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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.

Fatty acid (FA) profiles as potentially relevant components of Crohn’s disease (CD) have been insufficiently analyzed. We sought to explore the plasma profiles of n−3 and n−6 polyunsaturated fatty acids (PUFAs) in newly diagnosed untreated active CD. We included 26 consecutive CD pediatric patients (

Omega-3 polyunsatuarted fatty acids (PUFA) are associated with hypolipidemic and anti-inflammatory effects. However, omega-3 PUFA, usually administered as triacylglycerols or ethyl esters, could also compromise glucose metabolism, especially in obese type 2 diabetics. Phospholipids represent an alternative source of omega-3 PUFA, but their impact on glucose homeostasis is poorly explored. Male C57BL/6N mice were fed for 8 weeks a corn oil-based high-fat diet (cHF) alone or cHF-based diets containing eicosapentaenoic acid and docosahexaenoic acid (~3%; wt/wt), admixed either as a concentrate of re-esterified triacylglycerols (ω3TG) or Krill oil containing mainly phospholipids (ω3PL). Lean controls were fed a low-fat diet. Insulin sensitivity (hyperinsulinemic-euglycemic clamps), parameters of glucose homeostasis, adipose tissue function, and plasma levels of N-acylethanolamines, monoacylglycerols and fatty acids were determined. Feeding cHF induced obesity and worsened (~4.3-fold) insulin sensitivity as determined by clamp. Insulin sensitivity was almost preserved in ω3PL but not ω3TG mice. Compared with cHF mice, endogenous glucose production was reduced to 47%, whereas whole-body and muscle glycogen synthesis increased ~3-fold in ω3PL mice that showed improved adipose tissue function and elevated plasma adiponectin levels. Besides eicosapentaenoic and docosapentaenoic acids, principal component analysis of plasma fatty acids identified palmitoleic acid (C16:1n-7) as the most discriminating analyte whose levels were increased in ω3PL mice and correlated negatively with the degree of cHF-induced glucose intolerance. While palmitoleic acid from Krill oil may help improve glucose homeostasis, our findings provide a general rationale for using omega-3 PUFA-containing phospholipids as nutritional supplements with potent insulin-sensitizing effects.

The purpose of this study was to determine oxidation and oxidability of VLDL and LDL in connection with changes in their composition and content of FA in LDL after treatment with fenofibrate in patients with HTG.

A microscale procedure for a rapid extraction, re-extraction and methylation of serum or plasma free fatty acids (FFAs) is described. There is no necessity to evaporate extracting solvent or heat the reaction medium to prepare corresponding methyl esters for gas chromatographic analysis. The approach comprises three consecutive steps, carried out in two reaction vials, during which the neutral lipids are removed and the free fatty acids re-extracted and subsequently methylated. Methylation succeeds upon using methyl chloroformate in combination with a non-smelling organic base within seconds. The method proved to be highly reproducible, with intraassay variation coefficients being less than 5% for the major serum fatty acids.

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.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.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 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.

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.

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.

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 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.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.Changes in the profile of fatty acids during the metabolic syndrome results from the elevated lipogenesis and from the higher level of oxidative stress.

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.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 P0.001), waist circumference, systolic and diastolic blood pressure (all P0.01). At the same time they had higher levels of glucose, insulin (P0.001), C-peptide, CRP (P0.05), uric acid, conjugated diens in LDL and HOMA insulin resistance index (P0.001). After adjustation to the age, higher concentration of triglycerides (P0.001), apo B (P0.01), cholesterol and triglycerides in VLDL (both P0.001), triglycerides in LDL (P0.01) 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.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.

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.

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.For the period of twelve months 46 patients with primary HLP (group S) (LDL-C4.1 mmol/l a TG3.5 mmol/l), were treated with atorvastatine 20 mg or simvastatine 40 mg. Patients with LDL-C4.1 mmol/l along with TG3.5 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 P0.05); 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 P0.05) 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.

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.

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.

Recently, a new attention has been paid to beneficial effects of high-fat diet on the body weight reduction and metabolic profile in obese subjects. In this study we compared the effects of two hypocaloric diets with different proportion of fat on fatty acid composition (FA) in blood and adipose tissue (AT).Forty-four obese subjects were submitted to 10 weeks' low-calorie diet. Subjects were randomized into low-fat diet (LFD) (20-25% of energy content) and high-fat diet groups (HFD) (40-45%). Before and at the end of the intervention, samples of blood and subcutaneous AT were taken for the analysis of fatty acid composition. The diet-induced body weight and fat mass reduction were not different between the two diets. Plasma triacylglycerols (TAG) were reduced during HFD only. Both diets reduced proportion of n-3 polyunsaturated fatty acids in AT and of saturated fatty acid in blood TAG, with no difference between the diets. HFD induced a higher increase of monounsaturated fatty acids in blood TAG. No other diet-induced changes were found in proportion of major classes of fatty acids. In respect to individual fatty acids, the diets induced a number of changes in AT and blood, the changes, however, not being different between the diets.Hypocaloric diets induce a number of changes in fatty acid composition in blood and adipose tissue, with little differences in respect to the proportion of fat in the diet. The results suggest the diet-induced changes in fatty acid composition are controlled by the calorie deficit of the diet and the proportion of dietary fat plays a minor role.

The aim of the study was to determine how addition of n-3 polyenic fatty acids (PUFA) to the present treatment with statin + fibrate combination in diabetic dyslipidemia effects plasma lipids and lipoproteins, LDL lipoperoxidation, glucose homeostasis, concentration of serum homocysteine and selected inflammation indicators.24 patients with type 2 diabetes, who after the combined hypolipidemic treatment (pravastatin 20 mg + micronized fenofibrate 200 mg per day) cannot reach the recommended target values for long time, received for three consecutive months supplementation of 3,6 g PUFA n-3 per day or a placebo (olive oil). At the beginning of the study, after three months of PUFA supplementation and after another three months of placebo administration, concentrations of plasma lipids, composition of fatty acids, plasma phosphatidylcholine (PC), cholesterol esters (CE) and triglycerides (TG), concentration of tHcy, conjugated diens (CD) in LDL and selected inflammation indicators (IL-6, TNFalpha, VCAM-1) were determined. n-3 PUFA supplementation resulted in the significant decrease of tHcy concentration (-29%, P0.01) and TG (-28%, P0.05) in plasma. During the period of placebo administration, values returned to base line levels. CD concentration in LDL after n-3 PUFA increased by 15% (P0.15, not significant), meanwhile after the placebo containing oleic acid it decreased by 18% (P0.05).Our results show that n-3 PUFA supplementation together with statin + fibrate combination in DDL patients can significantly decrease the risk of cardiovascular diseases.

The connection between changes in lipid pattern in brain plasma membranes and long-term administration of therapeutically effective doses of antidepressants has not been sufficiently demonstrated so far. Therefore, we analyzed effect of antidepressants that differ in pharmacological selectivity on membrane lipid composition in the rat brain tissue. Laboratory rats were given desipramine, maprotiline, citalopram, moclobemide or lithium for a 4-week period. We observed a significant decrease in phosphatidylethanolamine representation after administration of maprotiline, citalopram and moclobemide when compared with controls. Membrane cholesterol content was decreased after desipramine administration and increased after citalopram or lithium treatment. Electroneutral phospholipids were decreased after the administration of all tested antidepressants except for desipramine. Decrease in phosphatidylserine was found following long-term administration of maprotiline or desipramine; relative representation of phosphatidylinositol was reduced after lithium treatment. Statistically significant negative correlation between cholesterol and electroneutral phospholipids was discovered. Membrane microviscosity evaluated by fluorescence anisotropy of membrane probes was only slightly decreased after desipramine and increased after citalopram administration. Hypothesis was supported that changes in brain neurotransmission produced by antidepressants could be, at least partially, associated with adaptive changes in membrane cholesterol and phospholipids.

Polyunsaturated fatty acids of n-3 family play an important role in the prevention of ischemic heart disease, as was shown in many epidemiological as well as intervention studies. These fatty acids are essential and human organism is fully dependent on their dietary intake from chloroplast of green plants and fat of aquatic animals. Cardioprotective action of these acids results from their complex effect (antiarrhytmic, antithrombotic, antiinflammatory, hypolipidemic etc.). These acids can, with the exception of glucose homeostasis, favourably influence individual components of the metabolic syndrome. Beneficial effects of n-3 polyunsaturated fatty acids are supposed also in chronic inflammatory and autoimmune diseases, psychiatric-neurological diseases and malignant tumours. In the case of rheumatoid arthritis, antiinflammatory effects of polyunsaturated fatty acids were proven. In general, favourable effects of the optimal income of n-3 polyunsaturated fatty acids can be explained by the influencing of cellular metabolic functions, incorporation into membrane phospholipids, modulation of enzymes and signal molecules as well as by direct impact on gene expression. Polyunsaturated fatty acids of n-3 family have high therapeutic potential, which results from the combined action on different levels of cell functions. In some diseases, their effect is nearly pharmacological - prevention of the sudden death and fatal myocardial infarction, treatment of hyper- and dyslipoproteinemias, suppression of the inflammatory activity in rheumatoid arthritis. In another group of diseases, they have supporting effect (prevention of the arterial hypertension in metabolic syndrome) and, finally, in the last one (psychiatric-neurological diseases and tumours), more data of defined clinical groups are necessary for final evaluation.

The aim of this study was to study the effect of adding polyunsaturated fatty acid (PUFA) n-3 or placebo (containing oleic acid) to a combined statin-fibrate treatment on plasma lipoproteins, lipoperoxidation, glucose homeostasis, total homocysteine (tHcy) and microalbuminuria (MA) in patients with diabetic dyslipidemia (DDL). Twenty-four patients, who did not fulfill the recommended target lipid values with combined hypolipidemic therapy (pravastatin 20 mg+micronized fenofibrate 200 mg daily), were supplemented with 3.6 g PUFA n-3 daily for 3 months or placebo (olive oil) for the next 3 months. The concentrations of plasma lipids, fatty acid (FA) profiles of phosphatidylcholine (PC), cholesteryl esters (CE) and triglycerides (TG), tHcy levels, concentrations of conjugated dienes (CD) in low-density lipoprotein (LDL), and MA were determined in baseline state, after the PUFA n-3 and placebo treatment period. Supplementation with PUFA n-3 led to a significant decrease in plasma tHcy (-29%, P < .01) and TG (-28%, P < .05) levels, as well as to a significant decrease in MA (-24%, P < .05). The decrease in MA correlated significantly with the increase in total PUFA n-3 (r = -.509, P < or = .05) and docosahexaenoic acid (r = -.52, P < .01) in TG. The concentrations of CD in LDL increased significantly (+15%, P < .05). The supplementation with PUFA n-3 to the combined statin-fibrate treatment in patients with DDL decreased the TG and tHcy levels as well as MA. It could lead to decreased risk of atherothrombosis and delay of diabetic nephropathy onset and progression.

VECKA, M., TVRZICKA, E., STAŇKOVA, B., NOVAK, F., NOVAKOVA, O. and ŽAK, A. Hypolipidemic Drugs Can Change the Composition of Rat Brain Lipids. Tohoku J. Exp. Med., 2004, 204 (4), 299-308 ││ Hypolipidemic drugs are potent serum cholesterol lowering agents used for prevention of coronary heart disease. In addition to their cholesterol lowering effect, these drugs exhibit both pleiotropic benefi cial and various neurological side effects. Therefore, we analysed effect of the hypolipidemic drugs, fenofibrate and statins, on membrane lipid composition in the rat brain tissue. Male Wistar rats were given 0.1 mg of fenofibrate, lovastatin, pravas tatin, fluvastatin or placebo (control) once daily for six weeks. In rats treated with lovastatin or pravastatin, decreased cholesterol and increased ceramide monohexoside contents in the brain tissue were observed in comparison with control. Treatment with fluvastatin or lovastatin resulted in increased sphingomyelin and decreased diphosphatidylglycerol contents. The most important changes in the fatty acid profile were observed in ceramide monohexosides; treatment with fluvastatin decreased the content of saturated and increased the content of polyunsaturated fatty acids. Fenofi brate treatment led to decreased content of saturated fatty acids in phosphatidylethanolamines. In conclusion, statin treatment resulted in the decreased content of cholesterol and diphosphatidylglycerol associated with the increased content of sphingolipids in the rat brain tissue. As cholesterol and sphingolipids are important components of brain membranes, the observed alterations in the composition brain lipids might be involved in genesis of neurological and mental symptoms following statin therapy. ││││ statin; fibrate; brain; lipids; fatty acid © 2004 Tohoku University Medical Press

Previous studies from our laboratory have indicated that secondary hyperaldosteronism affects phospholipids of rat colonic enterocytes. To assess whether this represents a direct effect of mineralocorticoids on enterocytes, the role of aldosterone and dexamethasone in the regulation of lipid metabolism was examined in Caco-2 cells during development of their enterocyte phenotype. Differentiation of Caco-2 cells was associated with increased levels of triglycerides (TG) and cholesteryl esters (CE), a decreased content of cholesterol and phospholipids and changes in individual phospholipid classes. The phospholipids of differentiated cells had a higher content of n-6 polyunsaturated fatty acids (PUFA) and lower amounts of monounsaturated (MUFA) and saturated fatty acids than subconfluent undifferentiated cells. Differentiated cells exhibited a higher ability to incorporate [3H]arachidonic acid (AA) into cellular phospholipids and a lower ability for incorporation into TG and CE. Incubation of subconfluent undifferentiated cells with aldosterone or dexamethasone was without effect on the content of lipids, their fatty acids and [3H]AA incorporation. In contrast, aldosterone treatment of differentiated cells diminished the content of TG, increased the content of phospholipids and modulated their fatty acid composition. The percentage of n-6 and n-3 PUFA in phospholipids was increased and that of MUFA decreased, whereas no changes in TG were observed. The incorporation of [3H]AA into phospholipids was increased and into TG decreased and these changes were blocked by spironolactone. Treatment of differentiated cells with dexamethasone increased their CE content but no effect was identified upon other lipids, their fatty acid composition and on the incorporation of [3H]AA. As expected for the involvement of corticosteroid hormones the mineralocorticoid and glucocorticoid receptors were identified in Caco-2 cells by RT-PCR. The results suggest that aldosterone had a profound influence on lipid metabolism in enterocytes and that its effect depends on the stage of differentiation. The aldosterone-dependent changes occurring in phospholipids and their fatty acid composition may reflect a physiologically important phenomenon with long-term consequences for membrane structure and function.

Anorexia nervosa is a model of simple starvation accompanied by secondary hyperlipoproteinemia. Plasma fatty acid pattern influences levels of plasma lipids and lipoproteins. Level of plasma lathosterol represents a marker of cholesterol synthesis de novo; levels of plant sterols reflect resorption of exogenous cholesterol. The aim of the study was to evaluate fatty acids in plasma lipid classes and their relationships to plasma lipids, lipoproteins, lathosterol, campesterol and beta-sitosterol.We examined 16 women with anorexia nervosa and 25 matched controls. Main lipid classes were separated by thin-layer chromatography, fatty acids and non-cholesterol sterols were evaluated by capillary gas chromatography. Patients with anorexia nervosa revealed increased concentrations of total cholesterol, triglycerides, HDL-cholesterol, campesterol and beta-sitosterol; changes in plasma levels of lathosterol did not reach statistical significance. The most consistent finding in fatty acid composition was a decreased content of linoleic acid and raised content of palmitoleic acid in all lipid classes.Changes of plasma lipids and lipoproteins in anorexia nervosa result from complex mechanisms including increased synthesis of triglyceride-rich lipoproteins along with unchanged cholesterol synthesis rate. Hypercholesterolemia in anorexia nervosa may also result from increased resorption of exogenous cholesterol.

Aim: To identify the total content of trans fatty acid (TFA) isomers and C18:1 trans isomers in subcutaneous fat samples from persons with atherosclerosis of the coronary arteries, as an indicator of dietary exposure. Methods: Using capillary gas chromatography, the authors determined total content of TFA isomers and C18:1 trans isomers in the subcutaneous fat of 34 patients with ischemic heart disease who had undergone aortocoronary bypass surgery and in 46 patients with no sign of coronary disease. Results: On average, the total TFAs in cardiac patients were 2.88 ± 1.19% of all fatty acids, in noncardiac patients 2.56 ± 0.89%. However, the difference is not statistically significant. The average concentration of C18:1 trans in cardiac patients (2.31 ± 1.09%) was statistically significantly higher (p = 0.05) than in the noncardiac group (1.95 ± 0.77%). Conclusions: The results obtained indicate a lower TFA load in comparison with previous studies in other countries. A higher concentration of 18:1 TFAs in the subcutaneous fat of patients with coronary disease might be an impulse to correct the dietary habits of this very high-risk population.

Four anthropometric parameters (body mass index, waist-to-hip circumference ratio, waist circumference, and ratio of subscapularis to triceps skinfold thickness), cutoff values being set according to the WHO guidelines, were compared as discriminative parameters for anthropometric, hemodynamic, and metabolic data relevant as risk factors of coronary heart disease. Waist circumference reflected differences between below and above cutoff values throughout all parameters, with the highest “effect size” values being for fat mass; blood pressure; glucose homeostasis parameters; plasma and LDL cholesterol; plasma, LDL, and VLDL apo B; and LDL oxidability (cumulative effect size value: 2777). Body mass index reflected most significantly plasma, LDL, and VLDL triglyceride; HDL and VLDL cholesterol; and content of linoleic acid in LDL phosphatidylcholine (cumulative effect size value: 2016). Waist-to-hip ratio dominated in effect size value only in VLDL oxidability (cumulative effect size value: 1497). Subscapularis to triceps skinfold thickness ratio had the lowest discriminating ability in all data.

Meta-analyses of epidemiological studies proved that hypertriacylglycerolemia (HTAG) is an independent CHD risk factor. The VLDL lipoproteins, which are the main TAG carrier, are precursors of atherogenic LDL and their increased concentration is related to the decrease of antiatherogenic HDL, increased ratio of small, dense LDL and represents one of the causes of the endothelial dysfunction. According to some authors, HTAG is one of the factors of the oxidation stress.45 patients of the studied group received 200 mg of micronized fenofibrate per day for six weeks. Before the beginning and after the end of treatment, following examinations were carried out: concentration of plasma lipids, lipoproteins, and apolipoproteins, composition of fatty acids (FA) in main lipid plasma classes and LDL (phosphatidylcholine--PC, TAG, cholesteryl esters--CE) and lipoperoxidation in VLDL and LDL, isolated by preparative ultracentrifugation.In plasma, the treatment of HTAG led to a significant decrease of TC, TAG and apo-B concentration and to the increase of cholesterol concentration in HDL and in both HDL2 and HDL3 subfractions. In isolated LDL particles we observed a decrease of the TAG portion (by 25%) together with significant lag phase prolongation (by 33%, P0.05) and peak time retardation (by 24%, P0.05). In VLDL particles the concentration of cholesterol became smaller (by 28%), TAG (by 26%), phospholipids (by 28%) (in all groups P0.005) and the lag phase became significantly longer (by 16%, P0.01). Treatment with fenofibrate significantly reduced the linoleic acid (18:2n-6) in PC and TAG plasma, CE and TG LDL, in a higher ratio of palmitoleic acid (16:1n-7) in CE LDL, oleic (18:1n-9) in PC LDL, in significant concentration of total monoenic FA in PC and CE LDL and to a significant increase of the concentration of myristic acid (14:0) in CE and myristic and stearic acids (18:0) in TAG LDL. From our results it is possible to conclude that the six-week long treatment of HTAG with micronized phenofibrate led to significant modification of LDL and VLDL composition accompanied by their lower lipoperoxidation indexes. These favourable changes in oxidability were accompanied with changes in the composition of FA in CE, TAG and PC plasma as well as LDL.

Fat distribution, not overweight and obesity per se, are supposed to be associated with hemodynamic, hemostatic and other metabolic disturbances (insulin resistance, hyperuricemia and dyslipidemia). Moreover, obesity increases the total risk of cardiovascular disease. Oxidative modification of lipoproteins, especially of LDL, is supposed to play a key role in the initiation and progression of atherosclerosis. Therefore we analysed VLDL a LDL composition and Cu(2+)-catalyzed conjugated diene formation in both lipoprotein fractions in patients with intraabdominal fat accumulation and in control group. Patients (33, 12 M/21 F) with intraabdominal fat accumulation (WHCR 1.00 for men, 0.85 for women) revealed, in comparison with control group (72, 47 M/25 F), after adjustment for the same age, increased plasma total cholesterol, apolipoprotein B, non-esterified fatty acid concentrations, and systolic blood pressure as well. In the group of patients increased levels of cholesterol, triglycerides, phospholipids, proteins and apolipoprotein B (only in the fraction of VLDL) were found in the both VLDL and LDL fractions. In this group of patients increased concentrations of conjugated dienes in VLDL and decreased length of lag phase of VLDL were found. Parameters of conjugated diene formation of LDL (basal absorbance, length of lag phase, propagation phase) did not differ significantly from controls. Concomitantly, persons with intraabdominal fat distribution showed decreased titres of antibodies against oxidative modified LDL. The results indicated that the patients with intraabdominal fat accumulation revealed not only adverse composition of VLDL and LDL particles, but also increased VLDL oxidation and oxidability.

Trans fatty acids (TFA) were analyzed by capillary gas chromatography in four groups of edible fats available on the Prague market. In animal fats, 1.9-2.5%, 2.8-5.5% and 11.3-13.5% TFA were found in the lard, butter, and butter enriched by vegetable fat, respectively. In shortenings, TFA content varied between 0.5 and 38%, in margarines from 0.6 to 13% and in table fats from 1.4 to 27%.

Both insulin resistance and hyperlipidaemia are connected with an increased oxidative stress, playing a significant role in the development of atherosclerosis. A significant event in the process being the oxidative modification of the lipoproteins, especially LDL. Aim of the study was to analyse relationships between the fatty acid composition of the plasma cholesteryl esters (CE), triglycerides (TG) and phosphatidylcholine (PC) and of the separated LDL, insulinaemia and oxidability of both VLDL and LDL particles. We have observed the group of 75 patients with hyperlipidaemia (52 men and 23 women), which was divided in the two subgroups after the basal insulinaemia (more resp. less than 13 mU/l). Fasting hyperinsulinaemia of the probands with normal glucose tolerance served as a marker of an insulin resistance. Patients with both hyperlipidaemia and basal hyperinsulinaemia were characterized by a significantly higher concentration of TG, apolipoprotein B in LDL, and lower concentration of cholesterol in HDL, especially in HDL3. We have observed only marginally significant elevation of concentration of the dihomo-gammalinolenic acid (DGLA) in plasma PC and also higher concentrations of alpha-linolenic and lower of arachidonic acid (AA) and in LDL-CE in the hyperinsulinaemic group. We have also found significantly positive correlations between the stearic acid in plasma PC, alpha-linolenic acid in plasma TG on one hand and the basal insulinaemia on the other hand. Significant positive correlation was also found between the ratio docosahexaenoic/docosapentaenic acid and insulinaemia in 120 min of oral glucose tolerance test. Significant negative correlation was observed between the ratio AA/DGLA and basal insulinaemia. Analysing the lipoperoxidation of VLDL and LDL using the method of conjugated diene kinetics we have found statistically non-significant decrease of lag phase duration of LDL and VLDL (their oxidability).

Previous studies have shown that aldosterone treatment of amphibian epithelial cells results not only in stimulation of Na + absorption but also in changes in phospholipid composition which are necessary for the mineralocorticoid action of aldosterone. The present study was designed to investigate the effect of aldosterone on phospholipids of mammalian epithelia. Phospholipid and fatty acid composition was examined in colonic epithelium (mineralocorticoid target tissue) and thymus (non-mineralocorticoid but glucocorticoid target tissue) of rats which had received aldosterone or vehicle by a miniosmotic pump for 7 days. Aldosterone increased the mass of colonic phospholipids relative to cellular proteins with concomitant changes in the percentage distribution of fatty acids, whereas the relative distribution of membrane phospholipds was not changed. Phosphatidylcholine increased the content of polyunsaturated and decreased that of monounsaturated fatty acids, which predominantly reflected the accretion of arachidonic and a decrease in oleic and palmitoleic acids. Within the phosphatidylethanolamine subclass, pretreatment of rats with aldosterone decreased the content of monounsaturated fatty acids (predominantly oleic and palmitoleic acid) and of n-3 fatty acids, and increased the content of saturated fatty acids (palmitic acid). The saturated-to-nonsaturated fatty acid ratio also significantly increased after aldosterone treatment. No changes in thymic phospholipids were seen. The results are consistent with the contention that aldosterone specifically modulates phospholipid concentration and metabolism in mineralocorticoid target tissue. The changes in phospholipid content and its fatty acid composition during the fully developed effect of aldosterone may reflect a physiologically important phenomenon with long-term consequences for membrane structure and function.

Oxidatively modified LDL play an important role in the pathogenesis of endothelial dysfunction, initiation and development of atherosclerosis and stability of the atheromatous plaque. The increased oxidative stress is apparent from a number of deviations, which are part of the insulin resistance syndrome (hypertension, hypoalphacholesterolaemia, diabetes and hyperlipoproteinaemia). The objective of the work was to examine the degree of oxidation and oxidability of LDL and VDL in subjects with dyslipidaemia.In 40 subjects with dyslipidaemia, defined as a triglyceride concentration above 2.30 mmol/l and a drop of HDL cholesterol below 0.90 mmol/l, the authors assessed the fatty acid profile in plasma lipid classes and LDL by capillary gas chromatography. Lipoperoxidation in VLDL and LDL was examined by the method of kinetics of conjugated dienes according to Esterbauser. The results were compared with a group of healthy controls. The group of dyslipidaemic subjects had higher concentrations of NEFA, IRI, blood sugar and uric acid. In these subjects the concentration of conjugated dienes in VLDL was significantly higher and the lag stage in VLDL and LDL was reduced. Both groups differed as to the composition of VLDD and LDL. The group of dyslipidaemic subjects had a higher concentration of cholesterol, phospholipids, triglycerides and apolipoprotein B. A constant finding in the fatty acid profile of all lipid classes was a raised concentration of palmitoleic acid and reduced linoleic acid concentration.Dyslipidaemic subjects have, as compared with a control group, higher NEFA, IRI and uric acid concentrations. Furthermore they differed not only by the composition of VLDL and LDL but also by a higher degree of VLDL oxidation and reduced resistance to lipoperoxidation of VLDL and LDL particles. A consistent finding in the fatty acid profile was an increased level of palmitoleic acid in all plasma lipid classes and LDL and a drop of linoleic acid in phosphatidylcholine LDL and plasma cholesterolesters.

High-performance liquid chromatography with evaporative light scattering detection (HPLC-ELSD) and thin layer chromatography with flame ionization detection (TLC-FID) have been applied to the separation of five main free bile acids present in humans: cholic (CA), chenodeoxycholic (CDCA), deoxycholic (DCA), lithocholic (LCA) and ursodeoxycholic (UDCA) acid. HPLC separation was performed on Biospher Si 100 column using a mixture of n-heptane, isopropanol, ethylacetate, methanol and glacial acetic acid as a mobile phase. All the compounds were separated in less than 12 minutes by using a gradient elution mode. TLC-FID separation was performed on S-II Chromarods with a mixture of isooctane, ethylacetate and glacial acetic acid as a mobile phase. HPLC-ELSD method was applied to the determination of CDCA and UDCA in pharmaceuticals and their purity control when LCA, DCA and CA were considered as impurities.

Epidemiological trials provided evidence that the cholesterol concentration in lipoproteins B, i.e. VDL, IDL and LDL, correlate significantly with the incidence of ischaemic heart disease (IHD). The objective of the present study was to assess how the fatty acid composition in plasma phosphatidyl choline affects the total and LDL cholesterol, triglyceride and apolipoprotein B concentrations in subjects with primary hyperlipoproteinaemia and dyslipidaemia.In a group of 142 subjects with primary hyperlipoproteinaemia and dyslipidaemia the concentrations of plasma lipids, lipoproteins apolipoproteins and fatty acids in plasma phosphatidyl choline (PC) were assessed. The authors provided evidence by discriminant analysis where the dependent variables were the lower quintiles (Q1 + Q2) and the upper quintiles (Q4 + Q5) of concentrations of total cholesterol, triglycerides, LDL-cholesterol and apolipoprotein B and the independent variables were FA concentrations in plasma PC, that the total cholesterol concentration was inversely associated with the concentration of docosahexaenic acid (22:6n-3). The concentration of LDL-cholesterol correlated inversely with the concentration of palmitoleic acid (16:1n-7). Triglyceridaemia was inversely associated with the linoleic acid concentration (18:2n-6). The concentration of apolipoprotein B correlated positively with myristic acid (14:0) and negatively with concentrations of oleic acid (18:1n-9) and linoleic acid (18:2n-6).The submitted results indicate that the fatty acid concentrations of PC in plasma are significantly and markedly correlated with concentrations of total cholesterol, triglycerides, LDL-cholesterol and apolipoprotein B. It is possible that atherogenic lipoproteins may be favourably influenced not only by the amount of fat but also by a suitable fatty acid composition.

Epidemiological trials revealed a significant inverse relationship between the cholesterol concentration in high density lipoproteins (HDL-C), apolipoprotein A-I and the incidence of ischaemic heart disease (IHD). It is assumed that the protective effects of HDL against the development of IHD are due to its important function during the reverse cholesterol transport. The HDL-C and apo A-I concentration are influenced by a number of genetic, racial, sexual, hormonal, metabolic and nutritional factors. The objective of the present investigation was to assess how the fatty acid (FA) composition in phosphatidyl choline in plasma affects the HDL-C and A-I concentration in subjects with primary hyperlipoproteinaemia and dyslipidaemia.In a group of 142 subjects with primary hyperlipoproteinaemia and dyslipidaemia the plasma concentrations of lipids, lipoproteins, apolipoproteins and fatty acids in plasma phosphatidyl choline (PC) were assessed. Using discriminant analysis where the dependent variables were the lower quintiles (Q1 + Q2) and upper quintiles (Q4 + Q5) of HDL-C and A-I concentrations and the independent variables FA concentrations in plasma PC, the authors provided evidence that low HDL-C concentrations are associated with 18:0 and conversely a rise of Apo-I is associated with concentrations of 18:1n-9, 18:2n-6, 18:3n-6 and 22:6n-3 in plasma phosphatidylcholine.The submitted results indicate that FA concentrations in plasma PC are significantly and markedly associated with HDL-C and A-I concentrations in subjects with hyperlipoproteinaemia and dyslipidaemia. This opens the opportunity to influence favourably the concentration of these parameters by changing the dietary fatty acid composition.

Some epidemiological, clinical and experimental studies have shown that intake of n-3 fatty acids (FA) lowers the incidence of coronary heart disease (CHD). The effects of fish oil and n-3 FA on the development of atherosclerosis include several factors such as the platelet-vascular wall interaction, modulation of eicosanoid metabolism as well as platelet aggregation and its survival time. There were also changes in the fibrinolytic system and cardiovascular reactivity observed. Effects of n-3 FA on lipid and lipoprotein metabolism exert antiatheromatous action as well. The aim of the study was to evaluate changes in plasma lipid risk factors for CHD in subjects with primary hyperlipoproteinemia (HLP) after the administration of fish oil rich in n-3 FA.A total of 82 patients (61 men and 21 women) were administered fish oil (3.5 g n-3 FA daily) for a period of 3 weeks. The group of hyperlipidemics included 9 patients with HLP IIA, 29 with HLP IIB, and 35 with HLP IV. Seven patients had HLP type V while two had HLP type III. Intake of fish oil led to a mild decrease in total plasma cholesterol which was significant in the whole group and in HLP type V. Triglyceride levels declined significantly in all HLP phenotypes, with the changes being most marked in HLP types IIB, IV, and V. We also observed a significant increase in cholesterol concentration in HDL and in the both HDL2 and HDL3 subfractions in the whole group and all HLP phenotypes as well. On the other hand no statistical significant changes were observed in LDL-cholesterol levels. The levels of apo B rose significantly only in HLP type V. A statistically significant increase was found in apo A-1 levels in the whole group and in the HLP IIB subgroup. Fish oil administration led to a mild reduction in diastolic pressure and uricemia. In part of patients fish oil induced decrease in lipoprotein(a) concentration was observed.

The authors discuss the effect of administration of fish oils rich in n-3 fatty acids in diabetic patients type 2 and draw attention to the possible deterioration of glucose homeostasis. The objective of the investigation was to assess changes of the lipid and carbohydrate metabolism in type 2 diabetics with associated dyslipidaemia after enrichment of the diet with n-3 fatty acids.To 17 patients with type 2 diabetes and dyslipidaemia fish oil containing 5.5 g n-3 fatty acids per day was administered. After six weeks a decline of triglycerides was recorded (-47%, P0.01), free fatty acids (-27%, P0.01) and a rise of HDL2-cholesterol (25%, P0.05). The concentration of apo B, apo A-1, LDL- and HDL cholesterol did not change significantly. There were no significant changes of the blood sugar level, glycosylated haemoglobin and fructosamine. The insulin and C-peptide concentration on fasting (and after glucagon stimulation) did not change significantly. With regard to the HDL2-cholesterol and 18:0 fatty acid concentration in serum the group can be divided into responders (with a decline of glycosylated haemoglobin) and non-responders. The two groups have a reverse trend of blood sugar levels and insulinaemia and differ as to the metabolism of 18:1 n-7 acid.Enrichment of the diet with n-3 fatty acids in diabetics with dyslipidaemia has a favourable effect on the plasma lipid spectrum without causing deterioration of parameters of diabetes compensation. Among the group of patients some can be found where fish oil administration improves also glucose homeostasis.

Number of drugs is used in human medicine for a long time therapy. Their side effects on lipid metabolism are mostly unknown. Clinical testing of drugs concerns usually biochemical parameters involved in the liver and kidney function. The aim of our study was to search the effect of ibuprofen on the lipid composition in the important organs. Ibuprofen was chosen as a representative of currently used nonsteroidal antiinflammatory drugs.Group of 14 Crl-NMRI-BR male mice, approximately 8 weeks old, 30.5 +/- 1.2 g initial body mass, was used in the experiment. Animals were divided into 2 identical groups. One of them received 0.6 mg of ibuprofen per day (animal model for human dose 1200 mg/day) in the diet for a period of 6 weeks. After this time, animals were killed by decapitation, individual organs were excised, washed with physiological saline and lyophilized. Total lipid content was determined gravimetrically. Individual lipid classes were separated by thin-layer chromatography. Fatty acid profiles (in the form of methyl esters) in these lipid classes were analyzed by capillary gas chromatography using fused silica column 25 m x 0.25 mm I.D. with the chemically bonded stationary phase CP-WAX 52 CB (Chrompack, The Netherlands). The treatment resulted in the increased body mass of 7.9 +/- 1.7 g, which, in comparison with that of control group (4.9 +/- 3.4 g) was not statistically significant. Liver mass increased from 1.62 +/- 0.21 g to 1.86 +/- 0.19 g (p0.05). Total lipid content in the liver increased from 52.8 +/- 15.4 to 91.7 +/- 10.9 mg/g (p0.01). Changes in the fatty acid composition were most important in the kidney tissue. Relative levels of polyunsaturated fatty acids increased in phosphatidylethanolamine from 27.6 +/- 6.1 mol% to 33.90.6 mol% (p0.05) for n6 fatty acids and from 8.7 +/- 2.1 to 14.7 +/- 1.1 mol% (p0.001) for n3 fatty acids. These changes were compensated by the opposite ones in the relative content of saturated fatty acids from 49.7 +/- 7.0 mol% to 41.1 +/- 0.7 mol% (p0.05) and monoenoic fatty acids from 14.0 +/- 2.0 mol% to 10.4 +/- 0.9 mol% (p0.01). Changes in the fatty acid composition of the liver and heart lipids were mostly not statistically significant.An unusual component was observed in the triacylglycerol fraction of heart tissue, which was identified by the gas chromatography-mass spectrometry as a mixture of approximately 80% of isopropyl myristate and 20% of isopropyl palmitate. Absolute content of this component was not determined.

Many patients suffering from ischaemic heart disease (IHD) were shown to be characterized by different deviations of lipoprotein metabolism without having plasma cholesterol and triglyceride levels increased. The aim of the study was to determine the parameters of lipoprotein metabolism most contributing to finding among normolipidemic men those with an elevated risk of myocardial infarction.We investigated 21 men with normal plasma cholesterol and triglyceride levels, who survived myocardial infarction (MI) in the period 6 months to 3 years before the investigation (group MI). In comparison with the control group of normolipidemic men without IHD, survivors of MI had significantly lower concentrations of HDL-C (-22%, P0.01), especially in HDL3 subfraction (-24%, P0.001), higher concentrations of apo B in LDL (+36%, P0.001) and lower values of cholesterol to apo B ratio in LDL (-25%, P0.05). The concentrations of total plasma cholesterol, triglycerides, LDL-cholesterol, HDL2-cholesterol, apo A-I and the ratio HDL-C/apo A-I did not differ significantly. Discriminant analysis revealed that for separating the two groups, determining apo B in LDL and HDL3-C was most advantageous as thus 80% patients in this set could be correctly classified.These results show the significance of the investigation of apo B and HDL-C including their subfractionism HDL2 and HDL3 for the estimation of MI risk in normolipidemic men.

The authors administered to a group of 60 patients with primary hyperlipoproteinaemia (HLP) HLP type IIA 9, IIB 16, type IV 35 (fish oil) (Activepa 30TG) rich in eicosapentaenic acid (EPA, 20:5-n-3) and docosahexaenic acid (DHA, 22:6n-3). Administration of fish oil, 10 g per day, for a period of 21 days led to a decline of the total cholesterol by 9.8%, triglycerides (TG) by 39.5% and a rise of HDL-cholesterol (HDL-C) by 12.8%. The concentration of LDL-C, apo B, and apo A-I did not change significantly. The content of individual fatty acids (FA) in phosphatidyl choline (PC) cholesteryl esters (CE) and plasma TG before treatment was used as an independent variable for discrimination analysis in relation to dependent variables such quintile 1 (Q1) and Q2 on the one hand and Q4 and Q5 differences of the above mentioned parameters on the other hand. The drop of TG after ingestion of n-3 FA correlates indirectly with concentrations of PC 20:5n-3, TG 18:3n-3 and TG 20:4n-6. The content of 20:0 and 20:1 in PC and 18:0 in TG are related to the rise of LDL-C after treatment. The drop of apo B is associated with the PC 22:6n-3 concentration. The rise of HDL-C and apo A-I is positively associated with the concentration of 16:1n-7 in PC and TG and negatively with the CE 16:0 content. The rise of HDL-C after treatment is moreover negatively influenced by concentrations of PC 18:3n-6 and TG 20:3n-6.(ABSTRACT TRUNCATED AT 250 WORDS)