[Regional features of obesity-associated gene polymorphism (rs9939609 FTO gene and gene Trp64Arg ADRB3) in Russian population].

Recent studies have shown a significant association with obesity polymorphisms: rs9939609 gene due to fat mass and obesity FTO in European and some Asian and African American populations Trp64Arg ADRB3 gene in several European populations. Association of variants rs9939609 and Trp64Arg obesity was studied in 1244 the inhabitants of Moscow and Sverdlovsk regions. Genotyping was performed using allele-specific amplification, detection results in real time using TaqMan-probes complementary DNA polymorphic sites. The frequency of the mutant allele of the FTO gene in the population of Moscow and Sverdlovsk region was 45.1%, with the TT genotype was detected in 30.2% of cases, AT--49.5%, AA--20.3%. Women had the presence of the mutant allele more likely than men (48.4 vs. 42.5%). People with obesity were more genotypes AA (26.3%) and AT (52.8%) compared to the surveyed with a BMI of less than 30 kg/m2 (respectively 18.1 and 50.7%). A significantly higher incidence of risk allele A was found in individuals with obesity (52.6 and 43.4%). The presence of the mutant allele of the gene ADRB3 among the population of Moscow and Sverdlovsk regions was noted in 7.4% of cases. While 15.5% of patients had a heterozygous genotype Trp64Arg ADRB3, that is consistent with international research. The frequency of the risk allele and genotype Arg64 Trp64Arg in women (9.3 and 18.5%) was significantly higher than men (6.2 and 12.2%). The presence of the mutant allele and genotype Trp64Arg ADRB3 (respectively, 9.1 and 18.1%) were significantly more marked in the examined obese compared with those with a body mass index less than 30 kg/m2 (7.4 and 14.9%), but these differences were not statistically significant. The results of these studies suggest that genetic variants of the FTO gene rs9939609 genotype and Trp64Arg ADRB3 contribute to the development of obesity among residents of Moscow and Sverdlovsk Region of Russia. The risk of obesity increases in the case of combined polymorphisms in both genes.

[Adipokines and the metabolism of key nutrients in patients with obesity].

AIM: To study the effect of adipokines on the metabolism of key nutrients in patients with obesity. SUBJECTS AND METHODS: Ninety patients aged 18 to 66 years old who were treated at the Department of Preventive and Rehabilitative Nutrition, Research Institute of Nutrition, Russian Academy of Medical Sciences, were examined. Carbohydrate and lipid metabolisms were assessed by turbidimetry and spectrophotometry. The levels of adipokines, insulin, and oxidized low-density lipoproteins (LDL) were measured by ELISA. Insulin resistance was assessed with HOMA-IR in all the patients. RESULTS: It was found that there were discoordinated changes in the content of adipokines. The patients with Grade 1 obesity, as compared to the control group, had a statistically significant decrease in the serum concentrations of adiponectin (5.94 +/- 0.90 and 15.34 +/- 0.45 microg/ml; p < 0.05) and ghrelin (215.50 +/- 104.50 and 540.67 +/- 0.76 pg/ml; (p < 0.05) and resistin levels above the normal values (7.34 +/- 1.24 and 5.12 +/- 0.22 ng/ml; p < 0.05; respectively). There was an inverse correlation between the content of adiponectin and ghrelin, and body mass index in obese patients (r1 = -0.25, r2 = -0.15; p < 0.05). There was evidence that there was also an inverse correlation between the levels of adiponectin, triglycerides, LDL, particularly oxidized LDL (p < 0.05). Adipokine-induced insulin resistance appeared as increases in the concentrations of glucose, insulin, and HOMA-IR, as compared to those in the control group. CONCLUSION: A comprehensive approach to evaluating metabolic disorders and adipokine synthesis in obese patients makes it possible to optimize the diagnosis of type 2 diabetes mellitus and cardiovascular diseases and to personalize diet therapy.

[Toxicological assessment of nanostructured silica. II. Enzymatic, biochemical indices, state of antioxidative defence].

Nanostructured silica (SiO2) "Aerosil" with the size of the primary nanoparticles (NPs) of 5-30 nm, in the form of ultrasound treated water suspension was administered to rats of 80 ± 4 g initial body weight for the first 30 days by intragastric gavage and then for 62 days with diets consumed in doses of 0.1; 1.0; 10 and 100 mg/kg body weight per day. The control group received vehicle of nanomaterial (NM)--deionized water. There were measured in liver of ani- mals the content of total cytochromes P450 and b5 in the microsomal fraction of liver, activity (Vmax) of microsomal monooxygenases with the mixed func- tion of isoforms CYP1A1, 1A2 and 2B1 on their specific substrates, the activity of conjugating liver enzymes glutathione-S-transferase and UDP-glucuronosyl-transferase in microsomal fraction and cytosol, the total and non sedimentable activity of lysosomal hydrolases (ß-glucuronidase, ß-galactozydase, arylsulphatase A, B). The content of PUFA's diene conjugates and TBA-reactive substances in the blood plasma and the activity of antioxidative enzymes (glutathionperoxidase, superoxidedismutase, glutathionreductase, katalase) in erytrocytes were estimated. A set of standard biochemical parameters of blood serum was also examined (total protein, albumin, glucose, creatinine, urea, uric acid, activities of hepatic transaminases). The studies revealed changes of a number of molecu lar markers that could be interpreted as unfavorable. These include isoforms of CYP2B1 activity decrease at a dose HM 1-10 mg/kg of body weight, decrease in the serum content of total protein, albumin and glucose levels in a dose range of 0.1-10 mg/kg. These changes were absent at the maximum dose of NM, which did not allow to clearly establish the dose-response. The remaining studied fig ures resided in the normal range or experienced changes that could not be interpreted as toxic.

[Effects of rutin on the activity of antioxidant enzymes and xenobiotic-metabolizing enzymes in liver of rats fed diets with different level of fat].

The study has been carried out on 6 groups of male Wistar rats, which received semi-synthetic diets within 28 days. Rats of 1st and 4th group received fat-free diet, 2nid.and 5th - diet containing standard amount of fat (10% by weight, 26% by caloric content; lard/sunflower oil - 1/1); 3rd and 6th group - a high-fat diet (30% by weight, 56% by caloric content). During the last 14 days of the experiment rats received rutin in the dose of 40 mg/kg b.w. AOA, MDA level and the activity of paraoxonase I have been evaluated in blood serum. In rat liver along with the parameters of the antioxidant status (MDA level, activity of paraoxonase 1, quinone reductase, heme oxygenase-1) the activity of xenobiotic-metabolizing enzymes (XME) (CYP1A1, CYP1A2, CYP3A1, CYP2B1, UDP-glucuronosyl transferase and glutathione transferase) and the activity of lysosomal enzymes (arylsulfatase A and B, ß-galactosidase and ß-glucuronidase) have been investigated. Elevation of the activity of antioxidant enzymes and XME in liver with the increase of diet fat content has been-noted. Rutin admihistration had no effect onparamete6rs of antioxidant status and decreased unsedimentable activity of lysosomal enzymes that did not depend on fat content in the diet. Rutin receiving increased the activity of all studied XME in rats fed standard diet, but practically did not effect on their activity in rats fed by fat-free and high-fat diets. Thus, rutin in pharmacological dose has no effect on the activity of antioxidant enzymes that doesn't depend on the level of fat in the diet, while the decrease or increase of diet fat content modulates (weakens) the influence of rutin on the XME activity.

[Bioaccumulation of silver and gold nanoparticles in organs and tissues of rats by neutron activation analysis].

Bioaccumulation of silver (Ag) and gold (Au) nanoparticles (NPs) with mean sizes of 6 nm and 35 nm, respectively, has been studied after their intragastric administration to rats at a dose of 100 µg/kg of body weight for 28 or 14 days. The organs and tissues (liver, kidney, spleen, heart, gonads brain, and blood) were subjected to thermal neutron activation, and, then, the activity of the 110mAg and 198Au isotopes generated was measured. The NPs of both metals were detected in all biological samples studied, the highest specific weight and content of Ag NP being found in the liver, and those of Au being found in kidneys of animals. The content of Ag NPs detected in the brain was 66.4 ± 5.6 ng (36 ng/g tissue), no more than 7% ofthese NPs being localized in the lumen of brain blood vessels. The content of Ag and Au NPs found in organs and tissues of rats could be regarded as nonhazardous (nontoxic) in accordance with the known literature data.

[About the human health safety estimation of ractopamine intake together with the food].

The analysis of scientific data including American and European scientific communities concerning use of ractopamine as a growth factor in food animal production and the argumentation of the maximum permitted levels of ractopamine and levels of ractopamine in meat and byproducts (offal) is carried out. The position of the Russian side stated at the Codex Alimentarius commission 35th session that acceptable ractopamine daily intake is insufficiently validated and cannot be used for the determination of maximum permitted levels of ractopamine in meat and byproducts (offal) is confirmed. It is represented that residual ractopamine intake together with food on the levels which are recommended by the Codex Alimentarius commission and by taking into account the levels of animal products consumption in Russian Federation will lead to unacceptable human health risk level that will promote increasing heart diseases and life expectancy reduction. In this connection Russia states against of acceptance of maximum permitted levels of ractopamine in food.

[Polymorphisms Ser447Ter of lipoprotein-lipase gene, Cys112Arg and Arg158Cys of apolipoprotein E gene in patients with obesity].

The distribution of allele Ser447Ter of lipoprotein lipase gene (LPL) and polymorphic markers E2 and E4 of the apolipoprotein E gene (ApoE) were examined in 100 obese patients at the age of 18-66 years (28 men and 72 women, 40.6 +/- 2.1 years old). The first group included patients with I degree of obesity (n = 26, BMI = 32.5 +/- 0.2), the second group--patients with II degree of obesity (n = 33, BMI = 37.1 +/- 0.2), the third group--patients with grade III obesity (n = 41, BMI = 46.3-1.1) and control group were 18 healthy individuals aged from 22 to 55 years (7 men and 11 women, 36.5 +/- 0.9 years old, BMI = 22.4 +/- 1.8). Maximal frequency of allelic polymorphism epsilon2 has been revealed in patients with I degree of obesity, and allele epsilon4--in patients with III degree of obesity. The most common genotype of ApoE gene was epsilon3/epsilon3 in all three groups of patients with obesity. In a comparative analysis of allelic variants of the Apo E gene occurrence it has been found that the frequency of a polymorphic variant epsilon2/epsilon2 tended to decrease with BMI increasing, whereas a higher rate of detection of genotypes epsilon4/epsilon3, epsilon4/epsilon4 and epsilon2/epsilon4 was found in patients with III degree of obesity. The data obtained suggest that the epsilon4 allele of the Apo E gene is associated with the development of morbid obesity, rather than allele epsilon2. This phenomenon can be explained by the fact that apoE4 isoform has reduced affinity for LDL in comparison with apolipoprotein E3. The maximum concentration of cholesterol, triglycerides and LDL cholesterol has been observed in patients with epsilon2/epsilon4 genotype of ApoE gene, and it was significantly higher than in the control group (p < 0.05). The content of blood lipid fractions in patients with epsilon3/epsilon4 genotype of ApoE gene, in contrast, was the lowest among obese and did not exceed the values of the control group (p > 0.05). These data indicates a small contribution of epsilon4 polymorphism in heterozygous form to the development of dyslipidemia in obesity. The most positive effect of diet treatment was achieved in patients with genotype epsilon3/epsilon3 and epsilon3/epsilon4. An integrated approach to the assessment of lipid metabolism in patients with obesity, including the analysis of polymorphic genetic loci, can optimize and personalize the diet therapy.

[Analysis of regulatory basis for organization of clinical nutrition in medical institutions of the Russian Federation].

The article analyzes regulatory basis for organization of clinical nutrition in medical institutions of Russia. It is shown that the strategy of therapeutic measures in acute and chronic diseases a central place to take dietary therapy with adequate provision of energy and plastic body's needs, correction of metabolic disorders and risk factors for comorbidity. Prior to the confirmation of the order of Ministry of Health of Russia from 05.08.2003, No 330 "On measures to improve nutritional care in health care institutions in the Russian Federation" clinical nutrition in medical institutions was based on the nosological principle, in the form of daily diet--a diet designed for each concrete Diseases which are identified by a number from 1 to 15. According to the order of Ministry of Health of Russia from 05.08.2003, No 330 in the health care practice has introduced a new range of diets (system standard diets), which is based on the principle of adapting the chemical composition and energy value of the diet to the individual clinical and pathogenic features of the disease and combines previously used diet numbering system. It is shown that the organization of clinical nutrition should be based on common requirements imposed on the federal level and at the level of the subject of the Russian Federation. In order to optimize clinical nutrition is necessary to determine the methodological approaches to personalization through the introduction of diet in health care practice of modern innovative technologies health food, performing preventive and treatment of the problem (implementation of Article 39 of the Federal Law of 21.11.2011 No 323--FZ "On the basis of health protection in the Russian Federation", the Order of the Government of the Russian Federation of 25.10.2010 No 1873-r "On the basis of the state policy in the field of nutrition to 2020 year").

[Biologically active substances of plant origin. Flavonols and flavones: prevalence, dietary sourses and consumption].

Flavonoids are the most numerous group of natural polyphenolic compounds, the secondary metabolites of plants that may play an important role in human health protection. Flavonols and flavones constitute the main two classes of flavonoids, whose antioxidant properties and high biological activity have been proofed both in vitro and in vivo. This review summarizes data, concerning the structure, occurrence and content of the main flavonols (quercetin, kaempherol, myricetin, isorhamnetin) and flavones (apigenin, luteolin) in some most widely consumed foodstuffs, including vegetables, fruits, berries, nuts, beverages and other products of plant origin. The products with high content of these biologically active food compounds--the major dietary sources of them--are noted. Forms of flavonols and flavones more often distributed among edible plants are characterized and some of their known glycosides occurred in foods are enumerated. Some peculiarities, characteristic to flavonol sand flavones glycosilation (O- and/or C-glycosides formation) are described. The data for flavonol and flavone glycosides composition (profiles) of some commonly consumed commodities rich by these flavonoids (onions, cabbage, apples at al.) are shown. Information about levels of daily dietary intake of total and individual flavonols and flavones in several countries is presented. The questions about dietary habits and lifestyle factors and the contribution of certain foods to flavonols and flavones in daily dietary consumption values are also discussed.

[The Trp64Arg polymorphism of beta3-adrenoreceptor gene study in persons with overweight and obesity].

The development of obesity is determined by lifestyle and genetic mechanisms. In particular, the polymorphisms in the adrenergic receptor genes (ADRB) have been extensively studied for association with obesity-related phenotypes. ADRB3 is an obvious candidate gene given its involvement in the regulation of lipolysis and thermogenesis. ADRB3 Trp64Arg polymorphism, a missense mutation in the first transmembrane domain of the R3-adrenergic receptor is associated with visceral obesity and insulin resistance in the Pima Indian, French, and Finnish populations. The recent meta-analysis that combined data of 6582 individuals from Japanese populations showed significant association the Arg64 allele with increased BMI. There are tested the polymorphisms in the beta3-Adrenoreceptor (ADRB3) gene in associated with body mass index (BMI), fat mass and biochemical parameters.We have been examined 91 persons from Moscow region with BMI >25 kg/m2. The Trp64Arg polymorphism of ADRB3 genes were genotyped with the use of an allelic discrimination assay. The TaqMan-based real-time PCR method was applied. There have been estimated of anthropometric and biochemicalparameters. The frequencies of the Trp64Trp and Trp64Arggenotypes of ADRB3 gene were 82% and 12%, respectively, the frequencies of mutant allele was 6%. Trp64Arg genotypes of ADRB3 compared to Trp64Trp genotypes had significantly higher body fat percentage (respectively 48,6 +/- 0,96% and 43,8 +/- 1,72%, p<0,05), serum glucose (6,51 +/- 0,18 mmol/l and 5,67 +/- 0,09 mmol/l, p<0,01) and uric acid concentrations (0,46 +/- 0,02 mmol/l and 0,38 +/- 0,01 mmol/l, p<0,05). The test of the ADRB3 gene polymorphisms can be used for the personalization of diet in persons with obesity.

[The study of FTO rs9939609-gene polymorphism in the Sverdlovsk Region].

Recently independent studies, including genome-wide scans, have shown that the rs9939609 single-nucleotide polymorphism (SNP) in the first intron of the fat mass and obesity associated (FTO) gene were significantly associated with obesity in populations of European origin, in certain Asian (e.g.,Japanese and Chinese) and African American populations. In this study we examined the association between rs9939609 FTO variant and obesity related parameters in 394 individuals (262 males and 132 females; ages 20-70 years) from the Sverdlovsk area, Russia. A SNP variant rs9939609 was genotyped with the use of an allelic discrimination assay. The TaqMan-based real-time PCR method was applied. The prevalence of TT, TA and AA genotypes of rs9939609 FTO gene of this study was 34%, 47.5%, 18.5%, respectively, the minor A-allele frequency was 42.3%. In comparison to males, females had significantly higher the frequency of minor A-allele and AA genotype. The AA genotype was significantly more frequent in obese individuals (defined as body mass index > or = 30 kg/m2) than in non-obese (27.7 and 13.0%, respectively). Compared to the carriers of TT genotype, the likelihood of obesity was 3.0 for the carriers of AA genotype and 1.73 for the carriers of AA+AT genotype. These results confirm that genetic variation (rs9939609) FTO gene contributes to the etiology of obesity in the Sverdlovsk area.

[Genetic approaches to nutrition personalization].

The paper presents the results of studies conducted in recent years, which show that nutrients and bioactive food components, directly or indirectly regulate the functional activity of genes influencing gene transcriptome, proteome and metabolome. A definition of "nutrigenomics" - the science that emerged at the turn of nutrition and genetics, and studies the relationship of human nutrition with the characteristics of its genome in order to understand how food affects gene expression, and ultimately, on human health. It is shown that the cellular and molecular level, nutrients, first serving as a ligand, the receptors are transcription factors, and secondly, as a substrate or intermediate metabolites are incorporated into metabolic pathways whose products control the expression of genes and, thirdly, positive or negative effect on signaling pathways. We present results of their research, which characterize the rate of prevalence of polymorphisms of genes that are markers of risk for obesity. On the basis of domestic and foreign studies concluded that genetic markers can be used for the diagnosis and prognosis of alimentary-dependent diseases such as obesity, and as well as a predictor for the development of a personalized diet and forecast its performance.

[The study of polymorphism rs9939609 FTO gene in patients with overweight and obesity].

In 94 persons living in the Moscow region, with a body mass index >25 kg/m2 were identified on the polymorphism rs9939609 FTO gene. The results showed that 83% of them were carriers of the mutant allele, and 43%--contained the mutant allele in the homozygous state. Carriers of the mutant allele rs9939609 FTO gene were distinguished by higher absolute and relative values of fat mass and triglycerides in serum.

[Effects of green tea extract and its components on antioxidant status and activities of xenobiotic metabolizing enzymes of rats].

Dietary administration of green tea extract (GTE) or epigallocatechin gallate (EGCG), quercetin (Qu) or caffeine (Cf) in doses equal to their concentration in GTE led to an increase of serum and liver antioxidant capacity and strengthening stability of microsomal and lysosomal membranes in rats. The antioxidant efficiency of EGCG and Qu was considerably higher than that of GTE. There were significant differences in the effects of EGCG, Qu and GTE on the activities and expression of mRNA for CYP1A1, CYP1A2 and CYP3A1. But feeding both GTE and Cf to rats results in similar elevated activities of CYP1A1, CYP1A2, UDP-glucuronosyl transferase and glutathion transferase. Our results suggest that Cf is the main contributor to GTE effects on activities of xenobiotic metabolizing enzymes.

[Assessment of the impact of GMO of plant origin on rat progeny development in 3 generations].

The publication presents the results of assessment of impact of genetically modified (GM) maize Liberty Link on prenatal and postnatal development of progeny of 3 generations of Wistar rats. A total of 630 adult animals and 2837 pups were used in the experiment. The animals were divided into 5 groups which got the diets with inclusion of maize: the animals of the experimental group got the diet with the GM-maize, animals of the control group - with near isogenic conventional analogue of the GM-maize, animals of the 1st, 2nd and 3rd reference groups - conventional varieties of maize ROSS 144 MV, ROSS 197 MVW, Dokuchayevskaya 250 MV respectively. The maize was included in the diet at maximum possible level not violating the balance of basic nutrients. Analysis of the data obtained during the study did not reveal any impact of GM-maize on rat progeny development.

[Biological active substances of plant origin. Flavanones: dietary sources, biovailability, the influence on xenobiotic metabolizing enzymes].

This review summarizes data concerning distribution, as well as the main food sources and daily consumption of flavanones, a relatively small group of flavonoids exhibiting wide range of biological activities, which are mainly specific for citrus fruits. The questions on their bioavailability and metabolism are discussed. The results of the in vitro and in vivo studies on the effects of flavanones on the activity of I and II phase drug metabolizing enzymes are shown.

[The role of the individual nutrition for high sport achievements].

It is established that individual menu, corresponded for personal nutritional need is a key factor for sport success of top athletes. A lot of questions and real approach for formation of the personal menu for top athletes are observed.

[Carotenoids. Biological activities].

The review provides data on the biological activities of the most prevalent carotenoids. Special attention is paid to theirs anticancer and antiatherogenic properties, immunomodulating action, cardioprotective, radioprotective and photoprotective effects.