Increase In Triglycerides Research Articles

Влияние иммунокорригирующей терапии на состояние липидного спектра крови у беременных с внутриутробным инфицированием

The objective: to study the effect of immunocorrecting therapy on the state of blood lipid spectrum in pregnant with intrauterine infection. Patients and methods. The study involved examination of three groups of pregnant with viral, bacterial and mixed infection. Each of the groups was divided into 2 subgroups: with subsequent implementation of infection in newborns and without it. Control group included patients with physiological pregnancy. The pregnant received immunocorrecting therapy. Blood serum was assessed to determine the levels of total cholesterol (TC), triglycerides (TG), high, low and very low density lipoproteins (HDL, LDL, VLDL). Results. The study implied the assessment of the effect of the elaborated immunocorrecting complex on the state of blood lipid spectrum in pregnant with intrauterine infection. In the group of patients with viral infections, regardless of its subsequent implementation, the use of the developed therapeutic complex triggered activation of cholesterol metabolism and reduction of hypertriglyceridemia to normal TG content in blood. In patients with bacterial infection, regardless of its implementation, the performed treatment resulted in cholesterol metabolism normalization. In the subgroup with mixed infection in its implementation, the treatment neutralized triglyceridemia and normalized TG level. In the subgroup with mixed infection without its implementation, the treatment allowed to normalize the level of TG and VLDL and increase HDL. Conclusions. The use of the elaborated immunocorrecting therapy has a positive effect on the metabolism of lipids, which reflects the lipid profile of blood. The main effect of the treatment is the normalization of the levels of triglycerides in pregnant and their carriers VLDL, and this effect is manifested with all the variants of infection under investigation. The detected increase in the level of HDL is indicative of an increase in the reverse transport of cholesterol and activation of its metabolism. This allows us to consider that the use of this therapeutic complex stimulates compensatory metabolic processes in the body of pregnant women, despite the presence of infection. Key words: intrauterine infection, lipid spectrum, immunocorrecting therapy.

СОДЕРЖАНИЕ ОБЩЕГО ХОЛЕСТЕРИНА И ТРИГЛИЦЕРИДОВ В НАЗОФАРИНГЕАЛЬНОМ АСПИРАТЕ ПРИ ЦЕРЕБРАЛЬНОЙ ИШЕМИИ СРЕДНЕЙ СТЕПЕНИ ТЯЖЕСТИ У НОВОРОЖДЕННЫХ ОТ МАТЕРЕЙ С ЦИТОМЕГАЛОВИРУСНОЙ ИНФЕКЦИЕЙ В ПЕРИОД БЕРЕМЕННОСТИ

The contents of total cholesterol (TC) and triglycerides (TG) in nasopharyngeal aspirate were studied in 233 mature newborns from mothers with normal pregnancy and complicated with cytomegalovirus infection (CMVI). The first (control) group included 30 babies of 38-40 weeks from mothers with physiological course of pregnancy. Among the newborns with moderate cerebral ischemia and antenatal history complicated with chronic CMVI in their mothers in the second trimester of pregnancy, four groups were distinguished and each of them was divided into two subgroups. Subgroup A had patients whose mothers did not have the threat of miscarriage during pregnancy and subgroup B had children from mothers who had the threat of miscarriage in the second trimester of gestation. The second group included 50 newborns whose mothers had a latent course of chronic CMVI; the third group included 50 children from mothers with reactivation of chronic CMVI (antibody titers of IgM to CMV were 1:200-1:400, antibody titers of IgG to CMV were 1:200-1:400, the avidity index of IgG antibodies to CMV was more than 65%); the fourth group consisted of 51 newborns whose mothers suffered an acute form of chronic CMVI (antibody titers of IgM to CMV were 1:200-1:400, antibody titers of IgG to CMV were 1:200-1:800, avidity index of IgG antibodies to CMV was more than 65%); and the fifth group had 52 children from mothers who suffered a reactivation of chronic CMVI (antibody titers of IgM to CMV were 1:200-1:400, antibody titers of IgG to CMV were 1:400-1:600, avidity index of IgG antibodies to CMV was more than 65%). The children of 2A, 3A and 4A subgroups, in comparison with the first group, in nasopharyngeal aspirate did not have any significant changes in the contents of TC and TG. In 5A subgroup against the absence of reliable differences of TG concentration there was registered a fall of TC level till 0.189±0.015 mmole/L (in control and 2A subgroup it was 0.250±0.016 mmole/L, p<0.01 and 0.246±0.015 mmole/L, p<0.01, respectively). When comparing the lipid composition of nasopharyngeal aspirate in newborns of 2B and 3B subgroups with the one taken from healthy children there were not found any significant differences in TC and TG. But in 4B and 5B subgroups there was a fall of TC till 0.191±0.014 mmol/L (p<0.01) and till 0.146±0.010 mmole/L (p<0.001), while the values of TG grew till 0.169±0.009 mmole/L (p<0.05) and till 0.198±0.009 mmole/L (p<0.001); at the same time the contents of TG in the first group was only 0.142±0.008 mmole/L. Thus in newborns with moderate cerebral ischemia and antenatal history complicated with 4 times growth of antibody titers of IgG to CMV and the threat of miscarriage in the second trimester of gestation, the decrease of TC can lead to less expressed compensatory-adaptive reactions, and the increase of TG, including fatty acids peroxides, results in the starting of mechanisms of intrauterine degradation of pulmonary surfactant and membrane-destructive processes in central nervous system.

Lactobacillus fermentum FTDC 8312 combats hypercholesterolemia via alteration of gut microbiota

In this study, hypercholesterolemic mice fed with Lactobacillus fermentum FTDC 8312 after a seven-week feeding trial showed a reduction in serum total cholesterol (TC) levels, accompanied by a decrease in serum low-density lipoprotein cholesterol (LDL-C) levels, an increase in serum high-density lipoprotein cholesterol (HDL-C) levels, and a decreased ratio of apoB100:apoA1 when compared to those fed with control or a type strain, L. fermentum JCM 1173. These have contributed to a decrease in atherogenic indices (TC/HDL-C) of mice on the FTDC 8312 diet. Serum triglyceride (TG) levels of mice fed with FTDC 8312 and JCM 1173 were comparable to those of the controls. A decreased ratio of cholesterol and phospholipids (C/P) was also observed for mice fed with FTDC 8312, leading to a decreased number of spur red blood cells (RBC) formation in mice. Additionally, there was an increase in fecal TC, TG, and total bile acid levels in mice on FTDC 8312 diet compared to those with JCM 1173 and controls. The administration of FTDC 8312 also altered the gut microbiota population such as an increase in the members of genera Akkermansia and Oscillospira, affecting lipid metabolism and fecal bile excretion in the mice. Overall, we demonstrated that FTDC 8312 exerted a cholesterol lowering effect that may be attributed to gut microbiota modulation.

Effects of a liquid high-fat meal on postprandial lipid metabolism in type 2 diabetic patients with abdominal obesity

BackgroundPostprandial lipemia and lipoprotein lipase (LPL) activity play crucial roles in the pathogenesis of accelerated atherosclerosis. This study aimed to evaluate the postprandial lipid metabolism after the ingestion of a liquid high-fat meal in type 2 diabetic patients with abdominal obesity, and determine if the PvuII polymorphisms of LPL influence their postprandial lipid responses.MethodsSerum glucose, insulin, triglycerides (TG), total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) were measured in fasting and postprandial state at 0.5, 1, 2, 4, 6 and 8 h after a liquid high-fat meal in 51 type 2 diabetic patients with abdominal obesity, 31 type 2 diabetic patients without abdominal obesity and 39 controls. Their PvuII polymorphisms of LPL were tested in fasting.ResultsType 2 diabetic patients with abdominal obesity had significantly higher postprandial areas under the curve (AUC) of glucose [least square mean difference (LSMD) = 30.763, 95% confidence interval (CI) = 23.071–38.455, F = 37.346, P < 0.05] and TC (LSMD = 3.995, 95% CI = 1.043–6.947, F = 3.681, P < 0.05) than controls. Postprandial AUCs for insulin, homeostasis model assessment-insulin resistance (HOMA-IR) and TG were higher (LSMD = 86.987, 95% CI = 37.421–136.553, F = 16.739, P < 0.05; LSMD = 37.456, 95% CI = 16.312–58.600, F = 27.012, P < 0.05; LSMD = 4.684, 95% CI = 2.662–6.705, F = 26.158, P < 0.05), whereas HDL-C AUC was lower (LSMD = −1.652, 95% CI = −2.685 – -0.620, F = 8.190, P < 0.05) in type 2 diabetic subjects with abdominal obesity than those without abdominal obesity. In type 2 diabetic patients with abdominal obesity, postprandial TG AUC was lower in P−/− than in P+/− (LSMD = −4.393, 95% CI = −9.278 – -0.491, F = 4.476, P < 0.05) and P+/+ (LSMD = −7.180, 95% CI = −12.319 – -2.014, F = 4.476, P < 0.05) phenotypes. Postprandial AUCs for glucose, insulin, HOMA-IR, TC and HDL-C were not different according to PvuII phenotypes.ConclusionsAbdominal obesity exacerbates the postprandial lipid responses in type 2 diabetic patients, which partly explains the excess atherogenic risk in these patients. In addition, the presence of P+ allele could contribute to a greater postprandial TG increase in type 2 diabetic patients with abdominal obesity.Trial registrationChiCTR-IOR-16008435. Registered 8 May 2016.

Lipid profile and pre – eclampsia

Objective: To assess if there are changes in lipid profile in preeclampsia and if these changes can be used as marker of severity of the condition.Study design: This study include 100 pregnant women divided into 3 groups.1) 25 pregnant women with sever pre-eclampsia in the third trimester.2) 25 pregnant women with mild-moderate pre-eclampsia in the thirdtrimester .3) 50 apparently healthy pregnant women of comparable age &amp;parity in the third trimester. All were investigated for serum lipid profile includingserum cholesterol(CH)serum triglyceride(TG)serum high density lipoprotein(HDL)serum low density lipoprotein(LDL)serum very low density lipoprotein(VLDL)&#x0D; Result: There was significant increase in serum TG ,VLDL and LDL level in women with pre -eclampsia than the control group and no significant difference in the serum cholesterol, while patient with preeclampsia had lower HDL level. When we compare patient with sever pre-eclampsia with patient with mild pre - eclampsia we found that women with sever pre -eclampsia has significantly higher level of TG and VLDL only.

Development of Metabolic Syndrome in Drug-Naive Adolescents After 12 Months of Second-Generation Antipsychotic Treatment.

Mental illness is often accompanied by poor physical health and shorter life expectancy. Second-generation antipsychotics (SGAs) are suspected of increasing cardiovascular risk, possibly through development of metabolic syndrome (MetS), and the risk of adverse outcome is even higher if obesity or metabolic aberration starts in childhood or adolescence. Drug-naive adolescents were recruited after contact with an outpatient Psychosis Team. Changes relative to baseline in body mass index (BMI), waist circumference (WC), blood pressure (BP), fasting blood glucose (FBG), triglycerides (TG), and high-density lipoprotein (HDL) cholesterol were determined through regular follow-ups. The sample included 35 SGA-naive patients aged 7-19 (mean: 15.5) with a diagnosis of psychosis. Over 12 months, the overall rate of MetS changed significantly (from 0% to 20% [p < 0.016]). There was a significant increase in BMI (18.4% [p < 0.001]), WC (14.3% [p < 0.001]), TG (25.2% [p = 0.039]), and FBG (3.6% [p = 0.038]), whereas there was a significant decrease in HDL (-11.5% [p < 0.001]). No significant change was found for BP. Compared with the 2014 Danish references BMI-for-age charts, after 12 months the participants' BMI had increased from 0.5 to 1.57 standard deviation (SD) above the 50th percentile for age and gender (p = 0.0001). To our knowledge, this is the first study to include all the aspects of MetS in a sample of drug-naive adolescents followed over the first 12 months after starting SGA treatment. A significant shift in all parameters (except BP) toward MetS was found, presumably due to SGA use. Therefore, these adolescents will need proper follow-up, consisting of not only monitoring but also preventive measures to diminish these effects of SGA use.

Antioxidant potential and hypolipidemic effect of whey protein against gamma irradiation induced damages in rats

PurposeEvaluation of the efficacy of whey protein as antioxidant against γ-irradiation induced oxidative stress and dyslipidemia in male rats. MethodRats were divided into groups; group 1 (control), rats in group 2 & 3 were exposed to γ-irradiation 5 & 10Gy respectively and rats in group 4 & 5 were orally administrated with whey protein after γ-irradiation. The antioxidant status (glutathione (GSH), Superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC) and malondialdehyde (MDA), lipid profile (total cholesterol (TC), triglyceride (TG) and high-density lipoprotein (HDL) as well as the hematological parameters were determined. Resultsγ-irradiation had depletion in GSH, SOD, CAT and TAC levels and elevation in MDA. Moreover, an increase in TC & TG coupled with decrease in HDL after γ-irradiation. The hematological parameters decreased after γ-irradiation. Treated rats with whey protein improved the antioxidant status and minimized the alterations of lipid and blood cells induced by γ-irradiation. Conclusionwhey protein has a positive effect on lipid and antioxidant status to minimize the oxidative stress due to exposure to γ-irradiation.

Antioxidant and anti-inflammatory effects of dimethyl fumarate in hypercholesterolemic rabbits

The present study aimed to determine the possible beneficial effects of dimethyl fumarate (DMF) against oxidative stress and inflammation in hypercholesterolemic rabbits. Twenty four New Zealand male rabbits were randomly allocated into 4 groups as the following: Group I (control): rabbits received standard rabbit chow; Group II high cholesterol diet (HCD): rabbits received 1% cholesterol-enriched chow for 4weeks; Group III (HCD-DMF): rabbits received 1% cholesterol-enriched chow and administered DMF (12.5mg/kg/day, orally) for 4weeks; Group IV (DMF): rabbits received standard chow plus DMF (12.5mg/kg/day, orally) for 4weeks. At the end of experiment (day 30), blood samples were collected for measuring serum total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C) and C-reactive protein (CRP). In addition, the aorta was removed for measurement of malondialdehyde (MDA), superoxide dismutase (SOD), mRNA expression of cholesteryl ester transfer protein (CETP) and histological assessment of intima/media (I/M) ratio. HCD-fed rabbits showed significant increases in TGs, TC, low-density lipoprotein cholesterol (LDL-C), aortic MDA and aortic I/M ratio levels while they significantly exhibited a reduced SOD level relative to control animals. Moreover, HCD rabbits demonstrated upregulated mRNA expression of CETP. DMF administration significantly decreased HCD-induced elevations in serum TC and LDL-C. Additionally, DMF decreased aortic level of MDA while increased SOD level. Moreover, DMF significantly downregulated mRNA expression of CETP and reduced the elevation in I/M ratio.In conclusion, this study suggests that DMF has the ability to improve HCD-induced vascular irregularities, possibly via its anti-inflammatory and antioxidant effect.

Evaluation of HIV therapeutic agents on immunological, lipid and lipoprotein indices in Ghanaian HIV-1 infected patients

HIV-1 infected patients initiating antiretroviral therapy (ART) in Ghana are placed on one of the two most commonly used non-nucleoside reverse transcriptase inhibitors (NNRTIs), nevirapine (NVP) and efavirenz (EFV), in combination with a nucleoside reverse transcriptase inhibitor backbone of either combivir (CBV) or stavudine (d4T)/lamivudine (3TC). This study sought to evaluate the effect of these therapeutic agents on weight, immunological, lipid and lipoprotein changes as well as the atherogenic indices of Ghanaian HIV-1 infected patients. This observational study was carried out at the ART clinic of the Regional Hospital, Bolgatanga in the Upper-East region of Ghana from September 2008 to September 2009 comprising 61 HIV-1 infected patients who were initiated on NVP or EFV in combination with either CBV or d4T/3TC. Out of the 61 enrolled patients, 27(44.3%) were on NVP and 34(55.7%) were on EFV. Within the NVP group, 16 (59.3%) were on CBV and 11(40.7%) on d4T/3TC whilst the EFV group had 26(76.5%) on CBV and 8 (23.5%) on d4T/3TC. Percentage changes in lipid profile components comprising total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-c) and low density lipoprotein cholesterol (LDL-c) was assessed over the 12-month period. Percentage changes in atherogenic index expressed as TC/HDL-c and LDL-c/HDL-c was also estimated. NVP elicited a 10.2% increase in weight compared to EFV and this was associated with CBV combination use. EFV further elicited a 9.1% increase in TC, 1.2% increase in TG, 39.3% increase in LDL-c and a 4.1% increase in HDL-c which resulted in concomitant percentage increases in TC/HDL-c (22%) and LDL-c/HDL-c (47.3%). CBV as a NRTI component of EFV elicited a 4.3% increase in TC/HDL-c and a 16.6% increase in LDL-c/HDL-c compared to d4T/3TC whilst conversely, d4T/3TC elicited a 3.6% increase in TC/HDL-c and a 34.0% when used in combination with NVP. NVP combination therapy elicited improvement in weight compared to EFV combination therapy for the different categories of patients. The less atherogenic lipid profile observed in patients taking NVP in comparison to those taking EFV and the reduction in CHD risk associated with NVP + CBV combination therapy observed in this study should be factored into considerations taken when selecting the most appropriate ART regimen for treatment naïve HIV-1 infected patients.Journal of Medical and Biomedical Sciences (2016) 5(3), 13-27Keywords: HIV-1, Antiretroviral therapy, Immunological, Lipids, Atherogenic indices, Bolgatanga, Ghana

ANGPTL8 requires ANGPTL3 to inhibit lipoprotein lipase and plasma triglyceride clearance

Angiopoietin-like (ANGPTL)3 and ANGPTL8 are secreted proteins and inhibitors of LPL-mediated plasma triglyceride (TG) clearance. It is unclear how these two ANGPTL proteins interact to regulate LPL activity. ANGPTL3 inhibits LPL activity and increases serum TG independent of ANGPTL8. These effects are reversed with an ANGPTL3 blocking antibody. Here, we show that ANGPTL8, although it possesses a functional inhibitory motif, is inactive by itself and requires ANGPTL3 expression to inhibit LPL and increase plasma TG. Using a mutated form of ANGPTL3 that lacks LPL inhibitory activity, we demonstrate that ANGPTL3 activity is not required for its ability to activate ANGPTL8. Moreover, coexpression of ANGPTL3 and ANGPTL8 leads to a far more efficacious increase in TG in mice than ANGPTL3 alone, suggesting the major inhibitory activity of this complex derives from ANGPTL8. An antibody to the C terminus of ANGPTL8 reversed LPL inhibition by ANGPTL8 in the presence of ANGPTL3. The antibody did not disrupt the ANGPTL8:ANGPTL3 complex, but came in close proximity to the LPL inhibitory motif in the N terminus of ANGPTL8. Collectively, these data show that ANGPTL8 has a functional LPL inhibitory motif, but only inhibits LPL and increases plasma TG levels in mice in the presence of ANGPTL3.

Enrichment of Triglyceride-Rich Lipoproteins with Apolipoprotein C-I Is Positively Associated with Their Delayed Plasma Clearance Independently of Other Transferable Apolipoproteins in Postmenopausal Overweight and Obese Women

Background: The role of plasma apolipoprotein (apo) C-I in cardiometabolic risk in humans is unclear. However, in vitro studies showed a dual role for apoC-I, both protective and harmful, depending on the carrier lipoprotein.Objective: We tested the hypothesis that triglyceride (TG)-rich lipoprotein (TRL) apoC-I, not total or HDL apoC-I, is associated with delayed postprandial plasma clearance of TRLs, independently of apoC-II, apoC-III, and apoE.Methods: This cross-sectional study examines the plasma clearance of a 13C-triolein–labeled high-fat meal (68% fat energy) in 20 postmenopausal overweight and obese women [body mass index (in kg/m2) ≥27; aged 45–74 y] as the increment change in area under the 6-h postprandial curves (iAUC6h) of TRL parameters. Lipoproteins were fractionated by fast-protein LC. Transferable apolipoproteins were measured by ELISA. TRL enrichment with apolipoproteins was calculated by dividing their TRL concentrations by TRL apoB. The effects of human apoC-I and apoC-III on the hydrolysis and storage of 3H-triolein–labeled TRLs were tested in 3T3-L1 adipocytes.Results: TRL apoC-I was positively associated with plasma apo B-48 and total and non-HDL TGs, cholesterol, and apoB (r = 0.52–0.97) and negatively with HDL cholesterol (r = −0.52) and LDL diameter (r = −0.91) (P < 0.05). Total and HDL apoC-I were correlated only with total (r = 0.62) and HDL (r = 0.75) cholesterol. Women with high fasting TRL enrichment with apoC-I (99–365 μmol apoC-I/μmol apoB), but not apoC-II, apoC-III, or apoE, had higher iAUC6h for TGs (+195%), 13C-TGs (+319%), and apo B-48 (+186%) than those with low enrichment (14–97 μmol apoC-I/μmol apoB). The 4-h postprandial increase in TRL apoC-I was associated with a 4-h increase in TRL TGs and iAUC6h for TGs, 13C-TGs, and apo B-48 (r = 0.74–0.86, P < 0.001), independently of 4-h changes in TRL apoB, apoC-II, apoC-III, or apoE. ApoC-I and apoC-III inhibited 3H-TRL clearance by adipocytes by >75% (P < 0.001).Conclusions: TRL enrichment with apoC-I is positively associated with postprandial hypertriglyceridemia and remnant accumulation in postmenopausal overweight and obese women, independently of apoC-II, apoC-III, or apoE, which may be due to inhibiting TRL clearance by adipocytes. Reducing TRL apoC-I may ameliorate delayed postprandial plasma clearance of TRLs and associated risks in humans.

Abstract 205: Inhibition of Angiopoietin-Like 3 Expression is a Potential Mechanism of Activation of Lipoprotein Lipase and of Lipid Lowering by Metformin

Dyslipidemias associated with primary lipid disorders or secondary to abnormal glucose metabolism are commonly seen metabolic disorders in the clinic. Of special interest is the diabetic dyslipidemia and its growing prevalence. Interestingly, metformin, a commonly used anti-diabetic drug also has potent lipid lowering activity. However, the mechanisms associated with this metformin activity are poorly understood. A key protein regulating the plasma lipid homeostasis is the enzyme lipoprotein lipase (LPL) which is found lining the capillary endothelium in tissue capillary beds. LPL hydrolyses the core triglycerides (TGs) of chylomicrons and very-low density lipoprotein (VLDL). Angiopoietin-like 3 (ANGPTL3), a secretory protein derived from liver, inhibits the lipolytic activity of LPL, resulting in an increase in plasma TGs. We investigated whether metformin regulates LPL and in effect plasma lipids, via regulation of ANGPTL3 in the liver. A single dose (150mg/kg) treatment of metformin for twenty-four hours in mice resulted in an increase in the LPL activity in plasma. Since metformin is frequently used in type 2 diabetes which is characterized by insulin resistance, a condition compounded by dietary fatty acids, we studied the relationship between metformin and ANGPTL3 in a human liver cell line treated with palmitic acid. Treatment with palmitic acid mimicked the conditions of insulin resistance in the liver and elevated the expression of ANGPTL3 in the liver which was inhibited by co-treatment with metformin. Gene and protein expression assays revealed a potent inhibition of ANGPTL3 expression and secretion from the hepatocytes upon treatment with metformin. We examined the role of sirtuin 1 (SIRT1)/adenosine monophosphate activated kinase (AMPK) in the metformin regulation of ANGPTL3 and observed that even though activation of SIRT1/AMPK axis inhibited the expression of ANGPTL3, metformin inhibition of ANGPTL3 was independent of SIRT1/AMPK as revealed by pharmacological inhibition and gene knockdown approaches. Our studies suggest that a potential mechanism of lipid lowering activity of metformin is the inhibition of expression of ANGPTL3, which results in an increase in LPL activity and a lowering of plasma lipids.

Abstract 194: Lipid and Apolipoprotein Size Profile Differences Between Low and High Body Mass Index Individuals in Response to Fat Challenge

Clearance of elevated triglycerides (TG) level in response to fat challenge is a clinically significant indicator of CVD risk. HDL can play a key role in facilitating TG metabolism explaining the reverse correlation of HDL levels with CVD risk. In this study 6 individuals, low BMI (21-25) and 3 high BMI (30-49) were challenged with a meal containing ~90 g of total fat. Blood samples were drawn in fasting state before meal and 3 times after meal in 2, 4 and 6 hours. Serum was analyzed by a quantitative, multiplexed analytical workflow which included analysis of whole serum and the separation of lipoproteins by asymmetric flow field-flow fractionation where fractions were collected with 1 nm increments of 7-15 nm (HDL), 20-30 nm (LDL) and &gt;30 nm lipoprotein classes. Dynamic light scattering was used to determine hydrodynamic size in each size fraction. Whole serum and individual fractions were analyzed to determine concentrations of apolipoproteins (apo A-I, A-II, A-IV, B, C-I, C-II, C-III and E), and non-polar lipids (FC, CE and TG), using two parallel liquid chromatography tandem mass spectrometry methods developed in our laboratory. In whole serum, the total TG levels for low and high BMI donors, relative to pre-meal levels (57-137 mg/dL and 111-183 md/dL), peaked at between the 2 and 4 hours post meal (103-214 mg/dL and 210-309 mg/dL). LCAT were lower (20%) and CETP levels were higher (30%), in low vs high BMI groups, but did not show change in repose to the fat challenge. In both low and high BMI groups, the most significant change between pre-meal and post-meal after 2 hours occurred in HDL-ApoC-I, HDL-ApoC-II, and HDL-ApoC-III levels mainly in the HDL size range of 9-12 nm (medium HDL) and at 13-16 nm (large HDL), with concurrent TG increase observed in LDL and remnant fractions (Prob-

The Effect of Triglyceride Concentration on Attainment of Lipid Targets in Patients with Diabetes.

To evaluate the effects of triglyceride (TG) and glycated hemoglobin (A1C) concentrations in the percentage of patients with diabetes who are within target (WT) for low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol (non-HDL-C) and apolipoprotein B (ApoB), as defined by the Canadian Lipid Guidelines, in a cohort of outpatients presenting at a 350-bed community hospital. Laboratory samples from 1919 patients, 18 years or older, who had A1C levels of 6.5% or above were used. Fasting lipid profiles were retrieved, and ApoB was measured. We found no significant difference in the percentage of those WT for LDL-C as TG increased from normal to intermediate and high levels. For non-HDL-C, we saw a substantial decrease in the percentage of patients WT as TG levels increased from normal (61%) to intermediate (30.4%) and high levels (14.0%). ApoB showed a similar pattern to non-HDL-C: decreasing from normal (68.8%) to intermediate (40.7%) and high levels (21.0%). No significant difference was seen in the percentage of patients WT for the 3 lipid parameters studied with the increase in A1C levels. As TG increases, we saw discordance in the percentage of patients WT for LDL-C in relation to non-HDL-C and ApoB. Alternative targets to LDL-C should preferentially be used when the TG concentration is elevated.

A serum lipidomic study of patients with non-alcoholic fatty liver disease

Objective: To investigate the serum lipidomic profile in patients with nonalcoholic fatty liver disease (NAFLD), and to analyze the lipid metabolism characteristics of NAFLD. Methods: The subjects were divided into control group (23 patients) and pathologically confirmed NAFLD group (42 patients), and ultra-high-performance liquid chromatography-tandem mass spectrometry was used to measure serum lipidomic metabolites. The partial least squares-discriminant analysis (PLS-DA) model was established to analyze the differences in lipid metabolism with reference to the univariate analysis. The t-test and Mann-Whitney U test were used for data analysis. Results: A total of 239 lipids were identified and qualitative and quantitative analyses were performed. The PLS-DA model (R2 = 0.753, Q2 = 0.456) and the univariate analysis showed that 77 lipids were metabolized differentially between the NAFLD group and the control group (VIP > 1, P < 0.05), including free fatty acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, lysophosphatidylcholine, lysophosphatidylinositol (LPI), choline plasmalogen (PlsCho), ethanolamine plasmalogen (PlsEtn), ceramide (Cer), sphingomyelin, and triglyceride (TG). Compared with the control group, the NAFLD group had significant increases in monounsaturated fatty acids (increased by 39%, t = -3.954, P < 0.05) and TGs (increased by 36%, Z = -2.662, P < 0.05), mainly TGs with low numbers of carbon atoms and unsaturated bonds, while there were reductions in TGs with high numbers of carbon atoms and unsaturated bonds. In addition, compared with the control group, the NAFLD group had significant increases in the levels of LPI (increased by 223%, t = -3.858, P < 0.05) and Cer (increased by 21%, t = -2.481, P < 0.05) and significant reductions in PlsCho (reduced by 18%, t = 3.184, P < 0.05) and PlsEtn (reduced by 20%, t = 2.363, P < 0.05). Conclusion: There is a significant difference in lipid metabolism profile between NAFLD patients and healthy people, and a serum lipidomic analysis of NAFLD helps to further clarify the characteristics of lipid metabolism in patients with NAFLD.

A comparative study of lipid profile, body mass index, and waist circumference among Type 2 diabetes mellitus patients with poor and good metabolic control and normal age-matched control group

Background: Prevalence of dyslipidemia is very common in Type 2 diabetes mellitus (DM), and lipid abnormalities are likely to play an important role in the development of the atherosclerotic vascular disease. Type 2 diabetic patients are obese, and obesity as an independent risk factor for diabetes also complicates the management and exacerbates the metabolic abnormalities in diabetes. Aims and Objectives: To compare the lipid profile, body mass index (BMI), and waist circumference (WC) in Type 2 diabetic patients with poor and good metabolic controls with that of normal controls and to study the correlation between glycosylated hemoglobin (HbA1c) values and triglycerides (TG), high-density lipoprotein (HDL) in patients with Type 2 DM. Materials and Methods: The descriptive comparative study group of 150 subjects was divided into three groups based on HbA1c values which included Type 2 diabetic patients with poor metabolic control, good metabolic control, and normal age-matched controls. Results: There is a significant increase in the mean levels of total cholesterol, TG, low-density lipoprotein (LDL), and Very low density lipoproteins (VLDL) values in diabetic patients with both poor metabolic control and good metabolic control when compared to normal controls. There is a significant decrease in mean HDL values and significant elevation of mean waist circumference and BMI values in both male and female diabetics with poor and good metabolic controls when compared to normal controls. Highly significant positive correlation was obtained between HbA1c and TG and a negative correlation between HbA1c and HDL. Conclusion: Increase in TG and decline in HDL with HbA1c rise shows the impact of glycemic control on lipoprotein levels. Majority of diabetic patients were overweight and had abdominal adiposity. Good metabolic control of hyperglycemia will prevent alteration of lipid metabolism helping in better prognosis and preventing manifestations of vascular and typical secondary complications.

DISTRIBUTION OF LIPID PROFILE VALUES IN ECONOMICALLY ACTIVE MEN AND WOMEN IN RUSSIAN FEDERATION: RESULTS OF THE ESSE-RF STUDY FOR THE YEARS 2012-2014

Elevated level of plasma cholesterol, together with arterial hypertension, is the main modifiable factor of cardiovascular diseases (CVD) development. Monitoring of lipid levels at populational level is an important instrument of the prevention medicine, applied for CVD populational risk assessment. Aim . Blood lipid levels assessment, with the data obatined during epidemiological study “ESSE-RF” (Epidemiology of cardiovascular diseases in various regions of Russian Federation) in 13 regions of Russia. Material and methods. In the study, the patients were included, of 25-64 y.o. All participants underwent specimens collection for total cholesterol (TC), triglycerides (TG), high density lipoproteides cholesterol (HDL-C) and low density lipoproteides cholesterol (LDL-C) by enzymatic methods on automatic analyzer Abbott Architect 8000. Also, in all the participants, hypolipidemic therapy was evaluated. Results . Totally, 21167 persons included into analysis, 7937 males and 13230 females. 807 (3,81%) had been taking hypolipidemic therapy and were ruled out from further analysis. Mean age 44±12 and 47±11 y.o., respectively. Mean values for men were TC 5,31±1,15 mM/L, TG 1,58±1,24 mM/L, HDL-C 1,30±0,33 mM/L and LDL-C 3,38±0,99 mM/L (7643 persons), for women — 5,48±1,18 mM/L, 1,36±0,85 mM/L, 1,47±0,35 mM/L and 3,42±1,04 mM/L, respectively (12717 persons). In the study we present percentile variations of the studied groups by the measured levels of TC, TG, HDL-C, LDL-C according to the age and sex. There were moderate correlations found of HDL-C with age and sex (r=0,34, p=0,000) and LDL-C (r=0,33, p=0,000). Correlation of TG with age and sex was low, but significant (r=0,18, p=0,000). There was no correlation of HDL-C with age and sex (r=-0,002, p=0,740). Also, a high prevalence is shown for severe lipid disorders. 23% of the participants had severely increased TC level (&gt;6,2 mM/L), and 20,6% — of LDL-C (&gt;4,2 mM/L). Severe increase of TG (&gt;5,0 mM/L) was found much more rarely (1,1%). Conclusion . In the ESSE-RF study the prevalence of significant lipid disorders was shown as high, that demands respective prevention and management. This study might be a starting point for lipids populational dynamics analysis in Russia.

Phospholipase D1 deficiency in mice causes nonalcoholic fatty liver disease via an autophagy defect.

Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of triglycerides (TG) as lipid droplets in the liver. Although lipid-metabolizing enzymes are considered important in NAFLD, the involvement of phospholipase D1 (PLD1) has not yet been studied. Here, we show that the genetic ablation of PLD1 in mice induces NAFLD due to an autophagy defect. PLD1 expression was decreased in high-fat diet-induced NAFLD. Subsequently, PLD1 deficiency led to an increase in hepatic TGs and liver weight. Autophagic flux was blocked in Pld1−/− hepatocytes, with decreased β-oxidation rate, reduced oxidation-related gene expression, and swollen mitochondria. The dynamics of autophagy was restored by treatment with the PLD product, phosphatidic acid (PA) or adenoviral PLD1 expression in Pld1−/− hepatocytes, confirming that lysosomal PA produced by PLD1 regulates autophagy. Notably, PLD1 expression in Pld1−/− liver significantly reduced hepatic lipid accumulation, compared with Pld1−/− liver. Thus, PLD1 plays an important role in hepatic steatosis via the regulation of autophagy.

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 &lt;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 &lt;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.

Hypertriglyceridemia Induced Acute Pancreatitis Associated with Diabetic Ketoacidosis and a Vaginal Estrogen Contraceptive Device (NuvaRing): Successfully Treated with Insulin Infusion, Plasmapheresis, and Ring Removal

We present a 27-year-old female with only past medical history of gestational diabetes, who presented to our hospital with abdominal pain. Physical exam was significant for mild tachypnea and tachycardia, dry mucous membranes, and moderate epigastric tenderness to light palpation. Blood work revealed an elevated glucose of 411 mg/dl, creatinine of 0.4 mg/dl, severe wide anion gap metabolic acidosis, lipase >6,000, triglycerides (TG) increased to 1,368 mg/dl. Computed tomography of abdomen and pelvis was consistent with acute pancreatitis. She was started on an insulin infusion and intravenous fluids. Her condition worsened rapidly with significant decline in mentation and severe tachypnea requiring intubation. Further blood work showed worsening creatinine at 1.5 with an arterial blood pH of 6.9. Insulin infusion continued and plasmapheresis was initiated given the worsening in her clinical status. Post plasmapheresis, her triglycerides decreased to 259 mg/dl, glucose trending in the 100 range, and anion gap closed. Her severely elevated triglyceride level was attributed to a combined effect of her new onset diabetes and vaginal estrogen ring, which was removed on presentation. Hypertriglyceridemia pancreatitis is a rare cause of pancreatitis. Usually a serum triglyceride (TG) level of more than 1,000 mg/dL is an inciting factor for the episode. In DKA, the deficiency of insulin activates lipolysis in adipose tissue releasing increased free fatty acids, which accelerates formation of VLDL in the liver. In addition, reduced activity of lipoprotein lipase in peripheral tissue decreases removal of VLDL from the plasma, resulting in hypertriglyceridemia. Furthermore, exogenous estrogen use can cause an increase in TG by induced stimulation of the secretion of hepatic triglyceride-rich lipoprotein. Plasmapheresis has been repeatedly shown in case reports and series to be effective in quickly removing TG from the serum of patients with hypertriglyceridemia pancreatitis. Although a clear benefit of plasmapheresis in reducing the severity and improving outcomes in such patients has not been conclusively shown, we report the possible benefit of such therapy as an add-on treatment modality in case the clinical situation deteriorates while they are on standard therapy.