[Composition of the nonesterified fatty acids and lipid peroxidation in metabolic syndrome]. / Slození esterifikovaných mastných kyselin a lipoperoxidace u metabolického syndromu.

BACKGROUND: Composition of the nonesterified fatty acids in plasma in metabolic syndrome patients and in other syndromes of insulin resistance is altered. Fatty acid profile in plasma is related to the composition of dietary fat and to the metabolic changes of fatty acids, e.g. to de novo lipogenesis, beta-oxidation and conversion accompanying the oxidative stress. The aim of the work was to study the fatty acid composition in the major plasma lipid classes in relation to the insulin resistance, to some polymorphisms of candidate genes with activity related to insulin resistance, and to the lipoprotein composition and parameters of lipid peroxidation. METHODS AND RESULTS: 95 patients with metabolic syndrome (56 M/39 F) and 195 healthy persons (99 M/96 F) were included into the cohort. Basic clinical data, parameters of glucose homeostasis, lipid concentration in plasma and conjugated diens in LDL were determined. Fatty acids were detected by capillary gas chromatography. Polymorphisms of apolipoprotein E, intestinal isoforms of fatty acid binding protein (Ala54Thr) and y-2 isoforms of peroxisomal activated receptor (Alal2Pro) were analyzed using combination of polymerase chain reaction methods and by the detection of polymorphisms of the restriction fragment length. Persons with metabolic syndrome had higher concentrations of CRP and conjugated diens in LDL. In all lipid classes we proved a decreased concentration of n-6 polyunsaturated fatty acids and an increase of unsaturated fatty acids. From all the acids, the only significant was the decrease of linolic acid concentration and the increase of palmitic and palmitoyl acids. Results showed an increase of delta 9 palmitic acid desaturase activity, delta 6 linolic acid desaturase and elongase activity. Concentration of conjugated diens in LDL inversely correlated with linolic acid. Clinical or laboratory parameters and homozygotic combination of polymorphism studied were not mutually related. CONCLUSIONS: Changes in the profile of fatty acids during the metabolic syndrome results from the elevated lipogenesis and from the higher level of oxidative stress.

[Factors modulating parameters of cholesterol homeostasis in the metabolic syndrome]. / Faktory ovlivnující ukazatele homeostázy cholesterolu u metabolického syndromu.

BACKGROUND: Newly described component of the metabolic syndrome is the elevated synthesis of cholesterol accompanied with its decreased intestinal absorption. The aim of our study was to ascertain the incidence of genotypes and alleles of several candidate genes, which modulate insulin resistance and metabolism of lipids and to find their role in lipid, lipoprotein and cholesterol homeostasis. The concentrations of cholesterol precursors (lathosterol, desmosterol, respectively their rations to cholesterol) are related to the synthesis of cholesterol; concentrations of fytosterols (kampesterol, sitosterol, respectively their rations to cholesterol) are related to the intestinal absorption of cholesterol. METHODS AND RESULTS: 95 patients with metabolic syndrome (56 M/39 F) and 195 healthy persons (99 M/96 F) were included into the study. Beside the basic clinical and anthropometric data, parameters of glucose homeostasis, plasma concentration of lipids, ultracentrifugation separated lipoproteins, and conjugated diens in LDL were determined. Non-cholesterol sterols were estimated by capillary gas chromatography. Polymorphisms of apolipoprotein E, intestinal isoforms of fatty acids binding protein (Ala54Thr), microsomal transfer protein (-493G/T), and gamma-2 isoforms of peroxisomal proliferator activated receptor (Ala12Pro) were analysed by combination of methods of polymerase chain reaction and by determination of polymorphism of the length of restriction fragments. After adjustation to the age, patients with metabolic syndrome had higher BMI, body fat and lean body weight (all P < 0.001), waist circumference, systolic and diastolic blood pressure (all P < 0.01). At the same time they had higher levels of glucose, insulin (P < 0.001), C-peptide, CRP (P < 0.05), uric acid, conjugated diens in LDL and HOMA insulin resistance index (P < 0.001). After adjustation to the age, higher concentration of triglycerides (P < 0.001), apo B (P < 0.01), cholesterol and triglycerides in VLDL (both P < 0.001), triglycerides in LDL (P < 0.01) were found. Incidence of alleles and genotypes of studied polymorphisms did not differ in both groups. Cholesterol synthesis is modulated by the presence of metabolic syndrome and by sex; cholesterol resorption is modulated only by the presence of metabolic syndrome. CONCLUSIONS: In patients with metabolic syndrome we found higher synthesis and lower intestinal absorption of cholesterol. We did not confirm relation between alleles of studied polymorphisms and clinical and anthropometric parameters, neither relation of these alleles to lipid or lipoprotein levels, oxidation stress, inflammation, or parameters of synthesis and absorption of cholesterol.

[Oxidation stress, insulin resistance and endothelial dysfunction during the treatment of hyperlipidaemia]. / Oxidacní stres, inzulínová rezistence a endoteliální dysfunkce v prubehu lécby hyperlipidémie.

BACKGROUND: Hyperlipidaemia represents one of the major risk factors of the type 2 diabetes mellitus (DM2). In the pathogenesis of insulin resistance (IR) development glucose homeostasis impairment and their progression into DM2, oxidative stress and endothelial dysfunction (ED) may play an important role. Recent papers indicate the possibility to prevent the development of DM2 by HLP treatment, which is characterised by increased oxidation stress and ED. METHODS AND RESULTS: For the period of twelve months 46 patients with primary HLP (group S) (LDL-C > 4.1 mmol/l a TG < 3.5 mmol/l), were treated with atorvastatine 20 mg or simvastatine 40 mg. Patients with LDL-C > 4.1 mmol/l along with TG > 3.5 mmol/l were randomly divided into two groups. The SF group was treated with a combination of statin + 200 mg micronized fenofibrate each day, and group SR received together with statin a compound containing n-3 polyene fatty acids (PUFA n-3) in the daily dose of 3.6 g. After one year lasting therapy we found beside the positively influenced concentration of atherogenic lipids and lipoproteins in the group S and SF a significantly reduced concentration of conjugated dienes (CD) in LDL ( -21, resp. 16%, both P < 0.05); the test of KD kinetics in LDL in the group S has marginal increase of the lag phase (P = 0.06) and in the groups S and SR also a significant improvement of ED (increase by the flow of mediated vasodilation, FMD) by 20%, resp. by 18% (both P < 0.05) and in the SR group a significant decrease of microalbuminuria. We did not proved significant concentrations of insulin, C-peptide or indexes showing the degree of IR (HOMA and QUICKI) CONCLUSIONS: Long-lasting hypolipidemic treatment positively affected in our study the oxidative stress and ED, however, it did not resulted in changes of IR.