[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.

[An analysis of the efficacy of low-calorie and isocaloric diets in obese patients with nonalcoholic steatohepatitis].

Diet modification is widely used for the treatment of non.alcoholic steatohepatitis (NASH). Caloric restriction was shown to be effective in normalizing bldod lipid profile, increasing insulin sensitivity and subsequent normalization of aminotrasferases blood level. The aim of the study was to compare low-calorie diet (LCD) with isocaloric diet (ICD) in patients w,ith NASH. 174 NASH patients [86 females (39,43±1,53 years old) and 88 males (41,7±2,0), BMI 36,8±0,8 kg/m2] were randomly assigned (as 1:2) for LCD (1600-1700 kcal/day) or ICD (2500-2700 kcal/day) calculated according to patients'sex, age, resting energy expenditures and daily physical activity. Caloric restriction was achieved by decreasing consumption of carbohydrates and fat in LCD, whereas for ICD the caloric consumption was established according to the recommended daily values for proteins, fat and carbohydrates for ideal BMI for every patient. Blood chemistry and body composition were assessed at baseline and after 1 mo of prescribed diets. Compliance for the diet was also evaluated using previously validated questionnaire. After 1 mo of dietetic interventions total body mass and lean mass significantly decreased in both groups, but in LCD group it was significantly more prominent decrease in compare to ICD group (9,3±1,8 vs 6,2±1,7 kg and 6,6±0,4 vs 1,4±0,6 kg, p<0,05), whereas fat mass decreased better in ICD group (4,8±0,7 vs 2, 7±0,8kg, p<0,05). Mean ALT level was decreased in ICD group (77,5±41,7 vs 98,8±45,7, p<0,01), but not in LCD group (81,2±50,6 vs 77,2±31,8, p=NS) whereas blood cholesterol, triglycerides, high density lipoprotein woere significantly decreased in both groups. Moreover during the diet intervention in 72% of patients from LCD group ALT increased. Compliance index was much higher in ICD group, than in LCD group (85% vs 54%). Thus, one month of lCD leads to decrease in ALT activity in majority of NASH patients, higher loss of fat mass, lower loss of lean mass and associated with better compliance in compare to LCD.

[Soluble apoptosis markers in obese patients with food intolerance].

For the soluble apoptosis markers study 151 patients with obesity (92 women and 59 men) aged between 18 and 63 years were examined. Diagnosis and degree of obesity was based on the body mass index (38.2 +/- 5.4 kg/m2). Generally food intolerance was identified in 36.4% of obese patients. Four groups of patients were formed: three groups of patients with obesity stage I (15 patients), II (18 patients) and III (22 patients), respectively, and with food intolerance, and a group of obese patients without food intolerance (control group, n = 31). Obese patients with food intolerance received standard version of hypocaloric diet with the exception of specific food allergens. Duration of observation was 39-43 days. Such soluble apoptosis markers as sFas-L, Caspase-9, Caspase-8 and sCD153 were significantly higher in stage III obesity patients compared obese patients without food allergy (0.120 +/- 0.030 vs 0.035 +/- 0.010; 13.2 +/- 3.2 vs 5.9 +/- 0.4; 1.4 +/- 0.18 vs 0.6 +/- 0.24; 0.123 +/- 0.010 vs 0.025 +/- 0.002 ng/ml respectively). Positive dynamic of sFas-L, Caspase-9 and Caspase-8 (decrease to 0.052 +/- 0.030; 7.7 +/- 2.2 and 0.4 +/- 0.18 ng/ml respectively) in patients with obesity stage III and intactness sCD153 during diet therapy course were revealed. Significant differences for only Caspase-9 in patients with obesity stage II were obtained. The data obtained are considered as normalization of apoptosis due to nutritional correction of immunological disorders. Study of sFas-L, Caspase-9 and Caspase-8 allows to predict the course of disease, as immunological research for early detection of food allergy makes possible to implement the principles of personalized diet therapy.

[Isomeric specific analysis of hydroxyeicosatetraenoic acid in blood samples from obese patients with non-alcoholic and alcoholic steatohepatitis].

The aim of the study was to perform isomeric analysis of hydroxyeicosatetraenoic acid (HETE) in blood samples from obese patients with non-alcoholic (NASH) and alcoholic (ASH) steatohepatitis. Sixty nine obese patients with liver steatosis according to abdominal US data and chronic ALT elevation were assign into two groups aecoriing to the evaluation of alcohol consumption by GAGE and AUDIT questionnaires: NASH - 39 patients and ASH - 30 patients. The identification and quantification of 5(S)-hydroxyeicosatetraenoic acid (5-HETE), 15-HETE and also non-enzymatic oxidation product 11-HETE in blood plasma were carried out by HPLC-MS-TOF with using 2-hydroxyoctanoic acid as internal standard. The position of hydroxyl group in HETE was elucidated by HPLC-MS/MS. The MS/MS transitions were for 15-HETE m/z 319 ---> m/z 219; for 11-HETE m/z 319 --> m/z 167; for5-HETE m/z 319 --> m/z 115. Patients' body composition was evaluated by bioelectrical impedance, resting energy expenditures (REE) were assessed by indirect calorimetry and nutrition pattern was examined by foodfrequency questionnaire. Mean age, BMI and ALT serum level were similar in patients from ASH and NASH groups. Blood plasma 8+12-HETE concentration was also similar in both groups of patients, but concentration of 15-HETE (21,6±20,2 vs 11,9±13,7µg/ml, p =0,02) and 11-HETE (20,8±21,3 vs 11,2+12,9 ug/ml, p =0,03) was significantly higher in NASH patients. ASHpatients demonstrated higher lean body mass (68,1±10,6 vs 57,9±9,8 kg, p<0,001) and muscle mass (39,3±6,1 vs 33,2±6,8 kg, p<0,04) and higher rate of protein oxidation (98,5±3 1 vs 76,2±21,1 g/day, p= 0,02) recalculated from REE. There were no differences found in blood lipids content as well as in consumption of total dietary fat, however, there was a trend to difference in saturated/unsaturated fatty acids ratio between groups (2,3±0,2.in NASH and 1,4±0,3 in ASH patients). In conclusion, the rate of production of eicosatetraenoic acid metabolites by lipoxygenase pathway is different in NASH and ASH overweight patients. It means that possibly different mechanisms are responsible for formation of potentially toxic fatty acids metabolites in these two types of patients. It seems likely that differences in fatty acids consumption pattern are related to this metabolic pathway.

[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.

[Modern concepts of gene polymorphisms, which regulate lipid metabolism].

This review discusses the present view on lipid metabolism regulation with emphasis on polymorphisms of key genes. Relying on the analysis of the literature, the blood lipid specter of carriers of the key genes allelic variants has been described. Therefore, reasonability of a more profound study of the influence of genetic polymorphisms on lipid metabolism regulation is substantiated. It is revealed, that the carriers of one of the abnormal alleles causes a higher risk for obesity and its associated complications. Polymorphic variants of the genes, that regulated lipid metabolism are widely presented in human population. It explains the big interest to studying of communication between dyslipidemia, adiposity and other pathologies with features of a genotype. However, abnormality of metabolic process and associated diseases in most cases represent multifactorial diseases. For today, the important problem for researchers still is a definition of a role of individual genetic features in development of pathological processes. The special attention in researches of last years is given to the genes, which products concern to leptin-melanokortin system of regulation of a energy metabolism; proteins-carriers lipid's blood fractions and cholesterol; and also the enzymes splitting lipids. Lipid metabolism is closely connected with an exchange of carbohydrates, especially a glucose metabolism. That is why genes mediating actions of insulin represent the greatest interest. Today, more than 400 genes are the potential candidates, capable to regulate lipid exchange. However, the further careful and extensive researches in this area are necessary.

[The clinical and immunological manifestations of food intolerance in obese patients].

The clinical and immunological manifestations of food intolerance in obese patients were studied. Food intolerance was diagnosed in 32.6 and 33.4% in obese patients stage 2 and stage 3 respectively, and was basically determined by 13 proteinaceous food products. The changes in immune status in obese patients created conditions for development of food intolerance. The timely diagnose food intolerance allows to personalize the diet therapy.