which at first are going in groups, forming clusters, then clusters are united, giving so-called "cap". Through the certain intervals of time is to segregate the part of cell of the surface together with receptor and insulin, to forming of vesicle and the insulin is to enter in inside of cells and is transferred in that or other its part. Released the vesicle again comes back to the cell surface. The quantity of receptors forming on cell surface is adjusted by the cell and by that is determined the sensitivity its to that or other hormones. So is introduce the insulin into the cells in healthy persons.

FIGURE 4 Reception and input of insulin in the cell at the healthy person (a) and patient with obesity (b). With the approach of insulin to cell of the healthy person on the cell surface will be formed clasters and then cap and insulin by the way endocitosis is entered into of a cell. With obesity is broken reception of insulin glycoproteins of the cell and insulin is not entered.

In patient with obesity under the approach of insulin to the cell on the surface will not be formed cluster from glycoproteins, as receptors, which answer for recognition of insulin, have other a carbohydrate's structure (replacement in glycoproteins of mannose and fucose on others monosaccharides). Accordingly, insulin cannot to get into cell. Therefore cells, for which functioning the presence of insulin is necessary, send signals in a brain about the lack insulin and organism begins secretion of insulin in a great quantities. Arises is syndrome "X" [7]. Thus syndrome can raise the quantity of insulin in blood of the patient with obesity up to 90 - 100 mkIU/mL with norm at the healthy person 5 - 15 mkIU/mL.

We carried out of researches of the contents of sugars in blood healthy and in patients with obesity by help of gas liquid chromatography with glass capillary columns on a known technique [9], and also impairment of the carbohydrate's structure the glycoproteins of a saliva (mucopolysaccharides) by reaction on contents of fucose [10].

In Table 2 are given the results of sugars researches by gas chromatography. In structure of sugars in blood healthy are identified of fucose, mannose, glucose and some not identified peaks present in small quantities. At structure of sugars in blood at the patients with obesity the mannose was present in small quantities, the level of glucose was in norm or hardly above than at healthy and increase the presence of peak X5 identified presumably as sialic acid. Thus, we see, that at the patients with obesity in blood the normal or little increased contents of glucose with decrease of quantity of minor sugars (mannose and fucose). Panneerselvam K et al. also have revealed impairment of synthesis normal glycoproteins with the lack of the mannose in a diet [11].

Table 2 Structure and contents of carbohydrates in blood at healthy and patients with obesity (mmol/L)

Sugar	Healthy	The patients with obesity, prescription of diseases, years
		3	5,5	7	10	11
Fucose	0,01	0	0	0	0	0
Mannose	0,46	0,07	0,07	0,11	0,13	0,08
Glucose	5,78	6,39	6,85	7,12	6,93	7,58
x1	0,07	0,09	0,06	0,08	0,10	0,09
x2	0,15	0,19	0,07	0,10	0,06	0,04
x3	0,01	0,05	0,08	0,09	0,08	0,06
Total	6,48	6,80	7,14	7,51	7,31	7,86

In table 3 are given the results of inspection of the patients with obesity on presence of fucose in structure of mucopolysaccharides of a saliva with simultaneous definition of glucose in blood by a colorimetric's method. In 32 patients with a various stage of obesity in the age from 15 till 68 years (on the average 49 years) the saliva was selected, by which flow the solution of sulfate acid with cysteine and visually was determined in the course of 3 minutes the coloring of the solution. It is revealed, that at the patients with obesity 1 degree in the saliva completely did not come to reaction on fucose, at the patients with obesity 2 degrees the reaction on fucose was poorly positive.

Table 3 Results of qualitative reaction on fucose at the patients with obesity, which has addressed in Stavropol regional clinical-diagnostic centre

Thus, on the basis of own researches of structure the carbohydrates of blood and structure of sugars the mucopolysaccharides of the saliva is established, that at the patients with obesity the very low level mannose in blood and is present the lack of fucose in structure mucopolysaccharides of the saliva. The revealed impairment in the structure of glycoproteins of the saliva at any rate can be identified and with impairments in to structure of carbohydrates others glycoproteins of organism in the patients with obesity.

It allows to assert, that the impairment reception of insulin at the patients with obesity is connected to impairment of the carbohydrate metabolism in organism, in particular the lack in blood of the mannose and lack fucose in structure of glycoproteins with the normal or increased level of glucose in blood.

GENETIC IMPAIRMENTS at HUMAN OBESITY

Many researchers have revealed, that those or other diseases arise per the certain years of the human life. The childhood leukaemia in England and Wales is displayed more often per 3 years [12], a uterine neck cancer in Russia at 45-50 of years [13]. Many scientists do not connect yet of obesity to genetic impairments in human organism and it does not get in candidate diseases for gene therapy [14]. By us is established earlier [15], that in human life there are genetic periods and the transitions from one period in other to put in increase in blood the contents many the hormones, and also to an aggravation of available diseases or occurrence new diseases.

355 patients with various diseases were surveyed which earlier or nowadays suffer of obesity. The received data are submitted in the fig. 5.

Figure 5 The age's features of disease with obesity. These results are based on inspection 355 patients with obesity. Most frequently of obesity there are in 30 - 35 years and 45 - 50 years. At this time there is a reorganization organism of man with reproductive in mature (at the women proceeds in this time the climacteric period).

From the fig. 5 it is visible, that obesity arises, as a rule, on genetic transitions, which are submitted on fig.6.

Figure 6 The basic genetic periods that is in life of man. In the life the man elapse hard and fast stages of the development from babyhood up to deep old age. These stages of development proceed in the strictly certain sequence. The 7 basic and 8 additional genetic periods revealed in life of man is offered on the basis of changes of his biochemical processes.

More often of obesity are formed in 12 -13 years, 15 - 18 years at a children. At the adult arise of obesity in 22 - 25 years, in 30 - 35 years and after 45. The women suffer from obesity also with a genetic transition from a stage of pregnancy, birth and education of a child in a normal period of puberty.

The comparison of the received data on occurrence of obesity in that or other age period with genetic transitions allows to assert, that obesity, as the disease, is more often formed during genetic transition with long functioning of organism with impairment of carbohydrate metabolism and lack in organism of mannose and fucose.

With the subsequent genetic transition, after occurrence of disease, the biochemical impairments, characteristic for obesity can be eliminated with normalization of carbohydrate metabolism, or to be kept with fastening given metabolism impairments at a genetic level as phenotypical of an attribute. Therefore to patient with obesity, for normalization of his biochemical processes, with the approach to the next genetic transition it is necessary to enter in nutrition of products with the high contents mannose, fucose or polysaccharides on their basis (fucoidan, mannane, galactomannane, glucomannane).

From the received own data on biochemical impairment of the carbohydrate metabolism in patients with obesity and features of functioning of a genetic control system the organism and literary data it is possible to offer the following scheme of restoration a metabolism of carbohydrates.

1. To normalize structure of carbohydrates in nutrition of patients up to norm according to the theory of the balanced foodstuffs, which is up to parity: 4 parts of carbohydrates, 2 parts of fats and 1 part proteins.

2. To enter in nutrition of the patients with obesity of a food with the contents of mannose, fucose or polysaccharides on their basis up to 50 - 100 g into day.

3. For normalization of metabolic processes to support such level of carbohydrates in nutrition during a long period before the following genetic transition. During the next genetic transition necessitate to supervise the contents of mannose in blood of the patient with obesity and fucose in structure mucopolysaccharides of a saliva.

4. With the following genetic transition, at the expense of normalization of biochemical processes to translate of energy reserve in organism from a adipose tissue to cell's glycogen.

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