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Sample records for elevated triglycerides tg

  1. Adipose triglyceride lipase is a TG hydrolase of the small intestine and regulates intestinal PPAR? signaling.

    PubMed

    Obrowsky, Sascha; Chandak, Prakash G; Patankar, Jay V; Povoden, Silvia; Schlager, Stefanie; Kershaw, Erin E; Bogner-Strauss, Juliane G; Hoefler, Gerald; Levak-Frank, Sanja; Kratky, Dagmar

    2013-02-01

    Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme mediating triglyceride (TG) hydrolysis. The lack of ATGL results in TG accumulation in multiple tissues, underscoring the critical role of ATGL in maintaining lipid homeostasis. Recent evidence suggests that ATGL affects TG metabolism via activation of peroxisome proliferator-activated receptor ? (PPAR?). To investigate specific effects of intestinal ATGL on lipid metabolism we generated mice lacking ATGL exclusively in the intestine (ATGLiKO). We found decreased TG hydrolase activity and increased intracellular TG content in ATGLiKO small intestines. Intragastric administration of [(3)H]trioleate resulted in the accumulation of radioactive TG in the intestine, whereas absorption into the systemic circulation was unchanged. Intraperitoneally injected [(3)H]oleate also accumulated within TG in ATGLiKO intestines, indicating that ATGL mobilizes fatty acids from the systemic circulation absorbed by the basolateral side from the blood. Down-regulation of PPAR? target genes suggested modulation of cholesterol absorption by intestinal ATGL. Accordingly, ATGL deficiency in the intestine resulted in delayed cholesterol absorption. Importantly, this study provides evidence that ATGL has no impact on intestinal TG absorption but hydrolyzes TGs taken up from the intestinal lumen and systemic circulation. Our data support the role of ATGL in modulating PPAR?-dependent processes also in the small intestine. PMID:23220585

  2. Triglycerides

    MedlinePLUS

    Triglycerides are a type of fat found in your blood. Too much of this type of fat ... especially in women. A blood test measures your triglycerides along with your cholesterol. Normal triglyceride levels are ...

  3. Obese First-Degree Relatives of Patients with Type 2 Diabetes with Elevated Triglyceride Levels Exhibit Increased ?-Cell Function

    PubMed Central

    Torres-Rasgado, Enrique; Porchia, Leonardo M.; Ruiz-Vivanco, Guadalupe; Gonzalez-Mejia, M. Elba; Bez-Duarte, Blanca G.; Pulido-Prez, Patricia; Rivera, Alicia; Romero, Jose R.

    2015-01-01

    Abstract Background: Type 2 diabetes mellitus (T2DM) is characterized as a disease continuum that is marked by metabolic changes that are present for several years, sometimes well before frank diagnosis of T2DM. Genetic predisposition, ethnicity, geography, alterations in BMI, and lipid profile are considered important markers for the pathogenesis of T2DM through mechanisms that remain unresolved and controversial. The aim of this study was to investigate the relationship between triglycerides (TGs) and ?-cell function, insulin resistance (IR), and insulin sensitivity (IS) in obese first-degree relatives of patients with T2DM (FDR-T2DM) among subjects from central Mexico with normal glucose tolerance (NGT). Methods: We studied 372 FDR-T2DM subjects (ages,1865) and determined body mass index (BMI), fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), insulin, and TGs levels. Subjects were categorized based on glycemic control [NGT, prediabetes (PT2DM), or T2DM]. NGT subjects were further categorized by BMI [normal weight (Ob?) or obese (Ob+)] and TGs levels (TG?, <150?mg/dL, or TG+, ?150?mg/dL). ?-cell function, IR, and IS were determined by the homeostasis model assessment of ?-cell function (HOMA2-?), homeostasis model assessment of insulin resistance (HOMA2-IR), and Quantitative Insulin Sensitivity Check Index (QUICKI) indices, respectively. Results: The obese subjects with elevated TGs levels had 21%60% increased ?-cell function when compared to all groups (P<0.05). In addition, this group had insulin levels, IS, and IR similar to PT2DM. Furthermore, only in obese subjects did TGs correlate with ?-cell function (?=0.502, P<0.001). Conclusion: We characterized FDR-T2DM subjects from central Mexico with NGT and revealed a class of obese subjects with elevated TGs and ?-cell function, which may precede PT2DM. PMID:25423015

  4. Acute high-intensity endurance exercise is more effective than moderate-intensity exercise for attenuation of postprandial triglyceride elevation.

    PubMed

    Trombold, Justin R; Christmas, Kevin M; Machin, Daniel R; Kim, Il-Young; Coyle, Edward F

    2013-03-15

    Acute exercise has been shown to attenuate postprandial plasma triglyceride elevation (PPTG). However, the direct contribution of exercise intensity is less well understood. The purpose of this study was to examine the effects of exercise intensity on PPTG and postprandial fat oxidation. One of three experimental treatments was performed in healthy young men (n = 6): nonexercise control (CON), moderate-intensity exercise (MIE; 50% Vo2peak for 60 min), or isoenergetic high-intensity exercise (HIE; alternating 2 min at 25% and 2 min at 90% Vo2peak). The morning after the exercise, a standardized meal was provided (16 kcal/kg BM, 1.02 g fat/kg, 1.36 g CHO/kg, 0.31 g PRO/kg), and measurements of plasma concentrations of triglyceride (TG), glucose, insulin, and β-hydroxybutyrate were made in the fasted condition and hourly for 6 h postprandial. Indirect calorimetry was used to determine fat oxidation in the fasted condition and 2, 4, and 6 h postprandial. Compared with CON, both MIE and HIE significantly attenuated PPTG [incremental AUC; 75.2 (15.5%), P = 0.033, and 54.9 (13.5%), P = 0.001], with HIE also significantly lower than MIE (P = 0.03). Postprandial fat oxidation was significantly higher in MIE [83.3 (10.6%) of total energy expenditure] and HIE [89.1 (9.8) %total] compared with CON [69.0 (16.1) %total, P = 0.039, and P = 0.018, respectively], with HIE significantly greater than MIE (P = 0.012). We conclude that, despite similar energy expenditure, HIE was more effective than MIE for lowering PPTG and increasing postprandial fat oxidation. PMID:23372145

  5. Effects of switching from omega-3-acid ethyl esters to icosapent ethyl in a statin-treated patient with elevated triglycerides.

    PubMed

    Kedia, Anurag W; Lynch, Erin

    2015-11-01

    In patients with dyslipidemia, elevated triglyceride (TG) levels, or TG-rich lipoproteins, and cardiovascular risk may remain despite statin therapy. Prescription omega-3 fatty acid formulations containing the ethyl esters of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) (omega-3-acid ethyl esters; Lovaza) or high-purity EPA ethyl ester (icosapent ethyl; Vascepa) are TG-lowering treatments that may be administered in addition to statins. Here we describe the effects of switching from omega-3-acid ethyl esters to icosapent ethyl in a 44-year-old obese man with dyslipidemia, hypertension, and hypothyroidism. The patient was receiving stable treatment with medications, including atorvastatin 40mg/day and extended-release niacin 1000mg/day. Owing to persistently elevated TG levels and other cardiovascular risk factors, the patient was initiated on omega-3-acid ethyl esters 4g/day. After approximately 2years on omega-3-acid ethyl esters, his total cholesterol (TC) level was 184mg/dL, low-density lipoprotein cholesterol (LDL-C) level was 81mg/dL, TG level was elevated at 307mg/dL despite statin therapy, and non-high-density lipoprotein cholesterol (non-HDL-C) level was 144mg/dL. After the switch to icosapent ethyl, TC level decreased by 34% to 121mg/dL, LDL-C level decreased by 28% to 58mg/dL, TG level decreased by 41% to 180mg/dL, and non-HDL-C level decreased by 44% to 81mg/dL. Switching from omega-3-acid ethyl esters containing both EPA and DHA to icosapent ethyl containing high-purity EPA resulted in beneficial and substantial changes in the lipid profile with a notable reduction of TG levels along with additional reductions in LDL-C levels in a statin-treated obese patient with persistently high TG levels. Treatment with icosapent ethyl was well tolerated. PMID:26453247

  6. CYP2E1-dependent elevation of serum cholesterol, triglycerides, and hepatic bile acids by isoniazid

    SciTech Connect

    Cheng, Jie; Krausz, Kristopher W.; Li, Feng; Ma, Xiaochao; Gonzalez, Frank J.

    2013-01-15

    Isoniazid is the first-line medication in the prevention and treatment of tuberculosis. Isoniazid is known to have a biphasic effect on the inhibition–induction of CYP2E1 and is also considered to be involved in isoniazid-induced hepatotoxicity. However, the full extent and mechanism of involvement of CYP2E1 in isoniazid-induced hepatotoxicity remain to be thoroughly investigated. In the current study, isoniazid was administered to wild-type and Cyp2e1-null mice to investigate the potential toxicity of isoniazid in vivo. The results revealed that isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice, but produced elevated serum cholesterol and triglycerides, and hepatic bile acids in wild-type mice, as well as decreased abundance of free fatty acids in wild-type mice and not in Cyp2e1-null mice. Metabolomic analysis demonstrated that production of isoniazid metabolites was elevated in wild-type mice along with a higher abundance of bile acids, bile acid metabolites, carnitine and carnitine derivatives; these were not observed in Cyp2e1-null mice. In addition, the enzymes responsible for bile acid synthesis were decreased and proteins involved in bile acid transport were significantly increased in wild-type mice. Lastly, treatment of targeted isoniazid metabolites to wild-type mice led to similar changes in cholesterol, triglycerides and free fatty acids. These findings suggest that while CYP2E1 is not involved in isoniazid-induced hepatotoxicity, while an isoniazid metabolite might play a role in isoniazid-induced cholestasis through enhancement of bile acid accumulation and mitochondria β-oxidation. -- Highlights: ► Isoniazid metabolites were elevated only in wild-type mice. ► Isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice. ► Isoniazid elevated serum cholesterol and triglycerides, and hepatic bile acids. ► Bile acid transporters were significantly decreased in isoniazid-treated mice.

  7. Genetically elevated levels of circulating triglycerides and brachial-ankle pulse wave velocity in a Chinese population.

    PubMed

    Yao, W-M; Zhang, H-F; Zhu, Z-Y; Zhou, Y-L; Liang, N-X; Xu, D-J; Zhou, F; Sheng, Y-H; Yang, R; Gong, L; Yin, Z-J; Chen, F-K; Cao, K-J; Li, X-L

    2013-04-01

    Elevated levels of circulating triglycerides and increased arterial stiffness are associated with cardiovascular disease. Numerous studies have reported an association between levels of circulating triglycerides and arterial stiffness. We used Mendelian randomization to test whether this association is causal. We investigated the association between circulating triglyceride levels, the apolipoprotein A-V (ApoA5) -1131T>C single nucleotide polymorphism and brachial-ankle pulse wave velocity (baPWV) by examining data from 4421 subjects aged 18-74 years who were recruited from the Chinese population. baPWV was significantly associated with the levels of circulating triglycerides after adjusting for age, sex, body mass index (BMI), systolic blood pressure, heart rate, waist-to-hip ratio, antihypertensive treatment and diabetes mellitus status. The -1131C allele was associated with a 5% (95% confidence interval 3-8%) increase in circulating triglycerides (adjusted for age, sex, BMI, waist-to-hip ratio, diabetes mellitus and antihypertensive treatment). Instrumental variable analysis showed that genetically elevated levels of circulating triglycerides were not associated with increased baPWV. These results do not support the hypothesis that levels of circulating triglycerides have a causal role in the development of arterial stiffness. PMID:22648266

  8. CYP2E1-dependent elevation of serum cholesterol, triglycerides, and hepatic bile acids by isoniazid.

    PubMed

    Cheng, Jie; Krausz, Kristopher W; Li, Feng; Ma, Xiaochao; Gonzalez, Frank J

    2013-01-15

    Isoniazid is the first-line medication in the prevention and treatment of tuberculosis. Isoniazid is known to have a biphasic effect on the inhibition-induction of CYP2E1 and is also considered to be involved in isoniazid-induced hepatotoxicity. However, the full extent and mechanism of involvement of CYP2E1 in isoniazid-induced hepatotoxicity remain to be thoroughly investigated. In the current study, isoniazid was administered to wild-type and Cyp2e1-null mice to investigate the potential toxicity of isoniazid in vivo. The results revealed that isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice, but produced elevated serum cholesterol and triglycerides, and hepatic bile acids in wild-type mice, as well as decreased abundance of free fatty acids in wild-type mice and not in Cyp2e1-null mice. Metabolomic analysis demonstrated that production of isoniazid metabolites was elevated in wild-type mice along with a higher abundance of bile acids, bile acid metabolites, carnitine and carnitine derivatives; these were not observed in Cyp2e1-null mice. In addition, the enzymes responsible for bile acid synthesis were decreased and proteins involved in bile acid transport were significantly increased in wild-type mice. Lastly, treatment of targeted isoniazid metabolites to wild-type mice led to similar changes in cholesterol, triglycerides and free fatty acids. These findings suggest that while CYP2E1 is not involved in isoniazid-induced hepatotoxicity, while an isoniazid metabolite might play a role in isoniazid-induced cholestasis through enhancement of bile acid accumulation and mitochondria ?-oxidation. PMID:23142471

  9. Time and dose relationships between schisandrin B- and schisandrae fructus oil-induced hepatotoxicity and the associated elevations in hepatic and serum triglyceride levels in mice

    PubMed Central

    Zhang, Yi; Pan, Si-Yuan; Zhou, Shu-Feng; Wang, Xiao-Yan; Sun, Nan; Zhu, Pei-Li; Chu, Zhu-Sheng; Yu, Zhi-Ling; Ko, Kam-Ming

    2014-01-01

    Background Schisandrin B (Sch B), a dibenzocyclooctadiene compound, is isolated from schisandrae fructus (SF). This study was conducted to compare the time- and dose-response between Sch B- and SF oil (SFO)-induced changes in hepatic and serum parameters in mice. Methods Institute of Cancer Research (ICR) mice were given a single oral dose of Sch B (0.1252 g/kg) or SFO (0.35 g/kg). Serum alanine aminotransferase (ALT) activity, hepatic malondialdehyde, and triglyceride (TG) levels were measured at increasing time intervals within 6120 hours postdosing. Results Serum ALT activity was elevated by 60%, with maximum effect (Emax) =45.77 U/L and affinity (KD) =1.25 g/kg at 4896 hours following Sch B, but not SFO, treatment. Sch B and SFO treatments increased hepatic malondialdehyde level by 70% (Emax =2.30 nmol/mg protein and KD =0.41 g/kg) and 22% (Emax =1.42 nmol/mg protein and KD =2.56 g/kg) at 72 hours postdosing, respectively. Hepatic index was increased by 16%60% (Emax =11.01, KD =0.68 g/kg) and 8%32% (Emax =9.88, KD =4.47 g/kg) at 12120 hours and 24120 hours after the administration of Sch B and SFO, respectively. Hepatic TG level was increased by 40%158% and 35%85%, respectively, at 1296 hours and 648 hours after Sch B and SFO treatment, respectively. The values of Emax and KD for Sch B/SFO-induced increase in hepatic TG were estimated to be 22.94/15.02 ?mol/g and 0.78/3.03 g/kg, respectively. Both Sch B and SFO increased serum TG (up to 427% and 123%, respectively), with the values of Emax =5.50/4.60 mmol/L and KD =0.43/2.84 g/kg, respectively. Conclusion The findings indicated that Sch B/SFO-induced increases in serum/hepatic parameters occurred in a time-dependent manner, with the time of onset being serum TG level < hepatic TG level < hepatic index < serum ALT activity. However, the time of recovery of these parameters to normal values varied as follow: serum TG level < hepatic TG level and liver injury < hepatic index. The Emax and affinity of Sch B on tissue/enzyme/receptor were larger than those of SFO. PMID:25278745

  10. Triglyceride-increasing alleles associated with protection against type-2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Elevated plasma triglyceride (TG) levels are an established risk factor for type-2 diabetes (T2D). However, recent studies have hinted at the possibility that genetic risk for TG may paradoxically protect against T2D. In this study, we examined the association of genetic risk for TG with incident T2...

  11. In vivo determination of triglyceride (TG) secretion in rats fed different dietary saturated fats using (2- sup 3 H)-glycerol

    SciTech Connect

    Lai, H.C.; Yang, H.; Lasekan, J.; Clayton, M.; Ney, D.M. )

    1990-02-26

    Male, Sprague-Dawley rats (154{plus minus}1 g) were fed diets containing 2% corn oil (CO) + 14% butterfat (BF), beef tallow (BT), olive oil (OO) or coconut oil (CN) vs a 16% CO control diet for 5 weeks. Changes in plasma TG specific activity (dpm/mg TG) were determined in individual unanesthetized rats after injection of 100 {mu}Ci (2-{sup 3}H)-glycerol via a carotid cannula. Fractional rate constants were obtained using a 2-compartment model and nonlinear regression analysis. Results demonstrated no difference in the fractional rate constants among dietary groups; but, differences in the rates of hepatic TG secretion were noted. Rats fed BT showed a higher rate of hepatic TG secretion than rats fed CO. Rats fed BF, OO or CN showed somewhat higher rates of hepatic TG secretion than CO. VLDL TG, phospholipid, and apolipoprotein B and E levels were higher with saturated fats vs CO. The data suggest that the higher plasma TG levels noted in response to feeding saturated fats vs corn oil can be explained, in part, by an increased flux of hepatic TG secretion.

  12. Patients with elevated triglyceride and cholesterol serum levels have a prolonged survival in amyotrophic lateral sclerosis.

    PubMed

    Dorst, J; Khnlein, P; Hendrich, C; Kassubek, J; Sperfeld, A D; Ludolph, A C

    2011-04-01

    Weight loss is a common phenomenon and an independent prognostic factor in amyotrophic lateral sclerosis (ALS). Several potential causal mechanisms, including intrinsic hypermetabolism and deficient food intake, have been discussed. We investigated the influence of fasting serum glucose, cholesterol, and triglyceride levels at time of diagnosis on survival in ALS. Serum cholesterol (LDL, HDL, and LDL/HDL ratio), triglycerides, and glucose were investigated in 488 patients (age of onset = 57.6 12.6 years) in relation to survival and revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALS-FRS) data. High serum levels of both fasting cholesterol and triglycerides had a significantly positive effect on survival (p < 0.05). We found a median prolonged life expectancy by 14 months for patients with serum triglyceride levels above the median of 1.47 mmol/l. The results suggest that the lipid metabolism and the nutritional status of ALS patients are important prognostic factors. These parameters should be thoroughly monitored during the clinical management of these patients. In case of progressive loss of body weight, a diet rich in lipids and calories should be considered. However, the final decision whether a lipid-rich diet should be recommended to ALS patients can only be based on a double-blind placebo-controlled interventional trial. Our results further imply that lipid-lowering drugs, e.g., statins, should be applied carefully in ALS patients although individual risk considerations must be made. PMID:21128082

  13. Fenofibrate Effect on Triglyceride and Postprandial Response of Apolipoprotein A5 Variants: The GOLDN Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Elevated plasma triglyceride (TG) levels (hypertriglyceridemia), one of the characteristic features of the Metabolic Syndrome (MS), have been recognized as an independent risk factor of coronary heart disease (CHD). Lowering TG concentration by dietary or drug intervention reduces CHD risk. Fenofibr...

  14. Triglycerides and gallstone formation.

    PubMed

    Smelt, A H M

    2010-11-11

    Changes in bile acid (BA) metabolism and gallbladder function are critical factors in the pathogenesis of gallstones. Patients with hypertriglyceridemia (HTG) - often overweight and insulin resistant - are at risk for gallstone disease. The question arises whether HTG itself contributes to gallstone formation or whether gallstone disease only associates with this disorder. Triglycerides are formed in response to fluxes of non-esterified fatty acids and glucose. Hypertriglyceridemia results from either overproduction of triglycerides by the liver, impaired lipolysis or a combination of both. Hyperinsulinemia, as observed in the insulin resistant state, stimulates very low-density lipoprotein (VLDL)-triglyceride synthesis. Peroxisome proliferator-activated receptors (PPARs), liver X receptors (LXRs), farnesoid X receptor (FXR) and hepatocyte nuclear factor 4? (HNF4?) are the nuclear receptors involved in the regulation of lipogenesis. Microsomal triglyceride transfer protein (MTP) is involved in the production of VLDL and its activation is also under control of transcription factors as FXR and Forkhead box-O1 (FoxO1). Triglyceride and BA metabolism are linked. There is an inverse relationship between bile acid fluxes and pool size and VLDL production and SHP (small heterodimer partner) and FXR are the link between BAs and TG metabolism. BAs are also ligands for FXR and G-protein-coupled receptors, such as TGR5. FXR activation by BAs suppresses the expression of MTP, transcription factor sterol regulatory element binding protein (SREBP)-1c and other lipogenic genes. LXRs stimulate lipogenesis whereas FXRs inhibit the metabolic process. Synthesis of BAs from cholesterol occurs either via the classical pathway (7?-hydroxylation of cholesterol; CYP7A1) or via the alternate pathway (CYP39A1 or CYP7B1). BAs induce FXR, which inhibits CYP7A1 transcription by activation of SHP and inhibition of HNF4? transactivation. Bile composition (supersaturation with cholesterol), gallbladder dysmotility, inflammation, hypersecretion of mucin gel in the gallbladder and slow large intestinal motility and increased intestinal cholesterol absorption may contribute to the pathogenesis of cholesterol gallstones. In HTG patients supersaturated bile may be related to the presence of obesity rather than to HTG itself. Contraction and relaxation of the gallbladder are regulated by neuronal, hormonal and paracrine factors. Postprandial gallbladder emptying is regulated by cholecystokinin (CCK). Poor postprandial gallbladder contraction may be due to the magnitude of the CCK response and to the amount of CCK receptors in the gallbladder smooth muscle cells. In the fasting state gallbladder motility is associated with the intestinal migrating motor complex (MMC) activity and with elevated plasma motilin levels. Fibroblast growth factor (FGF19), produced on arrival of bile acids in the ileum, is also important for gallbladder motility. Gallbladder motility is impaired in HTG patients compared to BMI matched controls. There is evidence that the gallbladder in HTG is less sensitive to CCK and that this sensitivity improves after reversal of high serum TG levels by use of TG lowering agents. In hypertriglyceridemia TG lowering therapy (fibrates or fish-oil) is essential to prevent cardiovascular disease and pancreatitis. Fibrates, however, also increase the risk for cholelithiasis by increasing biliary cholesterol saturation and by reduction of bile acid synthesis. On the other hand fish-oil decreases biliary cholesterol saturation. Fish-oil may increase bile acid synthesis by activation of 7alpha-hydroxylase and may inhibit VLDL production and secretion through activation of nuclear factors and increased apoB degradation. In HTG patients, gallbladder motility improves during bezafibrate as well as during fish-oil therapy. The question remains whether improvement of gallbladder motility and increased lithogenicity of bile by bezafibrate therapy counteract each other or still result in gallstone formation in HTG patients. PMID:20699090

  15. ELEVATED REMNANT-LIKE PARTICLE (RLP) CHOLESTEROL AND TRIGLYCERIDE LEVELS INDIABETIC MEN AND WOMENT IN THE FRAMINGHAM OFFSPRING STUDY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Remnants of triglyceride-rich lipoproteins are thought to be atherogenic. A new antibody-based assay allows isolation of remnant-like particles (RLP) from plasma or serum, and subsequent measurement of RLP cholesterol and triglyceride (RLPC and RLPTG). We hypothesized that diabetics (DM) would have ...

  16. Adult women with acne have a higher risk of elevated triglyceride levels with the use of oral isotretinoin.

    PubMed

    Schmitt, Juliano Vilaverde; Tavares, Mariana; Cerci, Felipe Bochnia

    2011-01-01

    There are restrictions associated with the use of isotretinoin because of its effects on the lipid profile. The records of ninety patients treated with this medication were reviewed to identify factors that would predispose patients to these abnormalities. A significant increase in cholesterol and triglyceride levels occurred. Patients in whom triglyceride levels increased were more likely to be female, although this difference was not present at baseline. Women with persistent acne may constitute a risk population for these side effects. PMID:21987157

  17. Hepatic ABCA1 and VLDL triglyceride production

    PubMed Central

    Liu, Mingxia; Chung, Soonkyu; Shelness, Gregory S.

    2011-01-01

    Elevated plasma triglyceride (TG) and reduced high density lipoprotein (HDL) concentrations are prominent features of metabolic syndrome (MS) and type 2 diabetes (T2D). Individuals with Tangier disease also have elevated plasma TG concentrations and a near absence of HDL, resulting from mutations in ATP binding cassette transporter A1 (ABCA1), which facilitates the efflux of cellular phospholipid and free cholesterol to assemble with apolipoprotein A-I (apoA-I), forming nascent HDL particles. In this review, we summarize studies focused on the regulation of hepatic very low density lipoprotein (VLDL) TG production, with particular attention on recent evidence connecting hepatic ABCA1 expression to VLDL, LDL, and HDL metabolism. Silencing ABCA1 in McArdle rat hepatoma cells results in diminished assembly of large (>10nm) nascent HDL particles, diminished PI3 kinase activation, and increased secretion of large, TG-enriched VLDL1 particles. Hepatocyte-specific ABCA1 knockout (HSKO) mice have a similar plasma lipid phenotype as Tangier disease subjects, with a twofold elevation of plasma VLDL TG, 50% lower LDL, and 80% reduction in HDL concentrations. This lipid phenotype arises from increased hepatic secretion of VLDL1 particles, increased hepatic uptake of plasma LDL by the LDL receptor, elimination of nascent HDL particle assembly by the liver, and hypercatabolism of apoA-I by the kidney. These studies highlight a novel role for hepatic ABCA1 in the metabolism of all three major classes of plasma lipoproteins and provide a metabolic link between elevated TG and reduced HDL levels that are a common feature of Tangier disease, MS, and T2D. PMID:22001232

  18. The Protective Effect of Transcription Factor 7-Like 2 Risk Allele rs7903146 against Elevated Fasting Plasma Triglyceride in Type 2 Diabetes: A Meta-Analysis

    PubMed Central

    Wang, Shuxia; Song, Kangxing; Srivastava, Roshni; Fathzadeh, Mohsen; Li, Na; Mani, Arya

    2015-01-01

    Background. The results from published studies regarding association of transcription factor 7-like 2 (TCF7L2) variant rs7903146 with dyslipidemia have been conflicting and inconclusive. Methods. We carried out a meta-analysis that aimed to investigate the association of the rs7903146 variant with plasma lipid levels using electronic database and published studies. Data was extracted by a standard algorithm. Dominant, recessive, homozygote, and heterozygote comparison models were utilized. Results. 24 studies incorporating 52,785 subjects were included in this meta-analysis. Overall, the minor allele (T) was associated with lower risk for hypertriglyceridemia in subjects with type 2 diabetes (dominant model: SMD = ?0.04, 95% CI (?0.08, 0.00), P = 0.048, Pheterogeneity = 0.47; recessive model: SMD = ?0.10, 95% CI (?0.18, ?0.02), P = 0.01, Pheterogeneity = 0.56). No association was found between minor (T) allele and plasma TC, LDL-c, or HDL-c levels in subjects with type 2 diabetes or metabolic syndrome (MetS) and no association was found between minor (T) allele and plasma TG levels in nondiabetic subjects. Conclusions. Our meta-analysis indicated the association between TCF7L2 rs7903146 polymorphism and low plasma triglyceride (TG) level in subjects with type 2 diabetes. No association was found between rs7903146 variant and plasma lipids in nondiabetic subjects. PMID:26576435

  19. The Effect of Elevated Triglycerides on the Onset and Progression of Coronary Artery Disease: A Retrospective Chart Review

    PubMed Central

    Daniel, Deepu; Hardigan, Patrick; Jawaid, Asif; Bhandari, Rohit; Daniel, Mithun

    2015-01-01

    Background. The American College of Cardiology and American Heart Association did not indicate a correlation between treating hypertriglyceridemia and reducing cardiovascular events. Objective. This study investigated whether patients with hypertriglyceridemia were more prone to worse outcomes during cardiac catheterization. Methods. Data collected over a one-year period analyzed lipid panels obtained at the time of cardiac catheterization. Triglyceride levels were categorized into three groups: <150?mg/dL, 150?mg/dL300?mg/dL, and >300?mg/dL. Controlled variables included age, gender, the presence of hypertension, diabetes, hyperlipidemia, and history of coronary artery disease. Results. Subjects with a triglyceride level <150?mg/dL have a 54% likelihood of being treated medically compared to 38% and 41% in the 150?mg/dL300?mg/dL and >300?mg/dL groups, respectively (p < 0.01). Subjects with a triglyceride level >300?mg/dL have a 20% percent chance of being treated with a coronary artery bypass graft compared to 12% and 15% in the <150?mg/dL and 150?mg/dL300?mg/dL groups, respectively (p < 0.01). Subjects with a triglyceride level between 150 and 300?mg/dL have a 44% percent of being treated with a percutaneous coronary intervention compared to 34% and 43% in the <150?mg/dL and >300?mg/dL groups, respectively (p < 0.01). Conclusion. Hypertriglyceridemia was associated with worse outcomes in percutaneous coronary intervention or surgery. PMID:26617998

  20. COOH-terminal disruption of lipoprotein lipase in mice is lethal in homozygotes, but heterozygotes have elevated triglycerides and impaired enzyme activity.

    PubMed

    Coleman, T; Seip, R L; Gimble, J M; Lee, D; Maeda, N; Semenkovich, C F

    1995-05-26

    The role of the enzyme lipoprotein lipase (LPL) in atherosclerosis is uncertain. To generate an animal model of LPL deficiency, we targeted the LPL gene in embryonic stem cells with a vector designed to disrupt the COOH terminus of the protein and used these cells to generate LPL-deficient mice. Germ line transmission of the disrupted LPL allele was achieved with two chimeric males, and offspring from each of these animals were phenotypically identical. Pups homozygous (-/-) for LPL deficiency died within 48 h of birth with extreme elevations of serum triglycerides (13,327 mg/dl) associated with essentially absent LPL enzyme activity in heart and carcass. Newborn heterozygous (+/-) LPL-deficient pups had lower LPL enzyme activity and higher triglycerides (370 versus 121 mg/dl) than wild type (+/+) littermates. Adult heterozygotes had higher triglycerides than wild type mice with ad libitum feeding (236 mg/dl for +/- versus 88 mg/dl for +/+) and after fasting for 4 h (98 mg/dl for +/- versus 51 for +/+) or 12 h (109 mg/dl for +/- versus 56 mg/dl for +/+). Triglycerides were present as very low density lipoprotein particles and chylomicrons, but high density lipoprotein cholesterol levels were not decreased in +/- animals. Plasma heparin-releasable LPL activity was 43% lower in +/- versus +/+ adult animals. LPL activity, mRNA, and protein were lower in the tissues of +/- versus +/+ mice. Homozygous LPL deficiency caused by disruption of the COOH terminus of the enzyme is lethal in mice. Heterozygous LPL deficiency caused by this mutation is associated with mild to moderate hypertriglyceridemia without affecting static HDL cholesterol levels. Heterozygous LPL-deficient mice could be useful for determining if hypertriglyceridemia, independently or in combination with other discrete defects, influences atherosclerosis. PMID:7759497

  1. A role of apolipoprotein D in triglyceride metabolism[S

    PubMed Central

    Perdomo, German; Kim, Dae Hyun; Zhang, Ting; Qu, Shen; Thomas, Elizabeth A.; Toledo, Frederico G. S.; Slusher, Sandra; Fan, Yong; Kelley, David E.; Dong, H. Henry

    2010-01-01

    Apolipoproteins (apo) are constituents of lipoproteins crucial for lipid homeostasis. Aberrant expression of apolipoproteins is associated with metabolic abnormalities. Here we characterized apolipoprotein D (apoD) in triglyceride metabolism. Unlike canonical apolipoproteins that are mainly produced in the liver, apoD is an atypical apolipoprotein with broad tissue distribution. We show that circulating apoD is present mainly in HDL and, to a lesser extent, in LDL and VLDL and that its plasma levels were reduced in db/db mice with visceral obesity and altered lipid metabolism. Elevated apoD production, derived from adenovirus-mediated gene transfer, resulted in significant reduction in plasma triglyceride levels in mice. This effect was attributable to en­hanced LPL activity and improved catabolism of triglyceride-rich particles. In contrast, VLDL triglyceride production remained unchanged in response to elevated apoD production. These findings were recapitulated in high-fat–induced obese mice. Obese mice with elevated apoD production exhibited significantly improved triglyceride profiles, correlating with increased plasma LPL activity and enhanced postprandial fat tolerance. ApoD was shown to promote LPL-mediated hydrolysis of VLDL in vitro, correlating with its TG-lowering action in vivo. Apolipoprotein D plays a significant role in lipid metabolism. These data provide important clues to clinical observations that genetic variants of apoD are associated with abnormal lipid metabolism and increased risk of metabolic syndrome. PMID:20124557

  2. Inhibition of Intestinal Bile Acid Transporter Slc10a2 Improves Triglyceride Metabolism and Normalizes Elevated Plasma Glucose Levels in Mice

    PubMed Central

    Snaith, Michael; Lindmark, Helena; Lundberg, Johanna; stlund-Lindqvist, Ann-Margret; Angelin, Bo; Rudling, Mats

    2012-01-01

    Interruption of the enterohepatic circulation of bile acids increases cholesterol catabolism, thereby stimulating hepatic cholesterol synthesis from acetate. We hypothesized that such treatment should lower the hepatic acetate pool which may alter triglyceride and glucose metabolism. We explored this using mice deficient of the ileal sodium-dependent BA transporter (Slc10a2) and ob/ob mice treated with a specific inhibitor of Slc10a2. Plasma TG levels were reduced in Slc10a2-deficient mice, and when challenged with a sucrose-rich diet, they displayed a reduced response in hepatic TG production as observed from the mRNA levels of several key enzymes in fatty acid synthesis. This effect was paralleled by a diminished induction of mature sterol regulatory element-binding protein 1c (Srebp1c). Unexpectedly, the SR-diet induced intestinal fibroblast growth factor (FGF) 15 mRNA and normalized bile acid synthesis in Slc10a2?/? mice. Pharmacologic inhibition of Slc10a2 in diabetic ob/ob mice reduced serum glucose, insulin and TGs, as well as hepatic mRNA levels of Srebp1c and its target genes. These responses are contrary to those reported following treatment of mice with a bile acid binding resin. Moreover, when key metabolic signal transduction pathways in the liver were investigated, those of Mek1/2 - Erk1/2 and Akt were blunted after treatment of ob/ob mice with the Slc10a2 inhibitor. It is concluded that abrogation of Slc10a2 reduces hepatic Srebp1c activity and serum TGs, and in the diabetic ob/ob model it also reduces glucose and insulin levels. Hence, targeting of Slc10a2 may be a promising strategy to treat hypertriglyceridemia and diabetes. PMID:22662222

  3. Triglyceride kinetics in fasted and fed E. coli septic rats

    SciTech Connect

    Lanza-Jacoby, S.; Tabares, A. )

    1990-02-26

    The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studies by examining the liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess the liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant intravenous infusion of (2-{sup 3}H) glycerol-labeled VLDL in fasted control, fasted E. coli-treated, fed control, and fed E.coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 {times} 10{sup 7} live E.coli colonies per 100 g body weight. Twenty-four hours following E.coli injection serum TG of fasted E.coli-treated rats was elevated by 170% which was attributed to a 67% decrease in the clearance rate of VLDL-TG in fasted E.coli-treated rats compared with their fasted controls. The secretion of VLDL-TG declined by 31% in the livers of the fasted E.coli-treated rats which was accompanied by a 2-fold increase in the composition of liver TG. In a second series of experiments control and E.coli-treated rats were fed intragastrically (IG) a balanced solution containing glucose plus fat as the sources of nonprotein calories. Serum TG were 26% lower in the fed E.coli-treated rats because the clearance rate increased by 86%. The secretion of TG in the fed septic rats increased by 40% but this difference was not significant. In the septic rat the ability to clear triglycerides from the plasma depends upon the nutritional state.

  4. Triglycerides Test

    MedlinePLUS

    ... Cholesterol ; LDL Cholesterol ; Direct LDL Cholesterol ; VLDL Cholesterol ; Lipid Profile ; Cardiac Risk Assessment All content on Lab ... tests for triglycerides are usually part of a lipid profile used to identify the risk of developing ...

  5. Triglyceride level

    MedlinePLUS

    ... The triglyceride level is usually included in a lipid panel or coronary risk profile. ... 18. No abstract available. Semenkovich CF. Disorders of lipid metabolism. In: Goldman L, Schafer AI, eds. Goldman's ...

  6. Triglyceride-Increasing Alleles Associated with Protection against Type-2 Diabetes

    PubMed Central

    Klimentidis, Yann C.; Chougule, Akshay; Arora, Amit; Frazier-Wood, Alexis C.; Hsu, Chiu-Hsieh

    2015-01-01

    Elevated plasma triglyceride (TG) levels are an established risk factor for type-2 diabetes (T2D). However, recent studies have hinted at the possibility that genetic risk for TG may paradoxically protect against T2D. In this study, we examined the association of genetic risk for TG with incident T2D, and the interaction of baseline TG with TG genetic risk on incident T2D in 13,247 European-Americans (EA) and 3,238 African-Americans (AA) from three prospective cohort studies. A TG genetic risk score (GRS) was calculated based on 31 validated single nucleotide polymorphisms (SNPs). We considered several baseline covariates, including body- mass index (BMI) and lipid traits. Among EA and AA, we find, as expected, that baseline levels of TG are strongly positively associated with incident T2D (p<2 x 10-10). However, the TG GRS is negatively associated with T2D (p=0.013), upon adjusting for only race, in the full dataset. Upon additionally adjusting for age, sex, BMI, high-density lipoprotein cholesterol and TG, the TG GRS is significantly and negatively associated with T2D incidence (p=7.0 x 10-8), with similar trends among both EA and AA. No single SNP appears to be driving this association. We also find a significant statistical interaction of the TG GRS with TG (pinteraction=3.3 x 10-4), whereby the association of TG with incident T2D is strongest among those with low genetic risk for TG. Further research is needed to understand the likely pleiotropic mechanisms underlying these findings, and to clarify the causal relationship between T2D and TG. PMID:26020539

  7. Genetic determinants of plasma triglycerides

    PubMed Central

    Johansen, Christopher T.; Kathiresan, Sekar; Hegele, Robert A.

    2011-01-01

    Plasma triglyceride (TG) concentration is reemerging as an important cardiovascular disease risk factor. More complete understanding of the genes and variants that modulate plasma TG should enable development of markers for risk prediction, diagnosis, prognosis, and response to therapies and might help specify new directions for therapeutic interventions. Recent genome-wide association studies (GWAS) have identified both known and novel loci associated with plasma TG concentration. However, genetic variation at these loci explains only ?10% of overall TG variation within the population. As the GWAS approach may be reaching its limit for discovering genetic determinants of TG, alternative genetic strategies, such as rare variant sequencing studies and evaluation of animal models, may provide complementary information to flesh out knowledge of clinically and biologically important pathways in TG metabolism. Herein, we review genes recently implicated in TG metabolism and describe how some of these genes likely modulate plasma TG concentration. We also discuss lessons regarding plasma TG metabolism learned from various genomic and genetic experimental approaches. Treatment of patients with moderate to severe hypertriglyceridemia with existing therapies is often challenging; thus, gene products and pathways found in recent genetic research studies provide hope for development of more effective clinical strategies. PMID:21041806

  8. Elevated serum semicarbazide-sensitive amine oxidase activity in non-insulin-dependent diabetes mellitus: correlation with body mass index and serum triglyceride.

    PubMed

    Mszros, Z; Szombathy, T; Raimondi, L; Kardi, I; Romics, L; Magyar, K

    1999-01-01

    Previous clinical studies reported elevated semicarbazide-sensitive amine oxidase (SSAO) activity in insulin-dependent diabetes mellitus (IDDM), but there are not sufficient data about SSAO in non-insulin-dependent diabetes mellitus (NIDDM). The present study was conducted to investigate serum SSAO activity in NIDDM patients compared with nondiabetic and IDDM patients. Serum SSAO activity in 61 patients with diabetes (n = 34 NIDDM and n = 27 IDDM) and 36 controls was determined using 14C-benzylamine as a substrate. NIDDM and IDDM patients exhibited higher SSAO activity compared with controls ([mean +/- SD] NIDDM, 164.60+/-69.43 pmol/mg protein/h, P<.0001; IDDM, 143.91+/-72.45 pmol/mg protein/h, P<.002; control, 91.46+/-28.11 pmol/mg protein/h). There was a significant positive correlation between serum SSAO activity and the body mass index (BMI), body weight, hemoglobin A1c (HbA1c), fasting plasma glucose, and triglycerides. Within the control group, SSAO correlated with total cholesterol levels. The progression and severity of diabetic complications such as angiopathy may be exacerbated by cytotoxic metabolites (e.g., formaldehyde and hydrogen peroxide) formed by SSAO. These results reveal the possibility that elevated serum SSAO activity in association with obesity and hyperlipidemia may be a cardiovascular risk factor in diabetes mellitus. PMID:9920154

  9. Acetylcholinesterase (AChE) inhibition aggravates fasting-induced triglyceride accumulation in the mouse liver

    PubMed Central

    Yokota, Shin-Ichi; Nakamura, Kaai; Ando, Midori; Kamei, Hiroyasu; Hakuno, Fumihiko; Takahashi, Shin-Ichiro; Shibata, Shigenobu

    2014-01-01

    Although fasting induces hepatic triglyceride (TG) accumulation in both rodents and humans, little is known about the underlying mechanism. Because parasympathetic nervous system activity tends to attenuate the secretion of very-low-density-lipoprotein-triglyceride (VLDL-TG) and increase TG stores in the liver, and serum cholinesterase activity is elevated in fatty liver disease, the inhibition of the parasympathetic neurotransmitter acetylcholinesterase (AChE) may have some influence on hepatic lipid metabolism. To assess the influence of AChE inhibition on lipid metabolism, the effect of physostigmine, an AChE inhibitor, on fasting-induced increase in liver TG was investigated in mice. In comparison with ad libitum-fed mice, 30 h fasting increased liver TG accumulation accompanied by a downregulation of sterol regulatory element-binding protein 1 (SREBP-1) and liver-fatty acid binding-protein (L-FABP). Physostigmine promoted the 30 h fasting-induced increase in liver TG levels in a dose-dependent manner, accompanied by a significant fall in plasma insulin levels, without a fall in plasma TG. Furthermore, physostigmine significantly attenuated the fasting-induced decrease of both mRNA and protein levels of SREBP-1 and L-FABP, and increased IRS-2 protein levels in the liver. The muscarinic receptor antagonist atropine blocked these effects of physostigmine on liver TG, serum insulin, and hepatic protein levels of SREBP-1 and L-FABP. These results demonstrate that AChE inhibition facilitated fasting-induced TG accumulation with up regulation of the hepatic L-FABP and SREBP-1 in mice, at least in part via the activation of muscarinic acetylcholine receptors. Our studies highlight the crucial role of parasympathetic regulation in fasting-induced TG accumulation, and may be an important source of information on the mechanism of hepatic disorders of lipid metabolism. PMID:25383314

  10. Acetylcholinesterase (AChE) inhibition aggravates fasting-induced triglyceride accumulation in the mouse liver.

    PubMed

    Yokota, Shin-Ichi; Nakamura, Kaai; Ando, Midori; Kamei, Hiroyasu; Hakuno, Fumihiko; Takahashi, Shin-Ichiro; Shibata, Shigenobu

    2014-01-01

    Although fasting induces hepatic triglyceride (TG) accumulation in both rodents and humans, little is known about the underlying mechanism. Because parasympathetic nervous system activity tends to attenuate the secretion of very-low-density-lipoprotein-triglyceride (VLDL-TG) and increase TG stores in the liver, and serum cholinesterase activity is elevated in fatty liver disease, the inhibition of the parasympathetic neurotransmitter acetylcholinesterase (AChE) may have some influence on hepatic lipid metabolism. To assess the influence of AChE inhibition on lipid metabolism, the effect of physostigmine, an AChE inhibitor, on fasting-induced increase in liver TG was investigated in mice. In comparison with ad libitum-fed mice, 30h fasting increased liver TG accumulation accompanied by a downregulation of sterol regulatory element-binding protein 1 (SREBP-1) and liver-fatty acid binding-protein (L-FABP). Physostigmine promoted the 30h fasting-induced increase in liver TG levels in a dose-dependent manner, accompanied by a significant fall in plasma insulin levels, without a fall in plasma TG. Furthermore, physostigmine significantly attenuated the fasting-induced decrease of both mRNA and protein levels of SREBP-1 and L-FABP, and increased IRS-2 protein levels in the liver. The muscarinic receptor antagonist atropine blocked these effects of physostigmine on liver TG, serum insulin, and hepatic protein levels of SREBP-1 and L-FABP. These results demonstrate that AChE inhibition facilitated fasting-induced TG accumulation with up regulation of the hepatic L-FABP and SREBP-1 in mice, at least in part via the activation of muscarinic acetylcholine receptors. Our studies highlight the crucial role of parasympathetic regulation in fasting-induced TG accumulation, and may be an important source of information on the mechanism of hepatic disorders of lipid metabolism. PMID:25383314

  11. Acute hypoxia induces hypertriglyceridemia by decreasing plasma triglyceride clearance in mice

    PubMed Central

    Shin, Mi-Kyung; Yao, Qiaoling; Bevans-Fonti, Shannon; Poole, James; Drager, Luciano F.; Polotsky, Vsevolod Y.

    2012-01-01

    Obstructive sleep apnea (OSA) induces intermittent hypoxia (IH) during sleep and is associated with elevated triglycerides (TG). We previously demonstrated that mice exposed to chronic IH develop elevated TG. We now hypothesize that a single exposure to acute hypoxia also increases TG due to the stimulation of free fatty acid (FFA) mobilization from white adipose tissue (WAT), resulting in increased hepatic TG synthesis and secretion. Male C57BL6/J mice were exposed to FiO2 = 0.21, 0.17, 0.14, 0.10, or 0.07 for 6 h followed by assessment of plasma and liver TG, glucose, FFA, ketones, glycerol, and catecholamines. Hypoxia dose-dependently increased plasma TG, with levels peaking at FiO2 = 0.07. Hepatic TG levels also increased with hypoxia, peaking at FiO2 = 0.10. Plasma catecholamines also increased inversely with FiO2. Plasma ketones, glycerol, and FFA levels were more variable, with different degrees of hypoxia inducing WAT lipolysis and ketosis. FiO2 = 0.10 exposure stimulated WAT lipolysis but decreased the rate of hepatic TG secretion. This degree of hypoxia rapidly and reversibly delayed TG clearance while decreasing [3H]triolein-labeled Intralipid uptake in brown adipose tissue and WAT. Hypoxia decreased adipose tissue lipoprotein lipase (LPL) activity in brown adipose tissue and WAT. In addition, hypoxia decreased the transcription of LPL, peroxisome proliferator-activated receptor-?, and fatty acid transporter CD36. We conclude that acute hypoxia increases plasma TG due to decreased tissue uptake, not increased hepatic TG secretion. PMID:22621867

  12. Large increases in adipose triacylglycerol flux in Cushingoid CRH-Tg mice are explained by futile cycling.

    PubMed

    Harris, Charles; Roohk, Donald J; Fitch, Mark; Boudignon, Benjamin M; Halloran, Bernard P; Hellerstein, Marc K

    2013-02-01

    Glucocorticoids are extremely effective anti-inflammatory therapies, but their clinical use is limited due to severe side effects, including osteoporosis, muscle wasting, fat redistribution, and skin thinning. Here we use heavy water labeling and mass spectrometry to measure fluxes through metabolic pathways impacted by glucocorticoids. We combine these methods with measurements of body composition in corticotropin-releasing hormone (CRH)-transgenic (Tg)(+) mice that have chronically elevated, endogenously produced corticosterone and a phenotype that closely mimics Cushing's disease in humans. CRH-Tg(+) mice had increased adipose mass, adipose triglyceride synthesis, and greatly increased triglyceride/fatty acid cycling in subcutaneous and abdominal fat depots and increased de novo lipogenesis in the abdominal depot. In bone, CRH-Tg(+) mice had decreased bone mass, absolute collagen synthesis rates, and collagen breakdown rate. In skin, CRH-Tg(+) mice had decreased skin thickness and absolute collagen synthesis rates but no decrease in the collagen breakdown rate. In muscle, CRH-Tg(+) mice had decreased muscle mass and absolute protein synthesis but no decrease in the protein breakdown rate. We conclude that chronic exposure to endogenous glucocorticoid excess in mice is associated with ongoing decreases in bone collagen, skin collagen, and muscle protein synthesis without compensatory reduction (coupling) of breakdown rates in skin and muscle. Both of these actions contribute to reduced protein pool sizes. We also conclude that increased cycling between triglycerides and free fatty acids occurs in both abdominal and subcutaneous fat depots in CRH-Tg(+) mice. CRH-Tg mice have both increased lipolysis and increased triglyceride synthesis in adipose tissue. PMID:23211515

  13. Mendelian Randomization Provides No Evidence for a Causal Role of Serum Urate in Increasing Serum Triglyceride Levels

    PubMed Central

    Rasheed, Humaira; Hughes, Kim; Flynn, Tanya J.; Merriman, Tony R.

    2014-01-01

    Background Triglycerides and their lipoprotein transport molecules are risk factors for heart disease. Observational studies have associated elevated levels of serum urate (SU) with triglycerides (Tg) and risk of heart disease. However, owing to unmeasured confounding, observational studies do not provide insight into the causal relationship between SU and Tg. The aim of this study was to test for a causal role of SU in increasing Tg using Mendelian randomisation that accounts for unmeasured confounding. Methods and Results Subjects were of European ancestry from the Atherosclerosis Risk in Communities (ARIC; n=5237) and Framingham Heart (FHS; n=2971) studies. Mendelian randomisation by the two-stage least squares regression method was done with SU as the exposure, a uric acid transporter genetic risk score as instrumental variable and Tg as the outcome. In ordinary linear regression SU was significantly associated with Tg levels (?=2.69 mmol/L change in Tg per mmol/L increase in SU). However, Mendelian randomisation-based estimation showed no evidence for a direct causal association of SU with Tg concentration - there was a non-significant 1.01 mmol/L decrease in Tg per mmol/L increase in SU attributable to the genetic risk score (P=0.21). The reverse analysis using a Tg genetic risk score provided evidence of a causal role for Tg in raising urate in men (PCorrected=0.018). Conclusions These data provide no evidence for a causal role for SU in raising Tg levels, consistent with a previous Mendelian randomisation report of no association between SU and ischaemic heart disease. PMID:25249548

  14. Apo B secretion is regulated by hepatic triglyceride, and not insulin, in a model of increased hepatic insulin signaling

    PubMed Central

    Moon, Byoung C.; Hernandez-Ono, Antonio; Stiles, Bangyan; Wu, Hong; Ginsberg, Henry N.

    2013-01-01

    Objective States of insulin resistance, hyperinsulinemia, and hepatic steatosis are associated with increased secretion of triglycerides (TG) and apolipoprotein B (apoB), even though insulin targets apoB for degradation. We used hepatic-specific (h) Pten knockout (ko) mice, with increased hepatic insulin signaling, to determine the relative roles of insulin signaling and hepatic TG in regulating apoB secretion. Results/Methods TG and apoB secretion were elevated in hPten-ko mice. When hepatic TG was reduced by inhibition of DGAT1/DGAT2 or SREBP-1c, both TG and apoB secretion fell without changes in hepatic insulin signaling. Acute reconstitution of hPten reduced hepatic TG content and both TG and apoB secretion fell within 4 days despite decreased hepatic insulin signaling. Acute depletion of hepatic Pten by adenoviral introduction of Cre into Pten Floxed mice caused steatosis within 4 days, and secretion of TG and apoB both increased despite increased hepatic insulin signaling. Even when steatosis after acute Pten depletion was prevented by pre-treatment with SREBP-1c ASO, apoB secretion was not reduced after 4 days. Ex vivo results were in primary hepatocytes were similar. Conclusion Either hepatic TG is the dominant regulator of apoB secretion or any inhibitory effects of hepatic insulin signaling on apoB secretion is very short-lived. PMID:22155452

  15. Impact of admission triglyceride for early outcome in diabetic patients with stable coronary artery disease

    PubMed Central

    2014-01-01

    Background The role of triglyceride (TG) in predicting the outcomes in diabetic patients with coronary artery disease (CAD) has not been well investigated. Methods A total of 329 cases with stable angina pectoris (SAP) were prospectively enrolled and followed up for an average of 12months. They were classified into the two groups according to the cut-off values of predicting early outcome of fasting TG level (low group <1.2mmol/L, n?=?103; High group ?1.2mmol/L, n?=?226). The relationship between the TG levels and early outcomes were evaluated. Results High TG group showed severer lipid profile and elevated inflammatory markers. During an average of 12-month follow-up, 47 out of 329 patients suffered from pre-specified outcomes. Area under the receivers operating characteristic curve suggested that TG, similar to serum Hemoglobin A1C (HbA1C), was a significant predictor of early outcome for diabetic patients with SAP (P?=?0.002). In Cox regression models, after adjusted age, gender, body mass index, other lipid parameters, fasting blood glucose, high sensitivity C-reactive protein, neutrophil count and HbA1C, TG remained as an independent predictor of adverse prognosis. Conclusions High level of fasting TG (?1.2mmol/L) was an independent predictor for early outcome of diabetic patients with SAP as like as HBA1c and number of affected coronary arteries in the era of revascularization and statin therapeutics. PMID:24766776

  16. Genetic risk score and adiposity interact to influence triglyceride levels in a cohort of Filipino women

    PubMed Central

    Zubair, N; Mayer-Davis, E J; Mendez, M A; Mohlke, K L; North, K E; Adair, L S

    2014-01-01

    Background/Objectives: Individually, genetic variants only moderately influence cardiometabolic (CM) traits, such as lipid and inflammatory markers. In this study we generated genetic risk scores from a combination of previously reported variants influencing CM traits, and used these scores to explore how adiposity levels could mediate genetic contributions to CM traits. Subjects/Methods: Participants included 1649 women from the 2005 Cebu Longitudinal Health and Nutrition Survey. Three genetic risk scores were constructed for C-reactive protein (CRP), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs). We used linear regression models to assess the association between each genetic risk score and its related trait. We also tested for interactions between each score and measures of adiposity. Results: Each genetic risk score explained a greater proportion of variance in trait levels than any individual genetic variant. We found an interaction between the TG genetic risk score (2.2914.34 risk alleles) and waist circumference (WC) (Pinteraction=1.66 10?2). Based on model predictions, for individuals with a higher TG genetic risk score (75th percentile=12), having an elevated WC (?80?cm) increased TG levels from 1.32 to 1.71?mmol?l?1. However, for individuals with a lower score (25th percentile=7), having an elevated WC did not significantly change TG levels. Conclusions: The TG genetic risk score interacted with adiposity to synergistically influence TG levels. For individuals with a genetic predisposition to elevated TG levels, our results suggest that reducing adiposity could possibly prevent further increases in TG levels and thereby lessen the likelihood of adverse health outcomes such as cardiovascular disease. PMID:24932782

  17. Intensity-dependent and sex-specific alterations in hepatic triglyceride metabolism in mice following acute exercise.

    PubMed

    Tuazon, Marc A; McConnell, Taylor R; Wilson, Gabriel J; Anthony, Tracy G; Henderson, Gregory C

    2015-01-01

    Precise regulation of hepatic triglyceride (TG) metabolism and secretion is critical for health, and exercise could play a significant role. We compared one session of high-intensity interval exercise (HIIE) vs. continuous exercise (CE) on hepatic TG metabolism. Female and male mice were assigned to CE, HIIE, or sedentary control (CON). HIIE was a 30-min session of 30-s running intervals (30 m/min) interspersed with 60-s walking periods (5 m/min). CE was a distance- and duration-matched run at 13.8 m/min. Hepatic content of TG and TG secretion rates, as well as expression of relevant genes/proteins, were measured at 3 h (day 1) and 28 h (day 2) postexercise. On day 1, hepatic [TG] in CE and HIIE were both elevated vs. CON in both sexes with an approximately twofold greater elevation in HIIE vs. CE in females. In both sexes, hepatic perilipin 2 (PLIN2) protein on day 1 was increased significantly by both exercise types with a significantly greater increase with HIIE than CE, whereas the increase in mRNA reached significance only after HIIE. On day 2 in both sexes the increases in hepatic TG and PLIN2 with exercise declined toward CON levels. Only HIIE on day 2 resulted in reduced hepatic TG secretion by ?20% in females with no effect in males. Neither exercise modality altered AMPK signaling or microsomal triglyceride transfer protein expression. Females exhibited higher hepatic TG secretion than males in association with different expression levels of related metabolic enzymes. These intensity-dependent and sex-specific alterations following exercise may have implications for sex-based exercise prescription. PMID:25257878

  18. A novel role for ABCA1-generated large pre-? migrating nascent HDL in the regulation of hepatic VLDL triglyceride secretion[S

    PubMed Central

    Chung, Soonkyu; Gebre, Abraham K.; Seo, Jeongmin; Shelness, Gregory S.; Parks, John S.

    2010-01-01

    In Tangier disease, absence of ATP binding cassette transporter A1 (ABCA1) results in reduced plasma HDL and elevated triglyceride (TG) levels. We hypothesized that hepatocyte ABCA1 regulates VLDL TG secretion through nascent HDL production. Silencing of ABCA1 expression in oleate-stimulated rat hepatoma cells resulted in: 1) decreased large nascent HDL (>10 nm diameter) and increased small nascent HDL (<10 nm) formation, 2) increased large buoyant VLDL1 particle secretion, and 3) decreased phosphatidylinositol-3 (PI3) kinase activation. Nascent HDL-containing conditioned medium from rat hepatoma cells or HEK293 cells transfected with ABCA1 was effective in increasing PI3 kinase activation and reducing VLDL TG secretion in ABCA1-silenced hepatoma cells. Addition of isolated large nascent HDL particles to ABCA1-silenced hepatoma cells inhibited VLDL TG secretion to a greater extent than small nascent HDL. Similarly, addition of recombinant HDL, but not human plasma HDL, was effective in attenuating TG secretion and increasing PI3 kinase activation in ABCA1-silenced cells. Collectively, these data suggest that large nascent HDL particles, assembled by hepatic ABCA1, generate a PI3 kinase-mediated autocrine signal that attenuates VLDL maturation and TG secretion. This pathway may explain the elevated plasma TG concentration that occurs in most Tangier subjects and may also account, in part, for the inverse relationship between plasma HDL and TG concentrations in individuals with compromised ABCA1 function. PMID:20215580

  19. Early hyperactivity in lateral entorhinal cortex is associated with elevated levels of AβPP metabolites in the Tg2576 mouse model of Alzheimer’s disease

    PubMed Central

    Xu, Wenjin; Fitzgerald, Shane; Nixon, Ralph A.; Levy, Efrat; Wilson, Donald A.

    2014-01-01

    Alzheimer’s disease (AD) is a neurodegenerative disorder that is the most common cause of dementia in the elderly today. One of the earliest symptoms of AD is olfactory dysfunction. The present study investigated the effects of amyloid β precursor protein (AβPP) metabolites, including amyloid-β (Aβ) and AβPP C-terminal fragments (CTF), on olfactory processing in the lateral entorhinal cortex (LEC) using the Tg2576 mouse model of human AβPP over-expression. The entorhinal cortex is an early target of AD related neuropathology, and the LEC plays an important role in fine odor discrimination and memory. Cohorts of transgenic and age-matched wild-type (WT) mice at 3, 6, and 16 months of age (MO) were anesthetized and acute, single-unit electrophysiology was performed in the LEC. Results showed that Tg2576 exhibited early LEC hyperactivity at 3 and 6 MO compared to WT mice in both local field potential and single-unit spontaneous activity. However, LEC single-unit odor responses and odor receptive fields showed no detectable difference compared to WT at any age. Finally, the very early emergence of olfactory system hyper-excitability corresponded not to detectable Aβ deposition in the olfactory system, but rather to high levels of intracellular AβPP-CTF and soluble Aβ in the anterior piriform cortex (aPCX), a major afferent input to the LEC, by 3 MO. The present results add to the growing evidence of AβPP-related hyper-excitability, and further implicate both soluble Aβ and non-Aβ AβPP metabolites in its early emergence. PMID:25500142

  20. [Triglyceride deposit cardiomyovasculopathy].

    PubMed

    Hirano, Ken-Ichi

    2013-09-01

    Cholesterol is a vital causal factor and focus of research into heart diseases, however the involvement of triglycerides remains unclear. We recently reported a patient suffering from severe congestive heart failure and needing cardiac transplantation. Massive accumulation of triglycerides was noted in coronary atherosclerotic lesions as well as in the myocardium. We named this phenotype"triglyceride deposit cardiomyovasculopathy (TGCV)". The patient was identified as homozygous for a genetic mutation in the adipose triglyceride lipase (ATGL), an essential molecule for hydrolysis of intracellular triglycerides. In this paper, we describe clinical characteristics of ATGL deficiency and discuss what we can learn from this disorder. PMID:24205734

  1. Effects of estrogen on very low-density lipoprotein triglyceride metabolism in fed and fasted chicks

    SciTech Connect

    Park, J.R.

    1988-01-01

    A single injection of estrogen into growing chicks resulted in a marked elevation in plasma triglyceride (TG) followed by phospholipid (PL) and cholesterol (CH) in both fed and fasted chicks. Estrogen caused a development of massive fatty liver in fed chicks. Hepatic malic enzyme and glucose-6-phosphate dehydrogenase activities also increased significantly in fed chicks and, to a small extent, in fasted chicks. Very low density lipoproteins (VLDL) were barely detectable in the fasted control plasma. However, the VLDL concentration increased markedly upon estrogen injection, becoming the most prevalent lipoprotein in the plasma. The administration of estrogen resulted in an increase in oleic acid and a decrease in linoleic acid content except in the cholesteryl ester of VLDL and LDL. VLDL of estrogenized birds had {beta}-mobility on agarose gel electrophoresis, and they eluted in two peaks on agarose gel filtration chromatography. Both peaks on gel filtration exhibited the same {beta}-mobility on agarose gel electrophoresis. Nevertheless, the apoprotein composition of these two peaks were substantially different from each other; apo B was not present in the first peak VLDL. VLDL-TG kinetic studies conducted in vivo, using {sup 14}C-TG-VLDL prepared endogenously from control and estrogenized chicks revealed that VLDL-TG produced from the former had a higher fractional catabolic rate (FCR) than VLDL-TG from the latter.

  2. Serum triglycerides and risk of cardiovascular disease.

    PubMed

    Boullart, A C I; de Graaf, J; Stalenhoef, A F

    2012-05-01

    Dyslipidemia, especially elevated serum levels of cholesterol, is causally related to cardiovascular disease. The specific role of triglycerides has long been controversial. In this article we discuss the role of serum triglycerides in relation to the risk of cardiovascular disease. First, the (patho)physiology of triglycerides is described, including the definition and a short summary of the primary and secondary causes of hypertriglyceridemia. Furthermore, we will give an overview of the published epidemiological studies concerning hypertriglyceridemia and cardiovascular disease to support the view that triglyceride-rich lipoproteins are an independently associated risk factor. Finally, treatment strategies and treatment targets are discussed. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease. PMID:22015388

  3. Postprandial metabolism of meal triglyceride in humans*,**

    PubMed Central

    Lambert, Jennifer E.; Parks, Elizabeth J.

    2012-01-01

    The intake of dietary fat above energy needs has contributed to the growing rates of obesity worldwide. The concept of disease development occurring in the fed state now has much support and dysregulation of substrate flux may occur due to poor handling of dietary fat in the immediate postprandial period. The present paper will review recent observations implicating cephalic phase events in the control of enterocyte lipid transport, the impact of varying the composition of meals on subsequent fat metabolism, and the means by which dietary lipid carried in chylomicrons can lead to elevated postprandial non-esterified fatty acid concentrations. This discussion is followed by an evaluation of the data on quantitative meal fat oxidation at the whole body level and an examination of dietary fat clearance to peripheral tissues with particular attention paid to skeletal muscle and liver given the role of ectopic lipid deposition in insulin resistance. Estimates derived from data of dietary-TG clearance show good agreement with clearance to the liver equaling 812% of meal fat in lean subjects and this number appears higher (1016%) in subjects with diabetes and fatty liver disease. Finally, we discuss new methods with which to study dietary fatty acid partitioning in vivo. Future research is needed to include a more comprehensive understanding of 1) the potential for differential oxidation of saturated versus unsaturated fatty acids which might lead to meaningful energy deficit and whether this parameter varies based on insulin sensitivity, 2) whether compartmentalization exists for diet-derived fatty acids within tissues vs. intracellular pools, and 3) the role of reduced peripheral fatty acid clearance in the development of fatty liver disease. Further advancements in the quantitation of dietary fat absorption and disposal will be central to the development of therapies designed to treat diet-induced obesity. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease. PMID:22281699

  4. Postprandial metabolism of meal triglyceride in humans.

    PubMed

    Lambert, Jennifer E; Parks, Elizabeth J

    2012-05-01

    The intake of dietary fat above energy needs has contributed to the growing rates of obesity worldwide. The concept of disease development occurring in the fed state now has much support and dysregulation of substrate flux may occur due to poor handling of dietary fat in the immediate postprandial period. The present paper will review recent observations implicating cephalic phase events in the control of enterocyte lipid transport, the impact of varying the composition of meals on subsequent fat metabolism, and the means by which dietary lipid carried in chylomicrons can lead to elevated postprandial non-esterified fatty acid concentrations. This discussion is followed by an evaluation of the data on quantitative meal fat oxidation at the whole body level and an examination of dietary fat clearance to peripheral tissues - with particular attention paid to skeletal muscle and liver given the role of ectopic lipid deposition in insulin resistance. Estimates derived from data of dietary-TG clearance show good agreement with clearance to the liver equaling 8-12% of meal fat in lean subjects and this number appears higher (10-16%) in subjects with diabetes and fatty liver disease. Finally, we discuss new methods with which to study dietary fatty acid partitioning in vivo. Future research is needed to include a more comprehensive understanding of 1) the potential for differential oxidation of saturated versus unsaturated fatty acids which might lead to meaningful energy deficit and whether this parameter varies based on insulin sensitivity, 2) whether compartmentalization exists for diet-derived fatty acids within tissues vs. intracellular pools, and 3) the role of reduced peripheral fatty acid clearance in the development of fatty liver disease. Further advancements in the quantitation of dietary fat absorption and disposal will be central to the development of therapies designed to treat diet-induced obesity. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease. PMID:22281699

  5. Identification of a small molecule that stabilizes lipoprotein lipase in vitro and lowers triglycerides in vivo.

    PubMed

    Larsson, Mikael; Caraballo, Rémi; Ericsson, Madelene; Lookene, Aivar; Enquist, Per-Anders; Elofsson, Mikael; Nilsson, Stefan K; Olivecrona, Gunilla

    2014-07-25

    Patients at increased cardiovascular risk commonly display high levels of plasma triglycerides (TGs), elevated LDL cholesterol, small dense LDL particles and low levels of HDL-cholesterol. Many remain at high risk even after successful statin therapy, presumably because TG levels remain high. Lipoprotein lipase (LPL) maintains TG homeostasis in blood by hydrolysis of TG-rich lipoproteins. Efficient clearance of TGs is accompanied by increased levels of HDL-cholesterol and decreased levels of small dense LDL. Given the central role of LPL in lipid metabolism we sought to find small molecules that could increase LPL activity and serve as starting points for drug development efforts against cardiovascular disease. Using a small molecule screening approach we have identified small molecules that can protect LPL from inactivation by the controller protein angiopoietin-like protein 4 during incubations in vitro. One of the selected compounds, 50F10, was directly shown to preserve the active homodimer structure of LPL, as demonstrated by heparin-Sepharose chromatography. On injection to hypertriglyceridemic apolipoprotein A-V deficient mice the compound ameliorated the postprandial response after an olive oil gavage. This is a potential lead compound for the development of drugs that could reduce the residual risk associated with elevated plasma TGs in dyslipidemia. PMID:24984153

  6. Thyroid function modifies the association between ratio of triglyceride to high-density lipoprotein cholesterol and renal function: a multicenter cross-sectional study.

    PubMed

    Yuan, Zhongshang; Zhao, Meng; Zhang, Bingchang; Zhang, Haiqing; Zhang, Xu; Guan, Qingbo; Ning, Guang; Gao, Ling; Xue, Fuzhong; Zhao, Jiajun

    2015-01-01

    Hypothyroidism was confirmed to be associated with both dyslipidemia and renal dysfunction. However, the impact of thyroid function on the relationship between serum lipid levels and renal function has never been given sufficient attention. In this large-scale multicenter cross-sectional study, the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL) and the prevalence of hypothyroidism in CKD subjects were significantly higher than those in non-CKD ones (P?TG/HDL was shown to be significantly associated with serum Cr levels (??=?0.551; 95%CI, 0.394-0.708), and eGFR (??=?-0.481; 95%CI, -0.731--0.230). The risk for CKD was significantly increased as TG/HDL ratio was elevated (adjusted odds ratio?=?1.20; 95%CI, 1.11-1.27). These significant associations were found among subjects with euthyroidism and hypothyroidism rather than hyperthyroidism. Furthermore, the associations between TG/HDL and Cr or CKD status were significantly greater in hypothyroidism than those in euthyroidism (P?elevated TG/HDL ratio was associated with renal dysfunction; it exhibited a significantly stronger association with Cr and CKD in hypothyroidism than in euthyroidism. Therefore, more attention should be paid on lipid profile to prevent or delay the occurrence and progression of renal dysfunction, especially for those with hypothyroidism. PMID:26179571

  7. Adipocyte ATP-binding cassette G1 promotes triglyceride storage, fat mass growth, and human obesity.

    PubMed

    Frisdal, Eric; Le Lay, Soazig; Hooton, Henri; Poupel, Lucie; Olivier, Maryline; Alili, Rohia; Plengpanich, Wanee; Villard, Elise F; Gilibert, Sophie; Lhomme, Marie; Superville, Alexandre; Miftah-Alkhair, Lobna; Chapman, M John; Dallinga-Thie, Geesje M; Venteclef, Nicolas; Poitou, Christine; Tordjman, Joan; Lesnik, Philippe; Kontush, Anatol; Huby, Thierry; Dugail, Isabelle; Clement, Karine; Guerin, Maryse; Le Goff, Wilfried

    2015-03-01

    The role of the ATP-binding cassette G1 (ABCG1) transporter in human pathophysiology is still largely unknown. Indeed, beyond its role in mediating free cholesterol efflux to HDL, the ABCG1 transporter equally promotes lipid accumulation in a triglyceride (TG)-rich environment through regulation of the bioavailability of lipoprotein lipase (LPL). Because both ABCG1 and LPL are expressed in adipose tissue, we hypothesized that ABCG1 is implicated in adipocyte TG storage and therefore could be a major actor in adipose tissue fat accumulation. Silencing of Abcg1 expression by RNA interference in 3T3-L1 preadipocytes compromised LPL-dependent TG accumulation during the initial phase of differentiation. Generation of stable Abcg1 knockdown 3T3-L1 adipocytes revealed that Abcg1 deficiency reduces TG storage and diminishes lipid droplet size through inhibition of Pparγ expression. Strikingly, local inhibition of adipocyte Abcg1 in adipose tissue from mice fed a high-fat diet led to a rapid decrease of adiposity and weight gain. Analysis of two frequent ABCG1 single nucleotide polymorphisms (rs1893590 [A/C] and rs1378577 [T/G]) in morbidly obese individuals indicated that elevated ABCG1 expression in adipose tissue was associated with increased PPARγ expression and adiposity concomitant to increased fat mass and BMI (haplotype AT>GC). The critical role of ABCG1 in obesity was further confirmed in independent populations of severe obese and diabetic obese individuals. This study identifies for the first time a major role of adipocyte ABCG1 in adiposity and fat mass growth and suggests that adipose ABCG1 might represent a potential therapeutic target in obesity. PMID:25249572

  8. Central effects of humanin on hepatic triglyceride secretion.

    PubMed

    Gong, Zhenwei; Su, Kai; Cui, Lingguang; Tas, Emir; Zhang, Ting; Dong, H Henry; Yakar, Shoshana; Muzumdar, Radhika H

    2015-08-01

    Humanin (HN) is an endogenous mitochondria-associated peptide that has been shown to protect against various Alzheimer's disease-associated insults, myocardial ischemia-reperfusion injury, and reactive oxygen species-induced cell death. We have shown previously that HN improves whole body glucose homeostasis by improving insulin sensitivity and increasing glucose-stimulated insulin secretion (GSIS) from the β-cells. Here, we report that intraperitoneal treatment with one of HN analogs, HNG, decreases body weight gain, visceral fat, and hepatic triglyceride (TG) accumulation in high-fat diet-fed mice. The decrease in hepatic TG accumulation is due to increased activity of hepatic microsomal triglyceride transfer protein (MTTP) and increased hepatic TG secretion. Both intravenous (iv) and intracerebroventricular (icv) infusion of HNG acutely increase TG secretion from the liver. Vagotomy blocks the effect on both iv and icv HNG on TG secretion, suggesting that the effects of HNG on hepatic TG flux are centrally mediated. Our data suggest that HN is a new player in central regulation of peripheral lipid metabolism. PMID:26058861

  9. Inborn errors of cytoplasmic triglyceride metabolism.

    PubMed

    Wu, Jiang Wei; Yang, Hao; Wang, Shu Pei; Soni, Krishnakant G; Brunel-Guitton, Catherine; Mitchell, Grant A

    2015-01-01

    Triglyceride (TG) synthesis, storage, and degradation together constitute cytoplasmic TG metabolism (CTGM). CTGM is mostly studied in adipocytes, where starting from glycerol-3-phosphate and fatty acyl (FA)-coenzyme A (CoA), TGs are synthesized then stored in cytoplasmic lipid droplets. TG hydrolysis proceeds sequentially, producing FAs and glycerol. Several reactions of CTGM can be catalyzed by more than one enzyme, creating great potential for complex tissue-specific physiology. In adipose tissue, CTGM provides FA as a systemic energy source during fasting and is related to obesity. Inborn errors and mouse models have demonstrated the importance of CTGM for non-adipose tissues, including skeletal muscle, myocardium and liver, because steatosis and dysfunction can occur. We discuss known inborn errors of CTGM, including deficiencies of: AGPAT2 (a form of generalized lipodystrophy), LPIN1 (childhood rhabdomyolysis), LPIN2 (an inflammatory condition, Majeed syndrome, described elsewhere in this issue), DGAT1 (protein loosing enteropathy), perilipin 1 (partial lipodystrophy), CGI-58 (gene ABHD5, neutral lipid storage disease (NLSD) with ichthyosis and "Jordan's anomaly" of vacuolated polymorphonuclear leukocytes), adipose triglyceride lipase (ATGL, gene PNPLA2, NLSD with myopathy, cardiomyopathy and Jordan's anomaly), hormone-sensitive lipase (HSL, gene LIPE, hypertriglyceridemia, and insulin resistance). Two inborn errors of glycerol metabolism are known: glycerol kinase (GK, causing pseudohypertriglyceridemia) and glycerol-3-phosphate dehydrogenase (GPD1, childhood hepatic steatosis). Mouse models often resemble human phenotypes but may diverge markedly. Inborn errors have been described for less than one-third of CTGM enzymes, and new phenotypes may yet be identified. PMID:25300978

  10. Gut triglyceride production.

    PubMed

    Pan, Xiaoyue; Hussain, M Mahmood

    2012-05-01

    Our knowledge of how the body absorbs triacylglycerols (TAG) from the diet and how this process is regulated has increased at a rapid rate in recent years. Dietary TAG are hydrolyzed in the intestinal lumen to free fatty acids (FFA) and monoacylglycerols (MAG), which are taken up by enterocytes from their apical side, transported to the endoplasmic reticulum (ER) and resynthesized into TAG. TAG are assembled into chylomicrons (CM) in the ER, transported to the Golgi via pre-chylomicron transport vesicles and secreted towards the basolateral side. In this review, we mainly focus on the roles of key proteins involved in uptake and intracellular transport of fatty acids, their conversion to TAG and packaging into CM. We will also discuss intracellular transport and secretion of CM. Moreover, we will bring to light few factors that regulate gut triglyceride production. Furthermore, we briefly summarize pathways involved in cholesterol absorption. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease. PMID:21989069

  11. Triglyceride-Lowering Response To Plant Sterol and Stanol Consumption

    PubMed Central

    Rideout, Todd C; Marinangeli, Christopher PF; Harding, Scott V

    2015-01-01

    Phytosterols (PS) have long been recognized for their cholesterol-lowering action, however, recent work has highlighted triglyceride (TG)-lowering responses to PS that may have been overlooked in previous human interventions and mechanistic animal model studies. This review assesses the current state of knowledge regarding the effect of dietary PS supplementation on blood TG concentrations by examining the average therapeutic response, potential mechanisms, and metabolic and genetic factors that may contribute to inter-individual variability. Data from human intervention trials demonstrates that, compared to baseline concentrations, PS supplementation results in a variable TG-lowering response ranging from 0.8 to 28%. It is evident that hypertriglyceridemic individuals (>1.7 mmol/L) have a greater TG-lowering response to PS (11–28%) than subjects with normal plasma TG concentrations (0.8–7%). Although a genetic basis for the variable TG-lowering effects of PS is probable, there are only limited studies to draw on. The available data suggest that polymorphisms in the apolipoprotein E (apoE) gene may affect responsiveness, with PS-induced reductions in TG more readily evident in apoE2 than apoE3 or E4 subjects. Although only a minimal number of animal model studies have been conducted to specifically examine the mechanisms whereby PS may reduce blood TG concentrations, it appears that there may be multiple mechanisms involved including interruption of intestinal fatty acid absorption and modulation of hepatic lipogenesis and VLDL packaging and secretion. In summary, the available data suggest that PS may be an effective therapy to lower blood TG, particularly in hypertriglyceridemic individuals. However, before PS can be widely recommended as a TG-lowering therapy, studies that are specifically powered and designed to fully access therapeutic responses and the mechanisms involved are required. PMID:25941890

  12. Fatty acid compositions of triglycerides and free fatty acids in sebum depend on amount of triglycerides, and do not differ in presence or absence of acne vulgaris.

    PubMed

    Akaza, Narifumi; Akamatsu, Hirohiko; Numata, Shigeki; Matsusue, Miyuki; Mashima, Yasuo; Miyawaki, Masaaki; Yamada, Shunji; Yagami, Akiko; Nakata, Satoru; Matsunaga, Kayoko

    2014-12-01

    To clarify the influence of the fatty acid composition of sebum in acne vulgaris, we investigated the amounts and fatty acid compositions of triglycerides (TG) and free fatty acids (FFA), and the amounts of cutaneous superficial Propionibacterium acnes in acne patients and healthy subjects. The foreheads of 18 female patients, 10 male patients, 10 healthy females and 10 healthy males were studied in a Japanese population. There were significant differences in the amounts of sebum, TG and cutaneous superficial P. acnes, as well as the fatty acid compositions of TG and FFA between acne patients and healthy subjects in females. Their fatty acid compositions were correlated with the amount of TG with or without acne. It was clarified that the fatty acid compositions of TG and FFA depended on the amount of TG, and there were no differences in the fatty acid composition in the presence and absence of acne. PMID:25388081

  13. Thyroglobulin (Tg) Testing Revisited: Tg Assays, TgAb Assays, and Correlation of Results With Clinical Outcomes

    PubMed Central

    Netzel, Brian C.; Grebe, Stefan K. G.; Carranza Leon, B. Gisella; Castro, M. Regina; Clark, Penelope M.; Hoofnagle, Andrew N.; Spencer, Carole A.; Turcu, Adina F.

    2015-01-01

    Context: Measurement of thyroglobulin (Tg) by mass spectrometry (Tg-MS) is emerging as a tool for accurate Tg quantification in patients with anti-Tg autoantibodies (TgAbs). Objective: The objective of the study was to perform analytical and clinical evaluations of two Tg-MS assays in comparison with immunometric Tg assays (Tg-IAs) and Tg RIAs (Tg-RIAs) in a cohort of thyroid cancer patients. Methods: A total of 589 samples from 495 patients, 243 TgAb?/252 TgAb+, were tested by Beckman, Roche, Siemens-Immulite, and Thermo-Brahms Tg and TgAb assays, two Tg-RIAs, and two Tg-MS assays. Results: The frequency of TgAb+ was 58%, 41%, 27%, and 39% for Roche, Beckman, Siemens-Immulite, and Thermo-Brahms, respectively. In TgAb? samples, clinical sensitivities and specificities of 100% and 74%100%, respectively, were observed across all assays. In TgAb+ samples, all Tg-IAs demonstrated assay-dependent Tg underestimation, ranging from 41% to 86%. In TgAb+ samples, the use of a common cutoff (0.5 ng/mL) for the Tg-MS, three Tg-IAs, and the USC-RIA improved the sensitivity for the Tg-MSs and Tg-RIAs when compared with the Tg-IAs. In up to 20% of TgAb+ cases, Tg-IAs failed to detect Tg that was detectable by Tg-MS. In Tg-RIAs false-high biases were observed in TgAb+ samples containing low Tg concentrations. Conclusions: Tg-IAs remain the method of choice for Tg quantitation in TgAb? patients. In TgAb+ patients with undetectable Tg by immunometric assay, the Tg-MS will detect Tg in up to 20% additional cases. The Tg-RIA will detect Tg in approximately 35% cases, but a significant proportion of these will be clinical false-positive results. The undetectable Tg-MS seen in approximately 40% of TgAb+ cases in patients with disease need further evaluation. PMID:26079778

  14. Central nervous system neuropeptide Y regulates mediators of hepatic phospholipid remodeling and very low-density lipoprotein triglyceride secretion via sympathetic innervation

    PubMed Central

    Rojas, Jennifer M.; Bruinstroop, Eveline; Printz, Richard L.; Alijagic-Boers, Aldijana; Foppen, Ewout; Turney, Maxine K.; George, Leena; Beck-Sickinger, Annette G.; Kalsbeek, Andries; Niswender, Kevin D.

    2015-01-01

    Objective Elevated very low-density lipoprotein (VLDL)-triglyceride (TG) secretion from the liver contributes to an atherogenic dyslipidemia that is associated with obesity, diabetes and the metabolic syndrome. Numerous models of obesity and diabetes are characterized by increased central nervous system (CNS) neuropeptide Y (NPY); in fact, a single intracerebroventricular (icv) administration of NPY in lean fasted rats elevates hepatic VLDL-TG secretion and does so, in large part, via signaling through the CNS NPY Y1 receptor. Thus, our overarching hypothesis is that elevated CNS NPY action contributes to dyslipidemia by activating central circuits that modulate liver lipid metabolism. Methods Chow-fed Zucker fatty (ZF) rats were pair-fed by matching their caloric intake to that of lean controls and effects on body weight, plasma TG, and liver content of TG and phospholipid (PL) were compared to ad-libitum (ad-lib) fed ZF rats. Additionally, lean 4-hfasted rats with intact or disrupted hepatic sympathetic innervation were treated with icv NPY or NPY Y1 receptor agonist to identify novel hepatic mechanisms by which NPY promotes VLDL particle maturation and secretion. Results Manipulation of plasma TG levels in obese ZF rats, through pair-feeding had no effect on liver TG content; however, hepatic PL content was substantially reduced and was tightly correlated with plasma TG levels. Treatment with icv NPY or a selective NPY Y1 receptor agonist in lean fasted rats robustly activated key hepatic regulatory proteins, stearoyl-CoA desaturase-1 (SCD-1), ADP-ribosylation factor-1 (ARF-1), and lipin-1, known to be involved in remodeling liver PL into TG for VLDL maturation and secretion. Lastly, we show that the effects of CNS NPY on key liporegulatory proteins are attenuated by hepatic sympathetic denervation. Conclusions These data support a model in which CNS NPY modulates mediators of hepatic PL remodeling and VLDL maturation to stimulate VLDL-TG secretion that is dependent on the Y1 receptor and sympathetic signaling to the liver. PMID:25737956

  15. TG-21 versus TG-25: a comparison for electrons.

    PubMed

    Followill, D S; Davis, D S; Hanson, W F

    1997-07-01

    Since 1984, the Radiological Physics Center (RPC) has used the American Association of Physicists in Medicine Task Group 21 (TG-21) protocol (absorbed dose determination) as the basis of its On-site Dosimetry Review visits to institutions participating in the National Cancer Institute's cooperative clinical trials. Subsequent to the TG-21 protocol, the Task Group 25 (TG-25) report on electron-beam dosimetry was published. The TG-25 report was not intended to supercede the TG-21 protocol, but to supplement it for depths other than dmax. However, both reports included measurement techniques and data regarding the calibration of electron beams. TG-25 was not intended for absolute calibrations made clear by the fact that it does not present all of the data required for plastic phantom calibrations, i.e., unrestricted stopping power ratios. As a result, some confusion has arisen at various institutions as to which protocol should be used for machine calibration. In this study, possible discrepancies that arise when using TG-21, a version of TG-21 modified by the RPC, and TG-25 are compared. The differences in the results are calculated as a function of energy (6 and 20 MeV), chamber type (cylindrical or parallel plate), and the type of phantom material (water, polystyrene, or acrylic). The largest discrepancies noted were between TG-25 and the two TG-21 methods for low-energy electrons in either water or polystyrene. The mean difference for all conditions was 0.8% with a maximum value of 3.3% in polystyrene. The definition of the effective point of measurement; determination of the mean nominal incident energy (E0), mean energy at depth (EZ) and most probable energy at the surface (Ep,0) for each protocol, and subsequent stopping power ratio, chamber replacement factor, and electron fluence correction factor are the major contributors to the calculated differences. PMID:9243474

  16. Coordinated Defects in Hepatic Long Chain Fatty Acid Metabolism and Triglyceride Accumulation Contribute to Insulin Resistance in Non-Human Primates

    PubMed Central

    Gastaldelli, Amalia; Casiraghi, Francesca; Halff, Glenn A.; Abrahamian, Gregory A.; Davalli, Alberto M.; Bastarrachea, Raul A.; Comuzzie, Anthony G.; Guardado-Mendoza, Rodolfo; Jimenez-Ceja, Lilia M.; Mattern, Vicki; Paez, Ana Maria; Ricotti, Andrea; Tejero, Mary E.; Higgins, Paul B.; Rodriguez-Sanchez, Iram Pablo; Tripathy, Devjit; DeFronzo, Ralph A.; Dick, Edward J.; Cline, Gary W.; Folli, Franco

    2011-01-01

    Non-Alcoholic fatty liver disease (NAFLD) is characterized by accumulation of triglycerides (TG) in hepatocytes, which may also trigger cirrhosis. The mechanisms of NAFLD are not fully understood, but insulin resistance has been proposed as a key determinant. Aims To determine the TG content and long chain fatty acyl CoA composition profile in liver from obese non-diabetic insulin resistant (IR) and lean insulin sensitive (IS) baboons in relation with hepatic and peripheral insulin sensitivity. Methods Twenty baboons with varying grades of adiposity were studied. Hepatic (liver) and peripheral (mainly muscle) insulin sensitivity was measured with a euglycemic clamp and QUICKI. Liver biopsies were performed at baseline for TG content and LCFA profile by mass spectrometry, and histological analysis. Findings were correlated with clinical and biochemical markers of adiposity and insulin resistance. Results Obese IR baboons had elevated liver TG content compared to IS. Furthermore, the concentration of unsaturated (LC-UFA) was greater than saturated (LC-SFA) fatty acyl CoA in the liver. Interestingly, LC-FA UFA and SFA correlated with waist, BMI, insulin, NEFA, TG, QUICKI, but not M/I. Histological findings of NAFLD ranging from focal to diffuse hepatic steatosis were found in obese IR baboons. Conclusion Liver TG content is closely related with both hepatic and peripheral IR, whereas liver LC-UFA and LC-SFA are closely related only with hepatic IR in non-human primates. Mechanisms leading to the accumulation of TG, LC-UFA and an altered UFA: LC-SFA ratio may play an important role in the pathophysiology of fatty liver disease in humans. PMID:22125617

  17. PCSK9 and triglyceride-rich lipoprotein metabolism

    PubMed Central

    Druce, Irena; Abujrad, Hussein; Ooi, Teik Chye

    2015-01-01

    Abstract Pro-protein convertase subtilisin-kexin 9 (PCSK9) is known to affect low-density lipoprotein (LDL) metabolism, but there are indications from several lines of research that it may also influence the metabolism of other lipoproteins, especially triglyceride-rich lipoproteins (TRL). This review summarizes the current data on this possible role of PCSK9. A link between PCSK9 and TRL has been suggested through the demonstration of (1) a correlation between plasma PCSK9 and triglyceride (TG) levels in health and disease, (2) a correlation between plasma PCSK9 and markers of carbohydrate metabolism, which is closely related to TG metabolism, (3) an effect of TG-lowering fibrate therapy on plasma PCSK9 levels, (4) an effect of PCSK9 on postprandial lipemia, (5) an effect of PCSK9 on adipose tissue biology, (6) an effect of PCSK9 on apolipoprotein B production from the liver and intestines, (7) an effect of PCSK9 on receptors other than low density lipoprotein receptor (LDLR) that are involved in TRL metabolism, and (8) an effect of anti-PCSK9 therapy on serum TG levels. The underlying mechanisms are unclear but starting to emerge. PMID:26320603

  18. Thyrotropin and Obesity: Increased Adipose Triglyceride Content Through Glycerol-3-Phosphate Acyltransferase 3

    PubMed Central

    Ma, Shizhan; Jing, Fei; Xu, Chao; Zhou, Lingyan; Song, Yongfeng; Yu, Chunxiao; Jiang, Dongqing; Gao, Ling; Li, Yujie; Guan, Qingbo; Zhao, Jiajun

    2015-01-01

    Epidemiological evidence indicates that thyrotropin (TSH) is positively correlated with the severity of obesity. However, the mechanism remains unclear. Here, we show that TSH promoted triglyceride (TG) synthesis in differentiated adipocytes in a thyroid hormone-independent manner. Mice with subclinical hypothyroidism, which is characterized by elevated serum TSH but not thyroid hormone levels, demonstrated a 35% increase in the total white adipose mass compared with their wild-type littermates. Interestingly, Tshr KO mice, which had normal thyroid hormone levels after thyroid hormone supplementation, resisted high-fat diet-induced obesity. TSH could directly induce the activity of glycerol-3-phosphate-acyltransferase 3 (GPAT3), the rate-limiting enzyme in TG synthesis, in differentiated 3T3-L1 adipocytes. However, following either the knockdown of Tshr and PPARγ or the constitutive activation of AMPK, the changes to TSH-triggered GPAT3 activity and adipogenesis disappeared. The over-expression of PPARγ or the expression of an AMPK dominant negative mutant reversed the TSH-induced changes. Thus, TSH acted as a previously unrecognized master regulator of adipogenesis, indicating that modification of the AMPK/PPARγ/GPAT3 axis via the TSH receptor might serve as a potential therapeutic target for obesity. PMID:25559747

  19. Fish oil how does it reduce plasma triglycerides?

    PubMed Central

    Shearer, Gregory C.; Savinova, Olga V.; Harris, William S.

    2012-01-01

    Long chain omega-3 fatty acids (FAs) are effective for reducing plasma triglyceride (TG) levels. At the pharmaceutical dose, 3.4 g/day, they reduce plasma TG by about 25-50% after one month of treatment, resulting primarily from the decline in hepatic very low density lipoprotein (VLDL-TG) production, and secondarily from the increase in VLDL clearance. Numerous mechanisms have been shown to contribute to the TG overproduction, but a key component is an increase in the availability of FAs in the liver. The liver derives FAs from three sources: diet (delivered via chylomicron remnants), de novo lipogenesis, and circulating non-esterified FAs (NEFAs). Of these, NEFAs contribute the largest fraction to VLDL-TG production in both normotriglyceridemic subjects and hypertriglyceridemic, insulin resistant patients. Thus reducing NEFA delivery to the liver would be a likely locus of action for fish oils (FO). The key regulator of plasma NEFA is intracellular adipocyte lipolysis via hormone sensitive lipase (HSL), which increases as insulin sensitivity worsens. FO counteracts intracellular lipolysis in adipocytes by suppressing adipose tissue inflammation. In addition, FO increases extracellular lipolysis by lipoprotein lipase (LpL) in adipose, heart and skeletal muscle and enhances hepatic and skeletal muscle ?-oxidation which contributes to reduced FA delivery to the liver. FO could activate transcription factors which control metabolic pathways in a tissue specific manner regulating nutrient traffic and reducing plasma TG. PMID:22041134

  20. Association of apolipoprotein A5 concentration with serum insulin and triglyceride levels and coronary artery disease in Korean men

    Technology Transfer Automated Retrieval System (TEKTRAN)

    OBJECTIVE: Whereas the relation between apolipoprotein A5 (APOA5) gene polymorphisms and triglycerides (TG) levels is well established, the associations between apoA5 concentrations, TG and coronary artery disease (CAD) remain controversial. Therefore, we investigated these relations in the setting ...

  1. Lack of triglyceride-lowering properties of fish oil in apolipoprotein e-deficient mice.

    PubMed

    Asset, G; Baug, E; Fruchart, J C; Dallongeville, J

    2001-03-01

    Fish oil is a potent triglyceride (TG)-lowering agent in humans. The goal of the present study was to assess the contribution of decreased triglyceride synthesis and of apoE in mediation of the triglyceride-lowering effect of fish oil. To this end, apoE-deficient mice and wild-type control mice were supplemented with either coconut oil, sunflower oil, or fish oil (20% wt/wt) for 2 weeks. Compared with coconut oil and sunflower oil, fish oil reduced the concentrations of cholesterol and triglycerides in the wild-type mice, whereas it had no effect on cholesterol concentration and it had a triglyceride-raising effect in apoE-deficient mice. The latter was due to increased triglyceride concentrations in the d<1.019 g/mL plasma density fraction. In apoE-deficient mice, but not in wild-type mice, the postprandial triglyceride area under the curve was higher after an intragastric load of fish oil than after a sunflower oil load. These data indicate an impairment of triglyceride metabolism in the fish oil-fed apoE-deficient mice. Compared with coconut oil and sunflower oil, fish oil lowered triglyceride production rates measured with the Triton method in both wild-type (P<0.0001) and apoE-deficient mice (P<0.0001). Similarly, in vitro lipoprotein lipase-mediated lipolysis of VLDL was lowered in the fish oil-fed wild-type and apoE-deficient mice, suggesting an alteration in VLDL lipolysis independent of the mice genotype. In conclusion, fish oil does not decrease triglyceride concentrations in apoE-deficient mice despite reducing triglyceride production rates, suggesting that decreased triglyceride synthesis is not sufficient to lower triglyceride concentrations in mice. ApoE appears to be necessary for fish oil to lower plasma triglyceride concentrations, indicating a critical role of apoE in this process. PMID:11231920

  2. Causes of the triglyceride-lowering effect of exercise training in rats

    NASA Technical Reports Server (NTRS)

    Mondon, C. E.; Dolkas, C. B.; Tobey, T.; Reaven, G. M.

    1984-01-01

    Studies conducted with human subjects and laboratory animals have consistently shown a reduction in serum triglyceride (TG) in exercise-trained subjects. The obtained data have suggested that this decrease was due to a reduction in hepatic TG secretion. The present investigation, which was conducted with rats trained to attain a high level of spontaneous running activity, provides support for the earlier results. In addition, insights are obtained regarding the mechanism by which exercise lowers TG levels. Since the liver accounts for the vast majority of endogenous very low density lipoprotein (VLDL)-TG secretion, the fall in TG secretion rate seen in exercise-trained (ET) rats must be due to a reduction in hepatic TG secretion.

  3. Postabsorptive VLDL-TG fatty acid storage in adipose tissue in lean and obese women.

    PubMed

    Nellemann, Birgitte; Gormsen, Lars C; Christiansen, Jens S; Jensen, Michael D; Nielsen, Sren

    2010-07-01

    Adipose tissue lipoprotein lipase (LPL) is a necessary enzyme for storage of very-low-density lipoprotein-triglyceride (VLDL-TG), but whether it is a rate-determining step is unknown. To test this hypothesis we included 10 upper-body obese (UBO), 11 lower-body obese (LBO), and 8 lean women. We infused ex vivo-labeled VLDL-(14)C-TG and then performed adipose tissue biopsies to understand the relationship between VLDL-TG storage and LPL activity in femoral and upper-body subcutaneous fat. Both fractional tracer storage and rate of storage of the VLDL-TG tracer were evaluated. VLDL-TG storage was also examined as a function of regional adipose tissue blood flow (ATBF), insulin, VLDL-TG turnover, regional fat mass, fat-free mass (FFM), and fat cell size. LPL activity per adipocyte was significantly greater in obese than lean women but not significantly different per gram lipid. Both VLDL-TG fractional tracer storage per kg lipid and VLDL-TG storage rate per kg lipid were similar in abdominal and femoral fat in all three groups and were not significantly different between groups. Multiple regression analysis identified FFM and femoral fat mass as significant independent predictors of VLDL-TG fractional tracer storage and insulin as a significant predictor of VLDL-TG fatty acid storage rate. LPL activity, ATBF, and VLDL-TG turnover did not predict VLDL-TG storage. We conclude that lower FFM and greater plasma insulin are associated with greater VLDL-TG deposition in abdominal subcutaneous and femoral fat. Greater femoral fat mass signals greater femoral VLDL-TG storage. We suggest that the differences in VLDL-TG storage in abdominal and femoral fat that occur with progressive obesity are regulated through mechanisms other than LPL activity. PMID:19875996

  4. The atherogenic dyslipidemia ratio [log(TG)/HDL-C] is associated with residual vascular risk, beta-cell function loss and microangiopathy in type 2 diabetes females

    PubMed Central

    2012-01-01

    Background Atherogenic dyslipidemia (AD), defined as low HDL-C plus elevated triglycerides (TG), comorbid to T2DM, increases cardiometabolic risk for CAD even when LDL-C is at target. In T2DM males, AD was shown to correlate with β-cell function loss, yet it is not established whether this applies across gender. Aim To establish the prevalence and severity of AD in T2DM females, and to determine how it relates to cardiometabolic phenotype, glucose homeostasis, micro- and macrovascular complications, and 10-year absolute CV risk (UKPDS Risk Engine). Methods 340 T2DM females were ranked according to quintiles (Q) of the continuous variable log(TG)/HDL-C, with AD prevalence defined as HDL-C <50 mg.dL-1 plus TG ≥150 mg.dL-1, and β-cell function assessed with HOMA. Results AD prevalence was 35%; mean HDL-C and TG were 52 (15) and 160 (105) mg.dL-1. AD was significantly related to central fat, metabolic syndrome, sedentarity and skeletal sarcopenia, as well as to hsCRP, fibrinogen, uric acid, cystatin-C, Big ET-1, and 10-year UKPDS CV risk. AD correlated stepwise with lower β-cell function and hyperbolic product, and with accelerated loss of residual insulin secretion, higher HbA1c and prevalent microangiopathy. Conclusions log(TG)/HDL-C is a simple means to grade AD and residual macrovascular risk in T2DM females. This ratio associates with major non-LDL cardiometabolic variables and ranks predicted CAD risk. In addition, log(TG)/HDL-C identifies worsening glucose homeostasis, poorer glycemic control, and prevalent microangiopathy. PMID:23046637

  5. High-Tg multifunctional photorefractive polymer

    NASA Astrophysics Data System (ADS)

    Hattemer, Erik; Zentel, Rudolf; Mecher, Erwin; Meerholz, Klaus

    1999-10-01

    We describe new high Tg multi-functional polymers. In order to develop a photorefractive system with stable phase behavior at elevated temperatures we synthesized a series of maleimide/methyl vinyl isocyanate copolymers with carbazole as charge transporting moieties. We chose carbazole substituents attached with different spacer groups to adjust Tg of the polymers between 60 degrees C and 194 degrees C. As NLO chromophores we used hydroxyl alkyl functionalized 2- (N-ethyl-4-(4-nitrogen-phenylazo)-anilino)-ethanol and 2- (2,5-dimethyl-4-(4-nitro-phenylazo)-ethanol and 1-(4- ethylhydroxyphenyl)-3-methyl-4-(4-diethylaminophenyl)imino- pyrazole-5-on. Chromophore contents up to 44 mol percent have been attached under mild conditions by polymer analogous reactions. The materials are amorphous and posses excellent solubility in common solvents, e.g. chloroform and THF. Holographic four-wave mixing experiments was performed on a device made from a polymer elasticized such that the glass-transition temperature was Tg equals 80 degrees C. For the grating formation two exponential response times were found wit (tau) 1 equals 100 ms and (tau) 2 equals 1,5 s and a logarithmically weighted average response time of 200 ms.

  6. [Triglycerides, fatty acids and cortisol in simple obesity in children].

    PubMed

    Krzanowska-Dyras, M; Ja?kiewicz, J

    1979-01-01

    In 50 children with obesitas simplex, 6-14 years of age, the triglycerides (TG), free fatty acids (FFA) and cortisol (F) levels in venous blood serum were estimated. In agreement with the development stages, studied patients were divided into the group of younger children in prematurity stage and the group of older children approaching the maturity. Obtained mean values of TG, FFA and F concentrations were analysed in the particular groups of obese children and compared with the healthy children of the same age. Mean concentrations of TG, FFA and cortisol in obese children were within the normal values and statistically did not differ from those of control healthy children. Also there was no difference in parameters studied if compared the younger and older groups of obese children. There was no interrelationship between the high birth weight and the degree of overweight as well as between the duration of obesity and the blood serum TG levels. In the course of obesitas simplex in children no detectable disturbances in the levels of TG, FFA and cortisol were found. It may depends on the more efficient adaptational mechanism connected with metabolism which are acting in the course of overfeed in the period of growth and development. PMID:535585

  7. Adipose Co-expression networks across Finns and Mexicans identify novel triglyceride-associated genes

    PubMed Central

    2012-01-01

    Background High serum triglyceride (TG) levels is an established risk factor for coronary heart disease (CHD). Fat is stored in the form of TGs in human adipose tissue. We hypothesized that gene co-expression networks in human adipose tissue may be correlated with serum TG levels and help reveal novel genes involved in TG regulation. Methods Gene co-expression networks were constructed from two Finnish and one Mexican study sample using the blockwiseModules R function in Weighted Gene Co-expression Network Analysis (WGCNA). Overlap between TG-associated networks from each of the three study samples were calculated using a Fishers Exact test. Gene ontology was used to determine known pathways enriched in each TG-associated network. Results We measured gene expression in adipose samples from two Finnish and one Mexican study sample. In each study sample, we observed a gene co-expression network that was significantly associated with serum TG levels. The TG modules observed in Finns and Mexicans significantly overlapped and shared 34 genes. Seven of the 34 genes (ARHGAP30, CCR1, CXCL16, FERMT3, HCST, RNASET2, SELPG) were identified as the key hub genes of all three TG modules. Furthermore, two of the 34 genes (ARHGAP9, LST1) reside in previous TG GWAS regions, suggesting them as the regional candidates underlying the GWAS signals. Conclusions This study presents a novel adipose gene co-expression network with 34 genes significantly correlated with serum TG across populations. PMID:23217153

  8. The genetic architecture of fasting plasma triglyceride response to fenofibrate treatment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Metabolic response to the triglyceride (TG)-lowering drug, fenofibrate, is shaped by interactions between genetic and environmental factors, yet knowledge regarding the genetic determinants of this response is primarily limited to single gene effects. Since very low density lipoprotein (VLDL) is the...

  9. Abdominal Obesity Associated with Elevated Serum Butyrylcholinesterase Activity, Insulin Resistance and Reduced High Density Lipoprotein-Cholesterol Levels.

    PubMed

    Tangvarasittichai, Surapon; Pongthaisong, Suthap; Meemark, Suwadee; Tangvarasittichai, Orathai

    2015-07-01

    Abdominal obesity (AO) has a strong correlation with cardiovascular disease and has been linked to Alzheimer's disease and type 2 diabetes. We investigated the association between AO and elevated serum butyrylcholinesterase (BChE) activity, insulin resistance and the serum lipid profile, including triglyceride (TG), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) levels in AO and non-AO women subjects. A total of 500 AO subjects (age 49.110.5years), and 142 non-AO women subjects (age 49.911.9years) were enrolled for the general biochemistry tests, serum BChE, fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR). Body mass index, waist circumference, Blood pressure (BP), plasma glucose (Glu), triglyceride (TG), BChE, insulin, HOMA-IR were significantly higher and HDL-C levels were significantly lower in AO subjects (p<0.05). Waist circumference was significantly correlated with BP, Glu, TG, BChE, insulin and HOMA-IR in AO subjects. Multiple logistic regression demonstrated that AO was associated with elevated BChE, HOMA-IR, hypertension and reduced HDL-C after adjusting for these variables. AO is associated with elevated BChE, insulin resistance, HT and reduced HDL-C. These may predict the development of type 2 diabetes mellitus and may be associated with cognitive disorder in the future, both are mediated through insulin resistance. PMID:26089612

  10. Triglycerides and atherogenic lipoproteins: rationale for lipid management.

    PubMed

    Krauss, R M

    1998-07-01

    Epidemiologic and clinical studies have demonstrated a relation between plasma triglyceride levels and risk of coronary artery disease and an amplification of risk with combined elevations of triglyceride and low-density lipoprotein (LDL) cholesterol. In patients with coronary disease, angiographic progression and clinical events have been correlated with concentrations of smaller very-low-density lipoproteins (VLDL) and intermediate-density lipoproteins (IDL), consistent with evidence for enhanced atherogenicity of lipolytic products of triglyceride-rich lipoprotein metabolism, including postprandial lipoproteins. IDL levels also have been shown to be strongly and independently predictive of progression of carotid artery intimal-medial thickness, a measure of early atherogenesis that is related to coronary disease risk. Although there is evidence that these triglyceride-rich lipoprotein species may have direct atherogenic effects, other lipoprotein changes associated with altered triglyceride metabolism may be of particular importance in the development of coronary artery disease. These include reductions in high-density lipoprotein (HDL) and increases in small, dense LDL particles (LDL subclass pattern B). Because of the strong interrelations among elevated triglyceride, reduced HDL, and small dense LDL, it is difficult to use statistical techniques to determine the independent contributions of these traits to coronary disease risk. Based on their biologic properties, it is likely that each are involved in multiple steps of the disease process. Moreover, this cluster of lipoprotein changes is associated with other conditions that can promote vascular disease, including increases in coagulation factors and reduced insulin sensitivity. Analyses from intervention trials in patients with coronary disease have indicated that measurement of plasma triglyceride and LDL particle distributions can be of value in predicting the benefits of specific lipid-altering therapies on disease progression. PMID:9707269

  11. Triglyceride accumulation and fatty acid profile changes in Chlorella (Chlorophyta) during high pH-induced cell cycle inhibition

    SciTech Connect

    Guckert, J.B.; Cooksey, K.E. )

    1990-03-01

    Alkaline pH stress resulted in triglyceride (TG) accumulation in Chlorella CHLOR1 and was independent of medium nitrogen or carbon levels. Based on morphological observations, alkaline pH inhibited autospore release, thus increasing the time for cell cycle completion. Autospore release has been postulated to coincide with TG utilization within the microalgal cell division cycle. The alkaline pH stress affected lipid accumulation by inhibiting the cell division cycle prior to autospore release and, therefore, prior to TG utilization. Cells inhibited in this manner showed an increase in TG accumulation but a decrease in both membrane lipid classes (glycolipid and polar lipid). Unlike TG fatty acid profiles, membrane lipid fatty acid profiles were not stable during TG accumulation. The membrane profiles became similar to the TG, i.e. less unsaturated than in the membrane lipids of unstressed control cells.

  12. Metabolic fate of an oral long-chain triglyceride load in humans.

    PubMed

    Binnert, C; Pachiaudi, C; Beylot, M; Croset, M; Cohen, R; Riou, J P; Laville, M

    1996-03-01

    To determine the steps involved in the metabolism of ingested triglycerides (TG), 10 healthy women were studied during 6 h after ingestion of 30 g olive oil labeled with [1,1,1-13C3] triolein. The appearance of 13C was followed in chylomicron-TG (CM-TG), nonesterified fatty acid (NEFA), very low-density lipoprotein (VLDL)-TG, and in expired gas. Indirect calorimetry was used to determine total lipid oxidation. After 90 min, labeling was higher in CM-TG than in NEFA or VLDL. At 180 min, a plateau of enrichment was obtained for CM-TG and NEFA, demonstrating the entry of exogenous lipids in the NEFA pool. After 300 min, a plateau was observed for VLDL-TG with levels of enrichment (0.38 +/- 0.04%) similar to those observed for NEFA (0.36 +/- 0.03%), suggesting a precursor-product relationship. Only 19 +/- 2% of the load was oxidized. From 300 to 360 min, 70% of total lipid oxidation was from exogenous TG. We conclude that, after ingestion of a lipid load, a cycle of fatty acids-TG occurs from CM to NEFA and from NEFA to VLDL. Furthermore, this lipid load has a sparing effect on endogenous lipid stores. PMID:8638691

  13. Genome-wide association study of triglyceride response to a high-fat meal among participants of the NHLBI genetics of lipid lowering drugs and diet network (GOLDN)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: The triglyceride (TG) response to a high-fat meal (postprandial lipemia, PPL) affects cardiovascular disease risk and is influenced by genes and environment. Genes involved in lipid metabolism have dominated genetic studies of PPL TG response. We sought to elucidate common genetic variant...

  14. Lowering triglycerides to modify cardiovascular risk: will icosapent deliver?

    PubMed

    Scherer, Daniel J; Nicholls, Stephen J

    2015-01-01

    Despite the clinical benefits of lowering levels of low-density lipoprotein cholesterol, many patients continue to experience cardiovascular events. This residual risk suggests that additional risk factors require aggressive modification to result in more effective prevention of cardiovascular disease. Hypertriglyceridemia has presented a considerable challenge with regard to understanding its role in the promotion of cardiovascular risk. Increasing evidence has established a clear causal role for elevated triglyceride levels in vascular risk. As a result, there is increasing interest in the development of specific therapeutic strategies that directly target hypertriglyceridemia. This has seen a resurgence in the use of omega-3 fatty acids for the therapeutic lowering of triglyceride levels. The role of these agents and other emerging strategies to reduce triglyceride levels in order to decrease vascular risk are reviewed. PMID:25848301

  15. Masoprocol decreases serum triglyceride concentrations in rats with fructose-induced hypertriglyceridemia.

    PubMed

    Scribner, K A; Gadbois, T M; Gowri, M; Azhar, S; Reaven, G M

    2000-09-01

    Historically, extracts of the creosote bush have been used by native healers of the Southwest region of North America to treat symptoms of type 2 diabetes. More recently, we have shown that masoprocol (nordihydroguaiaretic acid), a pure compound isolated from the creosote bush (Larrea tridentata), decreases serum glucose and triglyceride (TG) levels when administered orally in rodent models of type 2 diabetes. The present studies were undertaken to determine if masoprocol also decreases TG concentrations in rats with fructose-induced hypertriglyceridemia (HTG), a nondiabetic model of HTG associated with insulin resistance and hyperinsulinemia. Serum TG levels, which were significantly higher after rats ate a fructose-enriched (60% by weight) diet for 14 days as compared with chow-fed controls (411 v 155 mg/dL, P < .01), decreased in a stepwise fashion in fructose-fed rats treated orally with masoprocol for 4 to 8 days over a dose range of 10 to 80 mg/kg twice daily. Using the nonionic detergent Triton WR 1339 to compare TG secretion rates in masoprocol- and vehicle-treated rats, masoprocol at a dose of 40 or 80 mg/kg twice daily, significantly reduced hepatic TG secretion (P < .01) and liver TG content (P < .001), whereas lower doses of masoprocol decreased serum TG without an apparent reduction in hepatic TG secretion. Administration of Intralipid (a fat emulsion) showed that the half-time for removal of TG from serum was also shorter in masoprocol-treated rats versus vehicle-treated controls (31 v 64 minutes, P < .05). In addition adipose tissue lipoprotein lipase (LPL) activity was increased in masoprocol-treated rats and adipose tissue hormone-sensitive lipase (HSL) activity was decreased. We conclude that masoprocol administration to rats with fructose-induced HTG results in lower serum TG levels associated with reduced hepatic TG secretion and increased peripheral TG clearance. PMID:11016888

  16. Elevated sensitivity of macrosteatotic hepatocytes to hypoxia/reoxygenation stress is reversed by a novel defatting protocol.

    PubMed

    Nativ, Nir I; Yarmush, Gabriel; So, Ashley; Barminko, Jeffery; Maguire, Timothy J; Schloss, Rene; Berthiaume, Francois; Yarmush, Martin L

    2014-08-01

    Macrosteatotic livers exhibit elevated intrahepatic triglyceride (TG) levels in the form of large lipid droplets (LDs), reduced adenosine triphosphate (ATP) levels, and elevated reactive oxygen species (ROS) levels, and this contributes to their elevated sensitivity to ischemia/reperfusion injury during transplantation. Reducing macrosteatosis in living donors through dieting has been shown to improve transplant outcomes. Accomplishing the same feat for deceased donor grafts would require ex vivo exposure to potent defatting agents. Here we used a rat hepatocyte culture system exhibiting a macrosteatotic LD morphology, elevated TG levels, and an elevated sensitivity to hypoxia/reoxygenation (H/R) to test for such agents and ameliorate H/R sensitivity. Macrosteatotic hepatocyte preconditioning for 48 hours with a defatting cocktail that was previously developed to promote TG catabolism reduced the number of macrosteatotic LDs and intracellular TG levels by 82% and 27%, respectively, but it did not ameliorate sensitivity to H/R. Supplementation of this cocktail with l-carnitine, together with hyperoxic exposure, yielded a similar reduction in the number of macrosteatotic LDs and a 57% reduction in intrahepatic TG storage, likely by increasing the supply of acetyl coenzyme A to mitochondria, as indicated by a 70% increase in ketone body secretion. Furthermore, this treatment reduced ROS levels by 32%, increased ATP levels by 27% (to levels near those of lean controls), and completely abolished H/R sensitivity as indicated by approximately 85% viability after H/R and the reduction of cytosolic lactate dehydrogenase release to levels seen in lean controls. Cultures maintained for 48 hours after H/R were approximately 83% viable and exhibited superior urea secretion and bile canalicular transport in comparison with untreated macrosteatotic cultures. In conclusion, these findings show that the elevated sensitivity of macrosteatotic hepatocytes to H/R can be overcome by defatting agents, and they suggest a possible route for the recovery of discarded macrosteatotic grafts. PMID:24802973

  17. Dietary manipulation of serum triglycerides.

    PubMed

    Seakins, A; Arajo, C R; Ashworth, A; Flores, H

    1979-12-01

    A group of children who had been treated for protein-energy malnutrition with a high-energy, high-faty diet, presented very low levels of fasting serum triglycerides (50.8 +/- 5.9 mg/dl). When the diet was changed to a high-energy, low-fat formula, these levels increased rapidly to normal values (104.9 +/- 19.2 mg/dl). Reversing the dietary change produced the opposite effect within 2 days. This effect was also studied in 14 normal adults, who received a high-fat diet ad libitum during 5 days. Meals were prepared from common foodstuffs with a high fat content. The hypotriglyceridemic effect occurred in all volunteers. A close relationship was observed between the initial triglyceride concentration and the decrement produced by the high-fat diet (r = 0.97), which did not affect serum cholesterol levels. No consistent response of serum free-fatty acids was detected, while serum proteins remained within normal values. Despite the rather high energy intake, most subjects lost weight during the experimental period. The level of fasting serum triglycerides of the adult volunteers was negatively correlated to the fat content of their self-selected diets. These results are discussed in relation to current ideas about fat requirements. PMID:121689

  18. Sympathetic nervous system control of triglyceride metabolism: novel concepts derived from recent studies.

    PubMed

    Geerling, Janine J; Boon, Maritte R; Kooijman, Sander; Parlevliet, Edwin T; Havekes, Louis M; Romijn, Johannes A; Meurs, Illiana M; Rensen, Patrick C N

    2014-02-01

    Important players in triglyceride (TG) metabolism include the liver (production), white adipose tissue (WAT) (storage), heart and skeletal muscle (combustion to generate ATP), and brown adipose tissue (BAT) (combustion toward heat), the collective action of which determine plasma TG levels. Interestingly, recent evidence points to a prominent role of the hypothalamus in TG metabolism through innervating the liver, WAT, and BAT mainly via sympathetic branches of the autonomic nervous system. Here, we review the recent findings in the area of sympathetic control of TG metabolism. Various neuronal populations, such as neuropeptide Y (NPY)-expressing neurons and melanocortin-expressing neurons, as well as peripherally produced hormones (i.e., GLP-1, leptin, and insulin), modulate sympathetic outflow from the hypothalamus toward target organs and thereby influence peripheral TG metabolism. We conclude that sympathetic stimulation in general increases lipolysis in WAT, enhances VLDL-TG production by the liver, and increases the activity of BAT with respect to lipolysis of TG, followed by combustion of fatty acids toward heat. Moreover, the increased knowledge about the involvement of the neuroendocrine system in TG metabolism presented in this review offers new therapeutic options to fight hypertriglyceridemia by specifically modulating sympathetic nervous system outflow toward liver, BAT, or WAT. PMID:24285857

  19. Plasma triglycerides determine low density lipoprotein composition, physical properties, and cell-specific binding in cultured cells.

    PubMed Central

    McKeone, B J; Patsch, J R; Pownall, H J

    1993-01-01

    The relationship between the plasma triglycerides and the LDL triglycerides of 30 normal and 48 hypertriglyceridemic subjects has been quantified; the data fit a simple adsorption isotherm, LDL triglyceride/(LDL triglyceride+LDL cholesterol ester) = 0.65 plasma triglyceride/(464 + plasma triglyceride). In vitro transfer of triglyceride from concentrated VLDL to VLDL-depleted plasma produced triglyceride-rich LDL that had similar properties. LDL uptake by HepG2 cells increased with LDL triglyceride content whereas the reverse was found with skin fibroblasts. At 37 degrees C, the cores of both normal and hypertriglyceridemic LDL were isotropic liquids. Circular dichroic spectra revealed no difference in the secondary structure of normal and triglyceride-rich LDL. The affinity of monoclonal antibody MB47, which binds to the receptor ligand of apo B-100 was independent of LDL triglyceride content. MB3, which binds near residue 1022 of apo B-100, showed a triglyceride-dependent decrease in affinity for LDL from hypertriglyceridemic subjects and from in vitro incubations. LDL with an elevated triglyceride content formed in vitro had reduced proteolytic cleavage of apo B-100 by Staphylococcus aureus V8 protease. From these data, we infer that (a) LDL triglyceride is a predictable function of plasma triglyceride, (b) triglyceride induces subtle changes in apo B-100 structure at a site that is remote from the putative receptor binding ligand, and (c) the triglyceride-dependent receptor-binding determinants of apo B-100 are recognized differently by fibroblasts and HepG2 cells. Images PMID:8387537

  20. Impact of Chronic Hepatitis C Virus Genotype 1b Infection on Triglyceride Concentration in Serum Lipoprotein Fractions

    PubMed Central

    Nagano, Tomohisa; Seki, Nobuyoshi; Tomita, Yoichi; Sugita, Tomonori; Aida, Yuta; Itagaki, Munenori; Sutoh, Satoshi; Abe, Hiroshi; Tsubota, Akihito; Aizawa, Yoshio

    2015-01-01

    Reduced low-density lipoprotein (LDL) cholesterol level is a characteristic feature of dyslipidemia in chronic hepatitis C virus (HCV) infection. However, abnormality in serum triglyceride (TG) has not been fully investigated. To clarify the impact of HCV genotype 1b (G1b) infection and advanced fibrosis on serum TG profiles, TG concentrations in lipoprotein fractions were examined in fasting sera from 185 subjects with active or cleared HCV infection by high-performance liquid chromatography. Serum lipoproteins were fractionated into four classes: chylomicron, very low-density lipoprotein (VLDL), LDL, and high-density lipoprotein (HDL). Then, the significance of HCV G1b infection on TG levels in each lipoprotein fraction was determined using multiple regression models. We found that active HCV G1b infection was positively associated with high HDL-TG levels and low VLDL-TG levels, independent of other factors included in the regression model. In VLDL sub-fractions, active HCV infection was only found to be associated with low levels of large VLDL-TG. Similarly, advanced liver fibrosis in chronic HCV G1b infection was associated with high levels of LDL-TG, HDL-TG, and small VLDL-TG, independent of other clinical factors. These findings indicate that active HCV G1b infection and advanced fibrosis are closely associated with abnormal serum TG profiles. PMID:26334270

  1. Fenofibrate, a peroxisome proliferator-activated receptor α agonist, alters triglyceride metabolism in enterocytes of mice.

    PubMed

    Uchida, Aki; Slipchenko, Mikhail N; Cheng, Ji-Xin; Buhman, Kimberly K

    2011-03-01

    Fenofibrate, a drug in the fibrate class of amphiphathic carboxylic acids, has multiple blood lipid modifying actions, which are beneficial to the prevention of atherosclerosis. One of its benefits is in lowering fasting and postprandial blood triglyceride (TG) concentrations. The goal of this study was to determine whether the hypotriglyceridemic actions of fenofibrate in the postprandial state include alterations in TG and fatty acid metabolism in the small intestine. We found that the hypotriglyceridemic actions of fenofibrate in the postprandial state of high-fat (HF) fed mice include a decrease in supply of TG for secretion by the small intestine. A decreased supply of TG for secretion was due in part to the decreased dietary fat absorption and increased intestinal fatty acid oxidation in fenofibrate compared to vehicle treated HF fed mice. These results suggest that the effects of fenofibrate on the small intestine play a critical role in the hypotriglyceridemic effects of fenofibrate. PMID:21215818

  2. Genetic mutations in adipose triglyceride lipase and myocardial up-regulation of peroxisome proliferated activated receptor-γ in patients with triglyceride deposit cardiomyovasculopathy.

    PubMed

    Hirano, Ken-ichi; Tanaka, Tatsuya; Ikeda, Yoshihiko; Yamaguchi, Satoshi; Zaima, Nobuhiro; Kobayashi, Kazuhiro; Suzuki, Akira; Sakata, Yasuhiko; Sakata, Yasushi; Kobayashi, Kunihisa; Toda, Tatsushi; Fukushima, Norihide; Ishibashi-Ueda, Hatsue; Tavian, Daniela; Nagasaka, Hironori; Hui, Shu-Ping; Chiba, Hitoshi; Sawa, Yoshiki; Hori, Masatsugu

    2014-01-10

    Adipose triglyceride lipase (ATGL, also known as PNPLA2) is an essential molecule for hydrolysis of intracellular triglyceride (TG). Genetic ATGL deficiency is a rare multi-systemic neutral lipid storage disease. Information regarding its clinical profile and pathophysiology, particularly for cardiac involvement, is still very limited. A previous middle-aged ATGL-deficient patient in our institute (Case 1) with severe heart failure required cardiac transplantation (CTx) and exhibited a novel phenotype, "Triglyceride deposit cardiomyovasculopathy (TGCV)". Here, we tried to elucidate molecular mechanism underlying TGCV. The subjects were two cases with TGCV, including our second case who was a 33-year-old male patient (Case 2) with congestive heart failure requiring CTx. Case 2 was homozygous for a point mutation in the 5' splice donor site of intron 5 in the ATGL, which results in at least two types of mRNAs due to splicing defects. The myocardium of both patients (Cases 1 and 2) showed up-regulation of peroxisome proliferated activated receptors (PPARs), key transcription factors for metabolism of long chain fatty acids (LCFAs), which was in contrast to these molecules' lower expression in ATGL-targeted mice. We investigated the intracellular metabolism of LCFAs under human ATGL-deficient conditions using patients' passaged skin fibroblasts as a model. ATGL-deficient cells showed higher uptake and abnormal intracellular transport of LCFA, resulting in massive TG accumulation. We used these findings from cardiac specimens and cell-biological experiments to construct a hypothetical model to clarify the pathophysiology of the human disorder. In patients with TGCV, even when hydrolysis of intracellular TG is defective, the marked up-regulation of PPARγ and related genes may lead to increased uptake of LCFAs, the substrates for TG synthesis. This potentially vicious cycle of LCFAs could explain the massive accumulation of TG and severe clinical course for this rare disease. PMID:24332944

  3. Alcohol Dehydrogenase-1B (rs1229984) and Aldehyde Dehydrogenase-2 (rs671) Genotypes Are Strong Determinants of the Serum Triglyceride and Cholesterol Levels of Japanese Alcoholic Men

    PubMed Central

    Yokoyama, Akira; Yokoyama, Tetsuji; Matsui, Toshifumi; Mizukami, Takeshi; Kimura, Mitsuru; Matsushita, Sachio; Higuchi, Susumu; Maruyama, Katsuya

    2015-01-01

    Background Elevated serum triglyceride (TG) and high-density-lipoprotein cholesterol (HDL-C) levels are common in drinkers. The fast-metabolizing alcohol dehydrogenase-1B encoded by the ADH1B*2 allele (vs. ADH1B*1/*1 genotype) and inactive aldehyde dehydrogenase-2 encoded by the ALDH2*2 allele (vs. ALDH2*1/*1 genotype) modify ethanol metabolism and are prevalent (?90% and ?40%, respectively) in East Asians. We attempted to evaluate the associations between the ADH1B and ALDH2 genotypes and lipid levels in alcoholics. Methods The population consisted of 1806 Japanese alcoholic men (?40 years) who had undergone ADH1B and ALDH2 genotyping and whose serum TG, total cholesterol, and HDL-C levels in the fasting state had been measured within 3 days after admission. Results High serum levels of TG (?150 mg/dl), HDL-C (>80 mg/dl), and low-density-lipoprotein cholesterol (LDL-C calculated by the Friedewald formula ?140 mg/dl) were observed in 24.3%, 16.8%, and 15.6%, respectively, of the subjects. Diabetes, cirrhosis, smoking, and body mass index (BMI) affected the serum lipid levels. Multivariate analysis revealed that the presence of the ADH1B*2 allele and the active ALDH2*1/*1 genotype increased the odds ratio (OR; 95% confidence interval) for a high TG level (2.22 [1.672.94] and 1.39 [0.991.96], respectively), and decreased the OR for a high HDL-C level (0.37 [0.280.49] and 0.51 [0.370.69], respectively). The presence of the ADH1B*2 allele decreased the OR for a high LDL-C level (0.60 [0.450.80]). The ADH1B*2 plus ALDH2*1/*1 combination yielded the highest ORs for high TG levels and lowest OR for a high HDL-C level. The genotype effects were more prominent in relation to the higher levels of TG (?220 mg/dl) and HDL-C (?100 mg/dl). Conclusions The fast-metabolizing ADH1B and active ALDH2, and especially a combination of the two were strongly associated with higher serum TG levels and lower serum HDL-C levels of alcoholics. The fast-metabolizing ADH1B was associated with lower serum LDL-C levels. PMID:26284938

  4. Mechanisms of intrahepatic triglyceride accumulation

    PubMed Central

    Ress, Claudia; Kaser, Susanne

    2016-01-01

    Hepatic steatosis defined as lipid accumulation in hepatocytes is very frequently found in adults and obese adolescents in the Western World. Etiologically, obesity and associated insulin resistance or excess alcohol intake are the most frequent causes of hepatic steatosis. However, steatosis also often occurs with chronic hepatitis C virus (HCV) infection and is also found in rare but potentially life-threatening liver diseases of pregnancy. Clinical significance and outcome of hepatic triglyceride accumulation are highly dependent on etiology and histological pattern of steatosis. This review summarizes current concepts of pathophysiology of common causes of hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease, chronic HCV infections, drug-induced forms of hepatic steatosis, and acute fatty liver of pregnancy. Regarding the pathophysiology of NAFLD, this work focuses on the close correlation between insulin resistance and hepatic triglyceride accumulation, highlighting the potential harmful effects of systemic insulin resistance on hepatic metabolism of fatty acids on the one side and the role of lipid intermediates on insulin signalling on the other side. Current studies on lipid droplet morphogenesis have identified novel candidate proteins and enzymes in NAFLD. PMID:26819531

  5. Mechanisms of intrahepatic triglyceride accumulation.

    PubMed

    Ress, Claudia; Kaser, Susanne

    2016-01-28

    Hepatic steatosis defined as lipid accumulation in hepatocytes is very frequently found in adults and obese adolescents in the Western World. Etiologically, obesity and associated insulin resistance or excess alcohol intake are the most frequent causes of hepatic steatosis. However, steatosis also often occurs with chronic hepatitis C virus (HCV) infection and is also found in rare but potentially life-threatening liver diseases of pregnancy. Clinical significance and outcome of hepatic triglyceride accumulation are highly dependent on etiology and histological pattern of steatosis. This review summarizes current concepts of pathophysiology of common causes of hepatic steatosis, including non-alcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease, chronic HCV infections, drug-induced forms of hepatic steatosis, and acute fatty liver of pregnancy. Regarding the pathophysiology of NAFLD, this work focuses on the close correlation between insulin resistance and hepatic triglyceride accumulation, highlighting the potential harmful effects of systemic insulin resistance on hepatic metabolism of fatty acids on the one side and the role of lipid intermediates on insulin signalling on the other side. Current studies on lipid droplet morphogenesis have identified novel candidate proteins and enzymes in NAFLD. PMID:26819531

  6. The Paradox of ApoA5 Modulation of Triglycerides: Evidences from Clinical and Basic Research

    PubMed Central

    Garelnabi, Mahdi; Lor, Kenton; Jin, Jun; Chai, Fei; Santanam, Nalini

    2012-01-01

    Apolipoprotein A5 (ApoA5) is a key regulator of plasma triglycerides (TG), although its plasma concentration is very low compared to other known apoproteins. Over the years, researchers have attempted to elucidate the molecular mechanisms by which ApoA5 regulates plasma TG in vivo. Though still under debate, two theories broadly describe how ApoA5 modulates TG levels: (i) ApoA5 enhances the catabolism of TG-rich lipoproteins and (ii) it inhibits the rate of production of very low-density lipoprotein (VLDL), the major carrier of TGs. This review will summarize the basic and clinical studies that have attempted to describe the importance of ApoA5 in TG metabolism. Population studies conducted in various countries have demonstrated an association between single nucleotide polymorphisms (SNPs) in ApoA5 and the increased risk to cardiovascular disease and metabolic syndrome (including diabetes and obesity). ApoA5 is also highly expressed during liver regeneration and is an acute phase protein associated with HDL which was independent of its effects on TG metabolism. Conclusion Despite considerable evidences available from clinical and basic research studies, on the role of ApoA5 in TG metabolism and its indirect link to metabolic diseases, additional investigations are needed to understand the paradoxical role of this important apoprotein shown modulated by diet and from it polymorphism variants. PMID:23000317

  7. Relationship between plasma free fatty acid, intramyocellular triglycerides and long-chain acylcarnitines in resting humans

    PubMed Central

    Kanaley, Jill A; Shadid, Samyah; Sheehan, Michael T; Guo, ZengKui; Jensen, Michael D

    2009-01-01

    We hypothesized that plasma non-esterified fatty acids (NEFA) are trafficked directly to intramyocellular long-chain acylcarnitines (imLCAC) rather than transiting intramyocellular triglycerides (imTG) on the way to resting muscle fatty acid oxidation. Overnight fasted adults (n= 61) received intravenous infusions of [U-13C]palmitate (04000830 h) and [U-13C]oleate (08001400 h) labelling plasma NEFA, imTG, imLCAC and im-non-esterified FA (imNEFA). Two muscle biopsies (0830 and 1400 h) were performed following 6 h, overlapping, sequential palmitate/oleate tracer infusions. Enrichment of plasma palmitate was ?15 times greater than enrichment of imTG, imNEFA-palmitate and im-palmitoyl-carnitine. Fatty acid enrichment in LCAC was correlated with imTG and imNEFA; there was a significant correlation between imTG concentrations and imLCAC concentrations in women (r= 0.51, P= 0.005), but not men (r= 0.30, P= 0.11). We estimated that ?11% of NEFA were stored in imTG. imTG NEFA storage was correlated only with NEFA concentrations (r= 0.52, P= 0.004) in women and with (r= 0.45, P= 0.02) in men. At rest, plasma NEFA are trafficked largely to imTG before they enter LCAC oxidative pools; thus, imTG are an important, central pool that regulates the delivery of fatty acids to the intracellular environment. Factors relating to plasma NEFA storage into imTG differ in men and women. PMID:19858228

  8. Cholesterol, Triglycerides, and the Five-Factor Model of Personality

    PubMed Central

    Sutin, Angelina R.; Terracciano, Antonio; Deiana, Barbara; Uda, Manuela; Schlessinger, David; Lakatta, Edward G.; Costa, Paul T.

    2010-01-01

    Unhealthy lipid levels are among the leading controllable risk factors for coronary heart disease. To identify the psychological factors associated with dyslipidemia, this study investigates the personality correlates of cholesterol (total, LDL, and HDL) and triglycerides. A community-based sample (N=5,532) from Sardinia, Italy, had their cholesterol and triglyceride levels assessed and completed a comprehensive personality questionnaire, the NEO-PI-R. All analyses controlled for age, sex, BMI, smoking, drinking, hypertension, and diabetes. Low Conscientiousness and traits related to impulsivity were associated with lower HDL cholesterol and higher triglycerides. Compared to the lowest 10%, those who scored in top 10% on Impulsivity had a 2.5 times greater risk of exceeding the clinical threshold for elevated triglycerides (OR=2.51, CI=1.564.07). In addition, sex moderated the association between trait depression (a component of Neuroticism) and HDL cholesterol, such that trait depression was associated with lower levels of HDL cholesterol in women but not men. When considering the connection between personality and health, unhealthy lipid profiles may be one intermediate biomarker between personality and morbidity and mortality. PMID:20109519

  9. Packaged bulk micromachined triglyceride biosensor

    NASA Astrophysics Data System (ADS)

    Mohanasundaram, S. V.; Mercy, S.; Harikrishna, P. V.; Rani, Kailash; Bhattacharya, Enakshi; Chadha, Anju

    2010-02-01

    Estimation of triglyceride concentration is important for the health and food industries. Use of solid state biosensors like Electrolyte Insulator Semiconductor Capacitors (EISCAP) ensures ease in operation with good accuracy and sensitivity when compared to conventional sensors. In this paper we report on packaging of miniaturized EISCAP sensors on silicon. The packaging involves glass to silicon bonding using adhesive. Since this kind of packaging is done at room temperature, it cannot damage the thin dielectric layers on the silicon wafer unlike the high temperature anodic bonding technique and can be used for sensors with immobilized enzyme without denaturing the enzyme. The packaging also involves a teflon capping arrangement which helps in easy handling of the bio-analyte solutions. The capping solves two problems. Firstly, it helps in the immobilization process where it ensures the enzyme immobilization happens only on one pit and secondly it helps with easy transport of the bio-analyte into the sensor pit for measurements.

  10. Kisspeptin-10 Enhanced Egg Production in Quails Associated with the Increase of Triglyceride Synthesis in Liver

    PubMed Central

    Wu, J.; Fu, W.; Huang, Y.; Ni, Y.; Zhao, R.

    2013-01-01

    Our previous results showed that kisspeptin-10 (Kp-10) injections via intraperitoneal (i.p.) once daily for three weeks notably promoted the egg laying rate in quails. In order to investigate the mechanism behind the effects of Kp-10 on enhancing the egg laying rate in birds, this study focused on the alternations of lipids synthesis in liver after Kp-10 injections. 75 female quails (22 d of age) were allocated to three groups randomly, and subjected to 0 (control, Con), 10 nmol (low dosage, L) and 100 nmol (high dosage, H) Kp-10 injections via i.p. once daily for three weeks, respectively. At d 52, quails were sacrificed and sampled for further analyses. Serum E2 concentration was increased by Kp-10 injections, and reached statistical significance in H group. Serum triglyceride (TG) concentrations were increased by 46.7% in L group and 36.8% in H group, respectively, but did not reach statistical significance, and TG contents in liver were significantly elevated by Kp-10 injections in a dose-dependent manner. Serum total cholesterol (Tch) concentrations significantly decreased in H group, while in H group the hepatic Tch content was markedly increased. The level of non-esterified fatty acid (NEFA), apolipoprotein A1 and B (apoA1 and apoB) were not altered by Kp-10 injections. The genes expression of sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthetase (FAS), apolipoprotein VLDL-II (apoVLDL-II), cholesterol 7?-hydroxylase (CYP7A1) and vitellogenin II (VTG-II) were significantly up-regulated by high but not low dosage of Kp-10 injection compared to the control group. However, the expression of SREBP-2, acetyl-CoA carboxylase (ACC?), malic enzyme (ME), stearoyl-CoA (?9) desaturase 1 (SCD1), apolipoprotein A1 (apoA1), fatty acid binding protein 2 (FABP2), 3-hydroxyl-3-methyl glutaryl-coenzyme A reductases (HMGCR), estrogen receptor ?, ? (ER? and ?) mRNA were not affected by Kp-10 treatment. In line with hepatic mRNA abundance, hepatic SREBP1 protein content was significantly higher in H group. Although the mRNA expression was not altered, the content of ER? protein in liver was also significantly increased in H group. However, SREBP-2 protein content in liver was not changed by Kp-10 treatment. In conclusion, exogenous Kp-10 consecutive injections during juvenile stage significantly advanced the tempo of egg laying in quails, which was associated with the significant elevation in hepatic lipids synthesis and transport. PMID:25049888

  11. NASH Resolution is Associated with Improvements in HDL and Triglyceride Levels But Not Improvement in LDL or Non-HDL-C Levels

    PubMed Central

    Corey, Kathleen E.; Vuppalanchi, Raj; Wilson, Laura A.; Cummings, Oscar W.; Chalasani, Naga

    2014-01-01

    Background Nonalcoholic steatohepatitis (NASH) is associated with dyslipidemia and cardiovascular disease (CVD). Aim To determine the relationship between resolution of NASH and dyslipidemia. Methods Individuals in the Pioglitazone versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis (PIVENS) trial with paired liver biopsies and fasting lipid levels were included (N=222). In the PIVENS trial individuals were randomized to pioglitazone 30mg, vitamin E 800IU or placebo for 96 weeks. Change in lipid levels at 96 weeks was compared between those with and without NASH resolution. Results Dyslipidemia at baseline was frequent, with low high-density lipoprotein (HDL) (<40mg/dL in men or <50 mg/dL in women) in 63%, hypertriglyceridemia (?150 mg/dL) in 46%, hypercholesterolemia (?200 mg/dL) in 47%, and triglycerides (TG)/HDL>5.0 in 25%. Low-density lipoprotein (LD) ? 160 mg/dL was found in 16% and elevated non-HDL cholesterol (non-HDL-C) (?130 mg/dL) in 73%. HDL increased with NASH resolution but decreased in those without resolution (2.9mg/dL vs. ?2.5mg/dL, P<0.001). NASH resolution was associated with significant decreases in TG and TG/HDL ratio compared to those without resolution (TG: ?21.1 vs. ?2.3mg/dL, P=0.03 and TG/HDL: ?0.7 vs 0.1, P=0.003). Non-HDL-C, LDL and cholesterol decreased over 96 weeks in both groups but there was no significant difference between groups. Treatment group did not impact lipids. Conclusions NASH resolution is associated with improvements in TG and HDL but not in other CVD risk factors including LDL and non-HDL-C levels. Individuals with resolution of NASH may still be at increased risk of CVD. ClinicalTrials.gov identifier: NCT00063622 PMID:25429853

  12. Genetic mutations in adipose triglyceride lipase and myocardial up-regulation of peroxisome proliferated activated receptor-γ in patients with triglyceride deposit cardiomyovasculopathy

    SciTech Connect

    Hirano, Ken-ichi; Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 ; Tanaka, Tatsuya; Ikeda, Yoshihiko; Yamaguchi, Satoshi; Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 ; Zaima, Nobuhiro; Kobayashi, Kazuhiro; Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 ; Sakata, Yasuhiko; Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1, Seiryo-cho, Aoba-ku, Sendai 980-8574 ; and others

    2014-01-10

    Highlights: •Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare severe heart disease. •PPARγ is up-regulated in myocardium in patients with TGCV. •Possible vicious cycle for fatty acid may be involved in pathophysiology of TGCV. -- Abstract: Adipose triglyceride lipase (ATGL, also known as PNPLA2) is an essential molecule for hydrolysis of intracellular triglyceride (TG). Genetic ATGL deficiency is a rare multi-systemic neutral lipid storage disease. Information regarding its clinical profile and pathophysiology, particularly for cardiac involvement, is still very limited. A previous middle-aged ATGL-deficient patient in our institute (Case 1) with severe heart failure required cardiac transplantation (CTx) and exhibited a novel phenotype, “Triglyceride deposit cardiomyovasculopathy (TGCV)”. Here, we tried to elucidate molecular mechanism underlying TGCV. The subjects were two cases with TGCV, including our second case who was a 33-year-old male patient (Case 2) with congestive heart failure requiring CTx. Case 2 was homozygous for a point mutation in the 5′ splice donor site of intron 5 in the ATGL, which results in at least two types of mRNAs due to splicing defects. The myocardium of both patients (Cases 1 and 2) showed up-regulation of peroxisome proliferated activated receptors (PPARs), key transcription factors for metabolism of long chain fatty acids (LCFAs), which was in contrast to these molecules’ lower expression in ATGL-targeted mice. We investigated the intracellular metabolism of LCFAs under human ATGL-deficient conditions using patients’ passaged skin fibroblasts as a model. ATGL-deficient cells showed higher uptake and abnormal intracellular transport of LCFA, resulting in massive TG accumulation. We used these findings from cardiac specimens and cell-biological experiments to construct a hypothetical model to clarify the pathophysiology of the human disorder. In patients with TGCV, even when hydrolysis of intracellular TG is defective, the marked up-regulation of PPARγ and related genes may lead to increased uptake of LCFAs, the substrates for TG synthesis. This potentially vicious cycle of LCFAs could explain the massive accumulation of TG and severe clinical course for this rare disease.

  13. Carbohydrate-induced hypertriglyceridemia: an insight into the link between plasma insulin and triglyceride concentrations.

    PubMed

    McLaughlin, T; Abbasi, F; Lamendola, C; Yeni-Komshian, H; Reaven, G

    2000-09-01

    This study was initiated to test the hypothesis that endogenous hypertriglyceridemia results from a defect in the ability of insulin to inhibit the release of very low-density lipoprotein-triglyceride (TG) from the liver. To accomplish this goal, plasma glucose, insulin, free fatty acid (FFA), and TG concentrations were compared in 12 healthy volunteers, in response to diets containing either 40% or 60% of total calories as carbohydrate (CHO). The protein content of the two diets was similar (15% of calories), and the fat content varied inversely with the amount of CHO (45% or 25%). The diets were consumed in random order, and measurements were made of plasma glucose, insulin, FFA, and TG concentrations at the end of each dietary period, fasting, and at hourly intervals following breakfast and lunch. The results indicated that the 60% CHO diet resulted in higher fasting plasma TG concentrations associated with higher day-long plasma insulin and TG concentrations, and lower FFA concentrations. These results do not support the view that hypertriglyceridemia is secondary to a failure of insulin to inhibit hepatic TG secretion. PMID:10999790

  14. POSTPRANDIAL TRIGLYCERIDES AND ADIPOSE TISSUE STORAGE OF DIETARY FATTY ACIDS: IMPACT OF MENOPAUSE AND ESTRADIOL

    PubMed Central

    Bessesen, DH; Cox-York, KA; Hernandez, TL; Erickson, CB; Wang, H; Jackman, MR; Van Pelt, RE

    2014-01-01

    Objective Postprandial lipemia worsens after menopause, but the mechanism remains unknown. We hypothesized menopause-related postprandial lipemia would be: 1) associated with reduced storage of dietary fatty acids (FA) as triglyceride (TG) in subcutaneous adipose tissue (SAT); and 2) improved by short-term estradiol (E2). Design and Methods We studied 23 pre- (mean±SD; 42±4yr) and 22 postmenopausal (55±4yr) women with similar total adiposity. A subset of postmenopausal women (n=12) were studied following 2 weeks of E2 (0.15mg) and matching placebo in a random, cross-over design. A liquid meal containing 14C-oleic acid traced appearance of dietary FA in: serum (postprandial TG), breath (oxidation), and abdominal and femoral SAT (TG storage). Results Compared to premenopausal, healthy lean postmenopausal women had increased postprandial glucose and insulin and trend for higher TG, but similar dietary FA oxidation and storage. Adipocytes were larger in post- compared to premenopausal women, particularly in femoral SAT. Short-term E2 reduced postprandial TG and insulin, but had no effect on oxidation or storage of dietary FA. E2 increased the proportion of small adipocytes in femoral (but not abdominal) SAT. Conclusions Short-term E2 attenuated menopause-related increases in postprandial TG and increased femoral adipocyte hyperplasia, but not through increased net storage of dietary FA. PMID:25354893

  15. Excess S-adenosylmethionine reroutes phosphatidylethanolamine towards phosphatidylcholine and triglyceride synthesis

    PubMed Central

    Martnez-Ua, Maite; Varela-Rey, Marta; Cano, Ainara; Fernndez-Ares, Larraitz; Beraza, Naiara; Aurrekoetxea, Igor; Martnez-Arranz, Ibon; Garca-Rodrguez, Juan L; Buqu, Xabier; Mestre, Daniela; Luka, Zigmund; Wagner, Conrad; Alonso, Cristina; Finnell, Richard H; Lu, Shelly C; Martnez-Chantar, M Luz; Aspichueta, Patricia; Mato, Jos M

    2013-01-01

    Methionine adenosyltransferase 1A (MAT1A) and glycine N-methyltransferase (GNMT) are the primary genes involved in hepatic S-adenosylmethionine (SAMe) synthesis and degradation, respectively. Mat1a ablation in mice induces a decrease in hepatic SAMe, activation of lipogenesis, inhibition of triglyceride (TG) release, and steatosis. Gnmt deficient mice, despite showing a large increase in hepatic SAMe, also develop steatosis. We hypothesized that as an adaptive response to hepatic SAMe accumulation, phosphatidylcholine (PC) synthesis via the phosphatidylethanolamine (PE) N-methyltransferase (PEMT) pathway is stimulated in Gnmt?/? mice. We also propose that the excess PC thus generated is catabolized leading to TG synthesis and steatosis via diglyceride (DG) generation. We observed that Gnmt?/? mice present with normal hepatic lipogenesis and increased TG release. We also observed that the flux from PE to PC is stimulated in the liver of Gnmt?/? mice and that this results in a reduction in PE content and a marked increase in DG and TG. Conversely, reduction of hepatic SAMe following the administration of a methionine deficient diet reverted the flux from PE to PC of Gnmt?/? mice to that of wild type animals and normalized DG and TG content preventing the development of steatosis. Gnmt?/? mice with an additional deletion of perilipin2, the predominant lipid droplet protein, maintain high SAMe levels, with a concurrent increased flux from PE to PC, but do not develop liver steatosis. Conclusion These findings indicate that excess SAMe reroutes PE towards PC and TG synthesis, and lipid sequestration. PMID:23505042

  16. Overexpression of apolipoprotein C-III decreases secretion of dietary triglyceride into lymph.

    PubMed

    Wang, Fei; Kohan, Alison B; Dong, H Henry; Yang, Qing; Xu, Min; Huesman, Sarah; Lou, Danwen; Hui, David Y; Tso, Patrick

    2014-01-01

    Abstract Apolipoprotein C-III (apoC-III) is not only predominantly synthesized by the liver but also by the small intestine. Because apoC-III is secreted from the intestine on the chylomicron along with lipid absorption, we questioned whether apoC-III might play a role in intestinal lipid absorption and/or transport. Using both wild-type (WT) and apoC-III transgenic (apoC-III Tg) mice, we showed that apoC-III Tg mice have decreased lymphatic lipid transport compared with WT mice in response to an intraduodenal infusion of radiolabeled lipid. This is associated with accumulation of radiolabeled lipids in the luminal compartment of the apoC-III Tg mice, indicating delayed lipid uptake from the lumen. The total amount of radioactive lipids in the mucosal compartment did not differ between apoC-III Tg and WT mice, but the lipid distribution analysis indicated a predominance of free fatty acids and monoacylglycerol in the mucosa of apoC-III Tg mice, implying impaired esterification capacity. Thus, the mechanisms underlying the reduced lymphatic lipid transport in apoC-III Tg mice involve both a delayed lipid uptake into enterocytes, as well as impaired esterification to form triglyceride in the mucosa. These data document a novel role for apoC-III in the uptake, re-esterification, and lymphatic transport of dietary lipids in the intestine. PMID:24760506

  17. Polymorphisms, de novo lipogenesis, and plasma triglyceride response following fish oil supplementation

    PubMed Central

    Bouchard-Mercier, Annie; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

    2013-01-01

    Interindividual variability in the response of plasma triglyceride concentrations (TG) following fish oil consumption has been observed. Our objective was to examine the associations between single-nucleotide polymorphisms (SNPs) within genes encoding proteins involved in de novo lipogenesis and the relative change in plasma TG levels following a fish oil supplementation. Two hundred and eight participants were recruited in the greater Quebec City area. The participants completed a six-week fish oil supplementation (5 g fish oil/day: 1.9–2.2 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid. SNPs within SREBF1, ACLY, and ACACA genes were genotyped using TAQMAN methodology. After correction for multiple comparison, only two SNPs, rs8071753 (ACLY) and rs1714987 (ACACA), were associated with the relative change in plasma TG concentrations (P = 0.004 and P = 0.005, respectively). These two SNPs explained 7.73% of the variance in plasma TG relative change following fish oil consumption. Genotype frequencies of rs8071753 according to the TG response groups (responders versus nonresponders) were different (P = 0.02). We conclude that the presence of certain SNPs within genes, such as ACLY and ACACA, encoding proteins involved in de novo lipogenesis seem to influence the plasma TG response following fish oil consumption. PMID:23886516

  18. Progesterone-specific stimulation of triglyceride biosynthesis in a breast cancer cell line (T-47D)

    SciTech Connect

    Judge, S.M.; Chatterton, R.T. Jr.

    1983-09-01

    The purpose of this study was to examine the lactogenic response of human mammary cancer cell lines to hormones in vitro. Progesterone was found to stimulate the incorporation of 14C from (14C)acetate into triglycerides (TG) and to promote accumulation of TG with a fatty acid composition similar to that of human milk fat in T-47D cells. Lipid droplets were observed in larger numbers without concomitant accumulation of casein granules in cells incubated with progesterone, but secretion of lipid into the medium did not occur. An effect of progesterone on TG accumulation was detectable after 12 hr and was maximal at 72 hr. Increasing doses of progesterone (10(-9) to 10(-5) M) caused a progressive increase in TG accumulation. The presence of cortisol and/or prolactin did not alter TG formation nor the dose response of the cells to progesterone. The growth rate of T-47D cells was not altered by the presence of progesterone in the medium. Neither of the human mammary cancer cell lines, MCF-7 and HBL-100, nor the human fibroblast cell lines, 28 and 857, responded to progesterone. The data indicate that, while the normally lactogenic hormones do not stimulate milk product biosynthesis in the cell lines tested, progesterone specifically stimulated synthesis and accumulation of TG in the T-47D cells.

  19. Tocotrienol attenuates triglyceride accumulation in HepG2 cells and F344 rats.

    PubMed

    Burdeos, Gregor Carpentero; Nakagawa, Kiyotaka; Kimura, Fumiko; Miyazawa, Teruo

    2012-05-01

    Tocotrienol (T3) is an important phytonutrient found in rice bran and palm oil. T3 has gained much interest for lipid lowering effects, especially for cholesterol (Cho) by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Also, usefulness of T3 in improving triglyceride (TG) profiles has been suggested, but its efficacy and mechanism have been unclear. We investigated how T3 decreases TG concentration in cultured cells and animals. In a cell culture study, human hepatoma cells (HepG2) were incubated in a control or a fat (1 mM oleic acid)-loaded medium containing γ-T3 for 24 h. We found that 10-15 μM γ-T3 inhibited cellular TG accumulation significantly, especially in the fat-loaded medium. This manifestation was supported by mRNA and protein expressions of fatty acid synthase, carnitine palmitoyltransferase 1, and cytochrome P450 3A4. In concordance with these results, rice bran T3 supplementation to F344 rats (5 or 10 mg T3/day/rat) receiving a high fat diet for 3 weeks significantly reduced TG and the oxidative stress marker (phospholipid hydroperoxides, PLOOH) in the liver and blood plasma. T3 supplementation did not show changes in the Cho level. These results provided new information and the mechanism of the TG-lowering effect of T3. The lipid lowering effects of dietary T3 might be mediated by the reduction of TG synthesis. PMID:22367056

  20. [Influence of endogenous TgAb upon serum Tg measurement results and Tg positive rate in patients with differentiated thyroid carcinoma].

    PubMed

    Zhang, Wenjie; Deng, Houfu; Pan, Mingzhi; Huang, Rui; Tang, Gongshun

    2013-08-01

    The first aim of this study was to compare the serum thyroglobulin (Tg) positive rate between differentiated thyroid carcinoma (DTC) patients with positive thyroglobulin antibody (TgAb) and patients with negative TgAb. The second aim of this study was to investigate the correlation between serum Tg value and antithyroglobulin (TgAb) concentration of patients with DTC. We collected the serum Tg value and TgAb concentration of patients with DTC after thyroid ablation by operation and radioiodine therapy retrospectively. Then we investigated the Tg positive rate of DTC patients with positive TgAb and patients with negative TgAb separately. The scatter diagram between serum Tg value and TgAb concentration of DTC patients was performed to analyze their potential relationship. As a result, among 252 patients with DTC after thyroid ablation, 7 of 47 patients (14.89%) with positive TgAb (>115 IU/mL) had positive serum Tg (>10 microg/L), and 61 of 205 (29.76%) patients with negative TgAb (<115 IU/mL) had positive serum Tg. Eighty three of the 252 patients with DTC had accurate serum Tg and TgAb concentration. No correlation between serum Tg value and TgAb concentration was found among these Eighty three patients. Thus, it may be concluded that positive TgAb could cause much more TgAb interference in serum Tg value than negative TgAb could because of a different quality of TgAb. Serum Tg value is not correlated with serum TgAb concentration in patients with DTC after thyroid ablation. PMID:24059060

  1. Dog Age and Breeds Associated with High Plasma Cholesterol and Triglyceride Concentrations

    PubMed Central

    USUI, Shiho; MIZOGUCHI, Yasushi; YASUDA, Hidemi; ARAI, Nobuaki; KOKETSU, Yuzo

    2013-01-01

    ABSTRACT The objectives of this study were to set specific dog breed and sex standards for total cholesterol (T-Cho) and total triglyceride (T-TG) concentrations in dogs and to quantify the associations between dog age and concentrations of both lipids for different breeds. Increased age was associated with higher T-Cho and T-TG concentrations in all five breed groups (P<0.05); T-Cho concentrations increased by 62.5 mg/dl between 9 and 16 years of age, and T-TG concentrations increased by 4.8 mg/dl per year of age (P<0.05). Miniature Schnauzers had the highest T-Cho concentrations of the studied breeds, while Miniature Dachshunds had the lowest concentrations (P<0.05). Veterinarians should consider dog age and breed when they use the lipid concentrations for diagnostic purposes. PMID:24107429

  2. Krill oil supplementation lowers serum triglycerides without increasing low-density lipoprotein cholesterol in adults with borderline high or high triglyceride levels.

    PubMed

    Berge, Kjetil; Musa-Veloso, Kathy; Harwood, Melody; Hoem, Nils; Burri, Lena

    2014-02-01

    The aim of the study was to explore the effects of 12 weeks daily krill oil supplementation on fasting serum triglyceride (TG) and lipoprotein particle levels in subjects whose habitual fish intake is low and who have borderline high or high fasting serum TG levels (150-499 mg/dL). We hypothesized that Krill oil lowers serum TG levels in subjects with borderline high or high fasting TG levels. To test our hypothesis 300 male and female subjects were included in a double-blind, randomized, multi-center, placebo-controlled study with five treatment groups: placebo (olive oil) or 0.5, 1, 2, or 4 g/day of krill oil. Serum lipids were measured after an overnight fast at baseline, 6 and 12 weeks. Due to a high intra-individual variability in TG levels, data from all subjects in the four krill oil groups were pooled to increase statistical power, and a general time- and dose-independent one-way analysis of variance was performed to assess efficacy. Relative to subjects in the placebo group, those administered krill oil had a statistically significant calculated reduction in serum TG levels of 10.2%. Moreover, LDL-C levels were not increased in the krill oil groups relative to the placebo group. The outcome of the pooled analysis suggests that krill oil is effective in reducing a cardiovascular risk factor. However, owing to the individual fluctuations of TG concentrations measured, a study with more individual measurements per treatment group is needed to increase the confidence of these findings. PMID:24461313

  3. JTT-130, a microsomal triglyceride transfer protein (MTP) inhibitor lowers plasma triglycerides and LDL cholesterol concentrations without increasing hepatic triglycerides in guinea pigs

    PubMed Central

    Aggarwal, Dimple; West, Kristy L; Zern, Tosca L; Shrestha, Sudeep; Vergara-Jimenez, Marcela; Fernandez, Maria Luz

    2005-01-01

    Background Microsomal transfer protein inhibitors (MTPi) have the potential to be used as a drug to lower plasma lipids, mainly plasma triglycerides (TG). However, studies with animal models have indicated that MTPi treatment results in the accumulation of hepatic TG. The purpose of this study was to evaluate whether JTT-130, a unique MTPi, targeted to the intestine, would effectively reduce plasma lipids without inducing a fatty liver. Methods Male guinea pigs (n = 10 per group) were used for this experiment. Initially all guinea pigs were fed a hypercholesterolemic diet containing 0.08 g/100 g dietary cholesterol for 3 wk. After this period, animals were randomly assigned to diets containing 0 (control), 0.0005 or 0.0015 g/100 g of MTPi for 4 wk. A diet containing 0.05 g/100 g of atorvastatin, an HMG-CoA reductase inhibitor was used as the positive control. At the end of the 7th week, guinea pigs were sacrificed to assess drug effects on plasma and hepatic lipids, composition of LDL and VLDL, hepatic cholesterol and lipoprotein metabolism. Results Plasma LDL cholesterol and TG were 25 and 30% lower in guinea pigs treated with MTPi compared to controls (P < 0.05). Atorvastatin had the most pronounced hypolipidemic effects with a 35% reduction in LDL cholesterol and 40% reduction in TG. JTT-130 did not induce hepatic lipid accumulation compared to controls. Cholesteryl ester transfer protein (CETP) activity was reduced in a dose dependent manner by increasing doses of MTPi and guinea pigs treated with atorvastatin had the lowest CETP activity (P < 0.01). In addition the number of molecules of cholesteryl ester in LDL and LDL diameter were lower in guinea pigs treated with atorvastatin. In contrast, hepatic enzymes involved in maintaining cholesterol homeostasis were not affected by drug treatment. Conclusion These results suggest that JTT-130 could have potential clinical applications due to its plasma lipid lowering effects with no alterations in hepatic lipid concentrations. PMID:16188040

  4. Adipose triglyceride lipase is involved in the mobilization of triglyceride and retinoid stores of hepatic stellate cells

    PubMed Central

    Taschler, Ulrike; Schreiber, Renate; Chitraju, Chandramohan; Grabner, Gernot F.; Romauch, Matthias; Wolinski, Heimo; Haemmerle, Guenter; Breinbauer, Rolf; Zechner, Rudolf; Lass, Achim; Zimmermann, Robert

    2015-01-01

    Hepatic stellate cells (HSCs) store triglycerides (TGs) and retinyl ester (RE) in cytosolic lipid droplets. RE stores are degraded following retinoid starvation or in response to pathogenic stimuli resulting in HSC activation. At present, the major enzymes catalyzing lipid degradation in HSCs are unknown. In this study, we investigated whether adipose triglyceride lipase (ATGL) is involved in RE catabolism of HSCs. Additionally, we compared the effects of ATGL deficiency and hormone-sensitive lipase (HSL) deficiency, a known RE hydrolase (REH), on RE stores in liver and adipose tissue. We show that ATGL degrades RE even in the presence of TGs, implicating that these substrates compete for ATGL binding. REH activity was stimulated and inhibited by comparative gene identification-58 and G0/G1 switch gene-2, respectively, the physiological regulators of ATGL activity. In cultured primary murine HSCs, pharmacological inhibition of ATGL, but not HSL, increased RE accumulation. In mice globally lacking ATGL or HSL, RE contents in white adipose tissue were decreased or increased, respectively, while plasma retinol and liver RE levels remained unchanged. In conclusion, our study shows that ATGL acts as REH in HSCs promoting the degradation of RE stores in addition to its established function as TG lipase. HSL is the predominant REH in adipocytes but does not affect lipid mobilization in HSCs. PMID:25732851

  5. MicroRNA-192* impairs adipocyte triglyceride storage.

    PubMed

    Mysore, Raghavendra; Zhou, You; Sädevirta, Sanja; Savolainen-Peltonen, Hanna; Nidhina Haridas, P A; Soronen, Jarkko; Leivonen, Marja; Sarin, Antti-Pekka; Fischer-Posovszky, Pamela; Wabitsch, Martin; Yki-Järvinen, Hannele; Olkkonen, Vesa M

    2016-04-01

    We investigated the expression of miR-192* (miR-192-3p) in the visceral adipose tissue (VAT) of obese subjects and its function in cultured human adipocytes. This miRNA is a 3' arm derived from the same pre-miRNA as miR-192 (miR-192-5p) implicated in type 2 diabetes, liver disease and cancers, and is predicted to target key genes in lipid metabolism. In morbidly obese subjects undergoing bariatric surgery preceded by a very low calorie diet, miR-192* in VAT correlated negatively (r=-0.387; p=0.046) with serum triglyceride (TG) and positively with high-density lipoprotein (HDL) concentration (r=0.396; p=0.041). In a less obese patient cohort, the miRNA correlated negatively with the body mass index (r=-0.537; p=0.026). To characterize the function of miR-192*, we overexpressed it in cultured adipocytes and analyzed the expression of adipogenic differentiation markers as well as cellular TG content. Reduced TG and expression of the adipocyte marker proteins aP2 (adipocyte protein 2) and perilipin 1 were observed. The function of miR-192* was further investigated by transcriptomic profiling of adipocytes expressing this miRNA, revealing impacts on key lipogenic genes. A number of the mRNA alterations were validated by qPCR. Western analysis confirmed a marked reduction of the lipogenic enzyme SCD (stearoyl coenzyme A desaturase-1), the fatty aldehyde dehydrogenase ALDH3A2 (aldehyde dehydrogenase 3 family member A2) and the high-density lipoprotein receptor SCARB1 (scavenger receptor B, type I). SCD and ALDH3A2 were demonstrated to be direct targets of miR-192*. To conclude, the present data identify miR-192* as a novel controller of adipocyte differentiation and lipid homeostasis. PMID:26747651

  6. Mitochondrial triglyceride transfer protein inhibition: new achievements in the treatment of dyslipidemias.

    PubMed

    Kostapanos, Michael S; Rizos, Evangelos C; Papanas, Nikolaos; Maltezos, Efstratios; Elisaf, Moses S

    2013-01-01

    Current lipid-lowering drugs are often unable to achieve low density lipoprotein cholesterol (LDL-C) goals. Moreover, despite LDL-C lowering mostly by statins, a considerable residual vascular risk remains. This is partly associated with atherogenic dyslipidemia where apolipoprotein (apo) B-containing lipoproteins predominate. Mitochondrial Triglyceride (TG) transfer protein (MTP) is a key enzyme for apoB-containing lipoprotein assembly and secretion. This is mostly attributed to its capacity to transfer lipid components (TGs, cholesterol esters and phospholipids) to the endoplasmic reticulum lumen, where these lipoproteins are assembled. Several agents were developed to inhibit MTP wherever it is expressed, namely the liver and/or the intestine. Liver-specific MTP inhibitors reduce secretion of very low density lipoproteins (VLDL) mostly containing apoB100, while the intestine-specific ones reduce secretion of chylomicrons containing apoB48. These drugs can significantly reduce total cholesterol, LDL-C, TGs, VLDL cholesterol, as well as apoB levels in vivo. They may also exert anti-atherosclerotic and insulin-sensitizing effects. Limited clinical data suggest that these compounds can also improve the serum lipid profile in patients with homozygous familial hypercholesterolemia (HoFH). The accumulation of unsecreted fat in the liver and intestinal lumen is associated with elevation of aminotransferases and steatorrhea. Liver steatosis can be avoided by the use of intestine-specific MTP inhibitors, while steatorrhea by low-fat diet. Future indications for these developing drugs may include dyslipidemia associated with insulin resistant states, familial combined hyperlipidemia and HoFH. Future clinical trials are warranted to assess the efficacy and safety of MTP inhibitors in various clinical states. PMID:23317403

  7. ?-Lipoic acid as a triglyceride-lowering nutraceutical.

    PubMed

    Pashaj, Anjeza; Xia, Mengna; Moreau, Rgis

    2015-12-01

    Considering the current obesity epidemic in the United States (>100 million adults are overweight or obese), the prevalence of hypertriglyceridemia is likely to grow beyond present statistics of ?30% of the population. Conventional therapies for managing hypertriglyceridemia include lifestyle modifications such as diet and exercise, pharmacological approaches, and nutritional supplements. It is critically important to identify new strategies that would be safe and effective in lowering hypertriglyceridemia. ?-Lipoic acid (LA) is a naturally occurring enzyme cofactor found in the human body in small quantities. A growing body of evidence indicates a role of LA in ameliorating metabolic dysfunction and lipid anomalies primarily in animals. Limited human studies suggest LA is most efficacious in situations where blood triglycerides are markedly elevated. LA is commercially available as dietary supplements and is clinically shown to be safe and effective against diabetic polyneuropathies. LA is described as a potent biological antioxidant, a detoxification agent, and a diabetes medicine. Given its strong safety record, LA may be a useful nutraceutical, either alone or in combination with other lipid-lowering strategies, when treating severe hypertriglyceridemia and diabetic dyslipidemia. This review examines the current evidence regarding the use of LA as a means of normalizing blood triglycerides. Also presented are the leading mechanisms of action of LA on triglyceride metabolism. PMID:26235242

  8. Minor components of olive oil facilitate the triglyceride clearance from postprandial lipoproteins in a polarity-dependent manner in healthy men.

    PubMed

    Cabello-Moruno, Rosana; Martinez-Force, Enrique; Montero, Emilio; Perona, Javier S

    2014-01-01

    Postprandial triglyceride-rich lipoproteins (TRLs) are recognized as atherogenic particles whose lipid composition and function can be modified by the composition of dietary oils. This study was designed to test the hypothesis that minor components of pomace olive oil (POMACE) can not only change the composition of postprandial TRL but also affect the clearance of triglyceride (TG) molecular species of postprandial TRL. Meals enriched in either POMACE or refined olive oil (OLIVE) were administered to 10 healthy young men. TRL were isolated from serum at 2, 4, and 6 hours postprandially, and their fatty acid and TG molecular species compositions were analyzed by gas chromatography. The apolipoprotein B concentration was determined by immunoturbidimetry. POMACE and OLIVE, differing mainly in their unsaponifiable fraction, led to similar fatty acid and TG molecular species profiles in postprandial TRL. However, POMACE-TRL presented a higher particle size, estimated as TG to apolipoprotein B ratio, which was also found for the main TG molecular species (trioleoyl-glycerol, palmitoyl-dioleoyl-glycerol, palmitoyl-oeloyl-linoleoyl-glycerol, and dioleoyl-linoleoyl-glycerol). TG from POMACE-TRL also showed higher clearance rates. In this regard, apolar TG (with a higher equivalent carbon number) disappeared more rapidly from TRL particles obtained after the ingestion of either POMACE or OLIVE. In conclusion, minor components of POMACE facilitated TG clearance from TRL by modifying their particle size and the hydrolysis of the most apolar species. PMID:24418245

  9. Identification of TgAtg8-TgAtg3 interaction in Toxoplasma gondii.

    PubMed

    Chen, Di; Lin, Jiaxin; Liu, Yangyang; Li, Xiangzhi; Chen, Gaozhi; Hua, Qianqian; Nie, Qinqin; Hu, Xin; Tan, Feng

    2016-01-01

    Autophagy is a catabolic process in eukaryotic cells involved in the targeted degradation of cellular organelles and the cytoplasm. Recent works in Toxoplasma gondii suggest that the autophagy processes may serve as an important pathway in modulating parasite survival or death. As an important modulator of Atg8 lipidation and autophagy, Atg8-Atg3 interaction has been attracting increasing attention. However, there is no direct evidence that TgAtg8-TgAtg3 interaction occurs in the parasite. In this study, we firstly found TgAtg8 partially colocalized with TgAtg3 in GFP-TgAtg8 transgenic strains using IFA. Then, lysates from GFP-TgAtg8 tachyzoites were directly subject to large-scale tandem affinity purification with anti-GFP antibody. Western blot and tandem mass spectrometry (MS/MS) analysis determined the interaction between TgAtg8 and TgAtg3. Additionally, we performed real-time interaction analysis with a surface plasmon resonance biosensor using BIAcore system. As expected, the result demonstrated a concentration-dependent increases in resonance signals and indicated the TgAtg8 could bind directly TgAtg3 in vitro. Noteworthily, A KD of 34.9nM obtained from TgAtg8-TgAtg3 interaction indicate a high-affinity between Atg8-Atg3 in Toxoplasma. Furthermore, homology modeling and sequence alignment showed that TgAtg8 has greatest sequence and structural conservation. Within TgAtg3, this protein possesses the core E2 enzymatic activity structure and a truncated handle region which may contain AIM sequence. Taken together, our findings would help elucidate the formation mechanism of autophagosome in Toxoplasma and provide a possibility for looking into parasitic drug targets. PMID:26407821

  10. Reduced triglyceride secretion in response to an acute dietary fat challenge in obese compared to lean mice.

    PubMed

    Uchida, Aki; Whitsitt, Mary C; Eustaquio, Trisha; Slipchenko, Mikhail N; Leary, James F; Cheng, Ji-Xin; Buhman, Kimberly K

    2012-01-01

    Obesity results in abnormally high levels of triglyceride (TG) storage in tissues such as liver, heart, and muscle, which disrupts their normal functions. Recently, we found that lean mice challenged with high levels of dietary fat store TGs in cytoplasmic lipid droplets in the absorptive cells of the intestine, enterocytes, and that this storage increases and then decreases over time after an acute dietary fat challenge. The goal of this study was to investigate the effects of obesity on intestinal TG metabolism. More specifically we asked whether TG storage in and secretion from the intestine are altered in obesity. We investigated these questions in diet-induced obese (DIO) and leptin-deficient (ob/ob) mice. We found greater levels of TG storage in the intestine of DIO mice compared to lean mice in the fed state, but similar levels of TG storage after a 6-h fast. In addition, we found similar TG storage in the intestine of lean and DIO mice at multiple time points after an acute dietary fat challenge. Surprisingly, we found remarkably lower TG secretion from both DIO and ob/ob mice compared to lean controls in response to an acute dietary fat challenge. Furthermore, we found altered mRNA levels for genes involved in regulation of intestinal TG metabolism in lean and DIO mice at 6 h fasting and in response to an acute dietary fat challenge. More specifically, we found that many of the genes related to TG synthesis, chylomicron synthesis, TG storage, and lipolysis were induced in response to an acute dietary fat challenge in lean mice, but this induction was not observed in DIO mice. In fact, we found a significant decrease in intestinal mRNA levels of genes related to lipolysis and fatty acid oxidation in DIO mice in response to an acute dietary fat challenge. Our findings demonstrate altered TG handling by the small intestine of obese compared to lean mice. PMID:22375122

  11. Reduced Triglyceride Secretion in Response to an Acute Dietary Fat Challenge in Obese Compared to Lean Mice

    PubMed Central

    Uchida, Aki; Whitsitt, Mary C.; Eustaquio, Trisha; Slipchenko, Mikhail N.; Leary, James F.; Cheng, Ji-Xin; Buhman, Kimberly K.

    2012-01-01

    Obesity results in abnormally high levels of triglyceride (TG) storage in tissues such as liver, heart, and muscle, which disrupts their normal functions. Recently, we found that lean mice challenged with high levels of dietary fat store TGs in cytoplasmic lipid droplets in the absorptive cells of the intestine, enterocytes, and that this storage increases and then decreases over time after an acute dietary fat challenge. The goal of this study was to investigate the effects of obesity on intestinal TG metabolism. More specifically we asked whether TG storage in and secretion from the intestine are altered in obesity. We investigated these questions in diet-induced obese (DIO) and leptin-deficient (ob/ob) mice. We found greater levels of TG storage in the intestine of DIO mice compared to lean mice in the fed state, but similar levels of TG storage after a 6-h fast. In addition, we found similar TG storage in the intestine of lean and DIO mice at multiple time points after an acute dietary fat challenge. Surprisingly, we found remarkably lower TG secretion from both DIO and ob/ob mice compared to lean controls in response to an acute dietary fat challenge. Furthermore, we found altered mRNA levels for genes involved in regulation of intestinal TG metabolism in lean and DIO mice at 6 h fasting and in response to an acute dietary fat challenge. More specifically, we found that many of the genes related to TG synthesis, chylomicron synthesis, TG storage, and lipolysis were induced in response to an acute dietary fat challenge in lean mice, but this induction was not observed in DIO mice. In fact, we found a significant decrease in intestinal mRNA levels of genes related to lipolysis and fatty acid oxidation in DIO mice in response to an acute dietary fat challenge. Our findings demonstrate altered TG handling by the small intestine of obese compared to lean mice. PMID:22375122

  12. Micro RNA-124a Regulates Lipolysis via Adipose Triglyceride Lipase and Comparative Gene Identification 58

    PubMed Central

    Das, Suman K.; Stadelmeyer, Elke; Schauer, Silvia; Schwarz, Anna; Strohmaier, Heimo; Claudel, Thiery; Zechner, Rudolf; Hoefler, Gerald; Vesely, Paul W.

    2015-01-01

    Lipolysis is the biochemical pathway responsible for the catabolism of cellular triacylglycerol (TG). Lipolytic TG breakdown is a central metabolic process leading to the generation of free fatty acids (FA) and glycerol, thereby regulating lipid, as well as energy homeostasis. The precise tuning of lipolysis is imperative to prevent lipotoxicity, obesity, diabetes and other related metabolic disorders. Here, we present our finding that miR-124a attenuates RNA and protein expression of the major TG hydrolase, adipose triglyceride lipase (ATGL/PNPLA2) and its co-activator comparative gene identification 58 (CGI-58/ABHD5). Ectopic expression of miR-124a in adipocytes leads to reduced lipolysis and increased cellular TG accumulation. This phenotype, however, can be rescued by overexpression of truncated Atgl lacking its 3'UTR, which harbors the identified miR-124a target site. In addition, we observe a strong negative correlation between miR-124a and Atgl expression in various murine tissues. Moreover, miR-124a regulates the expression of Atgl and Cgi-58 in murine white adipose tissue during fasting as well as the expression of Atgl in murine liver, during fasting and re-feeding. Together, these results point to an instrumental role of miR-124a in the regulation of TG catabolism. Therefore, we suggest that miR-124a may be involved in the regulation of several cellular and organismal metabolic parameters, including lipid storage and plasma FA concentration. PMID:25894224

  13. Micro RNA-124a regulates lipolysis via adipose triglyceride lipase and comparative gene identification 58.

    PubMed

    Das, Suman K; Stadelmeyer, Elke; Schauer, Silvia; Schwarz, Anna; Strohmaier, Heimo; Claudel, Thiery; Zechner, Rudolf; Hoefler, Gerald; Vesely, Paul W

    2015-01-01

    Lipolysis is the biochemical pathway responsible for the catabolism of cellular triacylglycerol (TG). Lipolytic TG breakdown is a central metabolic process leading to the generation of free fatty acids (FA) and glycerol, thereby regulating lipid, as well as energy homeostasis. The precise tuning of lipolysis is imperative to prevent lipotoxicity, obesity, diabetes and other related metabolic disorders. Here, we present our finding that miR-124a attenuates RNA and protein expression of the major TG hydrolase, adipose triglyceride lipase (ATGL/PNPLA2) and its co-activator comparative gene identification 58 (CGI-58/ABHD5). Ectopic expression of miR-124a in adipocytes leads to reduced lipolysis and increased cellular TG accumulation. This phenotype, however, can be rescued by overexpression of truncated Atgl lacking its 3'UTR, which harbors the identified miR-124a target site. In addition, we observe a strong negative correlation between miR-124a and Atgl expression in various murine tissues. Moreover, miR-124a regulates the expression of Atgl and Cgi-58 in murine white adipose tissue during fasting as well as the expression of Atgl in murine liver, during fasting and re-feeding. Together, these results point to an instrumental role of miR-124a in the regulation of TG catabolism. Therefore, we suggest that miR-124a may be involved in the regulation of several cellular and organismal metabolic parameters, including lipid storage and plasma FA concentration. PMID:25894224

  14. Macrophage Adipose Triglyceride Lipase Deficiency Attenuates Atherosclerotic Lesion Development in Low-Density Lipoprotein Receptor Knockout Mice

    PubMed Central

    Lammers, Bart; Chandak, Prakash G.; Aflaki, Elma; Van Puijvelde, Gijs H.M.; Radovic, Branislav; Hildebrand, Reeni B.; Meurs, Illiana; Out, Ruud; Kuiper, Johan; Van Berkel, Theo J.C.; Kolb, Dagmar; Haemmerle, Guenter; Zechner, Rudolf; Levak-Frank, Sanja; Van Eck, Miranda; Kratky, Dagmar

    2011-01-01

    Objective The consequences of macrophage triglyceride (TG) accumulation on atherosclerosis have not been studied in detail so far. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme for the initial step in TG hydrolysis. Because ATGL knockout (KO) mice exhibit massive TG accumulation in macrophages, we used ATGL KO mice to study the effects of macrophage TG accumulation on atherogenesis. Methods and Results Low-density lipoprotein receptor (LDLr) KO mice were transplanted with bone marrow from ATGL KO (ATGL KO?LDLr KO) or wild-type (wild-type?LDLr KO) mice and challenged with a Western-type diet for 9 weeks. Despite TG accumulation in ATGL KO macrophages, atherosclerosis in ATGL KO?LDLr KO mice was 43% reduced associated with decreased plasma MCP-1 and macrophage interleukin-6 concentrations. This coincided with a reduced amount of macrophages, possibly because of a 39% increase in intraplaque apoptosis and a decreased migratory capacity of ATGL KO macrophages. The reduced number of white blood cells might be due to a 36% decreased Lin?Sca-1+cKit+ hematopoietic stem cell population. Conclusion We conclude that the attenuation of atherogenesis in ATGL KO?LDLr KO mice is due to decreased infiltration of less inflammatory macrophages into the arterial wall and increased macrophage apoptosis. PMID:21030715

  15. Overexpression of Rad in muscle worsens diet-induced insulin resistance and glucose intolerance and lowers plasma triglyceride level

    NASA Astrophysics Data System (ADS)

    Ilany, Jacob; Bilan, Philip J.; Kapur, Sonia; Caldwell, James S.; Patti, Mary-Elizabeth; Marette, Andre; Kahn, C. Ronald

    2006-03-01

    Rad is a low molecular weight GTPase that is overexpressed in skeletal muscle of some patients with type 2 diabetes mellitus and/or obesity. Overexpression of Rad in adipocytes and muscle cells in culture results in diminished insulin-stimulated glucose uptake. To further elucidate the potential role of Rad in vivo, we have generated transgenic (tg) mice that overexpress Rad in muscle using the muscle creatine kinase (MCK) promoter-enhancer. Rad tg mice have a 6- to 12-fold increase in Rad expression in muscle as compared to wild-type littermates. Rad tg mice grow normally and have normal glucose tolerance and insulin sensitivity, but have reduced plasma triglyceride levels. On a high-fat diet, Rad tg mice develop more severe glucose intolerance than the wild-type mice; this is due to increased insulin resistance in muscle, as exemplified by a rightward shift in the dose-response curve for insulin stimulated 2-deoxyglucose uptake. There is also a unexpected further reduction of the plasma triglyceride levels that is associated with increased levels of lipoprotein lipase in the Rad tg mice. These results demonstrate a potential synergistic interaction between increased expression of Rad and high-fat diet in creation of insulin resistance and altered lipid metabolism present in type 2 diabetes. diabetes mellitus | glucose transport | RGK GTPase | transgenic mouse

  16. Acute Administration of n-3 Rich Triglyceride Emulsions Provides Cardioprotection in Murine Models after Ischemia-Reperfusion

    PubMed Central

    Zirpoli, Hylde; Abdillahi, Mariane; Quadri, Nosirudeen; Ananthakrishnan, Radha; Wang, Lingjie; Rosario, Rosa; Zhu, Zhengbin; Deckelbaum, Richard J.; Ramasamy, Ravichandran

    2015-01-01

    Dietary n-3 fatty acids (FAs) may reduce cardiovascular disease risk. We questioned whether acute administration of n-3 rich triglyceride (TG) emulsions could preserve cardiac function and decrease injury after ischemia/reperfusion (I/R) insult. We used two different experimental models: in vivo, C57BL/6 mice were exposed to acute occlusion of the left anterior descending coronary artery (LAD), and ex-vivo, C57BL/6 murine hearts were perfused using Langendorff technique (LT). In the LAD model, mice treated with n-3 TG emulsion (1.5g/kg body weight), immediately after ischemia and 1h later during reperfusion, significantly reduced infarct size and maintained cardiac function (p<0.05). In the LT model, administration of n-3 TG emulsion (300mgTG/100ml) during reperfusion significantly improved functional recovery (p<0.05). In both models, lactate dehydrogenase (LDH) levels, as a marker of injury, were significantly reduced by n-3 TG emulsion. To investigate the mechanisms by which n-3 FAs protects hearts from I/R injury, we investigated changes in key pathways linked to cardioprotection. In the ex-vivo model, we showed that n-3 FAs increased phosphorylation of AKT and GSK3β proteins (p<0.05). Acute n-3 TG emulsion treatment also increased Bcl-2 protein level and reduced an autophagy marker, Beclin-1 (p<0.05). Additionally, cardioprotection by n-3 TG emulsion was linked to changes in PPARγ protein expression (p<0.05). Rosiglitazone and p-AKT inhibitor counteracted the positive effect of n-3 TG; GSK3β inhibitor plus n-3 TG significantly inhibited LDH release. We conclude that acute n-3 TG injection during reperfusion provides cardioprotection. This may prove to be a novel acute adjunctive reperfusion therapy after treating patients with myocardial infarction. PMID:25559887

  17. Mechanisms of triglyceride accumulation in activated macrophages

    PubMed Central

    Feingold, Kenneth R.; Shigenaga, Judy K.; Kazemi, Mahmood R.; McDonald, Carol M.; Patzek, Sophie M.; Cross, Andrew S.; Moser, Arthur; Grunfeld, Carl

    2012-01-01

    LPS treatment of macrophages induces TG accumulation, which is accentuated by TG-rich lipoproteins or FFA. We defined pathways altered during macrophage activation that contribute to TG accumulation. Glucose uptake increased with activation, accompanied by increased GLUT1. Oxidation of glucose markedly decreased, whereas incorporation of glucose-derived carbon into FA and sterols increased. Macrophage activation also increased uptake of FFA, associated with an increase in CD36. Oxidation of FA was markedly reduced, whereas the incorporation of FA into TGs increased, associated with increased GPAT3 and DGAT2. Additionally, macrophage activation decreased TG lipolysis; however, expression of ATGL or HSL was not altered. Macrophage activation altered gene expression similarly when incubated with exogenous FA or AcLDL. Whereas activation with ligands of TLR2 (zymosan), TLR3 (poly I:C), or TLR4 (LPS) induced alterations in macrophage gene expression, leading to TG accumulation, treatment of macrophages with cytokines had minimal effects. Thus, activation of TLRs leads to accumulation of TG in macrophages by multiple pathways that may have beneficial effects in host defense but could contribute to the accelerated atherosclerosis in chronic infections and inflammatory diseases. PMID:22753953

  18. De novo synthesis of milk triglycerides in humans

    PubMed Central

    Mohammad, Mahmoud A.; Sunehag, Agneta L.

    2014-01-01

    Mammary gland (MG) de novo lipogenesis contributes significantly to milk fat in animals but little is known in humans. Objective: To test the hypothesis that the incorporation of 13C carbons from [U-13C]glucose into fatty acids (FA) and glycerol in triglycerides (TG) will be greater: 1) in milk than plasma TG, 2) during a high-carbohydrate (H-CHO) diet than high-fat (H-FAT) diet, and 3) during feeding than fasting. Seven healthy, lactating women were studied on two isocaloric, isonitrogenous diets. On one occasion, subjects received diets containing H-FAT or H-CHO diet for 1 wk. Incorporation of 13C from infused [U-13C]glucose into FA and glycerol was measured using GC-MS and gene expression in RNA isolated from milk fat globule using microarrays. Incorporation of 13C2 into milk FA increased with increased FA chain length from C2:0 to C12:0 but progressively declined in C14:0 and C16:0 and was not detected in FA>C16. During feeding, regardless of diets, enrichment of 13C2 in milk FA and 13C3 in milk glycerol were ∼3- and ∼7-fold higher compared with plasma FA and glycerol, respectively. Following an overnight fast during H-CHO and H-FAT diets, 25 and 6%, respectively, of medium-chain FA (MCFA, C6–C12) in milk were derived from glucose but increased to 75 and 25% with feeding. Expression of genes involved in FA or glycerol synthesis was unchanged regardless of diet or fast/fed conditions. The human MG is capable of de novo lipogenesis of primarily MCFA and glycerol, which is influenced by the macronutrient composition of the maternal diet. PMID:24496312

  19. Low fasting serum triglyceride level as a precocious marker of autoimmune disorders.

    PubMed

    Iannello, Silvia; Cavaleri, Antonina; Milazzo, Paolina; Cantarella, Santi; Belfiore, Francesco

    2003-08-01

    The authors recently reported the occurrence of low fasting serum triglyceride (TG) and high free fatty acid (FFA) levels in idiopathic pulmonary fibrosis. TG estimation in diverse groups of patients with autoimmune disease or hyperactive immune response confirmed the occurrence of a similar decrease of TG. In some patients, serum FFA level was also evaluated. TG value in lean and obese patients was compared with that in lean (n = 108) and obese (n = 208) control subjects without autoimmune disease. In patients affected by autoimmune chronic thyroiditis with enhanced concentration of antithyroglobulin antibodies and without thyroidal failure (n = 24), lean and obese patients had reduced TG (-69/%, P < .01 and -52%, P < .0001, respectively). Both lean and obese patients affected by chronic active B or C hepatitis (n = 26), with autoantibodies and without signs of hepatic insufficiency or cirrhosis, presented reduced TG (-57%, P < .01 and -61%, P < .001, respectively). A marked TG decrease (-73%, P < .001) was observed in the lean patients affected by lupus-like syndrome (n = 7). The lean and obese patients with systemic lupus erythematosus or rheumatoid arthritis (n = 11) showed TG decrease (-66%, P < .01 and -55%, P < .05, respectively). In patients affected by anamnestic allergy or atopic dermatitis/asthma (n = 66), both lean and obese, TGs were reduced (-67%, P < .0001 and -62%, P < .001, respectively). In isolated cases of diverse autoimmune diseases (scleroderma, APECED [autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy], urticaria or urticarial vasculitis, Reiter or Sjogren syndromes, ulcerative colitis or Crohn's disease, multiple sclerosis or Guillain-Barr syndrome) (n = 14), decreased TG was also observed both in the lean and obese subjects (-59%, P < .01 and -57%, P < .01, respectively). Concerning FFA (n = 69), value in lean patients (n = 22) vs that in lean controls (n = 18) was increased (520 +/- 31 vs 299 +/- 30 mcEq/L, +74%, P < .001), whereas value in obese patients (n = 18) vs that in obese control subjects (n = 11) was decreased (542 +/- 34 vs 774 +/- 62, -30%, P < .01). This opposite behavior of FFA in lean and obese patients needs to be confirmed. Data in this study seem to indicate that low TG value may be a precocious marker of autoimmunity or immune system hyperreactivity. PMID:14600656

  20. Mice lacking prostaglandin E receptor subtype 4 manifest disrupted lipid metabolism attributable to impaired triglyceride clearance.

    PubMed

    Cai, Yin; Ying, Fan; Song, Erfei; Wang, Yu; Xu, Aimin; Vanhoutte, Paul M; Tang, Eva Hoi-Ching

    2015-12-01

    Upon high-fat feeding, prostaglandin E receptor subtype 4 (EP4)-knockout mice gain less body weight than their EP4(+/+) littermates. We investigated the cause of the lean phenotype. The mice showed a 68.8% reduction in weight gain with diminished fat mass that was not attributable to reduced food intake, fat malabsorption, or increased energy expenditure. Plasma triglycerides in the mice were elevated by 244.9%. The increase in plasma triglycerides was independent of changes in hepatic very low density lipoprotein (VLDL)-triglyceride production or intestinal chylomicron-triglyceride synthesis. However, VLDL-triglyceride clearance was drastically impaired in the EP4-knockout mice. The absence of EP4 in mice compromised the activation of lipoprotein lipase (LPL), the key enzyme responsible for trafficking of plasma triglycerides into peripheral tissues. Deficiency in EP4 reduced hepatic mRNA expression of the transcriptional factor cAMP response element binding protein H (by 36.8%) and LPL activators, including apolipoprotein (Apo)a5 (by 40.2%) and Apoc2 (by 61.3%). In summary, the lean phenotype of EP4-deficient mice resulted from reduction in adipose tissue and accretion of other peripheral organs caused by impaired triglyceride clearance. The findings identify a new metabolic dimension in the physiologic role played by endogenous EP4.-Cai, Y., Ying, F., Song, E., Wang, Y., Xu, A., Vanhoutte, P. M., Tang, E. H.-C. Mice lacking prostaglandin E receptor subtype 4 manifest disrupted lipid metabolism attributable to impaired triglyceride clearance. PMID:26271253

  1. Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease: New Insights From Epidemiology, Genetics, and Biology.

    PubMed

    Nordestgaard, Brge G

    2016-02-19

    Scientific interest in triglyceride-rich lipoproteins has fluctuated over the past many years, ranging from beliefs that these lipoproteins cause atherosclerotic cardiovascular disease (ASCVD) to being innocent bystanders. Correspondingly, clinical recommendations have fluctuated from a need to reduce levels to no advice on treatment. New insight in epidemiology now suggests that these lipoproteins, marked by high triglycerides, are strong and independent predictors of ASCVD and all-cause mortality, and that their cholesterol content or remnant cholesterol likewise are strong predictors of ASCVD. Of all adults, 27% have triglycerides >2 mmol/L (176 mg/dL), and 21% have remnant cholesterol >1 mmol/L (39 mg/dL). For individuals in the general population with nonfasting triglycerides of 6.6 mmol/L (580 mg/dL) compared with individuals with levels of 0.8 mmol/L (70 mg/dL), the risks were 5.1-fold for myocardial infarction, 3.2-fold for ischemic heart disease, 3.2-fold for ischemic stroke, and 2.2-fold for all-cause mortality. Also, genetic studies using the Mendelian randomization design, an approach that minimizes problems with confounding and reverse causation, now demonstrate that triglyceride-rich lipoproteins are causally associated with ASCVD and all-cause mortality. Finally, genetic evidence also demonstrates that high concentrations of triglyceride-rich lipoproteins are causally associated with low-grade inflammation. This suggests that an important part of inflammation in atherosclerosis and ASCVD is because of triglyceride-rich lipoprotein degradation and uptake into macrophage foam cells in the arterial intima. Taken together, new insights now strongly suggest that elevated triglyceride-rich lipoproteins represent causal risk factors for low-grade inflammation, ASCVD, and all-cause mortality. PMID:26892957

  2. Pleiotropic regulation of mitochondrial function by adipose triglyceride lipase-mediated lipolysis?

    PubMed Central

    Kratky, Dagmar; Obrowsky, Sascha; Kolb, Dagmar; Radovic, Branislav

    2014-01-01

    Lipolysis is defined as the catabolism of triacylglycerols (TGs) stored in cellular lipid droplets. Recent discoveries of essential lipolytic enzymes and characterization of numerous regulatory proteins and mechanisms have fundamentally changed our perception of lipolysis and its impact on cellular metabolism. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme for TG catabolism in most cells and tissues. This review focuses on recent advances in understanding the (patho)physiological impact due to defective lipolysis by ATGL deficiency on mitochondrial (dys)function. Depending on the type of cells and tissues investigated, absence of ATGL has pleiotropic roles in mitochondrial function. PMID:23827855

  3. Association between Myocardial Triglyceride Content and Cardiac Function in Healthy Subjects and Endurance Athletes

    PubMed Central

    Sai, Eiryu; Shimada, Kazunori; Yokoyama, Takayuki; Sato, Shuji; Miyazaki, Tetsuro; Hiki, Makoto; Tamura, Yoshifumi; Aoki, Shigeki; Watada, Hirotaka; Kawamori, Ryuzo; Daida, Hiroyuki

    2013-01-01

    Ectopic fat accumulation plays important roles in various metabolic disorders and cardiovascular diseases. Recent studies reported that myocardial triglyceride (TG) content measured by proton magnetic resonance spectroscopy (1H-MRS) is associated with aging, diabetes mellitus, and cardiac dysfunction. However, myocardial TG content in athletes has not yet been investigated. We performed 1H-MRS and cardiac magnetic resonance imaging in 10 male endurance athletes and 15 healthy male controls. Serum markers and other clinical parameters including arterial stiffness were measured. Cardiopulmonary exercise testing was also performed. There were no significant differences in clinical characteristics including age, anthropometric parameters, blood test results, or arterial stiffness between the two groups. Peak oxygen uptakes, end–diastolic volume (EDV), end–systolic volume (ESV), left ventricular (LV) mass, peak ejection rates and peak filling rates were significantly higher in the athlete group than in the control group (all P<0.02). Myocardial TG content was significantly lower in the athlete group than in the control group (0.60±0.20 vs. 0.89±0.41%, P<0.05). Myocardial TG content was negatively correlated with EDV (r = −0.47), ESV (r = −0.64), LV mass (r = −0.44), and epicardial fat volume (r = 0.47) (all P<0.05). In conclusion, lower levels of myocardial TG content were observed in endurance athletes and were associated with morphological changes related to physiological LV alteration in athletes, suggesting that metabolic imaging for measurement of myocardial TG content by 1H-MRS may be a useful technique for noninvasively assessing the “athlete’s heart”. PMID:23613879

  4. Serum Triglyceride Levels Independently Contribute to the Estimation of Visceral Fat Amount Among Nondiabetic Obese Adults

    PubMed Central

    Huang, Chiao-Yu; Huang, Hsien-Liang; Yang, Kuen-Cheh; Lee, Long-Teng; Yang, Wei-Shiung; Huang, Kuo-Chin; Tseng, Fen-Yu

    2015-01-01

    Abstract Determining the visceral fat amount is important in the risk stratification for the prevention of type 2 diabetes and obesity-related disorders. The area-based measurement of visceral fat area (VFA) via magnetic resonance imaging (MRI) is an accurate but expensive and time-consuming method for estimating visceral fat amount. The aim of our study was to identify a practical predictive parameter for visceral obesity in clinical settings. In this cross-sectional study, we recruited 51 nondiabetic obese (body mass index [BMI] ≥ 27 kg/m2) adults in Taiwan (21 men and 30 women, mean age 35.6 ± 9.2 years, mean BMI 33.3 ± 3.9 kg/m2). VFA was quantified by a single-slice MRI image. Anthropometric indices and biochemical parameters including fasting plasma glucose, serum level of alanine aminotransferase, and lipid profiles were measured. The associations between different variables and VFA were analyzed by linear regression analysis. Increases in BMI, waist circumference, serum levels of alanine aminotransferase and triglycerides (TGs), and decreased serum levels of high-density lipoprotein cholesterol were correlated with larger VFA. After adjustment for age, sex, and anthropometric indices, only serum TG level remained as an independent correlate of VFA. Besides demographic and anthropometric indices, adding TG level may explain a greater variance of VFA. In stepwise multivariate regression analysis, male sex, age, waist circumference, and serum TG level remained significant predictors of VFA. In a subgroup analysis among subjects with BMI ≥30 kg/m2, similar results were demonstrated and serum TG level remained as significant independent correlates of VFA in all of the predictive models. Among nondiabetic obese adults, serum TG level was positively associated with VFA. The combination of sex, age, anthropometric indices, and serum TG level may be used to estimate VFA in clinical settings. PMID:26061332

  5. Effect of acute cold exposure on the mobilization of intramuscular glycogen and triglycerides in the rat.

    PubMed

    Grski, J; Kuryliszyn, A; Wereszczy?ska, U

    1981-01-01

    Male Wistar rats, 300-360 g of body weight, were exposed to cold (1 degree) for 3 and 24 h. The levels of glycogen and triglycerides (TG) were estimated in "white" and "red" portions of the quadriceps muscle (FG and POG muscles respectively) in the soleus muscle (SO muscle), and in the heart muscle. It was found that 3 h cold exposure decreased significantly the glycogen level only in the heart muscle and had no effect in the other muscles examined. Exposure to cold for 24 h reduced the glycogen level in FG and FOG muscles, and lowered further the heart glycogen level. No change of glycogen level during cold exposure was observed in SO muscle. The level of TG in each examined muscle was significantly reduced already after 3 h of cold exposure. After 24 h it remained further unchanged in FG and FOG muscles whereas in SO and heart muscles a partial recovery of TG occurred. It is concluded that in warm-acclimatized rats the intramuscular TG play an important role as a local source of free fatty acids during the first period of acute exposure to cold. PMID:7348527

  6. Modified triglyceride oil through reactions with phenyltriazolinedione

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The synthesis of a modified triglyceride oil was achieved through the reactions with 4-phenyl-1,2-4-triazoline-3,5-dione (PTAD). 1H NMR was used for structure determination and to monitor the reactions. Several reaction products were produced, and their relative yields depended on the stoichiometry ...

  7. In vivo 2H2O administration reveals impaired triglyceride storage in adipose tissue of insulin-resistant humans.

    PubMed

    Allister, Candice A; Liu, Li-fen; Lamendola, Cindy A; Craig, Colleen M; Cushman, Samuel W; Hellerstein, Marc K; McLaughlin, Tracey L

    2015-02-01

    Indirect evidence suggests that impaired triglyceride storage in the subcutaneous fat depot contributes to the development of insulin resistance via lipotoxicity. We directly tested this hypothesis by measuring, in vivo, TG synthesis, de novo lipogenesis (DNL), adipocyte proliferation, and insulin suppression of lipolysis in subcutaneous adipose tissue of BMI-matched individuals classified as insulin resistant (IR) or insulin sensitive (IS). Nondiabetic, moderately obese subjects with BMI 25-35 kg/m(2), classified as IR or IS by the modified insulin suppression test, consumed deuterated water ((2)H2O) for 4 weeks. Deuterium incorporation into glycerol, palmitate, and DNA indicated TG synthesis, DNL, and adipocyte proliferation, respectively. Net TG synthesis and DNL in adipose cells were significantly lower in IR as compared with IS subjects, whereas adipocyte proliferation did not differ significantly. Plasma FFAs measured during an insulin suppression test were 2.5-fold higher in IR subjects, indicating resistance to insulin suppression of lipolysis. Adipose TG synthesis correlated directly with DNL but not with proliferation. These results provide direct in vivo evidence for impaired TG storage in subcutaneous adipose tissue of IR as compared with IS. Relative inability to store TG in the subcutaneous depot may represent a mechanism contributing to the development of insulin resistance in the setting of obesity. PMID:25418322

  8. Using high dose omega-3 fatty acid supplements to lower triglyceride levels in 1019 year-olds

    PubMed Central

    de Ferranti, Sarah D.; Milliren, Carly E.; Denhoff, Erica R.; Steltz, Sarah K.; Selamet Tierney, Elif Seda; Feldman, Henry A.; Osganian, Stavroula K.

    2015-01-01

    Background Omega-3 fatty acids (FA) supplements lower triglyceride (TG) levels in adults; little pediatric information is available. We evaluated their effect in hypertriglyceridemic adolescents. Methods 25 patients ages 1019 years with TG levels 1501000 mg/dL were randomized to 6 months double-blind trial of Lovaza [?3360 mg docosahexaenoic acid + eicosapentaenoic acid/day] vs. Placebo. Results Baseline mean TG levels were 227 mg/dl (SD 49). TG levels declined at 3 months in the Lovaza group by 54 27 mg/dL [mean standard error (SE)] (p=0.02) and by 34 26 mg/dL (p=0.16) in the Placebo group. The difference in TG lowering between groups was not significant (p=0.52). There were no between-group differences in endothelial function, blood pressure, body mass index, C-reactive protein or side effects. Conclusions High dose omega-3 FA supplements are well tolerated in adolescents. However, declines in TG levels did not differ significantly from Placebo in this small study. PMID:24707021

  9. Elevated vascular ?-butyrobetaine levels attenuate the development of high glucose-induced endothelial dysfunction.

    PubMed

    Vilskersts, Reinis; Zharkova-Malkova, Olga; Mezhapuke, Rudolfs; Grinberga, Solveiga; Cirule, Helena; Dambrova, Maija

    2013-08-01

    The aim of the present study was to investigate the effects of vascular tissue levels of l-carnitine and its precursor, ?-butyrobetaine (GBB), on the development of endothelial dysfunction induced by 5?mol/L lysophosphatidylcholine (LPC), 10mmol/L triglycerides (TG) or a high glucose concentration (44mmol/L). Changes in vascular tissue levels of l-carnitine and GBB were induced by administration of l-carnitine (100mg/kg), mildronate (100mg/kg; an inhibitor of l-carnitine synthesis) or their combination to male Wistar rats for 2weeks. Treatment with l-carnitine elevated vascular tissue levels of l-carnitine, whereas administration of mildronate reduced l-carnitine levels and increased GBB levels. Experimental animals that received the combination of both drugs showed elevated tissue levels of GBB. The results from organ bath experiments demonstrated that increased GBB levels with preserved l-carnitine content in vascular tissues attenuated the development of endothelial dysfunction induced by high glucose. However, changes in vascular tissue l-carnitine and GBB levels had no impact on endothelial dysfunction induced by TG or LPC. The results demonstrate that increased levels of GBB with preserved l-carnitine content in vascular tissue attenuate the development of endothelial dysfunction induced by high glucose concentrations. PMID:23710938

  10. Elevating your elevator talk

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An important and often overlooked item that every early career researcher needs to do is compose an elevator talk. The elevator talk, named because the talk should not last longer than an average elevator ride (30 to 60 seconds), is an effective method to present your research and yourself in a clea...

  11. Dietary walnut reduces hepatic triglyceride content in high-fat-fed mice via modulation of hepatic fatty acid metabolism and adipose tissue inflammation.

    PubMed

    Choi, Youngshim; Abdelmegeed, Mohamed A; Akbar, Mohammed; Song, Byoung-Joon

    2016-04-01

    In this study, we evaluated the protective effects of dietary walnuts on high-fat diet (HFD)-induced fatty liver and studied the underlying mechanisms. Male C57BL/6J mice were fed either a regular rodent chow or HFD (45% energy-derived) with or without walnuts (21.5% energy-derived) for 20weeks. Walnut supplementation did not change HFD-induced increase in body weight or visceral fat mass. However, dietary walnuts significantly decreased the amounts of hepatic triglyceride (TG) observed in HFD-fed mice. The addition of walnuts significantly altered the levels of proteins, involved in the hepatic lipid homeostasis, including AMP-activated protein kinase, fatty acid synthase and peroxisome proliferator-activated receptor-α. Since adipocyte inflammation and apoptosis are reportedly important in regulating hepatic fat accumulation, we also evaluated the protective effects of walnuts on adipose tissue injury. Real-time polymerase chain reaction results revealed that adipose tissues isolated from mice fed the HFD+walnut diets showed significantly decreased levels of macrophage infiltration with suppressed expression of proinflammatory genes compared to those significantly elevated in mice fed HFD alone. These improvements also coincided with reduction of HFD-induced apoptosis of adipocytes by dietary walnuts. However, the supplemented walnuts did not significantly alter HFD-induced peripheral glucose intolerance or insulin resistance despite a trend of improvement. Collectively, these results demonstrate that the protective effects of walnuts against HFD-induced hepatic TG accumulation in mice are mediated, at least partially, by modulating the key proteins in hepatic lipid homeostasis and suppression of the genes related to adipose tissue inflammation and macrophage infiltration as well as prevention of adipocyte apoptosis. PMID:27012628

  12. Pathway-Based Genome-Wide Association Studies for Plasma Triglycerides in Obese Females and Normal-Weight Controls

    PubMed Central

    Grant, Struan F. A.; Hakonarson, Hakon; Price, R. Arlen; Li, Wei-Dong

    2015-01-01

    Pathway-based analysis as an alternative approach can provide complementary information to single-marker genome-wide association studies (GWASs), which always ignore the epistasis and does not have sufficient power to find rare variants. In this study, using genotypes from a genome-wide association study (GWAS), pathway-based association studies were carried out by a modified Gene Set Enrichment Algorithm (GSEA) method (GenGen) for triglyceride in 1028 unrelated European-American extremely obese females (BMI?35kg/m2) and normal-weight controls (BMI<25kg/m2), and another pathway association analysis (ICSNPathway) was also used to verify the GenGen result in the same data. The GO0009110 pathway (vitamin anabolism) was among the strongest associations with triglyceride (empirical P<0.001); the result remained significant after FDR correction (P = 0.022). MMAB, an obesity-related locus, included in this pathway. The ABCG1 and BCL6 gene was found in several triglyceride-related pathways (empirical P<0.05), which were also replicated by ICSNPathway (empirical P<0.05, FDR<0.05). We also performed single-marked GWAS using PLINK for TG levels (log-transformed). Significant associations were found between ASTN2 gene SNPs and plasma triglyceride levels (rs7035794, P = 2.2410?10). Our study suggested that vitamin anabolism pathway, BCL6 gene pathways and ASTN2 gene may contribute to the genetic variation of plasma triglyceride concentrations. PMID:26308950

  13. Atherogenicity of triglyceride-rich lipoproteins.

    PubMed

    Krauss, R M

    1998-02-26

    There is increasing evidence that alterations in metabolism of triglyceride-rich lipoproteins are of importance in the pathogenesis of atherosclerosis and its clinical consequences. Particles with the characteristics of triglyceride-rich lipoprotein remnants have been related to the extent and severity of atherosclerosis in humans and in animal models. These particles can be identified using ultracentrifugal procedures as small, very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) with Svedberg flotation rates (Sf) of 12-60. Postprandial triglyceride levels also have been related to risk of coronary artery disease, consistent with a pathologic role for remnant lipoproteins. In studies in which measurements of lipoprotein subfractions have been carried out, levels of IDL have been more predictive than low-density lipoprotein (LDL) of atherosclerosis progression as assessed by coronary artery angiography or carotid artery ultrasonography. These findings suggest that a considerable portion of the coronary disease risk attributed to LDL may be accounted for by the IDL particles included in standard LDL measurements. Other metabolic changes associated with increased levels of plasma triglyceride may also adversely affect cardiovascular disease risk. These include reductions in HDL-cholesterol and apoprotein A1, increased levels of small dense LDL particles, redistribution of apoC-III from HDL to apoB-containing lipoproteins, diminished insulin sensitivity, and procoagulant changes, including increased levels of the fibrinolysis inhibitor, plasminogen-activator inhibitor-1 (PAI-1). A predominance of small dense LDL (subclass pattern B) is a discrete marker for this cluster of interrelated abnormalities and is found in 40-50% of patients with coronary artery disease. Therapeutic interventions with favorable effects on components of this dysmetabolic profile appear to be of value in decreasing atherosclerosis risk in a substantial proportion of the population. PMID:9526808

  14. Top Ten Things to Know: Triglycerides and Cardiovascular Disease

    MedlinePLUS

    ... and fatty liver. 2. According to NHANES data, Mexican-Americans have the highest rates of triglycerides (35. ... alcohol, and especially if there is an underlying genetic disorder of triglyceride metabolism. 10. It has not ...

  15. Analysis of the Triglycerides of Some Vegetable Oils.

    ERIC Educational Resources Information Center

    Farines, Marie; And Others

    1988-01-01

    Explains that triglycerides consist of a mixture of different compounds, depending on the total number of fatty acid constituents. Details the method and instrumentation necessary for students to analyze a vegetable oil for its triglyceride content. Describes sample results. (CW)

  16. Tissue-specific postprandial clearance is the major determinant of PPARgamma-induced triglyceride lowering in the rat.

    PubMed

    Laplante, Mathieu; Festuccia, William T; Soucy, Genevive; Blanchard, Pierre-Gilles; Renaud, Alexandra; Berger, Joel P; Olivecrona, Gunilla; Deshaies, Yves

    2009-01-01

    Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonism potently reduces circulating triglycerides (TG) in rodents and more modestly so in humans. This study aimed to quantify in vivo the relative contribution of hepatic VLDL-TG secretion and tissue-specific TG clearance to such action. Rats were fed an obesogenic diet, treated with the PPARgamma full agonist COOH (30 mg.kg(-1).day(-1)) for 3 wk, and studied in both the fasted and refed (fat-free) states. Hepatic VLDL-TG secretion rate was not affected by chronic COOH in the fasted state and was only modestly decreased (-30%) in refed rats. In contrast, postprandial VLDL-TG clearance was increased 2.6-fold by COOH, which concomitantly stimulated adipose tissue TG-derived lipid uptake and one of its major determinants, lipoprotein lipase (LPL) activity, in a highly depot-specific manner. TG-derived lipid uptake and LPL were indeed strongly increased in subcutaneous inguinal white adipose tissue and in brown adipose tissue, independently of the nutritional state, whereas of the three visceral fat depots examined (epididymal, retroperitoneal, mesenteric) only the latter responded consistently to COOH. Robust correlations (0.5 < r < 0.9) were observed between TG-derived lipid uptake and LPL in adipose tissues. The agonist did not increase LPL in muscle, and its enhancing action on postprandial muscle lipid uptake appeared to be mediated by post-LPL processes involving increased expression of fatty acid binding/transport proteins (aP2, likely in infiltrated adipocytes, FAT/CD36, and FATP-1). The study establishes in a diet-induced obesity model the major contribution of lipid uptake by specific, metabolically safe adipose depots to the postprandial hypotriglyceridemic action of PPARgamma agonism, and suggests a key role for LPL therein. PMID:18971352

  17. Echium oil reduces plasma triglycerides by increasing intravascular lipolysis in apoB100-only low density lipoprotein (LDL) receptor knockout mice.

    PubMed

    Forrest, Lolita M; Lough, Christopher M; Chung, Soonkyu; Boudyguina, Elena Y; Gebre, Abraham K; Smith, Thomas L; Colvin, Perry L; Parks, John S

    2013-07-01

    Echium oil (EO), which is enriched in SDA (18:4 n-3), reduces plasma triglyceride (TG) concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO) reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%), EO (10% EO + 10% PO), or FO (10% FO + 10% PO). Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE) content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL) particle size was ordered: PO (63 ± 4 nm) > EO (55 ± 3 nm) > FO (40 ± 2 nm). Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model. PMID:23857172

  18. Echium Oil Reduces Plasma Triglycerides by Increasing Intravascular Lipolysis in apoB100-Only Low Density Lipoprotein (LDL) Receptor Knockout Mice

    PubMed Central

    Forrest, Lolita M.; Lough, Christopher M.; Chung, Soonkyu; Boudyguina, Elena Y.; Gebre, Abraham K.; Smith, Thomas L.; Colvin, Perry L.; Parks, John S.

    2013-01-01

    Echium oil (EO), which is enriched in SDA (18:4 n-3), reduces plasma triglyceride (TG) concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO) reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%), EO (10% EO + 10% PO), or FO (10% FO + 10% PO). Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE) content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL) particle size was ordered: PO (63 ± 4 nm) > EO (55 ± 3 nm) > FO (40 ± 2 nm). Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model. PMID:23857172

  19. Hydrogen sulfide reduces serum triglyceride by activating liver autophagy via the AMPK-mTOR pathway.

    PubMed

    Sun, Li; Zhang, Song; Yu, Chengyuan; Pan, Zhenwei; Liu, Yang; Zhao, Jing; Wang, Xiaoyu; Yun, Fengxiang; Zhao, Hongwei; Yan, Sen; Yuan, Yue; Wang, Dingyu; Ding, Xue; Liu, Guangzhong; Li, Wenpeng; Zhao, Xuezhu; Liu, Zhaorui; Li, Yue

    2015-12-01

    Autophagy plays an important role in liver triglyceride (TG) metabolism. Inhibition of autophagy could reduce the clearance of TG in the liver. Hydrogen sulfide (H2S) is a potent stimulator of autophagic flux. Recent studies showed H2S is protective against hypertriglyceridemia (HTG) and noalcoholic fatty liver disease (NAFLD), while the mechanism remains to be explored. Here, we tested the hypothesis that H2S reduces serum TG level and ameliorates NAFLD by stimulating liver autophagic flux by the AMPK-mTOR pathway. The level of serum H2S in patients with HTG was lower than that of control subjects. Sodium hydrosulfide (NaHS, H2S donor) markedly reduced serum TG levels of male C57BL/6 mice fed a high-fat diet (HFD), which was abolished by coadministration of chloroquine (CQ), an inhibitor of autophagic flux. In HFD mice, administration of NaSH increased the LC3BII-to-LC3BI ratio and decreased the p62 protein level. Meanwhile, NaSH increased the phosphorylation of AMPK and thus reduced the phosphorylation of mTOR in a Western blot study. In cultured LO2 cells, high-fat treatment reduced the ratio of LC3BII to LC3BI and the phosphorylation of AMPK, which were reversed by the coadministration of NaSH. Knockdown of AMPK by siRNA in LO2 cells blocked the autophagic enhancing effects of NaSH. The same qualitative effect was observed in AMPKα2(-/-) mice. These results for the first time demonstrated that H2S could reduce serum TG level and ameliorate NAFLD by activating liver autophagy via the AMPK-mTOR pathway. PMID:26442880

  20. Triglyceride Is a Useful Surrogate Marker for Insulin Resistance in Korean Women with Polycystic Ovary Syndrome

    PubMed Central

    Park, So Yun; Cho, Yeon Jean; Lee, Sa Ra; Chung, Hyewon

    2015-01-01

    Purpose To evaluate lipid profiles and liver enzymes as surrogate markers used for recognizing insulin resistance in Korean women with polycystic ovary syndrome (PCOS). Materials and Methods 458 women with PCOS were divided into two groups: non-obese with a body mass index (BMI)<25.0 kg/m2 and obese with a BMI?25.0 kg/m2. Anthropometric measures and blood sampling for hormone assay, liver enzymes, lipid profiles and 75 g oral glucose tolerance test were performed. Insulin resistance was defined as homeostasis model assessment of insulin resistance (HOMA-IR)?2.5. Areas under the receiver operating characteristic (ROC) curves were used to compare the power of serum markers. Multiple linear regression analysis was used to evaluate the contribution of each confounding factor for HOMA-IR. Results In non-obese and obese groups, the ROC curve analyses demonstrated that the best marker for insulin resistance was triglyceride (TG), with the areas under the ROC curve of 0.617 and 0.837, respectively. Low-density lipoprotein cholesterol (LDL-C) was the significant marker for insulin resistance with areas under the ROC curve of 0.698 in obese group, but not significant in non-obese group. TG and LDL-C were significantly associated with HOMA-IR in both non-obese and obese PCOS women by multiple linear regression analysis. The optimal cut-off points of TG?68.5 was a marker for predicting insulin resistance in non-obese PCOS patients and TG?100.5 in obese group. Conclusion TG can be used as a useful marker for insulin resistance in Korean women with PCOS, especially for obese patients. PMID:25837186

  1. PROPERTY ANALYSIS OF TRIGLYCERIDE-BASED THERMOSETS. (R829576)

    EPA Science Inventory

    Triglycerides with acrylate functionality were prepared from various oils and
    model triglycerides. The triglyceride-acrylates were homopolymerized and copolymerized
    with styrene. The cross-link densities of the resulting polymer networks were
    predicted utilizing the F...

  2. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Triglyceride test system. 862.1705 Section 862....1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended to... diseases involving lipid metabolism, or various endocrine disorders. (b) Classification. Class I...

  3. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Triglyceride test system. 862.1705 Section 862....1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended to... diseases involving lipid metabolism, or various endocrine disorders. (b) Classification. Class I...

  4. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Triglyceride test system. 862.1705 Section 862....1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended to... diseases involving lipid metabolism, or various endocrine disorders. (b) Classification. Class I...

  5. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Triglyceride test system. 862.1705 Section 862....1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended to... diseases involving lipid metabolism, or various endocrine disorders. (b) Classification. Class I...

  6. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Triglyceride test system. 862.1705 Section 862....1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended to... diseases involving lipid metabolism, or various endocrine disorders. (b) Classification. Class I...

  7. Population-based estimates of breast cancer risks associated with ATM gene variants c.7271T>G and c.1066-6T>G (IVS10-6T>G) from the Breast Cancer Family Registry.

    PubMed

    Bernstein, J L; Teraoka, S; Southey, M C; Jenkins, M A; Andrulis, I L; Knight, J A; John, E M; Lapinski, R; Wolitzer, A L; Whittemore, A S; West, D; Seminara, D; Olson, E R; Spurdle, A B; Chenevix-Trench, G; Giles, G G; Hopper, J L; Concannon, P

    2006-11-01

    The ATM gene variants segregating in ataxia-telangiectasia families are associated with increased breast cancer risk, but the contribution of specific variants has been difficult to estimate. Previous small studies suggested two functional variants, c.7271T>G and c.1066-6T>G (IVS10-6T>G), are associated with increased risk. Using population-based blood samples we found that 7 out of 3,743 breast cancer cases (0.2%) and 0 out of 1,268 controls were heterozygous for the c.7271T>G allele (P=0.1). In cases, this allele was more prevalent in women with an affected mother (odds ratio [OR]=5.5, 95% confidence interval [CI]=1.2-25.5; P=0.04) and delayed child-bearing (OR=5.1; 95% CI=1.0-25.6; P=0.05). The estimated cumulative breast cancer risk to age 70 years (penetrance) was 52% (95% CI=28-80%; hazard ratio [HR]=8.6; 95% CI=3.9-18.9; P<0.0001). In contrast, 13 of 3,757 breast cancer cases (0.3%) and 10 of 1,268 controls (0.8%) were heterozygous for the c.1066-6T>G allele (OR=0.4; 95% CI=0.2-1.0; P=0.05), and the penetrance was not increased (P=0.5). These findings suggest that although the more common c.1066-6T>G variant is not associated with breast cancer, the rare ATM c.7271T>G variant is associated with a substantially elevated risk. Since c.7271T>G is only one of many rare ATM variants predicted to have deleterious consequences on protein function, an effective means of identifying and grouping these variants is essential to assess the contribution of ATM variants to individual risk and to the incidence of breast cancer in the population. PMID:16958054

  8. Contributions of de novo synthesis of fatty acids to total VLDL-triglyceride secretion during prolonged hyperglycemia/hyperinsulinemia in normal man.

    PubMed Central

    Aarsland, A; Chinkes, D; Wolfe, R R

    1996-01-01

    Triglycerides (TG) are synthesized in the liver principally from two sources of fatty acids (FA): FA synthesized de novo in the liver and preformed FA. We have measured the rate of secretion of de novo synthesized FA and total secretion of FA bound to VLDL-TG in healthy men (n = 5) in the basal state, and after 1 (day 1) and 4 d (day 4) of a hypercaloric carbohydrate diet (approximately 2.5 times energy expenditure) that generated a moderate endogenous hyperinsulinemia (plasma insulin approximately 60 microU/ml). Prolonged carbohydrate hyperalimentation/hyperinsulinemia increased plasma VLDL-TG approximately 10-fold in part due to a 3.4-fold increase in total VLDL-TG secretion rate (basal state = 72+/-23, day 4 = 242+/-78 micromol TG/kg/d). Although the secretion of de novo synthesized FA increased throughout the study (basal state = 1.1+/-0.4, day 1 = 15.9+/-7.9, day 4 = 50.0+/-18.8 micromol TG/ kg/d), the 2.7-fold increase in secretion rate of preformed FA (basal state = 70+/-23, day 4 = 191+/-57 micromol TG/kg/d) quantitatively contributed the most to total VLDL-TG secretion rate. Decreased catabolism of VLDL-TG also contributed to the hypertriglyceridemia as reflected by an approximately fourfold decrease in both fractional turnover rate (basal state = 9.2+/-3.8, day 1 = 2.1+/-0.2, day 4 = 2.1+/-0.3 pools/d) and rate of clearance (basal state = 0.35+/-0.08, day 1 = 0.11+/-0.01, day 4 = 0.09+/-0.01 liter/kg/d) of VLDL-TG. Thus, the primary difference between 1 and 4 d of hyperinsulinemia in conjunction with carbohydrate hyperalimentation is the increase in hepatic secretion of preformed FA into VLDL-TG. PMID:8903319

  9. The Impact of CDH13 Polymorphism and Statin Administration on TG/HDL Ratio in Cardiovascular Patients

    PubMed Central

    Choi, Jung Ran; Kim Yoon, Sungjoo; Park, Jong Keun; Sorn, Sungbin Richard; Park, Mi-Young

    2015-01-01

    Purpose Adiponectin is expressed in adipose tissue, and is affected by smoking, obesity, and genetic factors, such as CDH13 polymorphism, contributing to the development of coronary vascular diseases (CVDs). Materials and Methods We investigated the effect of genetic variations of CDH13 (rs3865188) on blood chemistry and adiponectin levels in 345 CVD patients undergoing statin-free or statin treatment. Results Genetic variation in CDH13 was significantly correlated with several clinical factors, including adiponectin, diastolic blood pressure, triglyceride (TG), and insulin levels. Subjects with the T allele (mutant form) had significantly lower adiponectin levels than those with the A allele. Total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), TG/high-density lipoprotein cholesterol (HDLc) ratio, and HDL3b subtype were markedly decreased in statin treated subjects regardless of having the A or T allele. TG and TG/HDL in the statin-free group with TT genotype of the rs3865188 was higher than in the others but they were not different in the statin-treated subjects. We observed a significant difference in adiponectin levels between patients with the A and T alleles in the statin-free group; meanwhile, no difference in adiponectin levels was noted in the statin group. Plasma levels of other cytokines, leptin, visfatin, interleukin-6 (IL-6), and tumor necrosis factor-? (TNF-?), were not different among the CDH13 genotypes according to statin administration. Body mass index (BMI), TG, insulin, HDL3b, and TG/HDL ratio showed negative correlations with adiponectin levels. Conclusion Plasma adiponectin levels and TG/HDL ratio were significantly different according to variants of CDH13 and statin administration in Korean patients with CVD. PMID:26446643

  10. FGF21 Lowers Plasma Triglycerides by Accelerating Lipoprotein Catabolism in White and Brown Adipose Tissues.

    PubMed

    Schlein, Christian; Talukdar, Saswata; Heine, Markus; Fischer, Alexander W; Krott, Lucia M; Nilsson, Stefan K; Brenner, Martin B; Heeren, Joerg; Scheja, Ludger

    2016-03-01

    FGF21 decreases plasma triglycerides (TGs) in rodents and humans; however, the underlying mechanism or mechanisms are unclear. In the present study, we examined the role of FGF21 in production and disposal of TG-rich lipoproteins (TRLs) in mice. Treatment with pharmacological doses of FGF21 acutely reduced plasma non-esterified fatty acids (NEFAs), liver TG content, and VLDL-TG secretion. In addition, metabolic turnover studies revealed that FGF21 facilitated the catabolism of TRL in white adipose tissue (WAT) and brown adipose tissue (BAT). FGF21-dependent TRL processing was strongly attenuated in CD36-deficient mice and transgenic mice lacking lipoprotein lipase in adipose tissues. Insulin resistance in diet-induced obese and ob/ob mice shifted FGF21 responses from WAT toward energy-combusting BAT. In conclusion, FGF21 lowers plasma TGs through a dual mechanism: first, by reducing NEFA plasma levels and consequently hepatic VLDL lipidation and, second, by increasing CD36 and LPL-dependent TRL disposal in WAT and BAT. PMID:26853749

  11. Use of random forest in FTIR analysis of LDL cholesterol and tri-glycerides for hyperlipidemia.

    PubMed

    Chen, Hua-Zhou; Tang, Guo-Qiang; Ai, Wu; Xu, Li-Li; Cai, Ken

    2015-11-01

    A quantitative determination method for the diagnosis of hyperlipidemia was developed using Fourier transform infrared (FTIR) spectroscopy. Random forest (RF) was demonstrated as a potential multivariate algorithm for the FTIR analysis of low-density lipoprotein cholesterol (LDL-C) and tri-glycerides (TG) in human serum samples. The informative wavebands for LDL-C and TG were selected based on the Gini importance. The selected wavebands were mainly within the fingerprint region. The RF modeling results were better than those derived using PLS in validation process, because the chance for over-fitting was possibly eliminated in RF algorithm. ARF also demonstrated favorable results in the test process. The prospective model exhibited a higher than 90% true prediction in negative/positive properties for male and female samples. These clinical statistical results indicated the optimization of RF algorithm performed accurately in the FTIR determination of LDL-C and TG. RF is evaluated as a promising tool for diagnosing and controlling hyperlipidemia in populations. The parameter optimization methodology is useful in the improving model accuracy using FTIR spectroscopic technology. 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:1693-1702, 2015. PMID:26317397

  12. Construction of triglyceride biosensor based on nickel oxide-chitosan/zinc oxide/zinc hexacyanoferrate film.

    PubMed

    Narang, J; Chauhan, N; Pundir, C S

    2013-09-01

    A method is described for construction of an amperometric triglyceride (TG) biosensor based on co-immobilization of lipase, glycerol kinase (GK) and glycerol-3-phosphate oxidase (GPO) onto nickel oxide nanoparticles (NiONPs)-chitosan (CHIT) nanocomposite adsorbed onto zinc oxide/zinc hexacyanoferrate (ZnO-ZnHCF) hybrid film electrodeposited on the surface of an Au electrode. The NiONPs-CHIT/ZnO-ZnHCF hybrid film was characterized by cyclic voltammetry (CV), atomic force microscopy (AFM) and electrochemical impedance spectroscopy (EIS). The biosensor showed optimum response within 4 s at pH 6.0 and 35 C, when polarized at +0.4 V against Ag/AgCl. There was a linear relationship between sensor response and triolein concentration in the range 50-700 mg/dl with sensitivity of 0.05 ?A/mg/dl. The sensor was employed for determination of TG in serum. The detection limit of the biosensor was 10 mg/dl. The biosensor was evaluated with 95-96% recovery of added triolein in sera and 2% and 3% within and between batch coefficients of variation (CVs) respectively. There was a good correlation (r=0.99) between serum TG values by standard enzymic colorimetric method and the present method. The biosensor lost 50% of its initial activity after its 100 uses over a period of 180 days, when stored at 4 C. PMID:23707748

  13. Impact of fatty acyl composition and quantity of triglycerides on bioaccessibility of dietary carotenoids.

    PubMed

    Huo, Tianyao; Ferruzzi, Mario G; Schwartz, Steven J; Failla, Mark L

    2007-10-31

    A carotenoid-rich salad meal with varying amounts and types of triglycerides (TG) was digested using simulated gastric and small intestinal conditions. Xanthophylls (lutein and zeaxanthin) and carotenes (alpha-carotene, beta-carotene, and lycopene) in chyme and micelle fraction were quantified to determine digestive stability and efficiency of micellarization (bioaccessibility). Micellarization of lutein (+zeaxanthin) exceeded that of alpha- and beta-carotenes, which was greater than that of lycopene for all test conditions. Micellarization of carotenes, but not lutein (+zeaxanthin), was enhanced (P < 0.05) by addition of TG (2.5% v/w) to the meal and was dependent on fatty acyl chain length in structured TG (c18:1 > c8:0 > c4:0). The degree of unsaturation of c18 fatty acyl chains in TG added to the salad purée did not significantly alter the efficiency of micellarization of carotenoids. Relatively low amounts of triolein and canola oil (0.5-1%) were required for maximum micellarization of carotenes, but more oil (approximately 2.5%) was required when TG with medium chain saturated fatty acyl groups (e.g., trioctanoin and coconut oil) was added to the salad. Uptake of lutein and beta-carotene by Caco-2 cells also was examined by exposing cells to micelles generated during the simulated digestion of salad purée with either triolein or trioctanoin. Cell accumulation of beta-carotene was independent of fatty acyl composition of micelles, whereas lutein uptake was slightly, but significantly, increased from samples with digested triolein compared to trioctanoin. The results show that the in vitro transfer of alpha-carotene, beta-carotene, and lycopene from chyme to mixed micelles during digestion requires minimal (0.5-1%) lipid content in the meal and is affected by the length of fatty acyl chains but not the degree of unsaturation in TG. In contrast, fatty acyl chain length has limited if any impact on carotenoid uptake by small intestinal epithelial cells. These data suggest that the amount of TG in a typical meal does not limit the bioaccessibility of carotenoids. PMID:17927194

  14. The Association of Human Apolipoprotein C-III Sialylation Proteoforms with Plasma Triglycerides

    PubMed Central

    Yassine, Hussein N.; Trenchevska, Olgica; Ramrakhiani, Ambika; Parekh, Aarushi; Koska, Juraj; Walker, Ryan W.; Billheimer, Dean; Reaven, Peter D.; Yen, Frances T.; Nelson, Randall W.; Goran, Michael I.; Nedelkov, Dobrin

    2015-01-01

    Introduction Apolipoprotein C-III (apoC-III) regulates triglyceride (TG) metabolism. In plasma, apoC-III exists in non-sialylated (apoC-III0a without glycosylation and apoC-III0b with glycosylation), monosialylated (apoC-III1) or disialylated (apoC-III2) proteoforms. Our aim was to clarify the relationship between apoC-III sialylation proteoforms with fasting plasma TG concentrations. Methods In 204 non-diabetic adolescent participants, the relative abundance of apoC-III plasma proteoforms was measured using mass spectrometric immunoassay. Results Compared with the healthy weight subgroup (n = 16), the ratios of apoC-III0a, apoC-III0b, and apoC-III1 to apoC-III2 were significantly greater in overweight (n = 33) and obese participants (n = 155). These ratios were positively correlated with BMI z-scores and negatively correlated with measures of insulin sensitivity (Si). The relationship of apoC-III1 / apoC-III2 with Si persisted after adjusting for BMI (p = 0.02). Fasting TG was correlated with the ratio of apoC-III0a / apoC-III2 (r = 0.47, p<0.001), apoC-III0b / apoC-III2 (r = 0.41, p<0.001), apoC-III1 / apoC-III2 (r = 0.43, p<0.001). By examining apoC-III concentrations, the association of apoC-III proteoforms with TG was driven by apoC-III0a (r = 0.57, p<0.001), apoC-III0b (r = 0.56. p<0.001) and apoC-III1 (r = 0.67, p<0.001), but not apoC-III2 (r = 0.006, p = 0.9) concentrations, indicating that apoC-III relationship with plasma TG differed in apoC-III2 compared with the other proteoforms. Conclusion We conclude that apoC-III0a, apoC-III0b, and apoC-III1, but not apoC- III2 appear to be under metabolic control and associate with fasting plasma TG. Measurement of apoC-III proteoforms can offer insights into the biology of TG metabolism in obesity. PMID:26633899

  15. Geoid determination in Turkey (TG-91)

    NASA Astrophysics Data System (ADS)

    Ayhan, M. Emin

    1993-03-01

    It is considered that precise geoid determination is one of the main current geodetic problems in Turkey since GPS defined coordinates require geoidal heights in practice. In order to determine the geoid by least squares collocation (LSC) the area covering Turkey was divided into 114 blocks of size 1 1. LSC approximation to the geoid based upon the tailored geopotential model GPM2-T1 is constructed within each block. The model GPM2-T1 complete to degree and order 200 has been developed by tailoring of the model GPM2 to mean free-air anomalies and mean heights of one degree blocks in Turkey. Terrain effect reduced point gravity data spaced 5' 5' within each block which the sides extended 0.5 were used in LSC. Residual terrain model (RTM) depends on point heights at 15?20? griding and 5'5' and 15'15' mean heights has been carried out in terrain effect reduction. Indirect effect of RTM on geoid is also taken into account. The geoid, called Turkish Geoid 1991 (TG-91), referenced to GRS-80 ellipsoid has been computed at 3' 3' griding nodes within each block. The quality of the TG-91 is also evaluated by comparing computed and GPS derived geoidal height differences, and 2.1 - 2.6 ppm accuracy for average baseline lenght of 45 km is obtained.

  16. ApoA-IV modulates the secretory trafficking of apoB and the size of triglyceride-rich lipoproteins.

    PubMed

    Weinberg, Richard B; Gallagher, James W; Fabritius, Melissa A; Shelness, Gregory S

    2012-04-01

    Although the evidence linking apoA-IV expression and triglyceride (TG)-rich lipoprotein assembly and secretion is compelling, the intracellular mechanisms by which apoA-IV could modulate these processes remain poorly understood. We therefore examined the functional impact of apoA-IV expression on endogenous apoB, TG, and VLDL secretion in stably transfected McA-RH7777 rat hepatoma cells. Expression of apoA-IV modified with the endoplasmic reticulum (ER) retention signal KDEL (apoA-IV-KDEL) dramatically decreased both the rate and efficiency of endogenous apoB secretion, suggesting a presecretory interaction between apoA-IV-KDEL and apoB or apoB-containing lipoproteins. Expression of native apoA-IV using either a constitutive or tetracycline-inducible promoter delayed the initial rate of apoB secretion and reduced the final secretion efficiency by ?40%. However, whereas apoA-IV-KDEL reduced TG secretion by 75%, expression of native apoA-IV caused a 20-35% increase in TG secretion, accompanied by a ?55% increase in VLDL-associated apoB, an increase in the TG:phospholipid ratio of secreted d < 1.006 lipoproteins, and a 10.1 nm increase in peak VLDL(1) particle diameter. Native apoA-IV expression had a negligible impact on expression of the MTP gene. These data suggest that by interacting with apoB in the secretory pathway, apoA-IV alters the trafficking kinetics of apoB-containing TG-rich lipoproteins through cellular lipidation compartments, which in turn, enhances particle expansion and increases TG secretion. PMID:22257482

  17. Regulation of microsomal triglyceride transfer protein

    PubMed Central

    Hussain, M Mahmood; Nijstad, Niels; Franceschini, Lisa

    2011-01-01

    Microsomal triglyceride transfer protein (MTP) facilitates the transport of dietary and endogenous fat by the intestine and liver by assisting in the assembly and secretion of triglyceride-rich apolipoprotein B-containing lipoproteins. Higher concentrations of apolipoprotein B lipoproteins predispose individuals to various cardiovascular and metabolic diseases such as atherosclerosis, diabetes, obesity and the metabolic syndrome. These can potentially be avoided by reducing MTP activity. In this article, we discuss regulation of MTP during development, cellular differentiation and diurnal variation. Furthermore, we focus on the regulation of MTP that occurs at transcriptional, post-transcriptional and post-translational levels. Transcriptional regulation of MTP depends on a few highly conserved cis-elements in the promoter. Several transcription factors that bind to these elements and either increase or decrease MTP expression have been identified. Additionally, MTP is regulated by macronutrients, hormones and other factors. This article will address the many ways in which MTP is regulated and advance the idea that reducing MTP levels, rather than its inhibition, might be an option to lower plasma lipids. PMID:21808658

  18. Multiple functions of microsomal triglyceride transfer protein

    PubMed Central

    2012-01-01

    Microsomal triglyceride transfer protein (MTP) was first identified as a major cellular protein capable of transferring neutral lipids between membrane vesicles. Its role as an essential chaperone for the biosynthesis of apolipoprotein B (apoB)-containing triglyceride-rich lipoproteins was established after the realization that abetalipoproteinemia patients carry mutations in the MTTP gene resulting in the loss of its lipid transfer activity. Now it is known that it also plays a role in the biosynthesis of CD1, glycolipid presenting molecules, as well as in the regulation of cholesterol ester biosynthesis. In this review, we will provide a historical perspective about the identification, purification and characterization of MTP, describe methods used to measure its lipid transfer activity, and discuss tissue expression and function. Finally, we will review the role MTP plays in the assembly of apoB-lipoprotein, the regulation of cholesterol ester synthesis, biosynthesis of CD1 proteins and propagation of hepatitis C virus. We will also provide a brief overview about the clinical potentials of MTP inhibition. PMID:22353470

  19. Genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the rat.

    PubMed

    Hodlov, Miloslava; edov, Lucie; K?enov, Drahomra; Lika, Frantiek; Krupkov, Michaela; Kazdov, Ludmila; Tremblay, Johanne; Hamet, Pavel; K?en, Vladimr; eda, Ond?ej

    2014-01-01

    The plasma profile of major lipoprotein classes and its subdivision into particular fractions plays a crucial role in the pathogenesis of atherosclerosis and is a major predictor of coronary artery disease. Our aim was to identify genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions and lipoprotein particle sizes in the recombinant inbred rat set PXO, in which alleles of two rat models of the metabolic syndrome (SHR and PD inbred strains) segregate together with those from Brown Norway rat strain. Adult male rats of 15 PXO strains (n?=?8-13/strain) and two progenitor strains SHR-Lx (n?=?13) and BXH2/Cub (n?=?18) were subjected to one-week of high-sucrose diet feeding. We performed association analyses of triglyceride (TG) and cholesterol (C) concentrations in 20 lipoprotein fractions and the size of major classes of lipoprotein particles utilizing 704 polymorphic microsatellite markers, the genome-wide significance was validated by 2,000 permutations per trait. Subsequent in silico focusing of the identified quantitative trait loci was completed using a map of over 20,000 single nucleotide polymorphisms. In most of the phenotypes we identified substantial gradient among the strains (e.g. VLDL-TG from 5.6 to 66.7 mg/dl). We have identified 14 loci (encompassing 1 to 65 genes) on rat chromosomes 3, 4, 7, 8, 11 and 12 showing suggestive or significant association to one or more of the studied traits. PXO strains carrying the SHR allele displayed significantly higher values of the linked traits except for LDL-TG and adiposity index. Cholesterol concentrations in large, medium and very small LDL particles were significantly associated to a haplotype block spanning part of a single gene, low density lipoprotein receptor-related protein 1B (Lrp1b). Using genome-wide association we have identified new genetic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the recombinant inbred panel of rat model strains. PMID:25296178

  20. Genomic Determinants of Triglyceride and Cholesterol Distribution into Lipoprotein Fractions in the Rat

    PubMed Central

    Hodlov, Miloslava; edov, Lucie; K?enov, Drahomra; Lika, Frantiek; Krupkov, Michaela; Kazdov, Ludmila; Tremblay, Johanne; Hamet, Pavel; K?en, Vladimr; eda, Ond?ej

    2014-01-01

    The plasma profile of major lipoprotein classes and its subdivision into particular fractions plays a crucial role in the pathogenesis of atherosclerosis and is a major predictor of coronary artery disease. Our aim was to identify genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions and lipoprotein particle sizes in the recombinant inbred rat set PXO, in which alleles of two rat models of the metabolic syndrome (SHR and PD inbred strains) segregate together with those from Brown Norway rat strain. Adult male rats of 15 PXO strains (n?=?813/strain) and two progenitor strains SHR-Lx (n?=?13) and BXH2/Cub (n?=?18) were subjected to one-week of high-sucrose diet feeding. We performed association analyses of triglyceride (TG) and cholesterol (C) concentrations in 20 lipoprotein fractions and the size of major classes of lipoprotein particles utilizing 704 polymorphic microsatellite markers, the genome-wide significance was validated by 2,000 permutations per trait. Subsequent in silico focusing of the identified quantitative trait loci was completed using a map of over 20,000 single nucleotide polymorphisms. In most of the phenotypes we identified substantial gradient among the strains (e.g. VLDL-TG from 5.6 to 66.7 mg/dl). We have identified 14 loci (encompassing 1 to 65 genes) on rat chromosomes 3, 4, 7, 8, 11 and 12 showing suggestive or significant association to one or more of the studied traits. PXO strains carrying the SHR allele displayed significantly higher values of the linked traits except for LDL-TG and adiposity index. Cholesterol concentrations in large, medium and very small LDL particles were significantly associated to a haplotype block spanning part of a single gene, low density lipoprotein receptor-related protein 1B (Lrp1b). Using genome-wide association we have identified new genetic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the recombinant inbred panel of rat model strains. PMID:25296178

  1. Adipophilin increases triglyceride storage in human macrophages by stimulation of biosynthesis and inhibition of beta-oxidation.

    PubMed

    Larigauderie, Guilhem; Cuaz-Prolin, Clarisse; Younes, Amena B; Furman, Christophe; Lasselin, Catherine; Copin, Corinne; Jaye, Michael; Fruchart, Jean-Charles; Rouis, Mustapha

    2006-08-01

    Lipid accumulation alters macrophage biology and contributes to lipid retention within the vessel wall. In this study, we investigated the role of adipophilin on triglyceride accumulation and lipid-droplet formation in THP-1-derived macrophages (THP-1 macrophages). In the presence of acetylated low-density lipoprotein, macrophages infected with an adenovirus expressing human adipophilin showed a 31% increase in triglyceride content and a greater number of lipid droplets compared with control cells. Incubation of macrophages with very low-density lipoprotein (VLDL) dramatically increased cellular triglyceride content similarly in control and adipophilin-overexpressing cells. By itself, VLDL increased adipophilin expression, which explains the lack of effect of adipophilin overexpression on cellular triglyceride content in macrophages loaded with VLDL. The lipid-droplet content of macrophages was increased by overexpression of adipophilin and/or loading with VLDL. In contrast, inhibition of adipophilin expression using siRNA prevented lipid-droplet formation and significantly reduced intracellular triglyceride content. Using inhibitors of beta-oxidation and acyl-coenzyme A synthetase, results were obtained which suggest that adipophilin elevates cellular lipids by inhibition of beta-oxidation and stimulation of long-chain fatty acid incorporation into triglycerides. Adipophilin expression in THP-1 macrophages altered the cellular content of different lipids and enhanced the size of lipid droplets, consistent with a role for adipophilin in human foam cell formation. PMID:16884492

  2. Serotonin (5-HT) receptor 5A sequence variants affect human plasma triglyceride levels.

    PubMed

    Zhang, Y; Smith, E M; Baye, T M; Eckert, J V; Abraham, L J; Moses, E K; Kissebah, A H; Martin, L J; Olivier, M

    2010-07-01

    Neurotransmitters such as serotonin (5-hydroxytryptamine, 5-HT) work closely with leptin and insulin to fine-tune the metabolic and neuroendocrine responses to dietary intake. Losing the sensitivity to excess food intake can lead to obesity, diabetes, and a multitude of behavioral disorders. It is largely unclear how different serotonin receptor subtypes respond to and integrate metabolic signals and which genetic variations in these receptor genes lead to individual differences in susceptibility to metabolic disorders. In an obese cohort of families of Northern European descent (n = 2,209), the serotonin type 5A receptor gene, HTR5A, was identified as a prominent factor affecting plasma levels of triglycerides (TG), supported by our data from both genome-wide linkage and targeted association analyses using 28 publicly available and 12 newly discovered single nucleotide polymorphisms (SNPs), of which 3 were strongly associated with plasma TG levels (P < 0.00125). Bayesian quantitative trait nucleotide (BQTN) analysis identified a putative causal promoter SNP (rs3734967) with substantial posterior probability (P = 0.59). Functional analysis of rs3734967 by electrophoretic mobility shift assay (EMSA) showed distinct binding patterns of the two alleles of this SNP with nuclear proteins from glioma cell lines. In conclusion, sequence variants in HTR5A are strongly associated with high plasma levels of TG in a Northern European population, suggesting a novel role of the serotonin receptor system in humans. This suggests a potential brain-specific regulation of plasma TG levels, possibly by alteration of the expression of HTR5A. PMID:20388841

  3. Effect of Dietary Fatty Acid Composition on Food Intake, Triglycerides, and Hypothalamic Peptides

    PubMed Central

    Barson, Jessica R.; Karatayev, Olga; Gaysinskaya, Valeriya; Chang, Guo-Qing; Leibowitz, Sarah F.

    2011-01-01

    While a high-fat diet when compared to low-fat diet is known to produce overeating and health complications, less is known about the effects produced by fat-rich diets differing in their specific composition of fat. This study examined the effects of a high-fat diet containing relatively high levels of saturated compared to unsaturated fatty acids (HiSat) to a high-fat diet with higher levels of unsaturated fatty acids (USat). A HiSat compared to USat meal caused rats to consume more calories in a subsequent chow test meal. The HiSat meal also increased circulating levels of triglycerides (TG) and expression of the orexigenic peptides, galanin (GAL) in the hypothalamic paraventricular nucleus (PVN) and orexin (OX) in the perifornical lateral hypothalamus (PFLH). A similar increase in TG levels and PVN GAL and PFLH OX was also seen in rats given chronic access to the HiSat compared to USat diet, while neuropeptide Y (NPY) and agouti-related protein (AgRP) in the arcuate nucleus showed decreased expression. The importance of TG in producing these changes was supported by the finding that the TG-lowering medication gemfibrozil as compared to vehicle, when peripherally administered before consumption of a HiSat meal, significantly decreased the expression of OX, while increasing the expression of NPY and AgRP. These findings substantiate the importance of the fat composition in a diet, indicating that those rich in saturated compared to unsaturated fatty acids may promote overeating by increasing circulating lipids and specific hypothalamic peptides, GAL and OX, known to preferentially stimulate the consumption of a fat-rich diet. PMID:21903140

  4. Noninvasive Measurement of Plasma Triglycerides and Free Fatty Acids from Exhaled Breath

    PubMed Central

    Minh, Timothy Do Chau; Oliver, Stacy R; Flores, Rebecca L; Ngo, Jerry; Meinardi, Simone; Carlson, Matthew K; Midyett, Jason; Rowland, F Sherwood; Blake, Donald R; Galassetti, Pietro Renato

    2012-01-01

    Background Although altered metabolism has long been known to affect human breath, generating clinically usable metabolic tests from exhaled compounds has proven challenging. If developed, a breath-based lipid test would greatly simplify management of diabetes and serious pathological conditions (e.g., obesity, familial hyperlipidemia, and coronary artery disease), in which systemic lipid levels are a critical risk factor for onset and development of future cardiovascular events. Methods We, therefore, induced controlled fluctuations of plasma lipids (insulin-induced lipid suppression or intravenous infusion of Intralipid) during 4-h in vivo experiments on 23 healthy volunteers (12 males/11 females, 28.0 0.3 years) to find correlations between exhaled volatile organic compounds and plasma lipids. In each subject, plasma triglycerides (TG) and free fatty acids (FFA) concentrations were both directly measured and calculated via individualized prediction equations based on the multiple linear regression analysis of a cluster of 4 gases. In the lipid infusion protocol, we also generated common prediction equations using a maximum of 10 gases. Results This analysis yielded strong correlations between measured and predicted values during both lipid suppression (r = 0.97 for TG; r = 0.90 for FFA) and lipid infusion (r = 0.97 for TG; r = 0.94 for FFA) studies. In our most accurate common prediction model, measured and predicted TG and FFA values also displayed very strong statistical agreement (r = 0.86 and r = 0.81, respectively). Conclusions Our results demonstrate the feasibility of measuring plasma lipids through breath analysis. Optimization of this technology may ultimately lead to the development of portable breath analyzers for plasma lipids, replacing blood-based bioassays. PMID:22401327

  5. Dynamical behavior in f (T, TG) cosmology

    NASA Astrophysics Data System (ADS)

    Kofinas, Georgios; Leon, Genly; Saridakis, Emmanuel N.

    2014-09-01

    The f(T,{{T}_{G}}) class of gravitational modification, based on the quadratic torsion scalar T as well as on the new quartic torsion scalar TG, which is the teleparallel equivalent of the Gauss-Bonnet term, is a novel theory, different from both f (T) and f(R,G) ones. We perform a detailed dynamical analysis of a spatially flat universe governed by the simplest non-trivial model of f(T,{{T}_{G}}) gravity which does not introduce a new mass scale. We find that the universe can result in dark-energy dominated, quintessence-like, cosmological-constant-like, or phantom-like solutions, according to the parameter choices. Additionally, it may result in a dark energy-dark matter scaling solution; thus it can alleviate the coincidence problem. Finally, the analysis at infinity reveals that the universe may exhibit future, past, or intermediate singularities, depending on the parameters.

  6. Short-term overexpression of CD36 in the liver augments hepatic lipid storage and VLDL-triglyceride secretion: Implications for diet-induced obesity and type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Type 2 diabetes (T2D) is associated with a high risk of cardiovascular disease. The management of dyslipidemia in T2D is one element in the multifactorial approach to prevent coronary heart disease. Since the levels of plasma fatty acids (FA), triglycerides (TG). and lipoproteins are primarily contr...

  7. Antisense oligonucleotide inhibition of apolipoprotein C-III reduces plasma triglycerides in rodents, nonhuman primates, and humans.

    TOXLINE Toxicology Bibliographic Information

    Graham MJ; Lee RG; Bell TA 3rd; Fu W; Mullick AE; Alexander VJ; Singleton W; Viney N; Geary R; Su J; Baker BF; Burkey J; Crooke ST; Crooke RM

    2013-05-24

    RATIONALE: Elevated plasma triglyceride levels have been recognized as a risk factor for the development of coronary heart disease. Apolipoprotein C-III (apoC-III) represents both an independent risk factor and a key regulatory factor of plasma triglyceride concentrations. Furthermore, elevated apoC-III levels have been associated with metabolic syndrome and type 2 diabetes mellitus. To date, no selective apoC-III therapeutic agent has been evaluated in the clinic.OBJECTIVE: To test the hypothesis that selective inhibition of apoC-III with antisense drugs in preclinical models and in healthy volunteers would reduce plasma apoC-III and triglyceride levels.METHODS AND RESULTS: Rodent- and human-specific second-generation antisense oligonucleotides were identified and evaluated in preclinical models, including rats, mice, human apoC-III transgenic mice, and nonhuman primates. We demonstrated the selective reduction of both apoC-III and triglyceride in all preclinical pharmacological evaluations. We also showed that inhibition of apoC-III was well tolerated and not associated with increased liver triglyceride deposition or hepatotoxicity. A double-blind, placebo-controlled, phase I clinical study was performed in healthy subjects. Administration of the human apoC-III antisense drug resulted in dose-dependent reductions in plasma apoC-III, concomitant lowering of triglyceride levels, and produced no clinically meaningful signals in the safety evaluations.CONCLUSIONS: Antisense inhibition of apoC-III in preclinical models and in a phase I clinical trial with healthy subjects produced potent, selective reductions in plasma apoC-III and triglyceride, 2 known risk factors for cardiovascular disease. This compelling pharmacological profile supports further clinical investigations in hypertriglyceridemic subjects.

  8. Hypertriglyceridemia is a Major Factor Associated With Elevated Levels of Small Dense LDL Cholesterol in Patients With Metabolic Syndrome

    PubMed Central

    Cho, Yonggeun; Lee, Sang-Guk; Jee, Sun Ha

    2015-01-01

    Background We aimed to determine the major contributing component of metabolic syndrome (MetS) that results in an elevated small dense LDL cholesterol (sdLDL-C) concentration and sdLDL-C/LDL-C ratio. Methods Four hundred and forty-seven subjects (225 men; 222 women) with MetS were randomly selected from the Korean Metabolic Syndrome Research Initiatives-Seoul cohort study. Age- and sex-matched healthy controls (181 men; 179 women) were also randomly selected from the same cohort. Results A comparison of the median values of the sdLDL-C concentration between subgroups, divided according to whether subjects met or did not meet the criteria for each MetS component in patients with MetS, revealed a significant difference in the sdLDL-C concentration only between subgroups divided according to whether subjects met or did not meet the triglyceride (TG) criteria (P<0.05 for each gender). The TG level showed a good correlation with sdLDL-C concentration (correlation coefficients [r]=0.543 for men; 0.653 for women) and the sdLDL-C/LDL-C ratio (r=0.789 for men; 0.745 for women). Multiple linear regression analyses conducted for the MetS group concordantly identified TG as one of the most significant contributors to sdLDL-C concentration (?=0.17470.0105, P<0.0001) and the sdLDL-C/LDL-C ratio (?=6.95180.3011, P<0.0001). Conclusions Among five MetS components, only the abnormal TG level was a differentiating factor for sdLDL-C concentration and sdLDL-C/LDL-C ratio. These results were reproducible in both genders, with or without MetS. PMID:26354346

  9. Bioconversion of Xylan to Triglycerides by Oil-Rich Yeasts

    PubMed Central

    Fall, Ray; Phelps, Patricia; Spindler, Diane

    1984-01-01

    A series of lipid-accumulating yeasts was examined for their potential to saccharify xylan and accumulate triglyceride. Of the genera tested, including Candida, Cryptococcus, Lipomyces, Rhodosporidium, Rhodotorula, and Trichosporon, only Cryptococcus and Trichosporon isolates saccharified xylan. All of the strains could assimilate xylose and accumuate triglyceride under nitrogen-limiting conditions. Strains of Cryptococcus albidus were found to be especially useful for a one-step saccharification of xylan coupled to triglyceride synthesis. Cryptococcus terricolus, a strain constitutive for lipid accumulation, lacked extracellular xylanase, but did assimilate xylose and xylobiose and was able to continuously convert xylan to triglyceride if the culture medium was supplemented with xylanase. PMID:16346541

  10. Triglyceride-to-HDL-cholesterol ratio and metabolic syndrome as contributors to cardiovascular risk in overweight patients.

    PubMed

    Marotta, Teodoro; Russo, Barbara F; Ferrara, L Aldo

    2010-08-01

    Insulin resistance increases cardiovascular risk of obese patients. Triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL) >or=3.0 (in mg/dl) is a marker of insulin resistance in overweight persons. We aimed at assessing cardiovascular risk profile in 301 overweight elderly Neapolitan outpatients, according to TG/HDL ratio and metabolic syndrome (MS), diagnosed by National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. TG/HDL ratio was >or=3.0 in 97 patients (group A) and <3.0 in 204 (group B). Overall, 93-97% of group A patients and 38-51% of group B patients had MS, depending on the diagnostic criterion. Group A patients with MS had significantly higher waist-to-hip ratio, total and non-HDL cholesterol than group B patients with MS. In group B, MS and non-MS patients had similar waist-to-hip ratio, blood pressure, total and non-HDL cholesterol. Ten year coronary risk, calculated by the Framingham equations (n = 243), was 10.3 +/- 5% in group B, non-MS patients; 13.1 +/- 6% in group B, MS patients; 19.9 +/- 8% in group A (F = 32.8; P < 0.001). At the multiple regression analysis, TG/HDL ratio was associated with coronary risk (r(2) = 0.227) more closely than gender, blood pressure, waist-to-hip ratio, non HDL cholesterol, and MS considered as a whole. A separate regression analysis showed that the logarithmically transformed TG/HDL ratio, an index of the HDL cholesterol esterification rate, is also associated with coronary risk (r(2) = 0.252). Thus, TG/HDL ratio could help to characterize high-risk overweight patients deserving a special therapeutic effort. Cardiovascular risk profile of insulin-sensitive patients, identified by lower values of this parameter, is only moderately affected by MS. PMID:20019684

  11. APOE modulates the correlation between triglycerides, cholesterol, and CHD through pleiotropy, and gene-by-gene interactions.

    PubMed

    Maxwell, Taylor J; Ballantyne, Christie M; Cheverud, James M; Guild, Cameron S; Ndumele, Chiadi E; Boerwinkle, Eric

    2013-12-01

    Relationship loci (rQTL) exist when the correlation between multiple traits varies by genotype. rQTL often occur due to gene-by-gene (G G) or gene-by-environmental interactions, making them a powerful tool for detecting G G. Here we present an empirical analysis of apolipoprotein E (APOE) with respect to lipid traits and incident CHD leading to the discovery of loci that interact with APOE to affect these traits. We found that the relationship between total cholesterol (TC) and triglycerides (ln TG) varies by APOE isoform genotype in African-American (AA) and European-American (EA) populations. The e2 allele is associated with strong correlation between ln TG and TC while the e4 allele leads to little or no correlation. This led to a priori hypotheses that APOE genotypes affect the relationship of TC and/or ln TG with incident CHD. We found that APOE*TC was significant (P = 0.016) for AA but not EA while APOE*ln TG was significant for EA (P = 0.027) but not AA. In both cases, e2e2 and e2e3 had strong relationships between TC and ln TG with CHD while e2e4 and e4e4 results in little or no relationship between TC and ln TG with CHD. Using ARIC GWAS data, scans for loci that significantly interact with APOE produced four loci for African Americans (one CHD, one TC, and two HDL). These interactions contribute to the rQTL pattern. rQTL are a powerful tool to identify loci that modify the relationship between risk factors and disease and substantially increase statistical power for detecting G G. PMID:24097412

  12. Intracellular pigment epithelium-derived factor contributes to triglyceride degradation.

    PubMed

    Dai, Zhiyu; Zhou, Ti; Li, Cen; Qi, Weiwei; Mao, Yuling; Lu, Juling; Yao, Yachao; Li, Lei; Zhang, Ting; Hong, Honghai; Li, Shuai; Cai, Weibin; Yang, Zhonghan; Ma, Jianxing; Yang, Xia; Gao, Guoquan

    2013-09-01

    Pigment epithelium-derived factor is well known as a secreted glycoprotein with multiple functions, such as anti-angiogenic, neuroprotective and anti-tumor activities. However, its intracellular role remains unknown. The present study was performed to demonstrate the intracellular function of pigment epithelium-derived factor on triglyceride degradation. Hepatic pigment epithelium-derived factor levels increased at the early stage and subsequently decreased after 16 weeks in high-fat-diet-fed mice compared to those in chow-fed mice. Similarly, oleic acid led to long-term downregulation of pigment epithelium-derived factor in HepG2 cells. Endogenous pigment epithelium-derived factor was an intracellular protein with cytoplasmic distribution in hepatocytes by immunostaining. Exogenous FITC-labeled pigment epithelium-derived factor could be absorbed into hepatocytes. Both signal peptide deletion and full-length pigment epithelium-derived factor transfection HeLa cells and hepatocytes promoted triglyceride degradation. Intracellular pigment epithelium-derived factor co-immunoprecipitated with adipose triglyceride lipase and promoted triglyceride degradation in an adipose triglyceride lipase-dependent manner. Additionally, pigment epithelium-derived factor bound to the C-terminal of adipose triglyceride lipase (aa268-504) and adipose triglyceride lipase-G0/G1 switch gene-2 complex simultaneously, which facilitated adipose triglyceride lipase-G0/G1 switch gene-2 translocation onto lipid droplet using bimolecular fluorescence complementation assay. Moreover, knockdown of endogenous pigment epithelium-derived factor in hepatocytes diminished triglyceride degradation. Taken together, these results indicate that hepatic pigment epithelium-derived factor was decreased in obese mice accompanied with hepatic steatosis. Intracellular pigment epithelium-derived factor binds to and facilitates adipose triglyceride lipase translocation onto lipid droplet, which promotes triglyceride degradation. These findings suggest that a decreased level of hepatic pigment epithelium-derived factor may contribute to hepatic steatosis in obesity. PMID:23886488

  13. Relationship between insulin sensitivity and the triglyceride-HDL-C ratio in overweight and obese postmenopausal women: a MONET study.

    PubMed

    Karelis, Antony D; Pasternyk, Stephanie M; Messier, Lyne; St-Pierre, David H; Lavoie, Jean-Marc; Garrel, Dominique; Rabasa-Lhoret, Rmi

    2007-12-01

    The objective of this cross-sectional study was to examine the relationship between the triglyceride-HDL-cholesterol ratio (TG:HDL-C) and insulin sensitivity in overweight and obese sedentary postmenopausal women. The study population consisted of 131 non-diabetic overweight and obese sedentary postmenopausal women (age; 57.7+/-5.0 y; body mass index (BMI), 32.2+/-4.3 kg/m2). Subjects were characterized by dividing the entire cohort into tertiles based on the TG:HDL-C (T1<0.86 vs. T2=0.86 to 1.35 vs. T3>1.35, respectively). We measured (i) insulin sensitivity (using the hyperinsulinenic-euglycemic clamp and homeostasis model assessment (HOMA)), (ii) body composition (using dual-energy X-ray absorptiometry), (iii) visceral fat (using computed tomography), (iv) plasma lipids, C-reactive protein, 2 h glucose concentration during an oral glucose tolerance test (2 h glucose), as well as fasting glucose and insulin, (v) peak oxygen consumption, and (vi) lower-body muscle strength (using weight training equipment). Significant correlations were observed between the TG:HDL-C and the hyperinsulinemic-euglycemic clamp (r=-0.45; p<0.0001), as well as with HOMA (r=0.42; p<0.0001). Moreover, the TG:HDL-C significantly correlated with lean body mass, visceral fat, 2 h glucose, C-reactive protein, and muscle strength. Stepwise regression analysis showed that the TG:HDL-C explained 16.4% of the variation in glucose disposal in our cohort, which accounted for the greatest source of unique variance. Other independent predictors of glucose disposal were 2 h glucose (10.1%), C-reactive protein (CRP; 7.6%), and peak oxygen consumption (5.8%), collectively (including the TG:HDL-C) explaining 39.9% of the unique variance. In addition, the TG:HDL-C was the second predictor for HOMA, accounting for 11.7% of the variation. High levels of insulin sensitivity were associated with low levels of the TG:HDL-C. In addition, the TG:HDL-C was a predictor for glucose disposal rates and HOMA values in our cohort of overweight and obese postmenopausal women. PMID:18059582

  14. N-3 Fatty Acid Rich Triglyceride Emulsions Are Neuroprotective after Cerebral Hypoxic-Ischemic Injury in Neonatal Mice

    PubMed Central

    Vannucci, Susan J.; Mastropietro, Christopher; Bazan, Nicolas G.; Ten, Vadim S.; Deckelbaum, Richard J.

    2013-01-01

    We questioned if acute administration of n-3 fatty acids (FA) carried in n-3 rich triglyceride (TG) emulsions provides neuroprotection in neonatal mice subjected to hypoxic-ischemic (H/I) brain injury. We examined specificity of FA, optimal doses, and therapeutic windows for neuroprotection after H/I. H/I insult was induced in C57BL/6J 10-day-old mice by right carotid artery ligation followed by exposure to 8% O2 for 15 minutes at 37C. Intraperitoneal injection with n-3-rich TG emulsions, n-6 rich TG emulsions or saline for control was administered at different time points before and/or after H/I. In separate experiments, dose responses were determined with TG containing only docosahexaenoic acid (Tri-DHA) or eicosapentaenoic acid (Tri-EPA) with a range of 0.10.375 g n-3 TG/kg, administered immediately after H/I insult. Infarct volume and cerebral blood flow (CBF) were measured. Treatment with n-3 TG emulsions both before- and after- H/I significantly reduced total infarct volume by a mean of 43% when administered 90 min prior to H/I and by 47% when administered immediately after H/I. In post-H/I experiments Tri-DHA, but not Tri-EPA exhibited neuroprotective effects with both low and high doses (p<0.05). Moreover, delayed post-H/I treatment with Tri-DHA significantly decreased total infarct volume by a mean of 51% when administered at 0 hr, by 46% at 1 hr, and by 51% at 2 hr after H/I insult. No protective effect occurred with Tri-DHA injection at 4 hr after H/I. There were no n-3 TG related differences in CBF. A significant reduction in brain tissue death was maintained after Tri-DHA injection at 8 wk after the initial brain injury. Thus, n-3 TG, specifically containing DHA, is protective against H/I induced brain infarction when administered up to 2 hr after H/I injury. Acute administration of TG-rich DHA may prove effective for treatment of stroke in humans. PMID:23437099

  15. [Change in the cholesterol and triglyceride content in the blood in self-stimulation and avoidance reactions].

    PubMed

    Simutenko, L V; Iastrebtsova, N L; Leontovich, T A

    1979-03-01

    The changes in the blood serum cholesterol and triglyceride content were studied or rabbits of both sexes during reactions of self-stimulation and avoidance. Self-stimulation was accompanied by a significant decrease in the blood serum cholesterol and triglyceride content. During the reaction of avoidance the character of the cholesterol changes varied. The reaction of avoidance of the "agression" type was accompanied by elevated blood serum cholesterol content, whereas the reaction of the "fear" type was associated with a decrease in its content. The maximal changes in the cholesterol and triglyceride content as compared to the initial level were observed in all types of the reactions 15--30 minutes following stimulation. PMID:427271

  16. High-density lipoprotein remains elevated despite reductions in total cholesterol in fasting adult male elephant seals (Mirounga angustirostris).

    PubMed

    Tift, Michael S; Houser, Dorian S; Crocker, Daniel E

    2011-08-01

    We examined changes in lipid profiles of 40 adult northern elephant seal bulls over the 3-month breeding fast and the 1-month molting fast to investigate impacts of fasting on serum total cholesterol (TC), triglycerides (TG) and lipoproteins. Total cholesterol and low-density lipoprotein (LDL) levels were initially high (3930 190mgL(-1)and 1610 170mgL(-1), respectively) and decreased significantly over the breeding season. Total cholesterol and LDL declined significantly with adipose tissue reserves (p<0.001), and LDL levels as low as 43 mgL(-1) were measured in seals late in the breeding fast. Less dramatic but similar changes in lipid metabolism were observed across the molting fast. High-density lipoproteins (HDL) remained consistently elevated (>1750 mgL(-1)) suggesting that elephant seals defend HDL concentrations, despite significant depletion of TC and LDL across the breeding fast. Triglyceride levels were significantly higher during the molt, consistent with lower rates of lipid oxidation needed to meet metabolic energy demands during this period. The maintenance of HDL during breeding is consistent with its role in delivering cholesterol from adipose tissue for steroidogenesis and spermatogenesis and potentially mitigates oxidative stress associated with fasting. PMID:21596155

  17. Long-term fatty acid stability in human serum cholesteryl ester, triglyceride, and phospholipid fractions.

    PubMed

    Matthan, Nirupa R; Ip, Blanche; Resteghini, Nancy; Ausman, Lynne M; Lichtenstein, Alice H

    2010-09-01

    Fatty acid profiles of biological specimens from epidemiological/clinical studies can serve as biomarkers to assess potential relationships between diet and chronic disease risk. However, data are limited regarding fatty acid stability in archived specimens following long-term storage, a variable that could affect result validity. Our objective was to determine the effect of prolonged storage at -80 degrees C on the fatty acid profiles of serum cholesteryl ester (CE), triglyceride (TG), and phospholipid (PL) fractions. This was accomplished by determining the fatty acid profile of frozen, archived, previously unthawed serum samples from 22 subjects who participated in a controlled feeding trial. Initial analysis was performed after trial completion and the repeat analysis after 8-10 years of storage using GC. No significant differences were observed among the majority of fatty acids regardless of lipid fraction. Reliability coefficients were high for the fatty acid classes (saturated fatty acid : 0.70, MUFA : 0.90, PUFA : 0.80). When differences were identified, they were limited to low abundance fatty acids (TG, or PL fatty acid profiles. PMID:20448292

  18. Changes in liver uptake of a radioiodinated triglyceride analog in ethanol-fed rats

    SciTech Connect

    Schwendner, S.W.; Skinner, R.S.W.; Gross, M.; Ruyan, M.; Counsell, R.E. VA Medical Center, Ann Arbor, MI )

    1991-03-11

    A radioiodinated triglyceride (TG) analog, ({sup 125}I)-glycerol-2-palmitoyl-1,3-di-15-(p-iodophenyl)pentadecanoate (DPPG) has been synthesized and shown to accumulate within the liver of normal rats within 15 min of i.v. administration. With time, the radioactivity clears and more activity appears as the fatty acid metabolite than as parent compound. In this study, rats were fed a commercial liquid diet containing 36% of the calories either as ethanol (ET) or sucrose (CON). After six weeks, the ET rats had significantly higher plasma and liver TG levels than CON rats. In addition, the ET rats showed fatty infiltration of the liver by histopathologic examination. DPPG formulated in a detergent-saline vehicle was administered and different patterns of both uptake and clearance were seen in these groups of rats. The CON rats showed greater uptake and more rapid clearance of radioactivity than ET rats. A similar pattern was observed noninvasively by gamma camera scintigraphy. In addition, PAGE analysis of the plasma revealed that 90% of the radioactivity in the plasma was associated with plasma lipoproteins within 5 m. By 120 m 40% of the plasma activity in CON rats was associated with albumin, indicating hydrolysis to the free fatty acid. In the ET rats only 22% was albumin bound at this time. Thus, DPPG shows promise as an agent to diagnose changes in liver lipid metabolism in such disease states as alcoholism.

  19. Triglyceride Levels Are Closely Associated with Mild Declines in Estimated Glomerular Filtration Rates in Middle-Aged and Elderly Chinese with Normal Serum Lipid Levels

    PubMed Central

    Zhang, Xiuping; Zhao, Xiangmin; Wang, Yulian; Li, Chengqiao; Li, Mei; Wang, Shaoyuan; Yang, Weifang; Ma, Zeqiang; Ma, Aixia; Zheng, Huizhen; Wu, Jiahui; Sun, Yu; Song, Jun; Lin, Peng; Liang, Kai; Gong, Lei; Wang, Meijian; Liu, Fuqiang; Li, Wenjuan; Xiao, Juan; Yan, Fei; Yang, Junpeng; Wang, Lingshu; Tian, Meng; Liu, Jidong; Zhao, Ruxing; Chen, Shihong; Chen, Li

    2014-01-01

    Objective To investigate the relationship between lipid profiles [including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)] and a mild decline in the estimated glomerular filtration rate (eGFR) in subjects with normal serum lipid levels. Design and Methods In this study, we included 2647 participants who were ?40 years old and had normal serum lipid levels. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to estimate the GFR. A mildly reduced eGFR was defined as 6090 mL/min/1.73 m2. First, multiple linear regression analysis was used to estimate the association of lipid profiles with the eGFR. Then, the levels of each lipid component were divided into four groups, using the 25th, 50th and 75th percentiles as cut-off points. Finally, multiple logistic regression analysis was used to investigate the association of different lipid components with the risk of mildly reduced eGFR. Results In the group with a mildly reduced eGFR, TG and LDL-C levels were significantly increased, but HDL-C levels were significantly decreased. After adjusting for age, gender, body mass index (BMI), systolic blood pressure (SBP), glycated hemoglobin (HbA1c), smoking and drinking, only TC and TG were independently related to the eGFR. Additionally, only TG showed a linear relationship with an increased risk of a mildly reduced eGFR, with the highest quartile group (TG: 108150 mg/dl [1.221.70 mmol/L]) having a significantly increased risk after adjusting for the above factors. Conclusions Triglyceride levels are closely associated with a mildly reduced eGFR in subjects with normal serum lipid levels. Dyslipidemia with lower TG levels could be used as new diagnostic criteria for subjects with mildly reduced renal function. PMID:25275610

  20. Effect of beta-adrenoceptor blockade on postexercise oxygen consumption and triglyceride/fatty acid cycling.

    PubMed

    Børsheim, E; Bahr, R; Høstmark, A T; Knardahl, S

    1998-04-01

    In the recovery period after strenuous exercise, there is increased O2 uptake, termed the excess postexercise O2 consumption (EPOC). One of the mechanisms suggested to explain EPOC is activation of the triglyceride/fatty acid (TG/FA) cycle by catecholamines. The purpose of this study was to determine the effect of selective beta1- and nonselective beta-adrenoceptor blockade on EPOC and the TG/FA cycle. Seven healthy young men each participated in three control and three exercise experiments in a randomized and balanced sequence. In the exercise experiments, subjects exercised for 90 minutes at 58% +/- 2% (mean +/- SD) of maximal O2 uptake on a cycle ergometer, followed by a 4.5-hour bedrest. The control experiments followed the same protocol, but without exercise. In one control and one exercise experiment, the selective beta1-adrenoceptor antagonist atenolol (0.062 mg.kg(-1) body weight) was administered intravenously immediately after the exercise (EXAT) and at the corresponding time in the rest-control experiment (REAT). In a second set of control and exercise experiments, the nonselective beta-adrenoceptor antagonist propranolol (0.15 mg.kg(-1) body weight) was administered (REPRO and EXPRO). In a third set of rest and exercise experiments, an injection of saline was given instead of beta-antagonist (RE and EX). TG/FA cycling was calculated by combining results obtained with a two-stage glycerol infusion and indirect calorimetry. O2 uptake was significantly increased above control levels throughout the recovery period after exercise with the nonselective beta-adrenoceptor antagonist, beta1-adrenoceptor antagonist, and saline. However, there was no difference between the time course or magnitude of EPOC in the three situations. After 4.5 hours of bedrest, the mean increase in O2 uptake was 8% to 9% in all three conditions. TG/FA cycling was increased after exercise, but no effects of beta-antagonists were observed. We conclude that EPOC and the rate of TG/FA cycling are not attenuated by selective beta1- or nonselective beta-adrenoceptor blockade after an acute prolonged exercise protocol. PMID:9550543

  1. Thermodynamic scaling of polymer dynamics versus T - Tg scaling

    NASA Astrophysics Data System (ADS)

    Guo, Jiaxi; Simon, Sindee L.

    2011-08-01

    A thermodynamic scaling law for the relaxation times of complex liquids as a function of temperature and volume has been proposed in the literature: ?(T,V) = (TV?), where ? is a material-dependent constant. We test this scaling for six materials, linear polystyrene, star polystyrene, two polycyanurate networks, poly(vinyl acetate), and poly(vinyl chloride), and compare the thermodynamic scaling to T - Tg scaling, where ? = (T - Tg). The thermodynamic scaling law successfully reduces the data for all of the samples; however, polymers with similar structures but different glass transition (Tg) and pressure-volume-temperature (PVT) behavior, i.e., the two polycyanurates, cannot be superposed unless the scaling law is normalized by TgVg?. On the other hand, the T - Tg scaling successfully reduced data for all polymers, including those having similar microstructures. In addition, the T - Tg scaling is easier to implement since it does not require knowledge of the PVT behavior of the material. The relationship between TgVg?/TV? and T - Tg scaling is clarified and is found to be weakly dependent on pressure.

  2. Joint analyses model for total cholesterol and triglyceride in human serum with near-infrared spectroscopy.

    PubMed

    Yao, Lijun; Lyu, Ning; Chen, Jiemei; Pan, Tao; Yu, Jing

    2016-04-15

    The development of a small, dedicated near-infrared (NIR) spectrometer has promising potential applications, such as for joint analyses of total cholesterol (TC) and triglyceride (TG) in human serum for preventing and treating hyperlipidemia of a large population. The appropriate wavelength selection is a key technology for developing such a spectrometer. For this reason, a novel wavelength selection method, named the equidistant combination partial least squares (EC-PLS), was applied to the wavelength selection for the NIR analyses of TC and TG in human serum. A rigorous process based on the various divisions of calibration and prediction sets was performed to achieve modeling optimization with stability. By applying EC-PLS, a model set was developed, which consists of various models that were equivalent to the optimal model. The joint analyses model of the two indicators was further selected with only 50 wavelengths. The random validation samples excluded from the modeling process were used to validate the selected model. The root-mean-square errors, correlation coefficients and ratio of performance to deviation for the prediction were 0.197mmolL(-1), 0.985 and 5.6 for TC, and 0.101mmolL(-1), 0.992 and 8.0 for TG, respectively. The sensitivity and specificity for hyperlipidemia were 96.2% and 98.0%. These findings indicate high prediction accuracy and low model complexity. The proposed wavelength selection provided valuable references for the designing of a small, dedicated spectrometer for hyperlipidemia. The methodological framework and optimization algorithm are universal, such that they can be applied to other fields. PMID:26827178

  3. Joint analyses model for total cholesterol and triglyceride in human serum with near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Yao, Lijun; Lyu, Ning; Chen, Jiemei; Pan, Tao; Yu, Jing

    2016-04-01

    The development of a small, dedicated near-infrared (NIR) spectrometer has promising potential applications, such as for joint analyses of total cholesterol (TC) and triglyceride (TG) in human serum for preventing and treating hyperlipidemia of a large population. The appropriate wavelength selection is a key technology for developing such a spectrometer. For this reason, a novel wavelength selection method, named the equidistant combination partial least squares (EC-PLS), was applied to the wavelength selection for the NIR analyses of TC and TG in human serum. A rigorous process based on the various divisions of calibration and prediction sets was performed to achieve modeling optimization with stability. By applying EC-PLS, a model set was developed, which consists of various models that were equivalent to the optimal model. The joint analyses model of the two indicators was further selected with only 50 wavelengths. The random validation samples excluded from the modeling process were used to validate the selected model. The root-mean-square errors, correlation coefficients and ratio of performance to deviation for the prediction were 0.197 mmol L- 1, 0.985 and 5.6 for TC, and 0.101 mmol L- 1, 0.992 and 8.0 for TG, respectively. The sensitivity and specificity for hyperlipidemia were 96.2% and 98.0%. These findings indicate high prediction accuracy and low model complexity. The proposed wavelength selection provided valuable references for the designing of a small, dedicated spectrometer for hyperlipidemia. The methodological framework and optimization algorithm are universal, such that they can be applied to other fields.

  4. Triglyceride sensing in the reward circuitry: A new insight in feeding behaviour regulation.

    PubMed

    Cansell, Celine; Luquet, Serge

    2016-01-01

    In both developed and emerging countries, sedentary life style and over exposition to high energy dense foods has led to a thermodynamic imbalance and consequently obesity. Obesity often involves a behavioural component in which, similar to drugs abuse, compulsive consumption of palatable food rich in lipids and sugar drives energy intake far beyond metabolic demands. The hypothalamus is one of the primary integration sites of circulating energy-related signals like leptin or ghrelin and is therefore considered as one of the main central regulators of energy balance. However, food intake is also modulated by sensory inputs, such as tastes and odours, as well as by affective or emotional states. The mesolimbic pathway is well established as a key actor of the rewarding aspect of feeding. Particularly, the hedonic and motivational aspects of food are closely tied to the release of the neurotransmitter dopamine (DA) in striatal structure such as the Nucleus Accumbens (Nacc). In both rodent and humans several studies shows an attenuated activity of dopaminergic signal associated with obesity and there is evidence that consumption of palatable food per se leads to DA signalling alterations. Furthermore impaired cognition in obese mice is improved by selectively lowering triglycerides (TG) and intracerebroventricular administration of TG induces by itself acquisition impairment in several cognitive paradigms in normal body weight mice. Together, these observations raise the possibility that nutritional lipids, particularly TG, directly affect cognitive and reward processes by modulating the mesolimbic pathway and might contribute to the downward spiral of compulsive consumption of palatable food and obesity. This review is an attempt to capture recent evolution in the field that might point toward a direct action of nutritional lipid in the reward circuitry. PMID:26159487

  5. Association between colon diverticula and hemoglobin, triglyceride and uric acid levels

    PubMed Central

    TOMIZAWA, MINORU; SHINOZAKI, FUMINOBU; HASEGAWA, RUMIKO; SHIRAI, YOSHINORI; MOTOYOSHI, YASUFUMI; SUGIYAMA, TAKAO; YAMAMOTO, SHIGENORI; ISHIGE, NAOKI

    2015-01-01

    Colon diverticula cause bleeding and acute diverticulitis. The present study analyzed laboratory test variables, aiming to predict the presence of diverticula. Patient records from between April 2011 and March 2014 were analyzed retrospectively (1,520 patients) and a one-way analysis of variance was performed to analyze the association between the presence of diverticula and each variable. A χ2 test was then used to assess the correlation between the prevalence of diverticula and the percentage of patients with uric acid (UA) levels ≥5.1 mg/dl. A receiver operating characteristic (ROC) analysis was performed to determine the threshold values required to predict the presence of diverticula. Hemoglobin (Hb) levels were lower in patients with diverticula than in those without diverticula (P=0.0027), and compared with patients without diverticula, UA and triglyceride (TG) levels were higher in patients with diverticula (P=0.0066 and P=0.0136, respectively). The patients were divided into two groups, as follows: Patients with UA levels ≥5.1 mg/dl (the median value) and those with UA levels <5.1 mg/dl. The prevalence of diverticula was significantly higher in patients with UA levels ≥5.1 mg/dl than in those with UA levels <5.1 mg/dl (P=0.0004). ROC analysis demonstrated that the threshold values of Hb, TG and UA were 12,400, 146 and 5.1 mg/dl, respectively. The sensitivity of the Hb and UA levels at the threshold values was 76.5 and 71.0%, respectively. The prevalence of diverticula was associated with low Hb levels, and high TG and UA levels. PMID:26668609

  6. Resveratrol regulates lipolysis via adipose triglyceride lipase.

    PubMed

    Lasa, Arrate; Schweiger, Martina; Kotzbeck, Petra; Churruca, Itziar; Simón, Edurne; Zechner, Rudolf; Portillo, María del Puy

    2012-04-01

    Resveratrol has been reported to increase adrenaline-induced lipolysis in 3T3-L1 adipocytes. The general aim of the present work was to gain more insight concerning the effects of trans-resveratrol on lipid mobilization. The specific purpose was to assess the involvement of the two main lipases: adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), in the activation of lipolysis induced by this molecule. For lipolysis experiments, 3T3-L1 and human SGBS adipocytes as well as adipose tissue from wild-type, ATGL knockout and HSL knockout mice were used. Moreover, gene and protein expressions of these lipases were analyzed. Resveratrol-induced free fatty acids release but not glycerol release in 3T3-L1 under basal and isoproterenol-stimulating conditions and under isoproterenol-stimulating conditions in SGBS adipocytes. When HSL was blocked by compound 76-0079, free fatty acid release was still induced by resveratrol. By contrast, in the presence of the compound C, an inhibitor of adenosine monophosphate-activated protein kinase, resveratrol effect was totally blunted. Resveratrol increased ATGL gene and protein expressions, an effect that was not observed for HSL. Resveratrol increased fatty acids release in epididymal adipose tissue from wild-type and HSL knockout mice but not in that adipose tissue from ATGL knockout mice. Taking as a whole, the present results provide novel evidence that resveratrol regulates lipolytic activity in human and murine adipocytes, as well as in white adipose tissue from mice, acting mainly on ATGL at transcriptional and posttranscriptional levels. Enzyme activation seems to be induced via adenosine monophosphate-activated protein kinase. PMID:21543206

  7. Targeted delivery of a model immunomodulator to the lymphatic system: comparison of alkyl ester versus triglyceride mimetic lipid prodrug strategies.

    PubMed

    Han, Sifei; Quach, Tim; Hu, Luojuan; Wahab, Anisa; Charman, William N; Stella, Valentino J; Trevaskis, Natalie L; Simpson, Jamie S; Porter, Christopher J H

    2014-03-10

    A lipophilic prodrug approach has been used to promote the delivery of a model immunomodulator, mycophenolic acid (MPA), to the lymphatic system after oral administration. Lymphatic transport was employed to facilitate enhanced drug uptake into lymphocytes, as recent studies demonstrate that targeted drug delivery to lymph resident lymphocytes may enhance immunomodulatory effects. Two classes of lymph-directing prodrugs were synthesised. Alkyl chain derivatives (octyl mycophenolate, MPA-C8E; octadecyl mycophenolate, MPA-C18E; and octadecyl mycophenolamide, MPA-C18AM), to promote passive partitioning into lipids in lymphatic transport pathways, and a triglyceride mimetic prodrug (1,3-dipalmitoyl-2-mycophenoloyl glycerol, 2-MPA-TG) to facilitate metabolic integration into triglyceride deacylation-reacylation pathways. Lymphatic transport, lymphocyte uptake and plasma pharmacokinetics were assessed in mesenteric lymph and carotid artery cannulated rats following intraduodenal infusion of lipid-based formulations containing MPA or MPA prodrugs. Patterns of prodrug hydrolysis in rat digestive fluid, and cellular re-esterification in vivo, were evaluated to examine the mechanisms responsible for lymphatic transport. Poor enzyme stability and low absorption appeared to limit lymphatic transport of the alkyl derivatives, although two of the three alkyl chain prodrugs - MPA-C18AM (6-fold) and MPA-C18E (13-fold) still increased lymphatic drug transport when compared to MPA. In contrast, 2-MPA-TG markedly increased lymphatic drug transport (80-fold) and drug concentrations in lymphocytes (103-fold), and this was achieved via biochemical incorporation into triglyceride deacylation-reacylation pathways. The prodrug was hydrolysed rapidly to 2-mycophenoloyl glycerol (2-MPA-MG) in the presence of rat digestive fluid, and 2-MPA-MG was subsequently re-esterified in the enterocyte with oleic acid (most likely originating from the co-administered formulation) prior to accessing the lymphatics and lymphocytes. Importantly, after administration of 2-MPA-TG, the concentrations of free MPA in the mesenteric lymph nodes were significantly enhanced (up to 28 fold) when compared to animals administered equimolar quantities of MPA, suggesting the efficient conversion of the esterified prodrug back to the pharmacologically active parent drug. The data suggest that triglyceride mimetic prodrugs have potential as a means of enhancing immunotherapy via drug targeting to lymphocytes and lymph nodes. PMID:24398334

  8. Identification of Type 2 Diabetes Risk Factors Using Phenotypes Consisting of Anthropometry and Triglycerides based on Machine Learning.

    PubMed

    Lee, Bum Ju; Kim, Jong Yeol

    2016-01-01

    The hypertriglyceridemic waist (HW) phenotype is strongly associated with type 2 diabetes; however, to date, no study has assessed the predictive power of phenotypes based on individual anthropometric measurements and triglyceride (TG) levels. The aims of the present study were to assess the association between the HW phenotype and type 2 diabetes in Korean adults and to evaluate the predictive power of various phenotypes consisting of combinations of individual anthropometric measurements and TG levels. Between November 2006 and August 2013, 11937 subjects participated in this retrospective cross-sectional study. We measured fasting plasma glucose and TG levels and performed anthropometric measurements. We employed binary logistic regression (LR) to examine statistically significant differences between normal subjects and those with type 2 diabetes using HW and individual anthropometric measurements. For more reliable prediction results, two machine learning algorithms, naive Bayes (NB) and LR, were used to evaluate the predictive power of various phenotypes. All prediction experiments were performed using a tenfold cross validation method. Among all of the variables, the presence of HW was most strongly associated with type 2 diabetes ( , adjusted odds ratio (OR) = 2.07 [95% CI, 1.72-2.49] in men; , adjusted OR = 2.09 [1.79-2.45] in women). When comparing waist circumference (WC) and TG levels as components of the HW phenotype, the association between WC and type 2 diabetes was greater than the association between TG and type 2 diabetes. The phenotypes tended to have higher predictive power in women than in men. Among the phenotypes, the best predictors of type 2 diabetes were waist-to-hip ratio + TG in men (AUC by NB = 0.653, AUC by LR = 0.661) and rib-to-hip ratio + TG in women (AUC by NB = 0.73, AUC by LR = 0.735). Although the presence of HW demonstrated the strongest association with type 2 diabetes, the predictive power of the combined measurements of the actual WC and TG values may not be the best manner of predicting type 2 diabetes. Our findings may provide clinical information concerning the development of clinical decision support systems for the initial screening of type 2 diabetes. PMID:25675467

  9. Leucine restores murine hepatic triglyceride accumulation induced by a low-protein diet by suppressing autophagy and excessive endoplasmic reticulum stress.

    PubMed

    Yokota, Shin-Ichi; Ando, Midori; Aoyama, Shinya; Nakamura, Kawai; Shibata, Shigenobu

    2016-04-01

    Although it is known that a low-protein diet induces hepatic triglyceride (TG) accumulation in both rodents and humans, little is known about the underlying mechanism. In the present study, we modeled hepatic TG accumulation by inducing dietary protein deficiency in mice and aimed to determine whether certain amino acids could prevent low-protein diet-induced TG accumulation in the mouse liver. Mice fed a diet consisting of 3 % casein (3C diet) for 7 days showed hepatic TG accumulation with up-regulation of TG synthesis for the Acc gene and down-regulation of TG-rich lipoprotein secretion from hepatocytes for Mttp genes. Supplementing the 3 % casein diet with essential amino acids, branched-chain amino acids, or the single amino acid leucine rescued hepatic TG accumulation. In the livers of mice fed the 3 % casein diet, we observed a decrease in the levels of the autophagy substrate p62, an increase in the expression levels of the autophagy marker LC3-II, and an increase in the splicing of the endoplasmic reticulum (ER) stress-dependent Xbp1 gene. Leucine supplementation to the 3 % casein diet did not affect genes related to lipid metabolism, but inhibited the decrease in p62, the increase in LC3-II, and the increase in Xbp1 splicing levels in the liver. Our results suggest that ER stress responses and activated autophagy play critical roles in low-protein diet-induced hepatic TG accumulation in mice, and that leucine suppresses these two major protein degradation systems. This study contributes to understanding the mechanisms of hepatic disorders of lipid metabolism. PMID:26707165

  10. Extended Tg Gradient Profile Across a Glassy-Rubbery Polymer-Polymer Interface with an 80 K Tg Difference

    NASA Astrophysics Data System (ADS)

    Baglay, Roman; Roth, Connie

    2014-03-01

    For decades Tg in confined systems has been studied with the hopes of uncovering the length scales that impact the glass transition. However, understanding length scales of Tg gradients near a free surface have been hampered by limitations of how to treat the enhanced mobility at the free surface theoretically. Here, we use a glassy-rubbery polymer-polymer interface to establish an 80 K Tg gradient from one well-defined Tg value to another. Multilayer films of high molecular weight polystyrene (PS) and poly(n-butyl methacrylate), a weakly immiscible system with a 7 nm interfacial width, are constructed. Ultrathin (10-15 nm) pyrene-labeled layers are inserted into the multilayer structure at different positions (z) from the glassy-rubbery interface. Temperature-dependent fluorescence intensity is collected to determine the local Tg(z) at a given position z from the interface. Using a series of different samples, we are able to map the Tg(z) profile across this glassy-rubbery interface. Our work reveals an asymmetric local mobility gradient propagating hundreds of nanometers away from the interface into the glassy PS side before bulk PS Tg is recovered. These results demonstrate that cooperative segmental Tg dynamics can be coupled across long length scales spanning multiple cooperatively rearranging regions (CRRs).

  11. UV irradiation promotes the accumulation of triglyceride in Lipomyces lipofer.

    PubMed

    Konno, Ayumu; Suzuki, Yoshihisa; Ogawa, Tomohisa; Taniuchi, Tetsuo

    2009-11-01

    Yeasts of the genus Lipomyces are known as fat yeasts, and they store large amounts of lipids. Because the major lipid produced by Lipomyces is triglyceride, which can be used as a food and energy resource, the control of lipid production by Lipomyces sp. is an important issue. Here we report the effects of UV irradiation on lipid production in Lipomyces lipofer cells. UV irradiation (315-400 nm) led to a 4-fold increase in the amount of triglyceride per cell. We discovered a novel phenomenon, that UV irradiation promotes triglyceride accumulation in L. lipofer. PMID:19897922

  12. Cholecystokinin elevates mouse plasma lipids.

    PubMed

    Zhou, Lichun; Yang, Hong; Lin, Xinghua; Okoro, Emmanuel U; Guo, Zhongmao

    2012-01-01

    Cholecystokinin (CCK) is a peptide hormone that induces bile release into the intestinal lumen which in turn aids in fat digestion and absorption in the intestine. While excretion of bile acids and cholesterol into the feces eliminates cholesterol from the body, this report examined the effect of CCK on increasing plasma cholesterol and triglycerides in mice. Our data demonstrated that intravenous injection of [Thr28, Nle31]-CCK at a dose of 50 ng/kg significantly increased plasma triglyceride and cholesterol levels by 22 and 31%, respectively, in fasting low-density lipoprotein receptor knockout (LDLR(-/-)) mice. The same dose of [Thr28, Nle31]-CCK induced 6 and 13% increases in plasma triglyceride and cholesterol, respectively, in wild-type mice. However, these particular before and after CCK treatment values did not achieve statistical significance. Oral feeding of olive oil further elevated plasma triglycerides, but did not alter plasma cholesterol levels in CCK-treated mice. The increased plasma cholesterol in CCK-treated mice was distributed in very-low, low and high density lipoproteins (VLDL, LDL and HDL) with less of an increase in HDL. Correspondingly, the plasma apolipoprotein (apo) B48, B100, apoE and apoAI levels were significantly higher in the CCK-treated mice than in untreated control mice. Ligation of the bile duct, blocking CCK receptors with proglumide or inhibition of Niemann-Pick C1 Like 1 transporter with ezetimibe reduced the hypercholesterolemic effect of [Thr28, Nle31]-CCK in LDLR(-/-) mice. These findings suggest that CCK-increased plasma cholesterol and triglycerides as a result of the reabsorption of biliary lipids from the intestine. PMID:23300532

  13. Medium Chain Triglycerides in Paediatric Practice

    PubMed Central

    Gracey, Michael; Burke, Valerie; Anderson, Charlotte M.

    1970-01-01

    Medium chain triglycerides (MCT) bypass the steps necessary for the absorption of long chain fats (LCT), and so have theoretical grounds for their use in various disease states, particularly malabsorptive disorders. In childhood, MCT have particular advantages since they allow restriction of dietary long chain fats without limiting the intake of protein necessary for growth while providing adequate calories. In malabsorptive states, MCT have been used mostly in cystic fibrosis, where they may reduce steatorrhoea. However, the long-term growth patterns of these children are dependent on the extent and severity of their chest disease. MCT may be a useful source of calories for those with anorexia due to infection or liver disease and in babies recovering from meconium ileus. The decrease in offensive stools, flatus, and abdominal discomfort improves well-being and social acceptability which is important for many schoolchildren and adolescents. Rectal prolapse may be helped. Where there is loss of the small intestinal absorptive surface, particularly after massive small bowel resection, MCT can help to maintain weight and nutrition. They may also be a useful supplementary nutritional measure in patients severely affected with coeliac disease while awaiting response to a gluten-free diet, and in patients with regional enteritis. In children with liver disease, MCT provide a ready source of calories while avoiding the loss of fat in their stools. Infants with neonatal hepatitis or biliary atresia remain well nourished, and some older children with liver disease grow more rapidly and have fewer and less offensive stools and less abdominal discomfort. Where an abnormal number of faecal organisms colonize the small intestine (`contaminated small bowel syndrome' or `blind loop syndrome') intraluminal bile salts become deconjugated and cause steatorrhoea. A combination of antibiotic and surgical treatment is usually indicated, but MCT can be used to improve nutrition before operation and may be indicated for associated conditions, such as massive intestinal resection. MCT have also been helpful in patients with defective chylomicron formation due to a-β-lipoproteinaemia. In the congenital and less commonly encountered acquired lymphatic disorders in childhood, MCT have given encouraging results. This group includes patients with gross protein and fat loss due to intestinal lymphangiectasia and others with lymphatic anomalies at other sites. Hyperchylomicronaemia (familial fat-induced hypertriglyceridaemia) responds well to dietary treatment with MCT. PMID:4918706

  14. Polymorphisms in genes involved in fatty acid ?-oxidation interact with dietary fat intakes to modulate the plasma TG response to a fish oil supplementation.

    PubMed

    Bouchard-Mercier, Annie; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

    2014-01-01

    A large inter-individual variability in the plasma triglyceride (TG) response to an omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been observed. The objective was to examine gene-diet interaction effects on the plasma TG response after a fish oil supplementation, between single-nucleotide polymorphisms (SNPs) within genes involved in fatty acid ?-oxidation and dietary fat intakes. Two hundred and eight (208) participants were recruited in the greater Quebec City area. The participants completed a six-week fish oil supplementation (5 g fish oil/day: 1.9-2.2 g EPA and 1.1 g DHA). Dietary fat intakes were measured using three-day food records. SNPs within RXRA, CPT1A, ACADVL, ACAA2, ABCD2, ACOX1 and ACAA1 genes were genotyped using TAQMAN methodology. Gene-diet interaction effects on the plasma TG response were observed for SNPs within RXRA (rs11185660, rs10881576 and rs12339187) and ACOX1 (rs17583163) genes. For rs11185660, fold changes in RXRA gene expression levels were different depending on SFA intakes for homozygotes T/T. Gene-diet interaction effects of SNPs within genes involved in fatty acid ?-oxidation and dietary fat intakes may be important in understanding the inter-individual variability in plasma TG levels and in the plasma TG response to a fish oil supplementation. PMID:24647074

  15. Polymorphisms in Genes Involved in Fatty Acid β-Oxidation Interact with Dietary Fat Intakes to Modulate the Plasma TG Response to a Fish Oil Supplementation

    PubMed Central

    Bouchard-Mercier, Annie; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

    2014-01-01

    A large inter-individual variability in the plasma triglyceride (TG) response to an omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been observed. The objective was to examine gene-diet interaction effects on the plasma TG response after a fish oil supplementation, between single-nucleotide polymorphisms (SNPs) within genes involved in fatty acid β-oxidation and dietary fat intakes. Two hundred and eight (208) participants were recruited in the greater Quebec City area. The participants completed a six-week fish oil supplementation (5 g fish oil/day: 1.9–2.2 g EPA and 1.1 g DHA). Dietary fat intakes were measured using three-day food records. SNPs within RXRA, CPT1A, ACADVL, ACAA2, ABCD2, ACOX1 and ACAA1 genes were genotyped using TAQMAN methodology. Gene-diet interaction effects on the plasma TG response were observed for SNPs within RXRA (rs11185660, rs10881576 and rs12339187) and ACOX1 (rs17583163) genes. For rs11185660, fold changes in RXRA gene expression levels were different depending on SFA intakes for homozygotes T/T. Gene-diet interaction effects of SNPs within genes involved in fatty acid β-oxidation and dietary fat intakes may be important in understanding the inter-individual variability in plasma TG levels and in the plasma TG response to a fish oil supplementation. PMID:24647074

  16. Genome-Wide Linkage Scan for Genes Influencing Plasma Triglyceride Levels in the Veterans Administration Genetic Epidemiology Study

    PubMed Central

    Coletta, Dawn K.; Schneider, Jennifer; Hu, Shirley L.; Dyer, Thomas D.; Puppala, Sobha; Farook, Vidya S.; Arya, Rector; Lehman, Donna M.; Blangero, John; DeFronzo, Ralph A.; Duggirala, Ravindranath; Jenkinson, Christopher P.

    2009-01-01

    OBJECTIVE—Elevated plasma triglyceride concentration is a component of the insulin resistance syndrome and is commonly associated with type 2 diabetes, obesity, and coronary heart disease. The goal of our study was to perform a genome-wide linkage scan to identify genetic regions that influence variation in plasma triglyceride levels in families that are enriched with individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS—We used phenotypic and genotypic data from 1,026 individuals distributed across 294 Mexican-American families, who were ascertained for type 2 diabetes, from the Veterans Administration Genetic Epidemiology Study (VAGES). Plasma triglyceride values were transformed, and a variance-components technique was used to conduct multipoint linkage analysis. RESULTS—After adjusting for the significant effects of sex and BMI, heritability for plasma triglycerides was estimated as 46 ± 7% (P < 0.0001). Multipoint linkage analysis yielded the strongest evidence for linkage of plasma triglycerides near marker D12S391 on chromosome 12p (logarithm of odds [LOD] = 2.4). Our linkage signal on chromosome 12p provides independent replication of a similar finding in another Mexican-American sample from the San Antonio Family Diabetes Study (SAFDS). Combined multipoint linkage analysis of the VAGES and SAFDS data yielded significant evidence for linkage of plasma triglycerides to a genetic location between markers GATA49D12 and D12S391 on 12p (LOD = 3.8, empirical P value = 2.0 × 10−5). This region on 12p harbors the gene-encoding adiponectin receptor 2 (AdipoR2), where we previously have shown that multiple single nucleotide polymorphisms are associated with plasma triglyceride concentrations in the SAFDS. In the present study, we provided suggestive evidence in favor of association for rs929434 with triglyceride concentrations in the VAGES. CONCLUSIONS—Collectively, these results provide strong evidence for a major locus on chromosome 12p that influences plasma triglyceride levels in Mexican Americans. PMID:18931038

  17. Profile of Free Fatty Acids and Fractions of Phospholipids, Cholesterol Esters and Triglycerides in Serum of Obese Youth with and without Metabolic Syndrome

    PubMed Central

    Bermúdez-Cardona, Juliana; Velásquez-Rodríguez, Claudia

    2016-01-01

    The study evaluated the profile of circulating fatty acids (FA) in obese youth with and without metabolic syndrome (MetS) to determine its association with nutritional status, lifestyle and metabolic variables. A cross-sectional study was conducted in 96 young people, divided into three groups: obese with MetS (OBMS), obese (OB) and appropriate weight (AW). FA profiles were quantified by gas chromatography; waist circumference (WC), fat folds, lipid profile, high-sensitivity C-reactive protein, glucose, insulin, the homeostasis model assessment (HOMA index), food intake and physical activity (PA) were assessed. The OBMS group had significantly greater total free fatty acids (FFAs), palmitic-16:0 in triglyceride (TG), palmitoleic-16:1n-7 in TG and phospholipid (PL); in the OB group, these FAs were higher than in the AW group. Dihomo-gamma-linolenic (DHGL-20:3n-6) was higher in the OBMS than the AW in PL and FFAs. Linoleic-18:2n-6 in TG and PL had the lowest proportion in the OBMS group. WC, PA, total FFA, linoleic-18:2n-6 in TG and DHGL-20:3n-6 in FFAs explained 62% of the HOMA value. The OB group presented some higher proportions of FA and biochemical values than the AW group. The OBMS had proportions of some FA in the TG, PL and FFA fractions that correlated with disturbances of MetS. PMID:26891317

  18. Detection of quantitative trait loci affecting serum cholesterol, LDL, HDL, and triglyceride in pigs

    PubMed Central

    2011-01-01

    Background Serum lipids are associated with many serious cardiovascular diseases and obesity problems. Many quantitative trait loci (QTL) have been reported in the pig mostly for performance traits but very few for the serum lipid traits. In contrast, remarkable numbers of QTL are mapped for serum lipids in humans and mice. Therefore, the objective of this research was to investigate the chromosomal regions influencing the serum level of the total cholesterol (CT), triglyceride (TG), high density protein cholesterol (HDL) and low density protein cholesterol (LDL) in pigs. For this purpose, a total of 330 animals from a Duroc Pietrain F2 resource population were phenotyped for serum lipids using ELISA and were genotyped by using 122 microsatellite markers covering all porcine autosomes for QTL study in QTL Express. Blood sampling was performed at approximately 175 days before slaughter of the pig. Results Most of the traits were correlated with each other and were influenced by average daily gain, slaughter date and age. A total of 18 QTL including three QTL with imprinting effect were identified on 11 different porcine autosomes. Most of the QTL reached to 5% chromosome-wide (CW) level significance including a QTL at 5% experiment-wide (GW) and a QTL at 1% GW level significance. Of these QTL four were identified for both the CT and LDL and two QTL were identified for both the TG and LDL. Moreover, three chromosomal regions were detected for the HDL/LDL ratio in this study. One QTL for HDL on SSC2 and two QTL for TG on SSC11 and 17 were detected with imprinting effect. The highly significant QTL (1% GW) was detected for LDL at 82 cM on SSC1, whereas significant QTL (5% GW) was identified for HDL/LDL on SSC1 at 87 cM. Chromosomal regions with pleiotropic effects were detected for correlated traits on SSC1, 7 and 12. Most of the QTL identified for serum lipid traits correspond with the previously reported QTL for similar traits in other mammals. Two novel QTL on SSC16 for HDL and HDL/LDL ratio and an imprinted QTL on SSS17 for TG were detected in the pig for the first time. Conclusion The newly identified QTL are potentially involved in lipid metabolism. The results of this work shed new light on the genetic background of serum lipid concentrations and these findings will be helpful to identify candidate genes in these QTL regions related to lipid metabolism and serum lipid concentrations in pigs. PMID:21752294

  19. Volumetric MRI and MRS provide sensitive measures of Alzheimer's disease neuropathology in inducible Tau transgenic mice (rTg4510).

    PubMed

    Yang, Dewen; Xie, Zhiyong; Stephenson, Diane; Morton, Daniel; Hicks, Carol D; Brown, Tracy M; Sriram, Renuka; O'Neill, Sharon; Raunig, David; Bocan, Thomas

    2011-02-14

    The purpose of this study was to determine if in vivo high resolution 3D MRI and localized (1)H MR spectroscopy (MRS) can detect brain findings resembling Alzheimer's disease in a transgenic mouse model of Tau pathology. Seven double transgenic rTg4510 female mice and 7 age-matched wild-type (wt) female mice were evaluated at 5 months of age. To confirm the usefulness and consistency of in vivo MRI/S, we also scanned the brains of 14 male mice (7 rTg4510 and 7 age-matched wt) at 8 months of age. Mean hippocampal and cerebral cortex volumes in the female rTg4510 mice were 26.7% and 20.6% smaller than that in the wt controls (p<0.0001), respectively. Mean hippocampal and cerebral cortex volumes in the male rTg4510 mice were 18.4% and 16.9% smaller than that in the wt controls (p<0.00005), respectively. The mean volumes of the cerebellum were not statistically different between the rTg4510 and the wt groups. MRS assessment revealed that the myo-inositol to total creatine ratios (mIns/tCr), a measure of gliosis, were significantly higher in the hippocampus of rTg4510 mice relative to wt mice (p=0.03 for the females; p=0.005 for the males). Immunohistochemistry and histology in the same animals verified previously published data showing elevation of hyperphosphorylated Tau, glial activation and cortical and hippocampal neuronal loss. This study demonstrates that in vivo MRI/S can be a non-invasive biomarker to assess brain atrophy and related biochemical changes in the rTg4510 mouse model. PMID:21035554

  20. The fatty liver dystrophy (fld) mutation: Developmentally related alterations in hepatic triglyceride metabolism and protein expression

    SciTech Connect

    Reue, K.; Rehnmark, S.; Cohen, R.D.; Leete, T.H.; Doolittle, M.H.; Giometti, C.S.; Mishler, K.; Slavin, B.G.

    1997-07-01

    Fatty liver dystrophy (fld) is an autosomal recessive mutation in mice characterized by hypertriglyceridemia and development of a fatty liver in the early neonatal period. Also associated with the fld phenotype is a tissue-specific deficiency in the expression of lipoprotein lipase and hepatic lipase, as well as elevations in hepatic apolipoprotein A-IV and apolipoprotein C-II mRNA levels. Although these lipid abnormalities resolve at the age of weaning, adult mutant mice exhibit a peripheral neuropathy associated with abnormal myelin formation. The fatty liver in fld/fld neonates is characterized by the accumulation of large triglyceride droplets within the parenchymal cells, and these droplets persist within isolated hepatocytes maintained in culture for several days. To identify the metabolic defect that leads to lipid accumulation, the authors investigated several aspects of cellular triglyceride metabolism. The mutant mice exhibited normal activity of acid triacylglycerol lipase, an enzyme thought to be responsible for hydrolysis of dietary triglycerides in the liver. Metabolic labeling studies performed with oleic acid revealed that free fatty acids accumulate in the liver of 3 day old fld/fld mice, but not in adults. This accumulation in liver was mirrored by elevated free fatty acid levels in plasma of fld/fld neonates, with levels highest in very young mice and returning to normal by the age of one month. Quantitation of fatty acid oxidation in cells isolated from fld/fld neonates revealed that oxidation rate is reduced 60% in hepatocytes and 40% in fibroblasts; hepatocytes from adult fld/fld mice exhibited an oxidation rate similar to those from wild-type mice.

  1. Antibodies against neo-epitope tTg complexed to gliadin are different and more reliable then anti-tTg for the diagnosis of pediatric celiac disease.

    PubMed

    Lerner, Aaron; Jeremias, Patricia; Neidhfer, Sandra; Matthias, Torsten

    2016-02-01

    The neo-epitope tTg (tTg-neo) autoantibody, never challenged the anti-tissue transglutaminase (tTg) premiership, recommended by ESPGHAN, for celiac disease (CD) diagnosis. Pediatric CD (PCD), abdominal pains and normal children, normal adults, and rheumatoid arthritis patients, were tested using the following ELISAs detecting IgA, IgG or both IgA and IgG (check): AESKULISA tTg (tTg; RUO) and AESKULISA tTg-neo. Higher OD activity was detected for tTg-neo IgA, IgG and IgA+IgG than for tTg. tTg-neo IgA, IgG correlated better with intestinal damage than tTg. The tTg-neo combined IgA+IgG ELISA kit had higher sensitivity and a comparable specificity for the diagnosis of PCD. The drop in the % competition was much higher with the tTg-neo then the tTg antibodies. The false positivity of the tTg was significantly higher than the tTg-neo one. Serological diagnostic performances, reflection of intestinal damage, diverse epitopes and false positivity were better with the tTg-neo. PMID:26684936

  2. Triglyceride-Lowering Effects of Two Probiotics, Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601, in a Rat Model of High-Fat Diet-Induced Hypertriglyceridemia.

    PubMed

    Choi, Il-Dong; Kim, Sung-Hwan; Jeong, Ji-Woong; Lee, Dong Eun; Huh, Chul-Sung; Hong, Seong Soo; Sim, Jae-Hun; Ahn, Young-Tae

    2016-03-28

    The triglyceride-lowering effect of probiotics Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601 were investigated. Male SD Wistar rats were randomly divided into three groups and fed high-fat diet (HFD), HFD and probiotics (5 X 10(9) CFU/day of L. plantarum KY1032 and 5 X 10(9) CFU/day of L. curvatus HY7601), or normal diet for 6 weeks. Probiotic treatment significantly lowered the elevated plasma triglyceride and increased plasma free fatty acid, glycerol, and plasma apolipoprotein A-V (ApoA-V) levels. The probiotic-treated group showed elevated hepatic mRNA expression of PPARα, bile acid receptor (FXR), and ApoA-V. These results demonstrate that L. plantarum KY1032 and L. curvatus HY7601 lower triglycerides in hypertriglyceridemic rats by upregulating ApoA-V, PPARα, and FXR. PMID:26699746

  3. The Hepatitis C Virus Core Protein Inhibits Adipose Triglyceride Lipase (ATGL)-mediated Lipid Mobilization and Enhances the ATGL Interaction with Comparative Gene Identification 58 (CGI-58) and Lipid Droplets*

    PubMed Central

    Camus, Gregory; Schweiger, Martina; Herker, Eva; Harris, Charles; Kondratowicz, Andrew S.; Tsou, Chia-Lin; Farese, Robert V.; Herath, Kithsiri; Previs, Stephen F.; Roddy, Thomas P.; Pinto, Shirly; Zechner, Rudolf; Ott, Melanie

    2014-01-01

    Liver steatosis is a common health problem associated with hepatitis C virus (HCV) and an important risk factor for the development of liver fibrosis and cancer. Steatosis is caused by triglycerides (TG) accumulating in lipid droplets (LDs), cellular organelles composed of neutral lipids surrounded by a monolayer of phospholipids. The HCV nucleocapsid core localizes to the surface of LDs and induces steatosis in cultured cells and mouse livers by decreasing intracellular TG degradation (lipolysis). Here we report that core at the surface of LDs interferes with the activity of adipose triglyceride lipase (ATGL), the key lipolytic enzyme in the first step of TG breakdown. Expressing core in livers or mouse embryonic fibroblasts of ATGL?/? mice no longer decreases TG degradation as observed in LDs from wild-type mice, supporting the model that core reduces lipolysis by engaging ATGL. Core must localize at LDs to inhibit lipolysis, as ex vivo TG hydrolysis is impaired in purified LDs coated with core but not when free core is added to LDs. Coimmunoprecipitation experiments revealed that core does not directly interact with the ATGL complex but, unexpectedly, increased the interaction between ATGL and its activator CGI-58 as well as the recruitment of both proteins to LDs. These data link the anti-lipolytic activity of the HCV core protein with altered ATGL binding to CGI-58 and the enhanced association of both proteins with LDs. PMID:25381252

  4. The hepatitis C virus core protein inhibits adipose triglyceride lipase (ATGL)-mediated lipid mobilization and enhances the ATGL interaction with comparative gene identification 58 (CGI-58) and lipid droplets.

    PubMed

    Camus, Gregory; Schweiger, Martina; Herker, Eva; Harris, Charles; Kondratowicz, Andrew S; Tsou, Chia-Lin; Farese, Robert V; Herath, Kithsiri; Previs, Stephen F; Roddy, Thomas P; Pinto, Shirly; Zechner, Rudolf; Ott, Melanie

    2014-12-26

    Liver steatosis is a common health problem associated with hepatitis C virus (HCV) and an important risk factor for the development of liver fibrosis and cancer. Steatosis is caused by triglycerides (TG) accumulating in lipid droplets (LDs), cellular organelles composed of neutral lipids surrounded by a monolayer of phospholipids. The HCV nucleocapsid core localizes to the surface of LDs and induces steatosis in cultured cells and mouse livers by decreasing intracellular TG degradation (lipolysis). Here we report that core at the surface of LDs interferes with the activity of adipose triglyceride lipase (ATGL), the key lipolytic enzyme in the first step of TG breakdown. Expressing core in livers or mouse embryonic fibroblasts of ATGL(-/-) mice no longer decreases TG degradation as observed in LDs from wild-type mice, supporting the model that core reduces lipolysis by engaging ATGL. Core must localize at LDs to inhibit lipolysis, as ex vivo TG hydrolysis is impaired in purified LDs coated with core but not when free core is added to LDs. Coimmunoprecipitation experiments revealed that core does not directly interact with the ATGL complex but, unexpectedly, increased the interaction between ATGL and its activator CGI-58 as well as the recruitment of both proteins to LDs. These data link the anti-lipolytic activity of the HCV core protein with altered ATGL binding to CGI-58 and the enhanced association of both proteins with LDs. PMID:25381252

  5. Effects of Polymorphisms in APOA4-APOA5-ZNF259-BUD13 Gene Cluster on Plasma Levels of Triglycerides and Risk of Coronary Heart Disease in a Chinese Han Population

    PubMed Central

    Su, Li; Zhang, Mingjun; Wang, Long; Jing, Jinjin; Zhou, Li

    2015-01-01

    Background/Aim Recent genome-wide association studies have identified several loci influencing lipid levels. The present study focused on the triglycerides (TG)-associated locus, the APOA4-APOA5-ZNF259-BUD13 gene cluster on chromosome 11, to explore the role of genetic variants in this gene cluster in the development of increasing TG levels and coronary heart disease (CHD). Methodology/Principal Findings Six single nucleotide polymorphisms (SNPs), rs4417316, rs651821, rs6589566, rs7396835, rs964184 and rs17119975, in the APOA4-APOA5-ZNF259-BUD13 gene cluster were selected and genotyped in 5374 healthy Chinese subjects. There were strong significant associations between the six SNPs and TG levels (P<1.0×10−8). Moreover, a weighted genotype score was found to be associated with TG levels (P = 3.28×10−13). The frequencies of three common haplotypes were observed to be significantly different between the high TG group and the low TG group (P<0.05). However, no significant effects were found for the SNPs regarding susceptibility to CHD in the Chinese case-control populations. Conclusions/Significance This study highlights the genotypes, genotype scores and haplotypes of the APOA4-APOA5-ZNF259-BUD13 gene cluster that were associated with TG levels in a Chinese population; however, the genetic variants in this gene cluster did not increase the risk of CHD in the Chinese population. PMID:26397108

  6. Endocrine and metabolic effects of consuming fructose- and glucose-sweetened beverages with meals in obese men and women: Influence of insulin resistance on plasma triglyceride responses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Context: Compared with glucose-sweetened beverages, consumption of fructose-sweetened beverages with meals elevates postprandial plasma triglycerides and lowers 24-h insulin and leptin profiles in normal weight women. The effects of fructose, compared with glucose, ingestion on metabolic profiles in...

  7. F3MB(PANDER) Decreases Mice Hepatic Triglyceride and Is Associated with Decreased DGAT1 Expression

    PubMed Central

    Mo, Xiaoqing; Yang, Chijiao; Wang, Xuelan; Burkhardt, Brant R.; Li, Yangbin; Xia, Haipeng; Cao, Xiaopei

    2015-01-01

    Objective Pancreatic-derived factor (PANDER, also named as FAM3B) is secreted by pancreatic α and β cells. Increasing evidence suggests that it may serve a hormonal function related to glycemic and lipid metabolism. In this study, we investigated the effects of PANDER overexpression on hepatic and adipose triglyceride metabolism in high-fat diet-fed male C57BL/6 mice. Methods PANDER overexpression was achieved by tail-vein injection of recombinant Ad-PANDER and Ad-GFP injected mice served as a control. The TG metabolism in both groups were compared. Results Adenoviral-mediated overexpression of PANDER did not affect body weight, food consumption, or liver enzymes. The triglyceride (TG) content of both liver and adipose tissue was significantly decreased in Ad-PANDER mice (liver: 6.16±1.89 mg/g vs. control 14.95±2.27 mg/g, P<0.05; adipose: 39.31±1.99 mg/100mg vs. 47.22±2.21 mg/100mg, P<0.05). The free fatty acid (FFA) content of adipose tissue in Ad-PANDER mice was also decreased (1.38±0.18 mg/g vs. 2.77±0.31 mg/g, P<0.01). The investigation of key enzymes of triglyceride hydrolysis and FFA oxidation in liver and adipose tissue showed that p-HSL/HSL was significantly increased and that DGAT1 gene and protein expression were significantly reduced in the liver of PANDER-overexpressing mice. PKA phosphorylation was also significantly increased in the livers of Ad-PANDER mice. No differences in ATGL, CPT1, ACOX1, or DGAT2 expression were observed. Conclusion Overexpression of PANDER is associated with observable decreases in TG, increases in PKA phosphorylation, and decreased DGAT1 expression, suggesting a possible interrelationship. The mechanisms by which this occurs remain to be elucidated. PMID:25679806

  8. Ultra high efficiency/low pressure supercritical fluid chromatography with superficially porous particles for triglyceride separation.

    PubMed

    Lesellier, E; Latos, A; de Oliveira, A Lopes

    2014-01-31

    This paper reports the development of the separation of vegetable oil triglycerides (TG) in supercritical chromatography (SFC), using superficially porous particles (SPPs). The SPP, having a small diameter (2-3?m), provide a higher theoretical plate number (N), which allows to improve separation of critical pairs of compounds. However, compared to fully porous particles of larger diameter (5?m), the pressure drop is also increased. Fortunately, supercritical fluids have a low viscosity, which allows coupling several columns to achieve high N values, while maintaining flow rate above 1ml/min, ensuring a ultra high efficiency (UHE) at low pressure (LP) (below 40MPa), with regards to the one reached with liquid and sub-two micron particles (around 100MPa). The use of two detector systems (UV and ELSD) connected in series to the UHE-LP-SFC system provides complementary responses, due to their specific detection principles. Working in a first part with three coupled Kinetex C18 columns (45cm total length), the effect of modifier nature and percentage were studied with two reference oils, argan and rapeseed, chosen for their different and well-known TG composition. The analytical method was developed from previous studies performed with fully porous particles (FPP). Optimized conditions with three Kinetex were as follows: 17C, 12% of ACN/MeOH (90/10; v/v). With these conditions, and by using an increased length of Kinetex C18 column (60cm), another additional column was selected from ten different commercial SPP C18 bonded phases, by applying a Derringer function on varied parameters: theoretical plate number (TPN), separation index (SI) for critical pairs of peaks (the peaks of compounds difficult to separate due to subtle structural differences), the analysis duration, and the total peak number. This function normalizes the values of any parameters, between 0 and 1, from the worst value to the better, allowing to take account of various parameters in the final choice. Finally, by using four Kinetex C18 plus one Accucore C18 (75cm total column length), a high-performance separation of triglycerides was achieved, with reasonable analysis duration and isocratic conditions. These conditions can be applied to varied vegetable oils. Identification of the numerous separated peaks of rapeseed oil was achieved by using published data and chromatographic retention behaviour. PMID:24411089

  9. Serum lipidomics profiling using LC-MS and high-energy collisional dissociation fragmentation: focus on triglyceride detection and characterization.

    PubMed

    Bird, Susan S; Marur, Vasant R; Sniatynski, Matthew J; Greenberg, Heather K; Kristal, Bruce S

    2011-09-01

    There is a growing need both clinically and experimentally to improve the characterization of blood lipids. A liquid chromatography-mass spectrometry (LC-MS) method, developed for the qualitative and semiquantitative detection of lipids in biological samples and previously validated in mitochondrial samples, was now evaluated for the profiling of serum lipids. Data were acquired using high-resolution, full scan MS and high-energy, collisional dissociation (HCD), all ion fragmentation. The method was designed for efficient separation and detection in both positive and negative ionization mode and evaluated using standards spanning seven lipid classes. Platform performance, related to the identification and characterization of serum triglycerides (TGs), was assessed using extracted ion chromatograms with mass tolerance windows of 5 ppm or less from full scan exact mass measurements determined using SIEVE nondifferential LC-MS analysis software. The platform showed retention time coefficients of variation (CV) of <0.3%, mass accuracy values of <2 ppm error, and peak area CV of <13%, with the majority of that error coming from sample preparation and extraction rather than the LC-MS analysis, and linearity was shown to be over 4 orders of magnitude (r(2) = 0.999) for the standard TG (15:0)(3) spiked into serum. Instrument mass accuracy and precision were critical to the identification of unknown TG species, in part because these parameters enabled us to reduce false positives. In addition to detection and relative quantitation of TGs in serum, TG structures were characterized through the use of alternating HCD scans at different energies to produce diagnostic fragmentations on all ions in the analysis. The lipidomics method was applied to serum samples from 192 rats maintained on diets differing in macronutrient composition. The analysis identified 86 TG species with 81 unique masses that varied over 3.5 orders of magnitude and showed diet-dependency, consistent with TGs linking diet and disease risk. PMID:21774539

  10. Triglyceride Glucose-Body Mass Index Is a Simple and Clinically Useful Surrogate Marker for Insulin Resistance in Nondiabetic Individuals

    PubMed Central

    Er, Leay-Kiaw; Wu, Semon; Chou, Hsin-Hua; Hsu, Lung-An; Teng, Ming-Sheng; Sun, Yu-Chen; Ko, Yu-Lin

    2016-01-01

    Background Insulin resistance (IR) and the consequences of compensatory hyperinsulinemia are pathogenic factors for a set of metabolic abnormalities, which contribute to the development of diabetes mellitus and cardiovascular diseases. We compared traditional lipid levels and ratios and combined them with fasting plasma glucose (FPG) levels or adiposity status for determining their efficiency as independent risk factors for IR. Methods We enrolled 511 Taiwanese individuals for the analysis. The clinical usefulness of various parameters—such as traditional lipid levels and ratios; visceral adiposity indicators, visceral adiposity index (VAI), and lipid accumulation product (LAP); the product of triglyceride (TG) and FPG (the TyG index); TyG with adiposity status (TyG-body mass index [BMI]) and TyG-waist circumference index [WC]); and adipokine levels and ratios—was analyzed to identify IR. Results For all lipid ratios, the TG/high-density lipoprotein cholesterol (HDL-C) ratio had the highest additional percentage of variation in the homeostasis model assessment of insulin resistance (HOMA-IR; 7.0% in total); for all variables of interest, TyG-BMI and leptin-adiponectin ratio (LAR) were strongly associated with HOMA-IR, with 16.6% and 23.2% of variability, respectively. A logistic regression analysis revealed similar patterns. A receiver operating characteristic (ROC) curve analysis indicated that TG/HDL-C was a more efficient IR discriminator than other lipid variables or ratios. The area under the ROC curve (AUC) for VAI (0.734) and TyG (0.708) was larger than that for TG/HDL-C (0.707). TyG-BMI and LAR had the largest AUC (0.801 and 0.801, respectively). Conclusion TyG-BMI is a simple, powerful, and clinically useful surrogate marker for early identification of IR. PMID:26930652

  11. Comparison of TG-43 and TG-186 in breast irradiation using a low energy electronic brachytherapy source

    SciTech Connect

    White, Shane A.; Landry, Guillaume; Reniers, Brigitte; Fonseca, Gabriel Paiva; Beaulieu, Luc; Verhaegen, Frank

    2014-06-15

    Purpose: The recently updated guidelines for dosimetry in brachytherapy in TG-186 have recommended the use of model-based dosimetry calculations as a replacement for TG-43. TG-186 highlights shortcomings in the water-based approach in TG-43, particularly for low energy brachytherapy sources. The Xoft Axxent is a low energy (<50 kV) brachytherapy system used in accelerated partial breast irradiation (APBI). Breast tissue is a heterogeneous tissue in terms of density and composition. Dosimetric calculations of seven APBI patients treated with Axxent were made using a model-based Monte Carlo platform for a number of tissue models and dose reporting methods and compared to TG-43 based plans. Methods: A model of the Axxent source, the S700, was created and validated against experimental data. CT scans of the patients were used to create realistic multi-tissue/heterogeneous models with breast tissue segmented using a published technique. Alternative water models were used to isolate the influence of tissue heterogeneity and backscatter on the dose distribution. Dose calculations were performed using Geant4 according to the original treatment parameters. The effect of the Axxent balloon applicator used in APBI which could not be modeled in the CT-based model, was modeled using a novel technique that utilizes CAD-based geometries. These techniques were validated experimentally. Results were calculated using two dose reporting methods, dose to water (D{sub w,m}) and dose to medium (D{sub m,m}), for the heterogeneous simulations. All results were compared against TG-43-based dose distributions and evaluated using dose ratio maps and DVH metrics. Changes in skin and PTV dose were highlighted. Results: All simulated heterogeneous models showed a reduced dose to the DVH metrics that is dependent on the method of dose reporting and patient geometry. Based on a prescription dose of 34 Gy, the average D{sub 90} to PTV was reduced by between ∼4% and ∼40%, depending on the scoring method, compared to the TG-43 result. Peak skin dose is also reduced by 10%–15% due to the absence of backscatter not accounted for in TG-43. The balloon applicator also contributed to the reduced dose. Other ROIs showed a difference depending on the method of dose reporting. Conclusions: TG-186-based calculations produce results that are different from TG-43 for the Axxent source. The differences depend strongly on the method of dose reporting. This study highlights the importance of backscatter to peak skin dose. Tissue heterogeneities, applicator, and patient geometries demonstrate the need for a more robust dose calculation method for low energy brachytherapy sources.

  12. Association of a Human FABP1 Gene Promoter Region Polymorphism with Altered Serum Triglyceride Levels

    PubMed Central

    Zhu, Yi-bing; Huang, Rong-dong; Lu, Qing-Qing; Lin, Xu

    2015-01-01

    Liver fatty acid-binding protein (L-FABP), also known as fatty acid-binding protein 1 (FABP1), is a key regulator of hepatic lipid metabolism. Elevated FABP1 levels are associated with an increased risk of cardiovascular disease (CVD) and metabolic syndromes. In this study, we examine the association of FABP1 gene promoter variants with serum FABP1 and lipid levels in a Chinese population. Four promoter single-nucleotide polymorphisms (SNPs) of FABP1 gene were genotyped in a cross-sectional survey of healthy volunteers (n = 1,182) from Fuzhou city of China. Results showed that only the rs2919872 G>A variant was significantly associated with serum TG concentration(P = 0.032).Compared with the rs2919872 G allele, rs2919872 A allele contributed significantly to reduced serum TG concentration, and this allele dramatically decreased the FABP1 promoter activity(P < 0.05). The rs2919872 A allele carriers had considerably lower serum FABP1 levels than G allele carriers (P < 0.01). In the multivariable linear regression analysis, the rs2919872 A allele was negatively associated with serum FABP1 levels (β = —0.320, P = 0.003), while serum TG levels were positively associated with serum FABP1 levels (β = 0.487, P = 0.014). Our data suggest that compared with the rs2919872 G allele, the rs2919872 A allele reduces the transcriptional activity of FABP1 promoter, and thereby may link FABP1 gene variation to TG level in humans. PMID:26439934

  13. Association of a Human FABP1 Gene Promoter Region Polymorphism with Altered Serum Triglyceride Levels.

    PubMed

    Peng, Xian-E; Wu, Yun-Li; Zhu, Yi-Bing; Huang, Rong-Dong; Lu, Qing-Qing; Lin, Xu

    2015-01-01

    Liver fatty acid-binding protein (L-FABP), also known as fatty acid-binding protein 1 (FABP1), is a key regulator of hepatic lipid metabolism. Elevated FABP1 levels are associated with an increased risk of cardiovascular disease (CVD) and metabolic syndromes. In this study, we examine the association of FABP1 gene promoter variants with serum FABP1 and lipid levels in a Chinese population. Four promoter single-nucleotide polymorphisms (SNPs) of FABP1 gene were genotyped in a cross-sectional survey of healthy volunteers (n = 1,182) from Fuzhou city of China. Results showed that only the rs2919872 G>A variant was significantly associated with serum TG concentration(P = 0.032).Compared with the rs2919872 G allele, rs2919872 A allele contributed significantly to reduced serum TG concentration, and this allele dramatically decreased the FABP1 promoter activity(P < 0.05). The rs2919872 A allele carriers had considerably lower serum FABP1 levels than G allele carriers (P < 0.01). In the multivariable linear regression analysis, the rs2919872 A allele was negatively associated with serum FABP1 levels (β = -0.320, P = 0.003), while serum TG levels were positively associated with serum FABP1 levels (β = 0.487, P = 0.014). Our data suggest that compared with the rs2919872 G allele, the rs2919872 A allele reduces the transcriptional activity of FABP1 promoter, and thereby may link FABP1 gene variation to TG level in humans. PMID:26439934

  14. Genomic study in Mexicans identifies a new locus for triglycerides and refines European lipid loci

    PubMed Central

    Weissglas-Volkov, Daphna; Aguilar-Salinas, Carlos A.; Nikkola, Elina; Deere, Kerry A.; Cruz-Bautista, Ivette; Arellano-Campos, Olimpia; Muoz-Hernandez, Linda Liliana; Gomez-Munguia, Lizeth; Ordoez-Snchez, Maria Luisa; Reddy, Prasad MV Linga; Lusis, Aldons J.; Matikainen, Niina; Taskinen, Marja-Riitta; Riba, Laura; Cantor, Rita M.; Sinsheimer, Janet S.; Tusie-Luna, Teresa; Pajukanta, Pivi

    2013-01-01

    Background The Mexican population and others with Amerindian heritage exhibit a substantial predisposition to dyslipidemias and coronary heart disease. Yet, these populations remain underinvestigated by genomic studies, and to date, no genome-wide association (GWA) studies have been reported for lipids in these rapidly expanding populations. Methods and Findings We performed a two-stage GWA study for hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) in Mexicans (n=4,361) and identified a novel Mexican-specific genome-wide significant locus for serum triglycerides (TGs) near the Niemann-Pick type C1 protein (NPC1) gene (P=2.4310?08). Furthermore, three European loci for TGs (APOA5, GCKR, and LPL) and four loci for HDL-C (ABCA1, CETP, LIPC and LOC55908) reached genome-wide significance in Mexicans. We utilized cross-ethnic mapping to narrow three European TG GWA loci, APOA5, MLXIPL, and CILP2 that were wide and contained multiple candidate variants in the European scan. At the APOA5 locus, this reduced the most likely susceptibility variants to one, rs964184. Importantly, our functional analysis demonstrated a direct link between rs964184 and postprandial serum apoAV protein levels, supporting rs964184 as the causative variant underlying the European and Mexican GWA signal. Overall, 52 of the 100 reported associations from European lipid GWA meta-analysis generalized to Mexicans. However, in 82 of the 100 European GWA loci, a different variant other than the European lead/best-proxy variant had the strongest regional evidence of association in Mexicans. Conclusions This first Mexican GWA study of lipids identified a novel GWA locus for high TG levels; utilized the inter-population heterogeneity to significantly restrict three previously known European GWA signals; and surveyed whether the European lipid GWA SNPs extend to the Mexican population. PMID:23505323

  15. Cytokeratin 18, Alanine Aminotransferase, Platelets and Triglycerides Predict the Presence of Nonalcoholic Steatohepatitis

    PubMed Central

    Cao, Wei; Zhao, Caiyan; Shen, Chuan; Wang, Yadong

    2013-01-01

    Background Nonalcoholic fatty liver disease (NAFLD) is one of the critical public health problems in China. The full spectrum of the disease ranges from simple steatosis and nonalcoholic steatohepatitis (NASH) to cirrhosis and hepatocellular carcinoma(HCC). The infiltration of inflammatory cells characterizes NASH. This characteristic contributes to the progression of hepatitis, fibrosis, cirrhosis, and HCC. Therefore, distinguishing NASH from NAFLD is crucial. Objective and Methods Ninety-five patients with NAFLD, 44 with NASH, and 51 with non-NASH were included in the study to develop a new scoring system for differentiating NASH from NAFLD. Data on clinical and biological characteristics, as well as blood information, were obtained. Cytokeratin-18 (CK-18) fragments levels were measured using an enzyme-linked immunosorbant assay. Results Several indexes show significant differences between the two groups, which include body mass index (BMI), waist-on-hip ratio (WHR), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), ?-glutamyl transpeptidase (?-GT), platelets, uric acid (UA), hs-C-reactive protein (hs-CRP), triglycerides (TG), albumin (ALB), and CK-18 fragments (all P < 0.05). The CK-18 fragment levels showed a significant positive correlation with steatosis severity, ballooning, lobular inflammation, and fibrosis stage (all P < 0.05). Therefore, a new model that combines ALT, platelets, CK-18 fragments, and TG was established by logistic regression among NAFLD patients. The AUROC curve in predicting NASH was 0.920 (95% CI: 0.866 - 0.974, cutoff value = 0.361, sensitivity = 89%, specificity = 86%, positive predictive value = 89%, negative predictive value = 89%). Conclusion The novel scoring system may be considered as a useful model in predicting the presence of NASH in NAFLD patients. PMID:24324749

  16. Interactions of the apolipoprotein C-III 3238C>G polymorphism and alcohol consumption on serum triglyceride levels

    PubMed Central

    2010-01-01

    Background Both apolipoprotein (Apo) C-III gene polymorphism and alcohol consumption have been associated with increased serum triglyceride (TG) levels, but their interactions on serum TG levels are not well known. The present study was undertaken to detect the interactions of the ApoC-III 3238C>G (rs5128) polymorphism and alcohol consumption on serum TG levels. Methods A total of 516 unrelated nondrinkers and 514 drinkers aged 15-89 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the ApoC-III 3238C>G was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Interactions of the ApoC-III 3238C>G genotype and alcohol consumption was assessed by using a cross-product term between genotypes and the aforementioned factor. Results Serum total cholesterol (TC), TG, high-density lipoprotein cholesterol (HDL-C), ApoA-I and ApoB levels were higher in drinkers than in nondrinkers (P < 0.05-0.001). There was no significant difference in the genotypic and allelic frequencies between the two groups. Serum TG levels in nondrinkers were higher in CG genotype than in CC genotype (P < 0.01). Serum TC, TG, low-density lipoprotein cholesterol (LDL-C) and ApoB levels in drinkers were higher in GG genotype than in CC or CG genotype (P < 0.01 for all). Serum HDL-C levels in drinkers were higher in CG genotype than in CC genotype (P < 0.01). Serum TC, TG, HDL-C and ApoA-I levels in CC genotype, TC, HDL-C, ApoA-I levels and the ratio of ApoA-I to ApoB in CG genotype, and TC, TG, LDL-C, ApoA-I and ApoB levels in GG genotype were higher in drinkers than in nondrinkers (P < 0.05-0.01). But the ratio of ApoA-I to ApoB in GG genotype was lower in drinkers than in nondrinkers (P < 0.01). Multivariate logistic regression analysis showed that the levels of TC, TG and ApoB were correlated with genotype in nondrinkers (P < 0.05 for all). The levels of TC, LDL-C and ApoB were associated with genotype in drinkers (P < 0.01 for all). Serum lipid parameters were also correlated with age, sex, alcohol consumption, cigarette smoking, blood pressure, body weight, and body mass index in both groups. Conclusions This study suggests that the ApoC-III 3238CG heterozygotes benefited more from alcohol consumption than CC and GG homozygotes in increasing serum levels of HDL-C, ApoA-I, and the ratio of ApoA-I to ApoB, and lowering serum levels of TC and TG. PMID:20716347

  17. Elevated Levels of Urinary Markers of Oxidative DNA and RNA Damage in Type 2 Diabetes with Complications

    PubMed Central

    Liu, Xinle; Gan, Wei; Zou, Yuangao; Su, Zhenzhen; Deng, Jin; Wang, Lanlan

    2016-01-01

    The mechanisms underlying progression of type 2 diabetes are complex and varied. Recent studies indicated that oxidative stress provided a new sight. To further assess the relationship between nucleic acid oxidation and complications in patients with type 2 diabetes and explore its possible molecular mechanisms, we studied 1316 subjects, including 633 type 2 diabetes patients and 683 age- and sex-matched healthy controls. Urinary levels of DNA oxidation marker 8-oxo-7,8-dihydro-2?-deoxyguanosine (8-oxodGuo) and RNA oxidation marker 8-oxo-7,8-dihydroguanosine (8-oxoGuo) were measured by ultraperformance liquid chromatography and mass spectrometry (UPLC-MS/MS). Serum glucose, HbA1c, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides (TG) were also determined. The results showed significantly elevated levels of both the urinary 8-oxodGuo and 8-oxoGuo in diabetes patients with/without complications compared with age-matched healthy control subjects (p = 0.02 and p < 0.001, resp.). Patients with complications, especially macrovascular complications, exhibited higher levels of 8-oxoGuo than those without complications, while there was no difference in the concentrations of serum glucose and lipids. The finding indicates the role for oxidative damage to DNA and RNA, as a molecular mechanism contributing to the progression of type 2 diabetes. Elevated levels of 8-oxoGuo may be a risk factor for type 2 diabetes complications, especially in diabetic macrovascular complications. PMID:26770653

  18. log(TG)/HDL-C is related to both residual cardiometabolic risk and β-cell function loss in type 2 diabetes males

    PubMed Central

    2010-01-01

    Background T2DM is associated with atherogenic dyslipidemia (AD), defined as decreased HDL-C plus raised triglycerides (TG). AD confers increased risk for CAD, even when LDL-C is at target. AD is rarely assessed due to lack of screening methods consensus. Aim To establish the prevalence and severity of AD from log(TG)/HDL-C in T2DM males, and to determine how it relates to cardiometabolic phenotype, glucose homeostasis, micro- and macrovascular complications, and 10-year UKPDS CV risk. Methods 585 T2DM males divided according to quintiles (Q) of log(TG)/HDL-C. AD prevalence defined as HDL-C <40 mg.dL-1 plus TG ≥150 mg.dL-1. β-cell function assessed with HOMA. Results Mean HDL-C and TG were 44 (13) and 204 (155) mg.dL-1. AD prevalence was 35%. AD correlated with lower β-cell function, with accelerated loss of insulin secretion, and with poorer HbA1c levels. AD was related to a high prevalence of CAD, and also to 10-year absolute CAD risk. Conclusions log(TG)/HDL-C is a simple means to estimate AD and the residual CV risk it confers in T2DM. AD closely associates with major cardiometabolic and glucose homeostasis determinants and poorer metabolic control. The ratio also relates to macroangiopathy prevalence and ranks future CAD risk, and is well-suited to capture non-LDL-related macrovascular residual risk and major glycemic determinants. PMID:21156040

  19. Effects of the short-chain triglyceride triacetin on intestinal mucosa and metabolic substrates in rats.

    PubMed

    Lynch, J W; Miles, J M; Bailey, J W

    1994-01-01

    Diets containing either triacetin (the water-soluble triglyceride of acetate) or long-chain triglycerides (LCTs) were fed to rats to determine the effects on intestinal mucosa cells and plasma substrates. Male Sprague-Dawley rats were fed one of three diets, a control diet containing 5% of energy as LCTs or one of two experimental diets that contained 30% of energy as lipid. The lipid component of the two experimental diets was either 100% LCTs or 95% triacetin/5% LCTs. Plasma lactate, glucose, and total ketone body concentrations were not significantly different among dietary treatment groups. Compared with animals fed LCTs and control diet, plasma pyruvate and free fatty acid concentrations were decreased in animals fed triacetin. In contrast, plasma triglyceride concentrations were elevated in animals fed triacetin compared with other groups. Intestinal biochemical measures included total DNA, RNA, protein, and the protein:DNA ratio. Histologic indices measured were villus height in the jejunum and crypt depth in the colon. No significant difference in mucosal protein concentration was observed in the jejunum and colon. Jejunal RNA was significantly decreased in animals fed triacetin compared with other diets. Triacetin feeding significantly increased the DNA content in the jejunum and colon (thereby lowering the protein:DNA ratio), indicating smaller, more numerous cells. Jejunal villus height and colonic crypt depth were not significantly different among dietary treatment groups. Provision of a balanced diet containing 28.5% of the total calories as triacetin had no adverse effects on metabolic substrates and resulted in smaller and more numerous mucosal cells in the jejunum and colon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7520510

  20. Low density lipoprotein delays clearance of triglyceride-rich lipoprotein by human subcutaneous adipose tissue

    PubMed Central

    Bissonnette, Simon; Salem, Huda; Wassef, Hanny; Saint-Pierre, Nathalie; Tardif, Annie; Baass, Alexis; Dufour, Robert; Faraj, May

    2013-01-01

    Delayed clearance of triglyceride-rich lipoprotein (TRL) by white adipose tissue (WAT) promotes hypertriglyceridemia and elevated apoB-lipoproteins, which are primarily in the form of LDL. This study examines whether LDL promotes delayed clearance of TRL by WAT. Following the ingestion of a 13C-triolein-labeled high-fat meal, obese women with high plasma apoB (> median 0.93 g/l, N = 11, > 98% as IDL/LDL) had delayed clearance of postprandial 13C-triglyceride and 13C-NEFA over 6 h compared with controls. AUC6 h of plasma 13C-triglyceride and 13C-NEFA correlated with plasma apoB but not with LDL diameter or adipocyte area. There was no group difference in 13C-triolein oxidation rate, which suggests lower 13C-NEFA storage in peripheral tissue in women with high apoB. Ex vivo/in vitro plasma apoB correlated negatively with WAT 3H-lipid following a 4 h incubation of women's WAT with synthetic 3H-triolein-TRL. LDL-differentiated 3T3-L1 adipocytes had lower 3H-TRL hydrolysis and 3H-NEFA storage. Treatment of women's WAT with their own LDL decreased 3H-TRL hydrolysis and 3H-NEFA uptake. Finally, LDL, although not an LPL substrate, reduced LPL-mediated 3H-TRL hydrolysis as did VLDL and HDL. Exposure to LDL decreases TRL clearance by human WAT ex vivo. This may promote production of apoB-lipoproteins and hypertriglyceridemia through a positive-feedback mechanism in vivo. PMID:23417739

  1. Bioactivity-guided fractionation of the triglyceride-lowering component and in vivo and in vitro evaluation of hypolipidemic effects of Calyx seu Fructus Physalis

    PubMed Central

    2012-01-01

    Background In folklore, some people take the decoction of Calyx seu Fructus Physalis (CSFP) for lowering blood lipids. The present study is designed to evaluate the lipid-lowering activities of CSFP, and search for its pharmacodynamical material. Methods CSFP was extracted by water and 75% ethanol, respectively. The extracts of CSFP for reducing serum lipid levels were evaluated on mouse model of hyperlipidemia. The optimized extract was subjected to the bioactivity-guided fractionation in which the liquid-liquid extraction, collumn chromatography, the in vivo and in vitro models of hyperlipidemia were utilized. The structure of active component was determined by 13 C-NMR and 1H-NMR. Results The 75% ethanol extract of CSFP decreased the serum total cholesterol (TC) and triglyceride (TG) levels in mouse model of hyperlipidemia. Followed a separation process for the 75% ethanol extract of CSFP, the fraction B was proved to be an active fraction for lowering lipid in vivo and in vitro experiments, which could significantly decrease the serum TC and TG levels in mouse model of hyperlipidemia, and remarkably decrease the increase of TG in primary mouse hepatocytes induced by high glucose and the increase of TG in HepG2 cells induced by oleic acid. The fraction B2, isolated from B on bioactivity-guided fractionation, could significantly decrease TG level in HepG2 cells. One compound with the highest content in B2 was isolated and determined as luteolin-7-O-beta-D-glucopyranoside by NMR spectra. It could significantly reduce the TG level in HepG2 cells, and inhibited the accumulation of lipids by oil red O stain. Conclusion Our results demonstrated that the 75% ethanol extract of CSFP could improve in vitro and in vivo lipid accumulation. Luteolin-7-O-beta-D-glucopyranoside might be a leading pharmacodynamical material of CSFP for lowering lipids. PMID:22413998

  2. The Role of Triglyceride in Cardiovascular Disease in Asian Patients with Type 2 Diabetes - A Systematic Review

    PubMed Central

    Chen, Ai-Hua; Tseng, Chin-Hsiao

    2013-01-01

    In Asian populations, diabetes mellitus is increasing and has become an important health problem in recent decades. Cardiovascular disease (CVD) is one of the most important complications and the most common cause of death in diabetic patients. Among the risk factors of CVD, elevated low-density lipoprotein cholesterol has been a major concern. Studies suggested that serum triglyceride may also play a role in predicting CVD in patients with type 2 diabetes mellitus, but the association is still debated. In this review, we summarized published studies focusing on the relationship between serum triglyceride and CVD disease in Asian diabetic patients. Ten studies conducted in six different Asian countries (three from Hong Kong, two from Taiwan, tow from Japan, one from Indonesia, one from South India, and one from South Korea) were summarized and discussed. CVD was subdivided into coronary heart disease, stroke, and peripheral arterial disease. Of the ten studies analyzed, one focused on CVD, five on coronary heart disease, three on stroke, three on peripheral arterial disease, and one on mortality from CVD. Studies from Hong Kong, Taiwan, and Japan suggested that triglyceride is a significant and independent risk factor for coronary heart disease, but not a significant risk factor for stroke (studies conducted in Japan and South Korea) or peripheral arterial disease (studies conducted in Taiwan, Indonesia, and South India). Although serum triglyceride may be a significant risk factor for coronary heart disease in Asian diabetic patients, clinical trials evaluating whether lowering triglycerides using fibrates can reduce the risk of coronary heart disease in these patients need to be initiated. PMID:24380086

  3. The role of triglyceride in cardiovascular disease in asian patients with type 2 diabetes--a systematic review.

    PubMed

    Chen, Ai-Hua; Tseng, Chin-Hsiao

    2013-01-01

    In Asian populations, diabetes mellitus is increasing and has become an important health problem in recent decades. Cardiovascular disease (CVD) is one of the most important complications and the most common cause of death in diabetic patients. Among the risk factors of CVD, elevated low-density lipoprotein cholesterol has been a major concern. Studies suggested that serum triglyceride may also play a role in predicting CVD in patients with type 2 diabetes mellitus, but the association is still debated. In this review, we summarized published studies focusing on the relationship between serum triglyceride and CVD disease in Asian diabetic patients. Ten studies conducted in six different Asian countries (three from Hong Kong, two from Taiwan, tow from Japan, one from Indonesia, one from South India, and one from South Korea) were summarized and discussed. CVD was subdivided into coronary heart disease, stroke, and peripheral arterial disease. Of the ten studies analyzed, one focused on CVD, five on coronary heart disease, three on stroke, three on peripheral arterial disease, and one on mortality from CVD. Studies from Hong Kong, Taiwan, and Japan suggested that triglyceride is a significant and independent risk factor for coronary heart disease, but not a significant risk factor for stroke (studies conducted in Japan and South Korea) or peripheral arterial disease (studies conducted in Taiwan, Indonesia, and South India). Although serum triglyceride may be a significant risk factor for coronary heart disease in Asian diabetic patients, clinical trials evaluating whether lowering triglycerides using fibrates can reduce the risk of coronary heart disease in these patients need to be initiated. PMID:24380086

  4. Mitochondrial dysfunction induces triglyceride accumulation in 3T3-L1 cells: role of fatty acid beta-oxidation and glucose.

    PubMed

    Vankoningsloo, Sbastien; Piens, Marie; Lecocq, Christophe; Gilson, Audrey; De Pauw, Aurlia; Renard, Patricia; Demazy, Catherine; Houbion, Andre; Raes, Martine; Arnould, Thierry

    2005-06-01

    Mitochondrial cytopathy has been associated with modifications of lipid metabolism in various situations, such as the acquisition of an abnormal adipocyte phenotype observed in multiple symmetrical lipomatosis or triglyceride (TG) accumulation in muscles associated with the myoclonic epilepsy with ragged red fibers syndrome. However, the molecular signaling leading to fat metabolism dysregulation in cells with impaired mitochondrial activity is still poorly understood. Here, we found that preadipocytes incubated with inhibitors of mitochondrial respiration such as antimycin A (AA) accumulate TG vesicles but do not acquire specific markers of adipocytes. Although the uptake of TG precursors is not stimulated in 3T3-L1 cells with impaired mitochondrial activity, we found a strong stimulation of glucose uptake in AA-treated cells mediated by calcium and phosphatidylinositol 3-kinase/Akt1/glycogen synthase kinase 3beta, a pathway known to trigger the translocation of glucose transporter 4 to the plasma membrane in response to insulin. TG accumulation in AA-treated cells is mediated by a reduced peroxisome proliferator-activated receptor gamma activity that downregulates muscle carnitine palmitoyl transferase-1 expression and fatty acid beta-oxidation, and by a direct conversion of glucose into TGs accompanied by the activation of carbohydrate-responsive element binding protein, a lipogenic transcription factor. Taken together, these results could explain how mitochondrial impairment leads to the multivesicular phenotype found in some mitochondria-originating diseases associated with a dysfunction in fat metabolism. PMID:15741651

  5. A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans.

    PubMed

    Timpson, Nicholas J; Walter, Klaudia; Min, Josine L; Tachmazidou, Ioanna; Malerba, Giovanni; Shin, So-Youn; Chen, Lu; Futema, Marta; Southam, Lorraine; Iotchkova, Valentina; Cocca, Massimiliano; Huang, Jie; Memari, Yasin; McCarthy, Shane; Danecek, Petr; Muddyman, Dawn; Mangino, Massimo; Menni, Cristina; Perry, John R B; Ring, Susan M; Gaye, Amadou; Dedoussis, George; Farmaki, Aliki-Eleni; Burton, Paul; Talmud, Philippa J; Gambaro, Giovanni; Spector, Tim D; Smith, George Davey; Durbin, Richard; Richards, J Brent; Humphries, Steve E; Zeggini, Eleftheria; Soranzo, Nicole

    2014-01-01

    The analysis of rich catalogues of genetic variation from population-based sequencing provides an opportunity to screen for functional effects. Here we report a rare variant in APOC3 (rs138326449-A, minor allele frequency ~0.25% (UK)) associated with plasma triglyceride (TG) levels (-1.43 s.d. (s.e.=0.27 per minor allele (P-value=8.0 10(-8))) discovered in 3,202 individuals with low read-depth, whole-genome sequence. We replicate this in 12,831 participants from five additional samples of Northern and Southern European origin (-1.0 s.d. (s.e.=0.173), P-value=7.32 10(-9)). This is consistent with an effect between 0.5 and 1.5 mmol l(-1) dependent on population. We show that a single predicted splice donor variant is responsible for association signals and is independent of known common variants. Analyses suggest an independent relationship between rs138326449 and high-density lipoprotein (HDL) levels. This represents one of the first examples of a rare, large effect variant identified from whole-genome sequencing at a population scale. PMID:25225788

  6. A rare variant in APOC3 is associated with plasma triglyceride and VLDL levels in Europeans

    PubMed Central

    Timpson, Nicholas J.; Walter, Klaudia; Min, Josine L.; Tachmazidou, Ioanna; Malerba, Giovanni; Shin, So-Youn; Chen, Lu; Futema, Marta; Southam, Lorraine; Iotchkova, Valentina; Cocca, Massimiliano; Huang, Jie; Memari, Yasin; McCarthy, Shane; Danecek, Petr; Muddyman, Dawn; Mangino, Massimo; Menni, Cristina; Perry, John R. B.; Ring, Susan M.; Gaye, Amadou; Dedoussis, George; Farmaki, Aliki-Eleni; Burton, Paul; Talmud, Philippa J.; Gambaro, Giovanni; Spector, Tim D.; Smith, George Davey; Durbin, Richard; Richards, J Brent; Humphries, Steve E.; Zeggini, Eleftheria; Soranzo, Nicole; Al Turki, Saeed; Anderson, Carl; Anney, Richard; Antony, Dinu; Soler Artigas, Maria; Ayub, Muhammad; Balasubramaniam, Senduran; Barrett, Jeffrey C.; Barroso, Inês; Beales, Phil; Bentham, Jamie; Bhattacharya, Shoumo; Birney, Ewan; Blackwood, Douglas; Bobrow, Martin; Bochukova, Elena; Bolton, Patrick; Bounds, Rebecca; Boustred, Chris; Breen, Gerome; Calissano, Mattia; Carss, Keren; Chatterjee, Krishna; Chen, Lu; Ciampi, Antonio; Cirak, Sebhattin; Clapham, Peter; Clement, Gail; Coates, Guy; Collier, David; Cosgrove, Catherine; Cox, Tony; Craddock, Nick; Crooks, Lucy; Curran, Sarah; Curtis, David; Daly, Allan; Danecek, Petr; Davey Smith, George; Day-Williams, Aaron; Day, Ian N. M.; Down, Thomas; Du, Yuanping; Dunham, Ian; Durbin, Richard; Edkins, Sarah; Ellis, Peter; Evans, David; Faroogi, Sadaf; Fatemifar, Ghazaleh; Fitzpatrick, David R.; Flicek, Paul; Flyod, James; Foley, A Reghan; Franklin, Christopher S; Futema, Marta; Gallagher, Louise; Gaunt, Tom; Geihs, Matthias; Geschwind, Daniel; Greenwood, Celia; Griffin, Heather; Grozeva, Detelina; Guo, Xueqin; Guo, Xiaosen; Gurling, Hugh; Hart, Deborah; Hendricks, Audrey; Holmans, Peter; Howie, Bryan; Huang, Jie; Huang, Liren; Hubbard, Tim; Humphries, Steve E.; Hurles, Matthew E.; Hysi, Pirro; Jackson, David K.; Jamshidi, Yalda; Jing, Tian; Joyce, Chris; Kaye, Jane; Keane, Thomas; Keogh, Julia; Kemp, John; Kennedy, Karen; Kolb-Kokocinski, Anja; Lachance, Genevieve; Langford, Cordelia; Lawson, Daniel; Lee, Irene; Lek, Monkol; Liang, Jieqin; Lin, Hong; Li, Rui; Li, Yingrui; Liu, Ryan; Lönnqvist, Jouko; Lopes, Margarida; Lotchkova, Valentina; MacArthur, Daniel; Marchini, Jonathan; Maslen, John; Massimo, Mangino; Mathieson, Iain; Marenne, Gaëlle; McCarthy, Shane; McGuffin, Peter; McIntosh, Andrew; McKechanie, Andrew G.; McQuillin, Andrew; Memari, Yasin; Metrustry, Sarah; Min, Josine; Mitchison, Hannah; Moayyeri, Alireza; Morris, James; Muddyman, Dawn; Muntoni, Francesco; Northstone, Kate; O'Donnovan, Michael; Onoufriadis, Alexandros; O'Rahilly, Stephen; Oualkacha, Karim; Owen, Michael J.; Palotie, Aarno; Panoutsopoulou, Kalliope; Parker, Victoria; Parr, Jeremy R.; Paternoster, Lavinia; Paunio, Tiina; Payne, Felicity; Perry, John; Pietilainen, Olli; Plagnol, Vincent; Quaye, Lydia; Quail, Michael A.; Raymond, Lucy; Rehnström, Karola; Richards, Brent; Ring, Susan; Ritchie, Graham R. S.; Roberts, Nicola; Savage, David B.; Scambler, Peter; Schiffels, Stephen; Schmidts, Miriam; Schoenmakers, Nadia; Semple, Robert K.; Serra, Eva; Sharp, Sally I.; Shihab, Hasheem; Shin, So-Youn; Skuse, David; Small, Kerrin; Soranzo, Nicole; Southam, Lorraine; Spasic-Boskovic, Olivera; Spector, Tim; St Clair, David; Stalker, Jim; Stevens, Elizabeth; St Pourcian, Beate; Sun, Jianping; Surdulescu, Gabriela; Suvisaari, Jaana; Tachmazidou, Ionna; Timpson, Nicholas; Tobin, Martin D.; Valdes, Ana; Van Kogelenberg, Margriet; Vijayarangakannan, Parthiban; Visscher, Peter M.; Wain, Louise V.; Walter, Klaudia; Walters, James T. R.; Wang, Guangbiao; Wang, Jun; Wang, Yu; Ward, Kirsten; Wheeler, Elanor; Whyte, Tamieka; Williams, Hywel; Williamson, Kathleen A.; Wilson, Crispian; Wilson, Scott G.; Wong, Kim; Xu, ChangJiang; Yang, Jian; Zeggini, Eleftheria; Zhang, Fend; Zhang, Pingbo; Zheng, Hou-Feng

    2014-01-01

    The analysis of rich catalogues of genetic variation from population-based sequencing provides an opportunity to screen for functional effects. Here we report a rare variant in APOC3 (rs138326449-A, minor allele frequency ~0.25% (UK)) associated with plasma triglyceride (TG) levels (−1.43 s.d. (s.e.=0.27 per minor allele (P-value=8.0 × 10−8)) discovered in 3,202 individuals with low read-depth, whole-genome sequence. We replicate this in 12,831 participants from five additional samples of Northern and Southern European origin (−1.0 s.d. (s.e.=0.173), P-value=7.32 × 10−9). This is consistent with an effect between 0.5 and 1.5 mmol l−1 dependent on population. We show that a single predicted splice donor variant is responsible for association signals and is independent of known common variants. Analyses suggest an independent relationship between rs138326449 and high-density lipoprotein (HDL) levels. This represents one of the first examples of a rare, large effect variant identified from whole-genome sequencing at a population scale. PMID:25225788

  7. Association of ADRB2 polymorphism with triglyceride levels in Tongans

    PubMed Central

    2013-01-01

    Background Our previous study demonstrated that the A-allele of the single nucleotide polymorphism (SNP) rs34623097 located in the upstream region of the ?2 adrenergic receptor gene (ADRB2) is significantly associated with risk for obesity in Oceanic populations. Methods To investigate whether the ADRB2 polymorphisms explain part of the individual differences in lipid mobilization, energy expenditure and glycogen breakdown, the associations of 10 ADRB2 SNPs with total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride levels were examined in 128 adults in Tonga. Results A multiple linear regression analysis adjusted for age, sex, and body mass index revealed that rs34623097 was significantly associated with triglyceride levels (P-value?=?0.037). A copy of the rs34623097-A allele increased serum triglyceride levels by 70.1mg/dL (0.791mmol/L). None of the ADRB2 SNPs showed a significant association with total-cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol. Conclusions In a Tongan population, a SNP located in the upstream region of ADRB2 is associated with triglyceride levels independent of body mass index. PMID:23875540

  8. Mutations of the microsomal triglyceride-transfer-protein gene in abetalipoproteinemia

    SciTech Connect

    Narcisi, T.M.E.; Shoulders, C.C.; Chester, S.A.

    1995-12-01

    Elevated plasma levels of apolipoprotein B (apoB)-containing lipoproteins constitute a major risk factor for the development of coronary heart disease. In the rare recessively inherited disorder abetalipoproteinemia (ABL) the production of apoB-containing lipoproteins is abolished, despite no abnormality of the apoB gene. In the current study we have characterized the gene encoding a microsomal triglyceride-transfer protein (MTP), localized to chromosome 4q22-24, and have identified a mutation of the MTP gene in both alleles of all individuals in a cohort of eight patients with classical ABL. Each mutant allele is predicted to encode a truncated form of MTP with a variable number of aberrant amino acids at its C-terminal end. Expression of genetically engineered forms of MTP in Cos-1 cells indicates that the C-terminal portion of MTP is necessary for triglyceride-transfer activity. Deletion of 20 amino acids from the carboxyl terminus of the 894-amino-acid protein and a missense mutation of cysteine 878 to serine both abolished activity. These results establish that defects of the MTP gene are the predominant, if not sole, cause of hereditary ABL and that an intact carboxyl terminus is necessary for activity. 49 refs., 4 figs., 5 tabs.

  9. Rice protein improves adiposity, body weight and reduces lipids level in rats through modification of triglyceride metabolism

    PubMed Central

    2012-01-01

    Background To elucidate whether rice protein can possess a vital function in improving lipids level and adiposity, the effects of rice proteins extracted by alkaline (RP-A) and ?-amylase (RP-E) on triglyceride metabolism were investigated in 7-week-old male Wistar rats fed cholesterol-enriched diets for 2 weeks, as compared with casein (CAS). Results Compared with CAS, plasma concentrations of glucose and lipids were significantly reduced by RP-feeding (P < 0.05), as well as hepatic accumulation of lipids (P < 0.05). RP-A and RP-E significantly depressed the hepatic activities of fatty acid synthase (FAS), glucose 6-phosphate dehydrogenase (G6PD) and malate dehydrogenase (MDH) (P < 0.05), whereas the activities of lipoprotein lipase (PL) and hepatic lipase (HL) were significantly stimulated (P < 0.05), as compared to CAS. Neither lipids level nor activities of enzymes were different between RP-A and RP-E (P > 0.05). There was a significant positive correlation between protein digestibility and deposit fat (r = 0.8567, P < 0.05), as well as the plasma TG concentration (r = 0.8627, P < 0.05). Conclusions The present study demonstrates that rice protein can modify triglyceride metabolism, leading to an improvement of body weight and adiposity. Results suggest that the triglyceride-lowering action as well as the potential of anti-adiposity induced by rice protein is attributed to upregulation of lipolysis and downregulation of lipogenesis, and the lower digestibility of rice protein may be the main modulator responsible for the lipid-lowering action. PMID:22330327

  10. Autoimmune Manifestations in the 3xTg-AD Model of Alzheimer's Disease

    PubMed Central

    Marchese, Monica; Cowan, David; Head, Elizabeth; Ma, Donglai; Karimi, Khalil; Ashthorpe, Vanessa; Kapadia, Minesh; Zhao, Hui; Davis, Paulina; Sakic, Boris

    2015-01-01

    Background Immune system activation is frequently reported in patients with Alzheimer's disease (AD). However, it remains unknown whether this is a cause, a consequence, or an epiphenomenon of brain degeneration. Objective The present study examines whether immunological abnormalities occur in a well-established murine AD model and if so, how they relate temporally to behavioral deficits and neuropathology. Methods A broad battery of tests was employed to assess behavioral performance and autoimmune/inflammatory markers in 3xTg-AD (AD) mice and wild type controls from 1.5 to 12 months of age. Results Aged AD mice displayed severe manifestations of systemic autoimmune/inflammatory disease, as evidenced by splenomegaly, hepatomegaly, elevated serum levels of anti-nuclear/anti-dsDNA antibodies, low hematocrit, and increased number of double-negative T splenocytes. However, anxiety-related behavior and altered spleen function were evident as early as 2 months of age, thus preceding typical AD-like brain pathology. Moreover, AD mice showed altered olfaction and impaired “cognitive” flexibility in the first 6 months of life, suggesting mild cognitive impairment-like manifestations before general learning/memory impairments emerged at an older age. Interestingly, all of these features were present in 3xTg-AD mice prior to significant amyloid-β or tau pathology. Conclusion The results indicate that behavioral deficits in AD mice develop in parallel with systemic autoimmune/inflammatory disease. These changes antedate AD-like neuropathology, thus supporting a causal link between autoimmunity and aberrant behavior. Consequently, 3xTg-AD mice may be a useful model in elucidating the role of immune system in the etiology of AD. PMID:24150111

  11. Chain length affects pancreatic lipase activity and the extent and pH-time profile of triglyceride lipolysis.

    PubMed

    Benito-Gallo, Paloma; Franceschetto, Alessandro; Wong, Jonathan C M; Marlow, Maria; Zann, Vanessa; Scholes, Peter; Gershkovich, Pavel

    2015-06-01

    Triglycerides (TG) are one of the most common excipients used in oral lipid-based formulations. The chain length of the TG plays an important role in the oral bioavailability of the co-administered drug. Fatty acid (FA) chain-length specificity of porcine pancreatic lipase was studied by means of an in vitro lipolysis model under bio-relevant conditions at pH 6.80. In order to determine the total extent of lipolysis, back-titration experiments at pH 11.50 were performed. Results suggest that there is a specific chain length range (C2-C8) for which pancreatic lipase shows higher activity. This specificity could result from a combination of physicochemical properties of TGs, 2-monoglycerides (2-MGs) and FAs, namely the droplet size of the TGs, the solubility of 2-MGs within mixed micelles, and the relative stability of the FAs as leaving groups in the hydrolysis reaction. During experimentation, it was evident that an optimisation of lipolysis conditions was needed for tighter control over pH levels so as to better mimic in vivo conditions. 1M NaOH, 3.5 mL/min maximum dosing rate, and 3 μL/min minimum dosing rate were the optimised set of conditions that allowed better pH control, as well as the differentiation of the lipolysis of different lipid loads. PMID:25936853

  12. Identification of a novel phosphorylation site in adipose triglyceride lipase as a regulator of lipid droplet localization.

    PubMed

    Xie, Xitao; Langlais, Paul; Zhang, Xiaodong; Heckmann, Bradlee L; Saarinen, Alicia M; Mandarino, Lawrence J; Liu, Jun

    2014-06-15

    Adipose triglyceride lipase (ATGL), the rate-limiting enzyme for triacylglycerol (TG) hydrolysis, has long been known to be a phosphoprotein. However, the potential phosphorylation events that are involved in the regulation of ATGL function remain incompletely defined. Here, using a combinatorial proteomics approach, we obtained evidence that at least eight different sites of ATGL can be phosphorylated in adipocytes. Among them, Thr³⁷² resides within the hydrophobic region known to mediate lipid droplet (LD) targeting. Although it had no impact on the TG hydrolase activity, substitution of phosphorylation-mimic Asp for Thr³⁷² eliminated LD localization and LD-degrading capacity of ATGL expressed in HeLa cells. In contrast, mutation of Thr³⁷² to Ala gave a protein that bound LDs and functioned the same as the wild-type protein. In nonstimulated adipocytes, the Asp mutation led to decreased LD association and basal lipolytic activity of ATGL, whereas the Ala mutation produced opposite effects. Moreover, the LD translocation of ATGL upon β-adrenergic stimulation was also compromised by the Asp mutation. In accord with these findings, the Ala mutation promoted and the Asp mutation attenuated the capacity of ATGL to mediate lipolysis in adipocytes under both basal and stimulated conditions. Collectively, these studies identified Thr³⁷² as a novel phosphorylation site that may play a critical role in determining subcellular distribution as well as lipolytic action of ATGL. PMID:24801391

  13. Brown adipose tissue takes up plasma triglycerides mostly after lipolysis

    PubMed Central

    Khedoe, P. Padmini S. J.; Hoeke, Geerte; Kooijman, Sander; Dijk, Wieneke; Buijs, Jeroen T.; Kersten, Sander; Havekes, Louis M.; Hiemstra, Pieter S.; Berbée, Jimmy F. P.; Boon, Mariëtte R.; Rensen, Patrick C. N.

    2015-01-01

    Brown adipose tissue (BAT) produces heat by burning TGs that are stored within intracellular lipid droplets and need to be replenished by the uptake of TG-derived FA from plasma. It is currently unclear whether BAT takes up FA via uptake of TG-rich lipoproteins (TRLs), after lipolysis-mediated liberation of FA, or via a combination of both. Therefore, we generated glycerol tri[3H]oleate and [14C]cholesteryl oleate double-labeled TRL-mimicking particles with an average diameter of 45, 80, and 150 nm (representing small VLDL to chylomicrons) and injected these intravenously into male C57Bl/6J mice. At room temperature (21°C), the uptake of 3H-activity by BAT, expressed per gram of tissue, was much higher than the uptake of 14C-activity, irrespective of particle size, indicating lipolysis-mediated uptake of TG-derived FA rather than whole particle uptake. Cold exposure (7°C) increased the uptake of FA derived from the differently sized particles by BAT, while retaining the selectivity for uptake of FA over cholesteryl ester (CE). At thermoneutrality (28°C), total FA uptake by BAT was attenuated, but the specificity of uptake of FA over CE was again largely retained. Altogether, we conclude that, in our model, BAT takes up plasma TG preferentially by means of lipolysis-mediated uptake of FA. PMID:25351615

  14. Effects of L-carnitine on serum triglyceride and cytokine levels in rat models of cachexia and septic shock.

    PubMed Central

    Winter, B. K.; Fiskum, G.; Gallo, L. L.

    1995-01-01

    Inappropriate hepatic lipogenesis, hypertriglyceridaemia, decreased fatty acid oxidation and muscle protein wasting are common in patients with sepsis, cancer or AIDS. Given carnitine's role in the oxidation of fatty acids (FAs), we anticipated that carnitine might promote FA oxidation, thus ameliorating metabolic disturbances in lipopolysaccharide (LPS)- and methylcholanthrene-induced sarcoma models of wasting in rats. In the LPS model, rats were injected with LPS (24 mg kg-1 i.p.), and treated with carnitine (100 mg kg-1 i.p.) at -16, -8, 0 and 8 h post LPS. Rat health was observed, and plasma inflammatory cytokines and triglycerides (TG) were measured before and 3 h post LPS. In the sarcoma model, rats were implanted subcutaneously with tumour, and treated continuously with carnitine (200 mg kg-1 day-1 i.p.) via implanted osmotic pumps. Tumour burden, TG and cytokines were measured weekly for 4 weeks. Carnitine treatment significantly lowered the tumour-induced rise in TG (% rise) in the sarcoma model (700 +/- 204 vs 251 +/- 51, P < 0.03) in control and carnitine groups respectively. Levels of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) (pg ml-1) were also lowered by carnitine in both LPS (IL-1 beta: 536 +/- 65 vs 378 +/- 44: IL-6: 271 +/- 29 vs 222 +/- 32; TNF-alpha: 618 +/- 86 vs 367 +/- 54, P < or = 0.02) and sarcoma models (IL-1 beta: 423 +/- 33 vs 221 +/- 60; IL-6: 222 +/- 18 vs 139 +/- 38; TNF-alpha: 617 +/- 69 vs 280 +/- 77, P < or = 0.05) for control and carnitine groups respectively. We conclude that carnitine has a therapeutic effect on morbidity and lipid metabolism in these disease models, and that these effects could be the result of down-regulation of cytokine production and/or increased clearance of cytokines. PMID:7577464

  15. Understanding triglyceride levels related to intravenous fat administration.

    PubMed

    Weaver, Karen

    2014-01-01

    Lipid is an essential macronutrient in parenteral nutrition (PN) support. intravenous (IV) lipid provides essential fatty acids and a concentrated calorie source. Preterm infants are at risk for essential fatty deficiency early in life. Lipid administration is associated with some risks, and there are guidelines for administration to minimize complications. Lipid emulsions in the United States are derived from soybean oil. Outside of the United States, lipid emulsions made from fish oil or combinations of fish, soybean, olive, and medium-chain triglycerides (MCTs) are under investigation for improved tolerance, lower plasma lipid levels, and improved fatty acid profiles, all of which are considered beneficial. Triglyceride levels are an important measurement to assess patient tolerance. PMID:24816878

  16. Modified QCD ghost f(T,TG) gravity

    NASA Astrophysics Data System (ADS)

    Jawad, Abdul; Rani, Shamaila; Chattopadhyay, Surajit

    2015-12-01

    In this paper, we explore the reconstruction scenario of modified QCD ghost dark energy model and newly proposed f(T,TG) gravity in flat FRW universe. We consider the well-known assumption of scale factor, i.e., power law form. We construct the f(T,TG) model and discuss its cosmological consequences through various cosmological parameters such as equation of state parameter, squared speed of sound and ω_{DE}-ω '_{DE}. The equation of state parameter provides the quintom-like behavior of the universe. The squared speed of sound exhibits the stability of model in the later time. Also, ω_{DE}- ω '_{DE} corresponds to freezing as well as thawing regions. It is also interesting to remark here that the results of equation of state parameter and w_{DE}-w'_{DE} coincide with the observational data.

  17. Studies on the Absorptive Defect for Triglyceride in Abetalipoproteinemia*

    PubMed Central

    Ways, P. O.; Parmentier, C. M.; Kayden, H. J.; Jones, J. W.; Saunders, D. R.; Rubin, C. E.

    1967-01-01

    The nature of the gastrointestinal absorptive defect for triglyceride in three subjects with abetalipoproteinemia has been investigated by studying peroral biopsies of the gastrointestinal mucosa. The following conclusions were reached. 1) In confirmation of other studies, the abnormal vacuoles within the duodenal absorptive cells of these individuals were lipophilic. 2) On chemical analysis there was significantly more mucosal lipid than found in normal fasting specimens, and almost the entire increase was due to triglyceride. 3) This excess mucosal lipid was reduced by a low fat diet, but even after 34 days on such a diet there was still an excess of lipophilic material near the villus tip and increased quantities of total lipid and triglyceride when compared with material from normal subjects similarly treated. 4) Although there are demonstrable qualitative changes in mucosal and plasma lipids after an acute fat load, they are not quantitatively as great as in normal individuals. Fat balance studies and the qualitative changes in plasma and tissue lipids that do occur after more extended periods on different types of dietary fat do indicate that a considerable percentage of the dietary fat is assimilated. The route by which it is absorbed remains to be clarified. Images PMID:6018748

  18. Plasma lipoproteins after triglyceride clearance in cholesterol-fed rats.

    PubMed Central

    Quarfordt, S H; Oswald, B S; Farouk, M O; Wehrenberg, D C; Morton, E B; Landis, B A

    1993-01-01

    The clearance of particulate triglyceride from the plasma of cholesterol-fed rats with appreciable stores of hepatic cholesterol ester produces a substantial increment in plasma cholesterol. Most of this plasma cholesterol increment arises from existing tissue sources. The increment begins from 4 to 6 h after clearance and is due to the appearance of larger cholesterol-rich, triglyceride-poor, beta migrating lipoproteins, which are isolated in the d < 1.063 fraction with an apoprotein (Apo) content consisting primarily of Apo E and smaller amounts of Apo B. A concurrent decrease in alpha lipoproteins occurs with the beta lipoprotein increment. Within 1 d of clearance the beta lipoproteins fall and alpha lipoproteins increase. The increase in total plasma Apo E and Apo B initially parallels that of the cholesterol, but it persists even when cholesterol falls. A modest decrease in plasma Apo A1 was observed during the time alpha lipoproteins declined. A significant increase in plasma lecithin cholesterol acyl transferase preceded the increase in beta lipoprotein cholesterol. This enzyme increment was absent in rats with little lipoprotein response despite increased hepatic cholesterol. In vivo inhibition of this enzyme with dithionitrobenzoic acid virtually eliminated the postclearance hypercholesterolemia. Plasma particulate triglyceride clearance induces an increase in beta lipoproteins. Coupling of this clearance and hepatic lipoprotein secretion occurs by an unknown mechanism modulated by lecithin cholesterol acyl transferase. Images PMID:8514865

  19. Interrupting Sitting Time with Regular Walks Attenuates Postprandial Triglycerides.

    PubMed

    Miyashita, M; Edamoto, K; Kidokoro, T; Yanaoka, T; Kashiwabara, K; Takahashi, M; Burns, S

    2016-02-01

    We compared the effects of prolonged sitting with the effects of sitting interrupted by regular walking and the effects of prolonged sitting after continuous walking on postprandial triglyceride in postmenopausal women. 15 participants completed 3 trials in random order: 1) prolonged sitting, 2) regular walking, and 3) prolonged sitting preceded by continuous walking. During the sitting trial, participants rested for 8?h. For the walking trials, participants walked briskly in either twenty 90-sec bouts over 8?h or one 30-min bout in the morning (09:00-09:30). Except for walking, both exercise trials mimicked the sitting trial. In each trial, participants consumed a breakfast (08:00) and lunch (11:00). Blood samples were collected in the fasted state and at 2, 4, 6 and 8?h after breakfast. The serum triglyceride incremental area under the curve was 15 and 14% lower after regular walking compared with prolonged sitting and prolonged sitting after continuous walking (4.732.50 vs. 5.522.95 vs. 5.502.59?mmol/L?8?h respectively, main effect of trial: P=0.023). Regularly interrupting sitting time with brief bouts of physical activity can reduce postprandial triglyceride in postmenopausal women. PMID:26509374

  20. A case for discotic liquid crystals in molten triglycerides.

    PubMed

    Corkery, Robert W; Rousseau, Drick; Smith, Paul; Pink, David A; Hanna, Charles B

    2007-06-19

    To date, essentially only two structural models have been proposed and debated in detail for explaining the liquid state order of triglycerides, and both invoke a form of thermotropic liquid crystalline order in triglyceride melts. These are the paralamellar model of Larsson et al. (J. Am. Oil Chem. Soc. 1992, 69, 835) and the nematic model of Cebula et al. (J. Am. Oil Chem Soc. 1992, 69, 130). An alternative discotic model is proposed here that adequately accounts for the broad small-angle X-ray diffraction peak often observed in the liquid state of fats and oils. In this alternative model, triglyceride molecules exist in the liquid state with fully splayed chains, approximating "Y"-shapes (Y-conformers). These are loosely bound within discs that stack into flexible, relatively short cylindrical rods of colloidal dimension, which in turn assemble into rod-packings with short-range order akin to disordered versions of thermotropic discotic liquid crystalline phases in other lipidic systems. PMID:17511482

  1. Locked nucleic acid antisense inhibitor targeting apolipoprotein C-III efficiently and preferentially removes triglyceride from large very low-density lipoprotein particles in murine plasma.

    PubMed

    Yamamoto, Tsuyoshi; Obika, Satoshi; Nakatani, Moeka; Yasuhara, Hidenori; Wada, Fumito; Shibata, Eiko; Shibata, Masa-Aki; Harada-Shiba, Mariko

    2014-01-15

    A 20-mer phosphorothioate antisense oligodeoxyribonucleotide having locked nucleic acids (LNA-AON) was used to reduce elevated serum triglyceride levels in mice. We repeatedly administered LNA-AON, which targets murine apolipoprotein C-III mRNA, to high-fat-fed C57Bl/6J male mice for 2 weeks. The LNA-AON showed efficient dose-dependent reductions in hepatic apolipoprotein C-III mRNA and decreased serum apolipoprotein C-III protein concentrations, along with efficient dose-dependent reductions in serum triglyceride concentrations and attenuation of fat accumulation in the liver. Through precise lipoprotein profiling analysis of sera, we found that serum reductions in triglyceride and cholesterol levels were largely a result of decreased serum very low-density lipoprotein (VLDL)-triglycerides and -cholesterol. It is noteworthy that larger VLDL particles were more susceptible to removal from blood than smaller particles, resulting in a shift in particle size distribution to smaller diameters. Histopathologically, fatty changes were markedly reduced in antisense-treated mice, while moderate granular degeneration was frequently seen the highest dose of LNA-AON. The observed granular degeneration of hepatocytes may be associated with moderate elevation in the levels of serum transaminases. In conclusion, we developed an LNA-based selective inhibitor of apolipoprotein C-III. Although it remains necessary to eliminate its potential hepatotoxicity, the present LNA-AON will be helpful for further elucidating the molecular biology of apolipoprotein C-III. PMID:24269597

  2. Triglyceride-Rich Lipoproteins Modulate the Distribution and Extravasation of Ly6C/Gr1low Monocytes

    PubMed Central

    Saja, MahaF.; Baudino, Lucie; Jackson, WilliamD.; Cook, H.Terence; Malik, TalatH.; Fossati-Jimack, Liliane; Ruseva, Marieta; Pickering, MatthewC.; Woollard, KevinJ.; Botto, Marina

    2015-01-01

    Summary Monocytes are heterogeneous effector cells involved in the maintenance and restoration of tissue integrity. However, their response to hyperlipidemia remains poorly understood. Here, we report that in the presence of elevated levels of triglyceride-rich lipoproteins, induced by administration of poloxamer 407, the blood numbers of non-classical Ly6C/Gr1low monocytes drop, while the number of bone marrow progenitors remains similar. We observed an increased crawling and retention of the Gr1low monocytes at the endothelial interface and a marked accumulation of CD68+ macrophages in several organs. Hypertriglyceridemia was accompanied by an increased expression of tissue, and plasma CCL4 and blood Gr1low monocyte depletion involved a pertussis-toxin-sensitive receptor axis. Collectively, these findings demonstrate that a triglyceride-rich environment can alter blood monocyte distribution, promoting the extravasation of Gr1low cells. The behavior of these cells in response to dyslipidemia highlights the significant impact that high levels of triglyceride-rich lipoproteins may have on innate immune cells. PMID:26344769

  3. Heterozygosity for a Loss-of-Function Mutation in GALNT2 Improves Plasma Triglyceride Clearance in Man

    PubMed Central

    Holleboom, Adriaan G.; Karlsson, Helen; Lin, Ruei-Shiuan; Beres, Thomas M.; Sierts, Jeroen A.; Herman, Daniel S.; Stroes, Erik S.G.; Aerts, Johannes M.; Kastelein, John J.P.; Motazacker, Mohammad M.; Dallinga-Thie, Geesje M.; Levels, Johannes H.M.; Zwinderman, Aeilko H.; Seidman, Jonathan G.; Seidman, Christine E.; Ljunggren, Stefan; Lefeber, Dirk J.; Morava, Eva; Wevers, Ron A.; Fritz, Timothy A.; Tabak, Lawrence A.; Lindahl, Mats; Hovingh, G. Kees; Kuivenhoven, Jan Albert

    2012-01-01

    SUMMARY Genome-wide association studies have identified GALNT2 as a candidate gene in lipid metabolism, but it is not known how the encoded enzyme ppGal-NAc-T2, which contributes to the initiation of mucin-type O-linked glycosylation, mediates this effect. In two probands with elevated plasma high-density lipoprotein cholesterol and reduced triglycerides, we identified a mutation in GALNT2. It is shown that carriers have improved postprandial triglyceride clearance, which is likely attributable to attenuated glycosylation of apolipoprotein (apo) C-III, as observed in their plasma. This protein inhibits lipoprotein lipase (LPL), which hydrolyses plasma triglycerides. We show that an apoC-III-based peptide is a substrate for ppGalNAc-T2 while its glycosylation by the mutant enzyme is impaired. In addition, neuraminidase treatment of apoC-III which removes the sialic acids from its glycan chain decreases its potential to inhibit LPL. Combined, these data suggest that ppGalNAc-T2 can affect lipid metabolism through apoC-III glycosylation, thereby establishing GALNT2 as a lipid-modifying gene. PMID:22152306

  4. Association of Serum Cholesterol, Triglyceride, High and Low Density Lipoprotein (HDL and LDL) Levels in Chronic Periodontitis Subjects with Risk for Cardiovascular Disease (CVD): A Cross Sectional Study

    PubMed Central

    Sandi, R.M.; Pol, K.G.; Basavaraj, P.; Khuller, Nitin; Singh, Shilpi

    2014-01-01

    Purpose: To assess serum cholesterol, triglycerides, high and low density lipoprotein (HDL and LDL) levels (serum lipid profile) in subjects with chronic periodontitis and the possible association for risk of cardiovascular disease (CVD). Materials and Methods: Total of 80 participants (42 males and 38 females) who were in the age range of 30-65 years were divided into test group (group I- 40 subjects with chronic periodontitis) and control group (group II- 40 subjects with healthy periodontium), based on their periodontal disease statuses. Three ml of venous blood samples were taken for measurement of parameters of lipid metabolism [serum cholesterol (chol); triglycerides (Tg); HDL and LDL. Results: Significant increase in serum cholesterol and LDL (P<0.05) were observed in test group (group I), whereas serum triglycerides and HDL (P>0.66) showed no significant increase in test group (group I) as compared to their values in the control group (group II). A P-value of < 0.05 was considered for statistical significance. Conclusions: Subjects with chronic periodontitis showed increased serum cholesterol and LDL levels. This may suggest that these subjects are potentially at a risk of getting CVD. PMID:24596778

  5. Monocular Elevation Deficiency - Double Elevator Palsy

    MedlinePLUS

    ... Eye Terms Conditions Frequently Asked Questions Español Condiciones Chinese Conditions Monocular Elevation Deficiency/ Double Elevator Palsy En Español Read in Chinese What is monocular elevation deficiency (Double Elevator Palsy)? ...

  6. Rapid and sensitive enzymatic-radiochemical assay for the determination of triglycerides

    SciTech Connect

    Khoo, J.C.; Miller, E.; Goldberg, D.I.

    1987-07-01

    An enzymatic-radiochemical method suitable for the determination of triglyceride levels of cells in culture is described. The method is based on the enzymatic hydrolysis of triglycerides to free fatty acids which then complex with /sup 63/Ni. The method is rapid, accurate, and inexpensive. The procedure extends the sensitivity of triglyceride measurement to as low as 0.25 nanomoles.

  7. Common variants associated with plasma triglycerides and risk for coronary artery disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common va...

  8. Elevation of fasting insulin and its association with cardiovascular disease risk in women with systemic lupus erythematosus.

    PubMed

    Tso, Tim K; Huang, Wen-Nan

    2009-05-01

    Systemic lupus erythematosus (SLE) is associated with premature atherosclerosis. We previously showed that SLE patients have a higher risk of insulin resistance (IR) and abnormal insulin secretion. The present study was to further investigate the relationship between fasting insulin levels and both classic and novel cardiovascular risk factors in patients with SLE. Body mass index (BMI), fasting glucose and insulin, lipid profile, oxidation markers, fibrinolytic factors, vascular function factors, and disease-specific variables were determined in a total of 87 female SLE patients. The homeostasis model assessment (HOMA) was used to evaluate the IR and secretion. SLE patients had significantly higher fasting insulin, HOMA IR, HOMA beta-cell, titers of autoantibodies against oxidized low density lipoprotein, systolic blood pressure, homocysteine, and brachial-ankle pulse wave velocity (baPWV) than age-matched healthy controls. There were no statistical differences in disease duration, anti-dsDNA, C3, C4, disease activity, and medication dosage between SLE patients stratified by fasting insulin levels. However, mean values for BMI, insulin, HOMA IR, HOMA beta-cell, triglyceride (TG), homocysteine, and baPWV were significantly higher in the SLE patients with hyperinsulinemia when compared with those SLE controls. In addition, fasting insulin levels were positively correlated with TG, homocysteine, blood pressure, plasminogen activator inhibitor 1, and baPWV in SLE patients. The elevation of fasting insulin levels in SLE patients is not only associated with IR, but is related to classic and novel cardiovascular risk factors. This study concludes that there is an insulin-related cardiovascular disease risk in SLE. PMID:19037607

  9. Elevated Transglutaminase 2 Activity is Associated with Hypoxia-Induced Experimental Pulmonary Hypertension in Mice

    PubMed Central

    DiRaimondo, Thomas R.; Klock, Cornelius; Warburton, Rod; Herrera, Zachary; Penumatsa, Krishna; Toksoz, Deniz; Hill, Nicholas; Khosla, Chaitan; Fanburg, Barry

    2013-01-01

    Previous studies in human patients and animal models have suggested that transglutaminase 2 (TG2) is upregulated in pulmonary hypertension (PH), a phenomenon that appears to be associated with the effects of serotonin (5-hydroxytryptamine; 5-HT) in this disease. Using chemical tools to interrogate and inhibit TG2 activity in vivo, we have shown that pulmonary TG2 undergoes marked post-translational activation in a mouse model of hypoxia-induced PH. We have also identified irreversible fluorinated TG2 inhibitors that may find use as non-invasive positron emission tomography probes for diagnosis and management of this debilitating, lifelong disorder. Pharmacological inhibition of TG2 attenuated the elevated right ventricular pressure but had no effect on hypertrophy of the right ventricle of the heart. A longitudinal study of pulmonary TG2 activity in PH patients is warranted. PMID:24152195

  10. Predictive value of early changes in triglycerides and weight for longer-term changes in metabolic measures during olanzapine, ziprasidone or aripiprazole treatment for schizophrenia and schizoaffective disorder post hoc analyses of 3 randomized, controlled clinical trials.

    PubMed

    Hoffmann, Vicki P; Case, Michael; Stauffer, Virginia L; Jacobson, Jennie G; Conley, Robert R

    2010-12-01

    The objective of this study was to determine if early changes in triglycerides and weight may be useful in predicting longer-term changes in weight and other metabolic parameters. Data were from three 24- to 28-week randomized, controlled studies comparing olanzapine to ziprasidone or aripiprazole for treatment of schizophrenia. Analyses were restricted to completers with fasting laboratory data at all protocol specified time points. Analyses were primarily descriptive and included mean changes and categorical outcomes. In all treatment groups, participants who did not experience a 20 mg/dL or greater increase in triglycerides at early time points were unlikely to experience a change of 50 mg/dL or more in triglycerides after 6 months. Negative predictive values were 83% to 95%. However, early change in triglycerides was not useful for predicting later change in glucose, cholesterol, or weight. Similarly, early weight change gave robust negative predictive values for longer-term weight change (≥10 kg), but not for change in glucose or cholesterol. Lack of early elevation in triglyceride concentrations was predictive of later lack of substantial increase in triglycerides in olanzapine-, ziprasidone-, and aripiprazole-treated participants. Lack of early elevation in weight was predictive of later lack of substantial increase in weight in all 3 treatment groups. Early monitoring of triglyceride concentrations and weight may help clinicians assess risk that individuals will experience significant increase in triglycerides or weight gain, allowing assessments of potential risks and benefits earlier in treatment. Clinical monitoring is advised throughout treatment for all patients. PMID:21105275

  11. AβPP-overexpressing transgenic rat model of Alzheimer's disease utilizing the Tg2576 mouse protocol.

    PubMed

    O'Hare, Eugene; Ardis, Tara; Page, Deaglan; Scopes, David I C; Kim, Eun-Mee

    2013-01-01

    The current study examined behavioral and histological effects of amyloid-β (Aβ) protein precursor (AβPP) overexpression in transgenic (Tg) rats created using the same gene, mutation, and promoter as the Tg2576 mouse model of Alzheimer's disease (AD). Male Tg+ rats were bred with female wild-type rats to generate litters of hemizygous Tg+ and Tg- offspring. Tg+ rats and Tg- littermates were tested for memory deficits at 4, 8, and 12 months old using a water-maze procedure. There were no significant behavioral differences between Tg+ rats and Tg- littermates at 4 months old but there were significant differences at 8 and 12 months old, and in probe trials at 8 and 12 months old, the Tg+ rats spent significantly less time and covered less distance in the platform zone. Under acquisition of a fixed-consecutive number schedule at 3 months old, Tg- littermates demonstrated a longer latency to learning the response rule than Tg+ rats; while this might seem paradoxical, it is consistent with the role of overexpression of AβPP in learning. Histological analyses revealed activated astrocytes in brains of Tg+ rats but not Tg- littermates at 6 months old, and thioflavin-S positive staining in the hippocampus and cortex of 17-month old Tg+ rats but not Tg- littermates. Quantification of Aβ load in the brain at 22 months indicated high levels of Aβ38, Aβ40, and Aβ42 in the Tg+ rats. These data suggest this model might provide a valuable resource for AD research. PMID:23780661

  12. Inactivation of ANGPTL3 reduces hepatic VLDL-triglyceride secretion.

    PubMed

    Wang, Yan; Gusarova, Viktoria; Banfi, Serena; Gromada, Jesper; Cohen, Jonathan C; Hobbs, Helen H

    2015-07-01

    Humans and mice lacking angiopoietin-like protein 3 (ANGPTL3) have pan-hypolipidemia. ANGPTL3 inhibits two intravascular lipases, LPL and endothelial lipase, and the low plasma TG and HDL-cholesterol levels in ANGPTL3 deficiency reflect increased activity of these enzymes. The mechanism responsible for the low LDL-cholesterol levels associated with ANGPTL3 deficiency is not known. Here we used an anti-ANGPTL3 monoclonal antibody (REGN1500) to inactivate ANGPTL3 in mice with genetic deficiencies in key proteins involved in clearance of ApoB-containing lipoproteins. REGN1500 treatment consistently reduced plasma cholesterol levels in mice in which Apoe, Ldlr, Lrp1, and Sdc1 were inactivated singly or in combination, but did not alter clearance of rabbit (125)I-?VLDL or mouse (125)I-LDL. Despite a 61% reduction in VLDL-TG production, VLDL-ApoB-100 production was unchanged in REGN1500-treated animals. Hepatic TG content, fatty acid synthesis, and fatty acid oxidation were similar in REGN1500 and control antibody-treated animals. Taken together, our findings indicate that inactivation of ANGPTL3 does not affect the number of ApoB-containing lipoproteins secreted by the liver but alters the particles that are made such that they are cleared more rapidly from the circulation via a noncanonical pathway(s). The increased clearance of lipolytic remnants results in decreased production of LDL in ANGPTL3-deficient animals. PMID:25954050

  13. n-3 Polyunsaturated Fatty Acid Supplementation Has No Effect on Postprandial Triglyceride-Rich Lipoprotein Kinetics in Men with Type 2 Diabetes

    PubMed Central

    Tremblay, André J.; Lamarche, Benoît; Hogue, Jean-Charles

    2016-01-01

    Dietary n-3 polyunsaturated fatty acids (PUFAs) have been proposed to modulate plasma lipids, lipoprotein metabolism, and inflammatory state and to reduce triglyceride (TG) concentrations. The present double-blind, randomized, placebo-controlled, crossover study investigated the effects of n-3 PUFA supplementation at 3 g/d for 8 weeks on the intravascular kinetics of intestinally derived apolipoprotein (apo) B-48-containing lipoproteins in 10 men with type 2 diabetes. In vivo kinetics of the TG-rich lipoprotein (TRL) apoB-48 and VLDL apoB-100 were assessed using a primed-constant infusion of L-[5,5,5-D3] leucine for 12 hours in a fed state. Compared with the placebo, n-3 PUFA supplementation significantly reduced fasting TG concentrations by −9.7% (P = 0.05) but also significantly increased plasma levels of cholesterol (C) (+6.0%, P = 0.05), LDL-C (+12.2%, P = 0.04), and HDL-C (+8.4, P = 0.007). n-3 PUFA supplementation had no significant impact on postprandial TRL apoB-48 and VLDL apoB-100 levels or on the production or catabolic rates of these lipoproteins. These data indicate that 8-week supplementation with n-3 PUFAs in men with type 2 diabetes has no beneficial effect on TRL apoB-48 and VLDL apoB-100 levels or kinetics.

  14. Adventures in transformations: TG, TA, oh my! (Poster abstract)

    NASA Astrophysics Data System (ADS)

    Ciocca, M.

    2015-12-01

    (Abstract only) AAVSO made available, through the great volunteer work of Gordon Myers and George Silvis, two very useful tools, Transform Generator and Transform Applier (TG and TA) for transforming instrumental magnitudes to the standard system. I will juxtapose the steps necessary to obtain transformation parameters "the old fashion way" and how can the same result be achieved with these two tools. I will present transformation parameters for the Eastern Kentucky University (EKU) telescope and obtained with the standard field M67. These parameters were applied to photometric results for AE Uma, a short-period, high-amplitude delta Scuti star (Period ~ 0.086 d).

  15. DynTG: A tool for Interactive, Dynamic Instrumentation

    SciTech Connect

    Schulz, M; May, J; Gyllenhaal, J

    2005-02-16

    With the increasing complexity of today's systems, detailed performance analysis is more important than ever. We have developed DynTG, a tool for interactive, dynamic instrumentation. It uses performance module plugins to reconfigure the data acquisition and provides a source browser that allows users to insert any probe functionality provided by the modules dynamically into the target application. Any instrumentation can be added both before and during the application's execution and the acquired data is presented in realtime within the source viewer. This enables users to monitor their applications' progress and interactively control and adapt the instrumentation based on their observations.

  16. Synthesis and characterization of triglyceride based thermosetting polymers

    NASA Astrophysics Data System (ADS)

    Can, Erde

    2005-07-01

    Plant oils, which are found in abundance in all parts of the world and are easily replenished annually, have the potential to replace petroleum as a chemical feedstock for making polymers. Within the past few years, there has been growing interest to use triglycerides as the basic constituent of thermosetting polymers with the necessary rigidity, strength and glass transition temperatures required for engineering applications. Plant oils are not polymerizable in their natural form, however various functional groups that can polymerize can easily be attached to the triglyceride structure making them ideal cross-linking monomers for thermosetting liquid molding resins. Through this research project a number of thermosetting liquid molding resins based on soybean and castor oil, which is a specialty oil with hydroxyls on its fatty acids, have been developed. The triglyceride based monomers were prepared via the malination of the alcoholysis products of soybean and castor oil with various polyols, such as pentaerythritol, glycerol, and Bisphenol A propoxylate. The malinated glycerides were then cured in the presence of a reactive diluent, such as styrene, to form rigid glassy materials with a wide range of properties. In addition to maleate half-esters, methacrylates were also introduced to the glyceride structure via methacrylation of the soybean oil glycerolysis product with methacrylic anhydride. This product, which contains methacrylic acid as by-product, and its blends with styrene also gave rigid materials when cured. The triglyceride based monomers were characterized via conventional spectroscopic techniques. Time resolved FTIR analysis was used to determine the curing kinetics and the final conversions of polymerization of the malinated glyceride-styrene blends. Dynamic Mechanical Analysis (DMA) was used to determine the thermomechanical behavior of these polymers and other mechanical properties were determined via standard mechanical tests. The use of lignin, another renewable resource, as a filler and its effects on the mechanical properties of the polymers based on soybean oil pentaerythritol glyceride maleates and styrene (SOPERMA) was also explored. These novel soybean and castor oil based thermosetting resins show comparable properties to those of commercially successful unsaturated polyester resins and show promise as an alternative to replace these completely petroleum based materials.

  17. TgM2AP participates in Toxoplasma gondii invasion of host cells and is tightly associated with the adhesive protein TgMIC2.

    PubMed

    Rabenau, K E; Sohrabi, A; Tripathy, A; Reitter, C; Ajioka, J W; Tomley, F M; Carruthers, V B

    2001-08-01

    Like other members of the medically important phylum Apicomplexa, Toxoplasma gondii is an obligate intracellular parasite that secretes several classes of proteins involved in the active invasion of target host cells. Proteins in apical secretory organelles known as micronemes have been strongly implicated in parasite attachment to host cells. TgMIC2 is a microneme protein with multiple adhesive domains that bind target cells and is mobilized onto the parasite surface during parasite attachment. Here, we describe a novel parasite protein, TgM2AP, which is physically associated with TgMIC2. TgM2AP complexes with TgMIC2 within 15 min of synthesis and remains associated with TgMIC2 in the micronemes, on the parasite surface during invasion and in the culture medium after release from the parasite plasma membrane. TgM2AP is proteolytically processed initially when its propeptide is removed during transit through the golgi and later while it occupies the parasite surface after discharge from the micronemes. We show that TgM2AP is a member of a protein family expressed by coccidian parasites including Neospora caninum and Eimeria tenella. This phylogenic conservation and association with a key adhesive protein suggest that TgM2AP is a fundamental component of the T. gondii invasion machinery. PMID:11532123

  18. Spatial training preserves associative memory capacity with augmentation of dendrite ramification and spine generation in Tg2576 mice

    PubMed Central

    Jiang, Xia; Chai, Gao-Shang; Wang, Zhi-Hao; Hu, Yu; Li, Xiao-Guang; Ma, Zhi-Wei; Wang, Qun; Wang, Jian-Zhi; Liu, Gong-Ping

    2015-01-01

    Alzheimer's disease (AD) is the most common neurodegenerative disorder and there is currently no efficient cure for this devastating disease. Cognitive stimulation can delay memory loss during aging and in patients with mild cognitive impairment. In 3 × Tg-AD mice, training decreased the neuropathologies with transient amelioration of memory decline. However, the neurobiological mechanisms underlying the learning-improved memory capacity are poorly understood. Here, we found in Tg2576 mice spatial training in Morris water maze (MWM) remarkably improved the subsequent associative memory acquisition detected by contextual fear conditioning. We also found that spatial training enhanced long term potentiation, dendrite ramification and spine generation in hippocampal dentate gyrus (DG) and CA1 neurons at 24 h after the training. In the molecular level, the MWM training remarkably activated calcium/calmodulin-dependent protein kinase II (CaMKII) with elevation of glutamate AMPA receptor GluA1 subunit (GluA1), postsynaptic density protein 93 (PSD93) and postsynaptic density protein 95 (PSD95) in the hippocampus. Finally, the training also significantly ameliorated AD-like tau and amyloid pathologies. We conclude that spatial training in MWM preserves associative memory capacity in Tg2576 mice, and the mechanisms involve augmentation of dendrite ramification and spine generation in hippocampus. PMID:25820815

  19. Spatial training preserves associative memory capacity with augmentation of dendrite ramification and spine generation in Tg2576 mice.

    PubMed

    Jiang, Xia; Chai, Gao-Shang; Wang, Zhi-Hao; Hu, Yu; Li, Xiao-Guang; Ma, Zhi-Wei; Wang, Qun; Wang, Jian-Zhi; Liu, Gong-Ping

    2015-01-01

    Alzheimer's disease (AD) is the most common neurodegenerative disorder and there is currently no efficient cure for this devastating disease. Cognitive stimulation can delay memory loss during aging and in patients with mild cognitive impairment. In 3 × Tg-AD mice, training decreased the neuropathologies with transient amelioration of memory decline. However, the neurobiological mechanisms underlying the learning-improved memory capacity are poorly understood. Here, we found in Tg2576 mice spatial training in Morris water maze (MWM) remarkably improved the subsequent associative memory acquisition detected by contextual fear conditioning. We also found that spatial training enhanced long term potentiation, dendrite ramification and spine generation in hippocampal dentate gyrus (DG) and CA1 neurons at 24 h after the training. In the molecular level, the MWM training remarkably activated calcium/calmodulin-dependent protein kinase II (CaMKII) with elevation of glutamate AMPA receptor GluA1 subunit (GluA1), postsynaptic density protein 93 (PSD93) and postsynaptic density protein 95 (PSD95) in the hippocampus. Finally, the training also significantly ameliorated AD-like tau and amyloid pathologies. We conclude that spatial training in MWM preserves associative memory capacity in Tg2576 mice, and the mechanisms involve augmentation of dendrite ramification and spine generation in hippocampus. PMID:25820815

  20. Open TG-GATEs: a large-scale toxicogenomics database

    PubMed Central

    Igarashi, Yoshinobu; Nakatsu, Noriyuki; Yamashita, Tomoya; Ono, Atsushi; Ohno, Yasuo; Urushidani, Tetsuro; Yamada, Hiroshi

    2015-01-01

    Toxicogenomics focuses on assessing the safety of compounds using gene expression profiles. Gene expression signatures from large toxicogenomics databases are expected to perform better than small databases in identifying biomarkers for the prediction and evaluation of drug safety based on a compound's toxicological mechanisms in animal target organs. Over the past 10 years, the Japanese Toxicogenomics Project consortium (TGP) has been developing a large-scale toxicogenomics database consisting of data from 170 compounds (mostly drugs) with the aim of improving and enhancing drug safety assessment. Most of the data generated by the project (e.g. gene expression, pathology, lot number) are freely available to the public via Open TG-GATEs (Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System). Here, we provide a comprehensive overview of the database, including both gene expression data and metadata, with a description of experimental conditions and procedures used to generate the database. Open TG-GATEs is available from http://toxico.nibio.go.jp/english/index.html. PMID:25313160

  1. Dramatic alteration of Tg of polystyrene confined in cylindrical nanopores

    NASA Astrophysics Data System (ADS)

    Xue, Gi; Teng, Chao; Xu, Jie; Li, Linling

    2014-03-01

    Vitrification of polystyrene melt infiltrated in AAO template was greatly altered by geometrical confinement. DSC detected two distinguish Tgs for PS slowly cooled from the melt in nanopores. One was at a lower temperature than the bulk Tg and the other was at a higher temperature. The deviation between the two Tgs could reach as big as 60 C and increased with decreasing pore size. Surprisingly, Tg for the PS nanorodes recovered back to the bulk value when the template was removed, indicating the importance of the interfacial interaction. The major factor which induced such a strong confinement is the cooling rate. The coefficient of thermal expansion (CTE) of AAO template is about one order lower than that for PS. The mismatch of CTEs causes a strain induced stress during cooling: the PS chains tend to shrink and to de-wet from the walls; meanwhile the interfacial interaction tends to hold the chains back. The chains are subjected to a high residual stress by a fast cooling and would peel off from the wall. When the cooling rate is sufficiently slow, and the stress was relaxed during cooling. Then the chains were still stick on the wall, resulting in a strong interfacial constraints for chains.

  2. Subcutaneous Implants of Buprenorphine-Cholesterol-Triglyceride Powder in Mice

    PubMed Central

    DeTolla, L.; Sanchez, R.; Khan, E.; Tyler, B.; Guarnieri, M.

    2014-01-01

    Subcutaneous drug implants are convenient systems for the long-term delivery of drugs in animals. Lipid carriers are logical tools because they generally allow for higher doses and low toxicity. The present study used an US Food and Drug Administration Target Animal Safety test system to evaluate the safety of a subcutaneous implant of a cholesterol-triglyceride-buprenorphine powder in 120 BALB/c mice. Mice were evaluated in 4- and 12-day trials with 1- and 5-fold doses of the intended 3?mg/kg dose of drug. One male mouse treated with three 3?mg/kg doses and surgery on days 0, 4, and 8 died on day 9. The cause of death was not determined. In the surviving 119 mice there was no evidence of skin reaction at the site of the implant. Compared to control animals treated with saline, weight measurements, clinical pathology, histopathology, and clinical observations were unremarkable. These results demonstrate that the lipid carrier is substantially safe. Cholesterol-triglyceride-drug powders may provide a valuable research tool for studies of analgesic and inflammatory drug implants in veterinary medicine. PMID:26464927

  3. A new multienzyme-type biosensor for triglyceride determination.

    PubMed

    Ycel, Alp; zcan, Hakk? Mevlt; Sa??ro?lu, Ayten

    2016-01-01

    An amperometric multienzyme biosensor for determination of triglycerides (TGs) was constructed by mounting three gelatin membrane-bound enzymes on a glassy carbon electrode (working electrode), then connecting it to electrometer along with an Ag/AgCl reference electrode and a Pt auxiliary electrode. Characterization and optimization of the multienzyme biosensor, which is prepared with glycerol kinase (GK) (E.C.2.7.1.30), glycerol-3-phosphate oxidase (GPO) (EC 1.1.3.21), and lipase (EC 3.1.1.3), were studied. In the optimization studies for the bioactive layer components of the prepared biosensor, the optimum amounts of gelatin, bovine serum albumin (BSA), and glutaraldehyde was calculated as 1mg/cm(2), 1mg/cm(2), and 2.5%, respectively. Optimum pH and temperature of the reaction of biosensor were determined as 7.0 and 40C, respectively. Linear range of triolein for the biosensor was found from the calibration curve between several substrate concentration and ? Current. After optimization and characterization of the biosensor, its operationability in triglycerides was also tested. PMID:25397961

  4. Use of a mixture of medium-chain triglycerides and longchain triglycerides versus long-chain triglycerides in critically ill surgical patients: a randomized prospective double-blind study.

    PubMed

    Nijveldt, R J; Tan, A M; Prins, H A; de Jong, D; van Rij, G L; Wesdorp, R I; van Leeuwen, P A

    1998-02-01

    Twenty critically-ill surgical patients who needed total parenteral nutrition were randomly enrolled in a double-blind study comparing two intravenous fat emulsions: one containing a mixture of 50% medium-chain triglycerides and 50% long-chain triglycerides and another containing 100% longchain triglycerides. The purpose of this study was to investigate metabolic and biochemical differences between both emulsions with special reference to liver enzymes. After a baseline period of 24 h with only glucose and NaCl infusion, the lipid emulsion was added continuously during 24 h over 5 days. The parenteral nutrition was administered in mixture bags containing amino-acids, glucose and lipids together. Two-thirds of the non-protein calories were administered as glucose 40% and one third as either long-chain triglycerides or a mixture of medium-chain triglycerides and long-chain triglycerides. The total amount of non-protein calories received was the measured energy expenditure during the baseline period plus 10% and was fixed during the study. Plasma substrate concentrations, energy expenditure, and nitrogen balance were determined and arterial blood samples were taken. No toxic effects or complications attributable to one of the two emulsions were observed. There was no significant difference in energy expenditure, nitrogen balance, liver function tests, carnitine, transferrin, pre-albumin, albumin, cholesterol, triglycerides and free fatty acids. The only parameter that showed a different pattern of reaction between the two emulsions was serum bilirubin concentration. In this study no evidence of any advantageous effect of a mixture of medium-chain triglycerides and long-chain triglycerides was seen. PMID:10205311

  5. Long term aging of selenide glasses: evidence of sub-Tg endotherms and pre-Tg exotherms.

    PubMed

    Chen, Ping; Boolchand, P; Georgiev, D G

    2010-02-17

    Long term aging, extending from months to several years, is studied on several families of chalcogenide glasses including the Ge-Se, As-Se, and Ge-As-Se systems. Special attention is given to the As-Se binary, a system that displays a rich variety of aging behavior intimately tied to sample synthesis conditions and the ambient environment in which samples are aged. Calorimetric (modulated DSC) and Raman scattering experiments are undertaken. Our results show all samples display a sub-Tg endotherm typically 10-70 C below Tg in glassy networks possessing a mean coordination number r in the 2.25 < r < 2.45 range. Two sets of As(x)Se(100-x) samples aged for eight years were compared, set A consisted of slow cooled samples aged in the dark, and set B consisted of melt-quenched samples aged at laboratory environment. Samples of set B in the As concentration range, 35% < x < 60%, display a pre-T(g) exotherm, but the feature is not observed in samples of set A. The aging behavior of set A presumably represents intrinsic aging in these glasses, while that of set B is extrinsic due to the presence of light. The reversibility window persists in both sets of samples, but is less well defined in set B. These findings contrast with a recent study by Golovchak et al (2008 Phys. Rev. B 78 014202), which finds the onset of the reversibility window moved up to the stoichiometric composition (x = 40%). Here we show that the up-shifted window is better understood as resulting due to demixing of As4Se4 and As4Se3 molecules from the backbone, i.e., nanoscale phase separation (NSPS). We attribute sub-Tg endotherms to compaction of the flexible part of the networks upon long term aging, while the pre-Tg exotherm is to NSPS. The narrowing and sharpening of the reversibility window upon aging is interpreted as the slow 'self-organizing' stress relaxation of the phases just outside the intermediate phase, which itself is stress free and displays little aging. PMID:21389364

  6. Dual regulation of adipose triglyceride lipase by pigment epithelium-derived factor: a novel mechanistic insight into progressive obesity.

    PubMed

    Dai, Zhiyu; Qi, Weiwei; Li, Cen; Lu, Juling; Mao, Yuling; Yao, Yachao; Li, Lei; Zhang, Ting; Hong, Honghai; Li, Shuai; Zhou, Ti; Yang, Zhonghan; Yang, Xia; Gao, Guoquan; Cai, Weibin

    2013-09-01

    Both elevated plasma free fatty acids (FFA) and accumulating triglyceride in adipose tissue are observed in the process of obesity and insulin resistance. This contradictory phenomenon and its underlying mechanisms have not been thoroughly elucidated. Recent studies have demonstrated that pigment epithelium-derived factor (PEDF) contributes to elevated plasma FFA and insulin resistance in obese mice via the activation of adipose triglyceride lipase (ATGL). However, we found that PEDF downregulated adipose ATGL protein expression despite of enhancing lipolysis. Plasma PEDF and FFA were increased in associated with a progressive high-fat-diet, and those outcomes were also accompanied by fat accumulation and a reduction in adipose ATGL. Exogenous PEDF injection downregulated adipose ATGL protein expression and elevated plasma FFA, while endogenous PEDF neutralization significantly rescued the adipose ATGL reduction and also reduced plasma FFA in obese mice. PEDF reduced ATGL protein expression in a time- and dose-dependent manner in differentiated 3T3-L1 cells. Small interfering RNA-mediated PEDF knockdown and antibody-mediated PEDF blockage increased endogenous ATGL expression, and PEDF overexpression downregulated ATGL. PEDF resulted in a decreased half-life of ATGL and regulated ATGL degradation via ubiquitin-dependent proteasomal degradation pathway. PEDF stimulated lipolysis via ATGL using ATGL inhibitor bromoenol lactone, and PEDF also downregulated G0/G1 switch gene 2 (G0S2) expression, which is an endogenous inhibitor of ATGL activation. Overall, PEDF attenuated ATGL protein accumulation via proteasome-mediated degradation in adipocytes, and PEDF also promoted lipolysis by activating ATGL. Elevated PEDF may contribute to progressive obesity and insulin resistance via its dual regulation of ATGL. PMID:23850519

  7. Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study

    PubMed Central

    2010-01-01

    Background Hypertriglyceridemia (HTG) is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG) metabolism has been described, including LPL, APOA5 and APOE. The combined analysis of these polymorphisms could produce clinically meaningful complementary information. Methods A subgroup of the ICARIA study comprising 1825 Spanish subjects (80% men, mean age 36 years) was genotyped for the LPL-HindIII (rs320), S447X (rs328), D9N (rs1801177) and N291S (rs268) polymorphisms, the APOA5-S19W (rs3135506) and -1131T/C (rs662799) variants, and the APOE polymorphism (rs429358; rs7412) using PCR and restriction analysis and TaqMan assays. We used regression analyses to examine their combined effects on TG levels (with the log-transformed variable) and the association of variant combinations with TG levels and hypertriglyceridemia (TG ≥ 1.69 mmol/L), including the covariates: gender, age, waist circumference, blood glucose, blood pressure, smoking and alcohol consumption. Results We found a significant lowering effect of the LPL-HindIII and S447X polymorphisms (p < 0.0001). In addition, the D9N, N291S, S19W and -1131T/C variants and the APOE-ε4 allele were significantly associated with an independent additive TG-raising effect (p < 0.05, p < 0.01, p < 0.001, p < 0.0001 and p < 0.001, respectively). Grouping individuals according to the presence of TG-lowering or TG-raising polymorphisms showed significant differences in TG levels (p < 0.0001), with the lowest levels exhibited by carriers of two lowering variants (10.2% reduction in TG geometric mean with respect to individuals who were homozygous for the frequent alleles of all the variants), and the highest levels in carriers of raising combinations (25.1% mean TG increase). Thus, carrying two lowering variants was protective against HTG (OR = 0.62; 95% CI, 0.39-0.98; p = 0.042) and having one single raising polymorphism (OR = 1.20; 95% CI, 1.39-2.87; p < 0.001) or more (2 or 3 raising variants; OR = 2.90; 95% CI, 1.56-5.41; p < 0.001) were associated with HTG. Conclusion Our results showed a significant independent additive effect on TG levels of the LPL polymorphisms HindIII, S447X, D9N and N291S; the S19W and -1131T/C variants of APOA5, and the ε4 allele of APOE in our study population. Moreover, some of the variant combinations studied were significantly associated with the absence or the presence of hypertriglyceridemia. PMID:20429872

  8. The interaction of Apolipoprotein A5 gene promoter region T-1131C polymorphism (rs12286037) and lifestyle modification on plasma triglyceride levels in Japanese

    PubMed Central

    Mutombo, Paulin Beya wa Bitadi; Iwamoto, Mamiko; Nogi, Akiko; Hashimoto, Michio; Nabika, Toru; Shiwaku, Kuninori

    2015-01-01

    BACKGROUND/OBJECTIVE Apolipoprotein A5 gene promoter region T-1131C polymorphism (APOA5 T-1131C) is known to be associated with elevated plasma TG levels, although little is known of the influence of the interaction between APOA5 T-1131C and lifestyle modification on TG levels. To investigate this matter, we studied APOA5 T-1131C and plasma TG levels of subjects participating in a three-month lifestyle modification program. SUBJECTS/METHODS A three-month lifestyle modification program was conducted with 297 participants (Age: 57 8 years) in Izumo City, Japan, from 2001-2007. Changes in energy balance (the difference between energy intake and energy expenditure) and BMI were used to evaluate the participants' responses to the lifestyle modification. RESULTS Even after adjusting for confounding factors, plasma TG levels were significantly different at baseline among three genotype subgroups: TT, 126 68 mg/dl; TC, 134 74 mg/dl; and CC, 172 101 mg/dl. Lifestyle modification resulted in significant reductions in plasma TG levels in the TT, TC, and CC genotype subgroups: -21.9 61.0 mg/dl, -20.9 51.0 mg/dl, and -42.6 78.5 mg/dl, respectively, with no significant differences between them. In a stepwise regression analysis, age, APOA5 T-1131C, body mass index (BMI), homeostasis model assessment-insulin resistance (HOMA-IR), and the 18:1/18:0 ratio showed independent association with plasma TG levels at baseline. In a general linear model analysis, APOA5 T-1131C C-allele carriers showed significantly greater TG reduction with decreased energy balance than wild type carriers after adjustment for age, gender, and baseline plasma TG levels. CONCLUSIONS The genetic effects of APOA5 T-1131C independently affected plasma TG levels. However, lifestyle modification was effective in significantly reducing plasma TG levels despite the APOA5 T-1131C genotype background. PMID:26244076

  9. Inhibition of adipose triglyceride lipase (ATGL) by the putative tumor suppressor G0S2 or a small molecule inhibitor attenuates the growth of cancer cells

    PubMed Central

    Zagani, Rachid; El-Assaad, Wissal; Gamache, Isabelle; Teodoro, Jose G.

    2015-01-01

    The G0/G1 switch gene 2 (G0S2) is methylated and silenced in a wide range of human cancers. The protein encoded by G0S2 is an endogenous inhibitor of lipid catabolism that directly binds adipose triglyceride lipase (ATGL). ATGL is the rate-limiting step in triglyceride metabolism. Although the G0S2 gene is silenced in cancer, the impact of ATGL in the growth and survival of cancer cells has never been addressed. Here we show that ectopic expression of G0S2 in non-small cell lung carcinomas (NSCL) inhibits triglyceride catabolism and results in lower cell growth. Similarly, knockdown of ATGL increased triglyceride levels, attenuated cell growth and promoted apoptosis. Conversely, knockdown of endogenous G0S2 enhanced the growth and invasiveness of cancer cells. G0S2 is strongly induced in acute promyelocytic leukemia (APL) cells in response to all trans retinoic acid (ATRA) and we show that inhibition of ATGL in these cells by G0S2 is required for efficacy of ATRA treatment. Our data uncover a novel tumor suppressor mechanism by which G0S2 directly inhibits activity of a key intracellular lipase. Our results suggest that elevated ATGL activity may be a general property of many cancer types and potentially represents a novel target for chemotherapy. PMID:26318046

  10. Fatty acid elongase-5 (Elovl5) regulates hepatic triglyceride catabolism in obese C57BL/6J mice[S

    PubMed Central

    Tripathy, Sasmita; Lytle, Kelli A.; Stevens, Robert D.; Bain, James R.; Newgard, Christopher B.; Greenberg, Andrew S.; Huang, Li-Shin; Jump, Donald B.

    2014-01-01

    Nonalcoholic fatty liver disease is a major public health concern in the obese and type 2 diabetic populations. The high-fat lard diet induces obesity and fatty liver in C57BL/6J mice and suppresses expression of the PPAR-target gene, FA elongase 5 (Elovl5). Elovl5 plays a key role in MUFA and PUFA synthesis. Increasing hepatic Elovl5 activity in obese mice lowered hepatic TGs and endoplasmic reticulum stress markers (X-box binding protein 1 and cAMP-dependent transcription factor 6α) and increased TG catabolism and fatty acyl carnitines. Increased hepatic Elovl5 activity did not increase hepatic capacity for β-oxidation. Elovl5 effects on hepatic TG catabolism were linked to increased protein levels of adipocyte TG lipase (ATGL) and comparative gene identification 58 (CGI58). Elevated hepatic Elovl5 activity also induced the expression of some (pyruvate dehydrogenase kinase 4 and fibroblast growth factor 21), but not other cytochrome P450 4A10 (CYP4A10), PPAR-target genes. FA products of Elovl5 activity increased ATGL, but not CGI58, mRNA through PPARβ-dependent mechanisms in human HepG2 cells. Treatment of mouse AML12 hepatocytes with the PPARβ agonist (GW0742) decreased 14C-18:2,n-6 in TGs but did not affect β-oxidation. These studies establish that Elovl5 activity regulates hepatic levels of FAs controlling PPARβ activity, ATGL expression, and TG catabolism, but not FA oxidation. PMID:24814977

  11. Postprandial triglyceride-rich lipoproteins regulate perilipin-2 and perilipin-3 lipid-droplet-associated proteins in macrophages.

    PubMed

    Varela, Lourdes M; Lpez, Sergio; Ortega-Gmez, Almudena; Bermdez, Beatriz; Buers, Insa; Robenek, Horst; Muriana, Francisco J G; Abia, Roco

    2015-04-01

    Lipid accumulation in macrophages contributes to atherosclerosis. Within macrophages, lipids are stored in lipid droplets (LDs); perilipin-2 and perilipin-3 are the main LD-associated proteins. Postprandial triglyceride (TG)-rich lipoproteins induce LD accumulation in macrophages. The role of postprandial lipoproteins in perilipin-2 and perilipin-3 regulation was studied. TG-rich lipoproteins (TRLs) induced the levels of intracellular TGs, LDs and perilipin-2 protein expression in THP-1 macrophages and in Apoe(-/-) mice bone-marrow-derived macrophages with low and high basal levels of TGs. Perilipin-3 was only synthesized in mice macrophages with low basal levels of TGs. The regulation was dependent on the fatty acid composition of the lipoproteins; monounsaturated and polyunsaturated fatty acids (PUFAs) more strongly attenuated these effects compared with saturated fatty acids. In THP-1 macrophages, immunofluorescence microscopy and freeze-fracture immunogold labeling indicated that the lipoproteins translocated perilipin-3 from the cytoplasm to the LD surface; only the lipoproteins that were rich in PUFAs suppressed this effect. Chemical inhibition showed that lipoproteins induced perilipin-2 protein expression through the peroxisome proliferator-activated nuclear receptor (PPAR) PPAR? and PPAR? pathways. Overall, our data indicate that postprandial TRLs may be involved in atherosclerotic plaque formation through the regulation of perilipin-2 and perilipin-3 proteins in macrophages. Because the fatty acid composition of the lipoproteins is dependent on the type of fat consumed, the ingestion of olive oil, which is rich in monounsaturated fatty acids, and fish oil, which is rich in omega-3 fatty acids, can be considered a good nutritional strategy to reduce the risk of atherosclerosis by LD-associated proteins decrease. PMID:25595097

  12. Nemonoxacin (TG-873870) for treatment of community-acquired pneumonia.

    PubMed

    Lai, Chung-Chih; Lee, Kuan-Yeh; Lin, Shu-Wen; Chen, Yen-Hsu; Kuo, Han-Yueh; Hung, Chien-Ching; Hsueh, Po-Ren

    2014-04-01

    With a broad-spectrum of activity, fluoroquinolones have been widely and successfully used for decades for the treatment of and prophylaxis against various bacterial infections, including community-acquired pneumonia (CAP). However, the use of fluoroquinolones has been compromised by the emergence and spreading of bacterial resistance and the potential for adverse effects. Therefore, there is an unmet need for newer compounds that have a broader spectrum of activity to overcome existing bacterial resistance as well as the potential to minimize the risk of adverse effects. Nemonoxacin (TG-873870), a newly developed quinolone, has demonstrated broad-spectrum activity against Gram-positive, Gram-negative and atypical pathogens, including drug-resistant Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus. Results from Phases I and II studies of treatment of CAP are encouraging. This article reviews the updated data on nemonoxacin, including the bacterial susceptibility, the pharmacologic characteristics, and toxicities, and clinical trials using nemonoxacin for treatment of CAP. PMID:24579813

  13. Bile acid-mediated control of liver triglycerides.

    PubMed

    Fuchs, Claudia; Claudel, Thierry; Trauner, Michael

    2013-11-01

    Bile acids (BAs) are steroidal molecules generated in the liver by cholesterol oxidation. Beside their well-established role in lipid absorption and cholesterol homeostasis, they function as signaling molecules and activate dedicated BA receptors such as the farnesoid X receptor (FXR) and the G-protein coupled receptor TGR5. Through activation of downstream signaling pathways of these key receptors, BAs regulate not only their own synthesis and enterohepatic circulation, but also impact on hepatic lipid, glucose, and energy homeostasis. Therefore, BA-regulated signaling pathways have emerged as attractive targets for understanding the regulation of hepatic triglyceride metabolism in health and disease and treating fatty liver disease and associated metabolic disorders. PMID:24222091

  14. miR-21 regulates triglyceride and cholesterol metabolism in non-alcoholic fatty liver disease by targeting HMGCR.

    PubMed

    Sun, Chuanzheng; Huang, Feizhou; Liu, Xunyang; Xiao, Xuefei; Yang, Mingshi; Hu, Gui; Liu, Huaizheng; Liao, Liangkan

    2015-03-01

    Non-alcoholic fatty liver disease (NAFLD) has emerged as a public health issue with a prevalence of 15-30% in Western populations and 6-25% in Asian populations. Certain studies have revealed the alteration of microRNA (miRNA or miR) profiles in NAFLD and it has been suggested that miR-21 is associated with NAFLD. In the present study, we measured the serum levels of miR-21 in patients with NAFLD and also performed in vitro experiments using a cellular model of NAFLD to further investigate the effects of miR-21 on triglyceride and cholesterol metabolism. Furthermore, a novel target through which miR-21 exerts its effects on NAFLD was identified. The results revealed that the serum levels of miR-21 were lower in patients with NAFLD compared with the healthy controls. In addition, 3-hydroxy-3-methylglutaryl-co-enzyme A reductase (HMGCR) expression was increased in the serum of patients with NAFLD both at the mRNA and protein level. To mimic the NAFLD condition in vitro, HepG2 cells were treated with palmitic acid (PA) and oleic acid (OA). Consistent with the results obtained in the in vivo experiments, the expression levels of miR-21 were decreased and those of HMGCR were increased in the in vitro model of NAFLD. Luciferase reporter assay revealed that HMGCR was a direct target of miR-21 and that miR-21 exerted an effect on both HMGCR transcript degradation and protein translation. Furthermore, the results from the in vitro experiments revealed that miR-21 decreased the levels of triglycerides (TG), free cholesterol (FC) and total cholesterol (TC) in the PA/OA-treated HepG2 cells and that this effect was attenuated by HMGCR overexpression. Taken together, to the best of our knowledge, the present study is the first to report that miR-21 regulates triglyceride and cholesterol metabolism in an in vitro model of NAFLD, and that this effect is achieved by the inhibition of HMGCR expression. We speculate that miR-21 may be a useful biomarker for the diagnosis and treatment of NAFLD. PMID:25605429

  15. Measurement of Myocardial Fatty Acid Esterification Using [1-11C]Palmitate and PET: Comparison with Direct Measurements of Myocardial Triglyceride Synthesis

    PubMed Central

    Coggan, Andrew R.; Kisrieva-Ware, Zulfia; Dence, Carmen S.; Eisenbeis, Paul; Gropler, Robert J.; Herrero, Pilar

    2010-01-01

    The purpose of the present study was to assess the accuracy of non-invasive estimates of the rate of myocardial fatty acid esterification (MFAE) obtained using positron emission tomography (PET). Methods Sixteen dogs were studied after an overnight fast (FAST), during a euglycemic hyperinsulinemic clamp (CLAMP), or during infusion of Intralipid (IL) or IL plus dobutamine (IL/DOB) (n=4/group). The rate of MFAE was quantified using a bolus injection of [1-11C]palmitate and compartmental modeling as described by Bergmann et al.3 and compared to the rate of triglyceride (TG) synthesis measured directly using a continuous infusion of [1-13C]palmitate and tissue sampling. Results Across groups, mean plasma free fatty acid (FFA) concentration varied ~20-fold, with this variation in FFA availability accompanied by a ~20-fold range in directly-measured TG synthesis (i.e., from 71 nmol/min/g in CLAMP to 12875 nmol/min/g in IL). PET-based estimates of MFAE varied to a similar degree (i.e., from 229 nmol/min/g in CLAMP to 543551 nmol/min/g in IL), and were significantly correlated with TG synthesis (i.e., R=0.77, P<0.001). MFAE, however, was 3- to 4-fold higher than TG synthesis in FAST, CLAMP, and IL, but comparable when cardiac work was increased in IL/DOB, suggesting that MFAE reflects, in part, the incorporation of label into amino acids via TCA cycle exchange reactions (e.g., ?-ketoglutarate ? glutamate) as well as the synthesis of TG and other lipids. Conclusions Changes in the rate of MFAE as determined using PET and the compartmental model of Bergmann et al.3 parallel changes in the rate of TG synthesis, at least in the basal state. Although such measurements are not as robust as rates of myocardial FFA uptake and oxidation as estimated by the model, this method should still be useful for quantifying acute changes in FFA storage by the heart in various pathophysiological states. PMID:19479313

  16. [Advances in Diagnosis and Treatment of Differentiated Thyroid Cancer in Patients Showing Thyroglobulin Elevative and Iodine Scintigraphy Negative].

    PubMed

    Ma, Ningshuai; Li, Suping

    2015-06-01

    Thyroglobulin (Tg) and radioiodine whole body scan (WBS) have been commonly used in follow-up of patients with differentiated thyroid carcinoma (DTC). Tg is associated with radioiodine uptake in local or distant metastases. In minority of patients, the follow-up scan shows no functioning thyroid tissue, but the serum thyroglobulin is still elevated. Therefore, we review recent developments of diagnosis and treatment of those patients with differentiated thyroid cancer and with thyroglobulin elevation but negative iodine scintigraphy. PMID:26486005

  17. Genetics and causality of triglyceride-rich lipoproteins in atherosclerotic cardiovascular disease.

    PubMed

    Rosenson, Robert S; Davidson, Michael H; Hirsh, Benjamin J; Kathiresan, Sekar; Gaudet, Daniel

    2014-12-16

    Triglycerides represent 1 component of a heterogeneous pool of triglyceride-rich lipoproteins (TGRLs). The reliance on triglycerides or TGRLs as cardiovascular disease (CVD) risk biomarkers prompted investigations into therapies that lower plasma triglycerides as a means to reduce CVD events. Genetic studies identified TGRL components and pathways involved in their synthesis and metabolism. We advocate that only a subset of genetic mechanisms regulating TGRLs contribute to the risk of CVD events. This "omic" approach recently resulted in new targets for reducing CVD events. PMID:25500239

  18. L-FABP T94A is associated with fasting triglycerides and LDL-cholesterol in women.

    PubMed

    Fisher, Eva; Weikert, Cornelia; Klapper, Maja; Lindner, Inka; Mhlig, Matthias; Spranger, Joachim; Boeing, Heiner; Schrezenmeir, Jrgen; Dring, Frank

    2007-07-01

    To determine the possible role of the common FABP1 T94A polymorphism in modulating susceptibility to traits of the metabolic syndrome, we analysed a random sample of 826 subjects from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort. Multivariate adjusted linear trend regression analysis of metabolic, anthropometric and blood pressure variables in FABP1 T94A genotypes were performed in both genders. In women, a significant trend of higher plasma triglyceride (P=0.01) and LDL-cholesterol (P=0.02) concentrations were seen for A-allele carriers after adjustment for age, menopausal status, hormone intake and Apo E genotype. Because elevated triglyceride and cholesterol levels are important risk factors of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), we additionally analysed the association of the T94A variant and disease risks in two studies enrolling 220 incident CVD and 192 incident T2DM patients of the EPIC-Potsdam cohort. After adjusting for age, sex, BMI and other covariates, we found no association between FABP1 T94A and CVD or T2DM. In conclusion, our study provides evidence for an association of the FABP1 T94A polymorphism and fasting triglycerides and LDL-cholesterol levels in females. These results support previous findings in fenofibrate-treated individuals and thereby provide some additional indication of the functional relevance of the FABP1 T94A SNP in hepatic fatty acid and lipid metabolism in humans. PMID:17485234

  19. Red Blood Cell Docosapentaenoic Acid (DPA n-3) is Inversely Associated with Triglycerides and C-reactive Protein (CRP) in Healthy Adults and Dose-Dependently Increases Following n-3 Fatty Acid Supplementation

    PubMed Central

    Skulas-Ray, Ann C.; Flock, Michael R.; Richter, Chesney K.; Harris, William S.; West, Sheila G.; Kris-Etherton, Penny M.

    2015-01-01

    The role of the long-chain omega-3 (n-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in lipid metabolism and inflammation has been extensively studied; however, little is known about the relationship between docosapentaenoic acid (DPA, 22:5 n-3) and inflammation and triglycerides (TG). We evaluated whether n-3 DPA content of red blood cells (RBC) was associated with markers of inflammation (interleukin-6 (IL-6), tumor necrosis factor ? (TNF-?), and C-reactive protein (CRP) and fasting TG prior to n-3 supplementation in two studies (Study 1: n = 115, aged 2044 years, body mass index (BMI) 2030 kg/m2, TG = 34176 mg/dL; Study 2: n = 28, aged 2265 years, BMI 2437 kg/m2, TG = 141339 mg/dL). We also characterized the dose-response effects of n-3 fatty acid supplementation on RBC n-3 DPA after five months of supplementation with fish oil (Study 1: 0, 300, 600, 900, and 1800 mg/day EPA + DHA) and eight weeks of prescription n-3 ethyl esters (Study 2: 0, 850, and 3400 mg/day EPA + DHA). In Study 1, RBC n-3 DPA was inversely correlated with CRP (R2 = 36%, p < 0.001) and with fasting TG (r = ?0.30, p = 0.001). The latter finding was replicated in Study 2 (r = ?0.33, p = 0.04). In both studies, n-3 supplementation significantly increased RBC n-3 DPA dose-dependently. Relative increases were greater for Study 1, with increases of 29%61% vs. 14%26% for Study 2. The associations between RBC n-3 DPA, CRP, and fasting TG may have important implications for the prevention of atherosclerosis and chronic inflammatory diseases and warrant further study. PMID:26247967

  20. Triglyceride depletion in THP-1 cells alters cholesteryl ester physical state and cholesterol efflux.

    PubMed

    Lada, Aaron T; Willingham, Mark C; St Clair, Richard W

    2002-04-01

    To study macrophage lipid droplet composition and the effects of TG on cholesteryl ester (CE) physical state, hydrolysis, and cholesterol efflux, a technique was developed to remove the majority of accumulated TG with minimal effect on CE content. THP-1 macrophages were incubated with acetylated LDL, and the accumulated TG was depleted by incubation with the acyl-CoA synthetase inhibitor triacsin D in the presence of albumin. Before TG removal, all cellular lipid droplets were isotropic as determined by polarizing light microscopy. When the TG concentration was reduced, anisotropic lipid droplets were visible, indicating a change in physical state, and suggesting that TG and CE originally accumulated in mixed lipid droplets. This change in physical state of lipid droplets was associated with slower rates of CE hydrolysis and cholesterol efflux. Although lipid droplets within the same cell had a similar physical state after TG depletion, there was considerable variability among cells in the physical state of their lipid droplets. In conclusion, THP-1 macrophages store accumulated CE and TG in mixed droplets, and the proportion of CE to TG varies among cells. Reducing accumulated TG altered CE physical state, which in turn affected hydrolysis of CE and cholesterol efflux. PMID:11907145

  1. Oral zinc reduces amyloid burden in Tg2576 mice

    PubMed Central

    Harris, Christopher J.; Voss, Kellen; Murchison, Charles; Ralle, Martina; Frahler, Kate; Carter, Raina; Rhoads, Alison; Lind, Betty; Robinson, Emily; Quinn, Joseph F.

    2014-01-01

    The aggregation of amyloid beta in Alzheimer’s disease can be affected by free transition metals such as copper and zinc in the brain. Addition of copper and zinc with amyloid acts to increase aggregation and copper additionally promotes the formation of reactive oxygen species. We propose that reduction of brain copper by blocking uptake of copper from the diet is a viable strategy to regulate the formation of insoluble amyloid beta in the brain of Tg2576 mice. Mice were treated with regimens of zinc acetate, which acts with metallothionein to block copper uptake in the gut, at various times along their lifespan to model prevention and treatment paradigms. We found that the mice tolerated zinc acetate well over the six month course of study. While we did not observe significant changes in cognition and behavior, there was a reduction in insoluble amyloid beta in the brain. This observation coincided with a reduction in brain copper and interestingly no change in brain zinc. Our findings show that blocking copper uptake from the diet can redistribute copper from the brain and reduce amyloid beta aggregation. PMID:24595193

  2. Precision compression molding process of low Tg glass aspheric lenses

    NASA Astrophysics Data System (ADS)

    Ma, Tao; Yu, Jingchi

    2009-05-01

    Precision Glass Molding Process is adopted for mass production of aspheric lenses, micro-lens array, diffractive optical elements and free-form lenses which are difficult to be manufactured by using conventional methods. In this research, high order aspheric lenses with 6th item are molded using the glass material P-SK57 which is characterized by a low glass transition temperature (Tg) 493°C and thermal expansion coefficient (TEC) 8.9×10-6. Some of the molding conditions are as follow: 1) the molding temperature is 565°C, 2) the pressure force is kept at 4KN for 90 seconds and 3) the lens is cooling at an annealing velocity of 1.5~2°C /s to a release temperature of 180°C. The total molding cycle time is about 16 minutes. Molded aspheric lenses are measured with a Taylorsurf contact profilometer and a Zygo Newview white-light interferometer. As a result, the shape accuracy of molded lenses is less than 0.5um (PV) and surface finish quality is less than 2nm.

  3. GPR56 Inhibits Melanoma Growth by Internalizing and Degrading Its Ligand TG2

    PubMed Central

    Yang, Liquan; Friedland, Scott; Corson, Nancy; Xu, Lei

    2014-01-01

    Excessive accumulation of extracellular matrix (ECM) is a hallmark of tumor microenvironment and plays active roles during tumor progression. How this process is regulated and whether it is reversible for cancer treatment are outstanding questions. The adhesion G protein-coupled receptor GPR56 inhibits melanoma growth and binds to tissue transglutaminase (TG2), a major cross-linking enzyme in ECM. To understand the function of TG2 in GPR56-mediated melanoma inhibition, we performed xenograft studies in immunodeficient Tg2?/? mice. Our results revealed an antagonistic relationship between GPR56 and TG2 in melanoma: while TG2 and its crosslinking activity promote melanoma growth, GPR56 antagonizes this effect by internalizing and degrading it. The negative regulation of TG2 by GPR56 associates with the decreased deposition of a major ECM protein, fibronectin, and impaired accumulation of focal adhesion kinase, indicating that the GPR56-TG2 interaction regulates ECM deposition and cell-ECM adhesion. Taken together, our findings establish the roles of TG2 in GPR56-mediated melanoma inhibition. The uncovered antagonistic relationship between GPR56 and TG2 proposes a mechanism by which ECM accumulation/crosslinking in tumors may be reversed, and thus could have therapeutic potential for cancer control and treatment. PMID:24356421

  4. Effects of dietary zinc and copper supplementation on serum triglyceride, total-cholesterol and HDL-cholesterol concentrations on young Sprague Dawley male rats

    SciTech Connect

    Frimpong, N.A.; Magee, A.C.

    1986-03-01

    To determine the effects of the level of zinc (Zn) and copper (Cu) supplementation and of Zn/Cu ratio on serum triglycerides (TG), total-cholesterol (TC), and HDL-cholesterol (HDL-C) concentrations, groups of weanling male Sprague Dawley rats were fed diets containing 4 levels of Cu (0, 0.56, 1.68, and 5.04 ppm) and 4 levels of Zn (0, 5, 10 and 20 ppm) for 6 weeks (Low supplementation, Expt I), or a high Zn and Cu supplements each at 4 levels (0, 5.6, 16.8, and 50.4 ppm Cu, plus 0, 50, 100, and 200 ppm Zn) for 6 weeks (Expt II). The effects of Zn/Cu ratios on the parameters were evaluated by combining data from Expt I and Expt II treatments with the same Zn/Cu ratios but different levels of Zn and Cu. Results of the combined data indicated that an increase in dietary Zn was associated with significant (p less than or equal to 0.01) increase in serum triglyceride concentrations, while an increase in dietary Cu was associated with significant (p less than or equal to 0.01) decrease in serum TC and HDL-C concentrations. Dietary Zn/Cu ratios had no significant effect on serum lipids. There is the indication that the absolute levels of the minerals in the diet may be more important in lipid metabolism. These results are in agreement with previous reports.

  5. Demographic, behavioral, biochemical, and dietary correlates of plasma triglycerides. Lipid Research Clinics Program Prevalence Study.

    PubMed

    Cowan, L D; Wilcosky, T; Criqui, M H; Barrett-Connor, E; Suchindran, C M; Wallace, R; Laskarzewski, P; Walden, C

    1985-01-01

    Few studies have simultaneously examined the relationship of triglyceride levels with a wide variety of potential covariates. Thus, the present study was designed to assess in a large, free-living population the association of fasting plasma triglyceride values with selected demographic, behavioral, biochemical, and dietary measures. These analyses were done using data obtained from 5189 white men and women aged 20 to 69 years who participated in the Lipid Research Clinics Program Prevalence Study. Of the eight nondietary factors examined, age, Quetelet Index, fasting plasma glucose, and cigarette smoking were strongly, positively associated (p less than 0.0001) with triglycerides in men and in women not using gonadal hormones. Among women using oral contraceptives or estrogens, only Quetelet Index (p less than 0.01) and cigarette smoking (p = 0.01) were significantly related to triglyceride values. Physical activity was inversely associated (p less than 0.0001) and use of diuretic medications was positively related (p less than 0.01) to triglycerides only in men. Results of analyses of triglycerides and six selected dietary measures varied by age, sex, and hormone-use subgroups. Although none of the dietary variables showed consistent associations with triglycerides across all of the subgroups, triglycerides tended to be inversely associated with total calories per kilogram of body weight and the percentage of calories as dietary fat. PMID:4038160

  6. Common variants associated with plasma triglycerides and risk for coronary artery disease

    PubMed Central

    Do, Ron; Willer, Cristen J.; Schmidt, Ellen M.; Sengupta, Sebanti; Gao, Chi; Peloso, Gina M.; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L.; Mora, Samia; Beckmann, Jacques S.; Bragg-Gresham, Jennifer L.; Chang, Hsing-Yi; Demirkan, Ayşe; Den Hertog, Heleen M.; Donnelly, Louise A.; Ehret, Georg B.; Esko, Tõnu; Feitosa, Mary F.; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M.; Freitag, Daniel F.; Gurdasani, Deepti; Heikkilä, Kauko; Hyppönen, Elina; Isaacs, Aaron; Jackson, Anne U.; Johansson, Åsa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E.; Li, Xiaohui; Luan, Jian'an; Lyytikäinen, Leo-Pekka; Magnusson, Patrik K.E.; Mangino, Massimo; Mihailov, Evelin; Montasser, May E.; Müller-Nurasyid, Martina; Nolte, Ilja M.; O'Connell, Jeffrey R.; Palmer, Cameron D.; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K.; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J.; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M.; Thorleifsson, Gudmar; Van den Herik, Evita G.; Voight, Benjamin F.; Volcik, Kelly A.; Waite, Lindsay L.; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Inês; Been, Latonya F.; Bolton, Jennifer L.; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S.; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S.F.; Döring, Angela; Elliott, Paul; Epstein, Stephen E.; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O.; Grallert, Harald; Gravito, Martha L.; Groves, Christopher J.; Hallmans, Göran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A.; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R.; Kaleebu, Pontiano; Kastelein, John J.P.; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimäki, Terho; Lin, Shih-Yi; Lindström, Jaana; Loos, Ruth J.F.; Mach, François; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D.; Müller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V.M.; Nsubuga, Rebecca N.; Olafsson, Isleifur; Ong, Ken K.; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J.; Reilly, Muredach P.; Ridker, Paul M.; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stančáková, Alena; Stirrups, Kathleen; Swift, Amy J.; Tiret, Laurence; Uitterlinden, Andre G.; van Pelt, L. Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H.; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F.; Young, Elizabeth H.; Zhao, Jing Hua; Adair, Linda S.; Arveiler, Dominique; Assimes, Themistocles L.; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O.; Boomsma, Dorret I.; Borecki, Ingrid B.; Bornstein, Stefan R.; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C.; Chen, Yii-Der Ida; Collins, Francis S.; Cooper, Richard S.; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B.; Ferrières, Jean; Ferrucci, Luigi; Freimer, Nelson B.; Gieger, Christian; Groop, Leif C.; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B.; Hingorani, Aroon; Hirschhorn, Joel N.; Hofman, Albert; Hovingh, G. Kees; Hsiung, Chao Agnes; Humphries, Steve E.; Hunt, Steven C.; Hveem, Kristian; Iribarren, Carlos; Järvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kaprio, Jaakko; Kesäniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S.; Koudstaal, Peter J.; Krauss, Ronald M.; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O.; Laakso, Markku; Lakka, Timo A.; Lind, Lars; Lindgren, Cecilia M.; Martin, Nicholas G.; März, Winfried; McCarthy, Mark I.; McKenzie, Colin A.; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D.; Munroe, Patricia B.; Njølstad, Inger; Pedersen, Nancy L.; Power, Chris; Pramstaller, Peter P.; Price, Jackie F.; Psaty, Bruce M.; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K.; Saramies, Jouko; Schwarz, Peter E.H.; Sheu, Wayne H-H; Shuldiner, Alan R.; Siegbahn, Agneta; Spector, Tim D.; Stefansson, Kari; Strachan, David P.; Tayo, Bamidele O.; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M.; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J.; Whitfield, John B.; Wolffenbuttel, Bruce H.R.; Altshuler, David; Ordovas, Jose M.; Boerwinkle, Eric; Palmer, Colin N.A.; Thorsteinsdottir, Unnur; Chasman, Daniel I.; Rotter, Jerome I.; Franks, Paul W.; Ripatti, Samuli; Cupples, L. Adrienne; Sandhu, Manjinder S.; Rich, Stephen S.; Boehnke, Michael; Deloukas, Panos; Mohlke, Karen L.; Ingelsson, Erik; Abecasis, Goncalo R.; Daly, Mark J.; Neale, Benjamin M.; Kathiresan, Sekar

    2013-01-01

    Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiologic studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P<5×10−8 for each) to examine the role of triglycerides on risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglycerides, and show that the direction and magnitude of both are factors in determining CAD risk. Second, we consider loci with only a strong magnitude of association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol, a polymorphism's strength of effect on triglycerides is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD. PMID:24097064

  7. Common variants associated with plasma triglycerides and risk for coronary artery disease.

    PubMed

    Do, Ron; Willer, Cristen J; Schmidt, Ellen M; Sengupta, Sebanti; Gao, Chi; Peloso, Gina M; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L; Mora, Samia; Beckmann, Jacques S; Bragg-Gresham, Jennifer L; Chang, Hsing-Yi; Demirkan, Ay?e; Den Hertog, Heleen M; Donnelly, Louise A; Ehret, Georg B; Esko, Tnu; Feitosa, Mary F; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M; Freitag, Daniel F; Gurdasani, Deepti; Heikkil, Kauko; Hyppnen, Elina; Isaacs, Aaron; Jackson, Anne U; Johansson, Asa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E; Li, Xiaohui; Luan, Jian'an; Lyytikinen, Leo-Pekka; Magnusson, Patrik K E; Mangino, Massimo; Mihailov, Evelin; Montasser, May E; Mller-Nurasyid, Martina; Nolte, Ilja M; O'Connell, Jeffrey R; Palmer, Cameron D; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M; Thorleifsson, Gudmar; Van den Herik, Evita G; Voight, Benjamin F; Volcik, Kelly A; Waite, Lindsay L; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Ins; Been, Latonya F; Bolton, Jennifer L; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S F; Dring, Angela; Elliott, Paul; Epstein, Stephen E; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O; Grallert, Harald; Gravito, Martha L; Groves, Christopher J; Hallmans, Gran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R; Kaleebu, Pontiano; Kastelein, John J P; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimki, Terho; Lin, Shih-Yi; Lindstrm, Jaana; Loos, Ruth J F; Mach, Franois; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D; Mller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V M; Nsubuga, Rebecca N; Olafsson, Isleifur; Ong, Ken K; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J; Reilly, Muredach P; Ridker, Paul M; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stan?kov, Alena; Stirrups, Kathleen; Swift, Amy J; Tiret, Laurence; Uitterlinden, Andre G; van Pelt, L Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F; Young, Elizabeth H; Zhao, Jing Hua; Adair, Linda S; Arveiler, Dominique; Assimes, Themistocles L; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O; Boomsma, Dorret I; Borecki, Ingrid B; Bornstein, Stefan R; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C; Chen, Yii-Der Ida; Collins, Francis S; Cooper, Richard S; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B; Ferrires, Jean; Ferrucci, Luigi; Freimer, Nelson B; Gieger, Christian; Groop, Leif C; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B; Hingorani, Aroon; Hirschhorn, Joel N; Hofman, Albert; Hovingh, G Kees; Hsiung, Chao Agnes; Humphries, Steve E; Hunt, Steven C; Hveem, Kristian; Iribarren, Carlos; Jrvelin, Marjo-Riitta; Jula, Antti; Khnen, Mika; Kaprio, Jaakko; Kesniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S; Koudstaal, Peter J; Krauss, Ronald M; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O; Laakso, Markku; Lakka, Timo A; Lind, Lars; Lindgren, Cecilia M; Martin, Nicholas G; Mrz, Winfried; McCarthy, Mark I; McKenzie, Colin A; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D; Munroe, Patricia B; Njlstad, Inger; Pedersen, Nancy L; Power, Chris; Pramstaller, Peter P; Price, Jackie F; Psaty, Bruce M; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K; Saramies, Jouko; Schwarz, Peter E H; Sheu, Wayne H-H; Shuldiner, Alan R; Siegbahn, Agneta; Spector, Tim D; Stefansson, Kari; Strachan, David P; Tayo, Bamidele O; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J; Whitfield, John B; Wolffenbuttel, Bruce H R; Altshuler, David; Ordovas, Jose M; Boerwinkle, Eric; Palmer, Colin N A; Thorsteinsdottir, Unnur; Chasman, Daniel I; Rotter, Jerome I; Franks, Paul W; Ripatti, Samuli; Cupples, L Adrienne; Sandhu, Manjinder S; Rich, Stephen S

    2013-11-01

    Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD. PMID:24097064

  8. Modeling the liquid-solid transition in saturated triglycerides

    NASA Astrophysics Data System (ADS)

    Hanna, C. B.; Pink, D. A.; MacDonald, A. J.; Thillainadarajah, K.; Corkery, R.; Rousseau, D.

    2007-03-01

    Corkery et al. have proposed that the high-temperature state of the triglyceride trilaurin (TL) is a Y-conformer, in which the three hydrocarbon chains are dynamically twisted with an average angle of ˜120 between them. Using computer simulations, we first show that the high-temperature state is indeed the Y conformation. We then develop a theory of the liquid-solid transition of this system, in which TL molecules are in a chair (h) conformation, with extended, possibly all-trans, chains at low-temperatures, and are in a Y conformation in the liquid phase at temperatures higher than the transition temperature, T* 319K. We map this ``h-Y model'' onto an Ising model in a temperature-dependent field, perform a mean-field approximation, and calculate the transition enthalpy, which is in good agreement with experiment. We also predict the temperature-dependence of the 1132 cm-1 Raman band. Our results support the proposal that the liquid state is made up of molecules in the Y conformation.

  9. The mechanism of protein release from triglyceride microspheres.

    PubMed

    Zaky, A; Elbakry, A; Ehmer, A; Breunig, M; Goepferich, A

    2010-10-15

    The purpose of this study was to reveal factors that have an impact on the protein release kinetics from triglyceride microspheres prepared by spray congealing. We investigated the effect of protein particle size, morphology and distribution on protein release from microspheres by confocal laser scanning microscopy (CLSM)(.) The microspheres were loaded with three types of model particles made of FITC-labeled bovine serum albumin: freeze dried protein, spherical particles obtained by precipitation in the presence of PEG and micronized material. Investigation by light microscopy and laser light diffraction revealed that the freeze dried material consisted mainly of app. 29 μm elongated shaped particles. The precipitated BSA consisted mainly of 9.0 μm diameter spherically shaped particles while the micronized protein prepared by jet milling consisted of 4.9 μm sized rounded particles of high uniformity. Microspheres were embedded into a cold-curing resin and cut with a microtome. Subsequent investigation by CLSM revealed major differences of distribution of the polydisperse protein particles inside the microsphere sections depending on the type of BSA that was used. Particles of micronized and precipitated protein were distributed almost throughout the microsphere cross section. The protein distribution had a marked impact on the release kinetics in phosphate buffer. Large protein particles led to a considerably faster release than small ones. By staining the release medium we demonstrated that in all three cases there was a strong correlation between protein release and buffer intrusion. PMID:20659511

  10. Medium chain triglycerides (MCT) in aging and arteriosclerosis.

    PubMed

    Kaunitz, H

    1986-01-01

    Some of the nutritional work with triglycerides consisting mainly of C8 and C10 fatty acids (MCT) lends itself to speculations about their influence on arteriosclerosis. Arteriosclerosis is thought to be part of the normal aging process which is due to age associated molecular biological changes. The lipid theory of arteriosclerosis is rejected. Pertinent studies with MCT include these observations. Feeding of MCT to rats resulted in animals of low body weight, small fat deposits and excellent survival rate. This deserves emphasis because of the beneficial influence of low body weight on aging and arteriosclerosis. MCT feeding was associated with low linoleate and low tocopherol requirements in rats. This may lead to reduced formation of those linoleate derived prostaglandins which favor thrombosis formation. Lower linoleate requirements may also lead to the presence of fewer uncontrolled free radicals in the cells. MCT feeding is associated with low levels of serum and liver cholesterol involving speculations that tissue conditions are such that an adaptive increase of cholesterol is unnecessary. The Demographic Yearbook of the United Nations (1978) reported that Sri Lanka has the lowest death rate from ischemic heart disease. Sri Lanka is the only of the countries giving reliable data where coconut oil (containing over 50% medium chain fatty acids) is the main dietary fat. PMID:3519928

  11. Calculations of phase equilibria for mixtures of triglycerides, fatty acids, and their esters in lower alcohols

    NASA Astrophysics Data System (ADS)

    Stepanov, D. A.; Ermakova, A.; Anikeev, V. I.

    2011-01-01

    The objects of study were mixtures containing triglycerides and lower alcohols and also the products of the transesterification of triglycerides, glycerol and fatty acid esters. The Redlich-Kwong-Soave equation of state was used as a thermodynamic model for the phase state of the selected mixtures over wide temperature, pressure, and composition ranges. Group methods were applied to determine the critical parameters of pure substances and their acentric factors. The parameters obtained were used to calculate the phase diagrams and critical parameters of mixtures containing triglycerides and lower alcohols and the products of the transesterification of triglycerides, glycerol and fatty acid esters, at various alcohol/oil ratios. The conditions of triglyceride transesterification in various lower alcohols providing the supercritical state of reaction mixtures were selected.

  12. The effect of training and diet on lipoprotein cholesterol, tissue lipoprotein lipase and hepatic triglyceride lipase in rats.

    PubMed

    Kimball, T J; Childs, M T; Applebaum-Bowden, D; Sembrowich, W L

    1983-05-01

    Treadmill training for 1 hr/day for 10 wk did not significantly affect chylomicron, very low density, low density, or high density lipoprotein cholesterol in rats fed either a high carbohydrate (glucose) or high fat (coconut oil) diet. Lipoprotein lipase activity of heart, adipose tissue, and skeletal muscle fibers was also unaffected by training. Carbohydrate feeding, however, when compared to fat feeding significantly lowered all lipoprotein cholesterol values as well as heart and fast-oxidative-glycolytic muscle fiber lipase activity and, conversely, significantly elevated hepatic triglyceride lipase activity. Thus, in the rat, an alteration in the serum lipid profile did not occur as a result of training, but dietary differences did independently influence serum lipid levels and tissue enzyme activity. It is suggested that human studies need to control for the possible independent influence of dietary differences when investigating the effects of training on lipoprotein metabolism. PMID:6843361

  13. Effect of fatty acid composition and positional distribution within the triglyceride on selected physical properties of dry-cured ham subcutaneous fat.

    PubMed

    Segura, J; Escudero, R; Romero de vila, M D; Cambero, M I; Lpez-Bote, C J

    2015-05-01

    Analysis of fatty acid (FA) positional distribution within the triglyceride (TG) and selected physical properties of dry-cured ham subcutaneous fat (SF) were carried out. The slip point (SP) of the SF was related to the concentration and positional distribution of FA. When C16:0 was in Sn-2, the SP depended on the FA present in Sn-1,3. Hardness was related to the FA concentration in external positions of TG. A significant direct linear correlation between hardness against C18:0, SFA and average chain length (ACL) and inverse against C18:1, C18:2 and PUFA and unsaturation index (UI) in external positions was found. Adhesiveness was related to SFA, C16:0, C18:0, C18:1, MUFA, UI and ACL exclusively in Sn-2 position. A different role of FA in Sn-2 and Sn-1,3 positions on SP and texture properties of fat was found. PMID:25644667

  14. Modeling the solid-liquid phase transition in saturated triglycerides

    NASA Astrophysics Data System (ADS)

    Pink, David A.; Hanna, Charles B.; Sandt, Christophe; MacDonald, Adam J.; MacEachern, Ronald; Corkery, Robert; Rousseau, Dérick

    2010-02-01

    We investigated theoretically two competing published scenarios for the melting transition of the triglyceride trilaurin (TL): those of (1) Corkery et al. [Langmuir 23, 7241 (2007)], in which the average state of each TL molecule in the liquid phase is a discotic "Y" conformer whose three chains are dynamically twisted, with an average angle of ˜120° between them, and those of (2) Cebula et al. [J. Am. Oil Chem. Soc. 69, 130 (1992)], in which the liquid-state conformation of the TL molecule in the liquid phase is a nematic h∗-conformer whose three chains are in a modified "chair" conformation. We developed two competing models for the two scenarios, in which TL molecules are in a nematic compact-chair (or "h") conformation, with extended, possibly all-trans, chains at low-temperatures, and in either a Y conformation or an h∗ conformation in the liquid state at temperatures higher than the phase-transition temperature, T∗=319 K. We defined an h-Y model as a realization of the proposal of Corkery et al. [Langmuir 23, 7241 (2007)], and explored its predictions by mapping it onto an Ising model in a temperature-dependent field, performing a mean-field approximation, and calculating the transition enthalpy ΔH. We found that the most plausible realization of the h-Y model, as applied to the solid-liquid phase transition in TL, and likely to all saturated triglycerides, gave a value of ΔH in reasonable agreement with the experiment. We then defined an alternative h-h∗ model as a realization of the proposal of Cebula et al. [J. Am. Oil Chem. Soc. 69, 130 (1992)], in which the liquid phase exhibits an average symmetry breaking similar to an h conformation, but with twisted chains, to see whether it could describe the TL phase transition. The h-h∗ model gave a value of ΔH that was too small by a factor of ˜3-4. We also predicted the temperature dependence of the 1132 cm-1 Raman band for both models, and performed measurements of the ratios of three TL Raman bands in the temperature range of -20 °C≤T ≤90 °C. The experimental results were in accord with the predictions of the h-Y model and support the proposal of Corkery et al. [Langmuir 23, 7241 (2007)] that the liquid state is made up of molecules that are each, on average, in a Y conformation. Finally, we carried out computer simulations of minimal-model TLs in the liquid phase, and concluded that although the individual TL molecules are, on average, Y conformers, long-range discotic order is unlikely to exist.

  15. Modeling the solid-liquid phase transition in saturated triglycerides.

    PubMed

    Pink, David A; Hanna, Charles B; Sandt, Christophe; MacDonald, Adam J; MacEachern, Ronald; Corkery, Robert; Rousseau, Drick

    2010-02-01

    We investigated theoretically two competing published scenarios for the melting transition of the triglyceride trilaurin (TL): those of (1) Corkery et al. [Langmuir 23, 7241 (2007)], in which the average state of each TL molecule in the liquid phase is a discotic "Y" conformer whose three chains are dynamically twisted, with an average angle of approximately 120 degrees between them, and those of (2) Cebula et al. [J. Am. Oil Chem. Soc. 69, 130 (1992)], in which the liquid-state conformation of the TL molecule in the liquid phase is a nematic h*-conformer whose three chains are in a modified "chair" conformation. We developed two competing models for the two scenarios, in which TL molecules are in a nematic compact-chair (or "h") conformation, with extended, possibly all-trans, chains at low-temperatures, and in either a Y conformation or an h* conformation in the liquid state at temperatures higher than the phase-transition temperature, T*=319 K. We defined an h-Y model as a realization of the proposal of Corkery et al. [Langmuir 23, 7241 (2007)], and explored its predictions by mapping it onto an Ising model in a temperature-dependent field, performing a mean-field approximation, and calculating the transition enthalpy DeltaH. We found that the most plausible realization of the h-Y model, as applied to the solid-liquid phase transition in TL, and likely to all saturated triglycerides, gave a value of DeltaH in reasonable agreement with the experiment. We then defined an alternative h-h* model as a realization of the proposal of Cebula et al. [J. Am. Oil Chem. Soc. 69, 130 (1992)], in which the liquid phase exhibits an average symmetry breaking similar to an h conformation, but with twisted chains, to see whether it could describe the TL phase transition. The h-h* model gave a value of DeltaH that was too small by a factor of approximately 3-4. We also predicted the temperature dependence of the 1132 cm(-1) Raman band for both models, and performed measurements of the ratios of three TL Raman bands in the temperature range of -20 degrees C < or = T < or = 90 degrees C. The experimental results were in accord with the predictions of the h-Y model and support the proposal of Corkery et al. [Langmuir 23, 7241 (2007)] that the liquid state is made up of molecules that are each, on average, in a Y conformation. Finally, we carried out computer simulations of minimal-model TLs in the liquid phase, and concluded that although the individual TL molecules are, on average, Y conformers, long-range discotic order is unlikely to exist. PMID:20136317

  16. Tissue transglutaminase (TG2) activity regulates osteoblast differentiation and mineralization in the SAOS-2 cell line

    PubMed Central

    Yin, Xiaoxue; Chen, Zhongqiang; Liu, Zhongjun; Song, Chunli

    2012-01-01

    Tissue transglutaminase (type II, TG2) has long been postulated to directly promote skeletal matrix calcification and play an important role in ossification. However, limited information is available on the expression, function and modulating mechanism of TG2 during osteoblast differentiation and mineralization. To address these issues, we cultured the well-established human osteosarcoma cell line SAOS-2 with osteo-inductive conditioned medium and set up three time points (culture days 4, 7, and 14) to represent different stages of SAOS-2 differentiation. Osteoblast markers, mineralization, as well as TG2 expression and activity, were then assayed in each stage. Furthermore, we inhibited TG activity with cystamine and then checked SAOS-2 differentiation and mineralization in each stage. The results showed that during the progression of osteoblast differentiation SAOS-2 cells presented significantly high levels of osteocalcin (OC) mRNA, bone morphogenetic protein-2 (BMP-2) and collagen I, significantly high alkaline phosphatase (ALP) activity, and the increased formation of calcified matrix. With the same tendency, TG2 expression and activity were up-regulated. Furthermore, inhibition of TG activity resulted in a significant decrease of OC, collagen I, and BMP-2 mRNA and of ALP activity and mineralization. This study demonstrated that TG2 is involved in osteoblast differentiation and may play a role in the initiation and regulation of the mineralization processes. Moreover, the modulating effects of TG2 on osteoblasts may be related to BMP-2. PMID:22527131

  17. Asiago classification of ASASSN-15tg as a Type-Ia SN: erratum

    NASA Astrophysics Data System (ADS)

    Benetti, S.; Tomasella, L.; Cappellaro, E.; Elias-Rosa, N.; Ochner, P.; Pastorello, A.; Tartaglia, L.; Terreran, G.; Turatto, M.; Milan, M.

    2015-12-01

    The observation and classification reported in ATEL#8350 refers to ASASSN-15tg (cf. ATEL#8347) and not to ASASSN-15gt. Therefore the correct report is: < pre > Name | Discovery UT | Obs. Date UT | z | Type | Phase |Notes ASASS -15tg | 20151130.21 | 20151201.73 |0.03561 | Ia | pre-max | (1) < /pre > We apologies for the typos.

  18. The role of TG2 in ECV304-related vasculogenic mimicry.

    PubMed

    Jones, Richard A; Wang, Zhuo; Dookie, Shakthi; Griffin, Martin

    2013-01-01

    Tumour vasculogenesis can occur by a process referred to as vasculogenic mimicry, whereby the vascular structures are derived from the tumour itself. These tumours are highly aggressive and do not respond well to anti-angiogenic therapy. Here, we use the well characterised ECV304 cell line, now known as the bladder cancer epithelial cell line T24/83 which shows both epithelial and endothelial characteristics, as a model of in vitro vasculogenic mimicry. Using optimised ratios of co-cultures of ECV304 and C378 human fibroblasts, tubular structures were identifiable after 8 days. The tubular structures showed high levels of TG2 antigen and TG in situ activity. Tubular structures and in situ activity could be blocked either by site-directed irreversible inhibitors of TG2 or by silencing the ECV304 TG2 by antisense transfection. In situ activity for TG2 showed co-localisation with both fibronectin and collagen IV. Deposition of these proteins into the extracellular matrix could be reduced by inclusion of non-cell penetrating TG inhibitors when analysed by Western blotting suggesting that the contribution of TG2 to tube formation is extracellular. Incubation of ECV304 cells with these same irreversible inhibitors reduced cell migration which paralleled a loss in focal adhesion assembly, actin cytoskeleton formation and fibronectin deposition. TG2 appears essential for ECV304 tube formation, thus representing a potential novel therapeutic target in the inhibition of vasculogenic mimicry. PMID:22231926

  19. Cognitive and non-cognitive behaviors in the triple transgenic mouse model of Alzheimer's disease expressing mutated APP, PS1, and Mapt (3xTg-AD).

    PubMed

    Filali, Mohammed; Lalonde, Robert; Theriault, Peter; Julien, Carl; Calon, Frederic; Planel, Emmanuel

    2012-10-01

    3xTg-AD mutant mice are characterized by parenchymal A? plaques and neurofibrillary tangles resembling those found in patients with Alzheimer's disease. The mutants were compared with non-transgenic controls in sensorimotor and learning tests. 3xTg-AD mutants were deficient in T-maze reversal, object recognition, and passive avoidance learning. In addition, the mutants showed hypoactivity in two open-field tests, fewer fecal boli in an observation jar, and reduced enclosed arm entries and head-dipping in the elevated plus-maze. On the contrary, the mutants did not differ from controls in pain thresholds, nest-building, and various reflexes determined by the SHIRPA primary screen and were even better on the rotorod test of motor coordination. PMID:22796601

  20. Independent effects of apolipoprotein AV and apolipoprotein CIII on plasma triglyceride concentrations

    SciTech Connect

    Baroukh, Nadine N.; Bauge, Eric; Akiyama, Jennifer; Chang, Jessie; Fruchart, Jean-Charles; Rubin, Edward M.; Fruchart, Jamila; Pennacchio, Len A.

    2003-08-15

    Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered triglycerides. To overcome these confounding factors and address their relationship, we generated independent lines of mice that either over-expressed (''double transgenic'') or completely lacked (''double knockout'') both apolipoprotein genes. We report that both ''double transgenic'' and ''double knockout'' mice display intermedia tetriglyceride concentrations compared to over-expression or deletion of either gene alone. Furthermore, we find that human ApoAV plasma protein levels in the ''double transgenic'' mice are approximately 500-fold lower than human ApoCIII levels, supporting ApoAV is a potent triglyceride modulator despite its low concentration. Together, these data indicate that APOA5 and APOC3 independently influence plasma triglyceride concentrations but in an opposing manner.

  1. Site-specific genome integration in alphaproteobacteria mediated by TG1 integrase.

    PubMed

    Morita, Kentaro; Morimura, Kohji; Fusada, Naoki; Komatsu, Mamoru; Ikeda, Haruo; Hirano, Nobutaka; Takahashi, Hideo

    2012-01-01

    The serine-type phage integrase is an enzyme that catalyzes site-specific recombination between two attachment sites of phage and host bacterial genomes (attP and attB, respectively) having relatively short but distinct sequences without host auxiliary factor(s). Previously, we have established in vivo and in vitro site-specific recombination systems based on the serine-type integrase produced by actinophage TG1 and determined the minimal sizes of attP(TG1) and attB(TG1) sites required for the in vitro TG1 integrase reaction as 43- and 39-bp, respectively. Here, DNA databases were surveyed by FASTA program with the authentic attB(TG1) sequence of Streptomyces avermitilis as a query. As a result, possible attB(TG1) sequences were extracted from genomes of bacterial strains belonging to Class Alphaproteobacteria in addition to those of Class Actinobacteria. Those sequences extracted with a high similarity score and high sequence identity (we took arbitrarily more than 80% identity) turned out to be located within a conserved region of dapC or related genes encoding aminotransferases and proved to be actually recognized as the cognate substrate of attP(TG1) site by the in vitro TG1 integrase assay. Furthermore, the possible attB(TG1) site of Rhodospirillum rubrum revealed to be used actually as a native (endogenous) attachment site for the in vivo TG1-based integration system. These features are distinct from other serine-type phage integrases and advantageous for a tool of genome technology in varied industrially important bacteria belonging to Class Alphaproteobacteria. PMID:21887508

  2. Farnesoid X receptor: a master regulator of hepatic triglyceride and glucose homeostasis

    PubMed Central

    Jiao, Yang; Lu, Yan; Li, Xiao-ying

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by the aberrant accumulation of triglycerides in hepatocytes in the absence of significant alcohol consumption, viral infection or other specific causes of liver disease. NAFLD has become a burgeoning health problem both worldwide and in China, but its pathogenesis remains poorly understood. Farnesoid X receptor (FXR), a member of the nuclear receptor (NR) superfamily, has been demonstrated to be the primary sensor for endogenous bile acids, and play a crucial role in hepatic triglyceride homeostasis. Deciphering the synergistic contributions of FXR to triglyceride metabolism is critical for discovering therapeutic agents in the treatment of NAFLD and hypertriglyceridemia. PMID:25500875

  3. Glucagon-Like Peptide 2 (GLP-2) Stimulates Postprandial Chylomicron Production and Postabsorptive Release of Intestinal Triglyceride Storage Pools via Induction of Nitric Oxide Signaling in Male Hamsters and Mice.

    PubMed

    Hsieh, Joanne; Trajcevski, Karin E; Farr, Sarah L; Baker, Christopher L; Lake, Elizabeth J; Taher, Jennifer; Iqbal, Jahangir; Hussain, Mahmood M; Adeli, Khosrow

    2015-10-01

    The intestinal overproduction of apolipoprotein B48 (apoB48)-containing chylomicron particles is a common feature of diabetic dyslipidemia and contributes to cardiovascular risk in insulin resistant states. We previously reported that glucagon-like peptide-2 (GLP-2) is a key endocrine stimulator of enterocyte fat absorption and chylomicron output in the postprandial state. GLP-2's stimulatory effect on chylomicron production in the postabsorptive state has been confirmed in human studies. The mechanism by which GLP-2 regulates chylomicron production is unclear, because its receptor is not expressed on enterocytes. We provide evidence for a key role of nitric oxide (NO) in mediating the stimulatory effects of GLP-2 during the postprandial and postabsorptive periods. Intestinal chylomicron production was assessed in GLP-2-treated hamsters administered the pan-specific NO synthase (NOS) inhibitor L-N(G)-nitroarginine methyl ester (L-NAME), and in GLP-2-treated endothelial NOS knockout mice. L-NAME blocked GLP-2-stimulated apoB48 secretion and reduced triglycerides (TGs) in the TG-rich lipoprotein (TRL) fraction of the plasma in the postprandial state. Endothelial NOS-deficient mice were resistant to GLP-2 stimulation and secreted fewer large apoB48-particles. When TG storage pools were allowed to accumulate, L-NAME mitigated the GLP-2-mediated increase in TRL-TG, suggesting that NO is required for early mobilization and secretion of stored TG and preformed chylomicrons. Importantly, the NO donor S-nitroso-L-glutathione was able to elicit an increase in TRL-TG in vivo and stimulate chylomicron release in vitro in primary enterocytes. We describe a novel role for GLP-2-mediated NO-signaling as a critical regulator of intestinal lipid handling and a potential contributor to postprandial dyslipidemia. PMID:26132919

  4. Defective macroautophagic turnover of brain lipids in the TgCRND8 Alzheimer mouse model: prevention by correcting lysosomal proteolytic deficits

    PubMed Central

    Stavrides, Philip; Saito, Mitsuo; Kumar, Asok; Rodriguez-Navarro, Jose A.; Pawlik, Monika; Huo, Chunfeng; Walkley, Steven U.; Saito, Mariko; Cuervo, Ana M.

    2014-01-01

    Autophagy, the major lysosomal pathway for the turnover of intracellular organelles is markedly impaired in neurons in Alzheimers disease and Alzheimer mouse models. We have previously reported that severe lysosomal and amyloid neuropathology and associated cognitive deficits in the TgCRND8 Alzheimer mouse model can be ameliorated by restoring lysosomal proteolytic capacity and autophagy flux via genetic deletion of the lysosomal protease inhibitor, cystatin B. Here we present evidence that macroautophagy is a significant pathway for lipid turnover, which is defective in TgCRND8 brain where lipids accumulate as membranous structures and lipid droplets within giant neuronal autolysosomes. Levels of multiple lipid species including several sphingolipids (ceramide, ganglioside GM3, GM2, GM1, GD3 and GD1a), cardiolipin, cholesterol and cholesteryl esters are elevated in autophagic vacuole fractions and lysosomes isolated from TgCRND8 brain. Lipids are localized in autophagosomes and autolysosomes by double immunofluorescence analyses in wild-type mice and colocalization is increased in TgCRND8 mice where abnormally abundant GM2 ganglioside-positive granules are detected in neuronal lysosomes. Cystatin B deletion in TgCRND8 significantly reduces the number of GM2-positive granules and lowers the levels of GM2 and GM3 in lysosomes, decreases lipofuscin-related autofluorescence, and eliminates giant lipid-containing autolysosomes while increasing numbers of normal-sized autolysosomes/lysosomes with reduced content of undigested components. These findings have identified macroautophagy as a previously unappreciated route for delivering membrane lipids to lysosomes for turnover, a function that has so far been considered to be mediated exclusively through the endocytic pathway, and revealed that autophagic-lysosomal dysfunction in TgCRND8 brain impedes lysosomal turnover of lipids as well as proteins. The amelioration of lipid accumulation in TgCRND8 by removing cystatin B inhibition on lysosomal proteases suggests that enhancing lysosomal proteolysis improves the overall environment of the lysosome and its clearance functions, which may be possibly relevant to a broader range of lysosomal disorders beyond Alzheimers disease. PMID:25270989

  5. Phase behaviour in binary mixed Langmuir Blodgett monolayers of triglycerides

    NASA Astrophysics Data System (ADS)

    Zdravkova, Aneliya N.; van der Eerden, J. P. J. M.

    2007-09-01

    Binary mixed monolayers of the triglycerides (TAGs)-tripalmitin (PPP), tristearin (SSS) and triarachidin (AAA) at the air-water interface are investigated with the Langmuir method. Langmuir-Blodgett (LB) layers obtained by deposition on mica are investigated by Atomic Force Microscopy. Combining Langmuir and AFM results the relation between the phase behaviour of binary mixed TAGs and their chain length is established. TAG mixtures form monolayers with molecules in trident conformation at the air-water interface, like pure TAGs. The area Acond=63 Å 2 and the pressure πcond=8-10 mN/m that separate "gas" and "condensed" film structures are the same for all mixtures and pure systems. In the π- A isotherms the sharpness of the transition from "gas" to "condensed" phase decreases with the average chain length for all systems. Using AFM data the monolayer thicknesses for mixtures and pure systems is found to be linearly dependent on the average chain length of the TAG molecules. A linear relation between film thickness and applied AFM force is established. The corresponding coefficient K˜ is higher for mixed monolayers ( K˜=0.08±0.01 nN) than for pure systems ( K˜=0.07±0.01 nN). AFM images show phase separation in the systems PPP-SSS and PPP-AAA. The solubility of the shorter PPP molecules in the "long" (SSS- and AAA-rich) phase is significant. For the mixture SSS-AAA, phase separation is not observed. In that mixture the monolayer thickness varies linearly with composition, supporting the conclusion that SSS and AAA mix almost ideally. The main driving force for phase separation is the difference in the alkyl chain length. Indeed PPP-AAA (length difference 4 C atoms) shows the most clear phase separation. The relatively weak phase separation in PPP-SSS and the absence of phase separation in SSS-AAA show that the influence of chain length difference decreases with increasing average chain length. In air PPP-SSS and PPP-AAA mixed monolayers are unstable and crystals with α- and β-like structure are formed on top of the monolayer as in pure PPP and SSS systems.

  6. Association between microRNA-21 concentration and lipid profile in patients with acute coronary syndrome without persistent ST-segment elevation.

    PubMed

    Mi?kowiec, Dawid; Lipiec, Piotr; Wierzbowska-Drabik, Karina; Kupczy?ska, Karolina; Michalski, B?a?ej; Wdowiak-Okrojek, Katarzyna; Wejner-Mik, Paulina; Kasprzak, Jaros?aw D

    2016-02-01

    INTRODUCTION MicroRNA (miRNAs) are noncoding RNAs involved in the regulation of gene expression. Certain miRNAs, especially miRNA-21 (miR-21), may be involved in lipid metabolism. OBJECTIVES The aim of the study was to evaluate the association between plasma free circulating miR-21 levels and lipid fractions: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and triglycerides (TG), as well as their atherogenic profile expressed as the ratio of individual lipid fractions (TC:LDL-C, TC:non-HDL-C, TG:HDL-C, and HDL-C:LDL-C) in patients with acute coronary syndromes without persistent ST -segment elevation (NSTE ACS). PATIENTS AND METHODS The study group consisted of 34 patients diagnosed with NSTE ACS on admission to the emergency department. Plasma miRNA levels were determined by real-time polymerase chain reaction and the ??Ct method. Serum lipid fractions were assessed after a minimum of 12-hour fasting during the first day of hospitalization. RESULTS MiR-21 levels showed a significant inverse correlation with TC (r = -0.5; P = 0.002), LDLC (r = -0.5; P = 0.001), and non-HDL-C (r = -0.6; P <0.001) levels. Moreover, they were inversely correlated with TC:HDL-Cratio (r = -0.6; P <0.001), LDL-C:HDL-Cratio (r = -0.6; P <0.001), TG:HDL-Cratio (r = -0.4; P = 0.037), and TC:non-HDLratio (r = 0.6; P <0.001). In a multivariate analysis, miR-21 levels (? = -0.41; P = 0.018) and the need for revascularization (? = 0.35; P = 0.027) were independent predictors of non-HDL-C levels. CONCLUSIONS Free circulating miR-21 levels inversely correlate with TC, LDL-C, and non-HDL-C and are an independent predictor of non-HDL-C levels in patients with NSTE ACS. Thus, the overexpression of miR-21 is associated with a less atherogenic lipid profile. PMID:26842377

  7. Regulation of TG-interacting factor by transforming growth factor-beta.

    PubMed Central

    Chen, Feifei; Ogawa, Kenji; Nagarajan, Raman P; Zhang, Meiyu; Kuang, Chenzhong; Chen, Yan

    2003-01-01

    TG-interacting factor (TGIF) is a transcriptional co-repressor that directly associates with Smad (Sma- and Mad-related protein) proteins and inhibits Smad-mediated transcriptional activation. By using Affymetrix (Santa Clara, CA, U.S.A.) oligonucleotide microarray analysis, we found that TGIF mRNA level was elevated by transforming-growth-factor-beta (TGF-beta) treatment in a human T-cell line, HuT78. Subsequent reverse-transcription PCR assays indicated that TGF-beta1 and activin were able to induce a rapid and transient increase in the level of TGIF in both HuT78 and HepG2 hepatoma cells. To analyse whether or not the regulation of TGIF mRNA occurs at the transcriptional level, a 2.4 kb human TGIF promoter was isolated. A primer extension assay was performed to localize the putative transcription initiation site of the promoter. When transiently expressed in HepG2 cells, this promoter was stimulated by TGF-beta1 and activin treatment in a time-dependent manner. A series of deletion mutants of the TGIF promoter were also generated to further characterize the TGF-beta responsive region of the promoter. In addition, expression of TGIF was able to cause a dose-dependent inhibition of TGF-beta and activin signalling. Taken together, these experiments indicated that TGIF is a novel transcriptional target of TGF-beta and activin signalling and is likely involved in a negative feedback loop to desensitize TGF-beta/activin action. PMID:12593671

  8. Thermodyanmic Scaling of Polymer Dynamics versus Shifting by T-Tg

    NASA Astrophysics Data System (ADS)

    Guo, Jiaxi; Simon, Sindee

    2011-03-01

    A universal scaling law for the relaxation time (?) of amorphous liquids as a function of temperature and volume has been proposed by Roland and coworkers: ? (T,V) = F(TV?) , where ? is a material-dependent constant. We test this law for four materials, linear polystyrene, star polystyrene, and two polycyanurate networks using PVT data obtained in our laboratory coupled with the temperature dependent shift factors used to reduce the viscoelastic bulk modulus at different pressures and the dynamic shear properties at ambient pressure. In all cases, ? can be reduced both by the scaling law and by shifting to account for the changes in Tg with pressure, i.e., by plotting versus T - Tg (P). In the polycyanurate case, time-crosslink density superposition holds and ? for the two materials can be reduced simply by shifting the temperature with respect to Tg to account for the changes in Tg with crosslink density; however, the thermodynamic scaling for the two materials does not superpose unless the thermodynamic function is normalized by Tg Vg ? . The validity of the scaling function and its relationship to T - Tg will be further examined. In addition, the impact of errors in T, Tg , and V on the ability to satisfactorily reduce data and obtain universal scaling will be discussed.

  9. Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase

    SciTech Connect

    Ma, Noelle; Nicholson, Catherine J.; Wong, Michael; Holloway, Alison C.; Hardy, Daniel B.

    2014-02-15

    While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1 mg/kg/day) for two weeks prior to mating until weaning. At postnatal day 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXRα), we measured LXRα expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXRα protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway. - Highlights: • Our data reveals the links nicotine exposure in utero and long-term hypertriglyceridemia. • It is due to nicotine-induced augmented expression of hepatic FAS and LXRα activity. • Moreover, this involves nicotine-induced enhanced acetylation of histone H3 [K9,14]. • This provides a mechanism for developmental origins of health and disease (DOHaD)

  10. Male Gender, Increased Blood Viscosity, Body Mass Index and Triglyceride Levels Are Independently Associated with Systemic Relative Hypertension in Sickle Cell Anemia

    PubMed Central

    Romana, Marc; Lemonne, Nathalie; Mougenel, Daniele; Waltz, Xavier; Tressières, Benoît; Etienne-Julan, Maryse; Tarer, Vanessa; Hardy-Dessources, Marie-Dominique; Connes, Philippe

    2013-01-01

    Patients with sickle cell anemia (SCA) have usually lower diastolic, systolic and mean blood pressure (BP) than the general population. However, BP values ≥120/70 mmHg considerably increase the risk for acute and chronic complications in SCA. The aim of this study was to identify biological factors associated with relative hypertension in adults with SCA. We compared the hematological, lipid and hemolytic profiles, as well as blood viscosity, between SCA patients with normal BP (<120/70 mmHg, n = 54) and those with relative hypertension (BP≥120/70 mmHg, n = 43). Our results demonstrated that male gender (OR: 3.49; 95%CI 1.20 to 10.16, p<0.05), triglycerides (OR: 9.19; 95% CI 2.29 to 36.95, p<0.01), blood viscosity (OR: 1.35; 95% CI 1.01 to 1.81, p<0.05) and body mass index (OR: 1.37; 95% CI 1.14 to 1.64, p<0.01) were independent risks factors for relative hypertension in SCA. No association was found between the BP status and the positive history of painful vaso-occlusive crisis or acute chest syndrome. An association between triglycerides level and the occurrence of these two major acute complications was detected. Our study suggests that male gender, increased triglycerides level, BMI and blood viscosity could increase the risk for developing relative hypertension in SCA. In addition, our results support a role of moderately elevated triglycerides in the pathophysiology of vaso-occlusive events. PMID:23785465

  11. High-Fat Diet with Acyl-Ghrelin Treatment Leads to Weight Gain with Low Inflammation, High Oxidative Capacity and Normal Triglycerides in Rat Muscle

    PubMed Central

    Barazzoni, Rocco; Zanetti, Michela; Semolic, Annamaria; Cattin, Maria Rosa; Pirulli, Alessia; Cattin, Luigi; Guarnieri, Gianfranco

    2011-01-01

    Obesity is associated with muscle lipid accumulation. Experimental models suggest that inflammatory cytokines, low mitochondrial oxidative capacity and paradoxically high insulin signaling activation favor this alteration. The gastric orexigenic hormone acylated ghrelin (A-Ghr) has antiinflammatory effects in vitro and it lowers muscle triglycerides while modulating mitochondrial oxidative capacity in lean rodents. We tested the hypothesis that A-Ghr treatment in high-fat feeding results in a model of weight gain characterized by low muscle inflammation and triglycerides with high muscle mitochondrial oxidative capacity. A-Ghr at a non-orexigenic dose (HFG: twice-daily 200-g s.c.) or saline (HF) were administered for 4 days to rats fed a high-fat diet for one month. Compared to lean control (C) HF had higher body weight and plasma free fatty acids (FFA), and HFG partially prevented FFA elevation (P<0.05). HFG also had the lowest muscle inflammation (nuclear NFkB, tissue TNF-alpha) with mitochondrial enzyme activities higher than C (P<0.05 vs C, P?=?NS vs HF). Under these conditions HFG prevented the HF-associated muscle triglyceride accumulation (P<0.05). The above effects were independent of changes in redox state (total-oxidized glutathione, glutathione peroxidase activity) and were not associated with changes in phosphorylation of AKT and selected AKT targets. Ghrelin administration following high-fat feeding results in a novel model of weight gain with low inflammation, high mitochondrial enzyme activities and normalized triglycerides in skeletal muscle. These effects are independent of changes in tissue redox state and insulin signaling, and they suggest a potential positive metabolic impact of ghrelin in fat-induced obesity. PMID:22039445

  12. Measurement of triglycerides concentration in human serum using near-infrared transmission spectroscopy and interval PLS

    NASA Astrophysics Data System (ADS)

    Huang, Furong; Yu, Jianhui; Li, Shiping

    2011-11-01

    In order to measurement of Triglycerides in human serum with reagent-less using near-infrared (NIR) spectroscopy. Interval partial least square (iPLS) was proposed as an effective variable selection approach for multivariate calibration. For this purpose, an independent sample set was employed to evaluate the prediction ability of the resulting model. The spectrum was split into different interval. Then, the informative region of Triglycerides (1654-1746nm), in which the PLS model has a low RMSEP with 0.157mmol/L and a high R with 0.967, is selected with 18 intervals. The results show that the informative region of Triglycerides can be obtained by iPLS and applied to design the simpler reagent-less NIR instruments for inexpensive Triglycerides measurement in future.

  13. Lapacho tea (Tabebuia impetiginosa) extract inhibits pancreatic lipase and delays postprandial triglyceride increase in rats.

    PubMed

    Kiage-Mokua, Beatrice Nyanchama; Roos, Nils; Schrezenmeir, Jrgen

    2012-12-01

    Earlier work in our laboratory indicated that ethanolic extracts of Tabebuia impetiginosa, Arctium lappa L., Calendula officinalis, Helianthus annuus, Linum usitatissimum and L. propolis, inhibit pancreatic lipase in vitro. In a follow-up study we assessed their effects on plasma triglycerides in rats fed on a fatty meal. Extracts, orlistat or only ethanol were given orally to the rats together with the test meal and the rate of increase of postprandial triglycerides was assessed over 4?h. Clearing of the triglycerides from the blood compartment was abolished by inhibiting lipoprotein lipase with Triton WR-1339. Our results showed that out of all the extracts, the bark of Tabebuia impetiginosa led to a significant delay in the postprandial increase of plasma triglycerides. However, lapachol, which is contained in the bark of Tabebuia impetiginosa and soluble in ethanol, had no lipase inhibitory effect in vitro and hence this substance did not seem to mediate the pertinent effect. PMID:22431070

  14. Antioxidant capacity and stability of liposomes containing a triglyceride derivative of lipoic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The multi-functional nutritional agent lipoic acid offers numerous beneficial effects to oxidatively stressed tissues. Lipoic acid was enzymatically incorporated into a triglyceride in conjunction with oleic acid, creating lipoyl dioleoylglycerol, and then chemically reduced to form dihydrolipoyl d...

  15. An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing.

    PubMed

    Pennacchio, L A; Olivier, M; Hubacek, J A; Cohen, J C; Cox, D R; Fruchart, J C; Krauss, R M; Rubin, E M

    2001-10-01

    Comparison of genomic DNA sequences from human and mouse revealed a new apolipoprotein (APO) gene (APOAV) located proximal to the well-characterized APOAI/CIII/AIV gene cluster on human 11q23. Mice expressing a human APOAV transgene showed a decrease in plasma triglyceride concentrations to one-third of those in control mice; conversely, knockout mice lacking Apoav had four times as much plasma triglycerides as controls. In humans, single nucleotide polymorphisms (SNPs) across the APOAV locus were found to be significantly associated with plasma triglyceride levels in two independent studies. These findings indicate that APOAV is an important determinant of plasma triglyceride levels, a major risk factor for coronary artery disease. PMID:11588264

  16. Patient Guide to the Assessment and Treatment of Hypertriglyceridemia (High Triglycerides)

    MedlinePLUS

    ... day because of the risk of liver damage. • Omega-3 (n-3) fatty acids eicosapentaenoic acid (EPA) and ... high triglycerides. You can get high doses of omega-3 fatty acids in a fish oil supplement or ...

  17. Analysis of apolipoprotein A5, C3 and plasma triglyceride concentrations in genetically engineered mice

    SciTech Connect

    Baroukh, Nadine; Bauge, Eric; Akiyama, Jennifer; Chang, Jessie; Afzal, Veena; Fruchart, Jean-Charles; Rubin, Edward M.; Fruchart, Jamila; Pennacchio, Len A.

    2004-03-11

    To address the relationship between the apolipoprotein A5 and C3 genes, we generated independent lines of mice that either over-expressed or completely lacked both genes. We report both lines display normal triglyceride concentrations compared to over-expression or deletion of either gene alone. Together, these data support that APOA5 and APOC3 independently influence plasma triglyceride concentrations but in an opposing manner.

  18. Two independent apolipoprotein a5 Haplotypes influence human plasma triglyceride levels

    SciTech Connect

    Pennacchio, Len A.; Olivier, Michael; Hubacek, Jaroslav A.; Krauss, Ronald M.; Rubin, Edward M.; Cohen, Jonathan C.

    2002-09-16

    The recently identified apolipoprotein A5 gene (APOA5) has been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. We previously identified an APOA5 haplotype (designated APOA5*2) that is present in {approx}16 percent of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA5*3) containing the rare allele of the single nucleotide polymorphism c.56C>G that changes serine to tryptophan at codon 19 and is independently associated with high plasma triglyceride levels in three different populations. In a sample of 264 Caucasian men and women with plasma triglyceride concentrations above the 90th percentile or below the 10th percentile, the APOA5*3 haplotype was more than three-fold more common in the group with high plasma triglyceride levels. In a second independently ascertained sample of Caucasian men and women (n 1/4 419) who were studied while consuming their self-selected diets as well as after high-carbohydrate diets and high-fat diets, the APOA5*3 haplotype was associated with increased plasma triglyceride levels on all three dietary regimens. In a third population comprising 2660 randomly selected individuals, the APOA5*3 haplotype was found in 12 percent of Caucasians, 14 percent of African-Americans and 28 percent of Hispanics and was associated with increased plasma triglyceride levels in both men and women in each ethnic group. These findings establish that the APOA5 locus contributes significantly to inter-individual variation in plasma triglyceride levels in humans. Together, the APOA5*2 and APOA5*3 haplotypes are found in 25 50 percent of African-Americans, Hispanics and Caucasians and support the contribution of common human variation to quantitative phenotypes in the general population.

  19. Bleed of and biologic response to triglyceride filler used in radiolucent breast implants.

    PubMed

    Young, V L; Lund, H; Ueda, K; Pidgeon, L; Schorr, M W; Kreeger, J

    1996-05-01

    Radiolucent breast implants filled with triglyceride oil have recently entered limited clinical trials. To investigate the questions of oil bleed and the fate of triglycerides that might escape from ruptured breast implants, experiments reported here used peanut oil labeled with radioisotopes so that it could be traced in the urine, feces, and organs of two groups of rabbits. In one experiment, 18 rabbits were implanted with peanut oil-filled implants labeled with tritium to determine whether triglycerides diffuse across silicone elastomer shells. In another experiment, 19 rabbits were injected with 14C-labeled peanut oil to study what might happen to the oil if an implant ruptures. At the end of the follow-up period, we measured radioisotope levels in tissue samples taken from the periprosthetic capsule or injection site of each rabbit, as well as from major organs and the subcutaneous fat on the dorsum opposite the experimental site. One experiment revealed that triglycerides do bleed across the implant shells. Tritium levels were highest in the implant capsule, the omentum, the aorta, and the subcutaneous fat on the nonexperimental side. In the experiment simulating implant rupture, 14C levels were above the background radiation count at the injection site and in the same tissue sites as in the bleed experiment. Both in vivo radiolabeling studies indicate that triglycerides freed from implants by means of bleed or rupture would be absorbed, metabolized, and either excreted or redistributed to the body's normal fat storage sites if they are not needed for energy. In a third in vitro experiment, triglyceride oil specimens were inoculated with various microorganisms associated with wound infections: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus epidermidis, and diphtheroids. The data demonstrate that neutral triglycerides used as a breast implant filler do not support growth of common infection-producing bacteria and suggest that triglycerides may have bactericidal properties. PMID:8628800

  20. Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels.

    PubMed

    Pennacchio, Len A; Olivier, Michael; Hubacek, Jaroslav A; Krauss, Ronald M; Rubin, Edward M; Cohen, Jonathan C

    2002-11-15

    The recently identified apolipoprotein A5 gene (APOA5) has been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. We previously identified an APOA5 haplotype (designated APOA5*2) that is present in approximately 16% of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA5*3) containing the rare allele of the single nucleotide polymorphism c.56C>G that changes serine to tryptophan at codon 19 and is independently associated with high plasma triglyceride levels in three different populations. In a sample of 264 Caucasian men and women with plasma triglyceride concentrations above the 90th percentile or below the 10th percentile, the APOA5*3 haplotype was more than three-fold more common in the group with high plasma triglyceride levels. In a second independently ascertained sample of Caucasian men and women (n=419) who were studied while consuming their self-selected diets as well as after high-carbohydrate diets and high-fat diets, the APOA5*3 haplotype was associated with increased plasma triglyceride levels on all three dietary regimens. In a third population comprising 2660 randomly selected individuals, the APOA5*3 haplotype was found in 12% of Caucasians, 14% of African-Americans and 28% of Hispanics and was associated with increased plasma triglyceride levels in both men and women in each ethnic group. These findings establish that the APOA5 locus contributes significantly to inter-individual variation in plasma triglyceride levels in humans. Together, the APOA5*2 and APOA5*3 haplotypes are found in 25-50% of African-Americans, Hispanics and Caucasians and support the contribution of common human variation to quantitative phenotypes in the general population. PMID:12417524

  1. New Agegraphic Pilgrim Dark Energy in f(T, TG) Gravity

    NASA Astrophysics Data System (ADS)

    Abdul, Jawad; Ujjal, Debnath

    2015-08-01

    In this work, we briefly discuss a novel class of modified gravity like f(T, TG) gravity. In this background, we assume the new agegraphic version of pilgrim dark energy and reconstruct f(T, TG) models for two specific values of s. We also discuss the equation of state parameter, squared speed of sound and wDE-w?DE plane for these reconstructed f(T, TG) models. The equation of state parameter provides phantom-like behavior of the universe. The wDE-w?DE plane also corresponds to ?CDM limit, thawing and freezing regions for both models.

  2. An insight on acyl migration in solvent-free ethanolysis of model triglycerides using Novozym 435.

    PubMed

    Snchez, Daniel Alberto; Tonetto, Gabriela Marta; Ferreira, Mara Lujn

    2016-02-20

    In this work, the ethanolysis of triglycerides catalyzed by immobilized lipase was studied, focusing on the secondary reaction of acyl migration. The catalytic tests were performed in a solvent-free reaction medium using Novozym 435 as biocatalyst. The selected experimental variables were biocatalyst loading (5-20mg), reaction time (30-90min), and chain length of the fatty acids in triglycerides with and without unsaturation (short (triacetin), medium (tricaprylin) and long (tripalmitin/triolein)). The formation of 2-monoglyceride by ethanolysis of triglycerides was favored by long reaction times and large biocatalyst loading with saturated short- to medium-chain triglycerides. In the case of long-chain triglycerides, the formation of this monoglyceride was widely limited by acyl migration. In turn, acyl migration increased the yield of ethyl esters and minimized the content of monoglycerides and diglycerides. Thus, the enzymatic synthesis of biodiesel was favored by long-chain triglycerides (which favor the acyl migration), long reaction times and large biocatalyst loading. The conversion of acylglycerides made from long-chain fatty acids with unsaturation was relatively low due to limitations in their access to the active site of the lipase. PMID:26795690

  3. L-type Ca2+ currents at CA1 synapses, but not CA3 or dentate granule neuron synapses, are increased in 3xTgAD mice in an age-dependent manner

    PubMed Central

    Wang, Yue; Mattson, Mark P.

    2013-01-01

    Abnormal neuronal excitability and impaired synaptic plasticity might occur before the degeneration and death of neurons in Alzheimers disease (AD). To elucidate potential biophysical alterations underlying aberrant neuronal network activity in AD, we performed whole-cell patch clamp analyses of L-type (nifedipine-sensitive) Ca2+ currents (L-VGCC), 4aminopyridine-sensitive K+ currents, and AMPA (2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid) and NMDA (N-methyl-D-aspartate) currents in CA1, CA3, and dentate granule neurons in hippocampal slices from young, middle-age, and old 3xTgAD mice and age-matched wild type mice. 3xTgAD mice develop progressive widespread accumulation of amyloid b-peptide, and selective hyperphosphorylated tau pathology in hippocampal CA1 neurons, which are associated with cognitive deficits, but independent of overt neuronal degeneration. An age-related elevation of L-type Ca2+ channel current density occurred in CA1 neurons in 3xTgAD mice, but not in wild type mice, with the magnitude being significantly greater in older 3xTgAD mice. The NMDA current was also significantly elevated in CA1 neurons of old 3xTgAD mice compared with in old wild type mice. There were no differences in the amplitude of K+ or AMPA currents in CA1 neurons of 3xTgAD mice compared with wild type mice at any age. There were no significant differences in Ca2+, K+, AMPA, or NMDA currents in CA3 and dentate neurons from 3xTgAD mice compared with wild type mice at any age. Our results reveal an age-related increase of L-VGCC density in CA1 neurons, but not in CA3 or dentate granule neurons, of 3xTgAD mice. These findings suggest a potential contribution of altered L-VGCC to the selective vulnerability of CA1 neurons to tau pathology in the 3xTgAD mice and to their degeneration in AD patients. PMID:23932880

  4. Long-term therapeutic silencing of miR-33 increases circulating triglyceride levels and hepatic lipid accumulation in mice

    PubMed Central

    Goedeke, Leigh; Salerno, Alessandro; Ramrez, Cristina M; Guo, Liang; Allen, Ryan M; Yin, Xiaoke; Langley, Sarah R; Esau, Christine; Wanschel, Amarylis; Fisher, Edward A; Surez, Yajaira; Baldn, Angel; Mayr, Manuel; Fernndez-Hernando, Carlos

    2014-01-01

    Plasma high-density lipoprotein (HDL) levels show a strong inverse correlation with atherosclerotic vascular disease. Previous studies have demonstrated that antagonism of miR-33 in vivo increases circulating HDL and reverse cholesterol transport (RCT), thereby reducing the progression and enhancing the regression of atherosclerosis. While the efficacy of short-term anti-miR-33 treatment has been previously studied, the long-term effect of miR-33 antagonism in vivo remains to be elucidated. Here, we show that long-term therapeutic silencing of miR-33 increases circulating triglyceride (TG) levels and lipid accumulation in the liver. These adverse effects were only found when mice were fed a high-fat diet (HFD). Mechanistically, we demonstrate that chronic inhibition of miR-33 increases the expression of genes involved in fatty acid synthesis such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) in the livers of mice treated with miR-33 antisense oligonucleotides. We also report that anti-miR-33 therapy enhances the expression of nuclear transcription Y subunit gamma (NFYC), a transcriptional regulator required for DNA binding and full transcriptional activation of SREBP-responsive genes, including ACC and FAS. Taken together, these results suggest that persistent inhibition of miR-33 when mice are fed a high-fat diet (HFD) might cause deleterious effects such as moderate hepatic steatosis and hypertriglyceridemia. These unexpected findings highlight the importance of assessing the effect of chronic inhibition of miR-33 in non-human primates before we can translate this therapy to humans. PMID:25038053

  5. One Day of Mixed Meal Overfeeding Reduces Hepatic Insulin Sensitivity and Increases VLDL Particle But Not VLDL-Triglyceride Secretion in Overweight and Obese Men

    PubMed Central

    Smith, Gordon I.; Magkos, Faidon; Reeds, Dominic N.; Okunade, Adewole L.; Patterson, Bruce W.

    2013-01-01

    Context: The exact mechanisms responsible for increased plasma triglyceride (TG) concentration in obese people are unclear, and it is not known whether excess energy intake per se is involved in the pathophysiology of this abnormality. Objective: The purpose of our study was to examine how excess energy intake from a balanced diet for 1 day affects very-low-density lipoprotein (VLDL)-TG kinetics and its putative regulators hepatic insulin sensitivity and plasma free fatty acid availability. Subjects and Design: We used stable isotope-labeled tracer methods to evaluate glucose and lipid kinetics in 8 overweight and obese men (age, 38 ± 3 years; body mass index, 33.7 ± 1.7 kg/m2; means ± SEM) on 2 occasions (randomized crossover design): once, the day after they consumed a balanced diet that provided an amount of energy that matched their energy expenditure, and another time, the day after they consumed a balanced diet that provided 30% excess calories. Eight healthy, lean men (34 ± 1 years; 22.5 ± 0.6 kg/m2) were studied under isocaloric conditions only to provide a reference for normal lipid kinetics. Results: VLDL-TG and VLDL-apolipoprotein B-100 (apoB-100) concentrations and secretion rates were significantly greater (P < .01) in overweight/obese compared with lean men. Hypercaloric, compared with isocaloric, feeding in overweight/obese men increased glucose rate of appearance in plasma (904 ± 21 vs 873 ± 26 μmol/min), the hepatic insulin resistance index (10.9 ± 2.2 vs 8.3 ± 1.8), and VLDL–apoB-100 concentration and secretion rate (1.91 ± 0.24 vs. 1.53 ± 0.13 nmol/min), whereas VLDL–apoB-100 plasma clearance rate, VLDL-TG secretion and plasma clearance rates, and free fatty acid rate of appearance in plasma were not affected by overfeeding. Conclusion: One day of moderate overfeeding (30% excess energy intake) stimulates hepatic glucose and VLDL–apo B-100 secretion rates but has no effect on hepatic and adipose tissue fatty acid metabolism in overweight/obese men. PMID:23750033

  6. Inhibition of steady-state intestinal absorption of long-chain triglyceride by medium-chain triglyceride in the unanesthetized rat

    PubMed Central

    Clark, Susanne Bennett; Holt, Peter R.

    1969-01-01

    Maximal steady-state intestinal absorption rates in unanesthetized rats for triolein, a long-chain triglyceride, and for trioctanoin, a medium-chain triglyceride, are known to differ. Both these lipids are hydrolyzed in the intestinal lumen but the products of hydrolysis are metabolized differently by the mucosal cell. Intraduodenal infusion of trioctanoin was found to reduce steady-state triolein absorption. Luminal lipolysis was shown not to be rate-controlling. High rates of trioctanoin infusion significantly lowered the pH of the luminal aqueous phase and altered the partition of oleic acid between aqueous and oil phases. Two possible mechanisms for the inhibition of triolein uptake are considered. In the intestinal lumen medium chain lipids might have lowered the activity of oleic acid monomers in the aqueous phase and reduced passive diffusion into mucosal cells. Alternatively, competition between long and medium chain fatty acids for some common receptor during transport into the intestinal mucosal cell may have occurred. Despite significant inhibition of triolein absorption by high levels of trioctanoin, the maximum number of calories absorbed from mixtures of triglycerides exceeded the maxima from either glyceride alone. The optimum proportion of triolein to trioctanoin in lipid infusion mixtures was about 3:4 by weight and the optimum dosages about half maximal for each triglyceride, which represented a caloric intake of 4 kcal/rat per 2 hr. The absorption coefficient for this lipid mixture was about 90%. It is suggested that in patients who have a limited intestinal absorptive capacity dietary fat intake might be doubled with a caloric supplement of medium-chain triglycerides without increase in steatorrhea of long-chain fat. PMID:5355337

  7. Arachidonic acid diet attenuates brain Aβ deposition in Tg2576 mice.

    PubMed

    Hosono, Takashi; Nishitsuji, Kazuchika; Nakamura, Toshiyuki; Jung, Cha-Gyun; Kontani, Masanori; Tokuda, Hisanori; Kawashima, Hiroshi; Kiso, Yoshinobu; Suzuki, Toshiharu; Michikawa, Makoto

    2015-07-10

    The amyloid β-protein (Aβ) is believed to play a causative role in the development of Alzheimer's disease (AD). Because the amyloid precursor protein (APP), a substrate of Aβ, and β-secretase and γ-secretase complex proteins, which process APP to generate Aβ, are all membrane proteins, it is possible to assume that alterations in brain lipid metabolism modulate APP and/or Aβ metabolism. However, the role of polyunsaturated fatty acids in Aβ metabolism remains unknown. We report here that 9 months-treatment of Tg2576 mice with arachidonic acid (ARA)-containing (ARA+) diet prevented brain Aβ deposition in 17-month-old Tg2576 mice. APP processing to generate soluble APPα, CTF-β, and Aβ synthesis was attenuated in Tg2576 mice fed with the ARA+ diet. These findings suggest that ARA+ diet could prevent Aβ deposition through the alteration of APP processing in Tg2576 mice. PMID:25881896

  8. Reaction Rate Acceleration and Tg Depression of Polycyanurate Under Nanopore Confinement

    NASA Astrophysics Data System (ADS)

    Lopez, Evelyn; Simon, Sindee L.

    2015-03-01

    Material properties such as Tg and the reaction kinetics are known to deviate from the bulk when subjected to nano-sized confinement. Previous work from our laboratory on the trimerization of cyanate esters found that the reaction kinetics were faster for a monofunctional reactant compared to a difunctional monomer, whereas the Tg depression was greater for the crosslinked product of the latter compared to the low molecular weight trimer of the former. The origin of the changes in nanoconfined reaction rates differs from those that govern changes in the Tg. The research objective is to further explore the effect that confinement has on reaction kinetics and Tg using a mixture consisting of mono- and di- cyanate ester monomers. The product is an uncrosslinked polycyanurate with Mn = 5240 g/mol and PDI = 1.78. The confinement mediums are controlled pore glasses with diameters ranging from 8.1 to 111.1 nm. The nanopore-confined material was synthesized in-situ and the reaction kinetics are followed by DSC; after the reaction, the Tg values of the nanoconfined polymer where also measured by DSC. An acceleration factor of 13 and a Tg depression of 38 °C are observed for the material confined in the smallest 8.1 nm-diameter pores. The Tg depression is between those of the trimer and network previously studied, while the acceleration of the reaction rate is lower. Our results are consistent with the reaction acceleration arising from packing effects at the pore wall and the Tg depression arising from intrinsic size effects.

  9. A Toxoplasma gondii phosphoinositide phospholipase C (TgPI-PLC) with high affinity for phosphatidylinositol

    PubMed Central

    Fang, Jianmin; Marchesini, Norma; Moreno, Silvia N. J.

    2005-01-01

    The Toxoplasma gondii phosphoinositide-specific phospholipase C gene (TgPI-PLC) was cloned, sequenced and expressed in Escherichia coli and its enzymatic characteristics were investigated. TgPI-PLC is present in the genome as a single-copy gene consisting of 22 exons interrupted by 21 introns, and encodes a polypeptide of 1097 amino acids with a predicted molecular mass of 121 kDa. In addition to the conserved catalytic X and Y domains, TgPI-PLC contains an apparent N-terminal PH domain, an EF hand motif and a C-terminal C2 domain. When compared with mammalian δ-type PI-PLC, TgPI-PLC has an additional extended N-terminus and two insertions in the region between the X and Y domains, with a 31–35% identity over the whole sequence. Recombinant TgPI-PLC, as well as the native enzyme obtained from crude membrane extracts of the parasite, was more active with phosphatidylinositol than with phosphatidylinositol 4,5-bisphosphate as substrate. Indirect immunofluorescence analysis using an affinity-purified antibody against TgPI-PLC revealed that this enzyme localizes in the plasma membrane of the parasites. PMID:16288600

  10. Aged Tg2576 mice are impaired on social memory and open field habituation tests.

    PubMed

    Deacon, R M J; Koros, E; Bornemann, K D; Rawlins, J N P

    2009-02-11

    In a previous publication [Deacon RMJ, Cholerton LL, Talbot K, Nair-Roberts RG, Sanderson DJ, Romberg C, et al. Age-dependent and -independent behavioral deficits in Tg2576 mice. Behav Brain Res 2008;189:126-38] we found that very few cognitive tests were suitable for demonstrating deficits in Tg2576 mice, an amyloid over-expression model of Alzheimer's disease, even at 23 months of age. However, in a retrospective analysis of a separate project on these mice, tests of social memory and open field habituation revealed large cognitive impairments. Controls showed good open field habituation, but Tg2576 mice were hyperactive and failed to habituate. In the test of social memory for a juvenile mouse, controls showed considerably less social investigation on the second meeting, indicating memory of the juvenile, whereas Tg2576 mice did not show this decrement.As a control for olfactory sensitivity, on which social memory relies, the ability to find a food pellet hidden under wood chip bedding was assessed. Tg2576 mice found the pellet as quickly as controls. As this test requires digging ability, this was independently assessed in tests of burrowing and directly observed digging. In line with previous results and the hippocampal dysfunction characteristic of aged Tg2576 mice, they both burrowed and dug less than controls. PMID:18977397

  11. Assessment of display performance for medical imaging systems: Executive summary of AAPM TG18 report

    SciTech Connect

    Samei, Ehsan; Badano, Aldo; Chakraborty, Dev

    2005-04-01

    Digital imaging provides an effective means to electronically acquire, archive, distribute, and view medical images. Medical imaging display stations are an integral part of these operations. Therefore, it is vitally important to assure that electronic display devices do not compromise image quality and ultimately patient care. The AAPM Task Group 18 (TG18) recently published guidelines and acceptance criteria for acceptance testing and quality control of medical display devices. This paper is an executive summary of the TG18 report. TG18 guidelines include visual, quantitative, and advanced testing methodologies for primary and secondary class display devices. The characteristics, tested in conjunction with specially designed test patterns (i.e., TG18 patterns), include reflection, geometric distortion, luminance, the spatial and angular dependencies of luminance, resolution, noise, glare, chromaticity, and display artifacts. Geometric distortions are evaluated by linear measurements of the TG18-QC test pattern, which should render distortion coefficients less than 2%/5% for primary/secondary displays, respectively. Reflection measurements include specular and diffuse reflection coefficients from which the maximum allowable ambient lighting is determined such that contrast degradation due to display reflection remains below a 20% limit and the level of ambient luminance (L{sub amb}) does not unduly compromise luminance ratio (LR) and contrast at low luminance levels. Luminance evaluation relies on visual assessment of low contrast features in the TG18-CT and TG18-MP test patterns, or quantitative measurements at 18 distinct luminance levels of the TG18-LN test patterns. The major acceptable criteria for primary/secondary displays are maximum luminance of greater than 170/100 cd/m{sup 2}, LR of greater than 250/100, and contrast conformance to that of the grayscale standard display function (GSDF) of better than 10%/20%, respectively. The angular response is tested to ascertain the viewing cone within which contrast conformance to the GSDF is better than 30%/60% and LR is greater than 175/70 for primary/secondary displays, or alternatively, within which the on-axis contrast thresholds of the TG18-CT test pattern remain discernible. The evaluation of luminance spatial uniformity at two distinct luminance levels across the display faceplate using TG18-UNL test patterns should yield nonuniformity coefficients smaller than 30%. The resolution evaluation includes the visual scoring of the CX test target in the TG18-QC or TG18-CX test patterns, which should yield scores greater than 4/6 for primary/secondary displays. Noise evaluation includes visual evaluation of the contrast threshold in the TG18-AFC test pattern, which should yield a minimum of 3/2 targets visible for primary/secondary displays. The guidelines also include methodologies for more quantitative resolution and noise measurements based on MTF and NPS analyses. The display glare test, based on the visibility of the low-contrast targets of the TG18-GV test pattern or the measurement of the glare ratio (GR), is expected to yield scores greater than 3/1 and GRs greater than 400/150 for primary/secondary displays. Chromaticity, measured across a display faceplate or between two display devices, is expected to render a u{sup '},v{sup '} color separation of less than 0.01 for primary displays. The report offers further descriptions of prior standardization efforts, current display technologies, testing prerequisites, streamlined procedures and timelines, and TG18 test patterns.

  12. USGS Elevation Monument

    USGS Multimedia Gallery

    USGS elevation monument for a level line run from Mojave, California to Keeler, California. The line ran through such places as 18-Mile Station, Dixie, Indan Wells, Little Lake, and Olancha. Elevations were based on Benecia datum....

  13. The Space Elevator

    NASA Astrophysics Data System (ADS)

    Laubscher, Bryan E.

    2005-09-01

    The Space Elevator is conceived to be a carbon nanotube ribbon stretching from an Earth station in the ocean on the equator to far beyond geosynchronous altitude. This elevator co-rotates with the Earth. Climbers ascend the ribbon using power beamed from Earth to launch spacecraft in orbit or to other worlds. The requirements of the ribbon material, challenges to the building of the space elevator, deployment and the promise of the space elevator are briefly discussed in this paper.

  14. National Elevation Dataset

    USGS Publications Warehouse

    U.S. Geological Survey

    1999-01-01

    The National Elevation Dataset (NED) is a new raster product assembled by the U.S. Geological Survey (USGS). The NED is designed to provide national elevation data in a seamless form with a consistent datum, elevation unit, and projection. Data corrections were made in the NED assembly process to minimize artifacts, permit edge matching, and fill sliver areas of missing data.

  15. 26-Week dermal oncogenicity study evaluating pure trans-capsaicin in Tg.AC hemizygous mice (FBV/N).

    PubMed

    Chanda, Sanjay; Erexson, Gregory; Frost, Denzil; Babbar, Sunita; Burlew, Jo-Anne; Bley, Keith

    2007-01-01

    The objective of this study was to assess the oncogenic potential of trans-capsaicin when administered weekly via topical application to the dorsal skin of Tg.AC mice for 26 weeks. Male and female Tg.AC mice (25 mice/sex/group) received dose formulations containing trans-capsaicin dissolved in diethylene glycol monoethyl ether (DGME). The positive control was tetradecanoylphorbol-13-acetate (TPA) dissolved in DGME. Appropriate controls, including a topical lidocaine local anesthetic pretreatment (4%w/w), were maintained. All groups were dosed once weekly, except for the TPA group, which was dosed twice per week. Analysis of the macroscopic observations after the final sacrifice revealed no noteworthy treatment-related findings, with the exception of dermal masses that were randomly dispersed throughout all treatment groups for both males and females. The frequency of dermal masses in the capsaicin-treated groups (at a dose level of up to 102 mg/kg and an application rate of 25.6 mg/cm2/kg/week) was not elevated in comparison to either concurrent vehicle or untreated controls. In contrast, a notable increase in the frequency of dermal masses was observed in the TPA-treated mice compared to both the concurrent vehicle and untreated controls. Dermal application of capsaicin resulted in no increased incidence of preneoplastic or neoplastic skin lesions. In contrast, over half the male and female mice exposed to TPA had multiple skin papillomas; the majority of the TPA-treated animals either died early or was humanely euthanized due to tumor load. Spontaneously occurring neoplasms were not appreciably increased in capsaicin-treated animals. Capsaicin-related non-neoplastic microscopic findings were seen sporadically in both genders and included acanthosis, hyperkeratosis/parakeratosis (primarily females), epidermal crusts, subepidermal fibrosis, epidermal ulcerations/erosions, and chronic-active inflammation. There was no evidence of a dose response in either the incidence or severity of these findings. The lidocaine- (at a dose level of 162 mg/kg and at an application rate of 40.5 mg/cm2/kg/week) and DGME-treated (at a dose level of 4.0 g/kg and at an application rate of 1 g/cm2/kg/week) control groups also did not display any evidence of increase in dermal masses. Based on these results, trans-capsaicin, lidocaine, and DGME should be considered nononcogenic in the Tg.AC mouse dermal model. PMID:17454252

  16. Beta-blockade lowers peripheral lipolysis in burn patients receiving growth hormone. Rate of hepatic very low density lipoprotein triglyceride secretion remains unchanged.

    PubMed Central

    Aarsland, A; Chinkes, D; Wolfe, R R; Barrow, R E; Nelson, S O; Pierre, E; Herndon, D N

    1996-01-01

    OBJECTIVE: The purpose of this study was to determine the effect of propranolol on peripheral lipolysis in massively burned children during treatment with recombinant human growth hormone (rhGH), and to ascertain whether decreased free fatty acid availability for re-esterification would alter the hepatic rate of secretion of triglycerides (TGs) bound to very low density lipoproteins (VLDLs). BACKGROUND: Fatty liver occurs in severely burned patients, often resulting in a twofold increase in liver size. This could be the result of an imbalance between increased provision of free fatty acids from peripheral lipolysis, coupled with no increase in fat oxidation, and insufficient rate of secretion of TGs from the liver. METHODS: In a cross-over study, six burned children were treated with either rhGH or rhGH plus propranolol. On the sixth day of treatment, isotopic tracer infusions were conducted to determine the rate of release of free fatty acid (Ra FFA) from peripheral tissue and the rate of secretion of VLDL-bound TGs by the liver. RESULTS: Exogenous rhGH increased Ra FFA in children with large third-degree burns. Propranolol decreased Ra FFA, but the rate of secretion of fatty acids in the form of VLDL-TG from the liver was maintained. Plasma FFA, as opposed to fatty acids newly synthesized in the liver, were the primary precursors for hepatic triglyceride synthesis. CONCLUSIONS: The administration of propranolol to burned children receiving rhGH is safe, has salutary cardiovascular effects, decreases the release of FFA from adipose tissue and increases the efficiency of the liver in secreting fatty acids as VLDL TGs. PMID:8645051

  17. Paraoxonase 1 protects macrophages from atherogenicity of a specific triglyceride isolated from human carotid lesion.

    PubMed

    Tavori, Hagai; Aviram, Michael; Khatib, Soliman; Musa, Ramadan; Mannheim, Dalit; Karmeli, Ron; Vaya, Jacob

    2011-07-01

    Human atherosclerotic lesions contain oxidized lipids that facilitate further oxidation of macrophages, LDLs, and oxidative stress (OS)-sensitive markers and inhibit the antiatherogenic enzyme paraoxonase 1 (PON1). Our aim was to isolate and identify the oxidizing agent in a human atherosclerotic lesion lipid extract (LLE) and to explore the mechanisms of oxidation and of PON1's effect on the oxidizing agent. Of the five main fractions separated from the LLE, only fraction 2 (F2) promoted macrophage reactive oxygen species (ROS) production via a mechanism requiring mitochondrial involvement, whereas the NADPH oxidase system was not involved. Incubation of F2 with PON1 abridged the former's peroxide value and reduced its capacity to oxidize OS markers. The active agent was a triglyceride composed of palmitic, oleic, and linoleic acids, with 0.3% of its linoleic moiety in oxidized form. Incubation of either F2 or an identical synthetic triglyceride with PON1 reduced their ability to oxidize macrophages, without affecting cellular accumulation of triglycerides. We conclude that macrophage ROS production by LLE occurs in the presence of a specific triglyceride and requires mitochondrial involvement. Lipid peroxide in the triglyceride can also facilitate lipid autoxidation. Both atherogenic pathways are suppressed by PON1, which acts as an antiatherogenic element. PMID:21530644

  18. Distinct metabolic and vascular effects of dietary triglycerides and cholesterol in atherosclerotic and diabetic mouse models.

    PubMed

    Laplante, Marc-Andr; Charbonneau, Alexandre; Avramoglu, Rita Kohen; Pelletier, Patricia; Fang, Xiangping; Bachelard, Hlne; Yl-Herttuala, Seppo; Laakso, Markku; Desprs, Jean-Pierre; Deshaies, Yves; Sweeney, Gary; Mathieu, Patrick; Marette, Andr

    2013-09-01

    Cholesterol and triglyceride-rich Western diets are typically associated with an increased occurrence of type 2 diabetes and vascular diseases. This study aimed to assess the relative impact of dietary cholesterol and triglycerides on glucose tolerance, insulin sensitivity, atherosclerotic plaque formation, and endothelial function. C57BL6 wild-type (C57) mice were compared with atherosclerotic LDLr(-/-) ApoB(100/100) (LRKOB100) and atherosclerotic/diabetic IGF-II LDLr(-/-) ApoB(100/100) (LRKOB100/IGF) mice. Each group was fed either a standard chow diet, a 0.2% cholesterol diet, a high-fat diet (HFD), or a high-fat 0.2% cholesterol diet for 6 mo. The triglyceride-rich HFD increased body weight, glucose intolerance, and insulin resistance but did not alter endothelial function or atherosclerotic plaque formation. Dietary cholesterol, however, increased plaque formation in LRKOB100 and LRKOB100/IGF animals and decreased endothelial function regardless of genotype. However, cholesterol was not associated with an increase of insulin resistance in LRKOB100 and LRKOB100/IGF mice and, unexpectedly, was even found to reduce the insulin-resistant effect of dietary triglycerides in these animals. Our data indicate that dietary triglycerides and cholesterol have distinct metabolic and vascular effects in obese atherogenic mouse models resulting in dissociation between the impairment of glucose homeostasis and the development of atherosclerosis. PMID:23820620

  19. Supplementation of Areca catechu L. extract alters triglyceride absorption and cholesterol metabolism in rats.

    PubMed

    Byun, S J; Kim, H S; Jeon, S M; Park, Y B; Choi, M S

    2001-01-01

    Areca extracts have already been found to exhibit a strong inhibitory activity on cholesterol absorption in high-cholesterol-fed rats. Accordingly, this study was performed to determine whether Areca extracts also exert an inhibitory activity on triglyceride absorption in triglyceride-fed rats. Male rats were fed a diet containing corn oil (10%, w/w) with or without an Areca nut extract supplement (0.5%, w/w). The supplementation of the Areca extract significantly lowered the absorption of triglyceride and the plasma lipid concentration. The absorbed triglyceride that appeared in the blood after an oral dose of [9,10(n)-(3)H] triglyceride was significantly lower in the rats supplemented with the Areca nut extract, compared with the control group. The supplementation also significantly lowered the small intestinal pCEase (pancreatic cholesterol esterase) activity by 22.5% compared to the control group. The hepatic and intestinal ACAT (acyl-CoA:cholesterol acyltransferase) activities were significantly decreased in the Areca group compared with the control group. Hence, further studies are needed to elucidate the structure and chemical properties of the active compound in the water-soluble Areca extract that lowers cholesterol absorption. PMID:11786651

  20. Mechanism of triglyceride lowering in mice expressing human apolipoprotein A5.

    PubMed

    Fruchart-Najib, Jamila; Baug, Eric; Niculescu, Loredan-Stefan; Pham, Tatiana; Thomas, Benoit; Rommens, Corinne; Majd, Zouher; Brewer, Bryan; Pennacchio, Len A; Fruchart, Jean-Charles

    2004-06-25

    Overexpression of human APOA5 in mice results in dramatically decreased plasma triglyceride levels. In this study we explored the mechanism underlying this hypotriglyceridemic effect. Initially we found that triglyceride turnover was faster in hAPOA5 transgenic mice compared to controls, and this strongly correlated with increased LPL activity in postheparin plasma. Furthermore, we show that in vitro recombinant apoAV interacts physically with lipoprotein lipase and significantly increased its activity. We show that both apoB and apoCIII are decreased in hAPOA5 transgenic mice indicating a decrease in VLDL number. To further investigate the mechanism of hAPOA5 in a hyperlipidemic background, we inter-crossed hAPOA5 and hAPOC3 transgenic mice. We found a marked decrease in VLDL triglyceride and cholesterol, as well as apolipoprotein B and CIII levels. These data indicated that apoAV induces a decrease in VLDL size by activating lipolysis and an increase of VLDL clearance. In a postprandial state, the normal triglyceride response found in wild-type mice was significantly reduced in hAPOA5 transgenics. In addition, we demonstrated that in response to this fat load in hAPOA5xhAPOC3 mice, apoAV, but not apoCIII, was redistributed from primarily HDL to VLDL. This shift of apoAV in VLDL appears to limit the increase of triglyceride by activating the lipoprotein lipase. PMID:15178420

  1. Biopolymer from microbial assisted in situ hydrolysis of triglycerides and dimerization of fatty acids.

    PubMed

    Kavitha, V; Radhakrishnan, N; Madhavacharyulu, E; Sailakshmi, G; Sekaran, G; Reddy, B S R; Rajkumar, G Suseela; Gnanamani, Arumugam

    2010-01-01

    The present study demonstrates biopolymer production by in situ bio-based dimerization of fatty acids by microorganism isolated from marine sediments. Microbial isolate grown in Zobell medium in the presence of triglycerides for the period of 24-240 h at 37 degrees C, hydrolyze the applied triglycerides and sequentially dimerized the hydrolyzed products and subsequently polymerized and transformed to a biopolymer having appreciable adhesive properties. Physical (nature, odour, stickyness and tensile strength), chemical (instrumentation) and biochemical (cell free broth) methods of analyses carried out provided the hypotheses involved in the formation of the product as well as the nature of the product formed. Results revealed, lipolytic enzymes released during initial period of growth and the biosurfactant production during later period, respectively, hydrolyze the applied triglycerides and initiate the dimerization and further accelerated when the incubation period extended. The existence and the non-existence of in situ hydrolysis of various triglycerides followed by dimerization and polymerization and the mechanism of transformation of triglycerides to biopolymer are discussed in detail. PMID:19720526

  2. Genomic interval engineering of mice identifies a novel modulator of triglyceride production.

    PubMed

    Zhu, Y; Jong, M C; Frazer, K A; Gong, E; Krauss, R M; Cheng, J F; Boffelli, D; Rubin, E M

    2000-02-01

    To accelerate the biological annotation of novel genes discovered in sequenced regions of mammalian genomes, we are creating large deletions in the mouse genome targeted to include clusters of such genes. Here we describe the targeted deletion of a 450-kb region on mouse chromosome 11, which, based on computational analysis of the deleted murine sequences and human 5q orthologous sequences, codes for nine putative genes. Mice homozygous for the deletion had a variety of abnormalities, including severe hypertriglyceridemia, hepatic and cardiac enlargement, growth retardation, and premature mortality. Analysis of triglyceride metabolism in these animals demonstrated a several-fold increase in hepatic very-low density lipoprotein triglyceride secretion, the most prevalent mechanism responsible for hypertriglyceridemia in humans. A series of mouse BAC and human YAC transgenes covering different intervals of the 450-kb deleted region were assessed for their ability to complement the deletion induced abnormalities. These studies revealed that OCTN2, a gene recently shown to play a role in carnitine transport, was able to correct the triglyceride abnormalities. The discovery of this previously unappreciated relationship between OCTN2, carnitine, and hepatic triglyceride production is of particular importance because of the clinical consequence of hypertriglyceridemia and the paucity of genes known to modulate triglyceride secretion. PMID:10655497

  3. Genomic interval engineering of mice identified a novel modulator of triglyceride production

    SciTech Connect

    Zhu, Y.; Jong, M.C.; Frazer, K.A.; Gong, E.; Krauss, R.M.; Cheng, J.F.; Boffelli, D.; Rubin, E.M.

    1999-10-01

    To accelerate the biological annotation of novel genes discovered in sequenced of mammalian genomes, we are creating large deletions in the mouse genome targeted to include clusters of such genes. Here we describe the targeted deletion of a 450 kb region on mouse chromosome 11 which, based on computational analysis of the deleted murine sequences and human 5q orthologous sequences, codes for nine putative genes. Mice homozygous for the deletion had a variety of abnormalities including severe hypertriglyceridemia, hepatic and cardiac enlargement, growth retardation and premature mortality. Analysis of triglyceride metabolism in these animals demonstrated a several-fold increase in hepatic very-low density lipoprotein (VLDL) triglyceride secretion, the most prevalent mechanism responsible for hypertriglyceridemia in humans. A series of mouse BAC and human YAC transgenes covering different intervals of the 450 kb deleted region were assessed for their ability to complement the deletion induced abnormalities. These studies revealed that OCTN2, a gene recently shown to play a role in carnitine transport, was able to correct the triglyceride abnormalities. The discovery of this previously unappreciated relationship between OCTN2, carnitine and hepatic triglyceride production is of particular importance due to the clinical consequence of hypertriglyceridemia and the paucity of genes known to modulate triglyceride secretion.

  4. Deletion of CGI-58 or adipose triglyceride lipase differently affects macrophage function and atherosclerosis.

    PubMed

    Goeritzer, Madeleine; Schlager, Stefanie; Radovic, Branislav; Madreiter, Corina T; Rainer, Silvia; Thomas, Gwynneth; Lord, Caleb C; Sacks, Jessica; Brown, Amanda L; Vujic, Nemanja; Obrowsky, Sascha; Sachdev, Vinay; Kolb, Dagmar; Chandak, Prakash G; Graier, Wolfgang F; Sattler, Wolfgang; Brown, J Mark; Kratky, Dagmar

    2014-12-01

    Cellular TG stores are efficiently hydrolyzed by adipose TG lipase (ATGL). Its coactivator comparative gene identification-58 (CGI-58) strongly increases ATGL-mediated TG catabolism in cell culture experiments. To investigate the consequences of CGI-58 deficiency in murine macrophages, we generated mice with a targeted deletion of CGI-58 in myeloid cells (macCGI-58(-/-) mice). CGI-58(-/-) macrophages accumulate intracellular TG-rich lipid droplets and have decreased phagocytic capacity, comparable to ATGL(-/-) macrophages. In contrast to ATGL(-/-) macrophages, however, CGI-58(-/-) macrophages have intact mitochondria and show no indications of mitochondrial apoptosis and endoplasmic reticulum stress, suggesting that TG accumulation per se lacks a significant role in processes leading to mitochondrial dysfunction. Another notable difference is the fact that CGI-58(-/-) macrophages adopt an M1-like phenotype in vitro. Finally, we investigated atherosclerosis susceptibility in macCGI-58/ApoE-double KO (DKO) animals. In response to high-fat/high-cholesterol diet feeding, DKO animals showed comparable plaque formation as observed in ApoE(-/-) mice. In agreement, antisense oligonucleotide-mediated knockdown of CGI-58 in LDL receptor(-/-) mice did not alter atherosclerosis burden in the aortic root. These results suggest that macrophage function and atherosclerosis susceptibility differ fundamentally in these two animal models with disturbed TG catabolism, showing a more severe phenotype by ATGL deficiency. PMID:25316883

  5. Deletion of CGI-58 or adipose triglyceride lipase differently affects macrophage function and atherosclerosis[S

    PubMed Central

    Goeritzer, Madeleine; Schlager, Stefanie; Radovic, Branislav; Madreiter, Corina T.; Rainer, Silvia; Thomas, Gwynneth; Lord, Caleb C.; Sacks, Jessica; Brown, Amanda L.; Vujic, Nemanja; Obrowsky, Sascha; Sachdev, Vinay; Kolb, Dagmar; Chandak, Prakash G.; Graier, Wolfgang F.; Sattler, Wolfgang; Brown, J. Mark; Kratky, Dagmar

    2014-01-01

    Cellular TG stores are efficiently hydrolyzed by adipose TG lipase (ATGL). Its coactivator comparative gene identification-58 (CGI-58) strongly increases ATGL-mediated TG catabolism in cell culture experiments. To investigate the consequences of CGI-58 deficiency in murine macrophages, we generated mice with a targeted deletion of CGI-58 in myeloid cells (macCGI-58−/− mice). CGI-58−/− macrophages accumulate intracellular TG-rich lipid droplets and have decreased phagocytic capacity, comparable to ATGL−/− macrophages. In contrast to ATGL−/− macrophages, however, CGI-58−/− macrophages have intact mitochondria and show no indications of mitochondrial apoptosis and endoplasmic reticulum stress, suggesting that TG accumulation per se lacks a significant role in processes leading to mitochondrial dysfunction. Another notable difference is the fact that CGI-58−/− macrophages adopt an M1-like phenotype in vitro. Finally, we investigated atherosclerosis susceptibility in macCGI-58/ApoE-double KO (DKO) animals. In response to high-fat/high-cholesterol diet feeding, DKO animals showed comparable plaque formation as observed in ApoE−/− mice. In agreement, antisense oligonucleotide-mediated knockdown of CGI-58 in LDL receptor−/− mice did not alter atherosclerosis burden in the aortic root. These results suggest that macrophage function and atherosclerosis susceptibility differ fundamentally in these two animal models with disturbed TG catabolism, showing a more severe phenotype by ATGL deficiency. PMID:25316883

  6. Upregulation of hepatic VLDLR via PPAR? is required for the triglyceride-lowering effect of fenofibrate.

    PubMed

    Gao, Yang; Shen, Wei; Lu, Boyu; Zhang, Qingjiong; Hu, Yang; Chen, Ying

    2014-06-01

    The liver and the VLDL receptor (VLDLR) play major roles in TG and VLDL metabolism. However, the exact role of liver VLDLR is not well known because of the absence of or difficulty in detecting VLDLR in the liver. In this study, we demonstrate that fenofibrate, a PPAR? agonist and widely used TG-lowering drug, markedly upregulated hepatic VLDLR, which is essential for lowering TG. This study also shows that the distinct regulatory roles of PPAR? agonists on VLDLR in the liver and peripheral tissues including adipose tissues, heart, and skeletal muscles are due to the pattern of expression of PPAR?. The in vivo portion of our study demonstrated that oral fenofibrate robustly increased liver VLDLR expression levels in hyperlipidemic and diabetic mice and significantly reduced the increase in serum TG observed in wt mice after feeding with high-fat diet (HFD) but not in Vldlr(-/-) mice or Ppar?(-/-) mice. However, overexpression of mouse VLDLR in livers of Vldlr(-/-) mice significantly prevented the increase in serum TG induced by HFD. The in vitro portion of our study showed that fenofibrate upregulated VLDLR transcriptional activity through PPAR response element binding to the VLDLR promoter. The conclusions of our study provide a novel mechanism for the TG-lowering effects of fenofibrate in the treatment of dyslipidemia. PMID:24899625

  7. Spaceflight influences both mucosal and peripheral cytokine production in PTN-Tg and wild type mice.

    PubMed

    McCarville, Justin L; Clarke, Sandra T; Shastri, Padmaja; Liu, Yi; Kalmokoff, Martin; Brooks, Stephen P J; Green-Johnson, Julia M

    2013-01-01

    Spaceflight is associated with several health issues including diminished immune efficiency. Effects of long-term spaceflight on selected immune parameters of wild type (Wt) and transgenic mice over-expressing pleiotrophin under the human bone-specific osteocalcin promoter (PTN-Tg) were examined using the novel Mouse Drawer System (MDS) aboard the International Space Station (ISS) over a 91 day period. Effects of this long duration flight on PTN-Tg and Wt mice were determined in comparison to ground controls and vivarium-housed PTN-Tg and Wt mice. Levels of interleukin-2 (IL-2) and transforming growth factor-beta1 (TGF-?1) were measured in mucosal and systemic tissues of Wt and PTN-Tg mice. Colonic contents were also analyzed to assess potential effects on the gut microbiota, although no firm conclusions could be made due to constraints imposed by the MDS payload and the time of sampling. Spaceflight-associated differences were observed in colonic tissue and systemic lymph node levels of IL-2 and TGF-?1 relative to ground controls. Total colonic TGF-?1 levels were lower in Wt and PTN-Tg flight mice in comparison to ground controls. The Wt flight mouse had lower levels of IL-2 and TGF-?1 compared to the Wt ground control in both the inguinal and brachial lymph nodes, however this pattern was not consistently observed in PTN-Tg mice. Vivarium-housed Wt controls had higher levels of active TGF-?1 and IL-2 in inguinal lymph nodes relative to PTN-Tg mice. The results of this study suggest compartmentalized effects of spaceflight and on immune parameters in mice. PMID:23874826

  8. Neuronal network activity in the hippocampus of tau transgenic (Tg4510) mice.

    PubMed

    Scott, Liam; Kiss, Tams; Kawabe, Thomas T; Hajs, Mihly

    2016-01-01

    Development of neurofibrillary tangles in Alzheimer's disease correlates with neuronal loss and dementia. Transgenic Tg4510 mice model the tauopathy of the disease, with these mice exhibiting progressive, region-specific neuronal loss, and behavioral deficits. In the present study, neuronal network activity in the hippocampus of 7-month-old Tg4510 mice was investigated and compared with age-matched wild-type (WT) mice. Multisite field potentials were recorded using 16-site silicon probes, inserted across the hippocampus in urethane anesthetized mice. The hippocampal network theta oscillation was evaluated in these mice by stimulating the brainstem nucleus pontis oralis. Subsequently, population spikes in the dentate gyrus were identified in response to perforant path stimulation, and long-term potentiation was elicited by theta burst stimulation. Tg4510 mice showed dramatically reduced dentate gyrus population spike amplitude; however, the magnitude of theta burst stimulation-induced long-term potentiation was identical in WT and transgenic mice. WT and Tg4510 mice showed identical increase in frequency to nucleus pontis oralis stimulation, whereas absolute theta power was severely reduced in the Tg4510 animals. Because total signal power over the entire frequency band range was reduced, there was no difference in relative theta power between WT and Tg4510 mice. These presently described electrophysiological findings can be directly attributed to the drastic reduction of pyramidal/granule neurons in Tg4510 mice, which could be the main contributing factor to their impaired behavior and cognitive function. However, the remaining synapses and neuronal circuitry seem to function properly in these assays. PMID:26610388

  9. Beyond the Intestinal Celiac Mucosa: Diagnostic Role of Anti-TG2 Deposits, a Systematic Review

    PubMed Central

    Gatti, Simona; Rossi, Matilde; Alfonsi, Simona; Mandolesi, Alessandra; Cobellis, Giovanni; Catassi, Carlo

    2014-01-01

    Aim: To review the existing literature on the role and significance of intestinal transglutaminase 2 immunoglobulin A deposits (TG2 deposits) in patients with overt celiac disease (CD), potential celiac disease (PCD), and other autoimmune or gluten-related conditions. Methods: We conducted a systematic review of studies published in English, evaluating presence and characteristics of TG2 deposits in subjects with overt CD, PCD, gluten-related diseases [dermatitis herpetiformis (DH), gluten-ataxia (GA)], autoimmune disorders (type-1 diabetes), and other conditions. Studies were identified through a MEDLINE search (19502013). Results: Twenty-three studies were included in the review. Eleven studies were performed in children. Overall TG2 deposits were present in 100% of adults with overt CD, while in children prevalence ranged from 73.2 to 100%. Six studies with an established definition of PCD were considered, prevalence of deposits ranging from 64.7 to 100%. A single study followed-up PCD patients with repeated biopsies and identified presence of intestinal deposits as the best marker to reveal progression toward villous atrophy. Two studies investigated presence of deposits in DH, reporting prevalence between 63 and 79%. A single study documented TG2 deposits in 100% of patients with GA. In children with type-1 diabetes (T1D), positivity of intestinal TG2 deposits ranged from 25 to 78%. Conclusion: Transglutaminase 2 IgA deposits seem to be a constant feature in overt CD patients and are frequently detectable in other gluten-related conditions (DH and GA). The vast majority of PCD patients express TG2 deposits at the intestinal level, but no sufficient data are available to exactly define their prognostic role as a marker of evolution toward overt CD. The frequent finding of TG2 deposits in the intestinal mucosa of patients with T1D is an interesting observation deserving further evaluation. PMID:25705622

  10. SU-E-J-110: TG 51 Dosimetry : With Or Without Lead

    SciTech Connect

    Shah, M

    2014-06-01

    TG-51 Dosimetry: With or Without Lead. Purpose: In this project, an analytical method has been introduced for adjustment of the TG-51 recommended KQ in order to produce accurate dosimetric data for high energy photons without the lead foil. Methods: These investigations were performed using a 30 cm × 30 cm × 30 cm CIVCO water tank, A12 EXRADIN Water proof Farmer Chamber, a Standard Imaging MAX 4000 electrometer, and 1 mm thick lead foil from Standard Imaging. Complete TG-51 was performed every month with and without lead. The results were analyzed and an analytical model has been developed for comparing the values of KQ. TG-51 Table I was used to obtain KQ values. Results: The dosimetric evaluations were obtained for Varian Linear accelerators Model 21ix and 21ex. These results indicates that the measured data with lead foil in place as recommended by TG-51 is in excellent agreement (within 0.1%) with the calculated data obtained by the new model, from our dosimetry data without-lead. If equation 15 of the TG-51 report is used without any adjustments, it will lead to differences of about 1.6 % (on the average) in relative data which will Resultin differences of about 0.3 % (on the average) in the KQ Values. The KQ value for 18 MV obtained consistently with the equation of TG-51 “with lead” and “without lead” were 0.971 and 0.974, respectively. The 0.3 % higher results for KQ without lead eventually will lead to 0.3% larger output. However, by considering this model the KQ value was found to be 0.971 for dosimetry without lead. Conclusion: The analytical model that was introduced in this project was able to reproduce the dosimetric data of the high energy linear accelerators to within 0.1% without the use of the lead foil.

  11. Comparative kinetic analysis on thermal degradation of some cephalosporins using TG and DSC data

    PubMed Central

    2013-01-01

    Background The thermal decomposition of cephalexine, cefadroxil and cefoperazone under non-isothermal conditions using the TG, respectively DSC methods, was studied. In case of TG, a hyphenated technique, including EGA, was used. Results The kinetic analysis was performed using the TG and DSC data in air for the first step of cephalosporins decomposition at four heating rates. The both TG and DSC data were processed according to an appropriate strategy to the following kinetic methods: Kissinger-Akahira-Sunose, Friedman, and NPK, in order to obtain realistic kinetic parameters, even if the decomposition process is a complex one. The EGA data offer some valuable indications about a possible decomposition mechanism. The obtained data indicate a rather good agreement between the activation energys values obtained by different methods, whereas the EGA data and the chemical structures give a possible explanation of the observed differences on the thermal stability. A complete kinetic analysis needs a data processing strategy using two or more methods, but the kinetic methods must also be applied to the different types of experimental data (TG and DSC). Conclusion The simultaneous use of DSC and TG data for the kinetic analysis coupled with evolved gas analysis (EGA) provided us a more complete picture of the degradation of the three cephalosporins. It was possible to estimate kinetic parameters by using three different kinetic methods and this allowed us to compare the Ea values obtained from different experimental data, TG and DSC. The thermodegradation being a complex process, the both differential and integral methods based on the single step hypothesis are inadequate for obtaining believable kinetic parameters. Only the modified NPK method allowed an objective separation of the temperature, respective conversion influence on the reaction rate and in the same time to ascertain the existence of two simultaneous steps. PMID:23594763

  12. Genetic Variation in SULF2 Is Associated with Postprandial Clearance of Triglyceride-Rich Remnant Particles and Triglyceride Levels in Healthy Subjects

    PubMed Central

    Romeo, Stefano; Hakkarainen, Antti; Adiels, Martin; Folkersen, Lasse; Eriksson, Per; Lundbom, Nina; Ehrenborg, Ewa; Orho-Melander, Marju; Taskinen, Marja-Riitta; Born, Jan

    2013-01-01

    Context Nonfasting (postprandial) triglyceride concentrations have emerged as a clinically significant cardiovascular disease risk factor that results from accumulation of remnant triglyceride-rich lipoproteins (TRLs) in the circulation. The remnant TRLs are cleared from the circulation by hepatic uptake, but the specific mechanisms involved are unclear. The syndecan-1 heparan sulfate proteoglycan (HSPG) pathway is important for the hepatic clearance of remnant TRLs in mice, but its relevance in humans is unclear. Objective We sought to determine whether polymorphisms of the genes responsible for HSPG assembly and disassembly contribute to atherogenic dyslipoproteinemias in humans. Patients And Design We performed an oral fat load in 68 healthy subjects. Lipoproteins (chylomicrons and very low density lipoproteins 1 and 2) were isolated from blood, and the area under curve and incremental area under curve for postprandial variables were calculated. Single nucleotide polymorphisms in genes encoding syndecan-1 and enzymes involved in the synthesis or degradation of HSPG were genotyped in the study subjects. Results Our results indicate that the genetic variation rs2281279 in SULF2 associates with postprandial clearance of remnant TRLs and triglyceride levels in healthy subjects. Furthermore, the SNP rs2281279 in SULF2 associates with hepatic SULF2 mRNA levels. Conclusions In humans, mild but clinically relevant postprandial hyperlipidemia due to reduced hepatic clearance of remnant TRLs may result from genetic polymorphisms that affect hepatic HSPG. PMID:24278138

  13. A study of the composition of fish liver and body oil triglycerides.

    PubMed

    McGill, A S; Moffat, C F

    1992-05-01

    Silver-ion high-performance liquid chromatography (Ag(+)-HPLC) was used to study the range and variations in molecular species of triglycerides from industrial, retail and laboratory extracted fish oils. These were contrasted with a typical plant oil. Selected fish oils were fractionated and the fatty acid distribution of the fractions determined by gas-liquid chromatography. Fish oils gave a characteristic Ag(+)-HPLC profile, typified by sharp, intense peaks at the start of the chromatogram and broad, multiple nongaussian peaks for the late eluting components. Triglycerides ranging from those that were wholly saturated to those containing 16 double bonds were isolated. Cod (Gadus spp.), saithe (Pollachius virens) and monkfish (Squatina squatina) liver oils gave similar triglyceride profiles. Mackerel (Scomber scombrus), capelin (Mallotus villosus) and herring (Clupea harengus) body oils gave characteristic triglyceride profiles which were associated with high concentrations of 20:1 and 22:1 fatty acids. Only small amounts of these particular triglycerides were observed for menhaden (Brevoortia spp.), South African anchovy (Engraulis capensis) and Indian sardine (Sardinella longiceps) oils, all of which contained minor amounts of these acids. The latter oils contained highly unsaturated triglycerides, whereas only traces of these were noted for the former. Chromatography with Ag(+)-HPLC can be used for the rapid screening of fish oils and for selecting those oils rich in polyunsaturated acids that may be suitable for enrichment. Cottonseed oil gave well-defined and discrete peaks. Similar peaks were observed in the chromatogram of Omega-combination, a mixture of primrose and fish oils. Thus, fish, plant and a mixture of these oils can be readily distinguished. PMID:1406065

  14. Metabolism of triglyceride-rich nascent rat hepatic high density lipoproteins

    SciTech Connect

    Winkler, K.E.; Marsh, J.B. )

    1989-07-01

    Nascent high density lipoprotein (HDL) and nascent very low density lipoprotein (VLDL) were isolated from rat livers that had been perfused with (3H)glycerol to label the triglyceride. When injected into intact rats, the labeled HDL-triglyceride disappeared as rapidly as the VLDL-triglyceride, with only 10% of the injected label remaining in the plasma after 30 min. The protein moiety of nascent HDL was labeled with (35S)methionine in a similar fashion and the labeled nascent HDL was separated into nonretained (NR) and retained (R) fractions by heparin-Sepharose affinity chromatography. When injected into rats, 55% of the injected label in nascent fraction NR and 72% of that in nascent fraction R was recovered from plasma at 30 min, compared to only 10% of the triglyceride label from unfractionated nascent HDL, indicating dissociation of triglyceride and apolipoprotein clearance. The plasma decay curves for both triglyceride and protein were biexponential. By 5 min, 15% of the 35S label remaining in plasma represented apoE and apoC that had been transferred from nascent HDL fractions NR and R to the d less than 1.063 g/ml fraction of plasma. Plasma HDL was labeled in vivo with (35S)methionine, separated into fractions NR and R, and the clearance of the two plasma HDL fractions was compared with that of the corresponding nascent HDL fractions. Except for a faster rate of removal of the nascent HDL fractions during the first 5 min, the serum decay curves were very similar.

  15. Sub-Tg relaxation patterns in Cu-based metallic glasses far from equilibrium

    NASA Astrophysics Data System (ADS)

    Wang, Caiwei; Hu, Lina; Wei, Chen; Tong, Xu; Zhou, Chao; Sun, Qijing; Hui, Xidong; Yue, Yuanzheng

    2014-10-01

    We investigate the sub-Tg relaxation patterns (RPs) in binary and quaternary Cu-based glass ribbons (GRs) by using the hyperquenching-sub-Tg annealing-calorimetric approach. This study contributes to revealing the structural or dynamic evolution in liquids related to the observed three-stage sub-Tg relaxation processes in GRs. In this work, we have achieved the following three findings. First, the abnormal three-stage relaxation behavior is not a general phenomenon for Cu-based metallic glasses and could not be simply predicted by the large difference in the enthalpy of mixing between different elements in alloys. Second, the abnormal three-stage RP is associated with the non-monotonic change of cluster size with medium range order in supercooled liquids. Third, the existence of the liquid-liquid phase transition depicted by anomalous viscosity drop during cooling in superheated liquids could be a signature of the unusual structural change causing the abnormal three-step sub-Tg RP in the GRs. This work helps to better understand the complex structural evolution from superheated to supercooled liquids approaching Tg.

  16. Object recognition memory and BDNF expression are reduced in young TgCRND8 mice.

    PubMed

    Francis, Beverly M; Kim, John; Barakat, Meredith E; Fraenkl, Stephan; Yücel, Yeni H; Peng, Shiyong; Michalski, Bernadeta; Fahnestock, Margaret; McLaurin, Joanne; Mount, Howard T J

    2012-03-01

    The TgCRND8 mouse model of Alzheimer's disease exhibits progressive cortical and hippocampal β-amyloid accumulation, resulting in plaque pathology and spatial memory impairment by 3 months of age. We tested whether TgCRND8 cognitive function is disrupted prior to the appearance of macroscopic plaques in an object recognition task. We found profound deficits in 8-week-old mice. Animals this age were not impaired on the Morris water maze task. TgCRND8 and littermate controls did not differ in their duration of object exploration or optokinetic responses. Thus, visual and motor dysfunction did not confound the phenotype. Object memory deficits point to the frontal cortex and hippocampus as early targets of functional disruption. Indeed, we observed altered levels of brain-derived neurotrophic factor (BDNF) messenger ribonucleic acid (mRNA) in these brain regions of preplaque TgCRND8 mice. Our findings suggest that object recognition provides an early index of cognitive impairment associated with amyloid exposure and reduced brain-derived neurotrophic factor expression in the TgCRND8 mouse. PMID:20447730

  17. [Intestinal absorption of fats in children using serum turbidity and triglyceride absorption tests].

    TOXLINE Toxicology Bibliographic Information

    Costa CD; Schmidt BJ; de Barros FJ; Tamega I das E

    1985-10-01

    Intestinal fat absorption was studied, using serum turbidity and serum triglyceride levels, which were determined before and after a test meal of 2 g neutral fat per kg b.w. in 33 children: 25 controls, four with cystic fibrosis, and four with celiac disease. The results proved that the easy-to-perform serum turbidity test was superior to the triglyceride absorption test in characterizing fat digestion and absorption. The most substantial increase in both tests occurred about three hours after the oral fat load.

  18. [Intestinal absorption of fats in children using serum turbidity and triglyceride absorption tests].

    PubMed

    Costa, C D; Schmidt, B J; de Barros, F J; Tamega I das, E

    1985-01-01

    Intestinal fat absorption was studied, using serum turbidity and serum triglyceride levels, which were determined before and after a test meal of 2 g neutral fat per kg b.w. in 33 children: 25 controls, four with cystic fibrosis, and four with celiac disease. The results proved that the easy-to-perform serum turbidity test was superior to the triglyceride absorption test in characterizing fat digestion and absorption. The most substantial increase in both tests occurred about three hours after the oral fat load. PMID:3837660

  19. Large restriction fragments containing poly-TG are highly polymorphic in a variety of vertebrates.

    PubMed

    Kashi, Y; Tikochinsky, Y; Genislav, E; Iraqi, F; Nave, A; Beckmann, J S; Gruenbaum, Y; Soller, M

    1990-03-11

    Southern blots of genomic DNA from a variety of species digested by restriction endonucleases having a four-bp specificity, were probed with a bovine genomic clone consisting of seven tandem poly-TG stretches separated by a 29bp linker sequence. Highly variable DNA 'fingerprint' patterns were obtained in chicken, sheep, and horse, moderately variable DNA 'fingerprints' in mouse and man, and a monomorphic pattern in Drosophila. In chicken, horse and man a (TG)10 synthetic oligonucleotide probe gave results identical to those given by the bovine probe. Furthermore, in chicken the DNA fingerprint variation showed typical Mendelian inheritance and differed from the fingerprints obtained with Jeffreys 33.6 and M13 minisatellite probes. Thus, for a variety of vertebrate species, poly-TG-containing probes can uncover useful genetic variation. PMID:1969619

  20. Local lymph node assay: how testing laboratories apply OECD TG 429 for REACH purposes.

    PubMed

    Rovida, Costanza

    2011-01-01

    The Local Lymph Node Assay (LLNA) is the official method for assessing the allergic contact dermatitis potential of chemicals for the purposes of REACH regulation. The LLNA went through a validation process that allowed the delineation of a robust protocol for performing new tests. The OECD accepted this method in 2002 and published OECD TG 429. The European Chemical Agency (ECHA) recently published data that were submitted in the registration dossiers of chemicals. This database was analysed to determine how testing laboratories apply OECD TG 429. This analysis comes after a detailed analysis of four full study reports that were also prepared for REACH purposes. Although the majority of the tests are fully compliant with OECD TG 429, some showed major deviations, and a number of others used more animals than necessary. This suggests that in vivo tests need to be planned more carefully and consciously to obtain meaningful results with the minimum animal number necessary. PMID:21625828

  1. Characterization of cure in model photocrosslinking acrylate systems: Relationships among tensile properties, Tg and ultraviolet dose

    SciTech Connect

    Rakas, M.A.

    1996-10-01

    The extent of cure of a thermosetting polymer is governed largely by polymerization kinetics and the difference between the polymerization temperature and the material`s ultimate glass transition temperature (Tg). For prepolymers which cure when exposed to ultraviolet (UV) radiation, other factors which strongly determine the extent of cure are the UV intensity and exposure time, and the interrelationship between the optical absorbance of the photoinitiator (PI) and the rate of formation of excited state PI radicals. Beers` Law can be used to understand the relationship between the PI`s molar absorptivity, its concentration, and adhesive film thickness. Many adhesives users are more concerned with bulk properties such as tensile modulus and Tg rather than a numerical measurement of degree of cure. Therefore, this research employed model acrylate formulations and determined changes in tensile properties and Tg as a function of film thickness and UV dose. These results enabled correlation of bulk and photoinitiator properties.

  2. 49. East elevation of elevated Mainline Structure (Section F5) ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    49. East elevation of elevated Mainline Structure (Section F-5) - looking West - toward Washington Street near Marcella Street. Highland Park and the Water Tower are in the background. - Boston Elevated Railway, Elevated Mainline, Washington Street, Boston, Suffolk County, MA

  3. MrBayes tgMC: a tight GPU implementation of MrBayes.

    PubMed

    Ling, Cheng; Hamada, Tsuyoshi; Bai, Jianing; Li, Xianbin; Chesters, Douglas; Zheng, Weimin; Shi, Weifeng

    2013-01-01

    MrBayes is model-based phylogenetic inference tool using Bayesian statistics. However, model-based assessment of phylogenetic trees adds to the computational burden of tree-searching, and so poses significant computational challenges. Graphics Processing Units (GPUs) have been proposed as high performance, low cost acceleration platforms and several parallelized versions of the Metropolis Coupled Markov Chain Mote Carlo (MC(3)) algorithm in MrBayes have been presented that can run on GPUs. However, some bottlenecks decrease the efficiency of these implementations. To address these bottlenecks, we propose a tight GPU MC(3) (tgMC(3)) algorithm. tgMC(3) implements a different architecture from the one-to-one acceleration architecture employed in previously proposed methods. It merges multiply discrete GPU kernels according to the data dependency and hence decreases the number of kernels launched and the complexity of data transfer. We implemented tgMC(3) and made performance comparisons with an earlier proposed algorithm, nMC(3), and also with MrBayes MC(3) under serial and multiply concurrent CPU processes. All of the methods were benchmarked on the same computing node from DEGIMA. Experiments indicate that the tgMC(3) method outstrips nMC(3) (v1.0) with speedup factors from 2.1 to 2.7. In addition, tgMC(3) outperforms the serial MrBayes MC(3) by a factor of 6 to 30 when using a single GTX480 card, whereas a speedup factor of around 51 can be achieved by using two GTX 480 cards on relatively long sequences. Moreover, tgMC(3) was compared with MrBayes accelerated by BEAGLE, and achieved speedup factors from 3.7 to 5.7. The reported performance improvement of tgMC(3) is significant and appears to scale well with increasing dataset sizes. In addition, the strategy proposed in tgMC(3) could benefit the acceleration of other Bayesian-based phylogenetic analysis methods using GPUs. PMID:23593277

  4. MrBayes tgMC3: A Tight GPU Implementation of MrBayes

    PubMed Central

    Ling, Cheng; Hamada, Tsuyoshi; Bai, Jianing; Li, Xianbin; Chesters, Douglas; Zheng, Weimin; Shi, Weifeng

    2013-01-01

    MrBayes is model-based phylogenetic inference tool using Bayesian statistics. However, model-based assessment of phylogenetic trees adds to the computational burden of tree-searching, and so poses significant computational challenges. Graphics Processing Units (GPUs) have been proposed as high performance, low cost acceleration platforms and several parallelized versions of the Metropolis Coupled Markov Chain Mote Carlo (MC3) algorithm in MrBayes have been presented that can run on GPUs. However, some bottlenecks decrease the efficiency of these implementations. To address these bottlenecks, we propose a tight GPU MC3 (tgMC3) algorithm. tgMC3 implements a different architecture from the one-to-one acceleration architecture employed in previously proposed methods. It merges multiply discrete GPU kernels according to the data dependency and hence decreases the number of kernels launched and the complexity of data transfer. We implemented tgMC3 and made performance comparisons with an earlier proposed algorithm, nMC3, and also with MrBayes MC3 under serial and multiply concurrent CPU processes. All of the methods were benchmarked on the same computing node from DEGIMA. Experiments indicate that the tgMC3 method outstrips nMC3 (v1.0) with speedup factors from 2.1 to 2.7. In addition, tgMC3 outperforms the serial MrBayes MC3 by a factor of 6 to 30 when using a single GTX480 card, whereas a speedup factor of around 51 can be achieved by using two GTX 480 cards on relatively long sequences. Moreover, tgMC3 was compared with MrBayes accelerated by BEAGLE, and achieved speedup factors from 3.7 to 5.7. The reported performance improvement of tgMC3 is significant and appears to scale well with increasing dataset sizes. In addition, the strategy proposed in tgMC3 could benefit the acceleration of other Bayesian-based phylogenetic analysis methods using GPUs. PMID:23593277

  5. Hole mobility enhancement of MEH-PPV film by heat treatment at Tg

    NASA Astrophysics Data System (ADS)

    Kajiya, Daisuke; Koganezawa, Tomoyuki; Saitow, Ken-ichi

    2015-12-01

    The hole mobility of poly[2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylene vinylene] (MEH-PPV) film was measured using the time-of-flight method. The hole mobility was enhanced 4-fold after annealing at around the glass transition temperature (Tg). Optical, atomic force, and Kelvin force microscopies, and grazing-incidence X-ray diffraction measurements indicate the enhancement can be attributed to a homogeneous film structure, a homogeneous Fermi level energy, and a face-on oriented structure, all of which were established by annealing at Tg.

  6. A lipasin/Angptl8 monoclonal antibody lowers mouse serum triglycerides involving increased postprandial activity of the cardiac lipoprotein lipase.

    PubMed

    Fu, Zhiyao; Abou-Samra, Abdul B; Zhang, Ren

    2015-01-01

    Lipasin/Angptl8 is a feeding-induced hepatokine that regulates triglyceride (TAG) metabolism; its therapeutical potential, mechanism of action, and relation to the lipoprotein lipase (LPL), however, remain elusive. We generated five monoclonal lipasin antibodies, among which one lowered the serum TAG level when injected into mice, and the epitope was determined to be EIQVEE. Lipasin-deficient mice exhibited elevated postprandial activity of LPL in the heart and skeletal muscle, but not in white adipose tissue (WAT), suggesting that lipasin suppresses the activity of LPL specifically in cardiac and skeletal muscles. Consistently, mice injected with the effective antibody or with lipasin deficiency had increased postprandial cardiac LPL activity and lower TAG levels only in the fed state. These results suggest that lipasin acts, at least in part, in an endocrine manner. We propose the following model: feeding induces lipasin, activating the lipasin-Angptl3 pathway, which inhibits LPL in cardiac and skeletal muscles to direct circulating TAG to WAT for storage; conversely, fasting induces Angptl4, which inhibits LPL in WAT to direct circulating TAG to cardiac and skeletal muscles for oxidation. This model suggests a general mechanism by which TAG trafficking is coordinated by lipasin, Angptl3 and Angptl4 at different nutritional statuses. PMID:26687026

  7. A lipasin/Angptl8 monoclonal antibody lowers mouse serum triglycerides involving increased postprandial activity of the cardiac lipoprotein lipase

    PubMed Central

    Fu, Zhiyao; Abou-Samra, Abdul B.; Zhang, Ren

    2015-01-01

    Lipasin/Angptl8 is a feeding-induced hepatokine that regulates triglyceride (TAG) metabolism; its therapeutical potential, mechanism of action, and relation to the lipoprotein lipase (LPL), however, remain elusive. We generated five monoclonal lipasin antibodies, among which one lowered the serum TAG level when injected into mice, and the epitope was determined to be EIQVEE. Lipasin-deficient mice exhibited elevated postprandial activity of LPL in the heart and skeletal muscle, but not in white adipose tissue (WAT), suggesting that lipasin suppresses the activity of LPL specifically in cardiac and skeletal muscles. Consistently, mice injected with the effective antibody or with lipasin deficiency had increased postprandial cardiac LPL activity and lower TAG levels only in the fed state. These results suggest that lipasin acts, at least in part, in an endocrine manner. We propose the following model: feeding induces lipasin, activating the lipasin-Angptl3 pathway, which inhibits LPL in cardiac and skeletal muscles to direct circulating TAG to WAT for storage; conversely, fasting induces Angptl4, which inhibits LPL in WAT to direct circulating TAG to cardiac and skeletal muscles for oxidation. This model suggests a general mechanism by which TAG trafficking is coordinated by lipasin, Angptl3 and Angptl4 at different nutritional statuses. PMID:26687026

  8. [Investigating patients with differentiated thyroid carcinoma and elevated serum thyroglobulin but negative whole-body scan].

    PubMed

    Rosário, Pedro Weslley S; Maia, Flávia Coimbra P; Barroso, Alvaro Luís; Purisch, Saulo

    2005-04-01

    Findings of elevated thyroglobulin (Tg) and a negative whole-body scan (WBS) are not uncommon during the follow-up of differentiated thyroid carcinoma. In 12% of our patients submitted to thyroidectomy and radioiodine with Tg >10 ng/ml during hypothyroidism had a negative diagnostic WBS. This finding generally corresponds to a false-negative WBS. Inadequate preparation in terms of iodine exposure and insufficient elevation of TSH should be excluded. Micrometastases which do not accumulate sufficient iodine to be detected by low radioiodine activity and the loss of the capacity to express the sodium/iodine symporter explain many cases. In patients with elevated Tg, metastases can be identified after the administration of a therapeutic radioiodine dose, with this procedure being indicated in cases with Tg >10 ng/ml during hypothyroidism or >5 ng/ml after recombinant TSH, after exclusion of lung and cervical macrometastases. In the present study, 5 of 7 patients with these criteria showed ectopic uptake on post-therapy WBS. If the post-therapy scan is negative or reveals discrete uptake in the thyroid bed, other methods (e.g. FDG PET) can be performed, and the physician should not insist on radioiodine therapy. If WBS detect lymph node metastases, surgery is indicated, while in cases of diffuse lung metastases radioiodine is indicated until the occurrence of a negative WBS or normalization of stimulated Tg levels. Patients with a positive post-therapy scan may show a significant reduction in Tg, with even complete remission in some cases after radioiodine, but the impact of this treatment on mortality remains controversial. PMID:16184253

  9. Enzymatic determination of cholesterol and triglycerides in serum lipoprotein profiles by asymmetrical flow field-flow fractionation with on-line, dual detection.

    PubMed

    Rambaldi, Diana Cristina; Reschiglian, Pierluigi; Zattoni, Andrea; Johann, Christoph

    2009-11-01

    Alterations of lipoproteins (LPs) and related lipid levels in blood serum are correlated to the risk of coronary artery disease (CAD). Fast, possibly automated methods to obtain complete, multi-parametric LP profiles are therefore welcome to be developed for routine, clinical analysis practice. In this work, asymmetrical flow field-flow fractionation (AF4) with on-line, dual post-fractionation reaction detection (PFRD) is applied to develop a method for single-run, simultaneous quantification of cholesterol (CHOL) and triglycerides (TGs) in each fractionated LP class. The enzymatic reagents used for the post-fractionation reaction are available as commercial kits for certified, standard clinical protocols for the analysis of CHOL and TGs in serum. Using CHOL and glycerol as reference standards, a new procedure is applied to optimize the experimental conditions for PFRD-based, quantitative analysis. Upon optimized PFRD and AF4 conditions, results obtained for the determination of total CHOL (TC), TGs, HDL-cholesterol (HDL-C), and LDL-cholesterol (LDL-C) in a set of serum samples from healthy donors are found in agreement with the values provided by a clinical laboratory. The intra-day and inter-day precisions of the method were found always lower than 10% (CV). When the method was applied to serum samples from patients affected by sepsis, differences in CHOL and TG profiles between patients and healthy donors were observed. PMID:19850170

  10. Comprehensive Experiment--Clinical Biochemistry: Determination of Blood Glucose and Triglycerides in Normal and Diabetic Rats

    ERIC Educational Resources Information Center

    Jiao, Li; Xiujuan, Shi; Juan, Wang; Song, Jia; Lei, Xu; Guotong, Xu; Lixia, Lu

    2015-01-01

    For second year medical students, we redesigned an original laboratory experiment and developed a combined research-teaching clinical biochemistry experiment. Using an established diabetic rat model to detect blood glucose and triglycerides, the students participate in the entire experimental process, which is not normally experienced during a…

  11. Heterogeneous catalysts for the transformation of fatty acid triglycerides and their derivatives to fuel hydrocarbons

    NASA Astrophysics Data System (ADS)

    Yakovlev, Vadim A.; Khromova, Sofia A.; Bukhtiyarov, Valerii I.

    2011-10-01

    The results of studies devoted to the catalysts for transformation of fatty acid triglycerides and their derivatives to fuel hydrocarbons are presented and described systematically. Various approaches to the use of heterogeneous catalysts for the production of biofuel from these raw materials are considered. The bibliography includes 134 references.

  12. Tissue distribution of lipase genes related to triglyceride metabolism in laying hens (Gallus gallus).

    PubMed

    Sato, Kan; Seol, Hyang Sook; Kamada, Toshihiko

    2010-01-01

    The triglyceride lipase gene family, including lipoprotein lipase (LPL), hepatic triglyceride lipase (HTGL), carboxyl ester lipase (CEL), endothelial lipase (EL), Lipase H, hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL), plays a critical role in lipid metabolism in mammals. In this study, we have identified and characterized the expression profile of these genes in the chicken, Gallus gallus. Chicken LPL and ATGL have been cloned, and HTGL, EL, Lipase H, and CEL sequences were found in the chicken genome database. The deduced amino acid sequences of HTGL, EL, Lipase H, and CEL were 66, 75, 63, and 65% identical with their respective human genes, suggesting conservation of important enzymatic functions. In contrast, a homologue of the HSL gene was not identified in the chicken genome. We performed RT-PCR using chicken liver, muscle, abdominal adipose tissue, or pancreas mRNA as the template, and all partial products were completely matched to the corresponding predicted sequences of triglyceride lipase gene members. Quantitation by qPCR of the transcript levels of these genes in 13 tissues indicates that the expression patterns diverge greatly between species. A particularly interesting pattern was observed in the distribution of EL and HTGL mRNA, which were highly expressed in kidney and ovary. This is the first report of HTGL, EL, Lipase H, and CEL in a pre-mammalian species and reveals novel details about specific features of the expression of these important molecules in lipid metabolism. PMID:19818411

  13. Effects of CETP inhibition on triglyceride-rich lipoprotein composition and apoB-48 metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cholesteryl ester transfer protein (CETP) facilitates the transfer of HDL cholesteryl ester (CE) to triglyceride-rich lipoproteins (TRL). This study aimed to determine the effects of CETP inhibition with torcetrapib on TRL composition and apoB-48 metabolism. Study subjects with low HDL cholesterol...

  14. Triglyceride synthesis by small-intestinal epithelium of the pig, sheep and chicken

    PubMed Central

    Bickerstaffe, R.; Annison, E. F.

    1969-01-01

    1. A comparative study was made of triglyceride synthesis by the intestinal epithelium of pigs, sheep and chickens. In pig and chicken tissue both the glycerol 3-phosphate and the monoglyceride pathway of triglyceride synthesis were operative, but the former pathway predominated in sheep tissue. 2. The fatty acid specificity of the glycerol 3-phosphate pathway was studied in pig and sheep total-homogenate preparations. Maximum incorporation was obtained with myristic acid and palmitic acid under optimum conditions for each fatty acid. Lauric acid, myristic acid, oleic acid, linoleic acid and linolenic acid were inhibitory at concentrations above their optimum, but octanoic acid, decanoic acid, palmitic acid and stearic acid did not show this effect. 3. Subcellular fractionation located the glycerol 3-phosphate and monoglyceride pathways of triglyceride synthesis in the microsomes in all instances. Phosphatidate phosphohydrolase was associated with both the microsomes and the particle-free supernatant. 4. Glycerol 1-mono-oleate was incorporated into triglycerides to a greater extent than glycerol 1-mono-palmitate or glycerol 1-monostearate by microsomal preparations from pig and chicken. 5. A lipase specific for monoglycerides was detected in the particle-free supernatant of all the species examined. PMID:4304509

  15. Triglyceride levels and risk of type 2 diabetes mellitus: a longitudinal large study.

    PubMed

    Beshara, Amani; Cohen, Eytan; Goldberg, Elad; Lilos, Pearl; Garty, Moshe; Krause, Ilan

    2016-02-01

    The relationship between triglyceridemia and diabetes mellitus remains unclear. This study evaluated the risk of diabetes and impaired fasting glucose associated with a wide range of triglyceride levels. A longitudinal retrospective study was carried out employing data from a screening center between the years 2000 and 2012. Inclusion criteria were absence of diabetes at baseline and attendance at the center at least twice over a 5-year period. Participants were divided by fasting blood glucose level (normal/impaired) at the first visit. A total of 5085 participants were eligible for the study. Of the 4164 normoglycemic participants at baseline, 40 (0.96%) had diabetes and 998 (24%) had impaired fasting glucose by the end of the study. On stepwise logistic regression analysis, every 10?mg/dL increase in triglyceride level significantly increased the risk of diabetes by 4% and of impaired fasting glucose by 2% (p<0.001). This association held true even when rising triglyceride levels remained within the accepted normal range (<150?mg/dL, p<0.001). Sustained increments in serum triglyceride level, even within the accepted normal range, are an independent risk factor for diabetes mellitus and impaired fasting glucose in normoglycemic participants. PMID:26911628

  16. Processing of coriander fruits for the production of essential oil, triglyceride, and high protein seed meal

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Coriander (Coriandrum sativum L.) is a summer annual traditionally grown for use as a fresh green herb or as a spice. The essential oil extracted from coriander fruit is also widely used as flavoring in a variety of food products. The fatty oil (triglyceride) fraction in the seed is rich in petrosel...

  17. Detection of triglycerides using immobilized enzymes in food and biological samples

    NASA Astrophysics Data System (ADS)

    Raichur, Ashish; Lesi, Abiodun; Pedersen, Henrik

    1996-04-01

    A scheme for the determination of total triglyceride (fat) content in biomedical and food samples is being developed. The primary emphasis is to minimize the reagents used, simplify sample preparation and develop a robust system that would facilitate on-line monitoring. The new detection scheme developed thus far involves extracting triglycerides into an organic solvent (cyclohexane) and performing partial least squares (PLS) analysis on the NIR (1100 - 2500 nm) absorbance spectra of the solution. A training set using 132 spectra of known triglyceride mixtures was complied. Eight PLS calibrations were generated and were used to predict the total fat extracted from commercial samples such as mayonnaise, butter, corn oil and coconut oil. The results typically gave a correlation coefficient (r) of 0.99 or better. Predictions were typically within 90% and better at higher concentrations. Experiments were also performed using an immobilized lipase reactor to hydrolyze the fat extracted into the organic solvent. Performing PLS analysis on the difference spectra of the substrate and product could enhance specificity. This is being verified experimentally. Further work with biomedical samples is to be performed. This scheme may be developed into a feasible detection method for triglycerides in the biomedical and food industries.

  18. Comprehensive Experiment--Clinical Biochemistry: Determination of Blood Glucose and Triglycerides in Normal and Diabetic Rats

    ERIC Educational Resources Information Center

    Jiao, Li; Xiujuan, Shi; Juan, Wang; Song, Jia; Lei, Xu; Guotong, Xu; Lixia, Lu

    2015-01-01

    For second year medical students, we redesigned an original laboratory experiment and developed a combined research-teaching clinical biochemistry experiment. Using an established diabetic rat model to detect blood glucose and triglycerides, the students participate in the entire experimental process, which is not normally experienced during a

  19. Osage Orange (Maclura pomifera L.) Seed Oil Poly(?-hydroxydibutylamine) Triglycerides: Synthesis and Characterization.

    PubMed

    Harry-O'kuru, Rogers E; Tisserat, Brent; Gordon, Sherald H; Gravett, Alan

    2015-07-29

    Milled Osage orange seeds (Maclura pomifera (Raf.) Schneid) were Soxhlet extracted with hexane, and portions of the extract were treated with activated carbon before solvent removal. The crude oil was winterized and degummed by centrifugation at low temperature. Decantation of the centrifugate gave an admixture of the triglycerides and free fatty acids. The free fatty acid content of the oil was removed when portions of the admixture were diluted with hexane and shaken with cold aqueous ammonium hydroxide (0.1 M) solution. The desiccant-dried organic phase was concentrated under reduced pressure to give the cleaned Osage orange triglyceride after solvent removal by rotary evaporation at 67 C. Epoxidation of the resulting cleaned triglyceride was effected by reaction with in situ generated peroxy performic acid in H2O2. The oxirane rings of the derivatized oil were then opened using N,N-dibutylamine catalyzed by anhydrous ZnCl2 to afford the poly(?-hydroxydibutylamine) triglyceride. The purpose of this work was to derivatize and thereby stabilize this highly unsaturated tree oil for its eventual use in lubrication applications. PMID:26189408

  20. Intercorrelations among plasma high density lipoprotein, obesity and triglycerides in a normal population

    SciTech Connect

    Albrink, M.J.; Krauss, R.M.; Lindgren, F.T.; von der Groeben, J.; Pan, S.; Wood, P.D.

    1980-01-01

    The interrelationships among fatness measures, plasma triglycerides and high density lipoproteins (HDL) were examined in 131 normal adult subjects: 38 men aged 27 to 46, 50 men aged 47 to 66, 29 women aged 27 to 46 and 24 women aged 47 to 66. None of the women were taking estrogens or oral contraceptive medication. The HDL concentration was subdivided into HDL/sub 2b/, HDL/sub 2a/ and HDL by a computerized fitting of the total schileren pattern to reference schlieren patterns. Anthropometric measures employed included skinfolds at 3 sites, 2 weight/height indices and 2 girth measurements. A high correlation was found among the various fatness measures. These measures were negatively correlated with total HDL, reflecting the negative correlation between fatness measures and HDL/sub 2/ (as the sum of HDL/sub 2a/ and /sub 2b/). Fatness measures showed no relationship to HDL/sub 3/. There was also an inverse correlation between triglyceride concentration and HDL/sub 2/. No particular fatness measure was better than any other for demonstrating the inverse correlation with HDL but multiple correlations using all of the measures of obesity improved the correlations. Partial correlations controlling for fatness did not reduce any of the significnt correlations between triglycerides and HDL/sub 2/ to insignificance. The weak correlation between fatness and triglycerides was reduced to insigifnicance when controlled for HDL/sub 2/.

  1. Genetic APOC3 mutation, serum triglyceride concentrations, and coronary heart disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent decades have witnessed an increased awareness of the importance of lowering triglyceride concentrations in conjunction with lowering LDL cholesterol (LDL-C) to achieve optimal reduction of the risk for coronary heart disease (CHD). Historically, LDL-C was the only target of pharmacologic ther...

  2. NATIONAL ELEVATION DATASET

    EPA Science Inventory

    The USGS National Elevation Dataset (NED) has been developed by merging the highest-resolution, best-quality elevation data available across the United States into a seamless raster format. NED is the result of the maturation of the USGS effort to provide 1:24,000-scale Digital ...

  3. NATIONAL ELEVATION DATASET HILLSHADE

    EPA Science Inventory

    The USGS National Elevation Dataset (NED) has been developed bymerging the highest-resolution, best-quality elevation data available across the United States into a seamless raster format. NED is the result of the maturation of the USGS effort to provide 1:24,000-scale Digital E...

  4. Serum A-FABP Is Increased and Closely Associated with Elevated NT-proBNP Levels in Type 2 Diabetic Patients Treated with Rosiglitazone

    PubMed Central

    Zhou, Mi; Bao, Yuqian; Lu, Junxi; Zhou, Jian; Jia, Weiping

    2011-01-01

    Background Adipocyte fatty acid-binding protein (A-FABP) has been shown to play important roles in the development of metabolic syndrome, diabetes, and cardiovascular diseases. In this study we investigated the possible role of A-FABP in the development of cardiac dysfunction related to rosiglitazone treatment. Methodology/Principal Findings A total of 84 patients with newly diagnosed type 2 diabetes were treated with rosiglitazone for 48 weeks. Circulating A-FABP and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were determined at baseline and repeated at 24 and 48 weeks. After the 48-week rosiglitazone treatment period, serum levels of both A-FABP and NT-proBNP increased progressively and significantly (P<0.01). Serum levels of A-FABP were demonstrated to be positively correlated with gender and waist circumference both at baseline and the end of the study, and with age, body mass index (BMI), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and NT-proBNP at 48 weeks (all P<0.05). In addition, changes in A-FABP were significantly and positively correlated with changes in NT-proBNP (r?=?0.239, P?=?0.039). Furthermore, multiple stepwise regression analysis showed that the changes in A-FABP were independently and positively associated with changes in NT-proBNP after adjusting for confounding factors (??=?0.320, P?=?0.007). Conclusions/Significance Rosiglitazone-mediated increase of A-FABP is closely associated with the elevation of NT-proBNP, a well-established marker of cardiac dysfunction. The findings of our study imply that A-FABP may mediate the cross-talk between heart and adipose tissue. PMID:22046439

  5. Mars elevation distribution

    NASA Technical Reports Server (NTRS)

    Wu, Sherman S. C.; Howington-Kraus, Annie E.; Ablin, Karyn K.

    1991-01-01

    A Digital Terrain Model (DTM) of Mars was derived with both Mercator and Sinusoidal Equal-Area projections from the global topographic map of Mars (scale 1:15 million, contour interval 1 km). Elevations on the map are referred to Mars' topographic datum that is defined by the gravity field at a 6.1-millibar pressure surface with respect to the center of mass of Mars. The DTM has a resolution at the equator of 1/59.226 degrees (exactly 1 km) per pixel. By using the DTM, the volumetric distribution of Mars topography above and below the datum has previously been calculated. Three types of elevation distributions of Mars' topography were calculated from the same DTM: (1) the frequency distribution of elevations at the pixel resolution; (2) average elevations in increments of 6 degrees in both longitude and latitude; and (3) average elevations in 36 separate blocks, each covering 30 degrees of latitude and 60 degrees of longitude.

  6. IgG anti-tTG responses in different autoimmune conditions differ in their epitope targets and subclass usage.

    PubMed

    Comerford, Ross; Kelly, Jacinta; Feighery, Conleth; Byrne, Greg

    2015-10-01

    Antibodies of the IgA class directed against the enzyme tissue transglutaminase (tTG) are highly specific for coeliac disease (CD). IgG antibodies to tTG also occur in CD, and have also been reported in autoimmune diseases such as type 1 diabetes mellitus and Crohn's disease. In comparison to the IgA anti-tTG response, little is known of the IgG anti-tTG response in terms of epitope specificity and IgG subclass usage. The aim of this study was to investigate and compare epitopes recognised by CD and non-CD IgG anti-tTG antibodies, and determine the relative proportions of the IgG subclasses comprising this response. IgG anti-tTG positive individuals who did not have CD were identified by screening groups of patients with type I diabetes mellitus, Crohn's disease and granulomatosis with polyangiitis. Results from ELISA blocking experiments and mutant tTG antigens demonstrate that non-CD IgG anti-tTG bind different epitopic determinants to CD IgG anti-tTG. The IgG subclass usage of coeliac disease and type 1 diabetes was dominated by IgG1, whereas this IgG subclass was infrequently a component of the IgG anti-tTG response in diseases such as granulomatosis with polyangiitis and Crohn's disease. The differences in epitope specificity and subclass usage of IgG anti-tTG observed between CD and non-CD individuals may be due to the differing mechanisms underlying tTG autoimmunity. PMID:26184652

  7. Immunomodulation targeting of both A? and tau pathological conformers ameliorates Alzheimers disease pathology in TgSwDI and 3xTg mouse models

    PubMed Central

    2013-01-01

    Background Central to the pathogenesis of Alzheimers disease (AD) and many other neurodegenerative diseases is the conformational change of a normal self-protein into toxic oligomeric species and amyloid deposits. None of these disorders have an effective therapy, but immunization approaches hold great promise. We have previously shown that active immunization with a novel peptide when polymerized into a stable oligomeric conformation, pBri, induced a humoral immune response to toxic A? species in an AD model, APP/PS1 transgenic (Tg) mice, reducing plaque deposits. pBri is a glutaraldehyde polymerized form of the carboxyl fragment of an amyloidogenic protein, which is deposited in the brains of patients with a rare autosomal dominant disease due to a missense mutation in a stop codon, resulting in the translation of an intronic sequence, with no known sequence homology to any mammalian protein. Methods In the current study we tested whether pBri-peptide-based immunomodulation is effective at reducing both vascular amyloid deposits and tau-related pathology using TgSwDI mice with extensive congophilic angiopathy and 3xTg mice with tau pathology. Results Our results indicate that this immunomodulation approach, which produces a humoral response to proteins in a pathological conformation, is effective at reducing both A? and tau-related pathologies. Conclusions This immunomodulatory approach has the advantage of using a non-self-immunogen that is less likely to be associated with autoimmune toxicity. Furthermore we found that it is able to target all the cardinal features of AD concurrently. PMID:24330773

  8. N-Glycoproteome of E14.Tg2a Mouse Embryonic Stem Cells

    PubMed Central

    Sun, Bingyun; Ma, Li; Yan, Xiaowei; Lee, Denis; Alexander, Vinita; Hohmann, Laura J.; Lorang, Cynthia; Chandrasena, Lalangi; Tian, Qiang; Hood, Leroy

    2013-01-01

    E14.Tg2a mouse embryonic stem (mES) cells are a widely used host in gene trap and gene targeting techniques. Molecular characterization of host cells will provide background information for a better understanding of functions of the knockout genes. Using a highly selective glycopeptide-capture approach but ordinary liquid chromatography coupled mass spectrometry (LC-MS), we characterized the N-glycoproteins of E14.Tg2a cells and analyzed the close relationship between the obtained N-glycoproteome and cell-surface proteomes. Our results provide a global view of cell surface protein molecular properties, in which receptors seem to be much more diverse but lower in abundance than transporters on average. In addition, our results provide a systematic view of the E14.Tg2a N-glycosylation, from which we discovered some striking patterns, including an evolutionarily preserved and maybe functionally selected complementarity between N-glycosylation and the transmembrane structure in protein sequences. We also observed an environmentally influenced N-glycosylation pattern among glycoenzymes and extracellular matrix proteins. We hope that the acquired information enhances our molecular understanding of mES E14.Tg2a as well as the biological roles played by N-glycosylation in cell biology in general. PMID:23405203

  9. Comparison between TG-51 and TRS-398: electron contamination effect on photon beam-quality specification.

    PubMed

    Lopez Medina, Antonio; Teijeiro, Antonio; Salvador, Francisco; Medal, Daniela; Vazquez, Julio; Salgado, Manuel; Carrion, Mara C

    2004-01-01

    Two dosimetry protocols based on absorbed dose to water have recently been implemented: TG-51 and TRS-398. These protocols use different beam-quality indices: %dd(10)x and TPR20,10. The effect of electron contamination in measurements of %dd(10)x has been proposed as a disadvantage of the TG-51. For actual measurements of %dd(10)x in five clinical beams (Primus 6-18 MV, SL-75/5 6 MV, SL-18 6-15 MV) a purging magnet was employed to remove the electron contamination. Also, %dd(10)x was measured in the different ways described in TG-51 for high-energy beams: with a lead foil at 50 cm from the phantom surface, at 30 cm, and for open beam. Moreover, TPR20,10 was determined. Also, periodic quality-control measurements were used for comparing both quality indices and variation over time, but D20,10 was used instead of TPR20,10 and measurements in open beam for the %dd(10)x determination. Considering both protocols, S(w,air) and kQ were calculated in order to compare the results with the experimental data. Significant differences (0.3% for kQ) were only found for the two high-energy beams, but when the electron contamination is underestimated by TG-51, the difference in kQ is lower. Differences in the other cases and variations over time were less than 0.1%. PMID:14971770

  10. Lymphocytic infiltration in the cutaneous lymphoma microenvironment after injection of TG1042

    PubMed Central

    2013-01-01

    Background Primary cutaneous lymphomas (CLs), characterized by an accumulation of clonal T or B lymphocytes preferentially localized in the skin, have been successfully treated with interferons (IFNs) which counterbalance the Th2-immunosuppressive state associated with this pathology. In a phase I/II clinical trial, we correlated the local immune infiltrate and the anti-tumor effects of repeated intralesional administrations of an adenovirus vector expressing human interferon-gamma (IFN-g) termed TG1042, in patients with advanced primary cutaneous T-cell lymphomas (CTCL) or multilesional cutaneous B-cell lymphomas (CBCL). Methods For each patient, variation in time of specific lymphocyte populations, defined by immunohistochemical stainings, was assessed in biopsies of injected lesions. For each patient, the change in local immune response was associated with the patients objective response at the end of the study. Results Immunohistochemical analyses of biopsies indicate that infiltration of CD8+ T lymphocytes and of TIA-1+ cytotoxic T-cells in lesions injected with TG1042 correlates with clinical benefit. Conclusions These data suggest for the first time that a CD8+ cytotoxic infiltrate, induced by local expression of IFN-g correlates with a clinical response. Trial registration The phase I step (TG1042.01) does not have a registration number. The phase II step (TG1042.06) registration number was NCT00394693. PMID:24063735

  11. Generalized second law of thermodynamics in f(T,TG) gravity

    NASA Astrophysics Data System (ADS)

    Zubair, M.; Jawad, Abdul

    2015-11-01

    We discuss the equilibrium picture of thermodynamic at the apparent horizon of FRW universe in f(T,TG) gravity, where T represents the torsion invariant and TG is the teleparallel equivalent of the Gauss-Bonnet term. It is found that one can translate the Friedmann equations to the standard form of first law of thermodynamics. We discuss GSLT in the locality of assumption that temperature of matter inside the horizon is similar to that of apparent horizon. Furthermore, we consider particular models in this theory and generate constraints on the coupling parameters for the validity of GSLT. For this purpose we set the present day values of cosmic parameters and find the possible constraints on f(T,TG) models. We also choose the power law cosmology and found that GSLT can be met in accelerated cosmic expansion. We have also presented the cosmological reconstruction of some viable f(T,TG) models and discussed the cosmic evolution and validity of GSLT.

  12. Sex difference in pathology and memory decline in rTg4510 mouse model of tauopathy.

    PubMed

    Yue, Mei; Hanna, Amanda; Wilson, Judith; Roder, Hanno; Janus, Christopher

    2011-04-01

    Abnormal phosphorylation of tau protein is a common event in many neurodegenerative disorders, including Alzheimer's disease and other tauopathies. We investigated the relationship between hyperphosphorylated tau in brain extracts and mnemonic functions in rTg4510 mouse model of tauopathy. We report that rTg4510 mice showed rapid deterioration in spatial learning and memory, which paralleled a significant increase of hyperphosphorylated tau in the brain between 3 and 5.5 months of age. At 5.5 months, rTg4510 females showed significantly higher levels of hyperphosphorylated tau than males, with no evidence of differential tau transgene expression between the sexes. The increased levels of hyperphosphorylated tau in females were associated with more severe impairment in spatial learning and memory as compared to transgenic males. We also showed that within studied age range, the decrease in memory performance was accompanied by other behavioral disturbances in the water maze related to search strategy, like thigmotaxic swim and cue response. These findings suggest that the onset of abnormal tau biochemistry and coincident cognitive deficits in the rTg4510 mouse model is sex-dependent with females being affected earlier and more aggressively than males. PMID:19427061

  13. Reduction of ?-amyloid and ?-secretase by calorie restriction in female Tg2576 mice.

    PubMed

    Schafer, Marissa J; Alldred, Melissa J; Lee, Sang Han; Calhoun, Michael E; Petkova, Eva; Mathews, Paul M; Ginsberg, Stephen D

    2015-03-01

    Research indicates that female risk of developing Alzheimer's disease (AD) is greater than that of males. Moderate reduction of calorie intake, known as calorie restriction (CR), reduces pathology in AD mouse models and is a potentially translatable prevention measure for individuals at-risk for AD, as well as an important tool for understanding how the brain endogenously attenuates age-related pathology. Whether sex influences the response to CR remains unknown. In this study, we assessed the effect of CR on beta-amyloid peptide (A?) pathology and hippocampal CA1 neuron specific gene expression in the Tg2576 mouse model of cerebral amyloidosis. Relative to ad libitum (AL) feeding, CR feeding significantly reduced hippocampal A? burden in 15-month-old female, but not age-matched male, Tg2576 mice. Sustained CR also significantly reduced expression of presenilin enhancer 2 (Psenen) and presenilin 1, components of the ?-secretase complex, in Tg2576 females. These results indicate that long-term CR significantly reduces age-dependent female Tg2576 A? pathology, which is likely to involve CR-mediated reductions in ?-secretase-dependent amyloid precursor protein (APP) metabolism. PMID:25556162

  14. Hippocampal hyperexcitability underlies enhanced fear memories in TgNTRK3, a panic disorder mouse model.

    PubMed

    Santos, Mnica; D'Amico, Davide; Spadoni, Ornella; Amador-Arjona, Alejandro; Stork, Oliver; Dierssen, Mara

    2013-09-18

    Panic attacks are a hallmark in panic disorder (PAND). During the panic attack, a strong association with the surrounding context is established suggesting that the hippocampus may be critically involved in the pathophysiology of PAND, given its role in contextual processing. We previously showed that variation in the expression of the neurotrophin tyrosine kinase receptor type 3 (NTRK3) in both PAND patients and a transgenic mouse model (TgNTRK3) may have a role in PAND pathophysiology. Our study examines hippocampal function and activation of the brain fear network in TgNTRK3 mice. TgNTRK3 mice showed increased fear memories accompanied by impaired extinction, congruent with an altered activation pattern of the amygdala-hippocampus-medial prefrontal cortex fear circuit. Moreover, TgNTRK3 mice also showed an unbalanced excitation-to-inhibition ratio in the hippocampal cornu ammonis 3 (CA3)-CA1 subcircuit toward hyperexcitability. The resulting hippocampal hyperexcitability underlies the enhanced fear memories, as supported by the efficacy of tiagabine, a GABA reuptake inhibitor, to rescue fear response. The fearful phenotype appears to be the result of hippocampal hyperexcitability and aberrant fear circuit activation. We conclude that NTRK3 plays a role in PAND by regulating hippocampus-dependent fear memories. PMID:24048855

  15. Creatine reduces hepatic TG accumulation in hepatocytes by stimulating fatty acid oxidation.

    PubMed

    da Silva, Robin P; Kelly, Karen B; Leonard, Kelly-Ann; Jacobs, Ren L

    2014-11-01

    Non-alcoholic fatty liver disease encompasses a wide spectrum of liver damage including steatosis, non-alcoholic steatohepatitis, fibrosis and cirrhosis. We have previously reported that creatine supplementation prevents hepatic steatosis and lipid peroxidation in rats fed a high-fat diet. In this study, we employed oleate-treated McArdle RH-7777 rat hepatoma cells to investigate the role of creatine in regulating hepatic lipid metabolism. Creatine, but not structural analogs, reduced cellular TG accumulation in a dose-dependent manner. Incubating cells with the pan-lipase inhibitor diethyl p-nitrophenylphosphate (E600) did not diminish the effect of creatine, demonstrating that the TG reduction brought about by creatine does not depend on lipolysis. Radiolabeled tracer experiments indicate that creatine increases fatty acid oxidation and TG secretion. In line with increased fatty acid oxidation, mRNA analysis revealed that creatine-treated cells had increased expression of PPAR? and several of its transcriptional targets. Taken together, this study provides direct evidence that creatine reduces lipid accumulation in hepatocytes by the stimulation of fatty acid oxidation and TG secretion. PMID:25205520

  16. Ruthenium polypyridyl TG6 dye for the sensitization of nanoparticle and nanocrystallite spherical aggregate photoelectrodes.

    PubMed

    Hosni, M; Kusumawati, Y; Farhat, S; Jouini, N; Ivansyah, A L; Martoprawiro, M A; Pauport, Th

    2015-01-28

    A ruthenium polypyridyl dye containing a hexasulfanyl-styryl modified bipyridyl group as ancillary ligand, coded TG6, is investigated as a sensitizer for ZnO-based dye-sensitized solar cells (DSSCs). The advantages of this dye are a broad wavelength absorption spectrum, a large loading in ZnO photoelectrodes, a significantly larger extinction coefficient compared to more classical Ru-polypyridyl dyes, and the formation of less agglomerate in the pores of the ZnO layers. TG6 has been used to sensitize ZnO nanorod particle layers of high structural quality and ZnO layers made of submicrometer spheres composed of aggregated nanocrystallites and that develop an internal surface area. The latter are highly light-scattering in the visible wavelength region but more difficult to sensitize correctly. The TG6 dye has been compared with the metal-free D149 dye and has been shown more efficient for photoconversion. The best performances have been obtained by combining TG6 with the nanorod layer, the optimal power conversion efficiency being measured at 5.30% in that case. The cells have been investigated by impedance spectroscopy over a large applied voltage range. We especially show that the submicrometer sphere layers exhibit lower conductivity and lower charge collection efficiency as compared to the nanorod particle ones. PMID:25546020

  17. Impairment of nesting behaviour in 3xTg-AD mice.

    PubMed

    Torres-Lista, Virginia; Gimnez-Llort, Lydia

    2013-06-15

    Deterioration in executive functions and daily life activities (DLA) are early signs of Alzheimer's disease (AD) that signal the need for caregiver attention. We have addressed this issue in the 3xTg-AD mice model for AD and studied nesting behaviour as a natural DLA of parental structures as well as at early- (6 month-old) and advanced-stages (12 month-old) of the disease in isolated animals. The results show genetic, gender and age-dependent impairment of nesting behaviour but also aware about the relevance of factors such as the temporal course of nest construction and the nesting material. Paper towel consistently showed the impairment of nesting behavior in 3xTg-AD mice since early stages of the disease and in both social conditions. Their nest construction was slow temporal pattern and of poor quality, especially in females and advanced stages of the disease where the deficits were shown from the first day. In all cases, cotton elicited an intense behaviour that lead to perfect nesting during the first 48 h. Genotype, gender and age differences were found in the onset of nesting behaviour, with a time delay in the 3xTg-AD mice, particularly in females. The reported impairment of nesting behaviour in 3xTg-AD provides another behavioral tool to assess the benefits of preventive and/or therapeutic strategies, as well as the potential action of risk factors of AD, in this animal model. PMID:23523959

  18. Evaluation of the accuracy of fetal dose estimates using TG-36 data

    SciTech Connect

    Kry, Stephen F.; Starkschall, George; Antolak, John A.; Salehpour, Mohammad

    2007-04-15

    The American Association of Physicists in Medicine Radiation Therapy Committee Task Group 36 report (TG-36) provides guidelines for managing radiation therapy of pregnant patients. Included in the report are data that can be used to estimate the dose to the fetus. The purpose of this study is to evaluate the accuracy of these fetal dose estimates as compared to clinically measured values. TG-36 calculations were performed and compared with measurements of the fetal dose made in vivo or in appropriately-designed phantoms. Calculation and measurement data was collected for eight pregnant patients who underwent radiation therapy at the MD Anderson Cancer Center as well as for several fetal dose studies in the literature. The maximum measured unshielded fetal dose was 47 cGy, which was 1.5% of the prescription dose. For all cases, TG-36 calculations and measured fetal doses differed by up to a factor of 3--the ratio of the calculated to measured dose ranged from 0.34 to 2.93. On average, TG-36 calculations underestimated the measured dose by 31%. No significant trends in the relationship between the calculated and measured fetal doses were found based on the distance from, or the size of, the treatment field.

  19. Reduction of ?-amyloid and ?-secretase by calorie restriction in female Tg2576 mice

    PubMed Central

    Schafer, Marissa J.; Alldred, Melissa J.; Lee, Sang Han; Calhoun, Michael E.; Petkova, Eva; Mathews, Paul M.; Ginsberg, Stephen D.

    2014-01-01

    Research indicates that female risk of developing Alzheimers disease (AD) is greater than that of males. Moderate reduction of calorie intake, known as calorie restriction (CR), reduces pathology in AD mouse models, and is a potentially translatable prevention measure for individuals at-risk for AD, as well as an important tool for understanding how the brain endogenously attenuates age-related pathology. Whether sex influences the response to CR remains unknown. In this study, we assessed the effect of CR on beta-amyloid peptide (A?) pathology and hippocampal CA1 neuron specific gene expression in the Tg2576 mouse model of cerebral amyloidosis. Relative to ad libitum (AL) feeding, CR feeding significantly reduced hippocampal A? burden in 15 month old female, but not age-matched male, Tg2576 mice. Sustained CR also significantly reduced expression of presenilin enhancer 2 (Psenen) and presenilin 1 (Ps1), components of the ?-secretase complex, in Tg2576 females. These results indicate that long-term CR significantly reduces age-dependent female Tg2576 A? pathology, which is likely to involve CR-mediated reductions in ?-secretase-dependent amyloid precursor protein (APP) metabolism. PMID:25556162

  20. Evaluation of even- and odd-chain medium-chain triglycerides as energy sources for neonatal piglets

    SciTech Connect

    Odle, J.

    1989-01-01

    Medium-chain triglycerides (MCT) were evaluated as a supplemental energy source for the newborn piglet. In three experiments, piglets were force-fed 12 mi of MCT, varying in fatty acid (FA) composition. Blood fatty acid and ketone body concentrations peaked 1-2 h after force feeding then returned to baseline by 4 h, illustrating rapid digestion, absorption and oxidation. Peak 3-OH-butyrate concentrations never exceeded 80 {mu}M which is dramatically lower than observed in rats (>2 mM). Improved clinical energy status was also documented by elevated blood glucose concentration and lower nitrogen excretion than observed in fasted controls. Piglets showed an improvement in ability to utilize MCT between 6 and 18 h of age based on a two fold increase in blood concentration of FA and 3-OH-butyrate but no further change between 18 and 48 h. Peak plasma FA concentration decreased progressively as triglyceride-FA chain length increased from C7 (2.1 mM) to C10 (0.4 mM). In two subsequent experiments, hepatocyte metabolism of FA was studied. Hepatocytes oxidized (1-{sup 14}C)- C7 or C9 (1 mM) greater than 40% faster and consumed oxygen 7% faster than cells given C8 or C10. L-carnitine (1 mM) was without effect. Theoretical calculations from FA flux accounted for 95-140% of observed O{sub 2} consumption, indicating the FA were the major fuel source for the cells. Hepatocytes from 2 d pigs oxidized FA 48% faster than cells from 6 h pigs, but this was likely due to an increased metabolic rate observed in the older animals. No differences were detected in ability of small (700-950 g) pigs to oxidize FA relative to large (1,050-1,800 g) littermates. In a final in vivo experiment, pigs were continuously infused with 10 {mu}Ci of (1-{sup 14}C)-C7,C8, C9 or C10 via a catheter passed through the umbilical artery to the heart at a rate of 20, 50 or 100 mole FA/min for 5 h.

  1. TG2-mediated activation of ?-catenin signaling has a critical role in warfarin-induced vascular calcification

    PubMed Central

    Beazley, Kelly E.; Deasey, Stephanie; Lima, Florence; Nurminskaya, Maria V.

    2011-01-01

    Objective Accumulating experimental evidence implicates ?-catenin signaling and enzyme transglutaminase 2 (TG2) in the progression of vascular calcification, and our previous studies have shown that TG2 can activate ?-catenin signaling in vascular smooth muscle cells (VSMCs). Here we investigated the role of the TG2/?-catenin signaling axis in vascular calcification induced by warfarin. Methods and Results Warfarin-induced calcification in rat A10 VSMCs is associated with the activation of ?-catenin signaling and is independent from oxidative stress. The canonical ?-catenin inhibitor Dkk1, but not the Wnt antagonist Wif-1,prevents warfarin-induced activation of ?-catenin, calcification, and osteogenic trans-differentiation in VSMCs. TG2 expression and activity are increased in warfarin-treated cells, in contrast to canonical Wnt ligands. Vascular cells with genetically or pharmacologically reduced TG2 activity fail to activate ?-catenin in response to warfarin. Moreover, warfarin-induced calcification is significantly reduced on the background of attenuated TG2 both in vitro and in vivo. Conclusions TG2 is a critical mediator of warfarin-induced vascular calcification that acts through the activation of ?-catenin signaling in VSMCs. Inhibition of canonical ?-catenin pathway or TG2 activity prevents warfarin-regulated calcification, identifying the TG2/?-catenin axis as a novel therapeutic target in vascular calcification. PMID:22034513

  2. Synaptic alterations in the rTg4510 mouse model of tauopathy.

    PubMed

    Kopeikina, Katherine J; Polydoro, Manuela; Tai, Hwan-Ching; Yaeger, Erich; Carlson, George A; Pitstick, Rose; Hyman, Bradley T; Spires-Jones, Tara L

    2013-04-15

    Synapse loss, rather than the hallmark amyloid-? (A?) plaques or tau-filled neurofibrillary tangles (NFT), is considered the most predictive pathological feature associated with cognitive status in the Alzheimer's disease (AD) brain. The role of A? in synapse loss is well established, but despite data linking tau to synaptic function, the role of tau in synapse loss remains largely undetermined. Here we test the hypothesis that human mutant P301L tau overexpression in a mouse model (rTg4510) will lead to age-dependent synaptic loss and dysfunction. Using array tomography and two methods of quantification (automated, threshold-based counting and a manual stereology-based technique) we demonstrate that overall synapse density is maintained in the neuropil, implicating synapse loss commensurate with the cortical atrophy known to occur in this model. Multiphoton in vivo imaging reveals close to 30% loss of apical dendritic spines of individual pyramidal neurons, suggesting these cells may be particularly vulnerable to tau-induced degeneration. Postmortem, we confirm the presence of tau in dendritic spines of rTg4510-YFP mouse brain by array tomography. These data implicate tau-induced loss of a subset of synapses that may be accompanied by compensatory increases in other synaptic subtypes, thereby preserving overall synapse density. Biochemical fractionation of synaptosomes from rTg4510 brain demonstrates a significant decrease in expression of several synaptic proteins, suggesting a functional deficit of remaining synapses in the rTg4510 brain. Together, these data show morphological and biochemical synaptic consequences in response to tau overexpression in the rTg4510 mouse model. PMID:23047530

  3. Impact of MDM2 309T>G polymorphism on sarcomagenesis

    PubMed Central

    Liu, Hua-Wei; Ni, Ming; Li, Xiang; Chen, Hui; Zhang, Guo-Qiang; Chai, Wei; Xu, Meng; Zhou, Yong-Gang; Chen, Ji-Ying; Wang, Yan

    2015-01-01

    Background: A series of epidemiological studies have attempted to evaluate the impact of 309T>G polymorphism in MDM2 gene frequently identified as a susceptibility loci for various cancers on malignant sarcomas, however the reported conclusions remain inconsistent and elusive. We pooled all usable data sets in order to systematically assess the association between 309T>G polymorphism and sarcoma risk. Methods: To identify as many informative studies with complete data as possible, we searched a number of databases (PubMed, EBSCO, BIOSIS, the Cochrane Library, ISI Web of Science, Wiley Online Library and Embase). Inclusion criteria were defined to select the eligible studies. The fixed effects meta-analysis was properly used to calculate the pooled ORs and 95% CIs. Major findings: We eventually identified six studies evaluating the association of sarcoma risk with 309T>G polymorphism. People with 309-GG were found to have 43% greater risk of sarcoma relative to people with 309-TT (OR, 1.43; 95% CI, 1.01~2.03; Pheterogeneity, 0.45). In the G vs. T genetic model, the risk reduced to 19% (OR, 1.19; 95% CI, 1.01~1.40; Pheterogeneity, 0.50). Statistical data showed no significant heterogeneity or publication bias in the meta-analysis. Conclusion: These data demonstrate that 309T>G polymorphism located within the MDM2 gene may act as modifier factor for sarcomas. A weakness of this analysis is that the findings cannot be explainable when the subtypes are separated and additional larger investigations are needed to identify the role of 309T>G polymorphism in each form of sarcoma. PMID:26550195

  4. Synaptic alterations in the rTg4510 mouse model of tauopathy

    PubMed Central

    Kopeikina, Katherine J; Polydoro, Manuela; Tai, Hwan-Ching; Yaeger, Erich; Carlson, George A; Pitstick, Rose; Hyman, Bradley T; Spires-Jones, Tara L

    2013-01-01

    Synapse loss, rather than the hallmark amyloid-? (A?) plaques or tau filled neurofibrillary tangles (NFT), is considered the most predictive pathological feature associated with cognitive status in the Alzheimer disease (AD) brain. The role of A? in synapse loss is well established, but despite data linking tau to synaptic function, the role of tau in synapse loss remains largely undetermined. Here we test the hypothesis that human mutant P301L tau over-expression in a mouse model (rTg4510) will lead to age-dependent synaptic loss and dysfunction. Using array tomography and two methods of quantification (automated, threshold-based counting and a manual stereology based technique) we demonstrate that overall synapse density is maintained in the neuropil, implicating synapse loss commensurate with the cortical atrophy known to occur in this model. Multi-photon in-vivo imaging reveals close to 30% loss of apical dendritic spines of individual pyramidal neurons suggesting these cells may be particularly vulnerable to tau-induced degeneration. Post-mortem, we confirm the presence of tau in dendritic spines of rTg4510-YFP mouse brain by array tomography. These data implicate tau-induced loss of a subset of synapses that may be accompanied by compensatory increases in other synaptic subtypes thereby preserving overall synapse density. Biochemical fractionation of synaptosomes from rTg4510 brain demonstrates a significant decrease in expression of several synaptic proteins, suggesting a functional deficit of remaining synapses in the rTg4510 brain. Together these data show morphological and biochemical synaptic consequences in response to tau over-expression in the rTg4510 mouse model. PMID:23047530

  5. [Elevated gastric lesions].

    PubMed

    de Careaga, B; Villagmez, G; Pabn, J; Caldern, O; Elo, D; Prez, J; Martnez, M; Patio, F; Ponce, R; Lora, J

    1986-01-01

    Elevated gastric lesions, represent an important group among gastric pathology. To establish its incidence in our experience, we studied the endoscopic reports of two important hospitals in La Paz city: Instituto de Gastroenterologa Boliviano Japons and Hospital Obrero No. 1. In order to make a good endoscopic diagnosis among different elevated lesions we use some parameters like: location, shape, size, diameter, surface of the lesion and surrounding mucosa and characteristics of the falls. 10.472 endoscopic reports were reviewed, 497 elevated gastric lesions were found, 475 corresponded to mucosal lesions (352 benign lesions and 123 malignant lesions), 11 to submucosal and 11 extragastric lesions. PMID:3661077

  6. Loaded sectioned space elevator

    NASA Astrophysics Data System (ADS)

    Sadov, Yu. A.; Nuralieva, A. B.

    2015-05-01

    New super strong materials discovered at the end of the 20th century have caused a surge of activity in work devoted to the space elevator (SE). A rather complete concept of the SE has been formulated. This concept, having many advantages, possesses, nevertheless, limited capabilities and insufficient reliability. In this paper we present a modified space elevator concept [1] that has higher reliability and extended capabilities. Such a construction is more complicated and its design is more expensive, so it can be realized only as a part of a large-scale space program. Inclusion of a space elevator in such a program will facilitate development of new technologies.

  7. Genetic Predisposition to Increased Blood Cholesterol and Triglyceride Lipid Levels and Risk of Alzheimer Disease: A Mendelian Randomization Analysis

    PubMed Central

    Proitsi, Petroula; Lupton, Michelle K.; Velayudhan, Latha; Newhouse, Stephen; Fogh, Isabella; Tsolaki, Magda; Daniilidou, Makrina; Pritchard, Megan; Kloszewska, Iwona; Soininen, Hilkka; Mecocci, Patrizia; Vellas, Bruno; Williams, Julie; Stewart, Robert; Sham, Pak; Lovestone, Simon; Powell, John F.

    2014-01-01

    Background Although altered lipid metabolism has been extensively implicated in the pathogenesis of Alzheimer disease (AD) through cell biological, epidemiological, and genetic studies, the molecular mechanisms linking cholesterol and AD pathology are still not well understood and contradictory results have been reported. We have used a Mendelian randomization approach to dissect the causal nature of the association between circulating lipid levels and late onset AD (LOAD) and test the hypothesis that genetically raised lipid levels increase the risk of LOAD. Methods and Findings We included 3,914 patients with LOAD, 1,675 older individuals without LOAD, and 4,989 individuals from the general population from six genome wide studies drawn from a white population (total n?=?10,578). We constructed weighted genotype risk scores (GRSs) for four blood lipid phenotypes (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], triglycerides, and total cholesterol) using well-established SNPs in 157 loci for blood lipids reported by Willer and colleagues (2013). Both full GRSs using all SNPs associated with each trait at p<510?8 and trait specific scores using SNPs associated exclusively with each trait at p<510?8 were developed. We used logistic regression to investigate whether the GRSs were associated with LOAD in each study and results were combined together by meta-analysis. We found no association between any of the full GRSs and LOAD (meta-analysis results: odds ratio [OR]?=?1.005, 95% CI 0.821.24, p?=?0.962 per 1 unit increase in HDL-c; OR?=?0.901, 95% CI 0.651.25, p?=?0.530 per 1 unit increase in LDL-c; OR?=?1.104, 95% CI 0.891.37, p?=?0.362 per 1 unit increase in triglycerides; and OR?=?0.954, 95% CI 0.761.21, p?=?0.688 per 1 unit increase in total cholesterol). Results for the trait specific scores were similar; however, the trait specific scores explained much smaller phenotypic variance. Conclusions Genetic predisposition to increased blood cholesterol and triglyceride lipid levels is not associated with elevated LOAD risk. The observed epidemiological associations between abnormal lipid levels and LOAD risk could therefore be attributed to the result of biological pleiotropy or could be secondary to LOAD. Limitations of this study include the small proportion of lipid variance explained by the GRS, biases in case-control ascertainment, and the limitations implicit to Mendelian randomization studies. Future studies should focus on larger LOAD datasets with longitudinal sampled peripheral lipid measures and other markers of lipid metabolism, which have been shown to be altered in LOAD. Please see later in the article for the Editors' Summary PMID:25226301

  8. Uridine prodrug improves memory in Tg2576 and TAPP mice and reduces pathological factors associated with Alzheimer's disease in related models.

    PubMed

    Saydoff, Joel A; Olariu, Ana; Sheng, Jin; Hu, Zhongyi; Li, Qin; Garcia, Rolando; Pei, Jiong; Sun, Grace Y; von Borstel, Reid

    2013-01-01

    Uridine prodrug PN401 has been shown to have neuroprotective effects in models of Parkinson's disease and Huntington's disease. These age-related neurodegenerative diseases including Alzheimer's disease (AD) are associated with mitochondrial dysfunction, oxidative stress, and inflammation. Attenuation of these pathological factors in AD, in addition to amyloid fibrils and neurofibrillary tangles, is critical to prevent cognitive impairment. The effects of PN401 treatment were tested in the Tg2576 and Tg2576 X P301L (TAPP) mouse models of AD. Treatment with PN401 reduced impairments in the Tg2576 mice in contextual fear conditioning and novel object recognition. In the TAPP mice, PN401 reduced the impairments in novel object recognition and social transmission of food preference. PN401 also improved motor behavior and reduced anxiety-like behavior in the TAPP mice. TAPP mouse hippocampal tau phosphorylation and lipid peroxidation were reduced by PN401 treatment. Increased tau phosphorylation was significantly correlated with worsening novel object recognition memory. PN401 did not affect amyloid plaque area in the AD mice. In other AD-related animal studies, PN401 treatment reduced blood-brain barrier damage due to intracortical LPS, elevation of serum TNFα due to systemic LPS, and hippocampal CA1 neuronal loss in the gerbil stroke model. Uridine dose-dependently protected cells from chemical hypoxia and ceramide, and decreased formation of reactive oxygen species and mitochondrial DNA damage due to hydrogen peroxide. These protective effects were achieved by raising uridine levels to at least 25-50 μM and serum uridine levels in this range in humans were obtained with oral PN401. PMID:23648515

  9. Phosphorylation of a Myosin Motor by TgCDPK3 Facilitates Rapid Initiation of Motility during Toxoplasma gondii egress.

    PubMed

    Gaji, Rajshekhar Y; Johnson, Derrick E; Treeck, Moritz; Wang, Mu; Hudmon, Andy; Arrizabalaga, Gustavo

    2015-11-01

    Members of the family of calcium dependent protein kinases (CDPK's) are abundant in certain pathogenic parasites and absent in mammalian cells making them strong drug target candidates. In the obligate intracellular parasite Toxoplasma gondii TgCDPK3 is important for calcium dependent egress from the host cell. Nonetheless, the specific substrate through which TgCDPK3 exerts its function during egress remains unknown. To close this knowledge gap we applied the proximity-based protein interaction trap BioID and identified 13 proteins that are either near neighbors or direct interactors of TgCDPK3. Among these was Myosin A (TgMyoA), the unconventional motor protein greatly responsible for driving the gliding motility of this parasite, and whose phosphorylation at serine 21 by an unknown kinase was previously shown to be important for motility and egress. Through a non-biased peptide array approach we determined that TgCDPK3 can specifically phosphorylate serines 21 and 743 of TgMyoA in vitro. Complementation of the TgmyoA null mutant, which exhibits a delay in egress, with TgMyoA in which either S21 or S743 is mutated to alanine failed to rescue the egress defect. Similarly, phosphomimetic mutations in the motor protein overcome the need for TgCDPK3. Moreover, extracellular Tgcdpk3 mutant parasites have motility defects that are complemented by expression of S21+S743 phosphomimetic of TgMyoA. Thus, our studies establish that phosphorylation of TgMyoA by TgCDPK3 is responsible for initiation of motility and parasite egress from the host-cell and provides mechanistic insight into how this unique kinase regulates the lytic cycle of Toxoplasma gondii. PMID:26544049

  10. Phosphorylation of a Myosin Motor by TgCDPK3 Facilitates Rapid Initiation of Motility during Toxoplasma gondii egress

    PubMed Central

    Gaji, Rajshekhar Y.; Johnson, Derrick E.; Treeck, Moritz; Wang, Mu; Hudmon, Andy; Arrizabalaga, Gustavo

    2015-01-01

    Members of the family of calcium dependent protein kinases (CDPK’s) are abundant in certain pathogenic parasites and absent in mammalian cells making them strong drug target candidates. In the obligate intracellular parasite Toxoplasma gondii TgCDPK3 is important for calcium dependent egress from the host cell. Nonetheless, the specific substrate through which TgCDPK3 exerts its function during egress remains unknown. To close this knowledge gap we applied the proximity-based protein interaction trap BioID and identified 13 proteins that are either near neighbors or direct interactors of TgCDPK3. Among these was Myosin A (TgMyoA), the unconventional motor protein greatly responsible for driving the gliding motility of this parasite, and whose phosphorylation at serine 21 by an unknown kinase was previously shown to be important for motility and egress. Through a non-biased peptide array approach we determined that TgCDPK3 can specifically phosphorylate serines 21 and 743 of TgMyoA in vitro. Complementation of the TgmyoA null mutant, which exhibits a delay in egress, with TgMyoA in which either S21 or S743 is mutated to alanine failed to rescue the egress defect. Similarly, phosphomimetic mutations in the motor protein overcome the need for TgCDPK3. Moreover, extracellular Tgcdpk3 mutant parasites have motility defects that are complemented by expression of S21+S743 phosphomimetic of TgMyoA. Thus, our studies establish that phosphorylation of TgMyoA by TgCDPK3 is responsible for initiation of motility and parasite egress from the host-cell and provides mechanistic insight into how this unique kinase regulates the lytic cycle of Toxoplasma gondii. PMID:26544049

  11. Perturbations of triglycerides but not of cholesterol metabolism are prevented by anti-tumour necrosis factor treatment in rats bearing an ascites hepatoma (Yoshida AH-130).

    PubMed Central

    Dess, S.; Batetta, B.; Spano, O.; Bagby, G. J.; Tessitore, L.; Costelli, P.; Baccino, F. M.; Pani, P.; Argils, J. M.

    1995-01-01

    Rats transplanted with the ascites hepatoma Yoshida AH-130 developed a severely progressive cachexia, characterised by marked alterations in protein and lipid metabolism. In particular, high levels of serum triglycerides and free fatty acids were associated with altered levels and distribution of plasma cholesterol, with increased total and very low-density lipoprotein-low-density lipoprotein (VLDL-LDL) cholesterol and reduced high-density lipoprotein (HDL) cholesterol. The tumour cells showed high rates of cholesterol synthesis and elevated content of free and esterified cholesterol, whereas total cholesterol synthesis was reduced in the host liver. To determine whether these perturbations could be related to the elevation of tumour necrosis factor alpha (TNF-alpha) previously shown in the AH-130 bearers (Tessitore L, Costelli P, Baccino FM 1993, Br J Cancer, 67, 15-23), either anti-TNF polyclonal antibodies or non-immune IgGs were injected daily after tumour transplantation. The anti-TNF treatment neither affected tumour growth nor prevented the serum cholesterol changes, while attenuating the hypertriglyceridaemia and the elevated serum free fatty acid levels. These data indicate that TNF does not appear to be directly involved in the altered cholesterol metabolism in AH-130 hosts, thus supporting the view that cholesterol metabolism and lipid metabolism are regulated differently during tumour growth. PMID:7577459

  12. WE-PIS-Exhibit Hall-01: Tools for TG-142 Linac Imaging QA II

    SciTech Connect

    Childress, N; Murray, B

    2014-06-15

    Partners in Solutions is an exciting new program in which AAPM partners with our vendors to present practical “hands-on” information about the equipment and software systems that we use in our clinics. The therapy topic this year is solutions for TG-142 recommendations for linear accelerator imaging QA. Note that the sessions are being held in a special purpose room built on the Exhibit Hall Floor, to encourage further interaction with the vendors. Using DoseLab to Perform TG-142 Imaging QA The goals of this session will be to present a clinical overview of acquiring images for TG-142 Imaging QA, as well as analyzing and evaluating results using DoseLab software. DoseLab supports planar imaging QA analysis using almost any QA phantom provided by numerous vendors. General advantages and disadvantages of selecting each of these phantoms will be briefly summarized. Best practices for selecting image acquisition parameters will be presented. A demonstration of using DoseLab software to perform a series of TG-142 tests will be performed. We will disuss why DoseLab uses its own set of imaging QA formulas, and why imaging QA measurement values of the same nominal properties will vary between TG- 142 software packages. Because TG-142 does not specify baseline and tolerance values for imaging QA, the presentation will recommend performing the manufacturer's acceptance test procedure to validate the equipment is functioning correctly. Afterwards, results can be obtained using the clinic's selected set of phantoms, image acquisition parameters, and TG-142 software to set proper baseline values. This presentation will highlight the reasons why comparing imaging QA results can be trickier than comparing linear accelerator treatment results and what physicists should keep in mind when comparing imaging QA results for different machines. Physicists are often unsure of the next step when there is an issue discovered during Imaging QA. Therefore, a few common examples of imaging issues and recommended solutions will be discussed. TG-142 Imaging QA Simplified: Lessons From Diagnostic Physics Collaboration There are many commercial options for the performance of imaging quality assurance tests for the linear accelerator imaging systems as required by the AAPM TG-142 report. Imaging quality assurance testing is largely performed by the diagnostic physicist so routine performance of these tests by the practicing oncology physicist can be complicated and confusing given all of the commercially available options. This presentation focuses on the performance of imaging quality assurance testing for linear accelerators using methods similar to that of diagnostic physicists. This presentation will address the ability to perform the required testing without complicated software and explores solutions for the performance of these tests in an efficient manner while still maintaining the ability to ascertain image quality changes that may ultimately affect clinical decisions.

  13. MO-PIS-Exhibit Hall-01: Tools for TG-142 Linac Imaging QA I

    SciTech Connect

    Clements, M; Wiesmeyer, M

    2014-06-15

    Partners in Solutions is an exciting new program in which AAPM partners with our vendors to present practical “hands-on” information about the equipment and software systems that we use in our clinics. The therapy topic this year is solutions for TG-142 recommendations for linear accelerator imaging QA. Note that the sessions are being held in a special purpose room built on the Exhibit Hall Floor, to encourage further interaction with the vendors. Automated Imaging QA for TG-142 with RIT Presentation Time: 2:45 – 3:15 PM This presentation will discuss software tools for automated imaging QA and phantom analysis for TG-142. All modalities used in radiation oncology will be discussed, including CBCT, planar kV imaging, planar MV imaging, and imaging and treatment coordinate coincidence. Vendor supplied phantoms as well as a variety of third-party phantoms will be shown, along with appropriate analyses, proper phantom setup procedures and scanning settings, and a discussion of image quality metrics. Tools for process automation will be discussed which include: RIT Cognition (machine learning for phantom image identification), RIT Cerberus (automated file system monitoring and searching), and RunQueueC (batch processing of multiple images). In addition to phantom analysis, tools for statistical tracking, trending, and reporting will be discussed. This discussion will include an introduction to statistical process control, a valuable tool in analyzing data and determining appropriate tolerances. An Introduction to TG-142 Imaging QA Using Standard Imaging Products Presentation Time: 3:15 – 3:45 PM Medical Physicists want to understand the logic behind TG-142 Imaging QA. What is often missing is a firm understanding of the connections between the EPID and OBI phantom imaging, the software “algorithms” that calculate the QA metrics, the establishment of baselines, and the analysis and interpretation of the results. The goal of our brief presentation will be to establish and solidify these connections. Our talk will be motivated by the Standard Imaging, Inc. phantom and software solutions. We will present and explain each of the image quality metrics in TG-142 in terms of the theory, mathematics, and algorithms used to implement them in the Standard Imaging PIPSpro software. In the process, we will identify the regions of phantom images that are analyzed by each algorithm. We then will discuss the process of the creation of baselines and typical ranges of acceptable values for each imaging quality metric.

  14. Cognitive and Disease-Modifying Effects of 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibition in Male Tg2576 Mice, a Model of Alzheimer's Disease.

    PubMed

    Sooy, Karen; Noble, June; McBride, Andrew; Binnie, Margaret; Yau, Joyce L W; Seckl, Jonathan R; Walker, Brian R; Webster, Scott P

    2015-12-01

    Chronic exposure to elevated levels of glucocorticoids has been linked to age-related cognitive decline and may play a role in Alzheimer's disease. In the brain, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies intracellular glucocorticoid levels. We show that short-term treatment of aged, cognitively impaired C57BL/6 mice with the potent and selective 11β-HSD1 inhibitor UE2316 improves memory, including after intracerebroventricular drug administration to the central nervous system alone. In the Tg2576 mouse model of Alzheimer's disease, UE2316 treatment of mice aged 14 months for 4 weeks also decreased the number of β-amyloid (Aβ) plaques in the cerebral cortex, associated with a selective increase in local insulin-degrading enzyme (involved in Aβ breakdown and known to be glucocorticoid regulated). Chronic treatment of young Tg2576 mice with UE2316 for up to 13 months prevented cognitive decline but did not prevent Aβ plaque formation. We conclude that reducing glucocorticoid regeneration in the brain improves cognition independently of reduced Aβ plaque pathology and that 11β-HSD1 inhibitors have potential as cognitive enhancers in age-associated memory impairment and Alzheimer's dementia. PMID:26305888

  15. Cognitive and Disease-Modifying Effects of 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibition in Male Tg2576 Mice, a Model of Alzheimer's Disease

    PubMed Central

    Sooy, Karen; Noble, June; McBride, Andrew; Binnie, Margaret; Yau, Joyce L. W.; Seckl, Jonathan R.; Walker, Brian R.

    2015-01-01

    Chronic exposure to elevated levels of glucocorticoids has been linked to age-related cognitive decline and may play a role in Alzheimer's disease. In the brain, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies intracellular glucocorticoid levels. We show that short-term treatment of aged, cognitively impaired C57BL/6 mice with the potent and selective 11β-HSD1 inhibitor UE2316 improves memory, including after intracerebroventricular drug administration to the central nervous system alone. In the Tg2576 mouse model of Alzheimer's disease, UE2316 treatment of mice aged 14 months for 4 weeks also decreased the number of β-amyloid (Aβ) plaques in the cerebral cortex, associated with a selective increase in local insulin-degrading enzyme (involved in Aβ breakdown and known to be glucocorticoid regulated). Chronic treatment of young Tg2576 mice with UE2316 for up to 13 months prevented cognitive decline but did not prevent Aβ plaque formation. We conclude that reducing glucocorticoid regeneration in the brain improves cognition independently of reduced Aβ plaque pathology and that 11β-HSD1 inhibitors have potential as cognitive enhancers in age-associated memory impairment and Alzheimer's dementia. PMID:26305888

  16. Ethnic Differences in the Link Between Insulin Resistance and Elevated ALT

    PubMed Central

    DeBoer, Mark D.; Wiener, R. Constance; Barnes, Barrett H.

    2013-01-01

    BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) exhibits tight links with insulin resistance (IR) and the metabolic syndrome (MetS), a cluster of cardiovascular risk factors. Compared with non-Hispanic whites, non-Hispanic black adolescents have more IR but a lower prevalence of NAFLD and MetS. Our hypothesis was that IR would be a better predictor of alanine aminotransferase (ALT) elevations than is MetS among non-Hispanic blacks. METHODS: We analyzed data from 4124 adolescents aged 12 to 19 years in the 1999 to 2010 NHANES, using unexplained elevations in ALT (>30 U/L) to characterize presumed NAFLD and using a pediatric adaptation of the Adult Treatment Panel III definition of MetS. RESULTS: Prevalence of elevated ALT varied by race/ethnicity (Hispanics 13.7%, non-Hispanic white 8.6%, non-Hispanic blacks 5.4%, P < .0001). Among non-Hispanic whites and Hispanics, a classification of MetS performed well in identifying adolescents with elevated ALT (odds ratios [ORs] 9.53 and 5.56, respectively), as did MetS-related indices. However, among non-Hispanic blacks, the association between MetS and ALT elevations was smaller in magnitude and technically nonsignificant (OR = 3.24, P = .051). Furthermore, among non-Hispanic blacks, the presence of IR and elevated waist circumference performed more poorly at identifying ALT elevations (ORs 3.93 and 2.28, respectively: significantly smaller than ORs for non-Hispanic whites, P < .05), with triglyceride elevations being a better predictor (OR = 4.44). CONCLUSIONS: Non-Hispanic black adolescents exhibit a lower relationship between IR and elevated ALT, supporting racial/ethnic differences in the link between MetS and NAFLD. These data may have implications regarding triggers for screening for NAFLD among non-Hispanic black adolescents, focusing particularly on those with triglyceride elevations. PMID:23940240

  17. Rheology of Hyperbranched Poly(triglyceride)-Based Thermoplastic Elastomers via RAFT polymerization

    NASA Astrophysics Data System (ADS)

    Yan, Mengguo; Cochran, Eric

    2014-03-01

    In this contribution we discuss how melt- and solid-state properties are influenced by the degree of branching and molecular weight in a family of hyperbranched thermoplastics derived from soybean oil. Acrylated epoxidized triglycerides from soybean oils have been polymerized to hyperbranched thermoplastic elastomers using reversible addition-fragmentation chain transfer (RAFT) polymerization. With the proper choice of chain transfer agent, both homopolymer and block copolymer can be synthesized. By changing the number of acrylic groups per triglycerides, the chain architectures can range from nearly linear to highly branched. We show how the fundamental viscoelastic properties (e.g. entanglement molecular weight, plateau modulus, etc.) are influenced by chain architecture and molecular weight.

  18. Process for enzymatic hydrolysis of fatty acid triglycerides with oat caryopses

    SciTech Connect

    Hammond, E.G.; Lee, I.

    1992-02-18

    This patent describes the process for enzymatic hydrolysis of fatty acid triglycerides to obtain free fatty acids and glycerol. It comprises: increasing the water content of dehulled whole oat caryopses to a total water content of 17 to 44% the thus moistened caryopses having active oat lipase associated with the outer surfaces thereof; contacting the moistened whole caryopses with a liquid medium, continuing the contacting until at least 20% by volume of the triglyceride reactant has been hydrolyzed to free fatty acids and glycerol, most of the free fatty acids dissolving in the oil phase external to the caryopses and most of the glycerol being absorbed into the water within the caryopses; and separating the glycerol-containing caryopses from the fatty acid-containing oil phase.

  19. Optimization of conjugated linoleic acid triglycerides via enzymatic esterification in no-solvent system

    NASA Astrophysics Data System (ADS)

    Yi, Dan; Sun, Xiuqin; Li, Guangyou; Liu, Fayi; Lin, Xuezheng; Shen, Jihong

    2009-09-01

    We compared four esterifiable enzymes. The lipase Novozym 435 possessed the highest activity for the conjugated linoleic acid esterification during the synthesis of triglycerides. The triglycerides were synthesized by esterification of glycerol and conjugated linoleic acid (CLA) in a no-solvent system using lipase catalysis. We investigated the effects of temperature, enzyme concentration, water content, and time on esterification. Enzyme and water concentrations of up to 1% of the total reaction volume and a system temperature of 60°C proved optimal for esterification. Similarly, when the esterification was carried out for 24 h, the reaction ratio improved to 94.11%. The esterification rate of the rotating screen basket remained high (87.28%) when the enzyme was re-used for the 5th time. We evaluated the substrate selectivity of lipase (NOVO 435) and determined that this lipase prefers the 10,12-octadacadienoic acid to the 9,11-octadecadienoic acid.

  20. Quantitation of adipose conversion and triglycerides by staining intracytoplasmic lipids with Oil red O.

    PubMed

    Ramírez-Zacarías, J L; Castro-Muñozledo, F; Kuri-Harcuch, W

    1992-07-01

    Cultured 3T3-F442A cells differentiate into adipocytes and accumulate lipid droplets in the cytoplasm. When fat cells are stained with Oil red O, the degree of staining seems to be proportional to the extent of cell differentiation. We report here a fast and simple method to quantitate the extent of adipose conversion by staining the accumulated lipid with Oil red O and determining the amount of extracted dye at 510 nm. The results show that Oil red O specifically stains triglycerides and cholesteryl oleate but no other lipids. This technique is a valuable tool for processing large numbers of cell cultures or samples in which adipose differentiation and/or accumulated triglycerides is to be quantitated. PMID:1385366

  1. Physico-chemical characteristics of burfi prepared by using medium chain triglyceride rich margarines.

    PubMed

    Tiwari, Shipra; Chetana, Ramakrishna; Puttaraju, Shashikala; Khatoon, Sakina

    2014-01-01

    Medium chain triglyceride rich margarines were prepared using palm, coconut oil blends in the ratio of 80:20 (Margarine 1) and 60:40 (Margarine 2). The margarines were used to prepare burfi and compared with products prepared using commercial margarine, ghee and butter. The physicochemical characteristics such as texture, color, free fatty acid, peroxide value, saponification value, unsaponifiable matter and fatty acid composition of oils, fats and margarines were carried out. Results showed that 11.0 and 21.9% of medium chain triglycerides were present in margarine 1 and 2 respectively. The texture, colour, moisture content, peroxide value and sensory evaluation were carried out for the burfi samples. Laboratory prepared margarines improved the textural quality of burfi compared to commercial margarine, ghee and butter. The sensory analyses of the burfi samples revealed that burfi prepared from margarine 1 was more acceptable compared to commercial margarine. PMID:24426059

  2. Age-dependent impairment of glucose tolerance in the 3xTg-AD mouse model of Alzheimer's disease.

    PubMed

    Vandal, Milene; White, Phillip J; Chevrier, Genevive; Tremblay, Cyntia; St-Amour, Isabelle; Planel, Emmanuel; Marette, Andre; Calon, Frederic

    2015-10-01

    Alzheimer's disease (AD) has been associated with type II diabetes (T2D) and obesity in several epidemiologic studies. To determine whether AD neuropathology can cause peripheral metabolic impairments, we investigated metabolic parameters in the triple-transgenic (3xTg)-AD mouse model of AD, compared with those in nontransgenic (non-Tg) controls, at 6, 8, and 14 mo of age. We found a more pronounced cortical A? accumulation (2- and 3.5-fold increase in A?42 in the soluble and insoluble protein fractions, respectively) in female 3xTg-AD mice than in the males. Furthermore, female 3xTg-AD mice displayed a significant deterioration in glucose tolerance (AUC, +118% vs. non-Tg mice at 14 mo). Fasting plasma insulin levels rose 2.5-fold from 6 to 14 mo of age in female 3xTg-AD mice. Glucose intolerance and cortical amyloid pathology worsened with age, and both were more pronounced in the females. Pancreatic amyloidopathy was revealed and could underlie the observed deficit in glycemic response in 3xTg-AD mice. The present results suggest that AD-like neuropathology extends to the pancreas in the 3xTg-AD mouse, leading to glucose intolerance and contributing to a pathologic self-amplifying loop between AD and T2D. PMID:26108977

  3. Northeast Elevation Mill #3, Northeast Elevation Mill #4 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Northeast Elevation - Mill #3, Northeast Elevation - Mill #4 (with Section of Courtyard), Southeast Elevation - Mill #4 North - Boott Cotton Mills, John Street at Merrimack River, Lowell, Middlesex County, MA

  4. Light: Isometric Casing with Lens, South Elevation, North Elevation, Top ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Light: Isometric Casing with Lens, South Elevation, North Elevation, Top Plan, Base Plan; Fresnel Lens: Isometric, Elevation, Plan - Fort Washington, Fort Washington Light, Northeast side of Potomac River at Fort Washington Park, Fort Washington, Prince George's County, MD

  5. Loss of FTO in adipose tissue decreases Angptl4 translation and alters triglyceride metabolism.

    PubMed

    Wang, Chao-Yung; Shie, Shian-Sen; Wen, Ming-Shien; Hung, Kuo-Chun; Hsieh, I-Chang; Yeh, Ta-Sen; Wu, Delon

    2015-01-01

    A common variant of the FTO (fat mass- and obesity-associated) gene is a risk factor for obesity. We found that mice with an adipocyte-specific deletion of FTO gained more weight than control mice on a high-fat diet. Analysis of mice lacking FTO in adipocytes fed a normal diet or adipocytes from these mice revealed alterations in triglyceride metabolism that would be expected to favor increased fatty acid storage by adipose tissue. Mice lacking FTO in adipocytes showed increased serum triglyceride breakdown and clearance, which was associated with lower serum triglyceride concentrations. In addition, lipolysis in response to ?-adrenergic stimulation was decreased in adipocytes and ex vivo adipose explants from the mutant mice. FTO is a nucleic acid demethylase that removes N(6)-methyladenosine (m(6)A) from mRNAs. We found that FTO bound to Angptl4, which encodes an adipokine that stimulates intracellular lipolysis in adipocytes. Unexpectedly, the adipose tissue of fasted or fed mice lacking FTO in adipocytes had greater Angptl4 mRNA abundance. However, after high-fat feeding, the mutant mice had less Angptl4 protein and more m(6)A-modified Angptl4 than control mice, suggesting that lack of FTO prevented the translation of Angptl4. Injection of Angptl4-encoding adenovirus into mice lacking FTO in adipocytes restored serum triglyceride concentrations and lipolysis to values similar to those in control mice and abolished excessive weight gain from a high-fat diet. These results reveal that FTO regulates fatty acid mobilization in adipocytes and thus body weight in part through posttranscriptional regulation of Angptl4. PMID:26671148

  6. Apolipoprotein E polymorphism influences postprandial retinyl palmitate but not triglyceride concentrations

    SciTech Connect

    Boerwinkle, E. ); Brown, S.; Patsch, W. ); Sharrett, A.R. ); Heiss, G. )

    1994-02-01

    To quantify the effect of the apolipoprotein (apo) E polymorphism on the magnitude of postprandial lipemia, the authors have defined its role in determining the response to a single high-fat meal in a large sample of (N = 474) individuals taking part in the biethnic Atherosclerosis Risk in Communities Study. The profile of postprandial response in plasma was monitored over 8 h by triglyceride, triglyceride-rich lipoprotein (TGRL)-triglyceride, apo B-48/apo B-100 ratio, and retinyl palmitate concentrations, and the apo E polymorphism was determined by DNA amplification and digestion. The frequency of the apo E alleles and their effects on fasting lipid levels in this sample with vitamin A was significantly different among apo E genotypes, with delayed clearance in individuals with an [var epsilon]2 allele, compared with [var epsilon]3/3 and [var epsilon]3/4 individuals. In the sample of 397 Caucasians, average retinyl palmitate response was 1,489 [mu]g/dl in [var epsilon]2/3 individuals, compared with 1,037 [mu]g/dl in [var epsilon]3/3 individuals and 1,108 [mu]g/dl in [var epsilon]3/4 individuals. The apo E polymorphism accounted for 7.1% of the interindividual variation in postprandial retinyl palmitate response, a contribution proportionally greater than its well-known effect on fasting LDL-cholesterol. However, despite this effect on postprandial retinyl palmitate, the profile of postprandial triglyceride response was not significantly different among apo E genotypes. The profile of postprandial response was consistent between the sample of Caucasians and a smaller sample of black subjects. While these data indicate that the removal of remnant particles from circulation is delayed in subjects with the [var epsilon]2/3 genotype, there is no reported evidence that the [var epsilon]2 allele predisposes to coronary artery disease (CAD). 82 refs., 6 figs., 4 tabs.

  7. Plasma thyroid hormone concentration is associated with hepatic triglyceride content in patients with type 2 diabetes.

    PubMed

    Bril, Fernando; Kadiyala, Sushma; Portillo Sanchez, Paola; Sunny, Nishanth E; Biernacki, Diane; Maximos, Maryann; Kalavalapalli, Srilaxmi; Lomonaco, Romina; Suman, Amitabh; Cusi, Kenneth

    2016-01-01

    The underlying mechanisms responsible for the development and progression of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM) are unclear. Since the thyroid hormone regulates mitochondrial function in the liver, we designed this study in order to establish the association between plasma free T4 levels and hepatic triglyceride accumulation and histological severity of liver disease in patients with T2DM and NAFLD. This is a cross-sectional study including a total of 232 patients with T2DM. All patients underwent a liver MR spectroscopy ((1)H-MRS) to quantify hepatic triglyceride content, and an oral glucose tolerance test to estimate insulin resistance. A liver biopsy was performed in patients with a diagnosis of NAFLD. Patients were divided into 5 groups according to plasma free T4 quintiles. We observed that decreasing free T4 levels were associated with an increasing prevalence of NAFLD (from 55% if free T4?1.18?ng/dL to 80% if free T4<0.80?ng/dL, p=0.016), and higher hepatic triglyceride accumulation by (1)H-MRS (p<0.001). However, lower plasma free T4 levels were not significantly associated with more insulin resistance or more severe liver histology (ie, inflammation, ballooning, or fibrosis). Decreasing levels of plasma free T4 are associated with a higher prevalence of NAFLD and increasing levels of hepatic triglyceride content in patients with T2DM. These results suggest that thyroid hormone may play a role in the regulation of hepatic steatosis and support the notion that hypothyroidism may be associated with NAFLD. No NCT number required. PMID:26755815

  8. Chronic Family Stress Moderates the Association between a TOMM40 Variant and Triglyceride Levels in Two Independent Caucasian Samples

    PubMed Central

    Jiang, Rong; Brummett, Beverly H.; Hauser, Elizabeth R.; Babyak, Michael A.; Siegler, Ilene C.; Singh, Abanish; Astrup, Arne; Pedersen, Oluf; Hansen, Torben; Holst, Claus; Srensen, Thorkild I.A.; Williams, Redford B.

    2013-01-01

    TOMM40 SNP rs157580 has been associated with triglyceride levels in Genome-wide association studies (GWAS). Chronic caregiving stress moderates the association between triglyceride levels and a nearby SNP rs439401 that is associated with triglyceride levels in GWAS. Here, we report data from two independent Caucasian samples (242 U.S. women and men; 466 Danish men) testing the hypothesis that chronic family stress also moderates the association between rs157580 and triglyceride levels. The interaction of rs157580 and family stress in predicting triglyceride levels was statistically significant in the U.S. sample (p = 0.004) and marginally significant (p = 0.075) in the Danish sample. The G allele of rs157580 was associated with increased triglyceride levels among family stressed cases in both samples compared with A/A cases, but not among controls. Chronic family stress moderates the association of rs157580 variants with triglyceride levels and should be taken into account for disease risk assessment and potential intervention. PMID:23435269

  9. Surface-enhanced Raman spectroscopic monitor of triglyceride hydrolysis in a skin pore phantom

    NASA Astrophysics Data System (ADS)

    Weldon, Millicent K.; Morris, Michael D.

    1999-04-01

    Bacterial hydrolysis of triglycerides is followed in a sebum probe phantom by microprobe surface-enhanced Raman scattering (SERS) spectroscopy. The phantom consists of a purpose-built syringe pump operating at physiological flow rates connected to a 300 micron i.d. capillary. We employ silicon substrate SERS microprobes to monitor the hydrolysis products. The silicon support allows some tip flexibility that makes these probes ideal for insertion into small structures. Propionibacterium acnes are immobilized on the inner surface of the capillary. These bacteria hydrolyze the triglycerides in a model sebum emulsion flowing through the capillary. The transformation is followed in vitro as changes in the SERS caused by hydrolysis of triglyceride to fatty acid. The breakdown products consists of a mixture of mono- and diglycerides and their parent long chain fatty acids. The fatty acids adsorb as their carboxylates and can be readily identified by their characteristic spectra. The technique can also confirm the presence of bacteria by detection of short chain carboxylic acids released as products of glucose fermentation during the growth cycle of these cells. Co-adsorption of propionate is observed. Spatial localization of the bacteria is obtained by ex-situ line imaging of the probe.

  10. Biocompatibility and erosion behavior of implants made of triglycerides and blends with cholesterol and phospholipids.

    PubMed

    Guse, C; Koennings, S; Maschke, A; Hacker, M; Becker, C; Schreiner, S; Blunk, T; Spruss, T; Goepferich, A

    2006-05-18

    Triglycerides are a promising class of material for the parenteral delivery of drugs and have become the focus of tremendous research efforts in recent years. The aim of this study was to investigate the biocompatibility of glyceroltripalmitate as well as the influence of cholesterol and distearoyl-phosphatidyl-choline (DSPC) on the erosion behavior of the lipid. For these investigations, two in vivo studies were carried out, in which cylindrical matrices of 2 mm diameter were manufactured and subcutaneously implanted in immunocompetent NMRI-mice. After excision of the implants, tissue reactions of the animals as well as changes in the weight, shape and microstructure of the implants were investigated. The triglyceride and cholesterol showed good biocompatibility, as indicated by their minimal encapsulation in connective tissue and the absence of inflammatory reactions. Increasing the levels of phospholipid in the implants, however, led to an increased inflammatory reaction. In contrast to cholesterol, which did not affect erosion, the incorporation of DSPC into the triglyceride matrices led to clearly visible signs of degradation. PMID:16517106

  11. Effect of cholesterol and triglycerides levels on the rheological behavior of human blood

    NASA Astrophysics Data System (ADS)

    Moreno, Leonardo; Calderas, Fausto; Sanchez-Olivares, Guadalupe; Medina-Torres, Luis; Sanchez-Solis, Antonio; Manero, Octavio

    2015-02-01

    Important public health problems worldwide such as obesity, diabetes, hyperlipidemia and coronary diseases are quite common. These problems arise from numerous factors, such as hyper-caloric diets, sedentary habits and other epigenetic factors. With respect to Mexico, the population reference values of total cholesterol in plasma are around 200 mg/dL. However, a large proportion has higher levels than this reference value. In this work, we analyze the rheological properties of human blood obtained from 20 donors, as a function of cholesterol and triglyceride levels, upon a protocol previously approved by the health authorities. Samples with high and low cholesterol and triglyceride levels were selected and analyzed by simple-continuous and linear-oscillatory shear flow. Rheometric properties were measured and related to the structure and composition of human blood. In addition, rheometric data were modeled by using several constitutive equations: Bautista-Manero-Puig (BMP) and the multimodal Maxwell equations to predict the flow behavior of human blood. Finally, a comparison was made among various models, namely, the BMP, Carreau and Quemada equations for simple shear rate flow. An important relationship was found between cholesterol, triglycerides and the structure of human blood. Results show that blood with high cholesterol levels (400 mg/dL) has flow properties fully different (higher viscosity and a more pseudo-plastic behavior) than blood with lower levels of cholesterol (tendency to Newtonian behavior or viscosity plateau at low shear rates).

  12. ELMOD2 is anchored to lipid droplets by palmitoylation and regulates adipocyte triglyceride lipase recruitment.

    PubMed

    Suzuki, Michitaka; Murakami, Tatsuro; Cheng, Jinglei; Kano, Hiroyuki; Fukata, Masaki; Fujimoto, Toyoshi

    2015-06-15

    Adipocyte triglyceride lipase (ATGL) is the major enzyme involved in the hydrolysis of triglycerides. The Arf1-coat protein complex I (COPI) machinery is known to be engaged in the recruitment of ATGL to lipid droplets (LDs), but the regulatory mechanism has not been clarified. In the present study, we found that ELMOD2, a putative noncanonical Arf-GTPase activating protein (GAP) localizing in LDs, plays an important role in controlling ATGL transport to LDs. We showed that knockdown of ELMOD2 by RNA interference induced an increase in the amount of ATGL existing in LDs and decreased the total cellular triglycerides. These effects of ELMOD2 knockdown were canceled by transfection of small interfering RNA-resistant cDNA of wild-type ELMOD2 but not by that of mutated ELMOD2 lacking the Arf-GAP activity. ELMOD2 was distributed in the endoplasmic reticulum and mitochondria as well as in LDs, but palmitoylation was required only for distribution to LDs. An ELMOD2 mutant deficient in palmitoylation failed to reconstitute the ATGL transport after the ELMOD2 knockdown, indicating that distribution in LDs is indispensable to the functionality of ELMOD2. These results indicate that ELMOD2 regulates ATGL transport and cellular lipid metabolism by modulating the Arf1-COPI activity in LDs. PMID:25904333

  13. Metabolic MR imaging of regional triglyceride and creatine content in the human heart.

    PubMed

    Weiss, Kilian; Martini, Nicola; Boesiger, Peter; Kozerke, Sebastian

    2012-12-01

    An optimized echo-planar spectroscopic imaging sequence is proposed to facilitate spatial mapping of triglyceride and total creatine content in the human heart. The sequence integrates local-look field of view reduction, cardiac and respiratory gating, and dedicated reconstruction steps to account for gradient channel delays, field inhomogeneity, and phase incoherence due to residual motion. The technique is demonstrated in 12 volunteers in comparison to single voxel point-resolved spectroscopy in the septal wall at 1.5 T. Triglyceride-to-water and total creatine-to-water ratios derived from echo-planar spectroscopic imaging (0.48 0.18% and 0.06 0.03%) and point-resolved spectroscopy (0.52 0.17% and 0.07 0.02%) were found to agree well. In the septal region, intraclass correlation coefficients ranging from 0.67 to 0.72 were estimated. A relatively weak agreement (intraclass correlation coefficients: 0.34 and 0.52) was found for sectors in the lateral wall due to field gradients induced by the posterior vein and limited sensitivity of the receive coil array in this area. On the basis of the findings, it is concluded that fast spectroscopic imaging of both cardiac triglyceride and total creatine content is feasible. Shimming and sensitivity challenges in the lateral region remain, however, to be addressed. PMID:22294511

  14. ELMOD2 is anchored to lipid droplets by palmitoylation and regulates adipocyte triglyceride lipase recruitment

    PubMed Central

    Suzuki, Michitaka; Murakami, Tatsuro; Cheng, Jinglei; Kano, Hiroyuki; Fukata, Masaki; Fujimoto, Toyoshi

    2015-01-01

    Adipocyte triglyceride lipase (ATGL) is the major enzyme involved in the hydrolysis of triglycerides. The Arf1coat protein complex I (COPI) machinery is known to be engaged in the recruitment of ATGL to lipid droplets (LDs), but the regulatory mechanism has not been clarified. In the present study, we found that ELMOD2, a putative noncanonical ArfGTPase activating protein (GAP) localizing in LDs, plays an important role in controlling ATGL transport to LDs. We showed that knockdown of ELMOD2 by RNA interference induced an increase in the amount of ATGL existing in LDs and decreased the total cellular triglycerides. These effects of ELMOD2 knockdown were canceled by transfection of small interfering RNA-resistant cDNA of wild-type ELMOD2 but not by that of mutated ELMOD2 lacking the Arf-GAP activity. ELMOD2 was distributed in the endoplasmic reticulum and mitochondria as well as in LDs, but palmitoylation was required only for distribution to LDs. An ELMOD2 mutant deficient in palmitoylation failed to reconstitute the ATGL transport after the ELMOD2 knockdown, indicating that distribution in LDs is indispensable to the functionality of ELMOD2. These results indicate that ELMOD2 regulates ATGL transport and cellular lipid metabolism by modulating the Arf1-COPI activity in LDs. PMID:25904333

  15. Cilostazol Inhibits Accumulation of Triglyceride in Aorta and Platelet Aggregation in Cholesterol-Fed Rabbits

    PubMed Central

    Ito, Hideki; Uehara, Kenji; Matsumoto, Yutaka; Hashimoto, Ayako; Nagano, Chifumi; Niimi, Manabu; Miyakoda, Goro; Nagano, Keisuke

    2012-01-01

    Cilostazol is clinically used for the treatment of ischemic symptoms in patients with chronic peripheral arterial obstruction and for the secondary prevention of brain infarction. Recently, it has been reported that cilostazol has preventive effects on atherogenesis and decreased serum triglyceride in rodent models. There are, however, few reports on the evaluation of cilostazol using atherosclerotic rabbits, which have similar lipid metabolism to humans, and are used for investigating the lipid content in aorta and platelet aggregation under conditions of hyperlipidemia. Therefore, we evaluated the effect of cilostazol on the atherosclerosis and platelet aggregation in rabbits fed a normal diet or a cholesterol-containing diet supplemented with or without cilostazol. We evaluated the effects of cilostazol on the atherogenesis by measuring serum and aortic lipid content, and the lesion area after a 10-week treatment and the effect on platelet aggregation after 1- and 10-week treatment. From the lipid analyses, cilostazol significantly reduced the total cholesterol, triglyceride and phospholipids in serum, and moreover, the triglyceride content in the atherosclerotic aorta. Cilostazol significantly reduced the intimal atherosclerotic area. Platelet aggregation was enhanced in cholesterol-fed rabbits. Cilostazol significantly inhibited the platelet aggregation in rabbits fed both a normal diet and a high cholesterol diet. Cilostazol showed anti-atherosclerotic and anti-platelet effects in cholesterol-fed rabbits possibly due to the improvement of lipid metabolism and the attenuation of platelet activation. The results suggest that cilostazol is useful for prevention and treatment of atherothrombotic diseases with the lipid abnormalities. PMID:22761774

  16. Hypoxia causes triglyceride accumulation by HIF-1-mediated stimulation of lipin 1 expression

    PubMed Central

    Mylonis, Ilias; Sembongi, Hiroshi; Befani, Christina; Liakos, Panagiotis; Siniossoglou, Symeon; Simos, George

    2012-01-01

    Summary Adaptation to hypoxia involves hypoxia-inducible transcription factors (HIFs) and requires reprogramming of cellular metabolism that is essential during both physiological and pathological processes. In contrast to the established role of HIF-1 in glucose metabolism, the involvement of HIFs and the molecular mechanisms concerning the effects of hypoxia on lipid metabolism are poorly characterized. Here, we report that exposure of human cells to hypoxia causes accumulation of triglycerides and lipid droplets. This is accompanied by induction of lipin 1, a phosphatidate phosphatase isoform that catalyzes the penultimate step in triglyceride biosynthesis, whereas lipin 2 remains unaffected. Hypoxic upregulation of lipin 1 expression involves predominantly HIF-1, which binds to a single distal hypoxia-responsive element in the lipin 1 gene promoter and causes its activation under low oxygen conditions. Accumulation of hypoxic triglycerides or lipid droplets can be blocked by siRNA-mediated silencing of lipin 1 expression or kaempferol-mediated inhibition of HIF-1. We conclude that direct control of lipin 1 transcription by HIF-1 is an important regulatory feature of lipid metabolism and its adaptation to hypoxia. PMID:22467849

  17. Controversy and progress for treatment of acute cholangitis after Tokyo Guidelines (TG13).

    PubMed

    Sun, Zhipeng; Zhu, Yubing; Zhu, Bin; Xu, Guangzhong; Zhang, Nengwei

    2016-01-01

    Tokyo Guideline 2013 (TG13) is an international guideline for the diagnosis, classification and treatment of acute cholangitis. Progress and controversy for the two years after TG13 was summarized. Endoscopic ultrasound (EUS) and magnetic resonance cholangiopancreatography (MRCP) are both effective imaging tests for common bile duct (CBD) stones. More factors e.g. obesity may be involved in severity assessment. Initiation of broad-spectrum antibiotics addressing the typical Gram-negative enteric bacteria spectrum and early biliary drainage are the mainstay therapeutic options. Early laparoscopic exploration is also an option for stone-related nonsevere acute cholangitis besides endoscopic retrograde cholangial or percutaneous transhepatic cholangial drainage. Surgical biliary drainage should be avoided in severe cholangitis. PMID:26961212

  18. East Elevation, East Portico Wall Elevation, Portico Column Details ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    East Elevation, East Portico Wall Elevation, Portico Column Details - National Home for Disabled Volunteer Soldiers, Mountain Branch, Administration Building, Lamont & Veterans Way, Johnson City, Washington County, TN

  19. Characterization of TgPuf1, a member of the Puf family RNA-binding proteins from Toxoplasma gondii

    PubMed Central

    2014-01-01

    Background Puf proteins act as translational regulators and affect many cellular processes in a wide range of eukaryotic organisms. Although Puf proteins have been well characterized in many model systems, little is known about the structural and functional characteristics of Puf proteins in the parasite Toxoplasma gondii. Methods Using a combination of conventional molecular approaches, we generated endogenous TgPuf1 tagged with hemagglutinin (HA) epitope and investigated the TgPuf1 expression levels and localization in the tachyzoites and bradyzoites. We used RNA Electrophoretic Mobility Shfit Assay (EMSA) to determine whether the recombination TgPuf1 has conserverd RNA binding activity and specificity. Results TgPuf1 was expressed at a significantly higher level in bradyzoites than in tachyzoites. TgPuf1 protein was predominantly localized within the cytoplasm and showed a much more granular cytoplasmic staining pattern in bradyzoites. The recombinant Puf domain of TgPuf1 showed strong binding affinity to two RNA fragments containing Puf-binding motifs from other organisms as artificial target sequences. However, two point mutations in the core Puf-binding motif resulted in a significant reduction in binding affinity, indicating that TgPuf1 also binds to conserved Puf-binding motif. Conclusions TgPuf1 appears to exhibit different expression levels in the tachyzoites and bradyzoites, suggesting that TgPuf1 may function in regulating the proliferation or/and differentiation that are important in providing parasites with the ability to respond rapidly to changes in environmental conditions. This study provides a starting point for elucidating the function of TgPuf1 during parasite development. PMID:24685055

  20. LPS- induced inflammation exacerbates phospho-tau pathology in rTg4510 mice.

    PubMed

    Lee, Daniel C; Rizer, Justin; Selenica, Maj-Linda B; Reid, Patrick; Kraft, Clara; Johnson, Amelia; Blair, Laura; Gordon, Marcia N; Dickey, Chad A; Morgan, Dave

    2010-01-01

    Inflammation and microglial activation are associated with Alzheimer's disease (AD) pathology. Somewhat surprisingly, injection of a prototypical inflammatory agent, lipopolysaccharide (LPS) into brains of amyloid precursor protein (APP) transgenic mice clears some of the pre-existing amyloid deposits. It is less well understood how brain inflammation modulates tau pathology in the absence of A?. These studies examined the role of LPS-induced inflammation on tau pathology. We used transgenic rTg4510 mice, which express the P301L mutation (4R0N TauP301L) and initiate tau pathology between 3-5 months of age. First, we found an age-dependent increase in several markers of microglial activation as these rTg4510 mice aged and tau tangles accumulated. LPS injections into the frontal cortex and hippocampus induced significant activation of CD45 and arginase 1 in rTg4510 and non-transgenic mice. In addition, activation of YM1 by LPS was exaggerated in transgenic mice relative to non-transgenic animals. Expression of Ser199/202 and phospho-tau Ser396 was increased in rTg4510 mice that received LPS compared to vehicle injections. However, the numbers of silver-positive neurons, implying presence of more pre- and mature tangles, was not significantly affected by LPS administration. These data suggest that inflammatory stimuli can facilitate tau phosphorylation. Coupled with prior results demonstrating clearance of A? by similar LPS injections, these results suggest that brain inflammation may have opposing effects on amyloid and tau pathology, possibly explaining the failures (to date) of anti-inflammatory therapies in AD patients. PMID:20846376

  1. Space Elevator: Stability

    NASA Astrophysics Data System (ADS)

    Perek, Lubos

    2008-04-01

    Many papers have been published on engineering and economic aspects of the Space Elevator. The Elevator, however, is a very special and unusual astronomical body. Its behavior in space is affected not only by the attraction of the Earth and by the "centrifugal force" but also by the attraction of the Sun and the Moon, by the detailed shape of the Earth, by the presence of space debris, etc. Not all of the minor effects have been adequately studied. The size of the Space Elevator and its lack of resistance against buckling or bending require a detailed study of its stability, both in its initial phase as a geostationary (GEO) satellite as well as in its operational phase as a "sling". Lunisolar perturbations and other minor forces may affect the stability in the initial phase and will cause oscillations in the operational phase. Station-keeping thrusters will have to be mounted at selected points along the cable in order to maintain stability. In addition, the thrusters will perform local maneuvers for avoiding collisions with passing space debris. The control system of thrusters has to be adaptive, reacting fast to actual situation and rectifying the attitude of the Elevator whenever necessary. A further advantage of the thrusters is a possibility to locate the Elevator at any longitude, possibly looking for a region with minimum traffic at GEO distance. Extensive numerical simulations will have to be performed in order to determine elements of the thrusters and their control system.

  2. The bradykinin B1 receptor regulates A? deposition and neuroinflammation in Tg-SwDI mice.

    PubMed

    Passos, Giselle F; Medeiros, Rodrigo; Cheng, David; Vasilevko, Vitaly; Laferla, Frank M; Cribbs, David H

    2013-05-01

    The deposition of amyloid-? peptides (A?) in the cerebral vasculature, a condition known as cerebral amyloid angiopathy, is increasingly recognized as an important component leading to intracerebral hemorrhage, neuroinflammation, and cognitive impairment in Alzheimer disease (AD) and related disorders. Recent studies demonstrated a role for the bradykinin B1 receptor (B1R) in cognitive deficits induced by A? in mice; however, its involvement in AD and cerebral amyloid angiopathy is poorly understood. Herein, we investigated the effect of B1R inhibition on AD-like neuroinflammation and amyloidosis using the transgenic mouse model (Tg-SwDI). B1R expression was found to be up-regulated in brains of Tg-SwDI mice, specifically in the vasculature, neurons, and astrocytes. Notably, administration of the B1R antagonist, R715, to 8-month-old Tg-SwDI mice for 8 weeks resulted in higher A?40 levels and increased thioflavin S-positive fibrillar A? deposition. Moreover, blockage of B1R inhibited neuroinflammation, as evidenced by the decreased accumulation of activated microglia and reactive astrocytes, diminished NF-?B activation, and reduced cytokine and chemokine levels. Together, our results indicate that B1R activation plays an important role in limiting the accumulation of A? in AD-like brain, likely through the regulation of activated glial cell accumulation and release of pro-inflammatory mediators. Therefore, the modulation of the receptor may represent a novel therapeutic approach for AD. PMID:23470163

  3. Interaction and kinetic analysis for coal and biomass co-gasification by TG-FTIR.

    PubMed

    Xu, Chaofen; Hu, Song; Xiang, Jun; Zhang, Liqi; Sun, Lushi; Shuai, Chao; Chen, Qindong; He, Limo; Edreis, Elbager M A

    2014-02-01

    This study aims to investigate the interaction and kinetic behavior of CO2 gasification of coal, biomass and their blends by thermogravimetry analysis (TG). The gas products evolved from gasification were measured online with Fourier Transform Infrared Spectroscopy (FTIR) coupled with TG. Firstly, TG experiments indicated that interaction between the coals and biomasses mainly occurred during co-gasification process. The most significant synergistic interaction occurred for LN with SD at the blending mass ratio 4:1. Furthermore, thermal kinetic analysis indicated that the activation energy involved in co-gasification decreased as the SD content increased until the blending ratio of SD with coal reached 4:1. The rise of the frequency factor indicated that the increase of SD content favored their synergistic interaction. Finally, FTIR analysis of co-gasification of SD with LN indicated that except for CO, most gases including CH3COOH, C6H5OH, H2O, etc., were detected at around 50-700C. PMID:24412857

  4. An EGSnrc Monte Carlo-calculated database of TG-43 parameters

    SciTech Connect

    Taylor, R. E. P.; Rogers, D. W. O.

    2008-09-15

    Monte Carlo methods are used to calculate a complete TG-43 dosimetry parameter data set for 27 low-energy photon emitting brachytherapy sources (18 {sup 125}I and 9 {sup 103}Pd). All Monte Carlo calculations are performed using the EGSnrc user-code BrachyDose. TG-43 dosimetry parameters, including dose rate constants, radial dose functions (with functional fitting parameters), and anisotropy data, are calculated with finer spatial resolution, greater range of distances, and smaller uncertainties than data currently available in the literature for many of these sources. In particular, for most of the seeds, this is the first time that anisotropy data have been tabulated at distances less than 0.5 cm from the source. These calculations employ the state-of-the-art XCOM photon cross sections, and detailed source geometries are modeled using Yegin's multigeometry package. This data set serves as a completely independent verification of the currently available dosimetry parameters calculated using other Monte Carlo codes, including MCNP and PTRAN. This report also describes the Carleton Laboratory for Radiotherapy Physics TG-43 Parameter Database, a publicly accessible web site (at http://www.physics.carleton.ca/clrp/seed{sub d}atabase/) through which all of the data calculated for this study can be accessed. Also available on the web site are descriptions of the methods and Monte Carlo models used in this study and comparisons of data calculated in this study with data calculated by other authors.

  5. Plastic Flow of Polymer Chains below Tg Induced by Jamming Transition

    NASA Astrophysics Data System (ADS)

    Teng, Chao; Xue, Gi

    2014-03-01

    Polymer chains begin to flow when they are heated above Tg. Other glassy systems, such as colloidal suspensions and granular materials, begin to flow when subjected to sufficiently large stresses. The equivalence of these two routes to flow is a basic tenet of jamming theory. However, a full understanding of jamming transition for polymer chains remains elusive. In this work, we adjust the polymer chain packing density by spry-drying and some other methods, and then apply shear stress at temperature far below its Tg. The resulting pellet shows very similar features as the hot processed or solution casting samples, which strongly indicates that the plastic flow of polymer chains ever happened below Tg. We found that the packing density and shear stress play important roles during the plastic flow process at low temperature, which is according with the jamming theory. This kind of plastic flow at low temperature shows its advantages when processing materials with bioactivity, which will be deactivated at high temperature. Furthermore, these findings also suggested an approach to understand the high mobility of surface layer of polymer thin film and nanoparticles. The authors appreciate the financial support of the NSF of China (21304003).

  6. Effects of the C57BL/6 strain background on tauopathy progression in the rTg4510 mouse model

    PubMed Central

    2014-01-01

    Background Cross-breeding of transgenic mice is commonly used to assess gene-gene interactions, particularly in the context of disease. Strain background changes can influence the phenotype of mouse models and can confound crossbreeding studies. We sought to determine if changing the strain background of a commonly used mouse model of tauopathy (rTg4510) would significantly impact the originally reported phenotype. On the original F1 FVB/N x 129S6 background, rTg4510 mice present with progressive cognitive decline, increased insoluble tau, robust tau pathology and age-dependent neurodegeneration. One of the most common strains in mouse modeling is C57BL/6. We and others have previously reported that this strain background alters the phenotypes of various models, including the JNPL3 model of tauopathy. To determine if the phenotype of rTg4510 mice was similarly affected by the introduction of the C57BL/6 background, we compared rTg4510 mice on the original F1 FVB/N x 129S6 background to rTg4510 mice on an F1 FVB/N x C57BL/6NTac (B6/NTac) background, herein termed rTg4510B6. Results Despite a small, but significant increase in soluble human tau levels, young rTg4510B6 mice had equivalent levels of tau phosphorylation, aggregation and cognitive impairments as age-matched rTg4510 mice. At 6.5months of age, rTg4510B6 mice displayed hyperphosphorylated insoluble tau and robust cortical tau neuropathology that was equivalent to age-matched rTg4510 mice; however, 10.5-month-old rTg4510B6 mice had greater amounts of phospho-tau in the cortex and hippocampus when compared to age-matched rTg4510 mice. Non-transgenic (NT) littermates of rTg4510B6 (NTB6) mice also had greater amounts of cortical and hippocampal phospho-tau at 10.5months of age when compared to NT littermates of rTg4510 mice. Additionally, older rTg4510B6 mice had gross forebrain neurodegeneration that was equivalent to age-matched rTg4510 mice. Conclusions Overall, our data shows that introduction of the C57BL/6 strain into the rTg4510 mouse background modestly alters the tau pathology that was originally reported in rTg4510 on the F1 FVB/129 background. In contrast, behavioral and neurodegenerative outcomes were not altered. These studies support the use of the rTg4510 mouse model on a partial C57BL/6 strain background without losing fidelity of the phenotype and suggest that the C57BL/6 background does not inherently protect against tauopathy. PMID:24428919

  7. Enhanced acetyl-CoA production is associated with increased triglyceride accumulation in the green alga Chlorella desiccata

    PubMed Central

    Avidan, Omri; Brandis, Alexander; Rogachev, Ilana; Pick, Uri

    2015-01-01

    Triglycerides (TAGs) from microalgae can be utilized as food supplements and for biodiesel production, but little is known about the regulation of their biosynthesis. This work aimed to test the relationship between acetyl-CoA (Ac-CoA) levels and TAG biosynthesis in green algae under nitrogen deprivation. A novel, highly sensitive liquid chromatography mass spectrometry (LC-MS/MS) technique enabled us to determine the levels of Ac-CoA, malonyl-CoA, and unacetylated (free) CoA in green microalgae. A comparative study of three algal species that differ in TAG accumulation levels shows that during N starvation, Ac-CoA levels rapidly rise, preceding TAG accumulation in all tested species. The levels of Ac-CoA in the high TAG accumulator Chlorella desiccata exceed the levels in the moderate TAG accumulators Dunaliella tertiolecta and Chlamydomonas reinhardtii. Similarly, malonyl-CoA and free CoA levels also increase, but to lower extents. Calculated cellular concentrations of Ac-CoA are far lower than reported K mAc-CoA values of plastidic Ac-CoA carboxylase (ptACCase) in plants. Transcript level analysis of plastidic pyruvate dehydrogenase (ptPDH), the major chloroplastic Ac-CoA producer, revealed rapid induction in parallel with Ac-CoA accumulation in C. desiccata, but not in D. tertiolecta or C. reinhardtii. It is proposed that the capacity to accumulate high TAG levels in green algae critically depends on their ability to divert carbon flow towards Ac-CoA. This requires elevation of the chloroplastic CoA pool level and enhancement of Ac-CoA biosynthesis. These conclusions may have important implications for future genetic manipulation to enhance TAG biosynthesis in green algae. PMID:25922486

  8. Elevated BP after AKI.

    PubMed

    Hsu, Chi-Yuan; Hsu, Raymond K; Yang, Jingrong; Ordonez, Juan D; Zheng, Sijie; Go, Alan S

    2016-03-01

    The connection between AKI and BP elevation is unclear. We conducted a retrospective cohort study to evaluate whether AKI in the hospital is independently associated with BP elevation during the first 2 years after discharge among previously normotensive adults. We studied adult members of Kaiser Permanente Northern California, a large integrated health care delivery system, who were hospitalized between 2008 and 2011, had available preadmission serum creatinine and BP measures, and were not known to be hypertensive or have BP>140/90 mmHg. Among 43,611 eligible patients, 2451 experienced AKI defined using observed changes in serum creatinine concentration measured during hospitalization. Survivors of AKI were more likely than those without AKI to have elevated BP-defined as documented BP>140/90 mmHg measured during an ambulatory, nonemergency department visit-during follow-up (46.1% versus 41.2% at 730 days; P<0.001). This difference was evident within the first 180 days (30.6% versus 23.1%; P<0.001). In multivariable models, AKI was independently associated with a 22% (95% confidence interval, 12% to 33%) increase in the odds of developing elevated BP during follow-up, with higher adjusted odds with more severe AKI. Results were similar in sensitivity analyses when elevated BP was defined as having at least two BP readings of >140/90 mmHg or those with evidence of CKD were excluded. We conclude that AKI is an independent risk factor for subsequent development of elevated BP. Preventing AKI during a hospitalization may have clinical and public health benefits beyond the immediate hospitalization. PMID:26134154

  9. National Elevation Dataset

    USGS Publications Warehouse

    U.S. Geological Survey

    2002-01-01

    The National Elevation Dataset (NED) is a new raster product assembled by the U.S. Geological Survey. NED is designed to provide National elevation data in a seamless form with a consistent datum, elevation unit, and projection. Data corrections were made in the NED assembly process to minimize artifacts, perform edge matching, and fill sliver areas of missing data. NED has a resolution of one arc-second (approximately 30 meters) for the conterminous United States, Hawaii, Puerto Rico and the island territories and a resolution of two arc-seconds for Alaska. NED data sources have a variety of elevation units, horizontal datums, and map projections. In the NED assembly process the elevation values are converted to decimal meters as a consistent unit of measure, NAD83 is consistently used as horizontal datum, and all the data are recast in a geographic projection. Older DEM's produced by methods that are now obsolete have been filtered during the NED assembly process to minimize artifacts that are commonly found in data produced by these methods. Artifact removal greatly improves the quality of the slope, shaded-relief, and synthetic drainage information that can be derived from the elevation data. Figure 2 illustrates the results of this artifact removal filtering. NED processing also includes steps to adjust values where adjacent DEM's do not match well, and to fill sliver areas of missing data between DEM's. These processing steps ensure that NED has no void areas and artificial discontinuities have been minimized. The artifact removal filtering process does not eliminate all of the artifacts. In areas where the only available DEM is produced by older methods, then "striping" may still occur.