The fatty acid composition of serum phospholipids in adolescents is associated with body composition in early adulthoods: an eight-year follow-up study.

The fatty acid composition is associated with obesity. Omega 3 polyunsaturated fatty acid (PUFA) could have a beneficial role in the prevention and treatment of many disorders, including cardiometabolic diseases. A cohort of 84 men and 131 women were examined in adolescence and after 8 years. Body weight (BW) and fat mass (FM) were measured. The composition of fatty acids (FAs) of serum phospholipids was assessed using gas chromatography. Statistics: PLS method. Aim: to determine the relationships between FAs in adolescence and FM (explanatory variable 1, EV1) and BW (explanatory variable 2, EV2) in adulthood. In the predictive models, a cluster of FAs in boys explained 47.2 % of EV1 and a cluster of 6 FAs in girls explained 32.3 % of EV1 measured in adulthood. FAs measured in adolescents explained 23.7 % of EV2 in early adults regardless of gender. A significant negative association was found between 18:1n-9c and EV1 in males and EV2 in both genders. We found a significant negative association between 18:2n-6 and 20:0 and both EV1 and EV2. In all analyses, we found a significant negative association of 20:1n-9 and 18:3n-3 with EV1-2 in both genders. A significant positive association was found in 20:3n-6 with EV1 and EV2 in males. 20:4n-6 was positively associated with EV1 in females and EV2 in both genders. A positive association between FM and very long chain n- 6 PUFAs was also observed. It is concluded that serum MUFAs and essential PUFAs in adolescence are associated with lower BW and FM in adulthood.

The assessment of plasma fatty acid profiles in newly diagnosed treatment-naive paediatric Crohn's disease.

Fatty acid (FA) profiles as potentially relevant components of Crohn's disease (CD) have been insufficiently analysed. We sought to explore the plasma profiles of n-3 and n-6 polyunsa-turated fatty acids (PUFAs) in newly diagnosed untreated active CD. We included 26 consecutive CD pediatric patients (<19 years) and 14 healthy controls (HCs). Disease characteristics, including inflammatory markers, dietary histories, and the Pediatric Crohn's Disease Activity Index (PCDAI), were obtained. The profiles of plasma FAs in plasma lipid classes were analysed by gas chromatography with FID detection of methyl esters. The erythrocyte sedimentation rate, C-reactive protein level and fecal calprotectin level (all p<0.001) were significantly higher in CD patients than in HCs. Most changes were observed in plasma phospholipids (PLs), such as a higher content of n-3 and changes in n-6 long-chain PUFAs in the CD group. The CD group had a lower ratio of n-6/n-3 PUFAs in PLs (p<0.001) and triacylglycerols (TAGs) (p<0.01). Correlations of the FA content in plasma PLs with disease activity scores of CD were also observed, which were positive for the sum of monounsaturated fatty acids (MUFAs) as well as oleic acid (18:1n-9) (both p<0.05). The metabolism of PUFAs is significantly altered even in treatment-naive newly diagnosed active pediatric CD, and the content of major FAs in PLs correlates with disease activity and inflammatory markers, thus probably contributing to the still unclear early disease pathogenesis.

Polymorphisms rs2167444 and rs508384 in the SCD1 Gene Are Linked with High ApoB-48 Levels and Adverse Profile of Cardiometabolic Risk Factors.

Elevated plasma concentration of apolipoprotein B-48 (apoB-48) is an independent risk factor of cardiovascular disease. Stearoyl-CoA desaturase-1 (SCD1) is a rate-limiting lipogenic enzyme and a key regulator of fuel metabolism. The aim of this study was to analyse associations between clinical, biochemical, and genetic factors and different apoB-48 levels in subjects at increased cardiometabolic risk. We examined 220 subjects exhibiting at least one metabolic syndrome (MetS) component. In conjunction with basic clinical, anthropometric and laboratory measurements, we analysed various polymorphisms of stearoyl-CoA desaturase-1 (SCD1). Subjects were divided into two groups according to the median apoB-48 level: (1) high apoB-48 (≥ 7.9 mg/l, N = 112) and (2) low apoB-48 (< 7.9 mg/l, N = 108). Neither group differed significantly in anthropometric measures. High plasma apoB-48 levels were associated with increased systolic blood pressure (+3 %; P < 0.05), MetS prevalence (59.8 vs. 32.4 %; P < 0.001), small-dense LDL frequency (46.4 vs. 20.4 %; P < 0.001), triglycerides (+97 %; P < 0.001), non-HDLcholesterol (+27 %; P < 0.001), and lower concentrations of HDL-cholesterol (-11 %; P < 0.01). This group was further characterized by a higher HOMA-IR index (+54 %; P < 0.001) and increased concentrations of conjugated dienes (+11 %; P < 0.001) and oxidatively modified LDL (+ 38 %; P < 0.05). Lower frequencies of SCD1 minor genotypes (rs2167444, rs508384, P < 0.05) were observed in subjects with elevated plasma concentrations of apoB-48. Elevated plasma concentrations of apoB-48 are associated with an adverse lipid profile, higher systolic blood pressure, insulin resistance, and oxidative stress. Lower proportions of minor SCD1 genotypes (rs2167444, rs508384) implicate the role of genetic factors in the pathogenesis of elevated levels of apoB-48.

Fatty acid composition of adipose tissue triglycerides in obese diabetic women after bariatric surgery: a 2-year follow up.

Bariatric surgery is the most effective method in the treatment of obesity and type 2 diabetes (T2DM). The aim of this study was to evaluate the effects of different types of bariatric procedures on remission of T2DM and on the fatty acid composition in subcutaneous adipose tissue. Patients included obese diabetic women who underwent bariatric surgery: biliopancreatic diversion (BPD), n=8, laparoscopic gastric banding (LAGB), n=9 or laparoscopic greater curvature plication (LGCP), n=12. Anthropometric characteristics and fatty acid composition of adipose tissue (FA AT) were analyzed before surgery, then 6 months and 2 years after surgery. FA AT was analyzed by gas chromatography. Diabetes remission was estimated. BPD was most efficient in inducing a remission of diabetes (p=0.004). Significantly higher increases in lauric (12:0), myristoleic (14:1n-5) and palmitoleic (16:1n-7) acids and delta-9 desaturase were found two years after BPD, suggesting higher lipogenesis in adipose tissue. Docosatetraenoic acid (22:4n-6) increased significantly after BPD, while docosapentaenoic acid (22:5n-3) decreased 6 months after BPD and increased after 2 years. No changes were found after LAGB and LGCP after 2 years. Bariatric surgery led to significant changes in the fatty acid composition of subcutaneous adipose tissue in severely obese diabetic women after six months and two years, and was partly influenced by the type of surgery used.

Association of plasma lipids fatty acid composition with metabolic profile of Czech adolescents.

Obesity in childhood increases the risk of obesity in adulthood and is predictive for the development of metabolic disorders. The fatty acid composition is associated with obesity and obesity-associated disorders. We investigated the relationship between serum fatty acids composition, adiposity, lipids profile, parameters of glucose metabolism and leptin. The study subjects were 380 adolescents aged 15.0-17.9 years. The study's variables included anthropometric measurements, levels of serum lipids and hormonal parameters. Individual fatty acids were determined in plasma by gas-liquid chromatography. Palmitoleic acid (16:1n-7, PA) significantly positively correlated with percentage of body fat. Saturated fatty acids in phospholipids (PL) positively correlated with BMI and percentage of body fat. PA content in all lipids classes positively correlated with total cholesterol (TC), HDL cholesterol, triglycerides (TG) levels. Stearoyl-CoA desaturase (SCD) activity positively correlated with percentage of body fat and positive correlations of SCD and PA level with leptin were found. Plasma PA content and SCD are associated with adiposity and leptin in obese adolescents. No significant correlation between PA level and insulin resistance was found. Palmitoleate positively correlated with TC, HDL cholesterol, TG and LDL cholesterol levels.

Fatty acid composition indicates two types of metabolic syndrome independent of clinical and laboratory parameters.

Dietary composition and metabolism of fatty acids (FA) influence insulin resistance, atherogenic dyslipidemia and other components of the metabolic syndrome (MS). It is known that patients with MS exhibit a heterogeneous phenotype; however, the relationships of individual FA to MS components have not yet been consistently studied. We examined the plasma phosphatidylcholine FA composition of 166 individuals (68F/98M) with MS and of 188 (87F/101M) controls. Cluster analysis of FA divided the groups into two clusters. In cluster 1, there were 65.7 % of MS patients and 37.8 % of controls, cluster 2 contained 34.3 % of patients and 62.2 % of controls (P<0.001). Those with MS within cluster 1 (MS1) differed from individuals with MS in cluster 2 (MS2) by concentrations of glucose (P<0.05), NEFA (P<0.001), HOMA-IR (P<0.05), and levels of conjugated dienes in LDL (P<0.05). The FA composition in MS1 group differed from MS2 by higher contents of palmitoleic (+30 %), gamma-linolenic (+22 %), dihomo-gamma-linolenic (+9 %) acids and by a lower content of linoleic acid (-25 %) (all P<0.01). These FA patterns are supposed to be connected with the progression and/or impaired biochemical measures of MS (lipolysis, oxidative stress, dysglycidemia, and insulin resistance).

Fatty acid composition of adipose tissue triglycerides after weight loss and weight maintenance: the DIOGENES study.

Fatty acid composition of adipose tissue changes with weight loss. Palmitoleic acid as a possible marker of endogenous lipogenesis or its functions as a lipokine are under debate. Objective was to assess the predictive role of adipose triglycerides fatty acids in weight maintenance in participants of the DIOGENES dietary intervention study. After an 8-week low calorie diet (LCD) subjects with > 8 % weight loss were randomized to 5 ad libitum weight maintenance diets for 6 months: low protein (P)/low glycemic index (GI) (LP/LGI), low P/high GI (LP/HGI), high P/low GI (HP/LGI), high P/high GI (HP/HGI), and a control diet. Fatty acid composition in adipose tissue triglycerides was determined by gas chromatography in 195 subjects before the LCD (baseline), after LCD and weight maintenance. Weight change after the maintenance phase was positively correlated with baseline adipose palmitoleic (16:1n-7), myristoleic (14:1n-5) and trans-palmitoleic acid (16:1n-7t). Negative correlation was found with baseline oleic acid (18:1n-9). Lower baseline monounsaturated fatty acids (14:1n-5, 16:1n-7 and trans 16:1n-7) in adipose tissue triglycerides predict better weight maintenance. Lower oleic acid predicts lower weight decrease. These findings suggest a specific role of monounsaturated fatty acids in weight management and as weight change predictors.

Polymorphisms of genes for brain-derived neurotrophic factor, methylenetetrahydrofolate reductase, tyrosine hydroxylase, and endothelial nitric oxide synthase in depression and metabolic syndrome.

The prevalence of metabolic syndrome as well as the occurrence of depressive disorder, which are both connected with increased risk of diabetes mellitus type 2 and cardiovascular diseases, is continually increasing worldwide. These disorders are interconnected at various levels; the genetic one seems to be promising. Contribution of genetic factors to the aetiopathogenesis of depressive disorder weighs within the range 40-50 %, whereas the genetic background for the manifestation of metabolic syndrome is more complicated. In this pilot study, we investigated the incidence of polymorphisms in several genes supposed to play a role in the development of both depressive disorder and metabolic syndrome such as brain-derived neurotrophic factor, methylenetetrahydrofolate reductase, tyrosine hydroxylase, and endothelial nitric oxide synthase. The entire group consisted of 42 patients with depressive disorder, 57 probands with metabolic syndrome and 41 control individuals. We found that genotype Met/Met of the Val66Met polymorphism of the brain-derived neurotrophic factor gene was positively associated with depressive disorder (P < 0.05), but we were not able to find any significant associations of both the depressive disorder and metabolic syndrome with the remaining polymorphisms studied (methylenetetrahydrofolate reductase 677CT, methylenetet rahydrofolate reductase 1298AC, endothelial nitric oxide synthase Glu298Asp, and tyrosine hydroxylase).

[Features of metabolic syndrome in patients with depressive disorder]. / Rysy metabolického syndromu u nemocných s depresivní poruchou.

BACKGROUND: Depressive disorder is a serious illness with a high incidence, proxime accessit after anxiety disorders among the psychiatric diseases. It is accompanied by an increased risk of development of type 2 diabetes mellitus, cardiovascular disease, and by increased all-cause mortality. Recently published data have suggested that factors connected with the insulin resistance are at the background of this association. METHODS AND RESULTS: In this pilot study we have investigated parameters of lipid metabolism and glucose homeostasis in consecutively admitted patients suffering from depressive disorder (DD) (group of 42 people), in 57 patients with the metabolic syndrome (MetS) and in a control group of 49 apparently healthy persons (CON). Depressive patients did not differ from the control group by age or body mass index (BMI) value, but they had statistically significantly higher concentrations of serum insulin, C-peptide, glucose, triglycerides (TG), conjugated dienes in LDL particles (CD-LDL), higher value of microalbuminuria and of insulin resistance (HOMA-IR) index. They simultaneously had significantly lower value of the insulin sensitivity (QUICKI) index. In comparison with the MetS group the depressive patients were characterized by significantly lower both systolic and diastolic blood pressure, BMI , serum TG, apolipoprotein B, uric acid, C-peptide and by higher concentrations of apolipoprotein A-I and HDL-cholesterol. On the contrary, we have not found statistically significant differences between the DD and MetS groups in the concentrations of serum insulin, glucose, HOMA and QUICKI indices, in CD-LDL and MAU. CONCLUSIONS: In this pilot study, we have found in patients with depressive disorder certain features of metabolic syndrome, especially insulin resistance and oxidative stress.

[Fatty acids--2. Clinical and physiological significance]. / Mastné kyseliny 2. Fyziologický a klinický význam.

Fatty acids play multiple roles in humans and other organisms. In triglycerides they are the source of metabolic energy, in adipose tissue they serve also as temperature and mechanical isolators, in the form of phospholipids they are structural components of membranes. Fatty acids originating from the sn-2 glycerol carbon of phosphatidylcholine can influence the activity of diglycerides as second messengers. Unsaturated FA with 18-20 carbon atoms are precursors of prostaglandins, leucotrienes and thromboxanes, which have a broad scale of regulatory properties and have autocrine as well as paracrine effects. Fatty acids are ligands of several nuclear receptors, which take part in the subcellular control of a number of metabolic pathways. Covalent modification of proteins by FA (acylation) enables FA incorporation into the membranes. Number of pathological stages is accompanied with changes in fatty acid composition, often expressed as decreased content of unsaturated and increased content of saturated fatty acids (e.g. dyslipidemia, malnutrition, inflammation and inherited diseases). Polyunsaturated fatty acids as dietary supplements are used in prevention and in the therapy of cardiovascular diseases and other metabolic disturbances.

[Fatty acids--1. occurrence and biological significance]. / Mastné kyseliny. 1. Výskyt a biologický význam.

Fatty acids are monocarboxylic acids with chain-length 2-36 carbon atoms and 0-6 double bonds. Their physico-chemical properties are reflected also in the compounds, where fatty acids represent an important component (phospholipids, triglycerides), as well as in higher organized structures (plasma membranes, lipoproteins). Fatty acids are synthesized from two-carbon precursors; their degradation by beta-oxidation is accompanied by energy-release. Fatty acids are classified with respect to double bonds into saturated, monounsaturated and polyunsaturated. Simple lipids are esters of fatty acids and organic alcohols - cholesterol, glycerol and sphingosine and their derivatives. Endogenous acids can be desaturated up to Delta9 position; desaturation to other position is possible only from exogenous (essential) acids [(linoleic (n-6 series) and alpha-linolenic (n-3 series)]. Circulating lipids (in form of lipoproteins) consist of cholesterol esters and triglycerides in nonpolar core and phosphatidylcholin and sphingomyelin in the polar envelope of lipoproteins. Nonesterified fatty acids (product of lipolysis and source for lipid synthesis) are bound to plasma albumin. Membrane lipids, which ensure membrane fluidity and other functions, consist of phosphatidylcholine, phosphatidylethanolamine, sphingomyelin and some other (minor) phospholipids.

Prominent role of liver in elevated plasma palmitoleate levels in response to rosiglitazone in mice fed high-fat diet.

UNLABELLED: In humans, antidiabetics thiazolidinediones (TZDs) upregulate stearoyl-CoA desaturase 1 (SCD1) gene in adipose tissue and increase plasma levels of SCD1 product palmitoleate, known to enhance muscle insulin sensitivity. Involvement of other tissues in the beneficial effects of TZDs on plasma lipid profile is unclear. In our previous study in mice, in which lipogenesis was suppressed by corn oil-based high-fat (cHF) diet, TZD rosiglitazone induced hepatic Scd1 expression, while liver triacylglycerol content increased, VLDL-triacylglycerol production decreased and plasma lipid profile and whole-body glycemic control improved. Aim of this study was to characterise contribution of liver to changes of plasma lipid profile in response to a 8-week-treatment by rosiglitazone in the cHF diet-fed mice. Rosiglitazone (10 mg/kg diet) upregulated expression of Scd1 in various tissues, with a stronger effect in liver as compared with adipose tissue or skeletal muscle. Rosiglitazone increased content of monounsaturated fatty acids in liver, adipose tissue and plasma, with palmitoleate being the most up-regulated fatty acid. In the liver, enhancement of SCD1 activity and specific enrichment of cholesteryl esters and phosphatidyl cholines with palmitoleate and vaccenate was found, while strong correlations between changes of various liver lipid fractions and total plasma lipids were observed (r=0.74-0.88). Insulin-stimulated glycogen synthesis was increased by rosiglitazone, with a stronger effect in muscle than in liver. CONCLUSIONS: changes in plasma lipid profile favouring monounsaturated fatty acids, mainly palmitoleate, due to the upregulation of Scd1 and enhancement of SCD1 activity in the liver, could be involved in the insulin-sensitizing effects of TZDs.

[Metabolic syndrome and depression--clinical relations]. / Metabolický syndrom a deprese--klinické vztahy.

The occurrence of both obesity and type 2 diabetes mellitus is rapidly increasing; according to WHO data, this can be considered as a worldwide epidemic. The obesity is one of the components of metabolic syndrome, the cluster of several risk factors of atherosclerosis such as dyslipidemia, hypertension, impaired glucose homeostasis, pro-thrombotic state and subclinical inflammation. The importance of the metabolic syndrome is confirmed by findings of the several times increased risk of both the type 2 diabetes mellitus and cardiovascular disease. Similarly, as in the case of obesity and diabetes, the incidence and prevalence of depressive disorder are still increasing and depressive disorder belongs to the most important causes of disability. The interrelations between depressive disorder and diabetes are known for a long time. Diabetics very often suffer from depression and vice versa, the depressive disorder is a significant risk factor of type 2 diabetes mellitus development and worsens the survival of diabetics. Those relationships have been recently intensively studied. Our paper reviews genetic, nutritional, metabolic and hormonal factors, contributing to the above mentioned syndrome.

Change in fatty acid composition of serum lipids in obese females after short-term weight-reducing regimen with the addition of n-3 long chain polyunsaturated fatty acids in comparison to controls.

Short-term weight-reducing regimens were shown to influence fatty acid composition of serum lipids unfavorably. Adding long chain n-3 polyunsaturated fatty acids (n-3 LC PUFA) to a low-calorie diet (LCD) could avoid these changes. The aim of this study was to examine the effect of a short-term in-patient weight-reducing regimen including LCD with yogurt enriched by low doses of n-3 PUFA (n-3 LCD). The enriched yogurt contained 790 mg of fish oil, predominantly eicosapentaenoic (20:5n-3; EPA) and docosahexaenoic (22:6n-3; DHA). Forty obese women were randomly assigned to the group consuming LCD and joghurt either with or without n-3 enrichment. Following the 3-week diet in the n-3 LCD group a significantly higher increase in the proportion of n-3 LC PUFA (sum of n-3 FA, EPA and DHA) in serum lipids was confirmed. In phospholipids (PL) a significant difference in the sum of n-6 fatty acids was found, a decrease in the n-3 LCD group and an increase in LCD group. Significantly higher increase in the PL palmitate (16:0) was shown in the LCD group. The results suggest that low doses of n-3 fatty acid enrichment can help to avoid unfavorable changes in fatty acid composition in serum lipids after a short-term weight-reducing regimen.

[Conjugated linoleic acid--the dietary supplement in the prevention of cardiovascular diseases]. / Konjugovaná kyselina linolenová - dietní suplement v prevenci kardiovaskulárních onemocnení?

Conjugated linoleic acid is an integral term for the mixture of positional and geometrical isomers of the octadecadienoic acids, whose two double-bonds are separated with one single-bond. The most common isomers are cis-9, trans-11, and trans-10, cis-12. Conjugated linoleic acid is present in the food namely in the red meat and dairy products which the contemporary dietary recommendations tend to limit. Those limitations should be compensated with dietary supplements. Experimental studies have shown the positive effects of the conjugated linoleic acid in the regulation of the body weight, in the reduction of risk factors of cardiovascular diseases, for improvement of immunity and in the reduction of risks of the development of some carcinomas. Those studies have also considered different effects of individual isomers. Stimulating results of experimental studies represent the basis of the research in human medicine, where the results are not so unequivocal. Studies are difficult to compare owing to the different arrangement (number of persons, daily dose, length of administration). Positive effects on the adiposity and proportion of the visceral fat was observed after the long-term administration, however, mechanism of the effect has not been explained yet. It can be due to the inhibition of lipoprotein lipase, rise of carnitine-palmitoyl transferase activity, induction of adipocyte apoptosis, modulation of PPARgamma effects. For the explanation some new long-term studies with defined clinics will be necessary. Present view on the indication of the conjugated linoleic acid administration from the point of complex modulation of risks of the development of cardiovascular and metabolic diseases is inconsistent.

[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.

[Phytosterols as a functional food]. / Rostlinné steroly jako funkní potraviny.

Many dietary recommendations which try to lower the concentration of total, respectively LDL cholesterol, force us to look back to vegetable-based diet. The plants synthesize many compounds similar to cholesterol, called phytosterols and phytostanols, and these sterols are consumed in average Western diet in amounts ranging from 200 to 500 mg/day. Phytosterols and phytostanols share the mechanisms of absorption with cholesterol molecule and influence the cholesterol metabolism inside the enterocytes. Both types of phytoanalogs of cholesterol were proven to be potent cholesterol-reducing agents; their daily intake about 2 g/day reduces the LDL-cholesterol by 15%. The underlying mechanisms involve the prevention of cholesterol absorption from the gut lumen and slower esterification rate of phytosterols (phytostanols) inside the enterocytes. In contrary to phytostanols, phytosterols are absorbed with yet-to-be-considered efficiency, appearing in plasma with concentrations reaching as much as 1% that of total cholesterol. The hypocholesterolemic effect of phytosterols (phytostanols) can be further supported with the combination of dietary (n-3 polyunsaturated fatty acids, fibre) regimen as well as pharmacological intervention (statins). To conclude, plant sterols represent safe dietary approach to lowering of plasma total cholesterol with the attention paid to the intake of lipid soluble vitamins.

[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.

[Effect of hypolipidemic treatment on the composition of bile and the risk or cholesterol gallstone disease]. / Vliv hypolipidemické lécby na slození zluce a riziko cholesterolove cholelitiáizy.

Obesity, diabetes mellitus type 2 and dyslipidemia, characterized by hypertriglyceridemia and low HDL-cholesterol levels, are risk factors for cholesterol gallstone disease. The common denominator of above-mentioned states is insulin resistance. Hypolipidemic treatment significantly influences not only the biliary lipid composition, but also other etiopathogenetic mechanisms of the disease. Three principal defects are involved in gallstone formation - cholesterol supersaturation, accelerated nucleation, and gallbladder dysmotility. The degree of cholesterol saturation in gallbladder bile is the most important predictor of cholesterol crystal formation. Cholesterol, lecithin and bile acids are the major components in bile. According to the molar ratios of the three main components, simple or mixed micelles, unstable unilamellar or multilamellar vesicles are formed in the bile. The cholesterol supersaturation of the gallbladder bile and cholesterol crystal formation from the unstable multilamellar vesicles initiates the onset of cholesterol cholelithiasis. The pool of unesterified cholesterol is the source for VLDL synthesis; together with HDL-cholesterol, it is also the source for cholesterol secretion into the bile. The main metabolic products of cholesterol degradation are bile acids, which are synthesized predominantly from LDL-cholesterol. The rate of the production of primary bile acids is principally regulated by cholesterol 7alpha-hydroxylase (CYP7A 1). The treatment of dyslipidemia with niacin and resins does not influence the saturation of bile with cholesterol or the incidence of cholelithiasis. The effects of ezetimibe in human patients with the respect of cholesterol cholelithiasis have not been published. The fibrate treatment is associated with increased cholesterol saturation of bile due to inhibition of CYP7A1 activity, enhanced flux of cholesterol via HDL and increased secretion of cholesterol into bile. The clinical studies describe cholesterol supersaturation in bile and increased frequency of cholelithiasis as well. The administration of pravastatin and simvastatin led to reduced cholesterol saturation indexes. The patients with endogenous hypertriglyceridemia and low HDL-cholesterol being administered with polyunsaturated fatty acids of n-3 family had decreased cholesterol concentration in bile. Other authors described beneficial effect of fish oil on the biliary cholesterol nucleation time, improvement of gallbladder sensitivity to cholecystokinin and the prevention of cholesterol gallstone formations caused by rapid weight loss.

[Nicotinic acid: an unjustly neglected remedy]. / Kyselina nikotinová: lek neprávem opomíjený.

In human organism, the administration of nicotinic acid (niacin) leads to two types of effects. Within the physiological range (approximately = 20 mg/day), niacin has a vitamin-like role as pellagra preventing factor. The pharmacological dosage (approximately 0,5-4,5 g/day) substantially influences the plasma lipid and lipoprotein concentrations: decreases VLDL and LDL concentrations, changes the profile of LDL subfractions towards the larger particles as well as particles with lower density; it also profoundly increases the concentration of HDL-C in consequence of elevated concentration of HDL2 subfraction. Niacin as the only hypolipidemic drug reduces the lipoprotein(a) concentration. The hypolipidemic mechanism of niacin is different from that of other hypolipidemic drugs. On the basis of clinically controlled trials (both interventional epidemiological and angiographical), which satisfy the criteria of evidence-based medicine, it is possible to conclude that niacin falls unambiguously into the class of hypolipidemic drugs with proven beneficial effect not only on cardiovascular mortality and morbidity, but also on total mortality. Therefore, niacin should have an indisputable role in the pharmacological control of dyslipidemias. With the respect of basic mechanism (inhibition of the lipolysis of adipose tissue) with subsequent decrease in the concentration of free fatty acids and their flux to liver, niacin fulfils the criteria for pathogenetic treatment of atherogenic dyslipidemia in metabolic syndrome. The prerequisite condition for the niacin treatment is the respect for serious adverse effects and possible health hazards of administration (skin flush, hepatotoxicity and deterioration of glucose homeostasis). Recently discovered extrahypolipidemic effects of niacin (antioxidative activity, facilitation of reverse cholesterol transport, activation of PPAR-gamma, antithrombotic effects) and the introduction of drug forms with sustained (extended resp.) release of active compound (that minimizes the adverse effects and administration hazards) form together the basis for firm statement that the derivatives of nicotinic acid should be introduced to the clinical practice in Czech Republic.