The aim of this study was to investigate the effects of troglitazone (TRO) - a new insulin-sensitizing agent - on some metabolic parameters in an experimental model of hypertriglyceridemia and insulin resistance, hereditary hypertriglyceridemic rats, and to compare its effects with those of vitamin E, an antioxidant agent. Three groups of the above rats were fed diets with a high content of sucrose (70 % of energy as sucrose) for four weeks. The first group was supplemented with TRO (120 mg/kg diet), the second one with vitamin E (500 mg/kg diet), and the third group served as the control. Vitamin E supplementation did not lower serum triglycerides (2.42±0.41 vs. 3.39±0.37 mmol/l, N.S.) while TRO did (1.87±0.24 vs. 3.39±0.37 mmol/l, p<0.01). Neither TRO nor vitamin E influenced the serum levels of free fatty acids (FFA). Both drugs influenced the spectrum of fatty acids in serum phospholipids - TRO increased the levels of polyunsaturated fatty acids (PUFA) n-6 (36.04±1.61 vs. 19.65±1.56 mol %, p<0.001), vitamin E increased the levels of PUFA n-3 (13.30±0.87 vs. 6.79±0.87 mol %, p<0.001) and decreased the levels of saturated fatty acids (32.97±0.58 vs. 51.45±4.01 mol %, p<0.01). In conclusion, TRO lowered the level of serum triglycerides but vitamin E did not have this effect in hypertriglyceridemic rats. Compared with TRO, vitamin E had a different effect on the spectrum of fatty acids in serum phospholipids., Š. Chvojková, L. Kazdová, J. Divišová., and Obsahuje bibliografii
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 obesityassociated 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., P. Hlavaty, E. Tvrzicka, B. Stankova, H. Zamrazilova, B. Sedlackova, L. Dusatkova, V. Hainer, M. Kunesova., and Obsahuje bibliografii
In the current study, we tested a hypothesis that CD36 fatty acid (FA) transporter might affect insulin sensitivity by indirect effects on FA composition of adipose tissue. We examined the effects of CD36 downregulation by RNA interference in 3T3-L1 adipocytes on FA transport and composition and on sensitivity to insulin action. Transfected 3T3-L1 adipocytes, without detectable CD36 protein, showed reduced neutral lipid levels and significant differences in FA composition when levels of essential FA and their metabolites were lower or could not be detected including gamma linolenic (C18:3 n6), eicosadienic (C20:2 n6), dihomo-gamma linolenic (C20:3 n6), eicosapentaenoic (EPA) (C20:5 n3), docosapentaenoic (DPA) (C22:5 n3), and docosahexaenoic (DHA) (C22:6 n3) FA. Transfected 3T3-L1 adipocytes exhibited a significantly higher n6/n3 FA ratio, reduced Δ5-desaturase and higher Δ9-desaturase activities. These lipid profiles were associated with a significantly reduced insulin-stimulated glucose uptake (4.02±0.1 vs. 8.42±0.26 pmol.10-3 cells, P=0.001). These findings provide evidence that CD36 regulates FA composition thereby affecting sensitivity to insulin action in 3T3-L1 adipocytes., K. Kontrová, J. Zídková, B. Bartoš, V. Skop, J. Sajdok, L. Kazdová, K. Mikulík, P. Mlejnek, V. Zídek, M. Pravenec., and Obsahuje bibliografii a bibliografické odkazy
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., P. Hlavatý, M. Kunešová, M. Gojová, E. Tvrzická, M. Vecka, P. Roubal, M. Hill, K. Hlavatá, P. Kalousková, V. Hainer, A. Žák, J. Drbohlav., and Obsahuje bibliografii a bibliografické odkazy
Postnatal heart development is characterized by critical periods of heart remodeling. In order to characterize the changes in the lipophilic fraction induced by free radicals, fatty acids and t heir oxidized products, lipofuscin -like pigments (LFP), were investigated. Fatty acids were analyz ed by gas chromatography and LFP were studied by fluorescence techniques. A fluorophore characterized by spectral methods was further resolved by HPLC. Major changes in the composition of fatty acids occurred immediately after birth and then during maturation. Fluorescence of LFP changed markedly on postnatal days 1, 4, 8, and 14, and differed from the adult animals. LFP comprise several fluorophores that were present since fetal state till adulthood. No new major fluorophores were formed during development, just the abundances of individual fluorophores have been modulated which produced changes in the shape of the spectral arrays. HPLC resolved the fluorophore with excitation maximum at 360 nm and emission maximum at 410 nm. New chromatographically distinct species appeared immediately on postnatal day 1, and then on days 30 and 60. Consumption of polyunsaturated fatty acids immediately after birth and subseque nt formation of LFP suggests that oxidative stress is involved in normal heart development., J. Wilhelm, J. Ivica, Z. Veselská, J. Uhlík, L. Vajner., and Obsahuje bibliografii
The effects of 8-days treatment with 17α-estradiol (33.3 μg/kg) and progesterone (1.7 mg/kg) on plasma lipids and fatty acid composition of plasma phospholipids were examined in intact (INT) and bilaterally common carotid arteries occluded (BCO) male Wistar rats. Significant decrease of triglyceride level was found in BCO rats after the estradiol treatment. Both hormones elevated proportion of 18:1n-7 fatty acid in INT, but they failed to have such an effect in BCO. Estradiol increased 22:5n-3 and total n-3 polyunsaturated fatty acids (PUFA) in intact, and decreased 18:2n-6 in BCO rats. Significantly lower level of total n-3 was found in progesterone-treated than in estradiol-treated BCO rats. Given that n-3 PUFA have many beneficial effects on cell and tissue function, while n-6 PUFA have mostly the opposite effects, estradiol, rather than progesterone, was seen to improve plasma lipids and phospholipids FA profiles in INT and BCO animals. Estradiol significantly elevated the estimated activity of Δ9-desaturases and progesterone of Δ5-desaturase in BCO group, with no effects in INT rats., S. Petrović, M. Takić, A. Arsić, V. Vučić, D. Drakulić, M. Milošević, M. Glibetić., and Obsahuje bibliografii
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 %), γ-linolenic (+22 %), dihomo-γ-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)., A. Žák, M. burda, M. Vecka, M. Zeman, E. Tvrzická, B. Staňková., and Obsahuje bibliografii
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., M. Kunešová, B. Sedláčková, O. Bradnová, E. Tvrzická, B. Staňková, P. Šrámková, K. Dolešalová, P. Kalousková, P. Hlavatý, M. Hill, B. Bendlová, M. Fried, V. Hainer, J. Vrbíková., and Obsahuje bibliografii
Leptin is a hormone primarily secreted by adipocytes and participating in the regulation of food intake and energy expenditure. Its blood levels usually correlate with adiposity. The secretion of this hormone is affected, among others, by food consumption, insulin, fasting and cold exposure. Regulation of leptin secretion depends on many intracellular events. It is known that the activation of mTOR (the mamma lian target of rapamycin) as well as increase in ATP and malonyl-CoA content in adipocytes enhance secretion of leptin. The rise in intracellular cAMP and fatty acids is thought to evoke the opposite effect. Moreover, the undisturbed action of endogenous adenosine in adipocytes and the proper intracellular Ca2+ concentration in these cells were also found to have an important function in leptin release. The role of mTOR, ATP, cAMP, fatty acids, malonyl-CoA, adenosine and Ca2+ in the regulation of leptin secretion from adipocytes is discussed., T. Szkudelski., and Obsahuje bibliografii a bibliografické odkazy
The apolipoprotein A-V (apo A-V) plays an important role in regulation of triglyceride (TG) concentration in serum. To better understand how apo A-V affects triglyceridemia and glucoregulation, the lipoprotein lipase (LPL) activity was determined using intravenous fat tolerance test (IVFTT) and oral glucose tolerance test (oGTT) was performed in carriers of apolipoprotein A-V gene ( APOAV) variants known to be associated with increased triglyceridemia. Twelve carriers of 19W variant, 16 carriers of -1131C variant, 1 combined heterozygote and 16 control subjects homozygous for wild type variants (19S/-1131T) were selected from a population sample and matched with respect to body mass index and age. The APOAV variants carriers had increased TG, very low density lipoprotein-TG, and apo B concentrations (p < 0.05). The LPL activity evaluated as k2 rate constant for clearance of Intralipid® was 14 % lower in APOAV variants carriers. The depression of nonesterified fatty acids (NEFA) concentration after glucose load was delayed in APOAV variants carriers in spite of the same insulinemia and glycemia. Our results suggest that variants of APOAV combined with increased triglyceridemia are associated with lower LPL activity in vivo and with disturbances of regulation of NEFA concentration after glucose load., J. Kovář, V. Adámková., and Obsahuje bibliografii a bibliografické odkazy