VLDL Concentrations Research Articles

The complex evaluation of lipid metabolism and blood coagulation system indicators for prediction and early diagnosis of the preeclampsia

Aim. To study informative and prognostic significance of lipid metabolism markers and coagulation system condition for PE early diagnostics in pregnant women during the second gestational trimester with risk evaluation of cardiovascular and metabolic pathologies in the given women category.Materials and methods. The analysis of blood serum samples in 267 pregnant women in II gestational trimester was carried out. The total cholesterol was determined by colorimetric method, enzymatic with CHOD/PAP, TG – by enzymatic colorimetric method, HDL – by homogeneous method, LDL – by direct method. VLDL concentration was calculated according to Fridvald's formula: VLDL = TG/2.2. AF was calculated according to the formula: AF = (TC-HDL-c)/HDL-c. Pregnant women in II and III gestational trimesters also were examined concerning the general assessment of coagulation system condition – the concentration in blood plasma of D-dimer, soluble fibrin (SFMC), fibrinogen, FIPF, protein C activity, AT III, blood plasma clotting time was determined by PT test.Results. Of the 267 pregnant women, in 43 (16.1 %) of them, which formed the main group for research, the development of PE was found. Those pregnant women, who had PE clinical picture of the different severity levels, from the second trimester had significantly elevated TG, VLDL, AF levels, and low level of HDL in blood serum with high concentration of D-dimer (from 80 to 713 ng/ml), as well as protein C low activity in 17.6 % of pregnant women. In the third trimester pregnant women, having PE, fibrinogen content was significantly higher (4.4±1.02); the accumulation of a significant amount of SF, accompanied by FIPF presence in 40 % of pregnant women, was found in 50 % of pregnant women; a significant reducing (˂70 %) of the protein C activity was found in 48 % of patients.Conclusion. Both significant increasing of the soluble fibrin in blood plasma, and reducing of the protein C activity below 70 % are thrombosis prognostic indexes. The control of lipid metabolism and coagulation system indexes is necessary during all stages of pregnancy for estimation of PE risk and cardiovascular,cerebral vascular and metabolic complications prevention

ATHEROGENIC PARAMETERS AND CARDIAC INDICES IN PROGNOSTICATION OF DEVELOPMENT OF PRE-ECLAMPSIA AND ITS CARDIOMETABOLIC CONSEQUENCES

Aim of the work. The study of interconnection between atherogenic parameters of the blood serum and cardiac indices during pregnancy with the risk of pre-eclampsia development and prognostication of remote cardio-vascular and/or metabolic pathology among pregnant. Materials and methods. The indices of lipid metabolism in the blood serum of 267 pregnant women were studied using diagnostic sets of reagents. The blood sampling was carried out in II (16-24 gestational weeks) trimester. The general cholesterol (GC) and triglycerides (TG) were determined by colorimetric and enzymatic method; high-density lipoproteins – HDL – by homogenous method of direct determination of HDL-cholesterol concentration in the blood serum without preliminary processing and centrifugation, low-density lipoproteins – LDL – by the direct method. VLDL concentration was calculated by Friedewald formula: LDL = TG/2,2. For evaluation of GC-VLDL concentration TG/2,2 parameter is used, if TG concentration is expressed in mmol/l (or TG/5, if concentration is expressed in mg/100 ml). Cardiac indices were calculated taking into account the lipid parameters according to the correspondent mathematical formulas. Lactate and LDH concentrations were determined by optimized method using diagnostic reagents. Lactate concentration was determined at the use of diagnostic set for determination of lactate concentration, and DLH was also determined by diagnostic set for determination of LDH (DL) activity by optimized method, elaborated taking into account the recommendations of German Association of clinical chemistry (DGKC) after correspondent calibration of automatic analyzer ACCENT-200 II GEN. Depending on the development of clinical presentation of PE 43 women were divided in groups with light and middle severity of course of this pathology. Results and discussion. Among the women with PE development was observed the essential changes in II trimester in the aspect of atherogenic parameters and cardiac indices mainly at the expense of progressing increase of TG in the blood serum (mmol/l: I group - 1,73 ± 0,14, II group - 1,86 ± 0,18 comparing with III control group - 1,51 ± 0,06. The gradual growth of cardiac (atherogenic) indices - AIP, CR and CА and connection between AIP and the levels of maternal serumal TG and arterial pressure were observed in women with PE development at the absence of such connection among the women of control group (p <0,05) . LDH level grew with the progressing of PE severity: for the women of I group LDH level was - 389 ± 1,6 U/l at 778 ± 0,25 in women of II group and 265 ± 0,19 in the control group (p <0,05). Conclusions. It was demonstrated, that hypertriglyceridemia at pregnancy is a predicator relative to PE development and together with progressive growth of atherogenic indices can be considered as prognostic factor for cardiometabolic pathology, especially in women with undergone severe forms of this pathology. It was established, that the increase of LDH level since the second trimester can also testify to the development of PE and remote cardiac pathology in this category of women.

Plasma lipids as risk factors in relapsing nephrotic syndrome

Background Nephrotic syndrome is primarily a pediatric disorderand is 15 times more common in children than in adults.Relapse rate after corticosteroid discontinuation is 39 - 59%.Hyperlipidemia is an important characteristic of nephroticsyndrome. The plasma concentrations of cholesterol, triglyceride,LDL, and VLDL are increased. Persistent hyperlipidemia afterremission can be found in frequent relapse nephrotic syndrome.Objective To determine plasma lipids as risk factor for relapsingnephrotic syndrome.Methods Thirty children with nephrotic syndrome were includedin this cohort study from March 2005 until June 2007 at WahidinSudirohusodo Hospital, Makassar. Thirty children without renal diseasewere enrolled as control. Blood specimens were collected to determineplasma lipids (cholesterol, triglyceride, LDL, and HDL) levels and LDUHDL ratio. Plasma lipids were examined in the acute and remissionphases. Follow up was carried out six months after remission todetermine the occurrence of relapsing nephrotic syndrome.Results Of 30 nephrotic syndrome patients, 12 had relapsed.There were highly significant differences in total cholesterol, HDL,LDL, triglyceride, and LDL/HDL ratio between acute nephroticsyndrome and nephrotic syndrome in remission. There were nosignificant differences in cholesterol, LDL, triglyceride, LDL!HDL ratio between nephrotic syndrome in remission and control.There was also no significant difference in the incidence in relapsebetween first attack and nephrotic syndrome with more than twoattacks. Acute lipid fraction levels were not risk factors in relapsingmephrotic syndrome. Remission triglyceride level was a risk factorin relapsing nephrotic syndrome with the prevalence risk of 5.2 andCI 95% of 1.06 to 25.3.Conclusion Persistent hypertriglyceride in remission phase isassociated with an increased risk of relapse in children withnephrotic syndrome.

Lean Seafood Intake Reduces Postprandial C-peptide and Lactate Concentrations in Healthy Adults in a Randomized Controlled Trial with a Crossover Design

Background: Recently we showed that lean seafood consumption reduced circulating triacylglycerol (TG) and VLDL concentrations and prevented an elevated total-to-HDL-cholesterol ratio relative to intake of a nonseafood diet.Objective: We aimed to elucidate whether diet-induced altered carbohydrate metabolism could be a contributing factor to the previously observed different lipoprotein patterns.Methods: This was a secondary outcome and explorative randomized controlled trial with a crossover design in 20 healthy adults (7 men and 13 women) that were 50.6 ± 3.4 (mean ± SEM) y old, weighed 75.7 ± 2.5 kg, and had a body mass index (BMI, in kg/m2) of 25.6 ± 0.7. After a 3-wk run-in period and separated by a 5-wk wash-out period, the participants consumed 2 balanced diets [in percentage of energy (energy%); 29% fat, 52% carbohydrates, 19% protein] for 4 wk. The diets varied in the main protein sources; 60 energy% of total protein was from either lean seafood or nonseafood sources. On the first and last day of each diet period, fasting and postprandial blood samples were collected before and after consumption of test meals (in energy%; 28% fat, 52% carbohydrates, 20% protein) with cod or lean beef.Results: The diets did not alter serum insulin and glucose concentrations. However, relative to the nonseafood diet period, the lean seafood diet period reduced postprandial C-peptide (P = 0.04) and lactate (P = 0.012) concentrations and fasting and postprandial TG/HDL-cholesterol ratios (P = 0.002). Hence, different postprandial lactate levels occurred at equal glucose concentrationsConclusions: Even though the diets did not alter serum insulin and glucose concentrations, intake of the lean seafood compared with the nonseafood diet reduced postprandial concentrations of C-peptide and lactate and the TG/HDL-cholesterol ratio in healthy adults in a manner that may affect the long-term development of insulin resistance, type 2 diabetes, and cardiovascular disease. This trial was registered at www.clinicaltrials.gov as NCT01708681.

English

The effect of methanolic extract of Citrullus lanatus seed on lipid profile and anti-oxidants in acetaminophen-induced hepatotoxic rats was investigated in the present study. A total of twenty (20) male Wistar rats were divided into five groups (n = 4). Group I served as normal control and were not exposed to paracetamol. Group II was exposed to 750 mg/kg body weight of paracetamol( intoxicated group),. Group III was administered with 0.5 ml distilled water, 5 mg/kg b. w of silymarin and group IV and V were administered with200 mg/kg and 400 mg/kg body weight of C. lanatus methanolic seed extract respectively.. We found that C. lanatus extract is safe at a dosage of up to 5000 mg/kg body weight. The biochemical analysis of current study showed significant (p 0.05) increase in VLDL, HDL and TAG concentration compared with the rats exposed to Paracetamol and 0.5 ml of distilled water (Vehicle). Moreover the animals exposed to 750 mg/kg b.w. of paracetamol and treated with 200 and 400 mg/kg b.w. of the extract showed significant (p< 0.05) increase in the antioxidant parameters compared to the animals exposed to 750 mg/kg b.w of paracetamol and0.5 ml of distilled water. The increase in the lipid profile of the treated animals reveal the ameliorating effect of dyslipidemia as observed in paracetamol intoxicated animals. Taken together methanolic seed extract of C. lanatus can substantiate its use as therapeutic agent against lipid imbalance and free radical generation in traditional system of medicine.

Up-regulation of Hnf1α gene expression in the liver of rats with experimentally induced chronic renal failure – A possible link between circulating PCSK9 and triacylglycerol concentrations

BackgroundThe aim of this study was to verify if an increase in Hnf1α gene expression could be a possible link between circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) and TAGs concentrations in chronic renal failure (CRF). MethodsRats underwent 5/6 nephrectomy or a sham surgery. Liver expressions of Pcsk9, Mttp, ApoB-100, Hnf1α, Hnf4α, lipogenic enzymes and β-actin genes were quantified by qPCR. Liver levels of proteins coding by these genes were analyzed by Western blotting. Serum apoB-100 and PCSK9 concentration were estimated with an immunoassay. ResultsCRF rats showed an increase in circulating concentrations of TAGs, VLDL, apoB-100 and PCSK9, along with an enhanced liver VLDL-TAG secretion rate and a coordinated liver up-regulation of genes coding: a) lipogenic enzymes; b) Mttp and ApoB-100; c) Pcsk9; d) Hnf1α and Hnf4α. Positive correlations were found between serum creatinine concentrations and: a) the liver levels of HNF1α mRNA (r = 0.79, p < 0.01) and HNF4α (r = 0.76, p < 0.01); b) the liver levels of PCSK9 mRNA (r = 0.88, p < 0.01) and serum PCSK9 concentrations (r = 0.73, p < 0.01); c) the liver levels of apoB-100 mRNA (r = 0.83, p < 0.01) and serum apoB-100 concentrations (r = 0.87, p < 0.01). Clofibrate treatment was shown to concomitantly decrease the liver levels of HNF1α, HNF4α and PCSK9 mRNA, as well as serum PCSK9, TAGs and total cholesterol concentrations in CRF rats. ConclusionThe results presented are consistent with a cause-effect relationship between the enhanced liver expression of Hnf1α gene and its target genes the products of which are involved in synthesis, assembly and secretion of VLDL, as well as Pcsk9 gene in CRF rats. This may at least in part explain an association between circulating PCSK9 and TAGs in CRF rats and possibly also in humans with chronic kidney disease (CKD).

Changes in serum fatty acid and lipoprotein subclass concentrations from prepuberty to adulthood and during aging.

Concentrations in serum were determined for 18 fatty acids (FAs) and 21 lipoprotein main and subclasses by chromatographic analyses and the average size was calculated for very low density (VLDL), low density (LDL) and high density (HDL) particles. 283 ethnic Norwegian children and adults from the rural Fjord region of Western Norway were compared with the objectives to reveal patterns and gender differences during the development from prepuberty to adulthood and during aging in adults. Both genders showed a large increase in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from child to adult. Males, but not females, show a significant increase in most C16–C18 FAs from prepuberty to adulthood. These changes in males correlate to a pattern of increased concentrations of triglycerides, VLDL and LDL particles, especially the atherogenic subclasses of small and very small LDL particles. Furthermore, concentrations of medium, large and very large HDL particles decrease, while concentration of very small HDL particles increase leading to reduced average size of HDL particles. Females only showed significant increase in concentrations of small and very small LDL particles, very small HDL particles and apolipoprotein B. While EPA and DHA continued to increase during aging in women, no validated model for connecting age to FA profile was obtained for men. Women showed significant increase in concentrations of all subclasses of LDL particles during aging, while men exhibited a more complex pattern with increase also in apolipoprotein A1 and HDL particles.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-016-0968-y) contains supplementary material, which is available to authorized users.

Alteration in different lipoprotein fractions in chronic renal failure patients

Background: Chronic renal failure, which is an inevitable terminal pathway of any chronic renal parenchymal disease, is more known for its morbidity than for its mortality. Objective: To note the alteration in different lipoprotein fractions among chronic renal failure patients. Methods: 70 Cases of chronic renal failure were taken for study. These patients were divided into two groups of 35 each. One group consisting of 35 Patients who were on conservative treatment, and the other group of 35 patients were on regular short term hemodialysis (6 months – 2 years). Patients were selected from Kasturba Medical College Hospitals and from Wenlock Government Hospital, Mangalore, from April 2001 to December 2003. Results: The HDL – cholesterol level was found to be significantly lower compared to control group. The total cholesterol and LDL was not raised significantly. The HDL/TC ratio was significantly reduced. Conclusion: Significant rise in triglyceride and VLDL concentration was seen in chronic renal failure patients.

Effect of adding L-carnitine and Protexin(R) probiotic on performance and some blood parameters of ostrich chickens

This study was conducted to investigate the effects of adding L-carnitine and Protexin(R) probiotic on performance and some blood parameters of ostrich chickens. In this study, a total of 48 one-day old ostrich chicks randomly divided into four treatment groups. Each treatment comprised of 4 replicates and 3 animals in each replicate and reared for 8 week. The experiment was arranged in a completely randomized design. The dietary treatments were: Treatment 1 (Control): Basal diet without supplementation; Treatment 2: Protexin(R) probiotic with level of 1 kg/t; Treatment 3: L-carnitine 500 mg/kg diet; Treatment 4: Protexin(R) probiotic with level of 500 kg/t + L-carnitine 250 mg/kg diet. The results of this study indicated that diet supplementation with L-carnitine and Protexin(R) probiotic increased ostrich chickens weight and feed intake at 8 weeks of age in comparison to other treatment groups. The other results showed no significant differences in feed conversion ratio (FCR) among different treatments at 8 week of ages and Broilers receiving L-carnitine + Protexin(R) probiotic had lowest FCR compared to the other tratment groups. Furthermore, diet supplementation with L-carnitine and Protexin(R) probiotic increased blood glucose concentration of ostrich chickens at 8 weeks of age in comparison to other treatment groups. Futher result showed that birds received L-carnitine + Protexin(R) probiotic had lowest total cholesterol in compersion to other treatment groups and birds receiving L-carnitine and Protexin(R) probiotic had lower HDL, LDL, and VLDL concentrations in compersion control group. There were no significant effect in calcium and phosphorus concentrations between control and other treatment groups.

Evacetrapib alone or in combination with statins lowers lipoprotein(a) and total and small LDL particle concentrations in mildly hypercholesterolemic patients

Potent CETP inhibitors reduce plasma concentrations of atherogenic lipoprotein biomarkers of cardiovascular risk. To evaluate the effects of the cholesteryl ester transfer protein (CETP) inhibitor evacetrapib, as monotherapy or with statins, on atherogenic apolipoprotein B (apoB)-containing lipoproteins in mildly hypercholesterolemic patients. VLDL and LDL particle concentrations and sizes (using nuclear magnetic resonance spectroscopy) and lipoprotein(a) concentration (using nephelometry) were measured at baseline and week 12 in a placebo-controlled trial of 393 patients treated with evacetrapib as monotherapy (30mg/d, 100mg/d, or 500mg/d) or in combination with statins (100mg plus simvastatin 40mg/d, atorvastatin 20mg/d, or rosuvastatin 10mg/d; Clinicaltrials.gov Identifier: NCT01105975). Evacetrapib monotherapy resulted in significant placebo-adjusted dose-dependent decreases from baseline in Lp(a) (up to -40% with evacetrapib 500mg), total LDL particle (LDL-P) (up to -54%), and small LDL particle (sLDL) (up to -95%) concentrations. Compared to statin alone, coadministration of evacetrapib and statins also resulted in significant reduction from baseline in Lp(a) (-31%), LDL-P (-22%), and sLDL (-60%) concentrations. The percentage of patients with concentrations above optimal concentrations for LDL-P (>1000nmol/L) and sLDL (>600nmol/L) decreased from 88% and 55% at baseline, respectively, to 20% and 12% at week 12, for patients treated with evacetrapib plus statins. Evacetrapib, alone or with statins, significantly increased LDL-P size. Evacetrapib, as monotherapy or with statins, significantly reduces the concentrations of atherogenic apoB-containing lipoproteins, including Lp(a), LDL-P, and sLDL.

INCLUSION OF DRIED AGRO-INDUSTRIAL STRAWBERRY BY- PRODUCTS IN GROWING RABBIT DIETS

This experiment was conducted to evaluate the effect of using dried strawberry by-product (ASB) in growing rabbit diets on growth performance, nutrients digestibility coefficients, some blood parameter and relative economic efficiency. Seventy two weaned male New Zealand White rabbits at 6 weeks received diets containing 0, 25, 50 and 75% ASB as a replace of berseem hay. The growth trial lasted for 8 weeks. Results obtained could be summarized as follows: There were significant increases in body weight gain with increasing ASB levels in the diets. Whereas, feed consumption and feed conversion ratio were not significantly affected by ASB feeding. Ether extract digestibility coefficients were significantly decreased with increasing dietary level of ASB, while the digestibility coefficients of DM, OM, CP and CF were higher in treatments containing ASB, while the digestibility coefficients of OM, CP and CF were significantly higher in treatments containing ASB. Dressing percentages of rabbits were significantly higher with 75% ASB feeding compared with other treatments. Dietary ASB treatments had no significant effects on meat chemical analysis (moisture, DM and CP contents). But EE and ash contents were decreased with ASB feeding. Blood plasma concentrations of triglycerides, cholesterol, LDL, vLDL and total lipids were significantly decreased with increasing the level of ASB in rabbit diets. Feeding ASB had a significant positive effect on blood plasma antioxidant profile. Leveling up dietary ASB inclusion rate decreased MDA level and increased the TAC capacity in an incremental manner with increasing ASB of the diet. Using ASB as a feed ingredient improved the relative economic efficiency of diets. It could be concluded that ASB can be used in the growing rabbit diets with no adverse effects on performance and health status of the rabbit. Besides, ASB could reduce the cost of the diet.

CHANGES OF STRESS HORMONES LEVELS AND SERUM LIPID SPECTRUM INDICATORS OF RATS IN ACUTE CEREBRAL ISCHEMIA

Objective: to study the changes of stress hormones levels and serum lipid spectrum indicators of Wistar male rats in acute cerebral ischemia (ACI). Material and methods . The study was performed on 40 mature Wistar male rats weighing 220-300 g. ACI simulation was performed by means of 3-hour chronic occlusion of bilateral common carotid arteries (n = 23). The control group consisted of intact animals (n = 17). The levels of total cholesterol (TC, mmol/l), triglyceride (TG, mmol/l), high density lipoproteins (HDL, mmol/l), low density lipoprotein (LDL, mmol/l), lipoproteins of very low density (VLDL mmol/l), adrenocorticotropic hormone (ACTH nmol/l), and cortisol (nmol/l) were assessed in the serum of the rats. Atherogenic index (AI) was calculated according to the formula: AI = (TC-HDL) / HDL. Results. TC concentration in the serum of the rats of the experimental group was 1.1 times as high (p = 0.03), the concentration of TG - 1.2 times as high (p = 0.012), the concentration of VLDL - 2 times as high (p = 0.01), cortisol concentration - 1.4 times as high (p = 0.02) compared with the control group. The rats of the experimental group revealed a moderate inverse correlation between the levels of cortisol and index AI (p = 0.025). The group of ACI rats observed a tendency of direct relation of ACTH with TG and LDL serum, p &gt; 0.05. The correlation of ACTH and serum triglycerides in the rats of the control group was statistically significant (p = 0.012). Conclusion: ACI during the period «therapeutic window» in rats is accompanied by a complex set of compensatory and adaptive reactions which may be characteristic of a generalized stress response.

Effects of Short-Period Whole-Body Vibration of 20 Hz on Selected Blood Biomarkers in Wistar Rats.

There is a growing interest in the use of vibration generated by oscillating/vibratory platforms - also known as whole-body vibration (WBV) - for achieving therapeutic, preventative and/or physical performance goals. This study investigated the effects of vibration generated by an oscillating platform on the concentration of blood biomarkers in rats. Wistar rats (n = 8) were divided in 2 groups, sedated and individually positioned on an oscillating platform. The experimental group (EG) was subjected to vibrations of 20 Hz for one min per day for one week while the control group (CG) experienced no vibration. Samples of heparinized whole blood were drawn by cardiac puncture for biochemical analysis. Concentrations of total cholesterol, triglycerides, HDL, LDL, VLDL, glucose, CK, albumin, alkaline phosphates, TGP, TGO, γGT, lipase, amylase, urea and creatinine were determined. White blood cell count and a platelet hemogram were also performed. Following seven sessions of exposure to the vibration, a significant (P < 0.05) reduction in γGT, VLDL and leukocytes was found. A weekly 1-min/day exposure of 20 Hz vibration can was shown to alter the concentrations of selected blood biomarkers in rats. The action mechanism associated with these effects seems highly complex, but the findings might contribute to the understanding of these mechanisms related to the exposure to 20 Hz vibration.

Endothelial nitric oxide synthase Glu298Asp gene polymorphism influences body composition and biochemical parameters but not the nitric oxide response to eccentric resistance exercise in elderly obese women

Both endothelial nitric oxide synthase (eNOS) gene polymorphism and nitric oxide (NO) are involved in important cardiovascular, muscular and inflammatory physiological mechanisms during ageing and response to exercise. The aim of this study was to investigate the NO kinetic response following an acute eccentric resistance exercise (ERE) session and the possible effect of the Glu298Asp eNOS gene polymorphism in elderly obese women. Eighty-seven women (age 69·4±6·1years, body weight 74·9±12·7kg, height 151·9±6·0cm and BMI 32·5±5·7kgm-2 ) completed seven sets of ten eccentric repetitions at 110% of the ten repetitions maximum (10RM). NO concentrations remained elevated up to 48h following the acute ERE session as compared with baseline, for GG and GT/TT groups (P<0·05), with no differences between genotypes. The GG genotype group had higher body weight, prevalence of obesity (BMI classification - 81% versus 56%), BMI and higher relative muscle strength, while they had significantly lower triglycerides, VLDL and urea concentrations as compared with TT/TG group. In conclusion, NO remains elevated for up to 48h after an acute ERE session, without genotype interaction. The TT/TG genotype had a negative impact on triglycerides, VLDL and urea concentrations. Thus, T carriers should increase their attention to cardiovascular risk factor and metabolic disorders.

Metabolic Abnormalities in Erythrocyte Membranes and Liver Tissue Homogenates in Experimental Diabetes Mellitus.

Considerable changes in serum lipids and lipoprotein profiles associated with hypertriglyceridemia, hypercholesterolemia, increased VLDL and LDL concentrations, and reduced HDL level occur at the early stages of streptozotocin-induced diabetes (day 7) in rats. The level of saturated palmitic fatty acid increased and the levels of monounsaturated fatty acids decreased at the expense of oleic acid, which considerably differed from changes in these parameters observed in patients with diabetes mellitus. Our findings suggest that changes in the lipid composition and fatty acid pool in erythrocytes and liver homogenates are pro-atherosclerotic already in the early stages of diabetes development.

Hepatocyte-Specific Depletion of UBXD8 Induces Periportal Steatosis in Mice Fed a High-Fat Diet.

We showed previously that UBXD8 plays a key role in proteasomal degradation of lipidated ApoB in hepatocarcinoma cell lines. In the present study, we aimed to investigate the functions of UBXD8 in liver in vivo. For this purpose, hepatocyte-specific UBXD8 knockout (UBXD8-LKO) mice were generated. They were fed with a normal or high-fat diet, and the phenotypes were compared with those of littermate control mice. Hepatocytes obtained from UBXD8-LKO and control mice were analyzed in culture. After 26 wk of a high-fat diet, UBXD8-LKO mice exhibited macrovesicular steatosis in the periportal area and microvesicular steatosis in the perivenular area, whereas control mice exhibited steatosis only in the perivenular area. Furthermore, UBXD8-LKO mice on a high-fat diet had significantly lower concentrations of serum triglyceride and VLDL than control mice. A Triton WR-1339 injection study revealed that VLDL secretion from hepatocytes was reduced in UBXD8-LKO mice. The decrease of ApoB secretion upon UBXD8 depletion was recapitulated in cultured primary hepatocytes. Accumulation of lipidated ApoB in lipid droplets was observed only in UBXD8-null hepatocytes. The results showed that depletion of UBXD8 in hepatocytes suppresses VLDL secretion, and could lead to periportal steatosis when mice are fed a high-fat diet. This is the first demonstration that an abnormality in the intracellular ApoB degradation mechanism can cause steatosis, and provides a useful model for periportal steatosis, which occurs in several human diseases.

Amount of hepatic fat predicts cardiovascular risk independent of insulin resistance among Hispanic-American adolescents.

BackgroundNonalcoholic fatty liver disease (NAFLD) has emerged as the major pediatric chronic liver disease, and it is estimated to affect more than one third of obese children in the U.S. Cardiovascular complications are a leading cause of increased mortality in adults with NAFLD and many adolescents with NAFLD already manifest signs of subclinical atherosclerosis including increased carotid intima-media thickness.MethodsVolume of intrahepatic fat was assessed in 50 Hispanic-American, overweight adolescents, using Magnetic Resonance Spectroscopy. Lipoprotein compositions were measured using Nuclear Magnetic Resonance.ResultsPlasma triglycerides (TG) (p = 0.003), TG/HDL ratio (p = 0.006), TG/apoB ratio (p = 0.011), large VLDL concentration (p = 0.019), VLDL particle size (p = 0.012), as well as small dense LDL concentration (p = 0.026) progressively increased across higher levels of hepatic fat severity, while large HDL concentration progressively declined (p = 0.043). This pattern of associations remained even after controlling for gender, BMI, visceral fat, and insulin resistance.ConclusionsOur findings suggest that increased hepatic fat is strongly associated with peripheral dyslipidemia and the amount of fat in the liver may influence cardiovascular risk. Further studies are needed to longitudinally monitor dyslipidemia in children with NAFLD and to examine whether the reduction of hepatic fat would attenuate their long-term CVD risk.

Compared to Regular Lutein, a Lutein Nano‐Emulsion Yields a More Atherogenic Lipoprotein Profile Associated with Higher Concentrations of Cholesterol in Adipose Tissue in Guinea Pigs

We challenged 24 guinea pigs (8/group) with a high cholesterol diet (0.25g/100g) alone (control group) or in combination with 3 mg/d of Regular lutein (R‐lutein) or 3 mg/d of lutein prepared in nano‐emulsion (NANO) (average particle diameter = 250 nm). After 6 weeks, guinea pigs were sacrificed and blood was collected to measure plasma lipids and lipoprotein size and number by Nuclear Magnetic Resonance and adipose was harvested to determine concentrations of both free and esterified cholesterol. Contrary to what we expected, guinea pigs from the NANO group had the greatest concentrations of plasma cholesterol (P&lt;0.001). In addition, the NANO group had higher concentrations of large VLDL and total LDL particles (p&lt;0.0001). Moreover, cholesterol concentration in the adipose tissue was highest in the NANO group (11.5 ± 2.5 mg/g), intermediate in the control group (10.2 ± 1.5 mg/g) and lowest in the R‐lutein group (9.2 ± 0.8 mg/g) (p&lt; 0.01). In contrast hepatic cholesterol concentrations were highest in the NANO compared to the R‐lutein and control groups (P &lt; 0.01). Further, we found a positive correlation between plasma cholesterol and free cholesterol in the adipose (r = 0.493, p = 0.014) and with large VLDL (r = 0.700, P &lt; 0.001). These data suggest that guinea pigs fed the NANO emulsion have lower concentrations of cholesterol in the liver because they are secreting cholesterol in the large VLDL particles and possibly both lipoproteins VLDL and LDL are depositing the excess cholesterol in extra‐hepatic tissues (adipose), possibly via scavenger receptors

Small-dense LDL/large-buoyant LDL ratio associates with the metabolic syndrome

ObjectiveHeterogeneous particles of intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) vary in atherogenesis. We investigated the association between the metabolic syndrome (MetS) score and lipoprotein subclasses. Design and methodsA total of 260 outpatients were scored into six groups, based on their number of MetS components. Lipoprotein subclass determined by polyacrylamide tube gel electrophoresis separates IDL particles into three midbands (MID-A to C) and LDL into larger-buoyant (LDL1 and LDL2) and small-dense LDL (LDL3 to LDL6). ResultsMean concentrations of VLDL, MIDC, LDL2, and LDL3 to LDL6 positively correlated with increasing MetS score, but those of MIDA, LDL1 and HDL-C inversely correlated. LDL2 and LDL3 to LDL6 increased while MIDA and LDL1 decreased with increasing visceral fat, HOMA-IR, and triglycerides, with a reverse pattern for HDL-C. MIDB and MIDC were unchanged. By logistic regression, LDL1 and LDL3 to LDL6 significantly associates with the MetS score (odds ratio=0.957 and 1.077, respectively). The ratio of (LDL3 to LDL6)/LDL1 in the presence of HDL-C, showed the strongest association with MetS. ConclusionsRespective subpopulations of IDL and LDL particles can vary in their ability to identify MetS. Because of the most strongly associated with MetS, (LDL3 to LDL6)/LDL1 ratio is proposed as an excellent marker for evaluating lipid metabolic status in patient with MetS.

Lipid spectrum changes and ECG in patients with paranoid schizophrenia in the course of therapy with atypical antipsychotics

To study correlations between parameters of lipid metabolism and ECG in patients with schizophrenia in light of therapy with atypical antipsychotics. We examined 42 patients with paranoid schizophrenia. All patients received atypical neuroleptics - seroquel, zyprexa, and rispolept. A group of controls included 25 healthy people. There was a significant increase (p=0.0002) in body mass (in average by 1.5 kg) in 88% patients. A significant increase in the concentration of serum triglycerides was identified as well. The concentration of VLDL in the patients with schizophrenia was 2 times higher compared to controls. After treatment, VLDL concentration increased even more considerably An increase in atherogenic index (AI) was up to 3.1 in patients with schizophrenia compared to 2.2 in controls. After treatment, Al increased up to 4 that demonstrated the high risk of development of atherosclerosis. A significant increase in QT interval in the ECG and heart rate (p=0.03) was revealed only in patients receiving rispolept. In patients receiving zyprexa and seroquel only heart rate was increased. The antipsychotics studied increase the risk of development of cardiovascular pathology.