Sample records for elevated triglycerides tg

  1. An elevation of triglycerides reflecting decreased triglyceride clearance may not be pathogenic – relevance to high-carbohydrate diets

    Microsoft Academic Search

    Mark F. McCarty

    2004-01-01

    The fact that carbohydrate-rich diets often increase plasma triglycerides has led some to question the wisdom of such diets. This increase is primarily attributable to a decrease in the efficiency of triglyceride clearance – whereas the elevation of triglycerides observed in insulin-resistant subjects stems mainly from increased hepatic production of VLDL particles. There is growing reason to suspect that the

  2. Galanin preproprotein is associated with elevated plasma triglycerides

    PubMed Central

    Plaisier, Christopher L; Kyttälä, Mira; Weissglas-Volkov, Daphna; Sinsheimer, Janet S.; Huertas-Vazquez, Adriana; Riba, Laura; Ramírez-Jiménez, Salvador; de Bruin, Tjerk W. A.; Tusié-Luna, Teresa; Aouizerat, Bradley E.; Pullinger, Clive R.; Malloy, Mary J.; Kane, John P.; Cruz-Bautista, Ivette; Herrera, Miguel F.; Aguilar-Salinas, Carlos; Kuusisto, Johanna; Laakso, Markku; Taskinen, Marja-Riitta; Kallen, Carla J. H. van der; Pajukanta, Päivi

    2009-01-01

    Objective There is increasing physiological evidence in rodents connecting the neuropeptide galanin to triglyceride (TG) levels. We hypothesized that variation in the galanin preproprotein (GAL) gene may contribute to hypertriglyceridemia (HTG) in humans. Methods and Results We investigated GAL as a TG candidate gene by genotyping four tagSNPs in Dutch, Finnish and Mexican familial combined hyperlipidemia (FCHL) families as well as in Caucasian combined hyperlipidemia cases/controls (n=2,471). The common allele of rs2187331, residing in the promoter region of GAL, was significantly associated with HTG (p-value=0.00038). In an unascertained population sample of 4,463 Finnish males, the rare allele of rs2187331 was associated with higher TGs (p-value=0.0028?0.00016). We also observed an allele specific difference with rs2187331 in reporter gene expression and nuclear factor binding in vitro. Furthermore, we detected differential expression of many key lipid genes in adipose tissue based on rs2187331 genotypes. Conclusions The SNP rs2187331 is associated with HTG in FCHL and Caucasian combined hyperlipidemia cases/controls and influences TG levels in the population. Further studies are warranted to elucidate the allelic difference observed between FCHL and the general population. Functional evidence shows that rs2187331 has an allele specific cis-regulatory function and influences the expression of lipid related genes in adipose. PMID:18988886

  3. 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 ...

  4. Elevated Serum Triglyceride and Retinol-Binding Protein 4 Levels Associated with Fructose-Sweetened Beverages in Adolescents

    PubMed Central

    Chan, Te-Fu; Lin, Wei-Ting; Chen, Yi-Ling; Huang, Hsiao-Ling; Yang, Wei-Zeng; Lee, Chun-Ying; Chen, Meng-Hsueh; Wang, Tsu-Nai; Huang, Meng-Chuan; Chiu, Yu-Wen; Huang, Chun-Chi; Tsai, Sharon; Lin, Chih-Lung; Lee, Chien-Hung

    2014-01-01

    Background The metabolic effect of fructose in sugar-sweetened beverages (SSB) has been linked to de novo lipogenesis and uric acid (UA) production. Objectives This study investigated the biological effects of SSB consumption on serum lipid profiles and retinol-binding protein 4 (RBP4) among Taiwanese adolescents. Methods We evaluated the anthropometric parameters and biochemical outcomes of 200 representative adolescents (98 boys and 102 girls) who were randomly selected from a large-scale cross-sectional study. Data were analyzed using multiple regression models adjusted for covariates. Results Increased SSB consumption was associated with increased waist and hip circumferences, body mass index (BMI) values and serum UA, triglyceride (TG) and RBP4 levels. Adolescents who consumed >500 ml/day of beverages half-to-heavily sweetened with high-fructose corn syrup (HFCS) exhibited TG and RBP4 levels 22.7 mg/dl and 13.92 ng/ml higher than non-drinkers, respectively. HFCS drinkers with hyperuricemia had higher TG levels than HFCS drinkers with normal UA levels (98.6 vs. 81.6 mg/dl). The intake of HFCS-rich SSBs and high value of BMI (?24) interactively reinforced RBP4 levels among overweight/obese adolescents. Circulating RBP4 levels were significantly correlated with weight-related outcomes and TG and UA concentration among HFCS drinkers (r?=?0.253 to 0.404), but not among non-drinkers. Conclusions High-quantity HFCS-rich beverage consumption is associated with higher TG and RBP4 levels. Hyperuricemia is likely to intensify the influence of HFCS-rich SSB intake on elevated TG levels, and in overweight and obese adolescents, high BMI may modify the action of fructose on higher circulating levels of RBP4. PMID:24475021

  5. Rare LPL gene variants attenuate triglyceride reduction and HDL cholesterol increase in response to fenofibric acid therapy in

    E-print Network

    Keinan, Alon

    Rare LPL gene variants attenuate triglyceride reduction and HDL cholesterol increase in response t Objective: Individuals with mixed dyslipidemia have elevated triglycerides (TG), low high-density lipo reserved. 1. Introduction Multiple studies have shown that genetic variants can affect triglycerides (TG

  6. Impaired brachial artery endothelial function is not predicted by elevated triglycerides

    Microsoft Academic Search

    Greg B. Schnell; Annette Robertson; Deborah Houston; Linda Malley; Todd J. Anderson

    1999-01-01

    OBJECTIVESThe purpose of this study was to determine if patients with modest hyperlipidemia, and no other risk factors for coronary artery disease (CAD), have impaired endothelium-dependent (ED) vasoactivity.BACKGROUNDHypercholesterolemia impairs ED vasodilation, but the impact of elevated triglycerides on endothelial function is not as well established.METHODSHigh-resolution ultrasound was used to determine flow-mediated dilation (FMD) in the brachial artery (BA) after a

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

    SciTech Connect

    Cheng, Jie; Krausz, Kristopher W. [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)] [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Li, Feng; Ma, Xiaochao [Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, 4089 KLSIC, MS 1018, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States)] [Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, 4089 KLSIC, MS 1018, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States); Gonzalez, Frank J., E-mail: fjgonz@helix.nih.gov [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    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. -- 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.

  8. 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 ?-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

  9. 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...

  10. 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

  11. Caspase-1 deficiency in mice reduces intestinal triglyceride absorption and hepatic triglyceride secretion[S

    PubMed Central

    van Diepen, Janna A.; Stienstra, Rinke; Vroegrijk, Irene O. C. M.; van den Berg, Sjoerd A. A.; Salvatori, Daniela; Hooiveld, Guido J.; Kersten, Sander; Tack, Cees J.; Netea, Mihai G.; Smit, Johannes W.A.; Joosten, Leo A. B.; Havekes, Louis M.; van Dijk, Ko Willems; Rensen, Patrick C. N.

    2013-01-01

    Caspase-1 is known to activate the proinflammatory cytokines IL-1? and IL-18. Additionally, it can cleave other substrates, including proteins involved in metabolism. Recently, we showed that caspase-1 deficiency in mice strongly reduces high-fat diet-induced weight gain, at least partly caused by an increased energy production. Increased feces secretion by caspase-1-deficient mice suggests that lipid malabsorption possibly further reduces adipose tissue mass. In this study we investigated whether caspase-1 plays a role in triglyceride-(TG)-rich lipoprotein metabolism using caspase-1-deficient and wild-type mice. Caspase-1 deficiency reduced the postprandial TG response to an oral lipid load, whereas TG-derived fatty acid (FA) uptake by peripheral tissues was not affected, demonstrated by unaltered kinetics of [3H]TG-labeled very low-density lipoprotein (VLDL)-like emulsion particles. An oral gavage of [3H]TG-containing olive oil revealed that caspase-1 deficiency reduced TG absorption and subsequent uptake of TG-derived FA in liver, muscle, and adipose tissue. Similarly, despite an elevated hepatic TG content, caspase-1 deficiency reduced hepatic VLDL-TG production. Intestinal and hepatic gene expression analysis revealed that caspase-1 deficiency did not affect FA oxidation or FA uptake but rather reduced intracellular FA transport, thereby limiting lipid availability for the assembly and secretion of TG-rich lipoproteins. The current study reveals a novel function for caspase-1, or caspase-1-cleaved substrates, in controlling intestinal TG absorption and hepatic TG secretion. PMID:23160218

  12. 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

  13. Supplementary Figure 1 TC HDL-C N-HDL-C TG

    E-print Network

    Paris-Sud XI, Université de

    -cholesterol, N-HDL-C : non-HDL-cholesterol, TG : triglycerides *** *** inserm-00591959,version1-10May2011 Author-density lipoprotein cholesterol; N-HDL-C, non-HDL-C; TG, triglycerides. inserm-00591959,version1-10May2011 #12 cholesterol; HDL-C, high-density lipoprotein cholesterol; N-HDL-C, non-HDL-C; TG, triglycerides. inserm

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

    SciTech Connect

    Lanza-Jacoby, S.; Tabares, A. (Jefferson Medical Coll., Philadelphia, PA (United States))

    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.

  15. Triglyceride kinetics, tissue lipoprotein lipase, and liver lipogenesis in septic rats

    SciTech Connect

    Lanza-Jacoby, S.; Tabares, A. (Jefferson Medical College, Philadelphia, PA (USA))

    1990-04-01

    The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studied by examining liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant iv infusion of (2-3H)glycerol-labeled VLDL. Clearance of VLDL-TG was also evaluated by measuring activities of lipoprotein lipase (LPL) in heart, soleus muscle, and adipose tissue from 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 x 10(7) live E. coli colonies per 100 g body wt. Twenty-four hours after E. coli injection, serum TG, free fatty acids (FFA), and cholesterol of fasted E. coli-treated rats were elevated by 170, 76, and 16%, respectively. The elevation of serum TG may be attributed to the 67% decrease in clearance rate of VLDL-TG in fasted E. coli-treated rats compared with their fasted controls. The suppressed activities of LPL in adipose tissue, skeletal muscle, and heart were consistent with reduced clearance of TG. Secretion of VLDL-TG declined by 31% in livers of fasted E. coli-treated rats, which was accompanied by a twofold increase in the composition of liver TG. Rates of in vivo TG synthesis in livers of the fasted E. coli-treated rats were twofold higher than in those of fasted control rats. Decreased rate of TG appearance along with the increase in liver synthesis of TG contributed to the elevation of liver lipids in the fasted E. coli-treated rats.

  16. Major loci influencing serum triglyceride levels on 2q14 and 9p21 localized by

    E-print Network

    Abney, Mark

    Major loci influencing serum triglyceride levels on 2q14 and 9p21 localized by homozygosity triglyceride (TG) level is a well-known risk factor for cardiovascular disease, a leading cause of morbidity (1­5). Variation in serum triglyceride (TG) levels among individuals results from both environmental

  17. Ruminal hydrolysis of dietary triglycerides in dairy cows fed lipid-supplemented diets

    E-print Network

    Paris-Sud XI, Université de

    Ruminal hydrolysis of dietary triglycerides in dairy cows fed lipid-supplemented diets D Bauchart1. Materials and Methods ― Triglyceride (TG) hydrolysis was determined by ruminal balance in 10 dairy

  18. 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 12 months. They were classified into the two groups according to the cut-off values of predicting early outcome of fasting TG level (low group <1.2 mmol/L, n?=?103; High group ?1.2 mmol/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 (?1.2 mmol/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

  19. Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c

    PubMed Central

    Watanabe, Mitsuhiro; Houten, Sander M.; Wang, Li; Moschetta, Antonio; Mangelsdorf, David J.; Heyman, Richard A.; Moore, David D.; Auwerx, Johan

    2004-01-01

    We explored the effects of bile acids on triglyceride (TG) homeostasis using a combination of molecular, cellular, and animal models. Cholic acid (CA) prevents hepatic TG accumulation, VLDL secretion, and elevated serum TG in mouse models of hypertriglyceridemia. At the molecular level, CA decreases hepatic expression of SREBP-1c and its lipogenic target genes. Through the use of mouse mutants for the short heterodimer partner (SHP) and liver X receptor (LXR) ? and ?, we demonstrate the critical dependence of the reduction of SREBP-1c expression by either natural or synthetic farnesoid X receptor (FXR) agonists on both SHP and LXR? and LXR?. These results suggest that strategies aimed at increasing FXR activity and the repressive effects of SHP should be explored to correct hypertriglyceridemia. PMID:15146238

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

    Microsoft Academic Search

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

    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

  1. Direct Antidiabetic Effect of Leptin through Triglyceride Depletion of Tissues

    Microsoft Academic Search

    Michio Shimabukuro; Kazunori Koyama; Guoxun Chen; May-Yun Wang; Falguni Trieu; Young Lee; Christopher B. Newgard; Roger H. Unger

    1997-01-01

    Leptin is currently believed to control body composition largely, if not entirely, via hypothalamic receptors that regulate food intake and thermogenesis. Here we demonstrate direct extraneural effects of leptin to deplete fat content of both adipocytes and nonadipocytes to levels far below those of pairfed controls. In cultured pancreatic islets, leptin lowered triglyceride (TG) content by preventing TG formation from

  2. Early hyperactivity in lateral entorhinal cortex is associated with elevated levels of A?PP metabolites in the Tg2576 mouse model of Alzheimer's disease.

    PubMed

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

    2015-02-01

    Alzheimer's disease (AD) is a neurodegenerative disorder which 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 ? precursor protein (A?PP) metabolites, including amyloid-? (A?) and A?PP C-terminal fragments (CTF), on olfactory processing in the lateral entorhinal cortex (LEC) using the Tg2576 mouse model of human A?PP 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 16months 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 6MO 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 A? deposition in the olfactory system, but rather to high levels of intracellular A?PP-CTF and soluble A? in the anterior piriform cortex (aPCX), a major afferent input to the LEC, by 3MO. The present results add to the growing evidence of A?PP-related hyper-excitability, and further implicate both soluble A? and non-A? A?PP metabolites in its early emergence. PMID:25500142

  3. Effects of icosapent ethyl on lipid and inflammatory parameters in patients with diabetes mellitus-2, residual elevated triglycerides (200–500 mg/dL), and on statin therapy at LDL-C goal: the ANCHOR study

    PubMed Central

    2013-01-01

    Background Icosapent ethyl (IPE) is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (?500 mg/dL) hypertriglyceridemia. ANCHOR was a 12-week, phase 3 study that evaluated the efficacy and safety of IPE in patients (N?=?702) with residual high fasting TG levels (?200 and <500 mg/dL) despite having optimized low-density lipoprotein cholesterol (LDL-C) levels (?40 and <100 mg/dL) on statin therapy. Among patients randomized to IPE (4 g/day or 2 g/day) or placebo, 514 (73%) had diabetes mellitus. Methods A post hoc subgroup analysis of the ANCHOR study was conducted to assess the effects of IPE on median placebo-adjusted percent change from baseline in efficacy end point parameters in 3 subgroups: total (all subjects with diabetes—overall median baseline glycosylated hemoglobin A1c [A1c]?=?6.8%), better-controlled diabetes (below median baseline A1c), and less-controlled diabetes (above median baseline A1c). Results Baseline efficacy parameters were similar among all groups except high-sensitivity C-reactive protein (hsCRP), which was higher in the total and less-controlled diabetes groups. Compared with placebo, IPE 4 g/day significantly reduced TG, non-high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol (VLDL-C), lipoprotein-associated phospholipase A2, apolipoprotein B (Apo B), total cholesterol, high-density lipoprotein cholesterol, VLDL-TG, oxidized LDL, and remnant-like particle cholesterol in all 3 diabetes groups, LDL-C in the total diabetes group, and hsCRP in the total and less-controlled diabetes groups. Decreases in hsCRP and Apo B were much greater in patients with less-controlled diabetes. There were no significant increases in fasting plasma glucose, A1c, insulin, or homeostasis model assessment-estimated insulin resistance in any group. Conclusion IPE 4 g/day significantly improved lipid and lipid-related parameters without worsening glycemic control in patients with diabetes and mixed dyslipidemia, with possibly greater effects among those with less-controlled diabetes. Trial registration Clinicaltrials.gov Identifier NCT01047501 PMID:23835245

  4. Increased plasma free fatty acid and triglyceride levels after single administation of toluene in rabbits

    SciTech Connect

    Takahashi, Setsunori; Tanabe, Koichi; Shiono, Hiroshi (Shimane Medical Univ., Izumo (Japan)); Maseda, Chikatoshi (Shimane Prefectural Police Headquarters, Matsue (Japan)); Fukui, Yuko (Kyoto Univ. (Japan))

    1988-01-01

    Changes of plasma lipids (triglyceride, TG: total cholesterol, Cho; and phospholipids, PL), free fatty acid (FFA), and blood glucose (BG) were studied in male rabbits after toluene administration (0.5 g/kg per os). Hypertriglyceridemia was observed at and after 2 h. Plasma FFA and BG were elevated temporarily during the early stage and lowered gradually thereafter. Initially, plasma Cho and PL were virtually unchanged, by the Cho levels increased slowly after 6 h. The hypertriglyceridemia observed may have some adverse effects on heart function.

  5. LDL and HDL enriched in triglyceride promote abnormal cholesterol transport

    Microsoft Academic Search

    Josephine W. Skeggs; Richard E. Morton

    Hypertriglyceridemia induces multiple changes in lipoprotein composition. Here we investigate how one of these modifications, triglyceride (TG) enrichment, affects HDL and LDL function when this alteration occurs under conditions in which more polar components can naturally re-equilibrate. TG-enriched lipoproteins were produced by co-incubating VLDL, LDL, and HDL with cholesteryl ester (CE) transfer protein. The resulting 2.5-fold increase in TG\\/CE ratio

  6. Dietary cholesterol stimulates hepatic biosynthesis of triglyceride and reduces oxidation of fatty acids in the rat

    Microsoft Academic Search

    Thomas V. Fungwe; Lauren M. Cagen; George A. Cook; Henry G. Wilcox; Murray Heimberg

    Experiments were conducted in the intact rat and in the isolated, perfused rat liver to investigate the possibility that the increase in the concentration of hepatic triglyceride and in- crease in the secretion of the very low density lipoprotein (VLDL)-triglyceride (TG) resulting from addition of cholesterol to the diet are due to stimulation of synthesis of triglyceride, reduced fatty acid

  7. Effect of Insulin on the Secretion and Content of Triglyceride in the Chicken Liver Slices

    Microsoft Academic Search

    2005-01-01

    Triglyceride (TG) secretion from liver and its storage in abdominal cavity of the broiler affects the net meat yield. So agents that affect the hepatic TG secretion may be important for poultry breeders. At present study, we have shown short term effects of insulin on the chicken liver TG secretion at the first, third, fifth and seventh weeks of breeding.

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

    Microsoft Academic Search

    Zsuzsa Mészáros; Tamás Szombathy; Laura Raimondi; István Karádi; László Romics; Kálmán Magyar

    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

  9. 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

  10. The effect of high-dose simvastatin on triglyceride-rich lipoprotein metabolism in patients with type 2 diabetes mellitus

    Microsoft Academic Search

    William L. Isley; John M. Miles; Bruce W. Patterson; William S. Harris

    2005-01-01

    Statins decrease triglycerides (TGs) in addition to decreasing low density lipoprotein-cholesterol. Although the mechanism for the latter effect is well understood, it is still unclear how TG decrease is achieved with statin therapy. Because hypertriglyceridemia is common in obese patients with type 2 diabetes mellitus, we studied triglyceride-rich lipoprotein triglyceride (TRL-TG) turnover in 12 such sub- jects using stable isotopically

  11. Cardiac-specific knock-out of lipoprotein lipase alters plasma lipoprotein triglyceride metabolism and cardiac gene expression.

    PubMed

    Augustus, Ayanna; Yagyu, Hiroaki; Haemmerle, Guenter; Bensadoun, André; Vikramadithyan, Reeba K; Park, So-Young; Kim, Jason K; Zechner, Rudolf; Goldberg, Ira J

    2004-06-11

    Fatty acids are the primary energy source for the heart. The heart acquires fatty acids associated with albumin or derived from lipoprotein lipase (LpL)-mediated hydrolysis of lipoprotein triglyceride (TG). We generated heart-specific LpL knock-out mice (hLpL0) to determine whether cardiac LpL modulates the actions of peroxisome proliferator-activated receptors and affects whole body lipid metabolism. Male hLpL0 mice had significantly elevated plasma TG levels and decreased clearance of postprandial lipids despite normal postheparin plasma LpL activity. Very large density lipoprotein-TG uptake was decreased by 72% in hLpL0 hearts. However, heart uptake of albumin-bound free fatty acids was not altered. Northern blot analysis revealed a decrease in the expression of peroxisome proliferator-activated receptor alpha-response genes involved in fatty acid beta-oxidation. Surprisingly, the expression of glucose transporters 1 and 4 and insulin receptor substrate 2 was increased and that of pyruvate dehydrogenase kinase 4 and insulin receptor substrate 1 was reduced. Basal glucose uptake was increased markedly in hLpL0 hearts. Thus, the loss of LpL in the heart leads to defective plasma metabolism of TG. Moreover, fatty acids derived from lipoprotein TG and not just albumin-associated fatty acids are important for cardiac lipid metabolism and gene regulation. PMID:15028738

  12. Soy protein reduces triglyceride levels and triglyceride fatty acid fractional synthesis rate in hypercholesterolemic subjects

    Microsoft Academic Search

    Yanwen Wanga; Peter J. H. Jones; Lynne M. Ausmanb; Alice H. Lichtenstein

    To examine the effects of protein source and isoflavones on triglyceride (TG) fatty acid (TGFA) and cholesterol biosynthesis, subjects (>50 years, LDL cholesterol >130 mg\\/dl) underwent a four-phase randomized cross-over feeding trial. Diets contained either isolated soy protein or common sources of animal protein (25 g\\/1000 kcal), without or with isoflavones (49 mg\\/1000 kcal) and were each fed for 6

  13. De novo synthesis of milk triglycerides in humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 tha...

  14. Stereospecific analysis of triglycerides

    Microsoft Academic Search

    H. Brockerhoff

    1971-01-01

    Stereospecific analysis determines how the fatty acids of triglycerides are distributed over the three different positions\\u000a of the glycerol. The special problem is the differentiation of position I-1 and L-3 of glycerol. In the presently known methods,\\u000a triglycerides are first degraded to mixtures of diglycerides, either by the action of a lipase or by degradation with a Grignard\\u000a reagent. The

  15. HPLC of triglycerides

    Microsoft Academic Search

    B. Herslöf; O. Podlaha; B. Töregård

    1979-01-01

    Triglyceride separation was investigated on a reverse phase high performance liquid chromatography (HPLC) column using two\\u000a different solvent systems. Complete separation of model compounds differing by two methylene groups was achieved. Partial\\u000a or complete separation was also observed in critical pairs; for example, the different types of triglycerides consisting of\\u000a palmitic and oleic acids. This observation was confirmed on natural

  16. The Association between Triglyceride/High-Density Lipoprotein Cholesterol Ratio and All-Cause Mortality in Acute Coronary Syndrome after Coronary Revascularization

    PubMed Central

    Wan, Ke; Zhao, Jianxun; Huang, Hao; Zhang, Qing; Chen, Xi; Zeng, Zhi; Zhang, Li; Chen, Yucheng

    2015-01-01

    Aims High triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) are cardiovascular risk factors. A positive correlation between elevated TG/HDL-C ratio and all-cause mortality and cardiovascular events exists in women. However, utility of TG to HDL-C ratio for prediction is unknown among acute coronary syndrome (ACS). Methods Fasting lipid profiles, detailed demographic data, and clinical data were obtained at baseline from 416 patients with ACS after coronary revascularization. Subjects were stratified into three levels of TG/HDL-C. We constructed multivariate Cox-proportional hazard models for all-cause mortality over a median follow-up of 3 years using log TG to HDL-C ratio as a predictor variable and analyzing traditional cardiovascular risk factors. We constructed a logistic regression model for major adverse cardiovascular events (MACEs) to prove that the TG/HDL-C ratio is a risk factor. Results The subject’s mean age was 64 ± 11 years; 54.5% were hypertensive, 21.8% diabetic, and 61.0% current or prior smokers. TG/HDL-C ratio ranged from 0.27 to 14.33. During the follow-up period, there were 43 deaths. In multivariate Cox models after adjusting for age, smoking, hypertension, diabetes, and severity of angiographic coronary disease, patients in the highest tertile of ACS had a 5.32-fold increased risk of mortality compared with the lowest tertile. After adjusting for conventional coronary heart disease risk factors by the logistic regression model, the TG/HDL-C ratio was associated with MACEs. Conclusion The TG to HDL-C ratio is a powerful independent predictor of all-cause mortality and is a risk factor of cardiovascular events. PMID:25880982

  17. Postprandial triglycerides and endothelial function.

    PubMed

    Jagla, A; Schrezenmeir, J

    2001-01-01

    Several studies support the association between postprandially elevated triglyceride levels and atherosclerosis. Histological and cell culture investigations revealed, that triglyceride rich postprandial lipoproteins are taken up by macrophages and smooth muscle cells and are detectable as part of foam cells in vascular lesions. Remnant particles, generated by lipolysis of postprandial lipoproteins in vitro and fatty acids increase the permeability of the endothelium and are cytotoxic for endothelial cells. Besides these morphological changes of cells, lipoproteins have been shown to exert effects on cellular functions like the expression of membrane proteins and the production or release of several bioactive substances regulating communication with blood cells and other cell systems of the vascular wall, blood pressure and hemostasis. This review concentrates on the influence of postprandial lipoproteins on factors involved in the interaction of endothelial cells with blood leukocytes and factors mediating blood pressure regulation. Increased expression of adhesion molecules has been detected immunehistochemically in atherosclerotic plaques in animals and humans. It was demonstrated that patients with elevated triglyceride levels have increased levels of soluble adhesion molecules. Furthermore, postprandial lipoproteins were shown to induce membrane expression of adhesion molecules. This effect seems to be at least in part mediated by the oxidative modification of the particles. Accordingly chylomicrons separated after ingestion of safflower oil, rich in polyunsaturated linoleic acid, induced higher adhesion molecule expression at higher oxidant concentration compared with chylomicrons separated after ingestion of olive oil, rich in monounsaturated oleic acid. Several authors described effects of fatty acids on the expression of adhesion molecules. On the one hand, they may exert stimulatory effects as such, on the other hand cytokine induced adhesion molecule expression may be enhanced by certain fatty acids and inhibited by others, implying an interference with signal transduction processes. Effects of lipoproteins on vasoactive substances seem to be implicated in endothelial dysfunction, too. The endothelium-derived relaxing factor nitric oxide (NO) has gained increasingly attention in the last two decades and is regarded as protective against hypertension and atherosclerosis. It was demonstrated that chylomicrons and their remnants inhibited endothelium-dependent relaxations in isolated aortas. Vasodilatatory responses and nitric oxide metabolism were shown to be affected by the amount and composition of dietary fat. Cell culture experiments revealed modulation of NO release by certain fatty acids. Plasma levels of endothelin-1, a strong vasoconstrictor, have been shown to be increased in patients with type 2 diabetes and metabolic syndrome, respectively. Postprandially elevated triglycerides increased endothelin-levels in addition to insulin in patients with metabolic syndrome. In summary, there is evidence that the association between postprandial triglycerides and the metabolic syndrome is driven by direct influences on endothelial functions because plasma triglyceride levels are associated with levels of humoral risk markers of endothelial origin, and postprandial lipoproteins stimulate the release and/or expression of endothelial mediators in vitro, which induce atherogenesis and hypertension. PMID:11453041

  18. 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 Ppar? 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 PPAR? 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

  19. Triglyceride species compositions of common edible vegetable oils and methods used for their identification and quantification

    Microsoft Academic Search

    Nikolaos K. Andrikopoulos

    2002-01-01

    The chromatographic, spectrophotometric, and spectroscopic methods used for detection, identification, and quantification of the triglyceride (TG) species present in common edible vegetable oils are reviewed. The TG species identified in each kind of oil and their percentage distributions reported in literature are presented in tabular form. Data on oils from the following 10 sources are reviewed: corn, cottonseed, grapeseed, linseed,

  20. Intramuscular triglyceride and muscle insulin sensitivity: Evidence for a relationship in nondiabetic subjects

    Microsoft Academic Search

    D. I. W. Phillips; S. Caddy; V. Ilic; B. A. Fielding; K. N. Frayn; A. C. Borthwick; R. Taylor

    1996-01-01

    Intracellular triglyceride (TG) is an important energy source for skeletal muscle. However, recent evidence suggests that if muscle contains abnormally high TG stores its sensitivity to insulin may be reduced, and this could predispose to type II diabetes. To test this hypothesis, we measured muscle lipid content in 27 women aged 47 to 55 years (mean, 52) and related it

  1. Vascular smooth muscle cells isolated from adipose triglyceride lipase-deficient mice exhibit distinct phenotype and phenotypic plasticity.

    PubMed

    Lin, Yanhui; Chiba, Shunmei; Suzuki, Akira; Yamaguchi, Satoshi; Nakanishi, Takaya; Matsumoto, Hirofumi; Ikeda, Yoshihiko; Ishibashi-Ueda, Hatsue; Hirano, Ken-ichi; Kato, Seiya

    2013-05-10

    The alteration of triglyceride (TG) metabolism in vascular smooth muscle cells (SMC) is likely to be correlated with certain phenotype, though this has not been elucidated. Adipose triglyceride lipase (ATGL) exerts major TG catalytic activity in both adipotic and non-adipotic cells. In the present study, we isolated SMC from ATGL-deficient mice (ATGL(-/-)mSMC). ATGL(-/-)mSMC showed spontaneous TG accumulation with lower mitogenic response and smooth muscle actin (SMA) expression compared to ATGL (+/+)mSMC. Percentage of senescence-associated ?-galactosidase positive cells was also increased in ATGL(-/-)mSMC. Real-time PCR followed by screening with focused DNA array analysis revealed up-regulated expression of glucokinase (1.7-fold), lipoprotein lipase (3.8-fold) and interleukin-6 (3.7-fold) and down-regulated expression of vascular endothelial growth factor-A (0.2-fold), type I collagen (0.5-fold), and transforming growth factor-? (0.4-fold) in ATGL(-/-)mSMC compared to ATGL(+/+)mSMC. Next, ectopic gene transfer of human ATGL was attempted using doxycycline (Dox)-regulatable myc-DDK-tagged adenovirus vector (AdvATGL). AdvATGL infection resulted in a reduction of TG accumulation with elevated mitogenic response and SMA expression, and decreased in senescent cell numbers in ATGL(-/-)mSMC. Moreover, deviated gene expression pattern in ATGL(-/-)mSMC was potentially corrected. Our data suggest that ATGL(-/-)mSMC have a distinct phenotype that may be related to vascular pathogenesis. Plasticity of SMC phenotypes correlated to lipid metabolism could be a therapeutic target. PMID:23583398

  2. 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-h fasted 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

  3. 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

  4. 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

  5. Effects of Glucagon and Insulin on Plasma Glucose, Triglyceride, and Triglyceride-Rich Lipoprotein Concentrations in Laying Hens Fed Diets Containing Different Types of Fats

    Microsoft Academic Search

    L. Pal; R. Grossmann; K. Dublecz; F. Husveth; L. Wagner; G. Kovacs

    The influence of dietary fat supplementa- tions differing in the ratio of n-6 to n-3 polyunsaturated fatty acids (PUFA) on the effects of glucagon and insulin on plasma glucose, triglyceride (TG), and TG-rich lipo- protein concentrations was investigated in laying hens. Birds were fed either a low-fat control diet (LF) or diets supplemented with 4% pumpkin seed oil (PO; rich

  6. Effect of bilirubin on triglyceride synthesis in streptozotocin-induced diabetic nephropathy.

    PubMed

    Xu, Jianwei; Lee, Eun Seong; Baek, Seon Ha; Ahn, Shin-Young; Kim, Sejoong; Na, Ki Young; Chae, Dong-Wan; Chin, Ho Jun

    2014-09-01

    We aimed to elucidate the effect of bilirubin on dyslipidemia and nephropathy in a diabetes mellitus (DM) type I animal model. Sprague-Dawley rats were separated into control, DM, and bilirubin-treated DM (Bil) groups. The Bil group was injected intraperitoneally with 60 mg/kg bilirubin 3 times per week and hepatoma cells were cultured with bilirubin at a concentration of 0.3 mg/dL. The Bil group showed lower serum creatinine levels 5 weeks after diabetes onset. Bilirubin treatment also decreased the amount of mesangial matrix, lowered the expression of renal collagen IV and transforming growth factor (TGF)-?1, and reduced the level of apoptosis in the kidney, compared to the DM group. These changes were accompanied by decreased tissue levels of hydrogen superoxide and NADPH oxidase subunit proteins. Bilirubin decreased serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), free fatty acids, and triglycerides (TGs), as well as the TG content in the liver tissues. Bilirubin suppressed protein expression of LXR?, SREBP-1, SCD-1, and FAS, factors involved in TG synthesis that were elevated in the livers of DM rats and hepatoma cells under high-glucose conditions. In conclusion, bilirubin attenuates renal dysfunction and dyslipidemia in diabetes by suppressing LXR? and SREBP-1 expression and oxidative stress. PMID:25317020

  7. 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 PPAR? or the constitutive activation of AMPK, the changes to TSH-triggered GPAT3 activity and adipogenesis disappeared. The over-expression of PPAR? 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/PPAR?/GPAT3 axis via the TSH receptor might serve as a potential therapeutic target for obesity. PMID:25559747

  8. 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 ...

  9. 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, Søren

    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

  10. Ethanol Extract of Fructus Schisandrae Decreases Hepatic Triglyceride Level in Mice Fed with a High Fat/Cholesterol Diet, with Attention to Acute Toxicity

    PubMed Central

    Pan, Si-Yuan; Yu, Zhi-Ling; Dong, Hang; Xiang, Chun-Jing; Fong, Wang-Fun; Ko, Kam-Ming

    2011-01-01

    Effects of the ethanol extract of Fructus Schisandrae (EtFSC) on serum and liver lipid contents were investigated in mice fed with high fat/cholesterol (HFC) diet for 8 or 15 days. The induction of hypercholesterolemia by HFC diet caused significant increases in serum and hepatic total cholesterol (TC) levels (up to 62% and 165%, resp.) and hepatic triglyceride (TG) levels (up to 528%) in mice. EtFSC treatment (1 or 5?g/kg/day for 7 days; from Day 1 to 7 or from Day 8 to 14, i.g.) significantly decreased the hepatic TG level (down to 35%) and slightly increased the hepatic index (by 8%) in hypercholesterolemic mice. Whereas fenofibrate treatment (0.1?g/kg/day for 7 days, i.g.) significantly lowered the hepatic TG level (by 61%), it elevated the hepatic index (by 77%) in hypercholesterolemic mice. Acute toxicity test showed that EtFSC was relatively non-toxic, with an LD50 value of 35.63 ± 6.46?g/kg in mice. The results indicate that EtFSC treatment can invariably decrease hepatic TG in hypercholesterolemic mice, as assessed by both preventive and therapeutic protocols, suggesting its potential use for fatty liver treatment. PMID:19592476

  11. Lipoprotein lipase deficiency is associated with elevated acylation stimulating protein plasma levels

    PubMed Central

    Paglialunga, Sabina; Julien, Pierre; Tahiri, Youssef; Cadelis, Francois; Bergeron, Jean; Gaudet, Daniel; Cianflone, Katherine

    2009-01-01

    Acylation stimulating protein (ASP, C3adesArg) is an adipose tissue derived hormone that stimulates triglyceride (TG) synthesis. ASP stimulates lipoprotein lipase (LPL) activity by relieving feedback inhibition caused by fatty acids (FA). The present study examines plasma ASP and lipids in male and female LPL-deficient subjects primarily with the P207L mutation, common in the population of Quebec, Canada. We evaluated the fasting and postprandial states of LPL heterozygotes and fasting levels in LPL homozygotes. Homozygotes displayed increased ASP (58–175% increase, P < 0.05–0.01), reduced HDL-cholesterol (64–75% decrease, P < 0.0001), and elevated levels of TG (19–38-fold, P < 0.0001) versus control (CTL) subjects. LPL heterozygotes with normal fasting TG (1.3–1.9 mmol/l) displayed increased ASP (101–137% increase, P < 0.05–0.01) and delayed TG clearance after a fatload; glucose levels remained similar to controls. Hypertriglyceridemics with no known LPL mutation also had increased ASP levels (63–192% increase, P < 0.001). High-TG LPL heterozygotes were administered a fatload before and after fibrate treatment. The treatment reduced fasting and postprandial plasma ASP, TG, and FA levels without changing insulin or glucose levels. ASP enhances adipose tissue fatty-acid trapping following a meal; however in LPL deficiency, high ASP levels are coupled with delayed lipid clearance. PMID:19237736

  12. Transcriptional regulation of human microsomal triglyceride transfer protein by hepatocyte nuclear factor-4

    Microsoft Academic Search

    Vered Sheena; Rachel Hertz; Janna Nousbeck; Ina Berman; Judith Magenheim; Jacob Bar-Tana

    2004-01-01

    Microsomal triglyceride transfer protein (MTP) catalyzes the assembly of triglyceride (TG)-rich apolipopro- tein B-containing liver (e.g., VLDL) and intestinal (e.g., chy- lomicron) lipoproteins. The human MTP gene promoter is reported here to associate in vivo with endogenous hepato- cyte nuclear factor-4 ? (HNF-4 ? ) and to be transactivated or transsuppressed by overexpressed or by dominant negative HNF-4 ? ,

  13. Acute pancreatitis owing to very high triglyceride levels treated with insulin and heparin infusion

    PubMed Central

    Aryal, Madan Raj; Mainali, Naba Raj; Gupta, Shobhit; Singla, Manoj

    2013-01-01

    Hypertriglyceridaemia is the third most common cause of acute pancreatitis in the USA. The treatment approach for hypertriglyceridaemia to date has largely been conservative including weight loss, exercise and avoidance of medications that raise triglyceride levels. This approach, however, is not practical in cases of acute pancreatitis due to severely elevated triglycerides. A small number of case reports have been published supporting the treatment of acute pancreatitis due to severely elevated triglyceride levels with insulin and heparin. We report a case of acute pancreatitis in a young woman due to a triglyceride level of 15?215?mg/dl who was successfully treated with insulin and heparin. PMID:23608843

  14. 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.

  15. Effect of prolonged exercise on the level of triglycerides in the rat liver

    Microsoft Academic Search

    Jan Górski; Miros?awa Nowacka; Zbigniew Namiot; Urszula Puch

    1988-01-01

    Summary  This study examined the effect of prolonged exercise on the level of triglycerides (TG) in rat liver. The rats were divided into groups: 1-control, 2-treated with nicotinic acid, 3-fed with glucose during exercise, 4-fasted, 5-adrenalectomized, 6-adrenalectomized and fed with oil. In the control group, there was gradual accumulation of TG in the liver and their level was doubled at exhaustion

  16. Reduced adipose tissue triglyceride synthesis and increased muscle fatty acid oxidation in C5L2 knockout mice.

    PubMed

    Paglialunga, Sabina; Schrauwen, Patrick; Roy, Christian; Moonen-Kornips, Esther; Lu, Huiling; Hesselink, Matthijs K C; Deshaies, Yves; Richard, Denis; Cianflone, Katherine

    2007-08-01

    Activation of C5L2, a G-protein-coupled receptor, by acylation-stimulating protein/complement C3adesArg (ASP/C3adesArg) has been shown to stimulate triglyceride (TG) synthesis in both mature adipocytes and preadipocytes. ASP is an adipocyte-derived hormone that acts by increasing diacylglycerol acyltransferase activity and glucose transport. ASP-deficient mice (C3KO, precursor protein) are lean, display delayed postprandial TG clearance, increased food intake, and increased energy expenditure. The present study shows that C5L2KO mice on a low fat diet are hyperphagic (~60% increase in total food intake) yet maintain the same body weight and adipose tissue mass as wild-type (WT) controls. However, on a high fat diet, average adipocyte size and adipose tissue TG/DNA content were significantly reduced and postprandial TG clearance was delayed in C5L2KO. Adipose tissue TG synthesis (WT: 47.2 +/- 5.6 versus C5L2KO: 7.8 +/- 1.8 pmol/microg protein, P < 0.001), TG lipolysis (WT: 227.6 +/- 36.4 versus C5L2KO: 45.8 +/- 5.0 nmol/microg protein, P < 0.001), and fatty acid re-esterification (WT: 85.3 +/- 2.4% versus C5L2KO: 59.5 +/- 6.8%, P < 0.001) were significantly reduced in C5L2KO mice. Indirect calorimetry measurements revealed C5L2KO mice have unchanged oxygen consumption levels yet reduced respiratory quotient value, suggesting preferential fatty acid utilization over carbohydrate. In agreement, fatty acid oxidation was elevated in heart and skeletal muscle tissue in C5L2KO mice and skeletal muscle levels of uncoupling protein 3 (425.5 +/- 86.3%, P < 0.0001), CD36 (277.6 +/- 49.5%, P < 0.05), cytochrome c (252.6 +/- 33.9%, P < 0.05), and phospho-acetyl CoA carboxylase (118.4 +/- 9.3%, P < 0.05) were significantly increased in C5L2KO mice versus WT (100%). The study shows that in response to reduced TG storage in white adipose tissue, C5L2KO mice have developed a compensatory mechanism of increased muscle fat oxidation. PMID:17641279

  17. Acute psychological stress reduces plasma triglyceride clearance.

    PubMed

    Stoney, Catherine M; West, Sheila G; Hughes, Joel W; Lentino, Lisa M; Finney, Montenique L; Falko, James; Bausserman, Linda

    2002-01-01

    Acute stress elevates blood lipids, with the largest increases among men and postmenopausal women. The mechanisms for the effect are unknown, but may be due to altered lipid metabolism. This study investigated if acute stress induces transient reductions in triglyceride clearance in middle-aged men and women, and determined if gender and menopause affect triglyceride metabolism. Of the 35 women, half were premenopausal, and half were naturally postmenopausal; men (n = 35) were age matched. Clearance of an intravenously administered fat emulsion was assessed twice: once during a nonstress session, and again during a stress-testing session. During the stress session, a battery of behavioral stressors (serial subtraction, speech, mirror tracing, and Stroop) were performed for 40 min. The clearance rate of exogenous fat was significantly diminished during the stress, relative to the nonstress session. Women had more efficient clearance, relative to men, but there were no effects of menopausal status. The diminished ability to clear an intravenous fat emulsion during stress suggests one mechanism for stress-induced elevations in lipids. PMID:12206298

  18. catabolism of triglyceride rich lipoprotein. Sev-eral studies have reported associations between

    E-print Network

    Paris-Sud XI, Université de

    serum lipid (TG, HDL) levels and restriction frag- ment length polymorphisms (RFLPs) of the LPL gene% as carbohydrates, dur- ing 3 months. Diabetic patients or patients using drugs known to modify lipid levels werecatabolism of triglyceride rich lipoprotein. Sev- eral studies have reported associations between

  19. 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. (Montana State Univ., Bozeman (USA))

    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.

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

    PubMed Central

    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.

  1. Triglyceride-to-HDL-cholesterol Ratio and Metabolic Syndrome as Contributors to Cardiovascular Risk in Overweight Patients

    Microsoft Academic Search

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

    2010-01-01

    Insulin resistance increases cardiovascular risk of obese patients. Triglyceride to high-density lipoprotein cholesterol ratio (TG\\/HDL) ?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)

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

    PubMed Central

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

    2014-01-01

    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

  3. Resistance to leptin action is the major determinant of hepatic triglyceride accumulation in vivo.

    PubMed

    Fishman, Sigal; Muzumdar, Radhika H; Atzmon, Gil; Ma, Xiaohui; Yang, Xiaoman; Einstein, Francine H; Barzilai, Nir

    2007-01-01

    Impairment of both insulin and leptin action has been implicated in the pathogenesis of nonalcoholic fatty liver disease. By assessing hepatic triglyceride (TG) stores in response to modulation of leptin action (by leptin infusion), we attempted to determine whether leptin has the major role in hepatic TG accumulation. TG were markedly decreased (by 63%, P<0.05) in young animals treated with leptin. However, this was also associated with improvement in hepatic insulin action (2-fold decrease in HGP during clamp, P<0.05). These effects on hepatic TG stores and insulin action were abolished in old rats who demonstrate leptin resistance. Since these experiments could not discern the role of leptin from the role of hepatic insulin action on hepatic TG stores, we further examined the effect of improvement of hepatic insulin action by visceral fat removal (VF-). Enhancement of hepatic insulin action in old VF-rats was associated with reduced hepatic TG stores (by 64% P<0.01). Because this manipulation may have induced an improvement in leptin action as well, we studied VF removal in a genetically leptin-resistant model (Zucker Diabetic Fatty rats, ZDF). Only in this mode was exclusive improvement of hepatic insulin action by VF removal not associated with reduced hepatic TG stores, suggesting that improved hepatic insulin action is not necessary for modulation of hepatic TG stores. By dissociating action of leptin from that of insulin, we suggest that the failure of leptin action is the major physiological mechanism for hepatic steatosis. PMID:17099068

  4. Triglycerides in fish oil affect the blood clearance of lipid emulsions containing long- and medium-chain triglycerides in mice.

    PubMed

    Qi, Kemin; Seo, Toru; Jiang, Zaifang; Carpentier, Yvon A; Deckelbaum, Richard J

    2006-11-01

    Lipid emulsions containing long-chain triglycerides (LCT) and medium chain triglycerides (MCT) are widely used in parenteral nutrition. Recently, fish oil (FO) triglyceride (TG)-derived emulsions are considered therapeutic because of their many beneficial biological modulatory actions. We investigated in mice whether adding 10% FO to an intravenous lipid emulsion with MCT and LCT (MCT:LCT:FO -50:40:10% by wt) would affect particle blood clearance and tissue targeting in comparison to LCT (100% by wt) and MCT:LCT (50:50% by wt) emulsions. The 3 emulsions were labeled with [3H] cholesteryl oleoyl ether and administered by bolus injection (400 microg TG/mouse) to C57BL/6J mice. Contributions of LDL receptor (LDL-R) and LDL-R-related protein to emulsion catabolism were assessed using LDL-R-deficient mice and preinjection of lactoferrin, and the effects of lipoprotein lipase (LPL) were determined by preinjection of heparin and Triton WR 1339. Although fractional catabolic rates did not differ among the 3 emulsions, blood removal at each time point after injection was greater for MCT:LCT:FO particles due to their higher initial margination volume. Compared with MCT:LCT and LCT emulsions, patterns of tissue uptake of the MCT:LCT:FO emulsions were different, e.g. MCT:LCT:FO emulsion particle uptake was lower in heart, adipose tissue, and muscle, and higher in lung, and the removal of MCT:LCT:FO emulsion particles was less dependent on LPL, LDL-R, and lactoferrin-sensitive pathways. These data suggest that the addition of a low percentage of FO to MCT:LCT emulsions substantially changes their particle clearance and tissue uptake mechanisms. PMID:17056798

  5. Triglycerides-based diesel fuels

    Microsoft Academic Search

    Anjana Srivastava; Ram Prasad

    2000-01-01

    Efforts are under way in many countries, including India, to search for suitable alternative diesel fuels that are environment friendly. The need to search for these fuels arises mainly from the standpoint of preserving the global environment and the concern about long-term supplies of conventional hydrocarbon-based diesel fuels. Among the different possible sources, diesel fuels derived from triglycerides (vegetable oils\\/animal

  6. Triglyceride response following an oral fat tolerance test in Burmese cats, other pedigree cats and domestic crossbred cats

    Microsoft Academic Search

    Elissa K. Kluger; Chloë Hardman; Merran Govendir; Randolph M. Baral; David R. Sullivan; David Snow; Richard Malik

    2009-01-01

    Primary lipid disorders causing fasting triglyceridaemia have been documented infrequently in Burmese cats. Due to the known increased risk of diabetes mellitus and sporadic reports of lipid aqueous in this breed, the aim of this study was to determine whether healthy Burmese cats displayed a more pronounced pre- or post-prandial triglyceridaemia compared to other cats. Serum triglyceride (TG) concentrations were

  7. Genome-wide scan for quantitative trait loci influencing LDL size and plasma triglyceride in familial hypertriglyceridemia

    Microsoft Academic Search

    Melissa A. Austin; Karen L. Edwards; Stephanie A. Monks; Kent M. Koprowicz; John D. Brunzell; Arno G. Motulsky; Michael C. Mahaney; James E. Hixson

    2003-01-01

    Small, dense LDLs and hypertriglyceridemia, two highly correlated and genetically influenced risk factors, are known to predict for risk of coronary heart disease. The ob- jective of this study was to perform a whole-genome scan for linkage to LDL size and triglyceride (TG) levels in 26 kindreds with familial hypertriglyceridemia (FHTG). LDL size was estimated using gradient gel electrophoresis, and

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

    Microsoft Academic Search

    Sébastien Vankoningsloo; Marie Piens; Christophe Lecocq; Audrey Gilson; Aurélia De Pauw; Patricia Renard; Catherine Demazy; Andrée Houbion; Martine Raes; Thierry Arnould

    2005-01-01

    Mitochondrial cytopathy has been associated with modifications of lipid metabolism in various situations, such as the acquisition of an abnormal adipocyte phenotype ob- served in multiple symmetrical lipomatosis or triglyceride (TG) accumulation in muscles associated with the myoclonic epilepsy with ragged red fibers syndrome. However, the mo- lecular signaling leading to fat metabolism dysregulation in cells with impaired mitochondrial activity

  9. Influence of light absorption rate by Nannochloropsis oculata on triglyceride production during nitrogen starvation.

    PubMed

    Kandilian, Razmig; Pruvost, Jérémy; Legrand, Jack; Pilon, Laurent

    2014-07-01

    This study aims to understand the role of light transfer in triglyceride fatty-acid (TG-FA) cell content and productivity from microalgae during nitrogen starvation. Large amounts of TG-FA can be produced via nitrogen starvation of microalgae in photobioreactors exposed to intense light. First, spectral absorption and scattering cross-sections of N. oculata were measured at different times during nitrogen starvation. They were used to relate the mean volumetric rate of energy absorption (MVREA) per unit mass of microalgae to the TG-FA productivity and cell content. TG-FA productivity correlated with the MVREA and reached a maximum for MVREA of 13 ?mol h?/gs. This indicated that TG-FA synthesis was limited by the photon absorption rate in the PBR. A minimum MVREA of 13 ?mol h?/gs was also necessary at the onset of nitrogen starvation to trigger large accumulation of TG-FA in cells. These results will be instrumental in defining protocols for TG-FA production in scaled-up photobioreactors. PMID:24835743

  10. Plasma triglyceride/HDL-cholesterol ratio, insulin resistance, and cardiometabolic risk in young adults

    PubMed Central

    Murguía-Romero, Miguel; Jiménez-Flores, J. Rafael; Sigrist-Flores, Santiago C.; Espinoza-Camacho, Miguel A.; Jiménez-Morales, Mayra; Piña, Enrique; Méndez-Cruz, A. René; Villalobos-Molina, Rafael; Reaven, Gerald M.

    2013-01-01

    Studies in mature adults suggest that the plasma concentration ratio of triglyceride (TG)/HDL-cholesterol (HDL-C) provides a simple way to identify apparently healthy individuals who are insulin resistant (IR) and at increased cardiometabolic risk. This study extends these observations by examining the clinical utility of the TG/HDL-C ratio and the metabolic syndrome (MetS) in 2,244 healthy college students (17–24 years old) of Mexican Mestizo ancestry. The TG/HDL-C ratio separating the 25% with the highest value was used to identify IR and increased cardiometabolic risk. Cardiometabolic risk factors were more adverse in men and women whose TG/HDL-C ratios exceeded 3.5 and 2.5, respectively, and approximately one third were identified as being IR. The MetS identified fewer individuals as being IR, but their risk profile was accentuated. In conclusion, both a higher TG/HDL-C ratio and a diagnosis of the MetS identify young IR individuals with an increased cardiometabolic risk profile. The TG/HDL-C ratio identified a somewhat greater number of “high risk” subjects, whereas the MetS found a group whose risk profile was somewhat magnified. These findings suggest that the TG/HDL-C ratio may serve as a simple and clinically useful approach to identify apparently healthy, young individuals who are IR and at increased cardiometabolic risk. PMID:23863983

  11. Metabolism of triglyceride-rich lipoproteins during alimentary lipemia.

    PubMed Central

    Karpe, F; Steiner, G; Olivecrona, T; Carlson, L A; Hamsten, A

    1993-01-01

    The metabolism of chylomicron remnants and VLDL was studied in healthy controls and normo- (NTG) and hypertriglyceridemic (HTG) patients with coronary artery disease after intake of an oral fat load. Specific determination of apo B-48 and B-100 enabled separation of the respective contribution of the two lipoprotein species. The postprandial plasma levels of small (Sf 20-60) and large (Sf 60-400) chylomicron remnants increased in controls and NTG patients. In contrast, only large chylomicron remnants increased in the HTG patients. An increase of large VLDL was seen in response to the oral fat load in all groups, whereas small VLDL were either unchanged in the controls and the NTG patients, or decreased in the HTG patient group. The whole plasma concentration of C apolipoproteins was essentially uninfluenced by the oral fat load, whereas the content in large triglyceride-rich lipoproteins paralleled the apo B elevations in controls and NTG patients. An even more prominent increase of apo B in large triglyceride-rich lipoproteins in the HTG group was not accompanied by an increase of C apolipoproteins. These findings indicate that chylomicrons compete with VLDL for removal of triglycerides by lipoprotein lipase and that the postprandial metabolism of triglyceride-rich lipoproteins is severely defective in hypertriglyceridemia. PMID:8450056

  12. Very long chain PUFA in murine testicular triglycerides and cholesterol esters

    Microsoft Academic Search

    Natalia E. Furland; Eduardo N. Maldonado; Marta I. Aveldaño

    2003-01-01

    Very long chain (VLC) PUFA of the n?6 and n?3 series are known to occur in mammalian testis. The aim of this work was to characterize\\u000a further two testicular lipid classes with VLCPUFA, cholesterol esters (CE) and total triglycerides (TG) in rat and mouse testis.\\u000a The VLCPUFA predominating in these lipids were a series of n?6 pentaenes and tetraenes with

  13. Modulation of plasma triglyceride levels by apoE phenotype: a meta-analysis

    Microsoft Academic Search

    J. Dallongeville; S. Lussier-Cacan; J. Davignon

    The relationship between apoE phenotype and plasma lipid levels was analyzed in the combined data of published studies. Accordingly, 45 population samples from 17 different countries were included in the analysis. The mean plasma values of cholesterol (CH), triglyceride (TG), and high density lipoprotein (HDL)-CH of the apoE 2\\/2, 3\\/2, 4\\/3, 4\\/4, and 4\\/2 groups were compared with the same

  14. Effects of dietary cholesterol and triglycerides on lipid concentrations in liver, plasma, and bile

    Microsoft Academic Search

    Michael L. Booker; Wayne W. LaMorte; Eve R. Beer; Susan R. Hopkins

    1997-01-01

    Dietary cholesterol (CHL) and triglycerides (TG) can influence plasma, hepatic, and biliary lipid composition, but effects\\u000a on lipids in these three compartments during the early stages of CHL gallstone formation have not been studied in parallel.\\u000a We fed prairie dogs diets containing one of four tes oils (safflower, coconut, olive, or menhaden) at either 5 or 40% of calories,\\u000a in

  15. Kisspeptin-10 enhanced egg production in quails associated with the increase of triglyceride synthesis in liver.

    PubMed

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

    2013-08-01

    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

  16. 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

  17. Amino acid supplementation decreases plasma and liver triglycerides in elderly

    PubMed Central

    Børsheim, Elisabet; Bui, Quynh-Uyen T.; Tissier, Sandrine; Cree, Melanie G.; Rønsen, Ola; Morio, Beatrice; Ferrando, Arny A.; Kobayashi, Hisamine; Newcomer, Bradley R.; Wolfe, Robert R.

    2009-01-01

    Objective Hypertriglyceridemia is a risk factor for coronary heart disease. The aim of this study was to determine the effect of AA supplementation on plasma, liver and muscle lipid concentrations and insulin sensitivity in elderly. Methods Twelve impaired glucose tolerant elderly (67.0 ± 5.6 (SD) years, 7 females, 5 males) ingested 11 g of essential AA + arginine twice a day for 16 weeks, after a 7 week control run in. Diet and activity were not otherwise modified. Plasma lipid concentrations and oral glucose tolerance were measured every 4th week, and tissue lipid concentrations (magnetic resonance spectroscopy) every 8th week. Results No changes in plasma lipids were observed during the control run-in. AA supplementation lowered plasma triglyceride (TG) (P < 0.001), total cholesterol (P = 0.048) and very low density lipoprotein (VLDL)-cholesterol (P < 0.001) concentrations. Plasma TG dropped ~20% from the initial value of 1.45 ± 0.18 (SE) mmol/l (128 ± 16 mg/dl), with greatest decrease in the subjects starting out with highest concentrations (r = ?0.83). Similarly, liver fat content (liver TG/intralipid standard) decreased ~50% from the initial value of 0.34 ± 0.06 (P = 0.021; n = 9), with greatest decrease in the subjects that initially had highest values (r = ?0.86). Intramuscular fat content and insulin sensitivity did not change. Conclusion Diet supplementation with AA lowers plasma TG, total cholesterol and VLDL-cholesterol concentrations, and liver lipid content in impaired glucose tolerant elderly. AA supplementation may have a potential role in treatment of hypertriglyceridemia or hepatic steatosis. PMID:19041223

  18. Mechanisms of hepatic very low density lipoprotein overproduction in insulin resistance. Evidence for enhanced lipoprotein assembly, reduced intracellular ApoB degradation, and increased microsomal triglyceride transfer protein in a fructose-fed hamster model.

    PubMed

    Taghibiglou, C; Carpentier, A; Van Iderstine, S C; Chen, B; Rudy, D; Aiton, A; Lewis, G F; Adeli, K

    2000-03-24

    A novel animal model of insulin resistance, the fructose-fed Syrian golden hamster, was employed to investigate the mechanisms mediating the overproduction of very low density lipoprotein (VLDL) in the insulin resistant state. Fructose feeding for a 2-week period induced significant hypertriglyceridemia and hyperinsulinemia, and the development of whole body insulin resistance was documented using the euglycemic-hyperinsulinemic clamp technique. In vivo Triton WR-1339 studies showed evidence of VLDL-apoB overproduction in the fructose-fed hamster. Fructose feeding induced a significant increase in cellular synthesis and secretion of total triglyceride (TG) as well as VLDL-TG by primary hamster hepatocytes. Increased TG secretion was accompanied by a 4.6-fold increase in VLDL-apoB secretion. Enhanced stability of nascent apoB in fructose-fed hepatocytes was evident in intact cells as well as in a permeabilized cell system. Analysis of newly formed lipoprotein particles in hepatic microsomes revealed significant differences in the pattern and density of lipoproteins, with hepatocytes derived from fructose-fed hamsters having higher levels of luminal lipoproteins at a density of VLDL versus controls. Immunoblot analysis of the intracellular mass of microsomal triglyceride transfer protein, a key enzyme involved in VLDL assembly, showed a striking 2.1-fold elevation in hepatocytes derived from fructose-fed versus control hamsters. Direct incubation of hamster hepatocytes with various concentrations of fructose failed to show any direct stimulation of its intracellular stability or extracellular secretion, further supporting the notion that the apoB overproduction in the fructose-fed hamster may be related to the fructose-induced insulin resistance in this animal model. In summary, hepatic VLDL-apoB overproduction in fructose-fed hamsters appears to result from increased intracellular stability of nascent apoB and an enhanced expression of MTP, which act to facilitate the assembly and secretion of apoB-containing lipoprotein particles. PMID:10722675

  19. Property analysis of triglyceride-based thermosets

    Microsoft Academic Search

    John La Scala; Richard P. Wool

    2005-01-01

    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 Flory–Stockmayer theory. Although the model predictions overestimated the cross-link density, the trends in the cross-link density predictions matched the experimental results. In both cases, the cross-link density was

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

    SciTech Connect

    Hirano, Ken-ichi, E-mail: khirano@cnt-osaka.com [Laboratory of Cardiovascular Disease, Novel, Non-Invasive, and Nutritional Therapeutics (CNT), Graduate School of Medicine, Osaka University, 6-2-3, Furuedai, Suita, Osaka 565-0874 (Japan) [Laboratory of Cardiovascular Disease, Novel, Non-Invasive, and Nutritional Therapeutics (CNT), Graduate School of Medicine, Osaka University, 6-2-3, Furuedai, Suita, Osaka 565-0874 (Japan); Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 (Japan); Tanaka, Tatsuya [Center for Medical Research and Education, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 (Japan)] [Center for Medical Research and Education, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 (Japan); Ikeda, Yoshihiko [Department of Pathology, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita 565-8565 (Japan)] [Department of Pathology, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita 565-8565 (Japan); Yamaguchi, Satoshi [Laboratory of Cardiovascular Disease, Novel, Non-Invasive, and Nutritional Therapeutics (CNT), Graduate School of Medicine, Osaka University, 6-2-3, Furuedai, Suita, Osaka 565-0874 (Japan) [Laboratory of Cardiovascular Disease, Novel, Non-Invasive, and Nutritional Therapeutics (CNT), Graduate School of Medicine, Osaka University, 6-2-3, Furuedai, Suita, Osaka 565-0874 (Japan); Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 (Japan); Zaima, Nobuhiro [Department of Applied Biochemistry, Kinki University, 3327-204, Nakamachi, Nara 631-8505 (Japan)] [Department of Applied Biochemistry, Kinki University, 3327-204, Nakamachi, Nara 631-8505 (Japan); Kobayashi, Kazuhiro [Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan)] [Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Suzuki, Akira [Laboratory of Cardiovascular Disease, Novel, Non-Invasive, and Nutritional Therapeutics (CNT), Graduate School of Medicine, Osaka University, 6-2-3, Furuedai, Suita, Osaka 565-0874 (Japan) [Laboratory of Cardiovascular Disease, Novel, Non-Invasive, and Nutritional Therapeutics (CNT), Graduate School of Medicine, Osaka University, 6-2-3, Furuedai, Suita, Osaka 565-0874 (Japan); Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 (Japan); Sakata, Yasuhiko [Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 (Japan) [Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 (Japan); Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1, Seiryo-cho, Aoba-ku, Sendai 980-8574 (Japan); and others

    2014-01-10

    Highlights: •Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare severe heart disease. •PPAR? 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 PPAR? 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.

  1. 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.

  2. Very-low-density lipoprotein triglyceride kinetics in acute and chronic carbohydrate-fed rats

    SciTech Connect

    Hirano, T.; Mamo, J.; Poapst, M.; Steiner, G.

    1988-09-01

    Very-low-density lipoprotein (VLDL)-triglyceride (TG) kinetics were examined in rats maintained on either chow and water (control) or chow and a 10% carbohydrate drinking solution (fructose or glucose). The hexose solutions were available for an acute (16 h) or chronic (14 day) period. The acute fructose (AF), acute glucose (AG), and chronic fructose (CF) groups were hypertriglyceridemic (HTG) compared with control. Plasma TG concentration in chronic glucose (CG)-fed rats was similar to control. VLDL-TG was endogenously radiolabeled in donor rats with (2-3H)-glycerol. The fractional catabolic rate (FCR) was then determined by monitoring the clearance of plasma (3H)VLDL-TG in recipient animals. Donors and recipients were treated in an identical manner. AF and CF groups had an FCR significantly lower than rats given glucose for comparable periods. Both fructose groups and the AG group also had a lower FCR than control. In contrast, FCR in the CG group was significantly higher than controls. TG production rate (TGPR) in both AF and CF fed rats did not significantly differ from controls, suggesting that the HTG observed in these animals was solely from a catabolic defect. AG- and CG-treated glucose animals both had TGPR significantly higher than controls. Therefore, overproduction of VLDL-TG contributed to the HTG associated with this carbohydrate.

  3. Intestinal DGAT1 deficiency reduces postprandial triglyceride and retinyl ester excursions by inhibiting chylomicron secretion and delaying gastric emptying

    PubMed Central

    Ables, Gene P.; Yang, Kryscilla Jian Zhang; Vogel, Silke; Hernandez-Ono, Antonio; Yu, Shuiqing; Yuen, Jason J.; Birtles, Susan; Buckett, Linda K.; Turnbull, Andrew V.; Goldberg, Ira J.; Blaner, William S.; Huang, Li-Shin; Ginsberg, Henry N.

    2012-01-01

    Acyl CoA:diacylglycerol acyltransferase (DGAT) 1 catalyzes the final step of triglyceride (TG) synthesis. We show that acute administration of a DGAT1 inhibitor (DGAT1i) by oral gavage or genetic deletion of intestinal Dgat1 (intestine-Dgat1?/?) markedly reduced postprandial plasma TG and retinyl ester excursions by inhibiting chylomicron secretion in mice. Loss of DGAT1 activity did not affect the efficiency of retinol esterification, but it did reduce TG and retinoid accumulation in the small intestine. In contrast, inhibition of microsomal triglyceride transfer protein (MTP) reduced chylomicron secretion after oral fat/retinol loads, but with accumulation of dietary TG and retinoids in the small intestine. Lack of intestinal accumulation of TG and retinoids in DGAT1i-treated or intestine-Dgat1?/? mice resulted, in part, from delayed gastric emptying associated with increased plasma levels of glucagon-like peptide (GLP)-1. However, neither bypassing the stomach through duodenal oil injection nor inhibiting the receptor for GLP-1 normalized postprandial TG or retinyl esters excursions in the absence of DGAT1 activity. In summary, intestinal DGAT1 inhibition or deficiency acutely delayed gastric emptying and inhibited chylomicron secretion; however, the latter occurred when gastric emptying was normal or when lipid was administered directly into the small intestine. Long-term hepatic retinoid metabolism was not impacted by DGAT1 inhibition. PMID:22911105

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

    Microsoft Academic Search

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

    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.AimsTo determine the TG content and long chain fatty acyl CoA composition profile in liver from obese non-diabetic insulin resistant (IR) and lean insulin

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

    PubMed

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

    2015-07-01

    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

  6. Proliferation, differentiation and amyloid-? production in neural progenitor cells isolated from TgCRND8 mice.

    PubMed

    Kanemoto, S; Griffin, J; Markham-Coultes, K; Aubert, I; Tandon, A; George-Hyslop, P S; Fraser, P E

    2014-03-01

    The amyloid precursor protein (APP) and amyloid-? (A?) peptide play central roles in the pathology and etiology of Alzheimer's disease. Amyloid-induced impairments in neurogenesis have been investigated in several transgenic mouse models but the mechanism of action remains to be conclusively demonstrated. The changes in neurogenesis during this transition of increasing A? levels and plaque formation were investigated in the present study. We found that the proliferation of newborn cell in the dentate gyrus was enhanced prior to elevations in soluble A? production as well as amyloid deposition in 5-week-old TgCRND8 mice, which are well-established Alzheimer's disease models, compared to non-transgenic (Non-Tg) mice. The number of BrdU-positive cells remained higher in TgCRND8 vs Non-Tg mice for a period of 8weeks. The numbers of BrdU/NeuN-positive cells were not significantly different in TgCRND8 compared to Non-Tg mice. A significant decrease in BrdU/GFAP but not in BrdU/S100? was found in Tg vs Non-Tg at 6-weeks of age. In addition, a unique observation was made using isolated neuroprogenitor cells from TgCRND8 mice which were found to be less viable in culture and produced substantial amounts of secreted A? peptides. This suggests that the proliferation of neural progenitors in vivo may be modulated by high levels of APP expression and the resulting A? generated directly by the progenitor cells. These findings indicate that cell proliferation is increased prior to A? deposition and that cell viability is decreased in TgCRND8 mice over time. PMID:24361736

  7. 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

  8. Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis.

    PubMed

    Wang, Yan; Quagliarini, Fabiana; Gusarova, Viktoria; Gromada, Jesper; Valenzuela, David M; Cohen, Jonathan C; Hobbs, Helen H

    2013-10-01

    Angiopoietin-like protein (ANGPTL)8 (alternatively called TD26, RIFL, Lipasin, and Betatrophin) is a newly recognized ANGPTL family member that has been implicated in both triglyceride (TG) and glucose metabolism. Hepatic overexpression of ANGPTL8 causes hypertriglyceridemia and increased insulin secretion. Here we examined the effects of inactivating Angptl8 on TG and glucose metabolism in mice. Angptl8 knockout (Angptl8(-/-)) mice gained weight more slowly than wild-type littermates due to a selective reduction in adipose tissue accretion. Plasma levels of TGs of the Angptl8(-/-) mice were similar to wild-type animals in the fasted state but paradoxically decreased after refeeding. The lower TG levels were associated with both a reduction in very low density lipoprotein secretion and an increase in lipoprotein lipase (LPL) activity. Despite the increase in LPL activity, the uptake of very low density lipoprotein-TG is markedly reduced in adipose tissue but preserved in hearts of fed Angptl8(-/-) mice. Taken together, these data indicate that ANGPTL8 plays a key role in the metabolic transition between fasting and refeeding; it is required to direct fatty acids to adipose tissue for storage in the fed state. Finally, glucose and insulin tolerance testing revealed no alterations in glucose homeostasis in mice fed either a chow or high fat diet. Thus, although absence of ANGPTL8 profoundly disrupts TG metabolism, we found no evidence that it is required for maintenance of glucose homeostasis. PMID:24043787

  9. Effects of glucagon and insulin on plasma glucose, triglyceride, and triglyceride-rich lipoprotein concentrations in laying hens fed diets containing different types of fats.

    PubMed

    Pál, L; Grossmann, R; Dublecz, K; Husvéth, F; Wagner, L; Bartos, A; Kovács, G

    2002-11-01

    The influence of dietary fat supplementations differing in the ratio of n-6 to n-3 polyunsaturated fatty acids (PUFA) on the effects of glucagon and insulin on plasma glucose, triglyceride (TG), and TG-rich lipoprotein concentrations was investigated in laying hens. Birds were fed either a low-fat control diet (LF) or diets supplemented with 4% pumpkin seed oil (PO; rich in n-6 PUFA) or 4% cod liver oil (CO; rich in n-3 PUFA). After 4 wk feeding of the experimental diets, hens were implanted with wing vein catheters and injected with porcine glucagon (20 microg/kg BW) and porcine insulin (0.5 IU/kg BW), 2 to 5 h after oviposition. Plasma glucose, TG, and TG-rich lipoprotein concentrations were determined from 10 min pre-injection to 60 min post-injection. PO diet resulted in a prolonged plasma glucose response to glucagon administration and altered hypoglycemic response to insulin. However, CO diet did not influence plasma glucose response to either glucagon or insulin administration compared to LF diet. The effects of glucagon and insulin on plasma TG and TG-rich lipoproteins were similar for all diets regardless of the amount or type of fat. The results suggest that feeding dietary fats with high n-6 to n-3 PUFA ratio alters the glucagon and insulin sensitivity of plasma glucose in laying hens. Fats rich in n-3 PUFA seem to have no influence on the plasma glucose response to glucagon and insulin. PMID:12455597

  10. 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

  11. Acute effects of exercise and calorie restriction on triglyceride metabolism in women

    PubMed Central

    Bellou, Elena; Siopi, Aikaterina; Galani, Maria; Maraki, Maria; Tsekouras, Yiannis E.; Panagiotakos, Demosthenes B.; Kavouras, Stavros A.; Magkos, Faidon; Sidossis, Labros S.

    2013-01-01

    The mechanisms by which exercise reduces fasting plasma triglyceride (TG) concentrations in women and the effect of negative energy balance independent of muscular contraction are not known. Purpose The aim of this study was to evaluate the effects of equivalent energy deficits induced by exercise or calorie restriction on basal very low-density lipoprotein (VLDL) TG metabolism in women. Methods Eleven healthy women (age: 23.5±2.7 years, BMI: 21.6±1.4 kg/m2) underwent a stable isotopically labeled tracer infusion study to determine basal VLDL-TG kinetics after performing, in random order, three experimental trials on the previous day: i) a single exercise bout (brisk walking at 60% of peak oxygen consumption for 123±18 min, with a net energy expenditure of 2.06±0.39 MJ (~500 kcal)), ii) dietary energy restriction of 2.10±0.41 MJ, and iii) a control day of isocaloric feeding and rest (zero energy balance). Results Fasting plasma VLDL-TG concentration was ~30% lower after the exercise trial compared to the control trial (P<0.001), whereas no significant change was detected after the calorie restriction trial (P=0.297 vs control). Relative to the control condition, exercise increased the plasma clearance rate of VLDL-TG by 22% (P=0.001) and reduced hepatic VLDL-TG secretion rate by ~17% (P=0.042), whereas hypocaloric diet had no effect on VLDL-TG kinetics (P>0.2). Conclusion (i) Exercise-induced hypotriglyceridemia in women manifests through a different mechanism (increased clearance and decreased secretion of VLDL-TG) than that previously described in men (increased clearance of VLDL-TG only), and (ii) exercise affects TG homeostasis by eliciting changes in VLDL-TG kinetics that cannot be reproduced by an equivalent diet-induced energy deficit, indicating that these changes are independent of the exercise-induced negative energy balance but instead are specific to muscular contraction. PMID:23073216

  12. Decrease in hepatic very-low-density lipoprotein–triglyceride secretion after weight loss is inversely associated with changes in circulating leptin

    PubMed Central

    Magkos, Faidon; Fabbrini, Elisa; McCrea, Jennifer; Patterson, Bruce W.; Eagon, J. Christopher; Klein, Samuel

    2012-01-01

    Aim Although weight loss usually decreases very-low-density lipoprotein–triglyceride (VLDL-TG) secretion rate, the change in VLDL-TG kinetics is not directly related to the change in body weight. Circulating leptin also declines with weight loss and can affect hepatic lipid metabolism. The aim of this study was to determine whether circulating leptin is associated with weight loss-induced changes in VLDL-TG secretion. Methods Ten extremely obese subjects were studied. VLDL-TG secretion rate and the contribution of systemic (derived from lipolysis of subcutaneous adipose tissue TG) and nonsystemic fatty acids (derived primarily from lipolysis of intrahepatic and intraperitoneal TG, and de novo lipogenesis) to VLDL-TG production were determined by using stable isotopically-labeled tracer methods before and 1 y after gastric bypass surgery. Results Subjects lost 33±12% of body weight, and VLDL-TG secretion rate decreased by 46±23% (p=0.001), primarily due to a decrease in the secretion of VLDL-TG from nonsystemic fatty acids (p=0.002). Changes in VLDL-TG secretion rates were not significantly related to reductions in body weight, body mass index, plasma palmitate flux, free fatty acid or insulin concentrations. The change in VLDL-TG secretion was inversely correlated with the change in plasma leptin concentration (r=?0.72, p=0.013), due to a negative association between changes in leptin and VLDL-TG secretion from nonsystemic fatty acids (r=?0.95, p<0.001). Conclusions Weight loss-induced changes in plasma leptin concentration are inversely associated with changes in VLDL-TG secretion rate. Additional studies are needed to determine whether the correlation between circulating leptin and VLDL-TG secretion represents a cause-and-effect relationship. PMID:20590733

  13. SCD1 activity in muscle increases triglyceride PUFA content, exercise capacity, and PPAR? expression in mice.

    PubMed

    Rogowski, Michael P; Flowers, Matthew T; Stamatikos, Alexis D; Ntambi, James M; Paton, Chad M

    2013-10-01

    Stearoyl-CoA desaturase (SCD)1 converts saturated fatty acids into monounsaturated fatty acids. Using muscle overexpression, we sought to determine the role of SCD1 expression in glucose and lipid metabolism and its effects on exercise capacity in mice. Wild-type C57Bl/6 (WT) and SCD1 muscle transgenic (SCD1-Tg) mice were generated, and expression of the SCD1 transgene was restricted to skeletal muscle. SCD1 overexpression was associated with increased triglyceride (TG) content. The fatty acid composition of the muscle revealed a significant increase in polyunsaturated fatty acid (PUFA) content of TG, including linoleate (18:2n6). Untrained SCD1-Tg mice also displayed significantly increased treadmill exercise capacity (WT = 6.6 ± 3 min, Tg = 71.9 ± 9.5 min; P = 0.0009). SCD1-Tg mice had decreased fasting plasma glucose, glucose transporter (GLUT)1 mRNA, fatty acid oxidation, mitochondrial content, and increased peroxisome proliferator-activated receptor (PPAR)? and Pgc-1 protein expression in skeletal muscle. In vitro studies in C2C12 myocytes revealed that linoleate (18:2n6) and not oleate (18:1n9) caused a 3-fold increase in PPAR? and a 9-fold increase in CPT-1b with a subsequent increase in fat oxidation. The present model suggests that increasing delta-9 desaturase activity of muscle increases metabolic function, exercise capacity, and lipid oxidation likely through increased PUFA content, which increases PPAR? expression and activity. However, the mechanism of action that results in increased PUFA content of SCD1-Tg mice remains to be elucidated. PMID:23918045

  14. Perfusion of hearts with triglyceride-rich particles reproduces the metabolic abnormalities in lipotoxic cardiomyopathy.

    PubMed

    Pillutla, Priya; Hwang, Yuying C; Augustus, Ayanna; Yokoyama, Masayoshi; Yagyu, Hiroaki; Johnston, Thomas P; Kaneko, Michiyo; Ramasamy, Ravichandran; Goldberg, Ira J

    2005-06-01

    Hearts with overexpression of anchored lipoprotein lipase (LpL) by cardiomyocytes (hLpL(GPI) mice) develop a lipotoxic cardiomyopathy. To characterize cardiac fatty acid (FA) and triglyceride (TG) metabolism in these mice and to determine whether changes in lipid metabolism precede cardiac dysfunction, hearts from young mice were perfused in Langendorff mode with [14C]palmitate. In hLpL(GPI) hearts, FA uptake and oxidation were decreased by 59 and 82%, respectively. This suggests reliance on an alternative energy source, such as TG. Indeed, these hearts oxidized 88% more TG. Hearts from young hLpL(GPI) mice also had greater uptake of intravenously injected cholesteryl ester-labeled Intralipid and VLDL. To determine whether perfusion of normal hearts would mimic the metabolic alterations found in hLpL(GPI) mouse hearts, wild-type hearts were perfused with [14C]palmitate and either human VLDL or Intralipid (0.4 mM TG). Both sources of TG reduced [14C]palmitate uptake (48% with VLDL and 45% with Intralipid) and FA oxidation (71% with VLDL and 65% with Intralipid). Addition of either heparin or LpL inhibitor P407 to Intralipid-containing perfusate restored [14C]palmitate uptake and confirmed that Intralipid inhibition requires local LpL. Our data demonstrate that reduced FA uptake and oxidation occur before mechanical dysfunction in hLpL(GPI) lipotoxicity. This physiology is reproduced with perfusion of hearts with TG-containing particles. Together, the results demonstrate that cardiac uptake of TG-derived FA reduces utilization of albumin-FA. PMID:15701679

  15. Independent Effects of Testosterone on Lipid Oxidation and VLDL-TG Production

    PubMed Central

    Høst, Christian; Gormsen, Lars C.; Christensen, Britt; Jessen, Niels; Hougaard, David M.; Christiansen, Jens S.; Pedersen, Steen B.; Jensen, Michael D.; Nielsen, Søren; Gravholt, Claus H.

    2013-01-01

    Low testosterone (T) levels in men have been shown to predict development of the metabolic syndrome, but the effects of T on lipid metabolism are incompletely understood. In a randomized, double-blind, placebo-controlled, crossover study, 12 healthy, young males received gonadotropin-releasing hormone agonist treatment 1 month prior to 3 of 4 trial days to induce castrate levels of T. On trial days, T gel was applied to the body containing either high or low physiological T dose or placebo. On the 4th trial day, participants constituted their own eugonadal controls. Each study comprised a 5-h basal period and a 3-h hyperinsulinemic-euglycemic clamp. Short-term hypogonadism did not affect VLDL triglyceride (TG) secretion, nor did it affect VLDL-TG concentrations. It was, however, characterized by lower total lipid oxidation. In addition, acute rescue with high physiological T increased VLDL-TG secretion during both basal and clamp conditions. These data show that T can act through fast nongenomic pathways in the liver. In addition, the early hypogonadal state is characterized by decreased total lipid oxidation, but whether these changes represent early hypogonadal metabolic dysfunction warrants further investigations. T is not a major determinant of resting VLDL-TG kinetics in men. PMID:23193189

  16. Quantitative gas-liquid chromatography of triglycerides

    Microsoft Academic Search

    Carter Litchfield; R. D. Harlow; Raymond Reiser

    1965-01-01

    To determine optimum operating conditions, an extensive study was made of the variables affecting quantitative recovery and\\u000a resolution of model triglyceride mixtures. Parameters investigated included: flash heater temperature, carrier gas flow rate,\\u000a type of carrier gas, column length, glass and metal columns, temperature program rate, linearity of detector response, physical\\u000a design of gas chromatograph, and molecular species of triglyceride.\\u000a \\u000a Results

  17. 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 GSK3? 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 PPAR? protein expression (p<0.05). Rosiglitazone and p-AKT inhibitor counteracted the positive effect of n-3 TG; GSK3? 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

  18. Triglyceride enrichment of HDL enhances in vivo metabolic clearance of HDL apo A-I in healthy men

    PubMed Central

    Lamarche, Benoît; Uffelman, Kristine D.; Carpentier, André; Cohn, Jeffrey S.; Steiner, George; Barrett, P. Hugh; Lewis, Gary F.

    1999-01-01

    Triglyceride (TG) enrichment of HDL resulting from cholesteryl ester transfer protein–mediated exchange with TG-rich lipoproteins may enhance the lipolytic transformation and subsequent metabolic clearance of HDL particles in hypertriglyceridemic states. The present study investigates the effect of TG enrichment of HDL on the clearance of HDL-associated apo A-I in humans. HDL was isolated from plasma of six normolipidemic men (mean age: 29.7 ± 2.7 years) in the fasting state and after a five-hour intravenous infusion with a synthetic TG emulsion, Intralipid. Intralipid infusion resulted in a 2.1-fold increase in the TG content of HDL. Each tracer was then whole-labeled with 125I or 131I and injected intravenously into the subject. Apo A-I in TG-enriched HDL was cleared 26% more rapidly than apo A-I in fasting HDL. A strong correlation between the Intralipid-induced increase in the TG content of HDL and the increase in HDL apo A-I fractional catabolic rate reinforced the importance of TG enrichment of HDL in enhancing its metabolic clearance. HDL was separated further into lipoproteins containing apo A-II (LpAI:AII) and those without apo A-II (LpAI). Results revealed that the enhanced clearance of apo A-I from TG-enriched HDL could be largely attributed to differences in the clearance of LpAI but not LpAI:AII. This is, to our knowledge, the first direct demonstration in humans that TG enrichment of HDL enhances the clearance of HDL apo A-I from the circulation. This phenomenon could provide an important mechanism explaining how HDL apo A-I and HDL cholesterol are lowered in hypertriglyceridemic states. PMID:10207171

  19. Cosmological applications of F (T ,TG) gravity

    NASA Astrophysics Data System (ADS)

    Kofinas, Georgios; Saridakis, Emmanuel N.

    2014-10-01

    We investigate the cosmological applications of F (T ,TG) gravity, which is a novel modified gravitational theory based on the torsion invariant T and the teleparallel equivalent of the Gauss-Bonnet term TG. F (T ,TG) gravity differs from both F (T ) theories as well as from F (R ,G ) class of curvature modified gravity, and thus its corresponding cosmology proves to be very interesting. In particular, it provides a unified description of the cosmological history from early-times inflation to late-times self-acceleration, without the inclusion of a cosmological constant. Moreover, the dark energy equation-of-state parameter can be quintessence or phantomlike, or experience the phantom-divide crossing, depending on the parameters of the model.

  20. Applications of chromatographic techniques to evaluate enzymatic hydrolysis of oxidized and polymeric triglycerides by pancreatic lipase in vitro

    Microsoft Academic Search

    G. Márquez-Ruiz; G. Guevel; M. C. Dobarganes

    1998-01-01

    With the aim of studying the susceptibility to enzymatic hydrolysis of oxidized and polymeric triglycerides (TG) that are\\u000a formed during frying, various chromatographic techniques were applied in combination, i.e., adsorption chromatography, high-performance\\u000a size-exclusion chromatography (HPSEC), and thin-layer chromatography-flame ionization detection (TLC-FID). Polar fractions,\\u000a isolated by adsorption chromatography from thermoxidized trilinolein as model system, and real used frying fats and oils,

  1. Triglyceride, total and 2-position fatty acid composition of Cornicabra virgin olive oil: Comparison with other Spanish cultivars

    Microsoft Academic Search

    F Aranda; S Gómez-Alonso; R. M Rivera del Álamo; M. D Salvador; G Fregapane

    2004-01-01

    The main triglycerides (TG) found in the Cornicabra virgin olive oil variety samples analyzed (n=224, from 1995\\/96 to 1999\\/2000 crop seasons) were OOO, SOL+POO, OLO+LnPP and OLA+SOO, as expected from the high oleic acid and low linoleic and linolenic acid contents observed for both the total and sn-2 position fatty acids (FA); these accounted for more than 85% of the

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

    PubMed

    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. 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

  4. Changes in Hepatic Microsomal Triglyceride Transfer Protein and Triglyceride in Periparturient Dairy Cattle

    Microsoft Academic Search

    D. R. Bremmer; S. J. Bertics; S. A. Besong; R. R. Grummer

    2000-01-01

    We determined the relationship between micro- somal triglyceride transfer protein (MTP) (activity, mass, and mRNA) and liver triglyceride concentration in 16 dairy cows (13 multiparous and three primipa- rous) from 27 d before expected calving (d -27) to 35 d postpartum (d 35), the time period when fatty liver is most likely to develop. In addition, dry matter intake, plasma

  5. Differences in the Triglyceride to HDL-Cholesterol Ratio between Palestinian and Israeli Adults

    PubMed Central

    Weiss, Ram; Nassar, Hisham; Sinnreich, Ronit; Kark, Jeremy D.

    2015-01-01

    Aims To evaluate differences in the triglyceride to HDL-cholesterol ratio (TG/HDL), thought to be a proxy measure of insulin resistance, between Palestinian and Israeli adults in view of the greater incidence of coronary heart disease and high prevalence of diabetes in Palestinian Arabs. Research Methods A population-based observational prevalence study of cardiovascular and diabetes risk factors in Jerusalem. Participants (968 Palestinians, 707 Israelis, sampled at ages 25-74 years) underwent fasting and 2h post-75g oral challenge plasma glucose determinations. Metabolic risk was assessed using the surrogate index TG/HDL. Sex-specific comparisons were stratified by categories of body mass index and sex-specific waist circumference quartiles, adjusted by regression for age, glucose tolerance status and use of statins. Results Prevalence of overweight and obesity was substantially larger in Palestinians (p = 0.005). Prevalence of diabetes was 2.4 and 4 fold higher among Palestinian men and women, respectively (p<0.001). Adjusted TG/HDL was higher in Palestinians than Israelis across BMI and waist circumference categories (p<0.001 for both). Higher TG/HDL in Palestinians persisted in analyses restricted to participants with normal glucose tolerance and off statins. Notably, higher TG/HDL among Palestinians prevailed at a young age (25-44 years) and in normal weight individuals of both sexes. Conclusions Palestinians have a higher TG/HDL ratio than Israelis. Notably, this is evident also in young, healthy and normal weight participants. These findings indicate the need to study the determinants of this biomarker and other measures of insulin resistance in urban Arab populations and to focus research attention on earlier ages: childhood and prenatal stages of development. PMID:25635396

  6. 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

  7. 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

  8. Using high dose omega-3 fatty acid supplements to lower triglyceride levels in 10–19 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 10–19 years with TG levels 150–1000 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. Influences of APOA5 Variants on Plasma Triglyceride Levels in Uyghur Population

    PubMed Central

    Wang, Yi; Wu, Di; Jin, Li; Wang, Xiaofeng

    2014-01-01

    Objective Single nucleotide polymorphisms (SNPs) in apolipoprotein A5 (APOA5) gene are associated with triglyceride (TG) levels. However, the minor allele frequencies and linkage disequilibriums (LDs) of the SNPs in addition to their effects on TG levels vary greatly between Caucasians and East Asians. The distributions of the SNPs/haplotypes and their associations with TG levels in Uyghur population, an admixture population of Caucasians and East Asians, have not been reported to date. Here, we performed a cross-sectional study to address these. Methods Genotyping of four SNPs in APOA5 (rs662799, rs3135506, rs2075291, and rs2266788) was performed in 1174 unrelated Uyghur subjects. SNP/haplotype and TG association analyses were conducted. Results The frequencies of the SNPs in Uyghurs were in between those in Caucasians and East Asians. The LD between rs662799 and rs2266788 in Uyghurs was stronger than that in East Asians but weaker than that in Caucasians, and the four SNPs resulted in four haplotypes (TGGT, CGGC, TCGT, and CGTT arranged in the order of rs662799, rs3135506, rs2075291, and rs2266788) representing 99.2% of the population. All the four SNPs were significantly associated with TG levels. Compared with non-carriers, carriers of rs662799-C, rs3135506-C, rs2075291-T, and rs2266788-C alleles had 16.0%, 15.1%, 17.1%, and 12.4% higher TG levels, respectively. When haplotype TGGT was defined as the reference, the haplotypes CGGC, TCGT, and CGTT resulted in 16.1%, 19.0%, and 19.8% higher TG levels, respectively. The proportions of variance in TG explained by APOA5 locus were 2.5%, 0.3%, 0.4%, and 1.9% for single SNP rs662799, rs3135506, rs2075291, and rs2266788, respectively, and 3.0% for the haplotypes constructed by them. Conclusions The association profiles between the SNPs and haplotypes at APOA5 locus and TG levels in this admixture population differed from those in Caucasians and East Asians. The functions of these SNPs and haplotypes need to be elucidated comprehensively. PMID:25313938

  10. Plasma triglyceride secretion in squirrel monkeys: effects of nicotine.

    PubMed

    Topping, D L; Turner, D M

    1975-01-01

    The acute effects of intravenous nicotine on the appearance of plasma triglycerides have been studied in anaesthetised squirrel monkeys given Triton-WR 1339. At both dose levels studied, 4 and 10 mug/kg/30 sec, nicotine caused a stimulation in the rate of accumulation of plasma glycerides, the larger dose producing the greater effect. Nicotine caused a transient elevation in plasma free fatty acids (FFA), also in proportion to the dose given. It is suggested the changes in plasma glycerides are due to enhanced hepatic secretion secondary to increased plasma FFA. The administration of Triton-WR 1339 caused a rapid and sustained fall in plasma cholesterol concentrations. This fall was similar to that observed in plasma Triton and evidence is presented to suggest that Triton and cholesterol are removed from the circulation by a similar mechanism. There was no effect of nicotine on plasma cholesterol. The implications of the effects of nicotine of plasma triglycerides in relation to coronary heart disease are discussed briefly. PMID:809729

  11. 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

  12. The GCKR rs780094 polymorphism is associated with susceptibility of type 2 diabetes, reduced fasting plasma glucose levels, increased triglycerides levels and lower HOMA-IR in Japanese population

    Microsoft Academic Search

    Hiroshi Onuma; Yasuharu Tabara; Ryuichi Kawamoto; Ikki Shimizu; Ryoichi Kawamura; Yasunori Takata; Wataru Nishida; Jun Ohashi; Tetsuro Miki; Katsuhiko Kohara; Hideichi Makino; Haruhiko Osawa

    2010-01-01

    It was recently reported that GCKR rs780094 was associated with fasting plasma glucose (FPG) and triglyceride (TG) levels in various ethnic populations (A allele for low FPG and high TG). An association between GCKR rs780094 and type 2 diabetes mellitus (T2DM) (A allele for low risk) has also been reported. We examined the association between GCKR rs780094 and T2DM in

  13. 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

  14. 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

  15. Adipose triglyceride lipase regulates lipid metabolism in dairy goat mammary epithelial cells.

    PubMed

    Li, Jun; Luo, Jun; Wang, Hui; Shi, Hengbo; Zhu, Jiangjiang; Sun, Yuting; Yu, Kang; Yao, Dawei

    2015-01-01

    Adipose triglyceride lipase (ATGL) catalyzes the initial step in the lipid lipolysis process, hydrolyzing triglyceride (TG) to produce diacylglycerol (DG) and free fatty acids (FFA). In addition, ATGL regulates lipid storage and release in adipocyte cells. However, its role in mammary gland tissue remains unclear. To assess the role of the ATGL gene in the goat mammary gland, this study analyzed the tissue distribution and expression of key genes together with lipid accumulation after knockdown of the ATGL gene. The mRNA of ATGL was highly expressed in subcutaneous adipose tissue, the lung and the mammary gland with a significant increase in expression during the lactation period compared with the dry period of the mammary gland. Knockdown of the ATGL gene in goat mammary epithelial cells (GMECs) using siRNA resulted in a significant decrease in both ATGL mRNA and protein levels. Silencing of the ATGL gene markedly increased lipid droplet accumulation and intracellular TG concentration (P<0.05), while it reduced FFA levels in GMECs (P<0.05). Additionally, the expression of HSL for lipolysis, FABP3 for fatty acid transport, PPAR? for fatty acid oxidation, ADFP, BTN1A1, and XDH for milk fat formation and secretion was down-regulated (P<0.05) after knockdown of the ATGL gene, with increased expression of CD36 for fatty acid uptake (P<0.05). In conclusion, these data suggest that the ATGL gene plays an important role in triglyceride lipolysis in GMECs and provides the first experimental evidence that ATGL may be involved in lipid metabolism during lactation. PMID:25307872

  16. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...DEVICES Clinical Chemistry Test Systems § 862.1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended to...lipid metabolism, or various endocrine disorders. (b)...

  17. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...DEVICES Clinical Chemistry Test Systems § 862.1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended to...lipid metabolism, or various endocrine disorders. (b)...

  18. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...DEVICES Clinical Chemistry Test Systems § 862.1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended to...lipid metabolism, or various endocrine disorders. (b)...

  19. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...DEVICES Clinical Chemistry Test Systems § 862.1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended to...lipid metabolism, or various endocrine disorders. (b)...

  20. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...DEVICES Clinical Chemistry Test Systems § 862.1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended to...lipid metabolism, or various endocrine disorders. (b)...

  1. 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)

  2. Roles of plasma interleukin-6 and tumor necrosis factor-? and FFA and TG in the development of insulin resistance induced by high-fat diet

    Microsoft Academic Search

    Kai Jiao; Hailong Liu; Jiankang Chen; Dengmei Tian; Junfeng Hou; Alan D. Kaye

    2008-01-01

    The role of adipokines in development of insulin resistance still remains controversial. The purpose of the present study was to examine the dynamic changes of fasting plasma levels of interleukin-6 (IL-6), tumor necrosis factor-? (TNF-?), free fatty acids (FFA) and insulin in a Sprague–Dawley rat insulin resistant model induced by high-fat diet. Heterotopic deposition of triglycerides (TG) in liver, skeletal

  3. Medium chain triglycerides and structured lipids

    Microsoft Academic Search

    Vigen K. Babayan

    1987-01-01

    Lipids are an essential component of our body composition and necessary in our daily food intake. Conventional fats and oils\\u000a are composed of glycerides of long chain fatty acids and are designated as long chain triglycerides (LCT). Body fat as well\\u000a as the fats and oils in our daily intake fall into this category. In enteral and parenteral hyperalimentation, we

  4. High glucose levels reduce fatty acid oxidation and increase triglyceride accumulation in human placenta.

    PubMed

    Visiedo, Francisco; Bugatto, Fernando; Sánchez, Viviana; Cózar-Castellano, Irene; Bartha, Jose L; Perdomo, Germán

    2013-07-15

    Placentas of women with gestational diabetes mellitus (GDM) exhibit an altered lipid metabolism. The mechanism by which GDM is linked to alterations in placental lipid metabolism remains obscure. We hypothesized that high glucose levels reduce mitochondrial fatty acid oxidation (FAO) and increase triglyceride accumulation in human placenta. To test this hypothesis, we measured FAO, fatty acid esterification, de novo fatty acid synthesis, triglyceride levels, and carnitine palmitoyltransferase activities (CPT) in placental explants of women with GDM or no pregnancy complication. In women with GDM, FAO was reduced by ~30% without change in mitochondrial content, and triglyceride content was threefold higher than in the control group. Likewise, in placental explants of women with no complications, high glucose levels reduced FAO by ~20%, and esterification increased linearly with increasing fatty acid concentrations. However, de novo fatty acid synthesis remained unchanged between high and low glucose levels. In addition, high glucose levels increased triglyceride content approximately twofold compared with low glucose levels. Furthermore, etomoxir-mediated inhibition of FAO enhanced esterification capacity by ~40% and elevated triglyceride content 1.5-fold in placental explants of women, with no complications. Finally, high glucose levels reduced CPT I activity by ~70% and phosphorylation levels of acetyl-CoA carboxylase by ~25% in placental explants of women, with no complications. We reveal an unrecognized regulatory mechanism on placental fatty acid metabolism by which high glucose levels reduce mitochondrial FAO through inhibition of CPT I, shifting flux of fatty acids away from oxidation toward the esterification pathway, leading to accumulation of placental triglycerides. PMID:23673156

  5. Palmitate induces insulin resistance without significant intracellular triglyceride accumulation in HepG2 cells.

    PubMed

    Lee, Jin-young; Cho, Hyang-Ki; Kwon, Young Hye

    2010-07-01

    Previous studies showed that increased release of free fatty acids from adipocytes leads to insulin resistance and triglyceride (TG) accumulation in the liver, which may progress into hepatic steatohepatitis. We and other investigators have previously reported that palmitate induces endoplasmic reticulum stress-mediated toxicity in several tissues. This work investigated whether palmitate could induce insulin resistance and steatosis in HepG2 cells. We treated cells with either saturated fatty acid (palmitate) or unsaturated fatty acid (oleate), and observed that palmitate significantly activated c-jun N-terminal kinase and inactivated protein kinase B. Both 4-phenylbutyric acid and glycerol significantly activated protein kinase B, confirming the involvement of endoplasmic reticulum stress in palmitate-mediated insulin resistance. Oleate, but not palmitate, significantly induced intracellular TG deposition and activated sterol regulatory element binding protein-1. Instead, diacylglycerol level and protein kinase C epsilon activity were significantly increased by palmitate, suggesting the possible role of diacylglycerol in palmitate-mediated lipotoxicity. Therefore, the present study clearly showed that palmitate impairs insulin resistance, but does not induce significant TG accumulation in HepG2 cells. PMID:20006364

  6. Metabolic effects of glucose, medium chain triglyceride and long chain triglyceride feeding before prolonged exercise in rats

    Microsoft Academic Search

    E. Auclair; P. Satabin; E. Servan; C. Y. Guezennec

    1988-01-01

    Summary  The purpose of this study was to test the hypothesis that oral ingestion of lipids could increase endurance by slowing the rate of glycogen depletion. Trained rats were killed after a 2 h run on a rodent treadmill, following an intragastric infusion of water, glucose, medium chain triglycerides (MCT) or long chain triglycerides (LCT). Glucose and triglycerides were administered in

  7. Polyunsaturated fatty acids effect on serum triglycerides concentration in presence of metabolic syndrome components. The Alaska-Siberia Project

    PubMed Central

    Lopez-Alvarenga, Juan C.; Ebbesson, Sven O E; Ebbesson, Lars O E; Tejero, M Elizabeth; Voruganti, V. Saroja; Comuzzie, Anthony G

    2009-01-01

    Serum fatty acids (FA) have wide effects on metabolism: Serum saturated fatty acids (SFA) increase triglyceride (TG) levels in plasma while polyunsaturated fatty acids (PUFA) reduce them. Traditionally, Eskimos have a high consumption of omega -3 fatty acids (?–3 FA), but the westernization of their food habits have increased their dietary SFAs, partly reflected in their serum concentrations. We studied the joint effect of serum SFAs and PUFAs on circulating levels of TG in the presence of metabolic syndrome components. We included 212 men and 240 women (age 47.9±15.7 y, BMI 26.9±5.3) from four villages located in Alaska for a cross sectional study. Generalized linear models were employed to build surface responses of TG as in functions of SFAs and PUFAs measured in blood samples adjusting by sex, BMI and village. The effects of individual FAs were assessed by multiple linear regression analysis and partial correlations (r) were calculated. The most important predictors for TG levels were glucose tolerance (r = 0.116, p = 0.018) and BMI (r = 0.42, p<0.001). TG concentration showed negative associations with 20:3?-6 (r =? 0.16, p = 0.001), 20:4?-6 (r = ?0.14, p=0.005), 20:5?-3 (r = ?0.17, p<0.001) and 22:5?-3 (r = ?0.26, p<0.001), and positive associations with palmitic acid (r = 0.16, p<0.001) and 18:3?-3 (r = 0.15, p<0.001). The surface response analysis suggested that the effect of palmitic acid on TG is blunted in different degrees according to the PUFA chemical structure. The long chain ?-3, even in presence of high levels of SF, was associated with lower triglyceride levels. Eicosapentanoic acid (20:5?3) had the strongest effect against palmitic acid on TG. The total FA showed moderate association with levels of TG, while SFA was positively associated, and large chain PUFA negatively. The westernized dietary habits among Eskimos are likely to change their metabolic profile and increase comorbidities related to metabolic disease. PMID:19766268

  8. 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

  9. 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...

  10. 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 ? and ? 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

  11. Evaluation of the Effect of Shift Work on Serum Cholesterol and Triglyceride Levels

    PubMed Central

    Akbari, Hamed; Mirzaei, Ramazan; Nasrabadi, Tahereh; Gholami-Fesharaki, Mohammad

    2015-01-01

    Background: Working outside daylight hours (7 am to 7 pm) is called shift work. Shift work is a common practice in many industries and factories such as steel industries, petroleum industries, power plants, and in some services such as medicine and nursing and police forces, in which professionals provide services during day and night. Objectives: Considering the contradictory reports of different studies, we decided to evaluate the effect of shift work on cholesterol and triglyceride (TG) levels through a historical cohort on steel industry workers. Patients and Methods: This retrospective cohort study was performed on all the staff of Isfahan’s Mobarakeh Steel Company between years 2002 and 2011. There were 5773 participants in this study. Data were collected from the medical records of the staff using the census method. For analysis of data, generalized estimating equation (GEE) regression was used. Results: The results showed a significant difference in cholesterol levels between shift workers and day workers on the first observation (P < 0.001), yet no such difference was observed for TG (P = 0.853). Moreover, the results showed that the variables of age, work experience and BMI were not similar between shift workers and day workers. Therefore, to remove the effect of such variables, we used GEE regression. Despite the borderline difference of cholesterol between regular shift workers and day workers, this correlation was not statistically significant (P = 0.051). The results for TG also showed no correlation with shift work. Conclusions: According to the findings of this study, there is no relationship between shift work and changes in serum TG and cholesterol. The lack of relationship can be due to shift plans for shift workers, nutrition, or the “Healthy Heart project” at Isfahan Mobarakeh Steel Company.

  12. 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

  13. 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

  14. Failure simulations of triglyceride-based adhesives

    NASA Astrophysics Data System (ADS)

    Lorenz, Christian D.; Stevens, Mark J.; Wool, Richard P.

    2004-03-01

    The use of natural plant oils in the production of adhesives has been the focus of a large amount of research because the natural oils are a renewable resource which have environmental and economic advantages over the petroleum-derived chemicals used in traditional adhesives. An off-lattice Monte Carlo simulation was used to model the formation of networks consisting of the triglycerides found in soybean, linseed and olive oils and networks made from other `theoretical' natural oils. Each of these networks has a different number of carbon-carbon double bonds n present in a given triglyceride molecule. The stress-strain behavior of these networks is studied using large-scale molecular dynamics simulations. Tensile strains are applied to the networks and it is observed that with increasing n the failure stress increases but the failure strain decreases. Also, at low values of n, the systems have large voids form while the system is strained and then the system fails cohesively. However for large n, no significant voiding is observed and the system fails close to the interface. The simulation results are shown to be consistent with vector percolation theoretical predictions for how the failure stress and the crosslink density relate to n.

  15. 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

  16. 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

  17. Age effects on plasma cholesterol and triglyceride profiles and metabolite concentrations in dogs

    PubMed Central

    2014-01-01

    Background In dogs, occurrence of lipid metabolism disorders such as obesity and diabetes mellitus has increased markedly in recent years. Hyperlipidemia has been regarded as a common characteristic for obese animals and hyperlipidemic condition may be associated with inflammation, oxidative stress and lipid composition changes. In this study, we investigated the changes in plasma cholesterol and triglyceride (TG) profiles and metabolite concentrations in 24 dogs (young group: 0-7 years old, n?=?12, aged group: 8-13 years old, n?=?12). Results Plasma adiponectin (ADN) concentrations were significantly lower in aged dogs than those in young dogs (mean?±?SD, 17.2?±?10.0 ?g mL-1 vs 29.3?±?12.5 ?g mL-1, respectively; P <0.05). Although there were no significant differences statistically, aged dogs showed significantly higher plasma alpha1- acid glycoprotein (alpah1-AG) levels compared to those in young dogs. Plasma cholesterol lipoprotein and TG lipoprotein were divided into four fractions by biphasic agarose gel electrophoresis technique. The levels of the third TG-lipoprotein fraction from the positive pole (TG Fraction 3) were significantly higher in aged dogs than in young dogs (mean?±?SD, 143.0?±?109.3 mg dL-1 vs 55.2?±?31.3 mg dL-1, respectively; P <0.05). On the correlation coefficient analysis by Peason’s method, moderate positive correlations were seen between the age and TG (r?=?0.446, P?=?0.029), TG Fraction 3 (r?=?0.516, P?=?0.010), malondialdehyde (r?=?0.146, P?=?0.043), alpha-1 AG (r?=?0.448, P?=?0.028) levels, respectively. Moderate negative correlations were seen the age and total cholesterol (TC) Fraction 2 (r?=?-0.446, P?=?0.029), glucose (r?=?-0.637, P?=?0.001), ADN (r?=?-0.408, P?=?0.048), respectively. Conclusions Present data suggest biochemical characteristics of lipid metabolism disorder may be affected by aging in dogs. PMID:24597741

  18. An inhibitor of the microsomal triglyceride transfer protein inhibits apoB secretion from HepG2 cells.

    PubMed Central

    Jamil, H; Gordon, D A; Eustice, D C; Brooks, C M; Dickson, J K; Chen, Y; Ricci, B; Chu, C H; Harrity, T W; Ciosek, C P; Biller, S A; Gregg, R E; Wetterau, J R

    1996-01-01

    The microsomal triglyceride (TG) transfer protein (MTP) is a heterodimeric lipid transfer protein that catalyzes the transport of triglyceride, cholesteryl ester, and phosphatidylcholine between membranes. Previous studies showing that the proximal cause of abetalipoproteinemia is an absence of MTP indicate that MTP function is required for the assembly of the apolipoprotein B (apoB) containing plasma lipoproteins, i.e., very low density lipoproteins and chylomicrons. However, the precise role of MTP in lipoprotein assembly is not known. In this study, the role of MTP in lipoprotein assembly is investigated using an inhibitor of MTP-mediated lipid transport, 2-[1-(3, 3-diphenylpropyl)-4-piperidinyl]-2,3-dihydro-1H-isoindol-1-o ne (BMS-200150). The similarity of the IC50 for inhibition of bovine MTP-mediated TG transfer (0.6 microM) to the Kd for binding of BMS-200150 to bovine MTP (1.3 microM) strongly supports that the inhibition of TG transfer is the result of a direct effect of the compound on MTP. BMS-200150 also inhibits the transfer of phosphatidylcholine, however to a lesser extent (30% at a concentration that almost completely inhibits TG and cholesteryl ester transfer). When BMS-200150 is added to cultured HepG2 cells, a human liver-derived cell line that secretes apoB containing lipoproteins, it inhibits apoB secretion in a concentration dependent manner. These results support the hypothesis that transport of lipid, and in particular, the transport of neutral lipid by MTP, plays a critical role in the assembly of apoB containing lipoproteins. PMID:8876250

  19. Pancreatic lipase hydrolysis of triglycerides by a semimicro technique

    Microsoft Academic Search

    F. E. Luddy; R. A. Barford; S. F. Herb; P. Magidman; R. W. Riemenschneider

    1964-01-01

    Procedures are described for rapid lipase hydrolysis of triglycerides, isolation of the hydrolytic products by TLC and their\\u000a conversion to methyl esters and fatty acid analysis by GLC. The techniques are applicable to a few mg of triglycerides or\\u000a fats. Examples of data obtained with purified triglycerides indicate that the specific action of pancreatic lipase for the\\u000a 1,3 ester groups

  20. Inhibitory activity of diacylglycerol acyltransferase (DGAT) and microsomal triglyceride transfer protein (MTP) by the flavonoid, taxifolin, in HepG2 cells: potential role in the regulation of apolipoprotein B secretion.

    PubMed

    Casaschi, Adele; Rubio, Brent K; Maiyoh, Geoffrey K; Theriault, Andre G

    2004-10-01

    The purpose of the present study was to examine the role of taxifolin, a plant flavonoid, on several aspects involving apolipoprotein B (apoB) secretion and triglyceride (TG) availability in HepG2 cells. Taxifolin was shown by ELISA to markedly reduce apoB secretion under basal and lipid-rich conditions up to 63% at 200 micromol/L. As to the mechanism underlying this effect, we examined whether taxifolin exerted its effect by limiting TG availability in the microsomal lumen essential for lipoprotein assembly. Taxifolin was shown to inhibit microsomal TG synthesis by 37% and its subsequent transfer into the lumen (-26%). The reduction in synthesis was due to a decrease in diacylglycerol acyltransferase (DGAT) activity (-35%). The effect on DGAT activity was found to be non-competitive and non-transcriptional in nature. Both DGAT-1 and DGAT-2 mRNA expression remained essentially unchanged suggesting the point of regulation may be at the post-transcriptional level. Evidence is accumulating that microsomal triglyceride transfer protein (MTP) is also involved in determining the amount of lumenal TG available for lipoprotein assembly and secretion. Taxifolin was shown to inhibit this enzyme by 41%. Whether the reduction in TG accumulation in the microsomal lumen is predominantly due to DGAT and/or MTP activity remains to be addressed. In summary, taxifolin reduced apoB secretion by limiting TG availability via DGAT and MTP activity. PMID:15380446

  1. Decreased liver triglyceride content in adult rats exposed to protein restriction during gestation and lactation: Role of hepatic triglyceride utilization.

    PubMed

    Qasem, Rani J; Li, Jing; Tang, Hee Man; Browne, Veron; Mendez-Garcia, Claudia; Yablonski, Elizabeth; Pontiggia, Laura; D'Mello, Anil P

    2015-04-01

    We have previously demonstrated that protein restriction throughout gestation and lactation reduces liver triglyceride content in adult rat offspring. However, the mechanisms mediating the decrease in liver triglyceride content are not understood. The aim of the current study was to use a new group of pregnant animals and their offspring and determine the contribution of increased triglyceride utilization via the hepatic fatty-acid oxidation and triglyceride secretory pathways to the reduction in liver triglyceride content. Pregnant Sprague-Dawley rats received either a control or a low protein diet throughout pregnancy and lactation. Pups were weaned onto laboratory chow on day 28 and killed on day 65. Liver triglyceride content was reduced in male, but not female, low-protein offspring, both in the fed and fasted states. The reduction was accompanied by a trend towards higher liver carnitine palmitoyltransferase-1a activity, suggesting increased fatty-acid transport into the mitochondrial matrix. However, medium-chain acyl coenzyme A dehydrogenase activity within the mitochondrial matrix, expression of nuclear peroxisome proliferator activated receptor-?, and plasma levels of ?-hydroxybutyrate were similar between low protein and control offspring, indicating a lack of change in fatty-acid oxidation. Hepatic triglyceride secretion, assessed by blocking peripheral triglyceride utilization and measuring serum triglyceride accumulation rate, and the activity of microsomal transfer protein, were similar between low protein and control offspring. Because enhanced triglyceride utilization is not a significant contributor, the decrease in liver triglyceride content in male low-protein offspring is likely due to alterations in liver fatty-acid transport or triglyceride biosynthesis. PMID:25641378

  2. Adipose triglyceride lipase activity is inhibited by long-chain acyl-coenzyme A.

    PubMed

    Nagy, Harald M; Paar, Margret; Heier, Christoph; Moustafa, Tarek; Hofer, Peter; Haemmerle, Guenter; Lass, Achim; Zechner, Rudolf; Oberer, Monika; Zimmermann, Robert

    2014-04-01

    Adipose triglyceride lipase (ATGL) is required for efficient mobilization of triglyceride (TG) stores in adipose tissue and non-adipose tissues. Therefore, ATGL strongly determines the availability of fatty acids for metabolic reactions. ATGL activity is regulated by a complex network of lipolytic and anti-lipolytic hormones. These signals control enzyme expression and the interaction of ATGL with the regulatory proteins CGI-58 and G0S2. Up to date, it was unknown whether ATGL activity is also controlled by lipid intermediates generated during lipolysis. Here we show that ATGL activity is inhibited by long-chain acyl-CoAs in a non-competitive manner, similar as previously shown for hormone-sensitive lipase (HSL), the rate-limiting enzyme for diglyceride breakdown in adipose tissue. ATGL activity is only marginally inhibited by medium-chain acyl-CoAs, diglycerides, monoglycerides, and free fatty acids. Immunoprecipitation assays revealed that acyl-CoAs do not disrupt the protein-protein interaction of ATGL and its co-activator CGI-58. Furthermore, inhibition of ATGL is independent of the presence of CGI-58 and occurs directly at the N-terminal patatin-like phospholipase domain of the enzyme. In conclusion, our results suggest that inhibition of the major lipolytic enzymes ATGL and HSL by long-chain acyl-CoAs could represent an effective feedback mechanism controlling lipolysis and protecting cells from lipotoxic concentrations of fatty acids and fatty acid-derived lipid metabolites. PMID:24440819

  3. Adipose triglyceride lipase activity is inhibited by long-chain acyl-coenzyme A

    PubMed Central

    Nagy, Harald M.; Paar, Margret; Heier, Christoph; Moustafa, Tarek; Hofer, Peter; Haemmerle, Guenter; Lass, Achim; Zechner, Rudolf; Oberer, Monika; Zimmermann, Robert

    2014-01-01

    Adipose triglyceride lipase (ATGL) is required for efficient mobilization of triglyceride (TG) stores in adipose tissue and non-adipose tissues. Therefore, ATGL strongly determines the availability of fatty acids for metabolic reactions. ATGL activity is regulated by a complex network of lipolytic and anti-lipolytic hormones. These signals control enzyme expression and the interaction of ATGL with the regulatory proteins CGI-58 and G0S2. Up to date, it was unknown whether ATGL activity is also controlled by lipid intermediates generated during lipolysis. Here we show that ATGL activity is inhibited by long-chain acyl-CoAs in a non-competitive manner, similar as previously shown for hormone-sensitive lipase (HSL), the rate-limiting enzyme for diglyceride breakdown in adipose tissue. ATGL activity is only marginally inhibited by medium-chain acyl-CoAs, diglycerides, monoglycerides, and free fatty acids. Immunoprecipitation assays revealed that acyl-CoAs do not disrupt the protein–protein interaction of ATGL and its co-activator CGI-58. Furthermore, inhibition of ATGL is independent of the presence of CGI-58 and occurs directly at the N-terminal patatin-like phospholipase domain of the enzyme. In conclusion, our results suggest that inhibition of the major lipolytic enzymes ATGL and HSL by long-chain acyl-CoAs could represent an effective feedback mechanism controlling lipolysis and protecting cells from lipotoxic concentrations of fatty acids and fatty acid-derived lipid metabolites. PMID:24440819

  4. 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 60–90 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: 108–150 mg/dl [1.22–1.70 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

  5. 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 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 ?-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

  6. Reduced kidney lipoprotein lipase and renal tubule triglyceride accumulation in cisplatin-mediated acute kidney injury.

    PubMed

    Li, Shenyang; Nagothu, Kiran; Ranganathan, Gouri; Ali, Syed M; Shank, Brian; Gokden, Neriman; Ayyadevara, Srinivas; Megyesi, Judit; Olivecrona, Gunilla; Chugh, Sumant S; Kersten, Sander; Portilla, Didier

    2012-08-01

    Peroxisome proliferator-activated receptor-? (PPAR?) activation attenuates cisplatin (CP)-mediated acute kidney injury by increasing fatty acid oxidation, but mechanisms leading to reduced renal triglyceride (TG) accumulation could also contribute. Here, we investigated the effects of PPAR? and CP on expression and enzyme activity of kidney lipoprotein lipase (LPL) as well as on expression of angiopoietin protein-like 4 (Angptl4), glycosylphosphatidylinositol-anchored-HDL-binding protein (GPIHBP1), and lipase maturation factor 1 (Lmf1), which are recognized as important proteins that modulate LPL activity. CP caused a 40% reduction in epididymal white adipose tissue (WAT) mass, with a reduction of LPL expression and activity. CP also reduced kidney LPL expression and activity. Angptl4 mRNA levels were increased by ninefold in liver and kidney tissue and by twofold in adipose tissue of CP-treated mice. Western blots of two-dimensional gel electrophoresis identified increased expression of a neutral pI Angptl4 protein in kidney tissue of CP-treated mice. Immunolocalization studies showed reduced staining of LPL and increased staining of Angptl4 primarily in proximal tubules of CP-treated mice. CP also increased TG accumulation in kidney tissue, which was ameliorated by PPAR? ligand. In summary, a PPAR? ligand ameliorates CP-mediated nephrotoxicity by increasing LPL activity via increased expression of GPHBP1 and Lmf1 and by reducing expression of Angptl4 protein in the proximal tubule. PMID:22622461

  7. Isoflavone supplementation influenced levels of triglyceride and luteunizing hormone in Korean postmenopausal women.

    PubMed

    Kim, Jinkyung; Lee, Hansongyi; Lee, Okhwa; Lee, Kyun-Hee; Lee, Yoon-Bok; Young, Kwon Dae; Jeong, Yang Hye; Choue, Ryowon

    2013-03-01

    We conducted a double-blind, randomized, placebo-controlled trial to evaluate the effects of soy-derived isoflavone on blood glucose, lipid profiles, and sex hormones related to cardiovascular disease in Korean postmenopausal women. One hundred thirteen postmenopausal women were recruited from the Seoul metropolitan area. To confirm postmenopausal and gynecologic status, the subjects were clinically examined by a gynecologist using ultra sound and X-ray. Finally, 85 postmenopausal women whose follicle-stimulating hormone (FSH) levels were higher than 40 IU/ml were enrolled. Subjects received either 70 mg isoflavone or placebo capsules daily for 12 weeks. As a result, the values of fasting glucose, insulin and HOMA-IR, as well as those of TC, LDL-C, HDL-C and FFA, were not different between the groups after supplementation. However, triglyceride (TG) levels in the treatment group decreased significantly compared with those of the placebo group (p = 0.0215). The levels of luteinizing hormone (LH) significantly decreased in the treatment group (p = 0.027); however, the levels of FSH, estrone and estradiol were not changed after intervention. In conclusion, isoflavone supplement of 70 mg/day for 12 weeks decreased blood levels of TG and LH in Korean postmenopausal women. PMID:23475289

  8. Molecular order and thermodynamics of the solid-liquid transition in triglycerides via Raman spectroscopy.

    PubMed

    Da Silva, Eric; Rousseau, Dérick

    2008-08-21

    The conformational and thermodynamic behavior of five monoacid saturated triglycerides (TGs) before, during, and above the beta polymorph --> liquid phase transition was studied using Raman spectroscopy. The Raman ratio I[upsilon(s)(CH(2))]/I[upsilon(as)(CH(2))], used to identify intramolecular order about TG hydrocarbon chains, demonstrated that a single conformation, geometry and symmetry existed in liquid-state TGs. The Raman ratio I(1080)/I(1130), used to determine the intermolecular order/disorder about the hydrocarbon chains and relative trans/gauche content, remained constant for TGs in the crystalline state, but steadily increased as a function of temperature in the liquid state. Use of the van't Hoff relation and the spectroscopically-determined trans/gauche content indicated the presence of distinctive pre- and post-transition enthalpies/entropies indicating that the beta --> liquid phase transition is "soft", with possible intermediate conformations. The liquid-state ester carbonyl stretching region, which gave rise to a broad peak between 1780-1700 cm(-1), was decomposed into multiple components. It demonstrated solid-like character 2-3 degrees C above the TG beta-polymorph melting point, above which no further change in spectral character was observed. These results indicate that the solid-liquid transition in TGs is of the "soft" type with non-lamellar conformations likely present in the melt. PMID:18665310

  9. Thyroid-Stimulating Hormone Inhibits Adipose Triglyceride Lipase in 3T3-L1 Adipocytes through the PKA Pathway

    PubMed Central

    Jiang, Dongqing; Ma, Shizhan; Jing, Fei; Xu, Chao; Yan, Fang; Wang, Aihong; Zhao, Jiajun

    2015-01-01

    Thyroid-stimulating hormone (TSH) has been shown to play an important role in the regulation of triglyceride (TG) metabolism in adipose tissue. Adipose triglyceride lipase (ATGL) is a rate-limiting enzyme controlling the hydrolysis of TG. Thus far, it is unclear whether TSH has a direct effect on the expression of ATGL. Because TSH function is mediated through the TSH receptor (TSHR), TSHR knockout mice (Tshr-/- mice) (supplemented with thyroxine) were used in this study to determine the effects of TSHR deletion on ATGL expression. These effects were verified in 3T3-L1 adipocytes and potential underlying mechanisms were explored. In the Tshr-/- mice, ATGL expression in epididymal adipose tissue was significantly increased compared with that in Tshr+/+ mice. ATGL expression was observed to increase with the differentiation process of 3T3-L1 preadipocytes. In mature 3T3-L1 adipocytes, TSH significantly suppressed ATGL expression at both the protein and mRNA levels in a dose-dependent manner. Forskolin, which is an activator of adenylate cyclase, suppressed the expression of ATGL in 3T3-L1 adipocytes. The inhibitory effects of TSH on ATGL expression were abolished by H89, which is a protein kinase A (PKA) inhibitor. These results indicate that TSH has an inhibitory effect on ATGL expression in mature adipocytes. The associated mechanism is related to PKA activation. PMID:25590597

  10. Quantitative proteomic analysis of cultured skin fibroblast cells derived from patients with triglyceride deposit cardiomyovasculopathy

    PubMed Central

    2013-01-01

    Background Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare disease, characterized by the massive accumulation of triglyceride (TG) in multiple tissues, especially skeletal muscle, heart muscle and the coronary artery. TGCV is caused by mutation of adipose triglyceride lipase, which is an essential molecule for the hydrolysis of TG. TGCV is at high risk for skeletal myopathy and heart dysfunction, and therefore premature death. Development of therapeutic methods for TGCV is highly desirable. This study aims to discover specific molecules responsible for TGCV pathogenesis. Methods To identify differentially expressed proteins in TGCV patient cells, the stable isotope labeling with amino acids in cell culture (SILAC) method coupled with LC-MS/MS was performed using skin fibroblast cells derived from two TGCV patients and three healthy volunteers. Altered protein expression in TGCV cells was confirmed using the selected reaction monitoring (SRM) method. Microarray-based transcriptome analysis was simultaneously performed to identify changes in gene expression in TGCV cells. Results Using SILAC proteomics, 4033 proteins were quantified, 53 of which showed significantly altered expression in both TGCV patient cells. Twenty altered proteins were chosen and confirmed using SRM. SRM analysis successfully quantified 14 proteins, 13 of which showed the same trend as SILAC proteomics. The altered protein expression data set was used in Ingenuity Pathway Analysis (IPA), and significant networks were identified. Several of these proteins have been previously implicated in lipid metabolism, while others represent new therapeutic targets or markers for TGCV. Microarray analysis quantified 20743 transcripts, and 252 genes showed significantly altered expression in both TGCV patient cells. Ten altered genes were chosen, 9 of which were successfully confirmed using quantitative RT-PCR. Biological networks of altered genes were analyzed using an IPA search. Conclusions We performed the SILAC- and SRM-based identification-through-confirmation study using skin fibroblast cells derived from TGCV patients, and first identified altered proteins specific for TGCV. Microarray analysis also identified changes in gene expression. The functional networks of the altered proteins and genes are discussed. Our findings will be exploited to elucidate the pathogenesis of TGCV and discover clinically relevant molecules for TGCV in the near future. PMID:24360150

  11. 1914G variant of BCHE gene associated with enzyme activity, obesity and triglyceride levels.

    PubMed

    Lima, Jovana Karoline; Leite, Neiva; Turek, Luciane Viater; Souza, Ricardo Lehtonen Rodrigues; da Silva Timossi, Luciana; Osiecki, Ana Claudia Vecchi; Osiecki, Raul; Furtado-Alle, Lupe

    2013-12-10

    Polymorphisms of butyrylcholinesterase (BChE) have been reported to be associated to weight, BMI variance and hypertriglyceridemia in adults and adolescents. The aim of the present study was to investigate the association of -116A (SNP: G/A; rs1126680) and 1914G (SNP: A/G; rs3495) variants of BCHE gene with anthropometric and biochemical variables associated with obesity in population sample of 115 individuals, from Southern Brazil. Participants were grouped in two categories: obese (BMI?30) and non-obese (BMI<30). The 1914G allele showed significantly higher frequency in the obese group, and carriers of 1914G allele showed lower mean BChE activity when compared to 1914A carriers (p=0.006). Higher means of BMI (p=0.02) and triglyceride (TG; p=0.01) were found in 1914G carriers (BMI=27.57 kg/m(2); TG=150.8 mg/dL) when compared to 1914A homozygotes (BMI=25.55 kg/m(2); TG=107.9 mg/dL). Carriers of the -116A allele showed lower mean BChE activity than usual homozygotes, and the -116A variant was found in cis with 1914G (p<0.0001; D'=1). The region of BCHE gene that contains the 1914G mutation site is target of microRNAs (miRs) and the response of BChE to glucocorticoids is especially influenced by these miRs. Therefore, it is possible that the 1914G allele can be interfering in gluconeogenesis, hyperglycemia, lipolysis and body fat distribution. This lower activity may cause an imbalance in lipid metabolism, which may lead to an increased predisposition to obesity and to a lower ability to maintain metabolic homeostasis. PMID:24001779

  12. Cognitive impairment in the Tg6590 transgenic rat model of Alzheimer’s disease

    PubMed Central

    Kloskowska, Ewa; Pham, Therese M; Nilsson, Tatjana; Zhu, Shunwei; Öberg, Johanna; Codita, Alina; Pedersen, Lars Ø; Pedersen, Jan T; Malkiewicz, Katarzyna; Winblad, Bengt; Folkesson, Ronnie; Benedikz, Eirikur

    2010-01-01

    Abstract Recently, interest in the rat as an animal model of Alzheimer’s disease (AD) has been growing. We have previously described the Tg6590 transgenic rat line expressing the amyloid precursor protein containing the Swedish AD mutation (K670M/N671L) that shows early stages of A? deposition, predominantly in cerebrovascular blood vessels, after 15 months of age. Here we show that by the age of 9 months, that is long before the appearance of A? deposits, the Tg6590 rats exhibit deficits in the Morris water maze spatial navigation task and altered spontaneous behaviour in the open-field test. The levels of soluble A? were elevated both in the hippocampus and cortex of transgenic animals. Magnetic resonance imaging showed no major changes in the brains of transgenic animals, although they tended to have enlarged lateral ventricles when compared to control animals. The Tg6590 transgenic rat line should prove a suitable model of early AD for advanced studies including serial cerebrospinal fluid sampling, electrophysiology, neuroimaging or complex behavioural testing. PMID:19538474

  13. Arterioscler Thromb Vasc Biol . Author manuscript Rexinoid bexarotene modulates triglyceride but not cholesterol

    E-print Network

    Paris-Sud XI, Université de

    triglyceride but not cholesterol metabolism via gene-specific permissivity of the RXR/LXR heterodimer is an increase in plasma triglycerides, an independent risk factor of cardiovascular disease. The molecular ; chemistry ; physiology ; Tetrahydronaphthalenes ; pharmacology ; Triglycerides ; metabolism Author Keywords

  14. Unreliability of triglyceride measurement to predict turbidity induced interference

    PubMed Central

    Twomey, P J; Don-Wauchope, A C; McCullough, D

    2003-01-01

    Lipaemic specimens are a common problem in clinical chemistry. Most laboratories will measure the concentration of triglycerides and then decide whether the analytical result is valid or not. There is a poor association between the concentration of triglycerides and an objective assessment of turbidity for visually turbid specimens. Extrapolation of triglyceride concentrations derived from the use of intravenous emulsions to visually turbid specimens found in clinical practice will overestimate the turbidity induced interference in assays (non-turbid interferences are probably the same). The evaluation of turbidity induced interference needs to be standardised using objective assessments of turbidity. PMID:14600133

  15. Clinical verification of TG18 methodology for display quality evaluation

    Microsoft Academic Search

    Ehsan Samei; S. Jeff Shepard; Kenneth A. Fetterly; Hee-Joung Kim; Hans Roehrig; Michael J. Flynn

    2003-01-01

    The American Association of Physicists in Medicine Task Group 18 (TG18) has recently developed guidelines for objective performance evaluation of medical displays. This paper reports on the first multi-institutional trial focusing on the implementation and clinical verification of the TG18 methodology for performance testing of medical image display devices in use at different clinical centers. A minimum of two newly-installed

  16. TG–DSC analysis applied to contemporary oil paints

    Microsoft Academic Search

    Francesca Caterina Izzo; Elisabetta Zendri; Guido Biscontin; Eleonora Balliana

    2011-01-01

    Thermogravimetry coupled with differential scanning calorimetry (TG–DSC) has been commonly used in the field of conservation\\u000a of Cultural Heritage for the study of art objects, especially for the characterisation of inorganic matrixes. In recent years,\\u000a thermal analyses have been applied to the study of organic painting materials. The advantages of performing TG–DSC are linked\\u000a to the fact that it is

  17. 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...

  18. 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. [West Los Angeles VA Medical Center, CA (United States). Lipid Research Lab.; [Univ. of California, Los Angeles, CA (United States). Dept. of Medicine; Giometti, C.S.; Mishler, K. [Argonne National Lab., IL (United States); Slavin, B.G. [Univ. of Southern California, Los Angeles, CA (United States)

    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.

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

    MedlinePLUS

    ... or use of unsaturated fats, especially those containing marine omega-3 fatty acids, lower triglyceride levels. 7. ... and Metabolism; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Nursing; and Council on the ...

  20. Impact of Serum Triglyceride and High Density Lipoprotein Cholesterol Levels on Early-Phase Insulin Secretion in Normoglycemic and Prediabetic Subjects

    PubMed Central

    Niwa, Tomohiro; Nakajima, Koji; Kobayashi, Mutsuhiro; Hanyu, Norinao; Nakayama, Tomohiro

    2014-01-01

    Background Increased triglycerides (TGs) and decreased high density lipoprotein cholesterol (HDL-C) levels are established as diabetic risks for nondiabetic subjects. The aim of this study was to investigate the relationship among TG, HDL-C, TG/HDL-C ratio, and early-phase insulin secretion in normoglycemic and prediabetic subjects. Methods We evaluated 663 Japanese subjects who underwent the 75-g oral glucose tolerance test. On the basis of these results, the subjects were divided into four groups: those with normal glucose tolerance (NGT; n=341), isolated impaired fasting glucose (i-IFG; n=211), isolated impaired glucose tolerance (i-IGT; n=71), and combined IFG and IGT (IFG+IGT; n=40). Insulin secretion was estimated by the insulinogenic index (IGI) (?insulin/?glucose [30 to 0 minutes]) and disposition index (DI) (IGI/homeostasis model assessment of insulin resistance). Results In prediabetic subjects (i-IFG, i-IGT, and IFG+IGT), linear regression analyses revealed that IGI and DI were positively correlated with HDL-C levels. Moreover, in subjects with i-IGT and (IFG+IGT), but not with i-IFG, the indices of insulin secretion were negatively correlated with the log-transformed TG and TG/HDL-C ratio. In both the subjects with i-IGT, multivariate linear regression analyses revealed that DI was positively correlated with HDL-C and negatively with log-transformed TG and TG/HDL-C ratio. On the other hand, in subjects with NGT, there was no association between insulin secretion and lipid profiles. Conclusion These results revealed that serum TG and HDL-C levels have different impacts on early-phase insulin secretion on the basis of their glucose tolerance status. PMID:25215276

  1. High performance reversed-phase chromatography of natural triglyceride mixtures

    Microsoft Academic Search

    A. H. El-Hamdy; E. G. Perkins

    1981-01-01

    High performance reversed-phase chromatography (HPRC) is an efficient and powerful tool gaining momentum in the separation\\u000a of triglycerides and other lipid components. In the present study the effect of different variables in triglyceride separation\\u000a has been studied. It was found that a longer hydrocarbon chain bonded to silica gel as well as the percent coverage improved\\u000a the separation. Smaller particle

  2. Cholesterol, triglycerides, and the Five-Factor Model of personality

    Microsoft Academic Search

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

    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=5532) from Sardinia, Italy, had their cholesterol and triglyceride levels assessed and completed a comprehensive personality questionnaire, the NEO-PI-R. All analyses

  3. The Determination of Triglycerides in Plasma and Tissues

    Microsoft Academic Search

    Vishwanafh M. Sardesai; Joan A. Manning

    A simplemethodfor the determination of plasmaandtissuetriglycerides is described. This procedureinvolvesthe extractionand saponification of triglycerides, the oxida- tion of the glycerolmoietyto formaldehyde, and the conversion of formaldehyde to a yellow-colored compound, 3,5 diacetyl-1-4 dihydrolulidine, the intensity of which is determined spectrophotometrically.The recoveriesof triglycerides added to plasma and tissues have been satisfactory. Plasma samples obtained from normal human subjects are found to

  4. 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, E-mail: brigitte.reniers@maastro.nl [Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC), Maastricht 6201 BN (Netherlands)] [Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC), Maastricht 6201 BN (Netherlands); Fonseca, Gabriel Paiva [Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC), Maastricht 6201 BN, The Netherlands and Instituto de Pesquisas Energéticas e Nucleares – IPEN-CNEN/SP, São Paulo CP 11049, 05422-970 (Brazil)] [Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC), Maastricht 6201 BN, The Netherlands and Instituto de Pesquisas Energéticas e Nucleares – IPEN-CNEN/SP, São Paulo CP 11049, 05422-970 (Brazil); Holt, Randy; Rusch, Thomas [Xoft, A Subsidiary of iCAD, Sunnyvale, California 94085-4115 (United States)] [Xoft, A Subsidiary of iCAD, Sunnyvale, California 94085-4115 (United States); Beaulieu, Luc [Centre Hospitalier Universitaire de Québec Université Laval, Radio-Oncologie et Centre de Recherche en Cancérologie de l’Université Laval, Québec, Québec G1R 2J6 Canada (Canada)] [Centre Hospitalier Universitaire de Québec Université Laval, Radio-Oncologie et Centre de Recherche en Cancérologie de l’Université Laval, Québec, Québec G1R 2J6 Canada (Canada); Verhaegen, Frank [Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC), Maastricht 6201 BN, The Netherlands and Department of Oncology, McGill University, Montreal, Quebec H3G 1A4 (Canada)] [Department of Radiation Oncology (MAASTRO), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center (MUMC), Maastricht 6201 BN, The Netherlands and Department of Oncology, McGill University, Montreal, Quebec H3G 1A4 (Canada)

    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.

  5. Variations in plasma apolipoprotein C-III levels are strong correlates of the triglyceride response to a high-monounsaturated fatty acid diet and a high-carbohydrate diet

    Microsoft Academic Search

    W. Roodly Archer; Sophie Desroches; Benoît Lamarche; Olivier Dériaz; Nancy Landry; Bénédicte Fontaine-Bisson; Jean Bergeron; Patrick Couture; Nathalie Bergeron

    2005-01-01

    The objective of this study was to examine how a diet rich in carbohydrates (high-CHO) vs a diet rich in monounsaturated fatty acids (high MUFA) consumed ad libitum modulated plasma apolipoprotein C-III (apo C-III) levels and to examine the extent to which diet-induced changes in plasma apo C-III were associated with concurrent variations in plasma triglyceride (TG) levels. Forty-seven men

  6. The use of fasting vs. non-fasting triglyceride concentration for estimating the prevalence of high LDL-cholesterol and metabolic syndrome in population surveys

    PubMed Central

    2011-01-01

    Background For practical reasons it is not easy to obtain fasting samples in large population health surveys. Non-fasting triglyceride (Tg) values are difficult to interpret. The authors compared the accuracy of statistically corrected non-fasting Tg values with true fasting values and estimated the misclassification of subjects with high low-density lipoprotein cholesterol (LDL-C) and the metabolic syndrome. Methods Non-fasting blood was obtained from a population-based sample of 4282 individuals aged 24-75 years in the National FINRISK 2007 Study. Fasting blood samples were drawn from the same persons 3 months later. Non-fasting serum Tg values were converted into fasting values using previously published formula. LDL-C was calculated and classification of the metabolic syndrome was carried out according to three different latest guidelines. Results The median (25th, 75th percentile) non-fasting serum Tg concentration was 1.18 (0.87, 1.72) mmol/L and after postprandial correction 1.06 (0.78, 1.52) mmol/L. The true-fasting serum Tg concentration was 1.00 (0.75, 1.38) mmol/L (P < 0.001) vs. non-fasting and corrected value. Bias of the corrected value was +5.9% compared with the true-fasting Tg. Of the true fasting subjects, 56.4% had LDL-C ?3.00 mmol/L. When calculated using non-fasting serum Tg, the prevalence of high LDL-C was 51.3% and using statistically corrected Tg it was 54.8%. The prevalence of metabolic syndrome was 35.5% among fully fasted persons and among non-fasting subjects 39.7%, which after statistical correction of Tg decreased to 37.6% (P < 0.001 for all comparisons). Conclusions Correction of non-fasting serum Tg to fasting values plays a minor role in population studies but nevertheless reduces misclassification of calculated high LDL-C from 5.1 to 1.6% and the metabolic syndrome from 4.2 to 2.1%. PMID:21569280

  7. 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: 17°C, 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

  8. J Biol Chem . Author manuscript Hepatitis C virus proteins induce lipogenesis and defective triglyceride

    E-print Network

    Boyer, Edmond

    and defective triglyceride secretion in transgenic mice Herv Leraté 1 * , H l ne L. Kammouné è 2 , Isabelle triglyceride levels. Triglyceride secretion was impaired while lipogenesis was activated. Increased lipogenic-length polyprotein at low, physiological levels, have decreased plasma triglyceride levels and develop hepatocellular

  9. Structural Insights into Triglyceride Storage Mediated by Fat Storage-Inducing Transmembrane (FIT) Protein 2

    E-print Network

    Snapp, Erik Lee

    Structural Insights into Triglyceride Storage Mediated by Fat Storage-Inducing Transmembrane (FIT in triglyceride lipid droplet formation. FIT proteins have been shown to mediate the partitioning of cellular triglyceride into lipid droplets, but not triglyceride biosynthesis. FIT proteins do not share primary sequence

  10. Influence of the position of unsaturated fatty acid esterified glycerol on the oxidation rate of triglyceride

    Microsoft Academic Search

    Shun Wada; Chiaki Koizumi

    1983-01-01

    The influence of the position of unsaturated fatty acid esterified glycerol on the oxidation rate of triglyceride was investigated\\u000a at 50 C. Randomized triglycerides used were prepared by random interesterification between saturated and unsaturated monoacid\\u000a triglycerides using sodium methoxide as catalyst. The monoacid triglycerides used were tripalmitin, tristearin, triolein and\\u000a trilinolein. The molecular species of the randomized triglycerides were analyzed

  11. Ultrasound assisted production of fatty acid methyl esters from transesterification of triglycerides with methanol in the presence of KOH catalyst: optimization, mechanism and kinetics.

    PubMed

    Thanh, Le Tu; Okitsu, Kenji; Maeda, Yasuaki; Bandow, Hiroshi

    2014-03-01

    Ultrasound assisted transesterification of triglycerides (TG) with methanol in the presence of KOH catalyst was investigated, where the changes in the reactants and products (diglycerides (DG), monoglycerides (MG), fatty acid methyl esters (FAME) and glycerin (GL)) concentrations were discussed to understand the reaction mechanism and kinetics under ultrasound irradiation. The optimum reaction condition for the FAME production was the concentration of KOH 1.0 wt.%, molar ratio of TG to methanol of 1:6, and irradiation time of 25 min. The rate constants during the TG transesterification with methanol into GL and FAME were estimated by a curve fitting method with simulated curves to the obtained experimental results. The rate constants of [Formula: see text] were estimated to be 0.21, 0.008, 0.23, 0.005, 0.14 and 0.001 L mol(-1)min(-1), respectively. The rate determining step for the TG transesterification with methanol into GL and FAME was the reaction of MG with methanol into GL and FAME. PMID:24161255

  12. TG4010: A therapeutic vaccine against MUC1 expressing tumors.

    PubMed

    Limacher, Jean-Marc; Quoix, Elisabeth

    2012-08-01

    TG4010 is a therapeutic cancer vaccine based on a viral vector, a modified vaccinia of Ankara (MVA), expressing MUC1 as well as interleukine 2. Today the clinical development is focused on advanced non-small cell lung cancer in combination with first line chemotherapy. Potential biomarkers predictive of activity have been identified. PMID:22934285

  13. T.G . BEVER Aesthetic Basis for CognitiveStructures

    E-print Network

    Bever, Thomas G.

    T.G . BEVER Aesthetic Basis for CognitiveStructures 3 15 The Aesthetic Basis for Cognitive is develop- mental: they facilitatethe experienceof languageacquisitionasan aesthetic and problem aestheticjudgments, a be- havior with no apparent direct hction. Aesthetic behavior reveals to us what the mind does

  14. Entm 307G: Exoskeleton.TG The Insect (Arthropod) Exoskeleton

    E-print Network

    Ginzel, Matthew

    Entm 307G: Exoskeleton.TG The Insect (Arthropod) Exoskeleton Appropriate Grades: 2-6 Think Ahead that insects, and other arthropods, have an external support system called an exoskeleton, which provides, in addition, the exoskeleton provides waterproofing to keep insects from drying out, protection from enemies

  15. 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-? 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

  16. Vector Percolation Analysis of Triglyceride-based Thermoset Polymers

    NASA Astrophysics Data System (ADS)

    Lascala, John J.; Wool, Richard P.

    2003-03-01

    Thermosetting Acrylated triglycerides (ATG) were prepared from various oils and model triglycerides. The distribution of acrylate groups was calculated from the distribution of unsaturation sites on unmodified oils, assuming a binomial distribution of acrylate groups. The ATG were both homopolymerized and copolymerized with styrene. The cross-link density v, of the polymers was calculated using the recursive method of Miller and Macosko from a knowledge of the acrylate distribution. The cross-link density was found to increase with the level of acrylation A, in a vector percolation manner, and the trends in the cross-link density predictions matched the experimental results. The deviation in the experimental results and model predictions were the result of intramolecular cross-linking. Approximately 0.5 and 0.8 acrylates per triglyceride were lost to intramolecular cyclization for homopolymerized acrylated triglycerides and triglycerides copolymerized with styrene, respectively. Equations for the level of perfection p, of the triglyceride networks and the percolation threshold pc, were developed using the calculated number of acrylates lost to cyclization. Polymers with p < 0.1 without styrene, and p < 0.39 with styrene did not have mechanical integrity, validating the definition of the level of perfection and percolation threshold pc. The tensile strength, S ˜ [p-p]^1/2 and modulus E ˜ [p-pc]^3 , were in accord with vector percolation theory, where p could be derived experimentally via A ˜ [p-pc] , v ˜ A and FTIR analysis of the extent of reaction of the C=C groups. These results also indicated how mechanical properties were controlled by the fatty acid distribution function of the plant oils, and which oil would give the best particular property. Supported by EPA and DoE.

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

    PubMed

    Narcisi, T M; Shoulders, C C; Chester, S A; Read, J; Brett, D J; Harrison, G B; Grantham, T T; Fox, M F; Povey, S; de Bruin, T W

    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. PMID:8533758

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

    SciTech Connect

    Narcisi, T.M.E.; Shoulders, C.C.; Chester, S.A. [Hammersmith Hospital, London (United Kingdom)] [and others

    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.

  19. Lpcat3-dependent production of arachidonoyl phospholipids is a key determinant of triglyceride secretion

    PubMed Central

    Rong, Xin; Wang, Bo; Dunham, Merlow M; Hedde, Per Niklas; Wong, Jinny S; Gratton, Enrico; Young, Stephen G; Ford, David A; Tontonoz, Peter

    2015-01-01

    The role of specific phospholipids (PLs) in lipid transport has been difficult to assess due to an inability to selectively manipulate membrane composition in vivo. Here we show that the phospholipid remodeling enzyme lysophosphatidylcholine acyltransferase 3 (Lpcat3) is a critical determinant of triglyceride (TG) secretion due to its unique ability to catalyze the incorporation of arachidonate into membranes. Mice lacking Lpcat3 in the intestine fail to thrive during weaning and exhibit enterocyte lipid accumulation and reduced plasma TGs. Mice lacking Lpcat3 in the liver show reduced plasma TGs, hepatosteatosis, and secrete lipid-poor very low-density lipoprotein (VLDL) lacking arachidonoyl PLs. Mechanistic studies indicate that Lpcat3 activity impacts membrane lipid mobility in living cells, suggesting a biophysical basis for the requirement of arachidonoyl PLs in lipidating lipoprotein particles. These data identify Lpcat3 as a key factor in lipoprotein production and illustrate how manipulation of membrane composition can be used as a regulatory mechanism to control metabolic pathways. DOI: http://dx.doi.org/10.7554/eLife.06557.001 PMID:25806685

  20. 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

  1. 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

  2. Pharmacological characterization of diethyl-2-({3-dimethylcarbamoyl-4-[(4'-trifluoromethylbiphenyl-2-carbonyl)amino]phenyl}acetyloxymethyl)-2-phenylmalonate (JTT-130), an intestine-specific inhibitor of microsomal triglyceride transfer protein.

    PubMed

    Mera, Yasuko; Odani, Naoya; Kawai, Takashi; Hata, Takahiro; Suzuki, Masahiro; Hagiwara, Atsushi; Katsushima, Takeo; Kakutani, Makoto

    2011-02-01

    Inhibitors of microsomal triglyceride transfer protein (MTP) expressed in the liver and small intestine are potential candidates for lipid-lowering agents. However, inhibition of hepatic MTP could lead to significant safety issues such as fatty liver disease. To develop a specific inhibitor of intestinal MTP, JTT-130 [diethyl-2-({3-dimethylcarbamoyl-4-[(4'-trifluoromethylbiphenyl-2-carbonyl)amino]phenyl}acetyloxymethyl)-2-phenylmalonate], was designed to be rapidly hydrolyzed in the absorption process. Here, we describe JTT-130, an intestine-specific MTP inhibitor, and evaluate its pharmacological properties. In in vitro metabolic stability tests, JTT-130 was readily hydrolyzed during incubation with liver S9 from humans, hamsters, and rats. In an in vitro triglyceride (TG) transfer assay with human intestinal MTP, JTT-130 potently inhibited TG transfer activity with an IC(50) value of 0.83 nM. When orally administered to hamsters, JTT-130 significantly suppressed an increase in chylomicron-TG after olive oil loading at 0.3 mg/kg and above but did not inhibit TG secretion from the liver at doses of up to 1000 mg/kg, indicating an inhibitory action highly specific for the small intestine. In rats orally administered [(14)C]triolein, JTT-130 potently suppressed an increase in blood (14)C radioactivity and increased (14)C radioactivity in the upper small intestine and the intestinal lumen. In hyperlipidemic hamsters fed a high-fat and high-cholesterol diet, repeated dosing with JTT-130 for 2 weeks reduced TG and cholesterol levels in the plasma and TG content in the liver. These results indicated that JTT-130 is a potent inhibitor specific to intestinal MTP and suggested that JTT-130 would be a useful compound for the treatment of dyslipidemia without inducing hepatotoxicity. PMID:20974698

  3. 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

  4. Silencing PP2A inhibitor by lenti-shRNA interference ameliorates neuropathologies and memory deficits in tg2576 mice.

    PubMed

    Liu, Gong-Ping; Wei, Wei; Zhou, Xin; Shi, Hai-Rong; Liu, Xing-Hua; Chai, Gao-Shang; Yao, Xiu-Qing; Zhang, Jia-Yu; Peng, Cai-Xia; Hu, Juan; Li, Xia-Chun; Wang, Qun; Wang, Jian-Zhi

    2013-12-01

    Deficits of protein phosphatase-2A (PP2A) play a crucial role in tau hyperphosphorylation, amyloid overproduction, and synaptic suppression of Alzheimer's disease (AD), in which PP2A is inactivated by the endogenously increased inhibitory protein, namely inhibitor-2 of PP2A (I2(PP2A)). Therefore, in vivo silencing I2(PP2A) may rescue PP2A and mitigate AD neurodegeneration. By infusion of lentivirus-shRNA targeting I2(PP2A) (LV-siI2(PP2A)) into hippocampus and frontal cortex of 11-month-old tg2576 mice, we demonstrated that expression of LV-siI2(PP2A) decreased remarkably the elevated I2(PP2A) in both mRNA and protein levels. Simultaneously, the PP2A activity was restored with the mechanisms involving reduction of the inhibitory binding of I2(PP2A) to PP2A catalytic subunit (PP2AC), repression of the inhibitory Leu309-demethylation and elevation of PP2AC. Silencing I2(PP2A) induced a long-lasting attenuation of amyloidogenesis in tg2576 mice with inhibition of amyloid precursor protein hyperphosphorylation and ?-secretase activity, whereas simultaneous inhibition of PP2A abolished the antiamyloidogenic effects of I2(PP2A) silencing. Finally, silencing I2(PP2A) could improve learning and memory of tg2576 mice with preservation of several memory-associated components. Our data reveal that targeting I2(PP2A) can efficiently rescue A? toxicities and improve the memory deficits in tg2576 mice, suggesting that I2(PP2A) could be a promising target for potential AD therapies. PMID:23922015

  5. Chronic Temporal Lobe Epilepsy Is Associated with Enhanced Alzheimer-Like Neuropathology in 3×Tg-AD Mice

    PubMed Central

    Yan, Xiao-Xin; Cai, Yan; Shelton, Jarod; Deng, Si-Hao; Luo, Xue-Gang; Oddo, Salvatore; LaFerla, Frank M.; Cai, Huaibin; Rose, Gregory M.; Patrylo, Peter R.

    2012-01-01

    The comorbidity between epilepsy and Alzheimer's disease (AD) is a topic of growing interest. Senile plaques and tauopathy are found in epileptic human temporal lobe structures, and individuals with AD have an increased incidence of spontaneous seizures. However, why and how epilepsy is associated with enhanced AD-like pathology remains unknown. We have recently shown ?-secretase-1 (BACE1) elevation associated with aberrant limbic axonal sprouting in epileptic CD1 mice. Here we sought to explore whether BACE1 upregulation affected the development of Alzheimer-type neuropathology in mice expressing mutant human APP, presenilin and tau proteins, the triple transgenic model of AD (3×Tg-AD). 3×Tg-AD mice were treated with pilocarpine or saline (i.p.) at 6–8 months of age. Immunoreactivity (IR) for BACE1, ?-amyloid (A?) and phosphorylated tau (p-tau) was subsequently examined at 9, 11 or 14 months of age. Recurrent convulsive seizures, as well as mossy fiber sprouting and neuronal death in the hippocampus and limbic cortex, were observed in all epileptic mice. Neuritic plaques composed of BACE1-labeled swollen/sprouting axons and extracellular A?IR were seen in the hippocampal formation, amygdala and piriform cortices of 9 month-old epileptic, but not control, 3×Tg-AD mice. Densities of plaque-associated BACE1 and A?IR were elevated in epileptic versus control mice at 11 and 14 months of age. p-Tau IR was increased in dentate granule cells and mossy fibers in epileptic mice relative to controls at all time points examined. Thus, pilocarpine-induced chronic epilepsy was associated with accelerated and enhanced neuritic plaque formation and altered intraneuronal p-tau expression in temporal lobe structures in 3×Tg-AD mice, with these pathologies occurring in regions showing neuronal death and axonal dystrophy. PMID:23155407

  6. Triglyceride accumulation protects against fatty acid-induced lipotoxicity

    Microsoft Academic Search

    Laura L. Listenberger; Xianlin Han; Sarah E. Lewis; Sylvaine Cases; Robert V. Farese Jr.; Daniel S. Ory; Jean E. Schaffer

    2003-01-01

    Excess lipid accumulation in non-adipose tissues is associated with insulin resistance, pancreatic -cell apoptosis and heart failure. Here, we demonstrate in cultured cells that the relative toxicity of two common dietary long chain fatty acids is related to channeling of these lipids to distinct cellular metabolic fates. Oleic acid supplementation leads to triglyceride accumulation and is well tolerated, whereas excess

  7. Absence of Microsomal Triglyceride Transfer Protein in Individuals with Abetalipoproteinemia

    Microsoft Academic Search

    John R. Wetterau; Lawrence P. Aggerbeck; Marie-Elisabeth Bouma; Claude Eisenberg; Anne Munck; Michel Hermier; Jacques Schmitz; Gerard Gay; Daniel J. Rader; Richard E. Gregg

    1992-01-01

    Abetalipoproteinemia is a human genetic disease that is characterized by a defect in the assembly or secretion of plasma very low density lipoproteins and chylomicrons. The microsomal triglyceride transfer protein (MTP), which is located in the lumen of microsomes isolated from the liver and intestine, has been proposed to function in lipoprotein assembly. MTP activity and the 88-kilodalton component of

  8. Triglycerides in the Human Kidney Cortex: Relationship with Body Size

    PubMed Central

    Bobulescu, Ion Alexandru; Lotan, Yair; Zhang, Jianning; Rosenthal, Tara R.; Rogers, John T.; Adams-Huet, Beverley; Sakhaee, Khashayar; Moe, Orson W.

    2014-01-01

    Obesity is associated with increased risk for kidney disease and uric acid nephrolithiasis, but the pathophysiological mechanisms underpinning these associations are incompletely understood. Animal experiments have suggested that renal lipid accumulation and lipotoxicity may play a role, but whether lipid accumulation occurs in humans with increasing body mass index (BMI) is unknown. The association between obesity and abnormal triglyceride accumulation in non-adipose tissues (steatosis) has been described in the liver, heart, skeletal muscle and pancreas, but not in the human kidney. We used a quantitative biochemical assay to quantify triglyceride in normal kidney cortex samples from 54 patients undergoing nephrectomy for localized renal cell carcinoma. In subsets of the study population we evaluated the localization of lipid droplets by Oil Red O staining and measured 16 common ceramide species by mass spectrometry. There was a positive correlation between kidney cortex trigyceride content and BMI (Spearman R?=?0.27, P?=?0.04). Lipid droplets detectable by optical microscopy had a sporadic distribution but were generally more prevalent in individuals with higher BMI, with predominant localization in proximal tubule cells and to a lesser extent in glomeruli. Total ceramide content was inversely correlated with triglycerides. We postulate that obesity is associated with abnormal triglyceride accumulation (steatosis) in the human kidney. In turn, steatosis and lipotoxicity may contribute to the pathogenesis of obesity-associated kidney disease and nephrolithiasis. PMID:25170827

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

    PubMed

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

    2014-05-01

    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 6?) and increased TG catabolism and fatty acyl carnitines. Increased hepatic Elovl5 activity did not increase hepatic capacity for ?-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 PPAR?-dependent mechanisms in human HepG2 cells. Treatment of mouse AML12 hepatocytes with the PPAR? agonist (GW0742) decreased (14)C-18:2,n-6 in TGs but did not affect ?-oxidation. These studies establish that Elovl5 activity regulates hepatic levels of FAs controlling PPAR? activity, ATGL expression, and TG catabolism, but not FA oxidation. PMID:24814977

  10. The APOA5 locus is a strong determinant of plasma triglyceride concentrations across ethnic groups in Singapore.

    PubMed

    Lai, Chao-Qiang; Tai, E-Shyong; Tan, Chee Eng; Cutter, Jeffery; Chew, Suok Kai; Zhu, Yue-Ping; Adiconis, Xian; Ordovas, Jose M

    2003-12-01

    Singapore comprises three ethnic groups: Chinese (76.7%), Malays (14%), and Asian-Indians (7.9%). Overall, Singaporeans experience coronary heart disease rates similar to those found in the United States. However, there is a dramatic interethnic gradient, with Asian-Indians having significantly higher risk than Chinese and Malays. These differences are associated with HDL cholesterol levels and cannot be solely explained by environmental exposure, and may be driven by genetic factors. The gene encoding apolipoprotein A-V (APOA5) has been located on chromosome 11, and it is emerging as an important candidate gene for lipoprotein metabolism. We investigated associations between APOA5 polymorphisms and plasma lipids in 3,971 Singaporeans to establish whether they accounted for some of the ethnic differences in plasma lipids. We found significant associations between the minor alleles at each of four common polymorphisms and higher plasma triglycerides (TGs) across ethnic groups. Haplotype analyses showed significant associations with TGs, explaining 6.9%, 5.2%, and 2.7% of the TG variance in Malays, Asian-Indians, and Chinese, respectively. Conversely, we observed significant inverse associations between the minor alleles and HDL cholesterol concentrations for Chinese and Malays. These data suggest that APOA5 plays a role in the ethnic differences observed for plasma TG and HDL cholesterol concentrations. PMID:12951359

  11. Reduced Expression of Adipose Triglyceride Lipase Enhances Tumor Necrosis Factor ?-induced Intercellular Adhesion Molecule-1 Expression in Human Aortic Endothelial Cells via Protein Kinase C-dependent Activation of Nuclear Factor-?B*

    PubMed Central

    Inoue, Tomoaki; Kobayashi, Kunihisa; Inoguchi, Toyoshi; Sonoda, Noriyuki; Fujii, Masakazu; Maeda, Yasutaka; Fujimura, Yoshinori; Miura, Daisuke; Hirano, Ken-ichi; Takayanagi, Ryoichi

    2011-01-01

    We examined the effects of adipose triglyceride lipase (ATGL) on the initiation of atherosclerosis. ATGL was recently identified as a rate-limiting triglyceride (TG) lipase. Mutations in the human ATGL gene are associated with neutral lipid storage disease with myopathy, a rare genetic disease characterized by excessive accumulation of TG in multiple tissues. The cardiac phenotype, known as triglyceride deposit cardiomyovasculopathy, shows massive TG accumulation in both coronary atherosclerotic lesions and the myocardium. Recent reports show that myocardial triglyceride content is significantly higher in patients with prediabetes or diabetes and that ATGL expression is decreased in the obese insulin-resistant state. Therefore, we investigated the effect of decreased ATGL activity on the development of atherosclerosis using human aortic endothelial cells. We found that ATGL knockdown enhanced monocyte adhesion via increased expression of TNF?-induced intercellular adhesion molecule-1 (ICAM-1). Next, we determined the pathways (MAPK, PKC, or NF?B) involved in ICAM-1 up-regulation induced by ATGL knockdown. Both phosphorylation of PKC and degradation of I?B? were increased in ATGL knockdown human aortic endothelial cells. In addition, intracellular diacylglycerol levels and free fatty acid uptake via CD36 were significantly increased in these cells. Inhibition of the PKC pathway using calphostin C and GF109203X suppressed TNF?-induced ICAM-1 expression. In conclusion, we showed that ATGL knockdown increased monocyte adhesion to the endothelium through enhanced TNF?-induced ICAM-1 expression via activation of NF?B and PKC. These results suggest that reduced ATGL expression may influence the atherogenic process in neutral lipid storage diseases and in the insulin-resistant state. PMID:21828047

  12. location plan, floor plan, west elevation, north elevation, north elevation ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    location plan, floor plan, west elevation, north elevation, north elevation with porch removed - Chopawamsic Recreational Demonstration Area - Cabin Camp 1, Staff Quarters, Prince William Forest Park, Triangle, Prince William County, VA

  13. location plan, floor plan, west elevation, south elevation, south elevation ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    location plan, floor plan, west elevation, south elevation, south elevation with porch removed - Chopawamsic Recreational Demonstration Area - Cabin Camp 1, Infirmary, Prince William Forest Park, Triangle, Prince William County, VA

  14. Fasting Blood Sugar and Serum Triglyceride as the Risk Factors of Colorectal Adenoma in Korean Population Receiving Screening Colonoscopy

    PubMed Central

    Pyo, Jeung Hui; Chun, Hoon Jai; Keum, Bora; Jeen, Yoon Tae; Lee, Hong Sik; Kim, Chang Duck; Ryu, Ho Sang; Kim, Young Ha; Lee, Jung Eun

    2013-01-01

    In several previously reported studies, metabolic syndrome (MS) was found to be associated with colorectal adenomas. While the incidence of colorectal adenoma is growing in Korean population, there are only few studies that examined the association between MS and colorectal adenoma in Korea. The aim of this study was to investigate relationships between prevalence of colorectal adenoma and MS components. We conducted a cross sectional study using data from individuals who had undergone complete colonoscopy for health examinations at the Health Promotion Center of Korea University Medical Center from July 1, 2004 to July 31, 2010. A total of 7481 subjects (4459 males and 3022 females) were included; 1733 subjects with pathologically proven adenoma were assigned to the case group, and other 5748 subjects were assigned to the non-case group. All the participants underwent colonoscopy and received blood biochemical tests (fasting blood sugar [FBS], insulin, lipid profile, hemoglobin, blood urea nitrogen [BUN], creatinine). Univariate analysis showed that the prevalence of colorectal adenoma was higher in individuals with higher blood pressure, body mass index (BMI), total cholesterol (TC), triglyceride (TG), FBS and lower high-density lipoprotein cholesterols (HDL-C) levels, compared to those with low levels. Multiple logistic regression analysis revealed that high levels of BMI (OR 1.17, 95% CI 1.01-1.34, P trend = 0.01), TG (OR 1.27, 95% CI 1.07-1.51, P trend = 0.006), and FBS (OR 1.19 95% CI 1.01-1.40, P trend = 0.05) were significantly associated with prevalence of colorectal adenoma. Subjects with high levels of BMI, TG and FBS have increased prevalence of developing colorectal adenoma in Korea. PMID:23429421

  15. 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

  16. IDENTIFICATION OF A TRIGLYCERIDE (GLYCERYL-1,2-DIOLEATE-3-PALMITATE)

    E-print Network

    Paris-Sud XI, Université de

    IDENTIFICATION OF A TRIGLYCERIDE (GLYCERYL-1,2-DIOLEATE-3-PALMITATE) AS A BROOD PHEROMONE OF THE HONEY BEE (APIS MELLIFERA L.) Identifizierung eines Tri-Glycerids (Glyceryl-1, 2-dioleat-3-palmitat) als

  17. Relationship between plasma plasminogen activator inhibitor-1 activity and VLDL triglyceride concentration, insulin levels and insulin sensitivity: studies in randomly selected normo- and hypertriglyceridaemic men

    Microsoft Academic Search

    A. Asplund-Carlson; A. Hamsten; B. Wiman; L. A. Carlson

    1993-01-01

    Summary  Impaired fibrinolytic function secondary to elevated plasma plasminogen activator inhibitor-1 activity, hypertriglyceridaemia and hyperinsulinaemia are frequent findings in patients with coronary heart disease. It has been debated whether VLDL or insulin is the major regulator of plasma plasminogen activator inhibitor-1 activity. This study examines the relationships between plasma plasminogen activator inhibitor-1 activity and VLDL triglyceride concentration, fasting and post-oral glucose

  18. Effect of Aqueous Extract of Ziziphus mauritiana Leaf on Cholesterol and Triglyceride Levels in Serum and Liver of Rats Administered Alcohol

    Microsoft Academic Search

    D. Dahiru; O. Obidoa

    2009-01-01

    2 Abstract: Effects of aqueous extract of Ziziphus mauritiana (Zm) leaf on serum and liver cholesterol and triacylglycerol were studied in chronic alcohol administered rats. Pretreatment co-administration and post treatment protocols were employed. Rats fed alcohol only for 6 weeks had significantly (p<0.05) elevated levels of both serum and liver cholesterol and triglyceride. Pretreatment of rats with 400 mg\\/kg bw

  19. 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

    Microsoft Academic Search

    Karen L. Teff; Joanne Grudziak; Raymond R. Townsend; Tamara N. Dunn; Ryan W. Grant; Sean H. Adams; Nancy L. Keim; Bethany P. Cummings; Kimber L. Stanhope; Peter J. Havel

    2009-01-01

    Context: Compared with glucose-sweetened beverages, consumption of fructose-sweetened beverages with meals elevates post- prandial 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 obese subjects has not been studied. Objective: Compare the effects of fructose- and glucose-sweetened beverages consumed with meals on hormones and

  20. 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

  1. 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

  2. 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...

  3. 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.

  4. Colorimetric Measurement of Triglycerides Cannot Provide an Accurate Measure of Stored Fat Content in

    E-print Network

    Zinn, Kai

    Colorimetric Measurement of Triglycerides Cannot Provide an Accurate Measure of Stored Fat Content methods for evaluating the levels of stored fat (triglycerides) in flies is a coupled colorimetric assay used for measurement of mammalian serum triglycerides, which are present in soluble lipoprotein

  5. Fat Mobilization in Adipose Tissue Is Promoted by Adipose Triglyceride Lipase

    Microsoft Academic Search

    Robert Zimmermann; Juliane G. Strauss; Guenter Haemmerle; Gabriele Schoiswohl; Ruth Birner-Gruenberger; Monika Riederer; Achim Lass; Georg Neuberger; Frank Eisenhaber; Albin Hermetter; Rudolf Zechner

    2004-01-01

    Mobilization of fatty acids from triglyceride stores in adipose tissue requires lipolytic enzymes. Dysfunctional lipolysis affects energy homeostasis and may contribute to the pathogenesis of obesity and insulin resistance. Until now, hormone-sensitive lipase (HSL) was the only enzyme known to hydrolyze triglycerides in mammalian adipose tissue. Here, we report that a second enzyme, adipose triglyceride lipase (ATGL), catalyzes the initial

  6. Adipose Triglyceride Lipase and Hormone-Sensitive Lipase Protein Expression Is Decreased in the Obese

    E-print Network

    Paris-Sud XI, Université de

    Adipose Triglyceride Lipase and Hormone-Sensitive Lipase Protein Expression Is Decreased discovered adipose triglyceride lipase (ATGL). The aim of the present study was to examine whether ATGL non- HSL lipase adipose triglyceride lipase (ATGL), being pre- dominantly expressed in adipose tissue

  7. Triglyceride-Rich Lipoproteins Prime Aortic Endothelium for an Enhanced Inflammatory Response to Tumor

    E-print Network

    Simon, Scott I.

    Triglyceride-Rich Lipoproteins Prime Aortic Endothelium for an Enhanced Inflammatory Response, Anne A. Knowlton, Anthony G. Passerini, Scott I. Simon Abstract--High levels of triglyceride. (Circ Res. 2007;100:381-390.) Key Words: triglyceride-rich lipoprotein endothelium monocyte NF B

  8. Endothelial inflammation correlates with subject triglycerides and waist size1 following a high fat meal2

    E-print Network

    Passerini, Tony

    1 Endothelial inflammation correlates with subject triglycerides and waist size1 following a high © 2010 by the American Physiological Society. #12;2 Abstract17 A rise in postprandial serum triglycerides triglyceride-rich lipoproteins (PP-TGRLs) in subjects ranging from normal to21 hypertriglyceridemic

  9. Effects of amount of dietary triglycerides on postprandial serum vitamin A in

    E-print Network

    Paris-Sud XI, Université de

    Effects of amount of dietary triglycerides on postprandial serum vitamin A in heathly adults. P the impor- tance of the amount of dietary triglyceride on the blood postprandial vitamin A response of triglycerides (0, 15, 30, 40 g as sun- flower oil). Fasting blood samples were obtained before the meal

  10. A method for the structural analysis of triglycerides and lecithins

    Microsoft Academic Search

    O. S. Privett; M. L. Blank

    1963-01-01

    The structural analysis of lecithins and triglycerides is described. The procedure is carried out on 2–5 mg of sample by a\\u000a combination of reductive ozonolysis and thin-layer chromatography (TLC). The ozonides as well as the aldehyde “cores” derived\\u000a from reduction of the ozonides are separated by TLC and analyzed quantitatively by densitometry. The constituent saturated\\u000a fatty acids of the separated

  11. Radiolysis of lipids: Mode of cleavage in simple triglycerides

    Microsoft Academic Search

    M. F. Dubravcic; W. W. Nawar

    1968-01-01

    The effect of gamma radiation on simple triglycerides was investigated. Trilaurin, trimyristin, tripalmitin, tristearin, tripalmitolein,\\u000a triolein and trilinolenin were irradiated under vacuum at 6 megarads. The volatile breakdown products were separated by vacuum\\u000a distillation and identified by gas chromatography and mass spectrometry. Qualitative and quantitative data show that the cleavage\\u000a in fatty acids essentially follows a specific pattern and is

  12. A high-fat diet and the threonine-encoding allele (Thr54) polymorphism of fatty acid-binding protein 2 reduce plasma triglyceride-rich lipoproteins.

    PubMed

    McColley, Steven P; Georgopoulos, Angeliki; Young, Lindsay R; Kurzer, Mindy S; Redmon, J Bruce; Raatz, Susan K

    2011-07-01

    The threonine-encoding allele (Thr54) of the fatty acid-binding protein 2 (FABP2) DNA polymorphism is associated with increased triglyceride (TG)-rich lipoproteins (TRL). We hypothesized that the TRL response to diets of varied fat content is affected by the FABP2 A54T polymorphism, specifically that a high-fat diet would reduce TRL and that the Thr54 allele would have an enhanced response. Sixteen healthy, postmenopausal women completed a crossover dietary intervention that included three 8-week, isoenergetic diet treatments. The treatments consisted of high fat (40% of energy as fat), low fat (20% of energy), and low fat + n-3 fatty acids (20% of energy plus 3% as n-3 fatty acids). Eight subjects were homozygous for the wild type (Ala54/Ala54) of the FABP2 polymorphism, whereas 8 subjects had at least 1 Thr54 allele (7, Ala54/Thr54; 1, Thr54/Thr54). High-fat diet showed significantly reduced plasma TGs, chylomicron TG, and very low-density lipoprotein TG from baseline in all participants. Although carriers of the Thr54 allele of the FABP2 polymorphism had significantly reduced TRL, there is no evidence of an interaction, which does not support our hypothesis. The alanine-encoding allele did not influence the dietary effects on the plasma lipids. PMID:21840466

  13. A Phellinus baumii extract reduces obesity in high-fat diet-fed mice and absorption of triglyceride in lipid-loaded mice.

    PubMed

    Noh, Jung-Ran; Lee, In-Kyoung; Ly, Sun-Yung; Yang, Keum-Jin; Gang, Gil-Tae; Kim, Yong-Hoon; Hwang, Jung-Hwan; Yun, Bong-Sik; Lee, Chul-Ho

    2011-03-01

    This study evaluated the anti-obesity effects of Phellinus baumii extract (PBE) in high-fat diet (HFD)-fed mice. Male 8-week-old C57BL/6 mice were randomly divided into four groups: control, normal chow diet plus vehicle; HFD-control, high-fat plus vehicle; HFD plus orlistat (Xenical(®), Roche, Basel, Switzerland) (50?mg/kg); and HFD plus PBE (500?mg/kg). PBE was administered daily by oral gavage for 12 weeks. Oral administration of PBE (500?mg/kg) significantly reduced body weight gain, hepatic lipid concentrations, and fat accumulation in epididymal adipocytes compared with mice fed HFD alone (P?triglyceride (TG) synthesis was suppressed in the PBE groups, and fatty acid synthase activity was also significantly inhibited (P?TG absorption and detected marked reduction in TG absorption in Xenical- and PBE-treated mice compared with the control group (P?

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

    PubMed

    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

  15. 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

  16. TG16 point target detection experiment POLLEX, Livorno 2001

    NASA Astrophysics Data System (ADS)

    de Jong, Arie N.; Winkel, Hans; Moerman, Marcel M.; Stein, Karin; Weiss-Wrana, Karin; Forand, J. Luc; Potvin, Guy; Buss, James R.; Cini, Andrea; Vogel, Henrik H.; Stark, Espen

    2003-01-01

    NATO Task group TG16 is cooperating on topics related to ship self-defence. One of these topics is related to IR Search and Track sensors, which are in development for detection of low altitude air targets. In particular the group is working on models to predict the range performance of these sensors. Newly developed models include marine boundary layer effects such as refraction due to temperature gradients, scintillation due to turbulence and particle size distributions. TG16 organized in May 2001a trial in the Mediterranean Sea near Livorno, Italy, called POLLEX to further validate these models. Seven nations particulated with complementary instruments for measurements of the target signatures and environmental characteristics. Three targets were provided, a series of small visual/IR sources at a fixed distance, visual/IR soruces on a ship moving in and out up-to and beyond the horizon and a helicopter. The weather conditions during the measurement period showed interesting variations in Air to Sea Temperature DIfference and atmospheric turbulence. Data have been analzyed and samples of the results, as collected and/or analyzed by the participants, are discussed in this paper.

  17. 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

  18. Comparison of chloroform-methanol-extracted and solvent-free triglyceride determinations in four fish species.

    PubMed

    Bennett, Pamela M; Weber, Lynn P; Janz, David M

    2007-09-01

    Lipids, including triglycerides, are important variables in fish bioenergetics and can be used to estimate overall fish condition. Triglycerides are the major energy storage form in fish and therefore are a more ecologically and physiologically relevant measure of bioenergetics than total lipids. Chloroform-methanol-extracted total body lipids (Bligh and Dyer) and total body triglycerides determined in chloroform-methanol extracts and unextracted whole-body fractions were measured in four fish species: northern pike Esox lucius, burbot Lota lota, slimy sculpin Cottus cognatus, and spottail shiners Notropis hudsonius. Determinations of total body lipids were consistently greater than those of total body triglycerides when measured in the same solvent-extracted fraction, although both measures followed similar trends. In an effort to eliminate the need for extraction with organic solvents, we compared the performance of an enzyme-based triglyceride assay in both the solvent-extracted fraction and a whole-body unextracted homogenate for each fish. The chloroform-methanol-extracted triglyceride values were consistently lower than triglycerides measured in the unextracted whole-body homogenate. In addition, comparison of triglyceride measurements revealed limitations to the solvent extraction and subsequent triglyceride determinations in lean fish. Thus, in addition to being simple, rapid, and not requiring organic solvents, determination of triglycerides in an unextracted whole-fish homogenate may be a useful alternative to chloroform-methanol-based methods of lipid extraction and subsequent triglyceride measurement. PMID:18201059

  19. p38 MAPK protects human monocytes from postprandial triglyceride-rich lipoprotein-induced toxicity.

    PubMed

    Lopez, Sergio; Jaramillo, Sara; Varela, Lourdes M; Ortega, Almudena; Bermudez, Beatriz; Abia, Rocio; Muriana, Francisco J G

    2013-05-01

    Postprandial triglyceride (TG)-rich lipoproteins (TRLs) transport dietary fatty acids through the circulatory system to satisfy the energy and structural needs of the tissues. However, fatty acids are also able to modulate gene expression and/or induce cell death. We investigated the underlying mechanism by which postprandial TRLs of different fatty acid compositions can induce cell death in human monocytes. Three types of dietary fat [refined olive oil (ROO), high-palmitic sunflower oil (HPSO), and butter] with progressively increasing SFA:MUFA ratios (0.18, 0.41, and 2.08, respectively) were used as a source of postprandial TRLs (TRL-ROO, TRL-HPSO, and TRL-BUTTER) from healthy men. The monocytic cell line THP-1 was used as a model for this study. We demonstrated that postprandial TRLs increased intracellular lipid accumulation (31-106%), reactive oxygen species production (268-349%), DNA damage (133-1467%), poly(ADP-ribose) polymerase 1 (800-1710%) and caspase-3 (696-1244%) activities, and phosphorylation of c-Jun NH2-terminal kinase (JNK) (54 kDa, 141-288%) and p38 (24-92%). These effects were significantly greater with TRL-BUTTER, and TRL-ROO did not induce DNA damage, DNA fragmentation, or p38 phosphorylation. In addition, blockade of p38, but not of JNK, significantly decreased intracellular lipid accumulation and increased cell death in postprandial TRL-treated cells. These results suggest that in human monocytes, p38 is involved in survival signaling pathways that protect against the lipid-mediated cytotoxicity induced by postprandial TRLs that are abundant in saturated fatty acids. PMID:23486980

  20. Formation of prebeta1-HDL during lipolysis of triglyceride-rich lipoprotein.

    PubMed

    Miyazaki, Osamu; Fukamachi, Isamu; Mori, Atsuo; Hashimoto, Hideyuki; Kawashiri, Masa-aki; Nohara, Atsushi; Noguchi, Tohru; Inazu, Akihiro; Yamagishi, Masakazu; Mabuchi, Hiroshi; Kobayashi, Junji

    2009-01-30

    Prebeta1-HDL, a putative discoid-shaped high-density lipoprotein (HDL) is known to participate in the retrieval of cholesterol from peripheral tissues. In this study, to clarify potential sources of this lipoprotein, we conducted heparin injection on four Japanese volunteer men and found that serum triglyceride (TG) level decreased in parallel with the increase in serum nonesterified fatty acids and plasma lipoprotein lipase (LPL) protein mass after heparin injection. Plasma prebeta1-HDL showed considerable increases at 15 min after the heparin injection in all of the subjects. In contrast, serum HDL-C levels did not change. Gel filtration with fast protein liquid chromatography system (FPLC) study on lipoprotein profile revealed that in post-heparin plasma, low-density lipoprotein and alphaHDL fractions did not change, whereas there was a considerable decrease in very low-density lipoprotein (VLDL) fraction and an increase in prebeta1-HDL fraction when compared with those in pre-heparin plasma. We also conducted in vitro analysis on whether prebeta1-HDL was produced during VLDL lipolysis by LPL. One hundred microliters of VLDL extracted from pooled serum by ultracentrifugation was incubated with purified bovine milk LPL at 37 degrees C for 0-120 min. Prebeta1-HDL concentration increased in a dose dependent manner with increased concentration of added LPL in the reaction mixture and with increased incubation time, indicating that prebeta1-HDL was produced during lipolysis of VLDL by LPL. Taken these in vivo and in vitro analysis together, we suggest that lipolysis of VLDL particle by LPL is an important source for formation of prebeta1-HDL. PMID:19070596

  1. Omega3 fatty acid supplementation accelerates chylomicron triglyceride clearance

    Microsoft Academic Search

    Yongsoon Park; William S. Harris

    2003-01-01

    Omega-3 fatty acids (FAs) reduce postprandial triacylglycerol (TG) concentrations. This study was under- taken to determine whether this effect was due to reduced production or increased clearance of chylomicrons. Healthy subjects (n ? 33) began with a 4-week, olive oil placebo (4 g\\/d) run-in period. After a 4-week wash-out period, subjects were randomized to supplementation with 4 g\\/d of ethyl

  2. High fat diet induced insulin resistance and elevated retinol binding protein 4 in female rats; treatment and protection with Berberis vulgaris extract and vitamin A.

    PubMed

    El-Sayed, Mohamed Mohammed; Ghareeb, Doaa Ahmad; Talat, Heba Allah; Sarhan, Eman Mohammed

    2013-11-01

    This research was conducted to investigate two main aims; the first aim was to find if there is a relationship between insulin resistance (IR) and retinol binding protein 4 (RBP4). The second aim was to use berberis vulgaris extract and vitamin A as protective and/or curative agents against insulin resistance. IR was developed by feeding the female rats a high fat diet (HFD) for six weeks then treating or protecting them with b. vulgaris extract (0.2 g/Kg body weight) or vitamin A (12.8?g/Kg/day) for two weeks. HFD intake elevated insulin level and RBP4 expression that associated with hyperglycemia and hyperlipidemia. Co-administration of vitamin A and B. vulgaris extracts reduced blood glucose level, insulin, body weight and RBP4 expression before, during and after HFD. Furthermore, vitamin A reduced the blood glucose, triglycerides (TG) and cholesterol levels. IR syndrome associated with the RBP 4 alteration that gives high indication about the role of RBP4 expression in the IR progression and development. Furthermore, the treatment with vitamin A and/or b. vulgaris alleviated the IR syndrome through the action on RBP4 and Insulin secretion. On the other hand, vitamin A must be avoided for the predisposed IR and prediabetic patients. PMID:24191325

  3. Angelica sinensis polysaccharide regulates glucose and lipid metabolism disorder in prediabetic and streptozotocin-induced diabetic mice through the elevation of glycogen levels and reduction of inflammatory factors.

    PubMed

    Wang, Kaiping; Cao, Peng; Shui, Weizhi; Yang, Qiuxiang; Tang, Zhuohong; Zhang, Yu

    2015-03-11

    The present study was designed to evaluate the potential hypoglycemic and hypolipidemic effects of Angelica sinensis polysaccharide (ASP), purified from the fresh roots of Angelica sinensis (AS), in prediabetic and streptozotocin (STZ)-induced diabetic BALB/c mice. It was observed that fasting blood glucose (FBG) levels in both models were reduced after a 4-week oral administration of ASP or metformin, and abnormal fasting serum insulin (FINS) concentrations were ameliorated as well. Moreover, the homeostasis model assessment-insulin resistance (HOMA-IR) index was decreased strikingly and body weight (BW) was reduced significantly in prediabetic mice after treatment with ASP. In addition, ASP also contributed to improving the dyslipidemia conditions. Elevated serum total cholesterol (TC) or triglyceride (TG) concentrations were reduced after treatment with ASP in prediabetic mice or STZ-induced diabetic mice. Meanwhile, hepatic glycogen (HG) and muscle glycogen (MG) concentrations were increased while insulin resistance (IR)-related inflammatory factors IL-6 and TNF-? in serum were reduced in STZ-induced diabetic mice. Histopathological examination indicated that the impaired pancreatic/hepatic tissues or adipose tissues were effectively restored in STZ-induced diabetic mice or prediabetic mice after the ASP treatment. Taken together, these results revealed that ASP efficiently exerted hypoglycemic and hypolipidemic benefits, and its potential effect was associated with the amelioration of IR. ASP can be applied in the prevention and treatment of diabetes. PMID:25630053

  4. Elevated Lipoprotein Lipids and Gestational Hormones in Women With Diet-Treated Gestational Diabetes Mellitus Compared to Healthy Pregnant Controls

    Microsoft Academic Search

    Sarah C Couch; Elliot H Philipson; Robert B Bendel; Lillian M Pujda; Robert A Milvae; Carol J Lammi-Keefe

    1998-01-01

    The objective of this study was to describe plasma and lipoprotein perturbations in gestational diabetes mellitus (GDM) compared to controls, and determine if alterations in lipids are related to gestational hormones and\\/or glucose control. Maternal HbA1c, free fatty acids (FFA), ?-estradiol, progesterone, prolactin, and plasma, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), HDL2 and HDL3 triglyceride (TG), cholesterol,

  5. TG and ORG as energy converters from low enthalpy sources

    SciTech Connect

    Arosio, S.; Parolini, P.

    1983-12-01

    Dealing with the expliotation of low enthalpy sources, different engines and systems have been studied for many years. Among them two were developed at Dipartimento di Energetica del Politecnico di MilAno with sharing of C.E.E. (European Economic Community), ENEL (National Electric Energy Board) and C.N.R. (National Research Council); one is the so called Thermogravimetric system (TG)which operates the different density of a single phase flow and a two phase flow running in two vertical columns producing a nethead used by a hydraulic turbine (Kaplan model), the other one is the O.R.C. which works with an appropriate Rankine cycle at organic fluids producing a nethead utilizes by a vapor turbine. As for these systems, two pilot plants were recently built in Italy and a large experimental stage was carried out.

  6. 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.

  7. Analysis of olive oil and seed oil triglycerides by capillary gas chromatography as a tool for the detection of the adulteration of olive oil.

    PubMed

    Andrikopoulos, N K; Giannakis, I G; Tzamtzis, V

    2001-04-01

    Individual triglyceride (TG) species of olive oil and several seed oils (corn, cottonseed, palm, peanut, soybean, and sunflower) are baseline separated on a WCOT TAP CB fused-silica capillary column by capillary gas chromatography (CGC) with a flame-ionization detector (FID) and either cold on-column or split injection. An adulteration of olive oil with a low content (< 5%) of these seed oils (except peanut oil) can be verified by the detection of the increasing levels of trilinolein or tripalmitin in olive oil in which these TG species are normally absent or present at very low levels (< 0.5%). An adulteration with over 20% peanut oil can be detected by the increasing levels of palmitodilinolein. TG species that can be coeluted with trilinolein in the reversed-phase high-performance liquid chromatographic (RP-HPLC) mode are baseline separated by the CGC technique, and their structures are identified by selective ion monitoring mass spectrometry. The following comparisons--the CGC-FID and RP-HPLC methods for detection of adulteration, cold on-column and split-injection modes for CGC-FID, and silylation or thin-layer chromatography pretreatment and simple dilution of one or more of the oil samples--are also presented. The normalized percentage area of the TG species is sufficient for the method limits used in this study. Mixtures of virgin olive oil with refined or residue olive oil could not be distinguished from the virgin type by the method used in this study. PMID:11318065

  8. Making the Tg-Confinement Effect Disappear in Thin Polystyrene Films: Good Physics vs. Inappropriate Analysis

    NASA Astrophysics Data System (ADS)

    Torkelson, John; Chen, Lawrence

    2013-03-01

    The Tg-confinement effect in polymers was first characterized in supported polystyrene (PS) films by Keddie et al. in 1994. Since then, many researchers have shown that (pseudo-)thermodynamic Tg measurements of supported PS films taken on cooling consistently yield the same qualitative results, with a decrease from bulk Tg beginning at 40-60 nm thickness and becoming very strong below 20 nm thickness. Some quantitative differences have been noted between studies, which may be ascribed to measurement method or the analysis employed. In 2004, we showed that the Tg-confinement effect in PS may be suppressed by adding several wt% of small-molecule diluents such as dioctyl phthalate. Recently, Kremer and co-workers (Macromolecules 2010, 43, 9937) reported that there was no Tg-confinement in supported PS films based on an analysis of the second derivative of ellipsometry data and use of a ninth order polynomial fit. Here, we demonstrate a new method for suppressing the Tg-confinement effect. In particular, PS made by emulsion polymerization yields no Tg-confinement effect as measured by ellipsometry or fluorescence, while PS made by anionic or conventional free radical polymerization yield strong Tg-confinement effects. The difference is hypothesized to result from surfactant in the emulsion polymerized PS. We also show that the absence of the Tg-confinement effect reported by Kremer is due to inappropriate analysis of ellipsometry data and that correct analysis yields Tg-confinement effects.

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

    PubMed

    Varela, Lourdes M; López, Sergio; Ortega-Gómez, Almudena; Bermúdez, Beatriz; Buers, Insa; Robenek, Horst; Muriana, Francisco J G; Abia, Rocío

    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

  10. 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

  11. Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat.

    PubMed

    Smith, S J; Cases, S; Jensen, D R; Chen, H C; Sande, E; Tow, B; Sanan, D A; Raber, J; Eckel, R H; Farese, R V

    2000-05-01

    Triglycerides (or triacylglycerols) represent the major form of stored energy in eukaryotes. Triglyceride synthesis has been assumed to occur primarily through acyl CoA:diacylglycerol transferase (Dgat), a microsomal enzyme that catalyses the final and only committed step in the glycerol phosphate pathway. Therefore, Dgat has been considered necessary for adipose tissue formation and essential for survival. Here we show that Dgat-deficient (Dgat-/-) mice are viable and can still synthesize triglycerides. Moreover, these mice are lean and resistant to diet-induced obesity. The obesity resistance involves increased energy expenditure and increased activity. Dgat deficiency also alters triglyceride metabolism in other tissues, including the mammary gland, where lactation is defective in Dgat-/- females. Our findings indicate that multiple mechanisms exist for triglyceride synthesis and suggest that the selective inhibition of Dgat-mediated triglyceride synthesis may be useful for treating obesity. PMID:10802663

  12. Functional deprivation promotes amyloid plaque pathogenesis in Tg2576 mouse olfactory bulb and piriform cortex

    PubMed Central

    Zhang, Xue-Mei; Xiong, Kun; Cai, Yan; Cai, Huaibin; Luo, Xue-Gang; Feng, Jia-Chun; Clough, Richard W.; Patrylo, Peter R.; Struble, Robert G.; Yan, Xiao-Xin

    2010-01-01

    Cerebral hypometabolism and amyloid accumulation are principal neuropathological manifestations of Alzheimer’s disease (AD). Whether and how brain/neuronal activity might modulate certain pathological process of AD are interesting topics of recent clinical and basic research in the field, and may be of potential medical relevance in regard to both the disease etiology and intervention. Using the Tg2576 transgenic mouse model of AD, this study characterized a promotive effect of neuronal hypoactivity associated with functional deprivation on amyloid plaque pathogenesis in the olfactory pathway. Unilateral naris-occlusion caused BACE1 elevation in neuronal terminals in the deprived relative to the non-deprived bulb and piriform cortex in young adult mice. In parallel with the overall age-related plaque development in the forebrain, locally-increased BACE1 immunoreactivity co-occurred with amyloid deposition first in the piriform cortex then within the bulb, more prominent on the deprived relative to the non-deprived side. Biochemical analyses confirmed elevated BACE1 protein levels, enzymatic activity and products in the deprived relative to non-deprived bulbs. Plaque-associated BACE1 immunoreactivity in the bulb and piriform cortex was localized preferentially to swollen/sprouting glutamatergic axonal terminals, with A? immunoreactivity occurred inside as well as around these terminals. Together, these findings suggest that functional deprivation or neuronal hypoactivity facilitates amyloid plaque formation in the forebrain in a transgenic model of AD, which operates synergistically with age effect. The data also implicate an intrinsic association of amyloid accumulation and plaque formation with progressive axonal pathology. PMID:20384814

  13. Positional analysis of triglycerides and phospholipids rich in long-chain polyunsaturated fatty acids

    Microsoft Academic Search

    L. Amate; M. Ramírez; A. Gil

    1999-01-01

    Four sources of long-chain polyunsaturated fatty acids (LCP) differing in their chemical structure (triglycerides or phospholipids)\\u000a and in their origin (tuna triglycerides, fungal triglycerides, egg phospholipids, and pig brain phospholipids) were analyzed\\u000a to determine the distribution of the component fatty acids within the molecule. Lipase and phospholipase A2 hydrolysis was performed to obtain 2-monoacylglycerols and lysophospholipids, respectively, which allowed us

  14. Comparison of Chloroform–Methanol-Extracted and Solvent-Free Triglyceride Determinations in Four Fish Species

    Microsoft Academic Search

    Pamela M. Bennett; Lynn P. Weber; David M. Janz

    2007-01-01

    Lipids, including triglycerides, are important variables in fish bioenergetics and can be used to estimate overall fish condition. Triglycerides are the major energy storage form in fish and therefore are a more ecologically and physiologically relevant measure of bioenergetics than total lipids. Chloroform–methanol-extracted total body lipids (Bligh and Dyer) and total body triglycerides determined in chloroform–methanol extracts and unextracted whole-body

  15. Stereospecific analysis of triglycerides of Glycine max, Glycine soya, Avena sativa and Avena sterilis strains

    Microsoft Academic Search

    W. P. Pan; E. G. Hammond

    1983-01-01

    A rapid method for the stereospecific analysis of triglycerides based on enzymatic hydrolysis on thin layer plates was applied\\u000a to a number ofGlycine max, Glycine soya, Avena sativa andAvena sterilis strains. The percentage of each fatty acid on thesn-1,sn-2- andsn-3-positions was linearly related to the total percentage of the fatty acid in the triglyceride. Large deviations from the\\u000a common triglyceride

  16. Fracture Simulation of Highly Crosslinked Polymer Networks: Triglyceride-Based Adhesives

    NASA Astrophysics Data System (ADS)

    Lorenz, Christian; Stevens, Mark; Wool, Richard

    2003-03-01

    The ACRES program at the U. of Delaware has shown that triglyceride oils derived from plants are a favorable alternative to the traditional adhesives. The triglyceride networks are formed from an initial mixture of styrene monomers, free-radical initiators and triglycerides. We have performed simulations to study the effect of physical composition and physical characteristics of the triglyceride network on the strength of triglyceride network. A coarse-grained, bead-spring model of the triglyceride system is used. The average triglyceride consists of 6 beads per chain, the styrenes are represented as a single bead and the initiators are two bead chains. The polymer network is formed using an off-lattice 3D Monte Carlo simulation, in which the initiators activate the styrene and triglyceride reactive sites and then bonds are randomly formed between the styrene and active triglyceride monomers producing a highly crosslinked polymer network. Molecular dynamics simulations of the network under tensile and shear strains were performed to determine the strength as a function of the network composition. The relationship between the network structure and its strength will also be discussed.

  17. Bioconversion of Xylan to triglycerides by oil-rich yeasts. [Cryptococcus albidus; Cryptococcus terricoluus; Trichosporon

    SciTech Connect

    Fall, R.; Phelps, P.; Spindler, D.

    1984-05-01

    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 Crytococcus 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. Crytococcus 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. 22 references.

  18. Gas-liquid chromatography of triglycerides from erucic acid oils and fish oils.

    PubMed

    Harlow, R D; Litchfield, C; Reiser, R

    1966-05-01

    By critically selecting optimum operating conditions, quantitative gas-liquid chromatography of triglycerides has been extended to molecules containing substantial amounts of C(20), C(22), and C(24) fatty acids. The triglycerides of four erucic acid oils (water cress, rapessed, nasturtium, andLunaria annua) and two fully hydrogenated fish oils (menhaden and tuna) have been quantitatively analyzed by this technique. The average fatty acid chain length calculated from the triglyceride composition of each oil agreed closely with that determined by GLC of its respective methyl esters. Several conclusions about the triglyceride composition of the fats analyzed are discussed. PMID:17805614

  19. 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

  20. 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

  1. High plasma cholesterol, but low triglycerides and plaque-free arteries, in Mexican free-tailed bats.

    PubMed

    Widmaier, E P; Gornstein, E R; Hennessey, J L; Bloss, J M; Greenberg, J A; Kunz, T H

    1996-11-01

    Female mammals typically become hyperphagic from mid- to late pregnancy and during lactation. Mexican free-tailed bats, Tadarida brasiliensis mexicana, double their nightly food intake from late pregnancy to peak lactation and consume an insect diet that is exceptionally high in fat. During late pregnancy and throughout lactation, fasting plasma levels of cholesterol in this insectivorous bat are high (215 +/- 8 mg/dl) and are nearly 10-fold higher than in three species of Old World frugivorous bats. Fasting triglycerides were unexpectedly low in T. brasiliensis (25 +/- 2 mg/dl), despite evidence of high fat intake during nightly feeding bouts (postprandial cholesterol and triglycerides, 268 +/- 18 and 122 +/- 20 mg/dl, respectively). High-density lipoprotein (HDL) cholesterol levels were extraordinarily high (124 +/- 5 mg/dl) and unaffected by feeding. Low-density lipoprotein cholesterol levels were correspondingly low (86 +/- 7 mg/dl). This unusual plasma lipid profile was not associated with coronary or aortic atherosclerosis, nor was there evidence of hyperglycemia or hyperinsulinemia. A high-fat diet and high levels of cholesterol in T. brasiliensis are not correlated with cardiovascular disease or (possibly) insulin resistance. Among several possible factors that might account for these observations, nightly bouts of powered flight (commuting and foraging for food) may contribute to elevated HDL cholesterol, which may protect this species from developing atherosclerosis. PMID:8945941

  2. Upregulation of myocellular DGAT1 augments triglyceride synthesis in skeletal muscle and protects against fat-induced insulin resistance

    PubMed Central

    Liu, Li; Zhang, Yiying; Chen, Nancy; Shi, Xiaojing; Tsang, Bonny; Yu, Yi-Hao

    2007-01-01

    Increased fat deposition in skeletal muscle is associated with insulin resistance. However, exercise increases both intramyocellular fat stores and insulin sensitivity, a phenomenon referred to as “the athlete’s paradox”. In this study, we provide evidence that augmenting triglyceride synthesis in skeletal muscle is intrinsically connected with increased insulin sensitivity. Exercise increased diacylglycerol (DAG) acyltransferase (DGAT) activity in skeletal muscle. Channeling fatty acid substrates into TG resulted in decreased DAG and ceramide levels. Transgenic overexpression of DGAT1 in mouse skeletal muscle replicated these findings and protected mice against high-fat diet–induced insulin resistance. Moreover, in isolated muscle, DGAT1 deficiency exacerbated insulin resistance caused by fatty acids, whereas DGAT1 overexpression mitigated the detrimental effect of fatty acids. The heightened insulin sensitivity in the transgenic mice was associated with attenuated fat-induced activation of DAG-responsive PKCs and the stress mediator JNK1. Consistent with these changes, serine phosphorylation of insulin receptor substrate 1 was reduced, and Akt activation and glucose 4 membrane translocation were increased. In conclusion, upregulation of DGAT1 in skeletal muscle is sufficient to recreate the athlete’s paradox and illustrates a mechanism of exercise-induced enhancement of muscle insulin sensitivity. Thus, increasing muscle DGAT activity may offer a new approach to prevent and treat insulin resistance and type 2 diabetes mellitus. PMID:17510710

  3. TG2 transamidating activity acts as a reostat controlling the interplay between apoptosis and autophagy.

    PubMed

    Rossin, Federica; D'Eletto, Manuela; Macdonald, Douglas; Farrace, Maria Grazia; Piacentini, Mauro

    2012-05-01

    Tissue transglutaminase (TG2) activity has been implicated in inflammatory disease processes such as Celiac disease, infectious diseases, cancer, and neurodegenerative diseases, such as Huntington's disease. Furthermore, four distinct biochemical activities have been described for TG2 including protein crosslinking via transamidation, GTPase, kinase and protein disulfide isomerase activities. Although the enzyme plays a complex role in the regulation of cell death and autophagy, the molecular mechanisms and the putative biochemical activity involved in each is unclear. Therefore, the goal of the present study was to determine how TG2 modulates autophagy and/or apoptosis and which of its biochemical activities is involved in those processes. To address this question, immortalized embryonic fibroblasts obtained from TG2 knock-out mice were reconstituted with either wild-type TG2 or TG2 lacking its transamidating activity and these were subjected to different treatments to induce autophagy or apoptosis. We found that knock out of the endogenous TG2 resulted in a significant exacerbation of caspase 3 activity and PARP cleavage in MEF cells subjected to apoptotic stimuli. Interestingly, the same cells showed the accumulation of LC3 II isoform following autophagy induction. These findings strongly suggest that TG2 transamidating activity plays a protective role in the response of MEF cells to death stimuli, because the expression of the wild-type TG2, but not its transamidation inactive C277S mutant, resulted in a suppression of caspase 3 as well as PARP cleavage upon apoptosis induction. Additionally, the same mutant was unable to catalyze the final steps in autophagosome formation during autophagy. Our findings clearly indicate that the TG2 transamidating activity is the primary biochemical function involved in the physiological regulation of both apoptosis and autophagy. These data also indicate that TG2 is a key regulator of cross-talk between autophagy and apoptosis. PMID:21479826

  4. 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 Ávila, M D; Cambero, M I; López-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

  5. Effects of triglycerides on the hydrophobic drug loading capacity of saturated phosphatidylcholine-based liposomes.

    PubMed

    Hong, Soon-Seok; Kim, So Hee; Lim, Soo-Jeong

    2015-04-10

    A high drug-loading capacity is a critical factor for the clinical development of liposomal formulations. The accommodation of hydrophobic drugs within the liposomal membrane is often limited in saturated phosphatidylcholine (PC)-based liposomes owing to the rigidity of the lipid acyl chain. In the current study, we explored the possibility of improving the hydrophobic drug loading capacity of liposomes by incorporating triglyceride into liposomal membranes. Incorporation of Captex 300, a medium chain triglyceride, into liposomes composed of dimyristoylphosphatidylcholine and cholesterol greatly increased the fluidity and lamellarity of the resultant liposomes. Liposomal incorporation of medium or long chain, but not short chain, triglycerides greatly enhanced the concentration of loaded paclitaxel (PTX) in saturated PC-based liposomes. The enhancing effect of triglyceride saturated at a triglyceride content corresponding to the amount required to fluidize the liposome structure. In addition, the enhancing effect was not observed in unsaturated PC-based liposomes and was not associated with the solubility of PTX in each triglyceride. Triglycerides also enhanced the loading of docetaxel, another hydrophobic drug. Taken together, our results suggest that triglyceride incorporation in saturated PC-based liposomes provide an improved dosage form that enables increased hydrophobic drug loading by altering the fluidity and structure of liposomal membranes. PMID:25667981

  6. 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, 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, Asa; 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; Stan?áková, 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

    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

  7. Mobilization of triglyceride but not cholesterol or tocopherol from human adipocytes during weight reduction13

    Microsoft Academic Search

    Ernst J Schaefer; Rosy Woo; Masayoshi Kibata; Loring Bjornsen; Paul H Schreibman

    Adipocyte triglyceride, cholesterol, and tocopherol contents were examined in three human obese subjects, all over 150% of ideal weight, who were placed on weight reduction formula diets for 11, 21, and 25 wk, respectively. Body weight decreased from 77 to 63 kg, 188 to 147 kg, and 147 to 99 kg, respectively. All subjects had normal serum cholesterol and triglyceride

  8. Interactions of triglycerides with phospholipids: Incorporation into the bilayer structure and formation of emulsions

    SciTech Connect

    Hamilton, J.A. (Boston Univ. School of Medicine, MA (USA))

    1989-03-21

    Interactions of carbonyl {sup 13}C-enriched triacylglycerols (TG) with phospholipid bilayers were studied by {sup 13}C NMR spectroscopy. In spectra of DPPC vesicles with TG at 40-50{degree}C, both triolein (TO) and tripalmitin (TP) had narrow carbonyl resonances, indicative of rapid motions, and chemical shifts indicative of H bonding of the TG carbonyls with solvent (H{sub 2}O) at the aqueous interfaces of the vesicle bilayer. Below the phase transition temperature of the DPPC/TG vesicles, most phospholipid peaks broadened markedly. In DPPC vesicles with TP, the TP carbonyl peaks broadened beyond detection below the transition, whereas in vesicles with TO, the TO carbonyl peaks showed little change in line width or chemical shift and no change in the integrated intensity. These properties (extent of solubility in the PC surface, conformation, solvent accessibility, and molecular mobility) may be important for enzymatic hydrolysis and protein-mediated transfer of TG. In gel-phase DPPC, the molecular mobility of the TG depends on the nature of the TG acyl chains. In the DPPC/TG mixtures studied, attempts to incorporate TG in excess of the bilayer solubility resulted in production of emulsion particles. The significance of these results for TG metabolism is discussed.

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

    PubMed

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

    2014-12-01

    Autophagy, the major lysosomal pathway for the turnover of intracellular organelles is markedly impaired in neurons in Alzheimer's 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 Alzheimer's disease. PMID:25270989

  10. 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.

  11. Inhibition of JAK2 Signaling by TG101209 Enhances Radiotherapy in Lung Cancer Models

    PubMed Central

    Sun, Yunguang; Moretti, Luigi; Giacalone, Nicholas J; Schleicher, Stephen; Speirs, Christina K.; Carbone, David P.; Lu, Bo

    2011-01-01

    Introduction Persistent STAT3 activation contributes to lung carcinogenesis. Survivin, one of STAT3-regulated genes, is antiapoptotic and confers cancer radioresistance. Methods We tested whether TG101209, a small-molecule inhibitor of JAK2 (a STAT3-activating tyrosine kinase), affected survivin expression and sensitized lung cancer to radiation. We investigated whether inhibition of JAK2 signaling with TG101209 can be used to reduce survivin expression and enhance radiosensitivity of lung cancer cells in vitro and tumor growth delay in vivo. JAK2 downstream signaling, including PI3-K/Akt and Ras/MAPK/ERK pathways, was also explored. Results TG101209 inhibited STAT3 activation and survivin expression, and sensitized HCC2429 (DER=1.34,p=0.002) and H460 (DER=1.09,p=0.006) cells to radiation in clonogenic assays. Radiation promoted phospho-Akt and phospho-ERK in H460 cells, while their levels were unchanged in HCC2429. After treatment with TG101209, phospho-ERK protein levels were reduced in both HCC2429 and H460 cells. HCC2429 cells transfected with K-Ras-12V mutant were more resistant to radiation- and TG101209-induced apoptosis than wild-type control cells. In vivo, addition of TG101209 to radiation in lung xenografts produced a significant tumor growth delay (>10 days) compared to radiation alone and was well tolerated. Immunohistochemistry staining of tumor sections showed that TG101209 increased apoptosis and decreased cell proliferation and vascular density, suggesting that TG101209 also has antiangiogenic effects. Conclusions TG101209 enhanced the effects of radiation in lung cancer in vitro and in vivo. This study suggests the potential utility of selecting lung cancer patients according to K-Ras mutation status for future clinical trials testing combination of TG101209 and radiotherapy. PMID:21325979

  12. Plasma cholesterol, triglyceride and high-density lipoprotein-cholesterol levels in 17-year-old Jerusalem offspring of Jews from 19 countries of birth.

    PubMed

    Halfon, S T; Eisenberg, S; Baras, M; Davies, A M; Halperin, G; Stein, Y

    1982-11-01

    The distribution of plasma cholesterol, triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C) was examined in 6,654 17-yr-old young men and women who attended an army medical examination. There were highly significant differences among the four main groups, classified according to their father's place of birth: Israel, the Asian Near East, North Africa and Europe (including the Americas, Oceania and Southern Africa). Mean levels of plasma cholesterol in each group varied in males from 126.9 to 137.4 mg/dl, TG from 72.1 to 77.8 mg/dl and HDL-C from 41.3 to 44.4 mg/dl. In females, the cholesterol levels ranged from 144.6 to 154.8 mg/dl, TG from 72.7 to 76.3 and HDL-C from 47.3 to 50.5 mg/dl. In the various groups, subjects of North African origin consistently had the lowest lipid values, and subjects whose fathers were born in Europe or Israel, the highest. When the subjects were classified according to their fathers' specific country of origin, mean cholesterol values ranged from a low of 126.2 mg/dl in Moroccan males to a high of 143.0 in Austrian and Swiss males, and from 137.6 mg/dl in Tunisian females to 161.6 in those whose fathers had emigrated from North American countries. HDL-C ranged in males from 40.0 mg/dl in the Egyptian group to 47.0 in the Austrian-Swiss-Lichtenstein group; in females, the values ranged from 46.0 mg/dl in the Algerian group to 53.4 in the Austrian-Swiss-Lichtenstein group. These findings are discussed in light of published reports of lipid and lipoprotein levels in individuals living in different countries. PMID:7161044

  13. 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 ?H. 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 ?H 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 ?H 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.

  14. Uptake of hypertriglyceridemic very low density lipoproteins and their remnants by HepG2 cells: the role of lipoprotein lipase, hepatic triglyceride lipase, and cell surface proteoglycans.

    PubMed

    Huff, M W; Miller, D B; Wolfe, B M; Connelly, P W; Sawyez, C G

    1997-07-01

    Hypertriglyceridemic very low density lipoproteins (HTG-VLDL, S(f) 60-400) are not taken up by HepG2 cells. However, addition of bovine milk lipoprotein lipase (LPL) at physiological concentrations markedly stimulates uptake. In the present study, we determined whether: a) LPL catalytic activity is required for uptake, b) LPL functions as a ligand, and c) cell surface hepatic triglyceride lipase (HL) and/or proteoglycans are involved. Incubation of HepG2 cells with HTG-VLDL plus LPL (8 ng/ml) increased cellular cholesteryl ester (CE) 3.5-fold and triglyceride (TG) 6-fold. Heat-inactivation of LPL abolished the effect. Addition of tetrahydrolipstatin (THL, an LPL active-site inhibitor) to HTG-VLDL + LPL, inhibited the cellular increase in both CE and TG by greater than 90%. Co-incubation of HTG-VLDL + LPL with heparin, heparinase, or heparitinase, blocked CE accumulation by 70%, 48%, and 95%, respectively, but had no effect on the increase in cellular TG. Pre-treatment of cells with 1 mM 4-methylumbelliferyl-beta-D-xyloside, (beta-xyloside) to reduce cell surface proteoglycans inhibited the increase in CE induced by HTG-VLDL + LPL by 78%. HTG-VLDL remnants, prepared in vitro and isolated free of LPL activity, stimulated HepG2 cell CE 2.8-fold in the absence of added LPL, a process inhibited with THL by 66%. Addition of LPL (8 ng/ml) to remnants did not further enhance CE accumulation. HepG2 cell HL activity, released by heparin, was inhibited 95% by THL. The amount of HL activity and immunoreactive mass, released by heparin, was reduced 50-60% in beta-xyloside-treated cells. These results indicate that physiological concentrations of LPL promote HepG2 cell uptake of HTG-VLDL primarily due to remnant formation and that LPL does not play a major role as a ligand. HL activity and cell surface proteoglycans significantly enhance the subsequent uptake of VLDL remnants. PMID:9254059

  15. Increased ?-Amyloid Deposition in Tg-SWDI Transgenic Mouse Brain Following In Vivo Lead Exposure

    PubMed Central

    Gu, Huiying; Robison, Gregory; Hong, Lan; Barrea, Raul; Wei, Xing; Farlow, Martin R.; Pushkar, Yulia N; Du, Yansheng; Zheng, Wei

    2012-01-01

    Previous studies in humans and animals have suggested a possible association between lead (Pb) exposure and the etiology of Alzheimer’s disease (AD). Animals acutely exposed to Pb display an over-expressed amyloid precursor protein (APP) and the ensuing accumulation of beta-amyloid (A?) in brain extracellular spaces. This study was designed to examine whether in vivo Pb exposure increased brain concentrations of A?, resulting in amyloid plaque deposition in brain tissues. Human Tg-SWDI APP transgenic mice, which genetically over-express amyloid plaques at age of 2-3 months, received oral gavages of 50 mg/kg Pb acetate once daily for 6 wk; a control group of the same mouse strain received the same molar concentration of Na acetate. ELISA results revealed a significant increase of A? in the CSF, brain cortex and hippocampus. Immunohistochemistry displayed a detectable increase of amyloid plaques in brains of Pb-exposed animals. Neurobehavioral test using Morris water maze showed an impaired spatial learning ability in Pb-treated mice, but not in C57BL/6 wild type mice with the same age. In vitro studies further uncovered that Pb facilitated A? fibril formation. Moreover, the synchrotron X-ray fluorescent studies demonstrated a high level of Pb present in amyloid plaques in mice exposed to Pb in vivo. Taken together, these data indicate that Pb exposure with ensuing elevated A? level in mouse brains appears to be associated with the amyloid plaques formation. Pb apparently facilitates A? fibril formation and participates in deposition of amyloid plaques. PMID:22796588

  16. 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.

  17. 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

    Wang, Yue; Mattson, Mark P

    2014-01-01

    Abnormal neuronal excitability and impaired synaptic plasticity might occur before the degeneration and death of neurons in Alzheimer's 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) Ca(2+) currents (L-VGCC), 4-aminopyridine-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 ?-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 Ca(2+) 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 Ca(2+), 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

  18. Rexinoid bexarotene modulates triglyceride but not cholesterol metabolism via gene-specific permissivity of the RXR/LXR heterodimer in the liver

    E-print Network

    Paris-Sud XI, Université de

    Rexinoid bexarotene modulates triglyceride but not cholesterol metabolism via gene is an increase in plasma triglycerides, an independent risk factor of cardio- vascular disease. The molecular, bexarotene administration induces an undesirable increase in plasma triglycerides7, 8 , an independent risk

  19. 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....

  20. Appropriate blood sampling sites for measuring Tg concentrations for forensic diagnosis.

    PubMed

    Hayakawa, Akira; Matoba, Kotaro; Horioka, Kie; Murakami, Manabu; Terazawa, Koichi

    2015-01-01

    Previous studies have reported that thyroglobulin (Tg) concentrations in heart blood are high in cases of asphyxia caused by neck compression such as hanging, strangulation, and throttling and in those with fatal traumatic brain injuries. However, even in cases without these findings presumed to increase the Tg concentration in the previous studies, we previously reported that in some cases the Tg concentration in right heart blood (RHB) and left heart blood (LHB) exceeded the standard value for diagnosis (200 ng/mL) defined in previous studies and the Tg concentration in RHB was significantly higher than that in LHB. In the present study, in our 46 forensic autopsy cases without findings presumed to increase Tg concentration, we separately collected external iliac venous blood (IVB) and external iliac arterial blood (IAB) in addition to RHB and LHB, measured Tg concentrations in RHB, LHB, IVB, and LAB (TRHB, TLHB, TIVB, and TIAB, respectively), and investigated the appropriate blood sampling site for measuring Tg concentrations for forensic diagnosis. TRHB, TLHB, TIVB, and TIAB were 386.3 ± 674.1, 105.8 ± 179.0, 109.2 ± 166.8, and 43.7 ± 90.9 ng/mL, respectively. There were statistically significant differences between TRHB and TLHB, TIVB and TIAB, TRHB and TIVB, and TLHB and TIAB. Tg is more readily diffused by the venous system (RHB, IVB) than by the arterial system (LHB, IAB) because the venous system retains more blood volume after death. Tg is more readily diffused to heart blood (RHB, LHB) than to peripheral blood (IVB, IAB) because of the proximity of the heart to the thyroid gland. Therefore, we conclude that Tg leaks into the vessels around the thyroid gland because of the influences of postmortem changes and subsequently diffuses through the blood after death, and therefore the Tg concentration increases after death. When Tg concentration values are used for forensic diagnosis, it is appropriate to measure them using peripheral arterial blood situated distant from the thyroid gland. PMID:25287273

  1. 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.

  2. Successful Treatment of Severe Hypertriglyceridemia with a Formula Diet Rich in Omega–3 Fatty Acids and Medium-Chain Triglycerides

    Microsoft Academic Search

    Annette Hauenschild; Reinhard G. Bretzel; Henning Schnell-Kretschmer; Hans-Ulrich Kloer; Philip D. Hardt; Nils Ewald

    2010-01-01

    Background: Patients with highly increased plasma triglyceride levels are at risk of developing serious complications such as pancreatitis, coronary heart disease and stroke. Therefore it is important to rapidly decrease plasma triglyceride levels. A sufficient control of triglyceride levels with drugs like fibrates, statins or nicotinic acid can usually only be attained after a couple of weeks. Plasma exchange appears

  3. High levels of dietary arachidonic acid triglyceride exhibit no subchronic toxicity in rats.

    PubMed

    Koskelo, E K; Boswell, K; Carl, L; Lanoue, S; Kelly, C; Kyle, D

    1997-04-01

    Arachidonic acid (AA), an n-6 long-chain polyunsaturated fatty acid (LC-PUFA), serves an important role in the body as a structural fatty acid of many tissues including neurological tissues. It is also a precursor of the n-6 class of eicosanoids and is the most abundant n-6 LC-PUFA found in human breast milk. We have optimized the production of a microfungal source of a triglyceride oil (ARASCO) which is enriched in AA to about 40% by weight. To establish the safety of this oil as a food, we evaluated the effect of ARASCO in Sprague-Dawley rats (20/sex/group) gavaged at dose levels of 1.0 and 2.5 g/kg/d for a period of 90 d, paying special attention to any potential neurotoxicity of the oil. Two groups of control animals received either untreated standard laboratory diet (untreated control) or the same diet and vehicle oil at the same dose volume administered to the treated animals (vehicle control). Physical observations, ophthalmoscopic examinations, body weight, food consumption, clinical chemistry, hematology parameters, neurobehavioral assessments, and macroscopic as well as microscopic postmortem evaluations were performed. Tissue fatty acid analyses indicated that the AA levels in the brain, heart, and liver of the high-dose ARASCO-fed animals increased by 8, 59, and 76%, respectively, indicating that the AA in the oil was readily incorporated into tissue lipids. In spite of this high elevation in tissue AA levels, no developmental, histopathological, or neuropathological differences were seen in the animals administered ARASCO compared with the vehicle control animals. Being highly enriched in AA, ARASCO offers the means to study the effect of this fatty acid in experimental settings and in human metabolic studies. PMID:9113628

  4. TG studies of a composite solid rocket propellant based on HTPB-binder

    Microsoft Academic Search

    J. A. F. F. Rocco; J. E. S. Lima; A. G. Frutuoso; K. Iha; M. Ionashiro; J. R. Matos; M. E. V Suárez-Iha

    2004-01-01

    Thermal decomposition kinetics of solid rocket propellants based on hydroxyl-terminated polybutadiene-HTPB binder was studied\\u000a by applying the Arrhenius and Flynn-Wall-Ozawa's methods. The thermal decomposition data of the propellant samples were analyzed\\u000a by thermogravimetric analysis (TG\\/DTG) at different heating rates in the temperature range of 300-1200 K. TG curves showed\\u000a that the thermal degradation occurred in three main stages regardless of

  5. Intracerebroventricular infusion of a triglyceride emulsion leads to both altered insulin secretion and hepatic glucose production in rats.

    PubMed

    Clément, Laurence; Cruciani-Guglielmacci, Céline; Magnan, Christophe; Vincent, Mylène; Douared, Laetitia; Orosco, Martine; Assimacopoulos-Jeannet, Françoise; Pénicaud, Luc; Ktorza, Alain

    2002-12-01

    We investigated here whether non-esterified fatty acids (NEFA) influence insulin secretion and action through a direct effect on central nervous system sites involved in the control of glucose homeostasis. Normal Wistar rats received a 48-h intracerebroventricular infusion of either a 10% triglyceride (Intralipid, IL)/heparin emulsion (IL/h) or saline/heparin solution (control). At 48 h, insulin secretion as measured by an intravenous glucose tolerance test, was more elevated in IL/h than in control rats. Pancreatic noradrenaline turnover was decreased by 57% in IL/h rats, suggesting low pancreatic sympathetic output that could account partly for the elevated insulin secretion. The time course of glycaemia was similar in both groups, suggesting insulin resistance. Euglycaemic-hyperinsulinaemic clamps were imposed to assess peripheral and hepatic insulin sensitivity. At each insulin concentration glucose utilization was increased to a similar extent in both groups, whereas hepatic glucose production decreased much less in IL/h than in control rats. Hepatic insulin insensitivity could be related partly to activation of the hypothalamic-pituitary-adrenocortical axis, since plasma corticosterone concentration was significantly increased in IL/h rats compared with controls. Our data indicate that lipids may alter both insulin secretion and hepatic sensitivity to insulin through their effect on central nervous system. PMID:12466940

  6. Low doses of eicosapentaenoic acid and docosahexaenoic acid from fish oil dose-dependently decrease serum triglyceride concentrations in the presence of plant sterols in hypercholesterolemic men and women.

    PubMed

    Ras, Rouyanne T; Demonty, Isabelle; Zebregs, Yvonne E M P; Quadt, Johan F A; Olsson, Johan; Trautwein, Elke A

    2014-10-01

    Plant sterols (PSs) lower LDL cholesterol (LDL-C) concentrations, whereas the n-3 (?-3) fish fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) lower triglyceride (TG) concentrations. Incorporating both PSs and EPA+DHA from fish oil (FO) in a single food format was expected to beneficially affect 2 blood lipid risk factors. The aim of this study was to investigate the dose-response relation between low doses (<2 g/d) of EPA+DHA from FO, incorporated in a low-fat PS-enriched spread, and TG concentrations. In addition, effects on LDL-C were investigated. The study was designed as a randomized, double-blind, placebo-controlled parallel study. After a 4-wk run-in period, subjects were randomly assigned to consume either a control (C) spread (no PSs, no FO) or 1 of 4 intervention spreads containing a fixed amount of PSs (2.5 g/d) and varying amounts of FO (0.0, 0.9, 1.3, and 1.8 g/d of EPA+DHA) for 4 wk. Before and after the intervention, fasting blood samples were drawn for measuring serum lipids and EPA and DHA in erythrocyte membranes. In total, 85 hypercholesterolemic men and 247 women with a mean age of 57.9 y (range: 25-74 y) were included. Eighteen subjects dropped out during the study. At baseline, mean TG and LDL-C concentrations were 1.09 and 4.00 mmol/L, respectively. After the intervention, a significant dose-response relation for the TG-lowering effect of EPA+DHA [?ln (TG) = -0.07 mmol/L per gram of EPA+DHA; P < 0.01] was found. Compared with the C group, TG concentrations were 9.3-16.2% lower in the different FO groups (P < 0.05 for all groups). LDL-C concentrations were 11.5-14.7% lower in the different PS groups than in the C group (P < 0.01 for all groups). EPA and DHA in erythrocyte membranes were dose-dependently higher after FO intake than after the C spread, indicating good compliance. Consumption of a low-fat spread enriched with PSs and different low doses of n-3 fatty acids from FO decreased TG concentrations in a dose-dependent manner and decreased LDL-C concentrations. This trial was registered at clinicaltrials.gov as NCT01313988. PMID:25122648

  7. The analysis of triglyceride-rich lipoproteins in human serum for clinical studies

    E-print Network

    Chandra, Richa

    2009-06-02

    dietary fats, which are positively correlated with cardiovascular disease. The mechanism behind which triglycerides cause cardiovascular disease is not well understood. The analysis of TRL by novel methods including density gradient ultracentrifugation...

  8. Esterification kinetics of triglycerides in n-hexane catalyzed by an immobilized lipase

    E-print Network

    Gomez Ruiz, Alejandro

    1998-01-01

    The kinetics of enzyme-catalyzed esterification of triglycerides over immobilized lipase in n-hexane was investigated. The reaction kinetics were described in terms of a mechanism developed following the Langmuir-Hinshelwood-Hougen-Watson (LHHW...

  9. 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 ...

  10. 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.

  11. Disappointment with triethers as markers for measuring triglyceride absorption in man

    PubMed Central

    Saunders, D. R.; O'Brien, T. K.

    1972-01-01

    Glycerol triethers were tried as non-absorbable, oil-phase markers for indirectly measuring triglyceride absorption in the human proximal jejunum. Tritium labelled 1-hexadecyl-2, 3-didodecyl glycerol, or 1,2,3-trioleyl glycerol, or 1,2,3-tridecyl glycerol was dissolved in linseed oil and egg yolk lipids; an aqueous emulsion of the lipid mixture was infused into the stomach. Unexpectedly, postprandial jejunal contents contained proportionately less triether than triglyceride compared with the test meals. These triethers were found to separate from an aqueous phase at a faster rate than the triglyceride. This dissociation occurred in the stomach and thwarted quantification of triglyceride absorption by this test system. PMID:4678697

  12. 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...

  13. Hypercholesterolemia and triglyceride secretion rates in monkeys fed different dietary fats.

    PubMed

    Nicolosi, R J; Hayes, K C; el Lozy, M; Herrera, M G

    1977-11-01

    The influence of hypercholesterolemia on the triglyceride secretion rate was studied in both squirrel and cebus monkeys fed coconut oil, corn oil, or safflower oil. The triglyceride secretion rate (TGSR) was determined in vivo following the administration of Triton WR1339, which blocks the clearance of very low density lipoprotein (VLDL). Thus, the increase observed in circulating triglyceride after Triton administration presumably reflecte hepatic triglyceride (VLDL) secretion in the fasted state. The VLDL-TGSR was lowest in hypercholesterolemic monkeys and highest in those fed unsaturated fat diets and having a low serum cholesterol. In all instances, TGSR was inversely correlated with the plasma cholesterol concentration. While a definitive explanation for these observations must await further investigation, the possibility that circulating low density lipoprotein (LDL) acts to feed back on VLDL secretion is discussed. The decreased TGSR associated with the diet-induced cholesterolemia also implies clearance of VLDL is impaired under these conditions. PMID:200815

  14. Relation of bovine loin, hip, and brisket depot triglycerides to reproductive performance

    E-print Network

    Cammack, Johnny Carl

    1967-01-01

    ) described fats as the fatty acid eaters of glycerol which have been commonly called triglycerides. Trigly- cerides have been reported to be the most abundant lipids in nature which have often been referred to as neutral fat or just "fat". The major... retention time, and the last unknown located after linolenic was determined to be an unsaturate due to its particular separation on silver nitrate plates. Results of Triglyceride Fatty Acid Analyses The appendix contains each cow's weight percent...

  15. Studies on effects of dietary fatty acids as related to their position on triglycerides

    Microsoft Academic Search

    J. Edward Hunter

    2001-01-01

    This article reviews published literature on how the stereospecific structure of dietary triglycerides may affect lipid metabolism\\u000a in humans. Animal studies have shown enhanced absorption of fatty acids in the sn-2 position of dietary triglycerides. Increasing the level of the saturated fatty acid palmitic acid in the sn-2 position (e.g., by interesterification of the fat to randomize the positions of

  16. Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia

    Microsoft Academic Search

    Daru Sharp; Laura Blinderman; Kelly A. Combs; Bernadette Kienzle; Beverly Ricci; Karen Wager-Smith; Cleris M. Gil; Christoph W. Turck; Marie-Elizabeth Boumas; Daniel J. Rader; Lawrence P. Aggerbeck; Richard E. Gregg; David A. Gordon; John R. Wetterau

    1993-01-01

    THE microsomal triglyceride transfer protein (MTP), which catalyses the transport of triglyceride, cholesteryl ester and phospho-lipid between phospholipid surfaces, is a heterodimer composed of the multifunctional protein, protein disulphide isomerase, and a unique large subunit with an apparent Mr of 88K (refs 1-3). It is isolated as a soluble protein from the lumen of the microsomal fraction of liver and

  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

    Microsoft Academic Search

    Len A. Pennacchio; Michael Olivier; Jaroslav A. Hubacek; Ronald M. Krauss; Edward M. Rubin; Jonathan C. Cohen

    2002-01-01

    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 â16 percent of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA5*3) containing the rare

  19. Dietary oligofructose lowers triglycerides, phospholipids and cholesterol in serum and very low density lipoproteins of rats

    Microsoft Academic Search

    Maria Fiordaliso; Nadine Kok; Jean-Pierre Desager; Fabienne Goethals; Dominique Deboyser; Marcel Roberfroid; Nathalie Delzenne

    1995-01-01

    The present study was aimed at answering the question why feeding rats an oligofructose (OFS) supplemented diet could cause\\u000a a significant reduction in plasma lipid levels. Daily administration of a 10% (w\\/w) OFS-containing diet to normolipidemic\\u000a male rats resulted in a decrease in plasma triglycerides, phospholipids and cholesterol. The triglyceride-lowering effect\\u000a was observed after one week and lasted for at

  20. VLDL compositional changes and plasma levels of triglycerides and high density lipoprotein

    Microsoft Academic Search

    Fernando D Brites; Carla D Bonavita; Marcelo Cloës; Mario J Yael; Jean-Charles Fruchart; Graciela R Castro; Regina W Wikinski

    1998-01-01

    VLDL chemical composition is related to plasma levels of triglycerides and HDL-cholesterol. We evaluated patients with primary hypertriglyceridemia with or without hypoalphalipoproteinemia and subjects with normotriglyceridemia with hypoalphalipoproteinemia. The pattern observed in all the groups was an enrichment in the triglyceride content of VLDL and in apo B-VLDL. Compared to controls, LpC-III:B levels were higher in hypertriglyceridemic patients with low

  1. Supplementation of Areca catechu L. Extract Alters Triglyceride Absorption and Cholesterol Metabolism in Rats

    Microsoft Academic Search

    Sung-June Byun; Hee-Sook Kim; Seon-Min Jeon; Yong Bok Park; Myung-Sook Choi

    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).

  2. Effects of Triglyceride Molecular Structure on Optimum Formulation of Surfactant-Oil-Water Systems

    Microsoft Academic Search

    Tri T. Phan; Jeffrey H. Harwell; David A. Sabatini

    2010-01-01

    The effects of triglyceride molecular structure on the formulation of surfactant-oil-water systems were evaluated by comparing\\u000a the optimum salinity and the dynamic interfacial tensions. The systems contained an anionic extended surfactant and triglyceride\\u000a oils with different chain lengths and degrees of unsaturation. The results show that with an increasing degree of oil unsaturation\\u000a (more double bonds), surfactant interactions with the

  3. Utilization of Triglycerides and Related Feedstocks for Production of Clean Hydrocarbon Fuels and Petrochemicals: A Review

    Microsoft Academic Search

    Iva Kubi?ková; David Kubi?ka

    2010-01-01

    Catalytic deoxygenation of triglycerides and related feedstocks for production of biofuels is reviewed in this paper. Green\\u000a diesel, triglyceride-based hydrocarbons in diesel boiling range, is an attractive alternative to biodiesel—a product of transesterification\\u000a of vegetable oils, particularly due to its superior fuel properties and full compatibility with current diesel fuels. Two\\u000a basic approaches to production of green diesel—(i) hydrodeoxygenation of

  4. Assessment of display performance for medical imaging systems: executive summary of AAPM TG18 report.

    PubMed

    Samei, Ehsan; Badano, Aldo; Chakraborty, Dev; Compton, Ken; Cornelius, Craig; Corrigan, Kevin; Flynn, Michael J; Hemminger, Bradley; Hangiandreou, Nick; Johnson, Jeffrey; Moxley-Stevens, Donna M; Pavlicek, William; Roehrig, Hans; Rutz, Lois; Shepard, Jeffrey; Uzenoff, Robert A; Wang, Jihong; Willis, Charles E

    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 (Lamb) 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/m2, 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',v' 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. PMID:15895604

  5. Long-term therapeutic silencing of miR-33 increases circulating triglyceride levels and hepatic lipid accumulation in mice

    PubMed Central

    Goedeke, Leigh; Salerno, Alessandro; Ramírez, Cristina M; Guo, Liang; Allen, Ryan M; Yin, Xiaoke; Langley, Sarah R; Esau, Christine; Wanschel, Amarylis; Fisher, Edward A; Suárez, Yajaira; Baldán, Angel; Mayr, Manuel; Fernández-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

  6. 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 ?cond=8-10 mN/m that separate "gas" and "condensed" film structures are the same for all mixtures and pure systems. In the ?- 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 ?- and ?-like structure are formed on top of the monolayer as in pure PPP and SSS systems.

  7. 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 cephalosporin’s 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 energy’s 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

  8. 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 (1950–2013). 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

  9. 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

  10. Capillary isotachophoresis study of lipoprotein network sensitive to apolipoprotein E phenotype. 2. ApoE and apoC-III relations in triglyceride clearance.

    PubMed

    Dergunov, Alexander D; Ponthieux, Anne; Mel'kin, Maxim V; Lambert, Daniel; Sokolova, Olga Yu; Akhmedzhanov, Nadir M; Visvikis-Siest, Sophie; Siest, Gerard

    2009-05-01

    The plasma (P), VLDL (V) triglyceride and apoB (B) clearance rates were measured both as 'mass' clearance (k (1)) and 'within the particle' clearance in three patient groups (E33, E23 and E34 phenotypes) at heparin-induced lipolysis in vivo. The lipid (C)- and apoE (E)-specific lipoprotein profiles both before and after heparin were followed by capillary isotachophoresis. The displacement of apoE by exogenous apoC-III at plasma titration in vitro was measured as well. The phenotype-sensitive lipoprotein networks were constructed based on an established set of metabolic rules. The k (1)(V) values did not differ between the three groups, but the lower k (1)(P) values showed significant differences. The k (1)(P) values for E33 and E23 groups were twofold higher compared to E34. A twofold increase in the rate constant for VLDL triglyceride clearance within the particle in E34 group compared to E23 reflected the inhibition of lipolysis by apoE2. For E33 group, (i) the k (1)(V) value was negatively correlated to the size of non-displaceable apoE pool in 2E lipoprotein and to the maximal apoE sorbtion capacity for 2E and 3E lipoproteins; (ii) the k (1)(P) value was not associated to the apoE binding parameters; (iii) the k (1)(V) value was positively correlated to the 4C level and the magnitude of apoC-III removal from VLDL particle; (iv) the k (1)(P) value was positively correlated to the content of apoE, while negatively with apoC-III, in VLDL remnants. For E34 group, the k (1)(V) value was positively correlated to 11C and 1-7C pool levels. Lipolysis- and receptor-mediated TG runways seem to be mostly balanced in E33 group, and VLDL TG clearance may be controlled by HDL through apoE dissociation from VLDLs and apolipoprotein accumulation within 'fast' HDLs at lipolysis. PMID:19139974

  11. The PNPLA3 Ile148Met interacts with overweight and dietary intakes on fasting triglyceride levels.

    PubMed

    Stojkovic, Ivana A; Ericson, Ulrika; Rukh, Gull; Riddestråle, Martin; Romeo, Stefano; Orho-Melander, Marju

    2014-03-01

    The Ile148Met (rs738409, G-allele) in the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) associates with liver fat content and may lead to loss-of-function (hydrolysis) or gain-of-function (CoA-dependent lysophosphatidic acid acyltransferase) defects. PNPLA3 is up-regulated by dietary carbohydrates, and interactions between rs738409 and carbohydrates, and sugar and ?6:?3-polyunsaturated fatty acid (PUFA) ratio on hepatic fat accumulation have been reported. We examined interaction between rs738409 and overweight, and between rs738409 and dietary intakes (carbohydrates, sucrose and ?6:?3-PUFA ratio), on fasting triglyceride levels. From the Malmo Diet and Cancer Study-Cardiovascular Cohort, 4,827 individuals without diabetes aged 58 ± 6 years, 2,346 with BMI ? 25 kg/m(2) and 2,478 with BMI > 25 kg/m(2), were included in cross-sectional analyses. Dietary data were collected by a modified diet history method. Overweight modified the association between rs738409 and fasting triglyceride levels (P interaction = 0.003). G-allele associated with lower triglycerides only among overweight individuals (P = 0.01). Nominally, significant interaction on triglyceride levels was observed between rs738409 and sucrose among normal-weight individuals (P interaction = 0.03). G-allele associated with lower triglycerides among overweight individuals in the lowest tertiles of carbohydrate and ?6:?3-PUFA ratio (P = 0.04 and P = 0.001) and with higher triglycerides among normal-weight individuals in the highest tertile of sucrose (P = 0.001). We conclude that overweight and dietary sucrose may modify the association between rs738409 and fasting triglyceride levels. PMID:24563329

  12. 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.

  13. A combined QXRD/TG method to quantify the phase composition of hydrated Portland cements

    SciTech Connect

    Soin, Alexander V.; Catalan, Lionel J.J. [Department of Chemical Engineering, Lakehead University, 955 Oliver Road, Thunder Bay, Ontario P7B 5E1 (Canada)] [Department of Chemical Engineering, Lakehead University, 955 Oliver Road, Thunder Bay, Ontario P7B 5E1 (Canada); Kinrade, Stephen D., E-mail: stephen.kinrade@lakeheadu.ca [Department of Chemistry, Lakehead University, 955 Oliver Road, Thunder Bay, Ontario P7B 5E1 (Canada)

    2013-06-15

    A new method is reported for quantifying the mineral phases in hydrated cement pastes that is based on a combination of quantitative X-ray diffractometry (QXRD) and thermogravimetry (TG). It differs from previous methods in that it gives a precise measure of the amorphous phase content without relying on an assumed stoichiometric relationship between the principal hydration products, calcium hydroxide (CH) and calcium silicate hydrate (C–S–H). The method was successfully applied to gray and white ordinary Portland cements (GOPC and WOPC, respectively) that were cured for up to 56 days. Phase distributions determined by QXRD/TG closely matched those from gray-level analysis of backscattered scanning electron microscope (BSEM) images, whereas elemental compositions obtained for the amorphous phase by QXRD/TG agreed well with those measured by quantitative energy dispersive X-ray spectroscopy (EDS)

  14. 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.

  15. 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

  16. How does Tg reduction affect the chain mobility in confined PS films?

    NASA Astrophysics Data System (ADS)

    Akgun, Bulent; Dimitriou, Michael; Satija, Sushil K.

    2013-03-01

    It is well established that the glass transition temperature (Tg) of supported polystyrene (PS) thin films decrease with decreasing film thickness. This Tg reduction due to the free surface effect is associated with enhanced mobility. However, the correlation between the enhanced mobility and Tg reduction has not been studied yet. To understand the effect of Tg reduction on the vertical mobility of PS chains across the interfaces we have investigated the interdiffusion between PS and deuterated PS (dPS) films in bilayer and trilayer geometries using neutron reflectivity (NR). Bilayer films of 42 nm thick dPS bottom layer and 20 nm thick PS top layer are created in such a way to mimic the films where large Tg reductions has been demonstrated by recent fluorescence measurements. Trilayer films were created using the same bottom layer but floating a 10 nm thick PS middle layer and 10 nm thick dPS top layer to compare the mobilities at the interfaces between the top/middle and middle/bottom layers. NR results showed that there is almost no mixing between the layers up to 90-95 C for both bilayer and trilayer films which is not consistent with large Tg reductions observed in the literature. Our results also indicate no difference in the mobility of PS chains at the top/middle and middle/bottom interfaces in the trilayer film which argues against the enhanced mobility reported in the literature for the top 10 nm of PS thin films. Diffusion of PS chains across the interface gets faster as the MW decreases.

  17. The cathepsin L of Toxoplasma gondii (TgCPL) and its endogenous macromolecular inhibitor, toxostatin?

    PubMed Central

    Huang, Robert; Que, Xuchu; Hirata, Ken; Brinen, Linda S.; Lee, Ji Hyun; Hansell, Elizabeth; Engel, Juan; Sajid, Mohammed; Reed, Sharon

    2008-01-01

    T. gondii is an obligate intracellular parasite of all vertebrates, including man. Successful invasion and replication requires the synchronized release of parasite proteins, many of which require proteolytic processing. Unlike most parasites, T. gondii has a limited number of Clan CA, family C1 cysteine proteinases with one cathepsin B (TgCPB), one cathepsin L (TgCPL) and three cathepsin Cs (TgCPC1, 2, 3). Previously, we characterized toxopain, the only cathepsin B enzyme, which localizes to the rhoptry organelle. Two cathepsin Cs are trafficked through dense granules to the parasitophorous vacuole where they degrade peptides. We now report the cloning, expression, and modeling of the sole cathepsin L gene and the identification of two new endogenous inhibitors. TgCPL differs from human cathepsin L with a pH optimum of 6.5 and its substrate preference for leucine (vs. phenylalanine) in the P2 position. This distinct preference is explained by homology modeling, which reveals a non-canonical aspartic acid (Asp 216) at the base of the predicted active site S2 pocket, which limits substrate access. To further our understanding of the regulation of cathepsins in T. gondii, we identified two genes encoding endogenous cysteine proteinase inhibitors (ICPs or toxostatins), which are active against both TgCPB and TgCPL in the nanomolar range. Over expression of toxostatin-1 significantly decreased overall cysteine proteinase activity in parasite lysates, but had no detectable effect on invasion or intracellular multiplication. These findings provide important insights into the proteolytic cascades of T. gondii and their endogenous control. PMID:19111576

  18. Physical transformation of niclosamide solvates in pharmaceutical suspensions determined by DSC and TG analysis.

    PubMed

    de Villiers, M M; Mahlatji, M D; Malan, S F; van Tonder, E C; Liebenberg, W

    2004-07-01

    This study reports the preparation of four niclosamide solvates and the determination of the stability of the crystal forms in different suspension vehicles by DSC and TG analysis. Thermal analysis showed that the niclosamide solvates were extremely unstable in a PVP-vehicle and rapidly changed to monohydrated crystals. A suspension in propylene glycol was more stable and TG analysis showed that crystal transformation was less rapid. In this vehicle, the crystals transformed to the anhydrate, rather than the monohydrate, since the vehicle was non-aqueous. The TEG-hemisolvate was the most stable in suspension and offered the best possibility of commercial exploitation. PMID:15296091

  19. Toxoplasma gondii Protein Disulfide Isomerase (TgPDI) Is a Novel Vaccine Candidate against Toxoplasmosis

    PubMed Central

    Wang, Hai-Long; Li, Ya-Qing; Yin, Li-Tian; Meng, Xiao-Li; Guo, Min; Zhang, Jian-Hong; Liu, Hong-Li; Liu, Juan-Juan; Yin, Guo-Rong

    2013-01-01

    Toxoplasma gondii is a ubiquitous protozoan parasite that can infect all warm-blooded animals, including both mammals and birds. Protein disulfide isomerase (PDI) localises to the surface of T. gondii tachyzoites and modulates the interactions between parasite and host cells. In this study, the protective efficacy of recombinant T. gondii PDI (rTgPDI) as a vaccine candidate against T. gondii infection in BALB/c mice was evaluated. rTgPDI was expressed and purified from Escherichia coli. Five groups of animals (10 animals/group) were immunised with 10, 20, 30, 40 ?g of rTgPDI per mouse or with PBS as a control group. All immunisations were performed via the nasal route at 1, 14 and 21 days. Two weeks after the last immunisation, the immune responses were evaluated by lymphoproliferative assays and by cytokine and antibody measurements. The immunised mice were challenged with tachyzoites of the virulent T. gondii RH strain on the 14th day after the last immunisation. Following the challenge, the tachyzoite loads in tissues were assessed, and animal survival time was recorded. Our results showed that the group immunised with 30 ?g rTgPDI showed significantly higher levels of specific antibodies against the recombinant protein, a strong lymphoproliferative response and significantly higher levels of IgG2a, IFN-gamma (IFN-?), IL-2 and IL-4 production compared with other doses and control groups. While no changes in IL-10 levels were detected. After being challenged with T. gondii tachyzoites, the numbers of tachyzoites in brain and liver tissues from the rTgPDI group were significantly reduced compared with those of the control group, and the survival time of the mice in the rTgPDI group was longer than that of mice in the control group. Our results showed that immunisation with rTgPDI elicited a protective immune reaction and suggested that rTgPDI might represent a promising vaccine candidate for combating toxoplasmosis. PMID:23967128

  20. 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

  1. Introduction to Grain Elevators

    NSDL National Science Digital Library

    1998-01-01

    The US Department of Agriculture has placed online this series of presentations on grain elevators. The presentations (VRML 2.0) demonstrate "the operation of an export elevator; the operation of a bulkweighing scale and the procedure for performing a build-up scale test; a description of electronic control systems; a 3-dimensional model of a shipping bin and diverter gates; and a simulation of a gate limit switch test." Demos include animated color images with fully labeled parts and summary paragraphs. From agricultural students to design engineers, as well as those who have always wanted to know, visitors will obtain a solid introduction to grain elevators from this informative resource.

  2. 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

  3. Structured Triglyceride Vehicles for Oral Delivery of Halofantrine: Examination of Intestinal Lymphatic Transport and Bioavailability in Conscious Rats

    Microsoft Academic Search

    René Holm; Christopher J. H. Porter; Anette Müllertz; Henning G. Kristensen; William N. Charman

    2002-01-01

    Purpose. To compare the influence of triglyceride vehicle intramolecular structure on the intestinal lymphatic transport and systemic absorption of halofantrine in conscious rats.\\u000aMethods. Conscious, lymph cannulated and nonlymph cannulated rats were dosed orally with three structurally different triglycerides; sunflower oil, and two structured triglycerides containing different proportion and position of medium-(M) and long-chain (L) fatty acids on the glycerol

  4. Oxidative stabilization of mixed mayonnaises made with linseed oil and saturated medium-chain triglyceride oil.

    PubMed

    Raudsepp, Piret; Brüggemann, Dagmar A; Lenferink, Aufried; Otto, Cees; Andersen, Mogens L

    2014-01-01

    Mayonnaises, made with either saturated medium chain triglyceride (MCT) oil or unsaturated purified linseed oil (LSO), were mixed. Raman confocal microspectrometry demonstrated that lipid droplets in mixed mayonnaise remained intact containing either MCT oil or LSO. Peroxide formation during storage was lower in mixed mayonnaise compared to LSO mayonnaise, while in mixed oil mayonnaise the level of peroxides was constantly low. Mixed oil mayonnaise had a lower rate of oxygen consumption than mixed mayonnaise, LSO mayonnaise having the highest rate. The decay of water-soluble nitroxyl radicals showed radicals are formed in the aqueous phase with the same rate independent of the lipids. This was also reflected in decay of ?-tocopherol during storage being similar in MCT and LSO mayonnaises, but being stable in mixed oil mayonnaise and mixed mayonnaise. Results suggest that other effects than simply diluting unsaturated triglycerides with saturated triglycerides is causing the oxidative stabilization observed for mixed mayonnaise and mixed oil mayonnaise. PMID:24444951

  5. Association of HS6ST3 gene polymorphisms with obesity and triglycerides: gene x gender interaction.

    PubMed

    Wang, Ke-Sheng; Wang, Liang; Liu, Xuefeng; Zeng, Min

    2013-12-01

    The heparan sulfate 6-O-sulfotransferase 3 (HS6ST3) gene is involved in heparan sulphate and heparin metabolism, and has been reported to be associated with diabetic retinopathy in type 2 diabetes.We hypothesized that HS6ST3 gene polymorphisms might play an important role in obesity and related phenotypes (such as triglycerides). We examined genetic associations of 117 single-nucleotide polymorphisms (SNPs) within the HS6ST3 gene with obesity and triglycerides using two Caucasian samples: the Marshfield sample (1442 obesity cases and 2122 controls), and the Health aging and body composition (Health ABC) sample (305 cases and 1336 controls). Logistic regression analysis of obesity as a binary trait and linear regression analysis of triglycerides as a continuous trait, adjusted for age and sex, were performed using PLINK. Single marker analysis showed that six SNPs in the Marshfield sample and one SNP in the Health ABC sample were associated with obesity (P < 0.05). SNP rs535812 revealed a stronger association with obesity in meta-analysis of these two samples (P = 0.0105). The T-A haplotype from rs878950 and rs9525149 revealed significant association with obesity in the Marshfield sample (P = 0.012). Moreover, nine SNPs showed associations with triglycerides in the Marshfield sample (P < 0.05) and the best signal was rs1927796 (P = 0.00858). In addition, rs7331762 showed a strong gene x gender interaction (P = 0.00956) for obesity while rs1927796 showed a strong gene x gender interaction (P = 0.000625) for triglycerides in the Marshfield sample. These findings contribute new insights into the pathogenesis of obesity and triglycerides and demonstrate the importance of gender differences in the aetiology. PMID:24371161

  6. Increased cellular triglyceride levels in human monocytic and rat smooth muscle cells after lovastatin.

    PubMed

    Hrboticky, N; Becker, A; Kruse, H J; Weber, P C

    1997-11-30

    Beta-hydroxy-beta-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors reduce plasma LDL cholesterol by upregulating hepatic LDL receptors. However, their effects on lipid metabolism in extrahepatic cells may also contribute to their therapeutic benefit. We examined the effects of lovastatin (LOV) on cellular lipid levels in the human monocytic Mono Mac 6sr and cultured rat smooth muscle cells. In both cell types, LOV produced a dose-dependent increase in cellular triglycerides. This increase was observed in cells grown in the absence of exogenous lipids in the culture medium, but was more pronounced after additions of oleic acid (50 to 200 microM) and VLDL (50 to 200 microg ml-1). In Mono Mac 6sr cells grown in medium containing 10% delipidated FCS for the last 16 h, the LOV-induced rise in triglyceride levels was completely reversed by 2 mM mevalonic acid and was associated with a decrease in cellular cholesterol. However, when cells were maintained in lipoprotein-replete medium, the LOV-induced rise in triglycerides did not correlate with cellular cholesterol. LOV also reduced cellular cholesterol esterification and increased the synthesis of fatty acids and their incorporation into triglycerides and phospholipids. Increased triglyceride levels were also seen in Mono Mac 6sr cells treated with the lanosterol demethylase inhibitor RS-21607 and the acylcoenzyme A:cholesterol acyltransferase inhibitor SaH 58035. Our findings suggest that the LOV-induced triglyceride accumulation involves changes in intracellular cholesterol pools regulating cellular fatty acid concentrations. Although decreased cholesterol levels in cells participating in plaque formation are beneficial, the impact of the herein described shift in intracellular neutral lipid metabolism on other cellular functions warrants further investigation. PMID:9434135

  7. Metabolic Imaging of Human Kidney Triglyceride Content: Reproducibility of Proton Magnetic Resonance Spectroscopy

    PubMed Central

    de Heer, Paul; Bizino, Maurice B.; Wolterbeek, Ron; Rabelink, Ton J.; Doornbos, Joost; Lamb, Hildo J.

    2013-01-01

    Objective To assess the feasibility of renal proton magnetic resonance spectroscopy for quantification of triglyceride content and to compare spectral quality and reproducibility without and with respiratory motion compensation in vivo. Materials and Methods The Institutional Review Board of our institution approved the study protocol, and written informed consent was obtained. After technical optimization, a total of 20 healthy volunteers underwent renal proton magnetic resonance spectroscopy of the renal cortex both without and with respiratory motion compensation and volume tracking. After the first session the subjects were repositioned and the protocol was repeated to assess reproducibility. Spectral quality (linewidth of the water signal) and triglyceride content were quantified. Bland-Altman analyses and a test by Pitman were performed. Results Linewidth changed from 11.5±0.4 Hz to 10.7±0.4 Hz (all data pooled, p<0.05), without and with respiratory motion compensation respectively. Mean % triglyceride content in the first and second session without respiratory motion compensation were respectively 0.58±0.12% and 0.51±0.14% (P?=?NS). Mean % triglyceride content in the first and second session with respiratory motion compensation were respectively 0.44±0.10% and 0.43±0.10% (P?=?NS between sessions and P?=?NS compared to measurements with respiratory motion compensation). Bland-Altman analyses showed narrower limits of agreement and a significant difference in the correlated variances (correlation of ?0.59, P<0.05). Conclusion Metabolic imaging of the human kidney using renal proton magnetic resonance spectroscopy is a feasible tool to assess cortical triglyceride content in humans in vivo and the use of respiratory motion compensation significantly improves spectral quality and reproducibility. Therefore, respiratory motion compensation seems a necessity for metabolic imaging of renal triglyceride content in vivo. PMID:23620813

  8. Diabetes mellitus is associated with increased intramyocellular triglyceride, but not diglyceride, content in obese humans.

    PubMed

    Anastasiou, Costas A; Kavouras, Stavros A; Lentzas, Yannis; Gova, Afrodite; Sidossis, Labros S; Melidonis, Adreas

    2009-11-01

    It has been suggested that intramyocellular diglycerides may be associated with insulin resistance and thus may be linked to the pathophysiology of diabetes. We aimed to investigate intramyocellular diglyceride as well as triglyceride levels in diabetic subjects and to explore a possible association with glycemic control. The participants of the study were 30 obese subjects stratified according to the presence of diabetes into nondiabetic obese (n = 19) and diabetic obese (n = 11). Intramyocellular triglycerides and diglycerides were determined in biopsies from the vastus lateralis muscle under fasting conditions. Glycemic control and insulin resistance were assessed by an oral glucose tolerance test and the homeostatic model, respectively. Higher levels of intramyocellular triglycerides were observed in the diabetic obese group compared with the nondiabetic obese group (66.67 +/- 23.75 vs 18.35 +/- 4.42 nmol.mg(-1) dry tissue, respectively; P < .05). Diglyceride levels were not significantly different between the study groups (1.65 +/- 0.27 vs 1.94 +/- 0.65 nmol.mg(-1) dry tissue, respectively). Monounsaturated fatty acids represented the major constituent of intramyocellular triglycerides in both groups, whereas diglycerides contained mainly saturated fatty acids. A significant correlation was found between intramyocellular levels of triglycerides, but not diglycerides, and glycemic control, expressed as the area under the glucose curve (r = 0.417, P < .05). No correlations were found between intramyocellular levels of both lipid classes and insulin resistance. Our data support a relationship between glycemic control and intramyocellular triglycerides, but not diglycerides. The total flux of fatty acids toward esterification may be a much more important factor in the pathophysiology of diabetes. PMID:19615699

  9. Colipase enhances hydrolysis of dietary triglycerides in the absence of bile salts.

    PubMed Central

    Bläckberg, L; Hernell, O; Bengtsson, G; Olivecrona, T

    1979-01-01

    This study explores how dietary lipids are digested when intraduodenal bile salts are low or absent. Long-chain triglycerides emulsified with phosphatidylcholine were found to be hydrolyzed very slowly by pancreatic lipase alone, as if the surface layer of phospholipids enveloping the triglycerides impeded the action of the enzyme. Colipase enhanced triglyceride hydrolysis severalfold, both when added before or after the lipase. Hydrolysis became even more rapid when the emulsion was first incubated with pancreatic phospholipase. Hydrolysis of long-chain triglycerides was also severely impeded when other proteins were added to the system, probably because they adsorbed to the oil-water interface of the emulsion droplets. It was previously known that bile salts can relieve such inhibition, presumably by desorbing the adsorbed proteins. Colipase was found to enhance hydrolysis severalfold in a dose-dependent manner even in the absence of bile salts, i.e., it could partially or completely relieve the inhibition depending upon the amount and the type of inhibitory protein added to the system. Prior exposure of a protein-coated triglyceride emulsion to another lipase also enhanced the rate at which pancreatic lipase could then hydrolyze the lipids. Most dietary triglycerides are probably presented for intestinal digestion in emulsions covered by proteins and/or phospholipids. These emulsions would be hydrolyzed slowly by pancreatic lipase alone. However, through the action of the lipase in stomach contents and of pancreatic phospholipase and through the lipolysis-promoting effects of collipase, these triglycerices can be rather efficiently hydrolyzed, even in the absence of bile salts. PMID:500812

  10. 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; Borén, 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

  11. A Nanotube Space Elevator

    NSDL National Science Digital Library

    2008-08-26

    In this video adapted from NOVA scienceNOW, find out about the discovery of a new building material, the carbon nanotube, whose physical properties could theoretically enable the creation of a 22,000-mile elevator to space.

  12. A replication study of GWAS-derived lipid genes in Asian Indians: the chromosomal region 11q23.3 harbors loci contributing to triglycerides.

    PubMed

    Braun, Timothy R; Been, Latonya F; Singhal, Akhil; Worsham, Jacob; Ralhan, Sarju; Wander, Gurpreet S; Chambers, John C; Kooner, Jaspal S; Aston, Christopher E; Sanghera, Dharambir K

    2012-01-01

    Recent genome-wide association scans (GWAS) and meta-analysis studies on European populations have identified many genes previously implicated in lipid regulation. Validation of these loci on different global populations is important in determining their clinical relevance, particularly for development of novel drug targets for treating and preventing diabetic dyslipidemia and coronary artery disease (CAD). In an attempt to replicate GWAS findings on a non-European sample, we examined the role of six of these loci (CELSR2-PSRC1-SORT1 rs599839; CDKN2A-2B rs1333049; BUD13-ZNF259 rs964184; ZNF259 rs12286037; CETP rs3764261; APOE-C1-C4-C2 rs4420638) in our Asian Indian cohort from the Sikh Diabetes Study (SDS) comprising 3,781 individuals (2,902 from Punjab and 879 from the US). Two of the six SNPs examined showed convincing replication in these populations of Asian Indian origin. Our study confirmed a strong association of CETP rs3764261 with high-density lipoprotein cholesterol (HDL-C) (p?=?2.03×10(-26)). Our results also showed significant associations of two GWAS SNPs (rs964184 and rs12286037) from BUD13-ZNF259 near the APOA5-A4-C3-A1 genes with triglyceride (TG) levels in this Asian Indian cohort (rs964184: p?=?1.74×10(-17); rs12286037: p?=?1.58×10(-2)). We further explored 45 SNPs in a ?195 kb region within the chromosomal region 11q23.3 (encompassing the BUD13-ZNF259, APOA5-A4-C3-A1, and SIK3 genes) in 8,530 Asian Indians from the London Life Sciences Population (LOLIPOP) (UK) and SDS cohorts. Five more SNPs revealed significant associations with TG in both cohorts individually as well as in a joint meta-analysis. However, the strongest signal for TG remained with BUD13-ZNF259 (rs964184: p?=?1.06×10(-39)). Future targeted deep sequencing and functional studies should enhance our understanding of the clinical relevance of these genes in dyslipidemia and hypertriglyceridemia (HTG) and, consequently, diabetes and CAD. PMID:22623978

  13. location map, floor plan, north elevation, north elevation with porch ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    location map, floor plan, north elevation, north elevation with porch removed, south elevation, building section - Chopawamsic Recreational Demonstration Area - Cabin Camp 1, Help's Quarters, Prince William Forest Park, Triangle, Prince William County, VA

  14. 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

  15. ADVISORY BASE FLOOD ELEVATIONS (ABFE)

    E-print Network

    Elevation due to new information. Which FEMA programs now require using Advisory Base Flood ElevationsADVISORY BASE FLOOD ELEVATIONS (ABFE) DURING REBUILDING What are the Advisory Base Flood Elevations (ABFE)? Answer: This is the NEW Base Flood Elevation for rebuilding. It has the same definition

  16. Analysis of triglycerides by consecutive chromatographic techniques. i. cuphea llavia seed fat

    Microsoft Academic Search

    Carter Litchfield; Margaret Farquhar; Raymond Reiser

    1964-01-01

    The triglycerides ofCuphea llavia var.miniata seed fat were separated according to the number of double bonds\\/molecule using preparative thin layer chromatography (TLC)\\u000a on silicic acid impregnated with silver ion. The recovered frac-tions were quantitated by the chromotropic acid technique.\\u000a Each fraction was then separated ac-cording to mol wt using gas-liquid chromatog-raphy (GLC). This multiple chromatography\\u000a procedure resolvedC. llavia triglycerides into

  17. Determination of mono-, di-, and triglycerides by molecular distillation and thin-layer chromatography

    Microsoft Academic Search

    O. S. Privett; M. L. Blank; W. O. Lundberg

    1961-01-01

    Analysis of mixtures of mono-, di-, and triglycerides by molecular distillation and thin-layer chromatography is described.\\u000a \\u000a Mono- and diglycerides undergo appreciable acyl migration through the effect of heat during molecular distillation. Nevertheless\\u000a this technique may be used for the quantitative analysis of mixtures of mono-, di-, and triglycerides, provided there are\\u000a no substances present which catalyze, disproportionation.\\u000a \\u000a \\u000a \\u000a Thin-layer chromatographic (TLC)

  18. 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

  19. Combination therapy of an intestine-specific inhibitor of microsomal triglyceride transfer protein and peroxisome proliferator-activated receptor ? agonist in diabetic rat.

    PubMed

    Sakata, Shohei; Mera, Yasuko; Kuroki, Yukiharu; Nashida, Reiko; Kakutani, Makoto; Ohta, Takeshi

    2014-01-01

    We investigated effects on glucose and lipid metabolism in combination of JTT-130, a novel intestine-specific microsomal triglyceride transfer protein (MTP) inhibitor, and pioglitazone, peroxisome proliferator-activated receptor (PPAR) ? agonist. Male Zucker diabetic fatty rats were divided into 4 groups: control group, JTT-130 treatment group, pioglitazone treatment group, and combination group. The Zucker diabetic fatty rats were fed a regular powdered diet with JTT-130 and/or pioglitazone as a food admixture for 6 weeks. Effects on glucose and lipid metabolism were compared mainly between JTT-130 treatment group and combination group. JTT-130 treatment showed good glycemic control, while the plasma glucose and glycated hemoglobin levels in combination group were significantly decreased as compared with those JTT-130 treatment group. The reduction in the plasma triglyceride and free fatty acid levels in combination group was higher than that in JTT-130 treatment group, and glucose utilization was significantly elevated in adipose tissues. In Zucker diabetic fatty rats, combination treatment of JTT-130 and pioglitazone showed better glycemic control and a strong hypolipidemic action with an enhancement of insulin sensitivity. Combination therapy of MTP inhibitor and PPAR ? agonist might be more useful in the treatment of type 2 diabetes accompanied with obesity and insulin resistance. PMID:24772450

  20. Bibliography Amin, T.G. (2001). A cognitive linguistics approach to the layperson's understanding of

    E-print Network

    Maryland at College Park, University of

    136 Bibliography Amin, T.G. (2001). A cognitive linguistics approach to the layperson Factors in Linguistic Structure. Stanford, CA: CSLI Publictions. Anderson, J.R. and Thompson, R. (1989 of Physics Teachers. Sacramento, CA. AAPT Announcer 33(2). #12;137 Brookes, D.T. (2003). Linguistics

  1. 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

  2. Proteolytic processing of TgIMC1 during maturation of the membrane skeleton of Toxoplasma gondii.

    E-print Network

    Arnold, Jonathan

    cell types. In the protozoan parasite Toxoplasma gondii this function is performed by the subpellicularProteolytic processing of TgIMC1 during maturation of the membrane skeleton of Toxoplasma gondii title: Assembly of Toxoplasma gondii membrane skeleton ¶ To whom correspondence should be addressed: Con

  3. 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

  4. Hippocampal hyperexcitability underlies enhanced fear memories in TgNTRK3, a panic disorder mouse model.

    PubMed

    Santos, Mónica; 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

  5. 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 patient’s 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

  6. Immunomodulation targeting of both A? and tau pathological conformers ameliorates Alzheimer’s disease pathology in TgSwDI and 3xTg mouse models

    PubMed Central

    2013-01-01

    Background Central to the pathogenesis of Alzheimer’s 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

  7. Dihydroisoxazole inhibitors of Anopheles gambiae seminal transglutaminase AgTG3

    PubMed Central

    2014-01-01

    Background Current vector-based malaria control strategies are threatened by the rise of biochemical and behavioural resistance in mosquitoes. Researching mosquito traits of immunity and fertility is required to find potential targets for new vector control strategies. The seminal transglutaminase AgTG3 coagulates male Anopheles gambiae seminal fluids, forming a ‘mating plug’ that is required for male reproductive success. Inhibitors of AgTG3 can be useful both as chemical probes of A. gambiae reproductive biology and may further the development of new chemosterilants for mosquito population control. Methods A targeted library of 3-bromo-4,5-dihydroxoisoxazole inhibitors were synthesized and screened for inhibition of AgTG3 in a fluorescent, plate-based assay. Positive hits were tested for in vitro activity using cross-linking and mass spectrometry, and in vivo efficacy in laboratory mating assays. Results A targeted chemical library was screened for inhibition of AgTG3 in a fluorescent plate-based assay using its native substrate, plugin. Several inhibitors were identified with IC50?TG3 were verified. Administration of an AgTG3 inhibitor to A. gambiae males by intrathoracic injection led to a 15% reduction in mating plug transfer in laboratory mating assays. Conclusions A targeted screen has identified chemical inhibitors of A. gambiae transglutaminase 3 (AgTG3). The most potent inhibitors are known inhibitors of human transglutaminase 2, suggesting a common binding pose may exist within the active site of both enzymes. Future efforts to develop additional inhibitors will provide chemical tools to address important biological questions regarding the role of the A. gambiae mating plug. A second use for transglutaminase inhibitors exists for the study of haemolymph coagulation and immune responses to wound healing in insects. PMID:24888439

  8. 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

  9. Hypertriglyceridemia and Cardiovascular Risk Reduction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Elevated triglyceride (TG) levels are prevalent among the US population, often occurring in persons who are overweight or obese, or who have type 2 diabetes or the metabolic syndrome. Meta-analysis indicates that elevated TG levels may be a significant independent risk factor for coronary heart dise...

  10. CHANGES IN BLOOD GLUCOSE, TRIGLYCERIDES AND LIPID PEROXIDATION PRODUCTS IN RABBITS AFTER HANGING FIXATION

    Microsoft Academic Search

    G. M. SAROV; T. I. VLAYKOVA

    Summary Sarov, G. M. & T. I. Vlaykova, 2005. Changes in blood glucose, triglycerides and lipid per- oxidation products in rabbits after hanging fixation. Bulg. J. Vet. Med., 8, No 3, 157-161. Psycho-emotional stress is one of the risk factors for metabolic syndrome and related diseases. We decided to investigate the changes in glucose and lipids levels, as well as

  11. Plasma triglycerides and chemical composition of quail's meat fed on bixin and supplementary niacin

    Microsoft Academic Search

    Newton Tavares; Escocard de Oliveira; José Brandão Fonseca; Rita da Trindade; Ribeiro Nobre; Karla Silva Ferreira

    2006-01-01

    The objective of this work was to assess the effect of spice's bixin and supplementary niacin on diets in the plasmatic levels of triglyceride and very low-density lipoprotein, and in the fat of breast, drumstick and thigh meat and carcass of japanese quails (Coturnix japonica). Two hundred and forty japanese male quails were used in a completely randomized design, with

  12. Reactivity of triglycerides and fatty acids of rapeseed oil in supercritical alcohols

    Microsoft Academic Search

    Yuichiro Warabi; Dadan Kusdiana; Shiro Saka

    2004-01-01

    A catalyst-free biodiesel production method with supercritical methanol has been developed that allows a simple process and high yield because of simultaneous transesterification of triglycerides and methyl esterification of fatty acids. From these lines of evidence, we expected that similar results would be attained with the use of various alcohols by the supercritical treatment. However, it still remains unclear which

  13. 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.

  14. Brown adipose tissue triglyceride content is associated with decreased insulin sensitivity, independently of age and obesity.

    PubMed

    Raiko, J; Holstila, M; Virtanen, K A; Orava, J; Saunavaara, V; Niemi, T; Laine, J; Taittonen, M; Borra, R J H; Nuutila, P; Parkkola, R

    2015-05-01

    The aim of the present study was to determine whether single-voxel proton magnetic resonance spectroscopy ((1) H-MRS) can non-invasively assess triglyceride content in both supraclavicular fat depots and subcutaneous white adipose tissue (WAT) to determine whether these measurements correlate to metabolic variables. A total of 25 healthy volunteers were studied using (18) F-fluorodeoxyglucose positron emission tomography (PET) and (15) O-H2 O PET perfusion during cold exposure, and (1) H-MRS at ambient temperature. Image-guided biopsies were collected from nine volunteers. The supraclavicular triglyceride content determined by (1) H-MRS varied between 60 and 91% [mean?±?standard deviation (s.d.) 77?±?10%]. It correlated positively with body mass index, waist circumference, subcutaneous and visceral fat masses and 8-year diabetes risk based on the Framingham risk score and inversely with HDL cholesterol and insulin sensitivity (M-value; euglycaemic-hyperinsulinaemic clamp). Subcutaneous WAT had a significantly higher triglyceride content, 76-95% (mean?±?s.d. 87?±?5%; p?=?0.0002). In conclusion, the triglyceride content in supraclavicular fat deposits measured by (1) H-MRS may be an independent marker of whole-body insulin sensitivity, independent of brown adipose tissue metabolic activation. PMID:25586670

  15. Phospholipase C mediated inhibition of factor VII requires triglyceride-rich lipoproteins.

    PubMed

    Hubbard, A R; Parr, L J

    1991-05-15

    The reduction of plasma factor VII (FVII) activity by phospholipase C (PLC), in vitro, has been proposed as a possible indication of a risk of cardiovascular disease. The ability of PLC to reduce FVII activity was found to require calcium ions and the presence of triglyceride-rich lipoproteins (e.g. chylomicra and very-low density lipoproteins) rather than high or low density lipoproteins. The PLC-mediated reduction of FVII activity was prevented by pre-incubation of PLC with chylomicra, before adding FVII, and this suggests that PLC may act on triglyceride-rich lipoproteins already bound to FVII in order to reduce FVII activity. At optimal PLC concentration, the extent of the reduction in FVII activity was proportional to the concentration of chylomicra. The detergent, Tween, prevented any loss of FVII activity, in both plasma and purified systems, if it was present at the beginning of the incubation with PLC. Addition of Tween, but not EDTA, after inhibition of FVII activity had occurred, caused a partial restoration of FVII activity. It is concluded that PLC reduces FVII activity by modifying triglyceride-rich lipoproteins to a form which binds to FVII, independently of calcium ions, and which inhibits procoagulant activity. The detection of PLC-sensitive procoagulant activity. The detection of PLC-sensitive FVII activity may therefore have no greater significance than the measurement of plasma triglyceride levels in predicting a risk of cardiovascular disease. PMID:1866715

  16. 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...

  17. Effects of dietary cholesterol on hepatic metabolism of triglyceride-rich lipopro-

    E-print Network

    Paris-Sud XI, Université de

    Effects of dietary cholesterol on hepatic metabolism of triglyceride-rich lipopro- teins to stimulate hepatic production of VLDL, cholesterol was given to 5 male Frie- sian preruminant calves (1 month replacer with or without cholesterol in which lipids (tallow) con- stituted 22.1 % dry matter (DM

  18. 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...

  19. 13Carbon mixed triglyceride breath test and pancreatic enzyme supplementation in cystic fibrosis

    Microsoft Academic Search

    S Amarri; M Harding; W A Coward; T J Evans; L T Weaver

    1997-01-01

    Children with cystic fibrosis have variable degrees of exocrine pancreatic insufficiency which, if untreated, is the main cause of fat malabsorption. The impact of pancreatic enzyme supplementation on fat digestion was measured in 41 children with cystic fibrosis, 11 healthy controls, and five children with mucosal diseases by a non-invasive test of intraluminal lipolysis using 13carbon (13C) labelled mixed triglyceride

  20. 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.

  1. Comparative effects of some carbohydrates on serum sugars, triglycerides and digestive hydrolases

    E-print Network

    Boyer, Edmond

    Comparative effects of some carbohydrates on serum sugars, triglycerides and digestive hydrolases carbohydrate in the form of starch (wheat flour), purified sucrose, commercial sugar or a commercial sweetner. Introduction. The nutritional impact of the dietary carbohydrate source has been widely studied

  2. 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…

  3. Continuous release of rh-interferon ?-2a from triglyceride matrices

    Microsoft Academic Search

    Silke Mohl; Gerhard Winter

    2004-01-01

    The use of biodegradable polymeric matrices as controlled release systems is known to be associated with various drawbacks. The objective of this study was to develop an alternative delivery system based on triglycerides, thereby aiming for sustained continuous protein release. Tristearin implants containing lyophilised rh-interferon ?-2a (IFN-?) and varying amounts of polyethylene glycol 6000 (PEG) were prepared by compression. Release

  4. Ketosis resistance in fibrocalculous pancreatic diabetes: II. Hepatic ketogenesis after oral medium-chain triglycerides

    Microsoft Academic Search

    C. S. Yajnik; B. S. Sardesai; D. S. Bhat; S. S. Naik; K. N. Raut; K. M. Shelgikar; H. Orskov; K. G. M. M. Alberti; T. D. R. Hockaday

    1997-01-01

    A majority of patients with fibrocalculous pancreatic diabetes (FCPD) do not become ketotic even in adverse conditions. It is not clear whether this ketosis resistance is due to reduced, fatty acid release from adipose tissue or to impaired hepatic ketogenesis. We tested hepatic ketogenesis in FCPD patients using a ketogenic challenge of oral medium-chain triglycerides (MCTs) and compared it with

  5. Enhancing energy and glucose metabolism by disrupting triglyceride synthesis: Lessons from mice lacking DGAT1

    PubMed Central

    Chen, Hubert C

    2006-01-01

    Although the ability to make triglycerides is essential for normal physiology, excess accumulation of triglycerides results in obesity and is associated with insulin resistance. Inhibition of triglyceride synthesis, therefore, may represent a feasible strategy for the treatment of obesity and type 2 diabetes. Acyl CoA:diacylglycerol acyltransferase 1 (DGAT1) is one of two DGAT enzymes that catalyze the final reaction in the known pathways of mammalian triglyceride synthesis. Mice lacking DGAT1 have increased energy expenditure and insulin sensitivity and are protected against diet-induced obesity and glucose intolerance. These metabolic effects of DGAT1 deficiency result in part from the altered secretion of adipocyte-derived factors. Studies of DGAT1-deficient mice have helped to provide insights into the mechanisms by which cellular lipid metabolism modulates systemic carbohydrate and insulin metabolism, and a better understanding of how DGAT1 deficiency enhances energy expenditure and insulin sensitivity may identify additional targets or strategies for the treatment of obesity and type 2 diabetes. PMID:16448557

  6. Triglyceride Concentration and Ischemic Heart Disease An Eight-Year Follow-up in the Copenhagen Male Study

    Microsoft Academic Search

    Jørgen Jeppesen; Hans Ole Hein; Poul Suadicani; Finn Gyntelberg

    2010-01-01

    Background—The role of triglycerides as a risk factor of ischemic heart disease (IHD) remains controversial. For the present study, we examined the relation between fasting triglycerides and risk of IHD in the Copenhagen Male Study. Methods and Results—Baseline measurements of fasting lipids and other IHD risk factors were obtained for 2906 white men (age range, 53 to 74 years) who

  7. Monocular elevation deficiency ("double elevator" palsy): a cautionary note.

    PubMed

    Brodsky, Michael C; Karlsson, Virginia

    2011-03-01

    Monocular elevation deficiency (or "double elevator" palsy) is a descriptive term denoting a congenital deficiency of monocular elevation that is equal in abduction and adduction. We describe a child with monocular elevation deficiency who displayed tethering and buckling of the central lower eyelid in downgaze. We caution that this manifestation of inferior rectus contracture can simulate impaired infraduction in the involved eye. PMID:21131851

  8. ELEVATOR PITCH WORKSHEET Important Notes About Your Elevator Pitch

    E-print Network

    Barnes, Elizabeth A.

    ELEVATOR PITCH WORKSHEET Important Notes About Your Elevator Pitch: · Just as you customize your resume and cover letter to individual companies, your elevator pitch can also be customized to highlight your most relevant skills and experience for a situation. · Your elevator pitch should have the ability

  9. 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<5×10?8 and trait specific scores using SNPs associated exclusively with each trait at p<5×10?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 0.82–1.24, p?=?0.962 per 1 unit increase in HDL-c; OR?=?0.901, 95% CI 0.65–1.25, p?=?0.530 per 1 unit increase in LDL-c; OR?=?1.104, 95% CI 0.89–1.37, p?=?0.362 per 1 unit increase in triglycerides; and OR?=?0.954, 95% CI 0.76–1.21, 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

  10. Effects of Calcium Fructoborate on Levels of C-Reactive Protein, Total Cholesterol, Low-Density Lipoprotein, Triglycerides, IL-1?, IL-6, and MCP-1: a Double-blind, Placebo-controlled Clinical Study.

    PubMed

    Rogoveanu, Otilia-Constantina; Mogo?anu, George Dan; Bejenaru, Cornelia; Bejenaru, Ludovic Everard; Croitoru, Octavian; Neam?u, Johny; Pietrzkowski, Zbigniew; Reyes-Izquierdo, Tania; Bi??, Andrei; Scorei, Iulia Daria; Scorei, Romulus Ion

    2015-02-01

    Calcium fructoborate (CFB) has been reported as supporting healthy inflammatory response. In this study, we assess the effects of CFB on blood parameters and proinflammatory cytokines in healthy subjects. This was a randomized, double-blinded, placebo-controlled trial. Participants received placebo or CFB at a dose of 112 mg/day (CFB-1) or 56 mg/day (CFB-2) for 30 days. Glucose, total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), C-reactive protein (CRP), homocysteine, interleukin 1 beta (IL-1?), IL-6, and monocyte chemoattractant protein-1 (MCP-1) were determined before and after supplementation. CFB-1 showed a reduction in blood levels of CRP by 31.3 % compared to baseline. CFB-1 and CFB-2 reduced LDL levels by 9.8 and 9.4 %, respectively. CFB-1 decreased blood homocysteine by 5.5 % compared with baseline, whereas CFB-2 did not have a significant effect. Blood levels of TG were reduced by 9.1 and 8.8 % for CFB-1 and CFB-2, respectively. Use of both CFB-1 and CFB-2 resulted in significantly reduced IL-6 levels, when compared within and between groups. IL-1? was reduced by 29.2 % in the CFB-1 group. Finally, CFB-1 and CFB-2 reduced MCP-1 by 31 and 26 %, respectively. Our data indicate that 30-day supplementation with 112 mg/day CFB (CFB-1) resulted in a significant reduction of LDL, TG, TC, IL-1?, IL-6, MCP-1, and CRP. HDL levels were increased, when compared to baseline and placebo. These results suggest that CFB might provide beneficial support to healthy cardiovascular systems by positively affecting these blood markers (ClinicalTrials.gov, ISRCTN90543844; May 24, 2012 ( http://www.controlled-trials.com/ISRCTN90543844 )). PMID:25433580

  11. Elevation Differences on Mars

    Microsoft Academic Search

    Carl Sagan; James B. Pollack

    1968-01-01

    Observations of apparent frost phenomena, occurring preferentially in the Martian bright areas, have in the past led to. the conclusion that the bright areas are elevations. The argument hinges on the implicit assumption that, near midday, highlands should be at lower temperatures than lowlands. On the earth, this assumption is valid, because of adiabatic cooling of rising air, a diminished

  12. 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

  13. Thermaldecomposition of two synthetic glycosides by TG, DSC and simultaneous Py-GC-MSanalysis

    Microsoft Academic Search

    W.-C. Xie; X.-H. Gu; Z.-C. Tan; J. Tang; G.-Y. Wang; C.-R. Luo; L.-X. Sun

    2007-01-01

    To develop thermal stable flavor, two glycosidic\\u000a bound flavor precursors, geranyl-tetraacetyl-?-D-glucopyranoside\\u000a (GLY-A) and geranyl-?-D-glucopyranoside\\u000a (GLY-B) were synthesized by the modified Koenigs–Knorr reaction. The\\u000a thermal decomposition process and pyrolysis products of the two glycosides\\u000a were extensively investigated by thermogravimetry (TG), differential scanning\\u000a calorimeter (DSC) and on-line pyrolysis-gas chromatography mass spectroscopy\\u000a (Py-GC-MS). TG showed the T\\u000a p\\u000a of GLY-A and GLY-B were

  14. A Monte Carlo derived TG-51 equivalent calibration for helical tomotherapy

    SciTech Connect

    Thomas, S.D.; Mackenzie, M.; Rogers, D.W.O.; Fallone, B.G. [Department of Medical Physics, Cross Cancer Institute, Departments of Oncology and Physics, University of Alberta, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada); Department of Medical Physics, Cross Cancer Institute, Department of Oncology, University of Alberta, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada); Department of Physics, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario, K1S 5B6 (Canada); Department of Medical Physics, Cross Cancer Institute, Departments of Oncology and Physics, University of Alberta, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada)

    2005-05-01

    Helical tomotherapy (HT) requires a method of accurately determining the absorbed dose under reference conditions. In the AAPM's TG-51 external beam dosimetry protocol, the quality conversion factor, k{sub Q}, is presented as a function of the photon component of the percentage depth-dose at 10 cm depth, %dd(10){sub x}, measured under the reference conditions of a 10x10 cm{sup 2} field size and a source-to-surface distance (SSD) of 100 cm. The value of %dd(10){sub x} from HT cannot be used for the determination of k{sub Q} because the design of the HT does not meet the following TG-51 reference conditions: (i) the field size and the practical SSD required by TG-51 are not obtainable and (ii) the absence of the flattening filter changes the beam quality thus affecting some components of k{sub Q}. The stopping power ratio is not affected because of its direct relationship to %dd(10){sub x}. We derive a relationship for the Exradin A1SL ion chamber converting the %dd(10){sub x} measured under HT 'reference conditions' of SSD=85 cm and a 5x10 cm{sup 2} field-size [%dd(10){sub x[HTRef]}], to the dosimetric equivalent value under for TG-51 reference conditions [%dd(10){sub x[HTTG-51]}] for HT. This allows the determination of k{sub Q} under the HT reference conditions. The conversion results in changes of 0.1% in the value of k{sub Q} for our particular unit. The conversion relationship should also apply to other ion chambers with possible errors on the order of 0.1%.

  15. CB 1 cannabinoid receptor: cellular regulation and distribution in N18TG2 neuroblastoma cells

    Microsoft Academic Search

    Helen H McIntosh; Chao Song; Allyn C Howlett

    1998-01-01

    In order to characterize cellular regulation of CB1 cannabinoid receptors, synthesis and turnover studies were performed. Metabolic labeling of N18TG2 cells with 35S-labeled amino acids was followed by immunoprecipitation from cell lysates using an affinity-purified antibody generated to the N-terminal 14-amino-acid segment of the CB1 receptor. During a 2 h labeling period, CB1 receptors were rapidly and constitutively synthesized (rate:

  16. TG and DTA Study of the Thermal Dehydration of Metal-exchanged Zeolite4A Samples

    Microsoft Academic Search

    M. Afzal; G. Yasmeen; M. Saleem; P. K. Butt; A. K. Khattak; J. Afzal

    2000-01-01

    Zeolite-4A is a hydrated aluminosilicate which becomes more hydrated when exchanged with transition metals. In this work,\\u000a the dehydration kinetics of cobalt, nickel and copper(II)-exchanged zeolite-4A were studied by means of TG and DTA over the\\u000a temperature range from 20 to 500C, and the numbers of water molecules in the metal-exchanged zeolite samples were calculated.\\u000a It was observed that, as

  17. 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 6.5 months 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 10.5 months 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

  18. Increased Proximal tubule PPAR? in KAP2-PPAR? Tg mice confers protection during acute kidney injury

    PubMed Central

    Li, Shenyang; Nagothu, Kiran; Desai, Varsha; Lee, Taewon; Branham, William; Moland, Carrie; Megyesi, Judit; Crew, Mark; Portilla, Didier

    2011-01-01

    In the present study we have generated transgenic mice that express Peroxisome Proliferator-Activated Receptor-alpha (PPAR?) in the proximal tubule under the control of kidney androgen-induced protein (KAP2) promoter. Up-regulation of proximal tubule PPAR? expression by testosterone treatment in KAP2-PPAR? female Transgenic (Tg) mice ameliorated kidney function from cisplatin (CP) or ischemia-reperfusion (I/R)-induced acute kidney injury (AKI). In addition, CP and I/R-mediated inhibition of fatty acid oxidation, and CP-mediated reduced expression of mitochondrial genes associated with oxidative phosphorylation, mitochondrial DNA, fatty acid metabolism, and tricarboxylic acid cycle were ameliorated in KAP2-PPAR? Tg mice treated with testosterone. Similarly, CP and I/R-mediated increased in 4-hydroxy-2-hexenal (HHE).-derived lipid peroxidation products were reduced, and CP and I/R-induced necrosis of the proximal tubule S3 segment was reduced. These results suggest an important function of proximal tubule PPAR? as a metabolic sensor, and demonstrate that its increased expression in KAP2-PPAR? Tg mice, without the use of exogenous ligand, is sufficient to protect kidney function and morphology, and to prevent abnormalities in lipid metabolism associated with CP or I/R-induced AKI. PMID:19710628

  19. The Bradykinin B1 Receptor Regulates A? Deposition and Neuroinflammation in Tg-SwDI Mice

    PubMed Central

    Passos, Giselle F.; Medeiros, Rodrigo; Cheng, David; Vasilevko, Vitaly; LaFerla, Frank M.; Cribbs, David H.

    2014-01-01

    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

  20. 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 50-700°C. PMID:24412857

  1. 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

  2. Disrupted Pancreatic Exocrine Differentiation and Malabsorption in Response to Chronic Elevated Systemic Glucocorticoid

    PubMed Central

    Wallace, Karen; Flecknell, Paul A.; Burt, Alastair D.; Wright, Matthew C.

    2010-01-01

    Glucocorticoids are antiinflammatory therapeutics that have potent effects on cell differentiation. The aim of this study was to establish whether systemic glucocorticoid exposure significantly affects pancreatic differentiation in vivo because hepatocyte-like cells have been documented to occur in the diseased rodent pancreas. Expression of hepatic markers was examined in pancreata from mice genetically modified to secrete elevated circulating endogenous glucocorticoid [Tg(Crh)]. Tg(Crh) mice with elevated glucocorticoid appeared cushingoid and by 21 weeks of age were obese, insulin-resistant, and had extensive areas of hepatic gene expression in exocrine tissue. Acinar cells from Tg(Crh) mice costained for both amylase and cyp2e1, suggesting direct acinar-hepatic transdifferentiation. Hepatic expression increased with age in the pancreas to such an extent that malabsorption and rapid weight loss occurred in a subset of aging mice; this effect was reversed by dietary porcine pancreatic enzyme supplementation. Indeed, pancreatic expression of hepatic markers was prevented by adrenalectomy, establishing a direct role for glucocorticoid. Elevated levels of circulating glucocorticoid therefore promote a transdifferentiation of adult exocrine pancreas into hepatocyte-like cells, and chronic exposure results in pancreatic malfunction. Glucocorticoids are thus capable of modulating the differentiation of terminally differentiated adult cells. PMID:20651242

  3. Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease

    PubMed Central

    2014-01-01

    Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G?A and IVS3+1G?T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1×10?20), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P = 8×10?10). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P = 4×10?6). Conclusions Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.) PMID:24941081

  4. Limitations of the TG-43 formalism for skin high-dose-rate brachytherapy dose calculations

    SciTech Connect

    Granero, Domingo, E-mail: dgranero@eresa.com [Department of Radiation Physics, ERESA, Hospital General Universitario, 46014 Valencia (Spain)] [Department of Radiation Physics, ERESA, Hospital General Universitario, 46014 Valencia (Spain); Perez-Calatayud, Jose [Radiotherapy Department, La Fe University and Polytechnic Hospital, Valencia 46026 (Spain)] [Radiotherapy Department, La Fe University and Polytechnic Hospital, Valencia 46026 (Spain); Vijande, Javier [Department of Atomic, Molecular and Nuclear Physics, University of Valencia, Burjassot 46100, Spain and IFIC (UV-CSIC), Paterna 46980 (Spain)] [Department of Atomic, Molecular and Nuclear Physics, University of Valencia, Burjassot 46100, Spain and IFIC (UV-CSIC), Paterna 46980 (Spain); Ballester, Facundo [Department of Atomic, Molecular and Nuclear Physics, University of Valencia, Burjassot 46100 (Spain)] [Department of Atomic, Molecular and Nuclear Physics, University of Valencia, Burjassot 46100 (Spain); Rivard, Mark J. [Department of Radiation Oncology, Tufts University School of Medicine, Boston, Massachusetts 02111 (United States)] [Department of Radiation Oncology, Tufts University School of Medicine, Boston, Massachusetts 02111 (United States)

    2014-02-15

    Purpose: In skin high-dose-rate (HDR) brachytherapy, sources are located outside, in contact with, or implanted at some depth below the skin surface. Most treatment planning systems use the TG-43 formalism, which is based on single-source dose superposition within an infinite water medium without accounting for the true geometry in which conditions for scattered radiation are altered by the presence of air. The purpose of this study is to evaluate the dosimetric limitations of the TG-43 formalism in HDR skin brachytherapy and the potential clinical impact. Methods: Dose rate distributions of typical configurations used in skin brachytherapy were obtained: a 5 cm × 5 cm superficial mould; a source inside a catheter located at the skin surface with and without backscatter bolus; and a typical interstitial implant consisting of an HDR source in a catheter located at a depth of 0.5 cm. Commercially available HDR{sup 60}Co and {sup 192}Ir sources and a hypothetical {sup 169}Yb source were considered. The Geant4 Monte Carlo radiation transport code was used to estimate dose rate distributions for the configurations considered. These results were then compared to those obtained with the TG-43 dose calculation formalism. In particular, the influence of adding bolus material over the implant was studied. Results: For a 5 cm × 5 cm{sup 192}Ir superficial mould and 0.5 cm prescription depth, dose differences in comparison to the TG-43 method were about ?3%. When the source was positioned at the skin surface, dose differences were smaller than ?1% for {sup 60}Co and {sup 192}Ir, yet ?3% for {sup 169}Yb. For the interstitial implant, dose differences at the skin surface were ?7% for {sup 60}Co, ?0.6% for {sup 192}Ir, and ?2.5% for {sup 169}Yb. Conclusions: This study indicates the following: (i) for the superficial mould, no bolus is needed; (ii) when the source is in contact with the skin surface, no bolus is needed for either {sup 60}Co and {sup 192}Ir. For lower energy radionuclides like {sup 169}Yb, bolus may be needed; and (iii) for the interstitial case, at least a 0.1 cm bolus is advised for {sup 60}Co to avoid underdosing superficial target layers. For {sup 192}Ir and {sup 169}Yb, no bolus is needed. For those cases where no bolus is needed, its use might be detrimental as the lack of radiation scatter may be beneficial to the patient, although the 2% tolerance for dose calculation accuracy recommended in the AAPM TG-56 report is not fulfilled.

  5. Increased serum triglycerides and reduced HDL cholesterol in male rats after intake of ammonium chloride for 3 weeks

    PubMed Central

    2013-01-01

    Background Previous data suggested that intake of sodas and other acid beverages might be associated with increased levels of serum triglycerides, lowered HDL cholesterol, and increased formation of mono unsaturated fatty acids, which are the preferred ones for triglyceride synthesis. The present work is an extension of these studies. Methods Thirty male rats were divided into 3 groups. All groups were given the same food, but various beverages: water (W), ammonium chloride, 200 mmol/L (AC), or sodium bicarbonate, 200 mmol/L (SB). Serum triglycerides, HDL cholesterol, and the fatty acid distribution in total serum lipids were determined. Delta9-desaturase in serum lipids was estimated by the ratio of palmitoleic to palmitic acid, and by the oleic/stearic acid ratio. Correlation and ANOVA were used to study associations and group differences. Results After 3 weeks, the AC group had higher triglyceride concentration and higher Delta9 desaturase indexes, but lower serum HDL and body weight as compared with the SB and W groups. In each of the groups, the oleic acid/stearic acid ratio correlated positively with serum triglycerides; in the pooled group the correlation coefficient was r?=?0.963, p<0.01. Conclusions Rats ingesting ammonium chloride as compared with sodium bicarbonate responded with increased desaturase indexes, increased serum triglycerides, and lowered HDL cholesterol concentration, thereby possibly contributing to explain the increased triglyceride concentration previously observed in subjects with a frequent intake of acid beverages, such as sodas containing carbonic acid, citric acid, and phosphoric acid. PMID:23800210

  6. Comparison of the effects of enteral feeding with continuous and intermittent parenteral nutrition on hepatic triglyceride secretion in human beings

    SciTech Connect

    Isabel-Martinez, L.; Skinner, C.; Parkin, A.; Hall, R.I.

    1989-03-01

    Plasma triglyceride turnover was measured during steady-state conditions in 22 postoperative patients. Nine had received nutritional support with an enteral regimen, seven had received an equivalent regimen as continuous parenteral nutrition, and six received the same parenteral regimen as a cyclical infusion. After 5 days of nutritional support, each patient received an intravenous bolus of tritiated glycerol. Plasma radiolabeled triglyceride content was measured during the subsequent 24 hours. The data were analyzed by means of a simple deterministic model of plasma triglyceride kinetics and compared with the results obtained by stochastic analysis. The rates of hepatic triglyceride secretion obtained by deterministic analysis were higher than those obtained by the stochastic approach. However, the mode of delivery of the nutritional regimen did not affect the rate of hepatic triglyceride secretion regardless of the method of analysis. The results suggest that neither complete nutritional bypass of the gastrointestinal tract nor interruption of parenteral nutrition in an attempt to mimic normal eating has any effect on hepatic triglyceride secretion. Any beneficial effect that enteral feeding or cyclical parenteral nutrition may have on liver dysfunction associated with standard parenteral nutrition appears to be unrelated to changes in hepatic triglyceride secretion.

  7. Elevated temperature crack growth

    NASA Technical Reports Server (NTRS)

    Yau, J. F.; Malik, S. N.; Kim, K. S.; Vanstone, R. H.; Laflen, J. H.

    1985-01-01

    The objective of the Elevated Temperature Crack Growth Project is to evaluate proposed nonlinear fracture mechanics methods for application to combustor liners of aircraft gas turbine engines. During the first year of this program, proposed path-independent (P-I) integrals were reviewed for such applications. Several P-I integrals were implemented into a finite-element postprocessor which was developed and verified as part of the work. Alloy 718 was selected as the analog material for use in the forthcoming experimental work. A buttonhead, single-edge notch specimen was designed and verified for use in elevated-temperature strain control testing with significant inelastic strains. A crack mouth opening displacement measurement device was developed for further use.

  8. Immunological changes induced by Toxoplasma gondii Glutathione-S-Transferase (TgGST) delivered as a DNA vaccine.

    PubMed

    Wang, Shuai; Hassan, Ibrahim A; Liu, XinChao; Xu, LiXin; Yan, RuoFeng; Song, XiaoKai; Li, XiangRui

    2015-04-01

    In this study, a DNA vaccine (pTgGST) encoding T.?gondii antioxidant glutathione-S-transferase (TgGST) inserted into eukaryotic expression vector pVAX I was constructed and the immune protective efficacy of intramuscular vaccination of mice with pTgGST was analyzed. Mice immunized with pTgGST elicited high titers of total IgG, IgG1, IgG2a, IgA and IgM antibodies, while IgE showed no changes. Also, significant cytokine production of IFN-?, IL-4 and IL-17 was detected in mice immunized with pTgGST, but not TGF-?1. CD8(+) T cells subsets and MHC-I molecules showed significant increase in contrast to CD4(+) subsets. Immunization with pTgGST significantly prolonged survival time (14 days) after challenge infection with the virulent T.?gondii RH strain, compared with the control groups which died within 8 days. These results suggested that TgGST DNA vaccine could trigger strong humoral and cellular responses and induce partial protection against acute toxoplasmosis. PMID:25648285

  9. Elevated temperature crack growth

    NASA Technical Reports Server (NTRS)

    Malik, S. N.; Vanstone, R. H.; Kim, K. S.; Laflen, J. H.

    1987-01-01

    The objective of the Elevated Temperature Crack Growth Program is to evaluate proposed nonlinear fracture mechanics methods for application to hot section components of aircraft gas turbine engines. Progress during the past year included linear-elastic fracture mechanics data reduction on nonlinear crack growth rate data on Alloy 718. The bulk of the analytical work centered on thermal gradient problems and proposed fracture mechanics parameters. Good correlation of thermal gradient experimental displacement data and finite element prediction was obtained.

  10. Contour Lines and Elevation

    NSDL National Science Digital Library

    Stephen J Reynolds

    This animation features a static image of a contour surface on the left and an oblique 3-D view of the same area. Upon starting the animation, by clicking adjacent arrows, a surface of water begins to rise. By examining the views in both windows, a simulated flood shows how contour lines trace out equal elevations and how concave/convex undulations in the contour lines would be represented in 3-D. The animation can be paused and rewound to stress important points.

  11. An omega-3 polyunsaturated fatty acid concentrate administered for one year decreased triglycerides in simvastatin treated patients with coronary heart disease and persisting hypertriglyceridaemia

    Microsoft Academic Search

    P N Durrington; D Bhatnagar; M I Mackness; J Morgan; K Julier; M A Khan

    2001-01-01

    BACKGROUNDOmega-3 fatty acids, such as those present in fish oil, have been reported to prolong life in myocardial infarction survivors. These fatty acids can decrease serum triglyceride concentrations, but so far the doses used in trials examining their effects on coronary end points have had only minimal triglyceride lowering effects.OBJECTIVETo examine the triglyceride lowering effectiveness, safety, and tolerability of Omacor,

  12. 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.

  13. 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.

  14. 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

  15. Pyrolysis of triglyceride materials for the production of renewable fuels and chemicals.

    PubMed

    Maher, K D; Bressler, D C

    2007-09-01

    Conversion of vegetable oils and animal fats composed predominantly of triglycerides using pyrolysis type reactions represents a promising option for the production of renewable fuels and chemicals. The purpose of this article was to collect and review literature on the thermo-chemical conversion of triglyceride based materials. The literature was divided and discussed as (1) direct thermal cracking and (2) combination of thermal and catalytic cracking. Typically, four main catalyst types are used including transition metal catalysts, molecular sieve type catalysts, activated alumina, and sodium carbonate. Reaction products are heavily dependant on the catalyst type and reaction conditions and can range from diesel like fractions to gasoline like fractions. Research in this area is not as advanced as bio-oil and bio-diesel research and there is opportunity for further study in the areas of reaction optimization, detailed characterization of products and properties, and scale-up. PMID:17166713

  16. Separation and determination of mono-, Di, and triglycerides in monoglyceride concentrates

    Microsoft Academic Search

    Patricia Quinlin; Herman J. Weiser

    1958-01-01

    Summary  Monoglyceride concentrates are quantitatively separated into mono-, di-, and triglyceride components on silica gel columns\\u000a by an adsorption chromatographic technique. The separated glycerides are determined gravimetrically. The adsorption on silica\\u000a gel is dependent on the number of hydroxyl groups in the molecule, and the influence of unsaturation and chain length is minimized.\\u000a Combinations of benzene and ethyl ether are used

  17. Production of biodiesel fuel from triglycerides and alcohol using immobilized lipase

    Microsoft Academic Search

    Mamoru Iso; Baoxue Chen; Masashi Eguchi; Takashi Kudo; Surekha Shrestha

    2001-01-01

    Transesterification reaction was performed using triglycerides and short-chain alcohol by immobilized lipase in non-aqueous conditions. The long-chain fatty acid ester, which is the product of this reaction, can be used as a diesel fuel that does not produce sulfur oxide and minimize the soot particulate. Immobilized Pseudomonas fluorescens lipase showed the highest activity in this reaction. Immobilization of lipase was

  18. Separation of triglycerides by chain length and degree of unsaturation on silica HPLC columns

    Microsoft Academic Search

    R. D. Plattner; Kathleen Payne-Wahl

    1979-01-01

    Triacylglycerols can be separated by both chain length and number of double bonds using micro particulate silica high pressure\\u000a liquid chromatography columns with isooctane, diethyl ether, and acetic acid solvent mixtures. The separations obtained are\\u000a the reverse of those observed with ?-Bondapak C18 columns (Waters Associates); i.e., longer chain length triglycerides elute from the column earlier than their shorter chain

  19. Cholesterol and triglycerides lowering activities of caraway fruits in normal and streptozotocin diabetic rats

    Microsoft Academic Search

    A. Lemhadri; L. Hajji; J.-B. Michel; M. Eddouks

    2006-01-01

    The purpose of this study was to examine the effect of single and repeated oral administration of the aqueous extract of Carum carvi L. fruits at a dose of (20mg\\/kg) on lipid metabolism in normal and streptozotocin-induced diabetic rats (STZ). After a single oral administration, Carum carvi extract produced a significant decrease on triglycerides levels in normal rats (p<0.05). In

  20. Droplet-based Microtexture Biochip System for Triglycerides and Methanol Measurement

    Microsoft Academic Search

    Ming-Yu Lin; Chih-Sheng Yu; Yi-Chiuen Hu; Shao-Chang Cheng; Heng-Tsang Hu

    2005-01-01

    A droplet-based microfluidic system was developed for biochemical assays of triglycerides and methanol as potential applications in medical rapid diagnostics and food safety. We present a novel platform to manipulate biology reaction droplets with features of self-moving, self-mixing, and self-positioning toward the detection spot. The driving force comes from the gradient of surface tension force generated by the hydrophobic microtexture

  1. Effect of diet on triglyceride structure and composition of egg yolk lipids

    Microsoft Academic Search

    J. R. Couch; A. E. Saloma

    1973-01-01

    Hens were fed a practical diet supplemented and unsupplemented with 5% menhaden oil and a synthetic fat-free diet for a period\\u000a of 90 days. Egg yolks from hens fed each of the three diets were analyzed for fatty acid composition and positional distribution\\u000a of the fatty acids by successive chromatographic techniques. The triglycerides were resolved into fractions containing, 0,\\u000a 1,

  2. Differential scanning calorimetry of confectionery fats. Pure triglycerides: Effects of cooling and heating rate variation

    Microsoft Academic Search

    Deryck J. Cebula; Kevin W. Smith

    1991-01-01

    Differential scanning calorimetry (DSC) measurements of the crystallization and melting phenomena of pure forms of the three\\u000a principal triglycerides present in cocoa butter and related confectionery fats are presented. The results are used to exhibit\\u000a the usefulness of the DSC technique for potential application in quality control of these types of material, but also as a\\u000a warning of the difficulties

  3. Recovery of triglycerides from used frying oil by extraction with liquid and supercritical ethane

    Microsoft Academic Search

    Jesusa Rincón; Fabiola Martínez; Luis Rodríguez; Virginia Ancillo

    2011-01-01

    The extraction of triglycerides from used frying oil with liquid and supercritical ethane has been studied in a semibatch system at different temperatures (25–80°C) and pressures (150–250kg\\/cm2). It has been found that isobaric decreases of temperature and isothermal increases of pressure lead to both increasing extraction yields and decreasing separation efficiencies. Lipid fractions recovered in the high density region had

  4. Induction of ATF3 Gene Network by Triglyceride-Rich Lipoprotein Lipolysis Products Increases Vascular Apoptosis and Inflammation

    PubMed Central

    Aung, Hnin H.; Lamé, Michael W.; Gohil, Kishorchandra; An, Chung-Il; Wilson, Dennis W.; Rutledge, John C.

    2013-01-01

    Objective Elevation of triglyceride-rich lipoproteins (TGRL) contributes to the risk for atherosclerotic cardiovascular disease (ASCVD). Our work has shown that TGRL lipolysis products in high physiological to pathophysiological concentrations cause endothelial cell injury; however, the mechanisms remain to be delineated. Approach and Results We analyzed the transcriptional signaling networks in arterial endothelial cells exposed to TGRL lipolysis products. When human aortic endothelial cells (HAEC) in culture were exposed to TGRL lipolysis products, activating transcription factor 3 (ATF3) was identified as a principal response gene. Induction of ATF3 mRNA and protein was confirmed by qRT-PCR and western blot. Immunofluorescence analysis showed that ATF3 accumulated in the nuclei of cells treated with lipolysis products. Nuclear expression of p-JNK, previously shown to be an initiator of the ATF3 signaling cascade, also was demonstrated. siRNA-mediated inhibition of ATF3 blocked lipolysis products-induced transcription of E-selectin and IL-8, but not IL-6 or NF?B. c-Jun, a downstream protein in the JNK pathway was phosphorylated while expression of NF?B-dependant JunB was down-regulated. Additionally, JNK siRNA suppressed ATF3 and p-c-Jun protein expression suggesting that JNK is up-stream of the ATF3 signaling pathway. In vivo studies demonstrated that infusion of TGRL lipolysis products into wild type mice induced nuclear ATF3 accumulation in carotid artery endothelium. ATF3?/? mice were resistant to vascular apoptosis precipitated by treatment with TGRL lipolysis products. Also peripheral blood monocytes isolated from postprandial humans had increased ATF3 expression as compared to fasting monocytes. Conclusion This study demonstrates that TGRL lipolysis products activate ATF3-JNK transcription factor networks and induce endothelial cells inflammatory response. PMID:23868936

  5. Refrigeration Plant, North Elevation, Second Floor Plan, East Elevation, Ground ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Refrigeration Plant, North Elevation, Second Floor Plan, East Elevation, Ground Floor Plan, Section A-A - Kennecott Copper Corporation, On Copper River & Northwestern Railroad, Kennicott, Valdez-Cordova Census Area, AK

  6. 49. EAST ELEVATION OF ASSEMBLING BUILDING #2 AND SOUTH ELEVATION ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    49. EAST ELEVATION OF ASSEMBLING BUILDING #2 AND SOUTH ELEVATION OF BODY BUILDING, 1980 (MMI) - Dodge Brothers Motor Car Company Plant, Between Joseph Campau & Conant Avenues, Hamtramck, Wayne County, MI

  7. location plan, floor plan, west elevation, east elevation Chopawamsic ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    location plan, floor plan, west elevation, east elevation - Chopawamsic Recreational Demonstration Area - Cabin Camp 1, Main Arts and Crafts Lodge, Prince William Forest Park, Triangle, Prince William County, VA

  8. location plan, floor plan, building section, north elevation, west elevation, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    location plan, floor plan, building section, north elevation, west elevation, louver window detail, mechanical room door profile, partition profile - Chopawamsic Recreational Demonstration Area - Cabin Camp 1, Staff Bath House, Prince William Forest Park, Triangle, Prince William County, VA

  9. location map, floor plan, building section, north elevation, west elevation, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    location map, floor plan, building section, north elevation, west elevation, door and window details - Chopawamsic Recreational Demonstration Area - Cabin Camp 1, Central Bath House, Prince William Forest Park, Triangle, Prince William County, VA

  10. north elevation, south elevation, building section, window details Chopawamsic ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    north elevation, south elevation, building section, window details - Chopawamsic Recreational Demonstration Area - Cabin Camp 1, Main Arts and Crafts Lodge, Prince William Forest Park, Triangle, Prince William County, VA

  11. location plan, floor plan, section, north elevation, west elevation and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    location plan, floor plan, section, north elevation, west elevation and window details - Chopawamsic Recreational Demonstration Area - Cabin Camp 1, Administration, Prince William Forest Park, Triangle, Prince William County, VA

  12. 33. Coal Fuel Elevator (diagonal in foreground), Fuel Elevator (left), ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    33. Coal Fuel Elevator (diagonal in foreground), Fuel Elevator (left), Fuel Storage Bins (center), and Power Plant (right) Photographs taken by Joseph E.B. Elliot - Huber Coal Breaker, 101 South Main Street, Ashley, Luzerne County, PA

  13. Insulin-independent regulation of hepatic triglyceride synthesis by fatty acids

    PubMed Central

    Vatner, Daniel F.; Majumdar, Sachin K.; Kumashiro, Naoki; Petersen, Max C.; Rahimi, Yasmeen; Gattu, Arijeet K.; Bears, Mitchell; Camporez, João-Paulo G.; Cline, Gary W.; Jurczak, Michael J.; Samuel, Varman T.; Shulman, Gerald I.

    2015-01-01

    A central paradox in type 2 diabetes is the apparent selective nature of hepatic insulin resistance—wherein insulin fails to suppress hepatic glucose production yet continues to stimulate lipogenesis, resulting in hyperglycemia, hyperlipidemia, and hepatic steatosis. Although efforts to explain this have focused on finding a branch point in insulin signaling where hepatic glucose and lipid metabolism diverge, we hypothesized that hepatic triglyceride synthesis could be driven by substrate, independent of changes in hepatic insulin signaling. We tested this hypothesis in rats by infusing [U-13C] palmitate to measure rates of fatty acid esterification into hepatic triglyceride while varying plasma fatty acid and insulin concentrations independently. These experiments were performed in normal rats, high fat-fed insulin-resistant rats, and insulin receptor 2?-O-methoxyethyl chimeric antisense oligonucleotide-treated rats. Rates of fatty acid esterification into hepatic triglyceride were found to be dependent on plasma fatty acid infusion rates, independent of changes in plasma insulin concentrations and independent of hepatocellular insulin signaling. Taken together, these results obviate a paradox of selective insulin resistance, because the major source of hepatic lipid synthesis, esterification of preformed fatty acids, is primarily dependent on substrate delivery and largely independent of hepatic insulin action. PMID:25564660

  14. Paraoxonase 2 attenuates macrophage triglyceride accumulation via inhibition of diacylglycerol acyltransferase 1.

    PubMed

    Rosenblat, Mira; Coleman, Raymond; Reddy, Srinivasa T; Aviram, Michael

    2009-05-01

    This study questioned the role of paraoxonase 2 (PON2) in attenuation of macrophage lipids accumulation. Mouse peritoneal macrophages (MPMs) harvested from PON2-deficient mice versus control C57BL/6 mice, look like foam cells and were larger in size and filled with lipid droplets. Macrophage triglyceride (but not cholesterol) content, biosynthesis rate, and microsomal acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) activity (not mRNA and protein) in PON2-deficient versus control MPM were all significantly increased by 4.6-, 3.6-, and 4.4-fold, respectively. Similarly, microsomal DGAT1 activity and cellular triglyceride content were significantly decreased in human PON2-transfected cells as well as upon incubation of PON2-deficient MPM with recombinant PON2. In all the above experimental systems, PON2 also decreased macrophage oxidative state. Incubation of PON2-deficient MPM with the free radicals generator 2,2'-amidinopropane hydrochloride increased cellular oxidative stress and DGAT1 activity by 2.2- and 3.4-fold, respectively, whereas incubation of microsomes from PON2-deficient MPM with superoxide dismutase decreased DGAT1 activity by 40%. We thus conclude that PON2 attenuates macrophage triglyceride accumulation and foam cell formation via inhibition of microsomal DGAT1 activity, which appears to be sensitive to oxidative state. PMID:19091699

  15. 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).

  16. 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.

  17. Fractionation of human serum lipoproteins and simultaneous enzymatic determination of cholesterol and triglycerides.

    PubMed

    Qureshi, Rashid Nazir; Kok, Wim Th; Schoenmakers, Peter J

    2009-11-01

    A method based on Asymmetric Flow Field-Flow Fractionation (AF4) was developed to separate different types of lipoproteins from human serum. The emphasis in the method optimization was on the possibilities to characterize the largest lipoprotein fractions (LDL and VLDL), which is usually not possible with the size-exclusion chromatography methods applied in routine analysis. Different channel geometries and flow programs were tested and compared. The use of a short fractionation channel was shown to give less sample dilution at the same fractionation power compared to a conventional, long channel. Different size selectivities were obtained with an exponential decay and a linear cross flow program. The ratio of the UV absorption signal to the light scattering signal was used to validate the relation between retention time and size of the fractionated particles. An experimental setup was developed for the simultaneous determination of the cholesterol and triglycerides distribution over the lipoprotein fractions, based on enzymatic reactions followed by UV detection at 500 nm. Coiled and knitted PTFE tubing reactors were compared. An improved peak sharpness and sensitivity were observed with the knitted tubing reactor. After optimization of the experimental conditions a satisfactory linearity and precision (2-3% rsd for cholesterol and 5-6% rsd for triglycerides) were obtained. Finally, serum samples, a pooled sample from healthy volunteers and samples of sepsis patients, were analyzed with the method developed. Lipoprotein fractionation and cholesterol and triglyceride distributions could be correlated with the clinical background of the samples. PMID:19850173

  18. Whole-body lipolysis and triglyceride-fatty acid cycling in cachectic patients with esophageal cancer.

    PubMed Central

    Klein, S; Wolfe, R R

    1990-01-01

    Whole-body lipolytic rates and the rate of triglyceride-fatty acid cycling (reesterification of fatty acids released during lipolysis) were measured with stable isotopic tracers in the basal state and during beta-adrenergic blockade with propranolol infusion in five cachectic patients with squamous cell carcinoma of the esophagus, five cachectic cancer-free, nutritionally-matched control patients, and 10 healthy volunteers. Resting energy expenditure and plasma catecholamines were normal in all three groups. The basal rate of glycerol appearance in blood in the patients with cancer (2.96 +/- 0.45 mumol.kg-1.min-1) was similar to that in the nutritionally matched controls (3.07 +/- 0.28 mumol.kg-1.min-1), but 48% greater than in the normal-weight volunteers (2.00 +/- 0.16 mumol.kg-1.min-1) (P = 0.028). The antilipolytic effect of propranolol and the rate of triglyceride-fatty acid cycling in the patients with cancer were also similar in the cachectic control group and approximately 50% greater than in the normal-weight volunteers, but the differences were not statistically significant because of the variability in the data. We conclude that the increase in lipolysis and triglyceride-fatty acid cycling in "unstressed" cachectic patients with esophageal cancer is due to alterations in their nutritional status rather than the presence of tumor itself. Increased beta-adrenergic activity may be an important contributor to the stimulation of lipolysis. PMID:2243120

  19. Expression of microsomal triglyceride transfer protein in lipoprotein-synthesizing tissues of the developing chicken embryo?

    PubMed Central

    Eresheim, Christine; Plieschnig, Julia; Ivessa, N. Erwin; Schneider, Wolfgang J.; Hermann, Marcela

    2014-01-01

    In contrast to mammals, in the chicken major sites of lipoprotein synthesis and secretion are not only the liver and intestine, but also the kidney and the embryonic yolk sac. Two key components in the assembly of triglyceride-rich lipoproteins are the microsomal triglyceride transfer protein (MTP) and apolipoprotein B (apoB). We have analyzed the expression of MTP in the embryonic liver, small intestine, and kidney, and have studied the expression of MTP in, and the secretion of apoB from, the developing yolk sac (YS). Transcript and protein levels of MTP increase during embryogenesis in YS, liver, kidney, and small intestine, and decrease in YS, embryonic liver, and kidney after hatching. In small intestine, the MTP mRNA level rises sharply during the last trimester of embryo development (after day 15), while MTP protein is detectable only after hatching (day 21). In the YS of 15- and 20-day old embryos, apoB secretion was detected by pulse-chase metabolic radiolabeling experiments and subsequent immunoprecipitation. Taken together, our data reveal the importance of coordinated production of MTP and apoB in chicken tissues capable of secreting triglyceride-rich lipoproteins even before hatching. PMID:24394625

  20. Triglycerides Test

    MedlinePLUS

    ... Cholesterol ; LDL Cholesterol ; Direct LDL Cholesterol ; VLDL Cholesterol ; Lipid Profile ; Cardiac Risk Assessment At a Glance Test Sample ... When to Get Tested? As part of a lipid profile during a regular medical exam (at least once ...

  1. Apolipoprotein A-V Deficiency Results in MarkedHypertriglyceridemia Attributable to Decreased Lipolysis ofTriglyceride-Rich Lipoproteins and Removal of Their Remnants

    SciTech Connect

    Grosskopf, Itamar; Baroukh, Nadine; Lee, Sung-Joon; Kamari,Yehuda; Harats, Dror; Rubin, Edward M.; Pennacchio, Len A.; Cooper, AllenD.

    2005-09-01

    Objective--ApoAV, a newly discovered apoprotein, affectsplasma triglyceride level. To determine how this occurs, we studiedtriglyceride-rich lipoprotein (TRL) metabolism in mice deficient inapoAV. Methods and Results No significant difference in triglycerideproduction rate was found between apoa5_/_ mice and controls. Thepresence or absence of apoAV affected TRL catabolism. After the injectionof 14C-palmitate and 3H-cholesterol labeled chylomicrons and 125I-labeledchylomicron remnants, the disappearance of 14C, 3H, and 125I wassignificantly slower in apoa5_/_ mice relative to controls. This wasbecause of diminished lipolysis of TRL and the reduced rate of uptake oftheir remnants in apoa5_/_ mice. Observed elevated cholesterol level wascaused by increased high-density lipoprotein (HDL) cholesterol inapoa5_/_ mice. VLDL from apoa5_/_ mice were poor substrate forlipoprotein lipase, and did not bind to the low-density lipoprotein (LDL)receptor as well as normal very-low-density lipoprotein (VLDL). LDLreceptor levels were slightly elevated in apoa5_/_ mice consistent withlower remnant uptake rates. These alterations may be the result of thelower apoE-to-apoC ratio found in VLDL isolated from apoa5_/_mice.Conclusions These results support the hypothesis that the absence ofapoAV slows lipolysis of TRL and the removal of their remnants byregulating their apoproteins content after secretion.

  2. Mechanism of action of hypoglycemic effects of an intestine-specific inhibitor of microsomal triglyceride transfer protein (MTP) in obese rats.

    PubMed

    Sakata, Shohei; Katsumi, Sohei; Mera, Yasuko; Kuroki, Yukiharu; Nashida, Reiko; Kakutani, Makoto; Ohta, Takeshi

    2015-01-01

    Diminished insulin sensitivity in the peripheral tissues and failure of pancreatic beta cells to secrete insulin are known major determinants of type 2 diabetes mellitus. JTT-130, an intestine-specific microsomal transfer protein inhibitor, has been shown to suppress high fat-induced obesity and ameliorate impaired glucose tolerance while enhancing glucagon-like peptide-1 (GLP-1) secretion. We investigated the effects of JTT-130 on glucose metabolism and elucidated the mechanism of action, direct effects on insulin sensitivity and glucose-stimulated insulin secretion in a high fat diet-induced obesity rat model. Male Sprague Dawley rats fed a high-fat diet were treated with a single administration of JTT-130. Glucose tolerance, hyperglycemic clamp and hyperinsulinemic-euglycemic testing were performed to assess effects on insulin sensitivity and glucose-stimulated insulin secretion, respectively. Plasma GLP-1 and tissue triglyceride content were also determined under the same conditions. A single administration of JTT-130 suppressed plasma glucose elevations after oral glucose loading and increased the disposition index while elevating GLP-1. JTT-130 also enhanced glucose-stimulated insulin secretion in hyperglycemic clamp tests, whereas increased insulin sensitivity was observed in hyperinsulinemic-euglycemic clamp tests. Single-dose administration of JTT-130 decreased lipid content in the liver and skeletal muscle. JTT-130 demonstrated acute and direct hypoglycemic effects by enhancing insulin secretion and/or insulin sensitivity. PMID:25704025

  3. Sex steroid levels and AD-like pathology in 3xTgAD mice

    PubMed Central

    Ma, Chunqi; Taves, Matthew D.; Soma, Kiran K.; Mufson, Elliott J.

    2014-01-01

    Decreases in testosterone (T) and 17?-oestradiol (E2) are associated with an increased risk for Alzheimer's disease (AD), which has been attributed to an increase in beta amyloid (A?) and tau pathologic lesions. While recent studies have used transgenic animal models to test the effects of sex steroid manipulations on AD-like pathology, virtually none have systematically characterised the associations between AD lesions and sex steroid levels in the blood or brain in any mutant model. The present study evaluated age-related changes in T and E2 concentrations, as well as androgen receptor (AR) and oestrogen receptor (ER) ? and ? expression, in brain regions displaying AD pathology in intact male and female 3xTgAD and non-transgenic (ntg) mice. We report for the first time that circulating and brain T levels significantly increase in male 3xTgAD mice with age, but without changes in AR-immunoreactive (ir) cell number in either the hippocampal CA1 or medial amygdala. The age-related increase in hippocampal T levels correlated positively with increases in the conformational tau isoform, Alz50. These data suggest that the over-expression of human tau may up regulate the hypothalamic-pituitary-gonadal axis in these mice. Although circulating and brain E2 levels remained stable with age in both male and female 3xTgAD and ntg mice, ER-ir cell number in the hippocampus and medial amygdala decreased with age in female transgenic mice. Further, E2 levels were significantly higher in the hippocampus than in serum, suggesting local production of E2. Although triple transgenic mice mimic AD-like pathology, they do not fully replicate changes in human sex steroid levels, and may not be the best model for studying the effects of sex steroids on AD lesions. PMID:22889357

  4. The effect of tobacco smoke and some of its constitutents on triglyceride secretion in the squirrel monkey.

    PubMed

    Turner, D M; Topping, D L

    1975-09-01

    The acute effects of tobacco smoke and some of its constituents on plasma free fatty acid levels and on triglyceride secretion were studied in anaesthetized squirrel monkeys given Triton WR-1339. All the treatments raised plasma free fatty acids in the order high tar smoke greater than medium tar vapour phase = air:CO greater than medium tar smoke. Plasma triglyceride secretion in animals inhaling high tar smoke did not differ from controls. There was a transient rise in triglyceride secretion in animals inhaling vapour phase but the largest increase (after a significant delay) was in monkeys breathing air:CO. Maximal concentrations of blood carboxyhaemoglobin did not differ between the experimental groups. It is suggested that, under these experimental conditions, there are present in the particulate phase of tobacco smoke factors which inhibit hepatic triglyceride secretion. PMID:810833

  5. QUANTITATIVE DETERMINATION OF THE NUTRITIONAL STATUS OF DETRITAL MICROBIOTA AND THE GRAZING FAUNA BY TRIGLYCERIDE GLYCEROL ANALYSIS

    EPA Science Inventory

    Endogenous lipid storage components are accumulated or utilized by both microorganisms and marine invertebrates, depending upon their nutritional status. Triglycerides are commonly the lipid endogenous storage materials utilized by fungi, marine vertebrates and many invertebrates...

  6. Elevate America's State Voucher Strategy

    E-print Network

    Bernstein, Phil

    Elevate America's State Voucher Strategy to Promote Employability Lessons Learned April 2011 #12 ...............................................................................................................................15 Additional information about Elevate America is available at: http://microsoft.com/elevateamerica #12;2 Elevate America's State Voucher Strategy to Promote Employability Preface On February 22, 2009

  7. Rapid nuclear transit and impaired degradation of amyloid ? and glypican-1-derived heparan sulfate in Tg2576 mouse fibroblasts.

    PubMed

    Cheng, Fang; Fransson, Lars-Åke; Mani, Katrin

    2015-05-01

    Anhydromannose (anMan)-containing heparan sulfate (HS) derived from S-nitrosylated glypican-1 is generated in endosomes by an endogenously or ascorbate induced S-nitrosothiol-catalyzed reaction. Expression and processing of amyloid precursor protein (APP) is required to initiate formation and endosome-to-nucleus translocation of anMan-containing HS in wild-type mouse embryonic fibroblasts (WT MEF). HS is then transported to autophagosomes and finally degraded in lysosomes. To investigate how APP-derived amyloid ? (A?) peptide affects intracellular trafficking of HS, we have studied nuclear transit as well as autophagosome/lysosome targeting and degradation in transgenic Alzheimer disease mouse (Tg2576) MEF which produce increased amounts of A?. Deconvolution immunofluorescence microscopy with an anMan-specific monoclonal antibody showed anMan staining in the nuclei of Tg2576 MEF after 5 min of ascorbate treatment and after 15 min in WT MEF. There was also greater nuclear accumulation of HS in Tg2576 MEF as determined by (35)S-sulfate-labeling experiments. Tg2576 MEF was less sensitive to inhibition of NO production and copper-chelation than WT MEF. By using APP- and A?-recognizing antibodies, we observed nuclear translocation of A? peptide in Tg2576 MEF but not in WT MEF. HS remained in the nucleus of WT MEF for at least 8 h and was then transported to autophagosomes. By 8 h, HS had disappeared from the nuclei of Tg2576 MEF but colocalized poorly with the autophagosome marker LC3. A? also disappeared rapidly from the nuclei of Tg2576 MEF. Initially, it appeared in acidic vesicles and later it accumulated extracellularly. Thus, in Tg2576 MEF there is nuclear accumulation as well as secretion of A? and impaired degradation of HS. PMID:25527428

  8. Study on the pyrolytic behaviour of xylan-based hemicellulose using TG–FTIR and Py–GC–FTIR

    Microsoft Academic Search

    D. K. Shen; S. Gu; A. V. Bridgwater

    2010-01-01

    Two sets of experiments, categorized as TG–FTIR and Py–GC–FTIR, are employed to investigate the mechanism of the hemicellulose pyrolysis and the formation of main gaseous and bio-oil products. The “sharp mass loss stage” and the corresponding evolution of the volatile products are examined by the TG–FTIR graphs at the heating rate of 3–80K\\/min. A pyrolysis unit, composed of fluidized bed

  9. Age-dependent skin tumorigenesis and transgene expression in the Tg.AC (v-Ha-ras) transgenic mouse

    Microsoft Academic Search

    Michael St J. Battalora; Judson W. Spalding; Carl J. Szczesniak; James E. Cape; Rebecca J. Morris; Carol S. Trempus; Carl D. Bortner; Byung M. Lee; Raymond W. Tennant

    Transgenic Tg.AC (v-Ha-ras ) mice develop skin tumors in response to specific carcinogens and tumor promoters. The Tg.AC mouse carries the coding sequence of v-Ha ras, linked to a ?-globin promoter and an SV40 polyadenylation signal sequence. The transgene confers on these mice the property of genetically initiated skin. This study examines the age-dependent sensitivity of the incidence of skin

  10. Study on the thermal degradation of high performance fibers by TG\\/FTIR and Py-GC\\/MS

    Microsoft Academic Search

    Guang Ming Cai; Wei Dong Yu

    2011-01-01

    The thermal degradation behaviors of Kevlar 49, Kevlar 129 (Poly(p-phenylene terephthamide), Nomex (polyisophthaloyl metaphenylene diamine), and PBO(poly(p-phenylene benzobisoxazole)) fibers were measured by TG\\/FTIR and Py-GC\\/MS. The characteristic temperatures of the fibers in\\u000a air were obtained by TG. It indicated that the initial degradation temperature of the PBO is the highest. The initial degradation\\u000a temperature of Nomex fiber is the lowest,

  11. Identification of TgCBAP, a Novel Cytoskeletal Protein that Localizes to Three Distinct Subcompartments of the Toxoplasma gondii Pellicle

    PubMed Central

    Tilley, Lucas D.; Krishnamurthy, Shruthi; Westwood, Nicholas J.; Ward, Gary E.

    2014-01-01

    The cytoskeletons of Toxoplasma gondii and related apicomplexan parasites are highly polarized, with apical and basal regions comprised of distinct protein complexes. Components of these complexes are known to play important roles in parasite shape, cell division, and host cell invasion. During an effort to discover the biologically relevant target of a small-molecule inhibitor of T. gondii invasion (Conoidin A), we discovered a novel cytoskeletal protein that we named TgCBAP (Conserved Basal Apical Peripheral protein). Orthologs of TgCBAP are only found in the genomes of other apicomplexans; they contain no identifiable domains or motifs and their function(s) is unknown. As a first step toward elucidating the function of this highly conserved family of proteins, we disrupted the TgCBAP gene by double homologous recombination. Parasites lacking TgCBAP are as sensitive to the effects of Conoidin A as wild-type parasites, demonstrating that TgCBAP is not the biologically relevant target of Conoidin A. However, ?TgCBAP parasites are significantly shorter than wild-type parasites and have a growth defect in culture. Furthermore, TgCBAP has an unusual subcellular localization, forming small rings at the apical and basal ends of the parasite and localizing to punctate, ring-like structures around the parasite periphery. These data identify a new marker of the apical and basal subcompartments of T. gondii, reveal a potentially novel compartment along the parasite periphery, and identify TgCBAP as a determinant of parasite size that is required for a maximally efficient lytic cycle. PMID:24887026

  12. Effects of dietary triglyceride on the properties and lipid composition of plasma lipoproteins: Acute experiments in rats fed safflower oil

    Microsoft Academic Search

    G. Dewey Dunn; Henry G. Wilcox; Murray Heimberg

    1975-01-01

    Male rats were administered 1.5 ml safflower oil by gastric intubation 0, 4, and 8 hr after a 16 hr fast. Plasma, liver, and\\u000a adipose tissue were collected 16 hr after the last fatty meal. Rats fasted for 16 hr served as controls. Following fat feeding,\\u000a the fatty acid composition of the very low density lipoprotein, triglyceride, and hepatic triglyceride

  13. Colocalization of SCD1 and DGAT2: implying preference for endogenous monounsaturated fatty acids in triglyceride synthesis

    Microsoft Academic Search

    Weng Chi Man; Makoto Miyazaki; Kiki Chu; James Ntambi

    2006-01-01

    Stearoyl-coenzyme A desaturase (SCD) is an endo- plasmic reticulum (ER) protein that catalyzes the D9-cis desaturation of saturated fatty acids. Mice with targeted disruption in SCD1 (Scd12\\/2) have significant reduction in the tissue content of triglycerides, suggesting that mono- unsaturated fatty acids endogenously synthesized by SCD1 are important for triglyceride synthesis. Acyl-coenzyme A: diacylglycerol acyltransferase (DGAT) is the enzyme that

  14. A non-transgenic mouse model (icv-STZ mouse) of Alzheimer’s disease: Similarities to and differences from the transgenic model (3xTg-AD mouse)

    PubMed Central

    Chen, Yanxing; Liang, Zhihou; Blanchard, Julie; Dai, Chun-Ling; Sun, Shenggang; Lee, Moon H.; Grundke-Iqbal, Inge; Iqbal, Khalid; Liu, Fei

    2012-01-01

    Alzheimer’s disease (AD) can be divided into sporadic AD (SAD) and familial AD (FAD). Most AD cases are sporadic and result from multiple etiologic factors, including environmental, genetic and metabolic factors, whereas FAD is caused by mutations in the presenilins or amyloid-? (A?) precursor protein (APP) genes. A commonly used animal model for AD is the 3xTg-AD transgenic mouse model, which harbors mutated presenilin 1, APP and tau genes and thus represents a model of FAD. There is an unmet need to in the field to characterize animal models representing different AD mechanisms, so that potential drugs for SAD can be evaluated preclinically in these animal models. A mouse model generated by intracerebroventricular (icv) administration of streptozocin (STZ), the icv-STZ mouse, shows many aspects of SAD. In this study, we compared the non-cognitive and cognitive behaviors as well as biochemical and immunohistochemical alterations between the icv-STZ mouse and the 3xTg-AD mouse. We found that both mouse models showed increased exploratory activity as well as impaired learning and spatial memory. Both models also demonstrated neuroinflammation, altered synaptic proteins and insulin/IGF-1 (insulin-like growth factor-1) signaling, and increased hyperphosphorylated tau in the brain. The most prominent brain abnormality in the icv-STZ mouse was neuroinflammation, and in the 3xTg-AD mouse it was elevation of hyperphosphorylated tau. These observations demonstrate the behavioral and neuropathological similarities and differences between the icv-STZ mouse and the 3xTg-AD mouse models and will help guide future studies using these two mouse models for the development of AD drugs. PMID:23150171

  15. Renal Tubule Angiotensin II Type 1 Receptor–Associated Protein Promotes Natriuresis and Inhibits Salt?Sensitive Blood Pressure Elevation

    PubMed Central

    Wakui, Hiromichi; Uneda, Kazushi; Tamura, Kouichi; Ohsawa, Masato; Azushima, Kengo; Kobayashi, Ryu; Ohki, Kohji; Dejima, Toru; Kanaoka, Tomohiko; Tsurumi?Ikeya, Yuko; Matsuda, Miyuki; Haruhara, Kotaro; Nishiyama, Akira; Yabana, Machiko; Fujikawa, Tetsuya; Yamashita, Akio; Umemura, Satoshi

    2015-01-01

    Background Angiotensin II type 1 receptor (AT1R)–associated protein (ATRAP; Agtrap gene) promotes AT1R internalization along with suppression of pathological AT1R activation. In this study, we examined whether enhancement of ATRAP in the renal distal tubules affects sodium handling and blood pressure regulation in response to high salt (HS) loading, using ATRAP transgenic mice on a salt?sensitive C57BL/6J background. Methods and Results Renal ATRAP transgenic (rATRAP?Tg) mice, which exhibit renal tubule–dominant ATRAP enhancement, and their wild?type littermate C57BL/6J mice on a normal salt diet (0.3% NaCl) at baseline were subjected to dietary HS loading (4% NaCl) for 7 days. In rATRAP?Tg mice, the dietary HS loading–mediated blood pressure elevation was suppressed compared with wild?type mice, despite similar baseline blood pressure. Although renal angiotensin II level was comparable in rATRAP?Tg and wild?type mice with and without HS loading, urinary sodium excretion in response to HS loading was significantly enhanced in the rATRAP?Tg mice. In addition, functional transport activity of the amiloride?sensitive epithelial Na+ channel was significantly decreased under saline volume–expanded conditions in rATRAP?Tg mice compared with wild?type mice, without any evident change in epithelial Na+ channel protein expression. Plasma membrane AT1R expression in the kidney of rATRAP?Tg mice was decreased compared with wild?type mice. Conclusions These results demonstrated that distal tubule–dominant enhancement of ATRAP inhibits pathological renal sodium reabsorption and blood pressure elevation in response to HS loading. The findings suggest that ATRAP?mediated modulation of sodium handling in renal distal tubules could be a target of interest in salt?sensitive blood pressure regulation. PMID:25792129

  16. Availability of autoantigenic epitopes controls phenotype, severity, and penetrance in TCR Tg autoimmune gastritis

    PubMed Central

    Levin, Ditza; DiPaolo, Richard J.; Brinster, Carine; Revilleza, Maria Jamela R.; Boyd, Lisa F.; Teyton, Luc; Natarajan, Kannan; Mage, Michael G.; Shevach, Ethan M.; Margulies, David H.

    2009-01-01

    We examined TCR: MHC/peptide interactions and in vivo epitope availability to explore the Th1- or Th2-like phenotype of autoimmune disease in two TCR Tg mouse models of autoimmune gastritis (AIG). The TCR of strains A23 and A51 recognize distinct IAd-restricted peptides from the gastric parietal cell H/K-ATPase. Both peptides form extremely stable MHC/peptide (MHC/p) complexes. All A23 animals develop a Th1-like aggressive, inflammatory AIG early in life, while A51 mice develop indolent Th2-like AIG at 6–8wk with incomplete penetrance. A51 T cells were more sensitive than A23 to low doses of soluble antigen and to MHC/p complexes. Staining with IAd/peptide tetramers was only detectable on previously activated T cells from A51. Thus, despite inducing a milder AIG, the A51 TCR displays a higher avidity for its cognate IAd/peptide. Nonetheless, in vivo proliferation of adoptively transferred A51 CFSE-labeled T cells in the gastric lymph node was relatively poor compared with A23 T cells. Also, DC from WT gastric lymph node, presenting processed antigen available in vivo, stimulated proliferation of A23 T cells better than A51. Thus, the autoimmune potential of these TCR in their respective Tg lines is strongly influenced by the availability of the peptide epitope, rather than by differential avidity for their respective MHC/p complexes. PMID:19039784

  17. Positron Emission Tomography Imaging of Fibrillar Parenchymal and Vascular Amyloid-? in TgCRND8 Mice

    PubMed Central

    2013-01-01

    Few quantitative diagnostic and monitoring, tools are available to clinicians treating patients with Alzheimer’s disease. Further, many of the promising quantitative imaging tools under development lack clear specificity toward different types of Amyloid-? (A?) pathology such as vascular or oligomeric species. Antibodies offer an opportunity to image specific types of A? pathology because of their excellent specificity. In this study, we developed a method to translate a panel of anti-A? antibodies, which show excellent histological performance, into live animal imaging contrast agents. In the TgCRND8 mouse model of Alzheimer’s disease, we tested two antibodies, M64 and M116, that target parenchyma aggregated A? plaques and one antibody, M31, that targets vascular A?. All three antibodies were administered intravenously after labeling with both poly(ethylene glycol) to enhance circulation and 64Cu to allow detection via positron emission tomography (PET) imaging. We were clearly able to differentiate TgCRND8 mice from wild type controls by PET imaging using either M116, the anti-A? antibody targeting parenchymal A? or M31, the antivascular A? antibody. To confirm the validity of the noninvasive imaging of specific A? pathology, brains were examined after imaging and showed clear evidence of binding to A? plaques. PMID:23509918

  18. Intracerebroventricular streptozotocin exacerbates Alzheimer-like changes of 3xTg-AD mice1

    PubMed Central

    Chen, Yanxing; Liang, Zhihou; Tian, Zhu; Blanchard, Julie; Dai, Chun-ling; Chalbot, Sonia; Iqbal, Khalid; Liu, Fei; Gong, Cheng-Xin

    2013-01-01

    Alzheimer’s disease (AD) involves several possible molecular mechanisms, including impaired brain insulin signaling and glucose metabolism. To investigate the role of metabolic insults in AD, we injected streptozotocin (STZ), a diabetogenic compound if used in the periphery, into the lateral ventricle of the 6-month old 3xTg-AD mice and studied the cognitive function as well as AD-like brain abnormalities, such as tau phosphorylation and A? accumulation, 3–6 weeks later. We found that STZ exacerbated impairment of short-term and spatial reference memory in 3xTg-AD mice. We also observed an increase of tau hyperphosphorylation and neuroinflammation, a disturbance of brain insulin signaling, and a decrease of synaptic plasticity and amyloid ? peptides in the brain after STZ treatment. The expression of 20 AD-related genes, including those involved in the processing of amyloid precursor protein, cytoskeleton, glucose metabolism, insulin signaling, synaptic function, protein kinases and apoptosis, was altered, suggesting that STZ disturbs multiple metabolic and cell signaling pathways in the brain. These findings provide experimental evidence of the role of metabolic insult in AD. PMID:23996345

  19. Intracerebroventricular streptozotocin exacerbates Alzheimer-like changes of 3xTg-AD mice.

    PubMed

    Chen, Yanxing; Liang, Zhihou; Tian, Zhu; Blanchard, Julie; Dai, Chun-Ling; Chalbot, Sonia; Iqbal, Khalid; Liu, Fei; Gong, Cheng-Xin

    2014-02-01

    Alzheimer's disease (AD) involves several possible molecular mechanisms, including impaired brain insulin signaling and glucose metabolism. To investigate the role of metabolic insults in AD, we injected streptozotocin (STZ), a diabetogenic compound if used in the periphery, into the lateral ventricle of the 6-month-old 3xTg-AD mice and studied the cognitive function as well as AD-like brain abnormalities, such as tau phosphorylation and A? accumulation, 3-6 weeks later. We found that STZ exacerbated impairment of short-term and spatial reference memory in 3xTg-AD mice. We also observed an increase in tau hyperphosphorylation and neuroinflammation, a disturbance of brain insulin signaling, and a decrease in synaptic plasticity and amyloid ? peptides in the brain after STZ treatment. The expression of 20 AD-related genes, including those involved in the processing of amyloid precursor protein, cytoskeleton, glucose metabolism, insulin signaling, synaptic function, protein kinases, and apoptosis, was altered, suggesting that STZ disturbs multiple metabolic and cell signaling pathways in the brain. These findings provide experimental evidence of the role of metabolic insult in AD. PMID:23996345

  20. Availability of autoantigenic epitopes controls phenotype, severity, and penetrance in TCR Tg autoimmune gastritis.

    PubMed

    Levin, Ditza; DiPaolo, Richard J; Brinster, Carine; Revilleza, Maria Jamela R; Boyd, Lisa F; Teyton, Luc; Natarajan, Kannan; Mage, Michael G; Shevach, Ethan M; Margulies, David H

    2008-12-01

    We examined TCR:MHC/peptide interactions and in vivo epitope availability to explore the Th1- or Th2-like phenotype of autoimmune disease in two TCR Tg mouse models of autoimmune gastritis (AIG). The TCR of strains A23 and A51 recognize distinct IA(d)-restricted peptides from the gastric parietal cell H/K-ATPase. Both peptides form extremely stable MHC/peptide (MHC/p) complexes. All A23 animals develop a Th1-like aggressive, inflammatory AIG early in life, while A51 mice develop indolent Th2-like AIG at 6-8 wk with incomplete penetrance. A51 T cells were more sensitive than A23 to low doses of soluble antigen and to MHC/p complexes. Staining with IA(d)/peptide tetramers was only detectable on previously activated T cells from A51. Thus, despite inducing a milder AIG, the A51 TCR displays a higher avidity for its cognate IA(d)/peptide. Nonetheless, in vivo proliferation of adoptively transferred A51 CFSE-labeled T cells in the gastric lymph node was relatively poor compared with A23 T cells. Also, DC from WT gastric lymph node, presenting processed antigen available in vivo, stimulated proliferation of A23 T cells better than A51. Thus, the autoimmune potential of these TCR in their respective Tg lines is strongly influenced by the availability of the peptide epitope, rather than by differential avidity for their respective MHC/p complexes. PMID:19039784

  1. Elevated temperature crack growth

    NASA Technical Reports Server (NTRS)

    Kim, K. S.; Vanstone, R. H.

    1992-01-01

    The purpose of this program was to extend the work performed in the base program (CR 182247) into the regime of time-dependent crack growth under isothermal and thermal mechanical fatigue (TMF) loading, where creep deformation also influences the crack growth behavior. The investigation was performed in a two-year, six-task, combined experimental and analytical program. The path-independent integrals for application to time-dependent crack growth were critically reviewed. The crack growth was simulated using a finite element method. The path-independent integrals were computed from the results of finite-element analyses. The ability of these integrals to correlate experimental crack growth data were evaluated under various loading and temperature conditions. The results indicate that some of these integrals are viable parameters for crack growth prediction at elevated temperatures.

  2. Impact of medium and long chain triglycerides consumption on appetite and food intake in overweight men

    PubMed Central

    St-Onge, Marie-Pierre; Mayrsohn, Brian; O’Keeffe, Majella; Kissileff, Harry R.; Choudhury, Arindam Roy; Laferrère, Blandine

    2014-01-01

    Background Medium chain triglycerides (MCT) enhance thermogenesis and may reduce food intake relative to long chain triglycerides (LCT). The goal of this study was to establish the effects of MCT on appetite and food intake and determine whether differences were due to differences in hormone concentrations. Methods Two randomized, crossover studies were conducted in which overweight men consumed 20 g of MCT or corn oil (LCT) at breakfast. Blood samples were obtained over 3 h. In Study 1 (n=10), an ad lib lunch was served after 3 h. In Study 2 (n=7), a pre-load containing 10 g of test oil was given at 3 h and lunch was served 1 h later. Linear mixed model analyses were performed to determine the effects of MCT and LCT oil on change in hormones and metabolites from fasting, adjusting for body weight. Correlations were computed between differences in hormones just before the test meals and differences in intakes after the two oils for Study 1 only. Results Food intake at the lunch test meal after the MCT pre-load (Study 2) was (mean ± SEM) 532 ± 389 kcal vs. 804 ± 486 kcal after LCT (P < 0.05). MCT consumption resulted in a lower rise in triglycerides (P = 0.014) and glucose (P = 0.066) and a higher rise in peptide YY (P = 0.017) and leptin (P = 0.036) compared to LCT (combined data). Correlations between differences in hormone levels (GLP-1, PYY) and differences in food intake were in the opposite direction to expectations. Conclusions MCT consumption reduced food intake acutely but this does not seem to be mediated by changes in GLP-1, PYY, and insulin. PMID:25074387

  3. ReaxFF molecular dynamics simulations of the initial pyrolysis mechanism of unsaturated triglyceride.

    PubMed

    Zhang, Zhiqiang; Yan, Kefeng; Zhang, Jilong

    2014-03-01

    To understand the impact of C?=?C double bonds in acyl chains of unsaturated triglycerides on the reaction mechanism and product composition in their initial pyrolysis process, ReaxFF molecular dynamics simulations were carried out using a molecular model, trilinolenin, at temperatures of 2000, 2250, and 2500 K. Analyses indicated that the observed pyrolysis mechanisms of unsaturated triglyceride are nearly identical to the saturated triglyceride, and the pyrolysis products also include alkanes, alkenes, alkadienes, aromatics, oxygenated species, CO?, and H?. The formation of intermediates and products is a sequential process. Three C--O bonds in trilinolenin molecule are usually successive dissociated first, leading to the formation of unsaturated C?H?· radical and straight-chain C??H??O?· (RCOO·) radicals. Following that, the deoxygenated alkenyl chain is produced through decarboxylation of RCOO?·?radicals with consequent release of CO?. The resulting hydrocarbon radicals undergo a variety of disproportionation, isomerization, and hydrogen-transfer reactions, yielding straight and branched-chain hydrocarbons. It was found that the scission of C--O bond and decarboxylation should preferentially occur before the cleavage of the C--C bond ? to the C?=?C bond in the initial decomposition process of unsaturated trilinolenin. In addition, the formation of cyclic hydrocarbons could proceed through intramolecular cyclization mechanisms, including non-radical electrocyclic, biradical cyclization and cyclization of alkenyl radical, which are inconsistent with previously proposed bimolecular Diels-Alder addition mechanisms. More rapid pyrolysis of trilinolenin would occur at higher temperatures without significantly affecting the apparent reaction mechanisms of trilinolenin pyrolysis in the considered temperature range. Aromatic ring structures are observed to be stable after formation and do not decay within the 500 ps simulation period. PMID:24567153

  4. Chronic treatment with krill powder reduces plasma triglyceride and anandamide levels in mildly obese men

    PubMed Central

    2013-01-01

    We have previously shown that treatment of Zucker rats and mice with diet-induced obesity with dietary docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids in the form of krill oil reduces peripheral levels of endocannabinoids, ectopic fat formation and hyperglycemia. We reported that such treatment reduces plasma endocannabinoid levels also in overweight and obese human individuals, in whom high triglycerides may correlate with high circulating endocannabinoid levels. In this study, we report the effects of krill powder, which contains proteins (34%) in addition to krill oil (61.8%), on these two parameters. We submitted 11 obese men (average BMI of 32.3 kg/m2, age of 42.6 years and plasma triglycerides of 192.5?±?96.3 mg/dl) to a 24 week dietary supplementation with krill powder (4 g/day per os) and measured anthropometric and metabolic parameters, as well as blood endocannabinoid (anandamide and 2-arachidonoylglycerol) and esterified DHA and EPA levels. Six subjects were included as control subjects and not given any supplements. The treatment produced, after 12 and 24 weeks, a significant increase in DHA and EPA in total plasma, a 59 and 84% decrease in anandamide plasma levels, and a 22.5 and 20.6% decrease in triglyceride levels, respectively. There was also a significant decrease in waist/hip ratio and visceral fat/skeletal muscle mass ratio at 24 weeks, but no change in body weight. These data confirm that dietary krill powder reduces peripheral endocannabinoid overactivity in obese subjects, and might ameliorate some parameters of the metabolic syndrome. PMID:23706001

  5. Elevated plasma homocysteine in type 2 diabetes mellitus: a risk factor for cardiovascular diseases

    PubMed Central

    Ebesunun, Maria Onomhaguan; Obajobi, Esther Odunayo

    2012-01-01

    Background Elevated plasma total homocysteine (tHcy) concentration has been associated with an increased risk for cardiovascular events in type 2 diabetic individuals independent of conventional risk factors. Available study in Nigerian-Africans is scare. Methods Seventy (30 males) and (40 females) type 2 diabetes mellitus, with age mean of 54 ± 11.52 years were selected for this study and thirty apparently healthy volunteers were included as controls. The biochemical parameters and anthropometric indices were determined using standard procedures. Results Significant increases were obtained in body weight, body mass index (p<0.001) and waist circumference (p<0.012) when compared with the corresponding control values respectively. The fasting plasma glucose (p<0.01), tHcy (p<0.02), and triglyceride (p<0.03) were significantly higher in the diabetes group when compared with the corresponding control values. The plasma folic acid and vitamin B12 (p<0.05) were significantly reduced compared to the control values. The tHcy (p<0.01) was significantly higher in the males when compared with the corresponding female value. Significant decrease was obtained in the plasma triglyceride (p<0.003) in the male patients when compared with the female patients. Conclusion Our result showed increased plasma tHcy, triglyceride and waist circumference as well as decreased folic acid and vitamin B12 in type 2 diabetes mellitus. These alterations are risk factors for premature CVD events. PMID:22937188

  6. Droplet-based Microtexture Biochip System for Triglycerides and Methanol Measurement.

    PubMed

    Lin, Ming-Yu; Yu, Chih-Sheng; Hu, Yi-Chiuen; Cheng, Shao-Chang; Hu, Heng-Tsang

    2005-01-01

    A droplet-based microfluidic system was developed for biochemical assays of triglycerides and methanol as potential applications in medical rapid diagnostics and food safety. We present a novel platform to manipulate biology reaction droplets with features of self-moving, self-mixing, and self-positioning toward the detection spot. The driving force comes from the gradient of surface tension force generated by the hydrophobic microtexture PDMS surface. We also demonstrate the experiments in water, and blood droplets running uphill to overcome the gravity. These findings support the ongoing works to develop the multifunctional biosensors in medicine and food safety. PMID:17282234

  7. Synthesis of spin-labeled neutral lipids: Nitroxyl derivatives of triglycerides and sterol esters

    Microsoft Academic Search

    Joel D. Morrisett

    1974-01-01

    Methods for the preparation of useful spin-labeled neutral lipids are described. A spin-labeled triglyceride has been prepared\\u000a by acylation of 1,3-distearoylglycerol with stearic acid anhydride bearing the 4?,4?-dimethyloxazolidine-N-oxyl ring at carbon-12.\\u000a The same fatty acid anhydride has been used to acylate the 3-hydroxy group of cholesterol to obtain a cholesteryl ester with\\u000a the nitroxyl function in the fatty acyl chain.

  8. Analysis of motor function in 6-month-old male and female 3xTg-AD mice.

    PubMed

    Stover, Kurt R; Campbell, Mackenzie A; Van Winssen, Christine M; Brown, Richard E

    2015-03-15

    The 3xTg-AD mouse has high validity as a model of Alzheimer's disease (AD) because it develops both amyloid beta plaques and neurofibrillary tangles. Human patients with AD typically develop motor deficits, which worsen as the disease progresses, but 3xTg-AD mice have been reported to show enhanced motor abilities. We investigated the motor behaviour phenotype of male and female 3xTg-AD and B6129SF2 wildtype mice on a battery of motor behaviours at 6 months of age. Compared to wildtype mice, the 3xTg-AD mice had enhanced motor performance on the Rotarod, but worse performance on the grid suspension task. In gait analysis 3xTg-AD mice had a longer stride length and made more foot slips on the balance beam than wildtype mice. There was no overall difference in voluntary wheel-running activity between genotypes, but there was a disruption in circadian activity rhythm in 3xTg-AD mice. In some motor tasks, such as the Rotarod and balance beam, females appeared to perform better than males, but this sex differences was accounted for by differences in body weight. Our results indicate that while the 3xTg-AD mice show enhanced performance on the Rotarod, they have poorer performance on other motor behaviour tasks, indicating that their motor behaviour phenotype is more complex than previously reported. The presence of the P301L transgene may explain the enhancement of Rotarod performance but the poorer performance on other motor behaviour tasks may be due to other transgenes. PMID:25486177

  9. TG-43 U1 based dosimetric characterization of model 67-6520 Cs-137 brachytherapy source

    SciTech Connect

    Meigooni, Ali S.; Wright, Clarissa; Koona, Rafiq A.; Awan, Shahid B.; Granero, Domingo; Perez-Calatayud, Jose; Ballester, Facundo [Department of Radiation Medicine, North Shore University Hospital, 300 Community Drive, Manhasset, New York 11030 and Department of Radiation Medicine, University of Kentucky Chandler Medical Center, Lexington, Kentucky 40536-0084 (United States); Department of Radiation Medicine, University of Kentucky Chandler Medical Center, Lexington, Kentucky 40536-0084 (United States); Department of Radiation Physics, ERESA, Hospital General Universitario, Avenida Tres Cruces, 2, E-46014 Valencia (Spain); Department of Oncology, Physics Section, ''La Fe'' University Hospital, Avenida Campanar 21, E-46009 Valencia (Spain); Department of Atomic, Molecular and Nuclear Physics, University of Valencia, C/ Dr. Moliner 50, E-46100 Burjassot, Spain and Instituto de Fisica Corpuscular (IFIC), C/ Dr. Moliner 50, E-46100 Burjassot (Spain)

    2009-10-15

    Purpose: Brachytherapy treatment has been a cornerstone for management of various cancer sites, particularly for the treatment of gynecological malignancies. In low dose rate brachytherapy treatments, {sup 137}Cs sources have been used for several decades. A new {sup 137}Cs source design has been introduced (model 67-6520, source B3-561) by Isotope Products Laboratories (IPL) for clinical application. The goal of the present work is to implement the TG-43 U1 protocol in the characterization of the aforementioned {sup 137}Cs source. Methods: The dosimetric characteristics of the IPL {sup 137}Cs source are measured using LiF thermoluminescent dosimeters in a Solid Water phantom material and calculated using Monte Carlo simulations with the GEANT4 code in Solid Water and liquid water. The dose rate constant, radial dose function, and two-dimensional anisotropy function of this source model were obtained following the TG-43 U1 recommendations. In addition, the primary and scatter dose separation (PSS) formalism that could be used in convolution/superposition methods to calculate dose distributions around brachytherapy sources in heterogeneous media was studied. Results: The measured and calculated dose rate constants of the IPL {sup 137}Cs source in Solid Water were found to be 0.930({+-}7.3%) and 0.928({+-}2.6%) cGy h{sup -1} U{sup -1}, respectively. The agreement between these two methods was within our experimental uncertainties. The Monte Carlo calculated value in liquid water of the dose rate constant was {Lambda}=0.948({+-}2.6%) cGy h{sup -1} U{sup -1}. Similarly, the agreement between measured and calculated radial dose functions and the anisotropy functions was found to be within {+-}5%. In addition, the tabulated data that are required to characterize the source using the PSS formalism were derived. Conclusions: In this article the complete dosimetry of the newly designed {sup 137}Cs IPL source following the AAPM TG-43 U1 dosimetric protocol and the PSS formalism is provided.

  10. Modulation of ?-secretase by EVP-0015962 reduces amyloid deposition and behavioral deficits in Tg2576 mice

    PubMed Central

    2012-01-01

    Background A hallmark of Alzheimer’s disease is the presence of senile plaques in human brain primarily containing the amyloid peptides A?42 and A?40. Many drug discovery efforts have focused on decreasing the production of A?42 through ?-secretase inhibition. However, identification of ?-secretase inhibitors has also uncovered mechanism-based side effects. One approach to circumvent these side effects has been modulation of ?-secretase to shift A? production to favor shorter, less amyloidogenic peptides than A?42, without affecting the overall cleavage efficiency of the enzyme. This approach, frequently called ?-secretase modulation, appears more promising and has lead to the development of new therapeutic candidates for disease modification in Alzheimer’s disease. Results Here we describe EVP-0015962, a novel small molecule ?-secretase modulator. EVP-0015962 decreased A?42 in H4 cells (IC50 = 67 nM) and increased the shorter A?38 by 1.7 fold at the IC50 for lowering of A?42. A?Total, as well as other carboxyl-terminal fragments of amyloid precursor protein, were not changed. EVP-0015962 did not cause the accumulation of other ?-secretase substrates, such as the Notch and ephrin A4 receptors, whereas a ?-secretase inhibitor reduced processing of both. A single oral dose of EVP-0015962 (30 mg/kg) decreased A?42 and did not alter A?Total peptide levels in a dose-dependent manner in Tg2576 mouse brain at an age when overt A? deposition was not present. In Tg2576 mice, chronic treatment with EVP-0015962 (20 or 60 mg/kg/day in a food formulation) reduced A? aggregates, amyloid plaques, inflammatory markers, and cognitive deficits. Conclusions EVP-0015962 is orally bioavailable, detected in brain, and a potent, selective ?-secretase modulator in vitro and in vivo. Chronic treatment with EVP-0015962 was well tolerated in mice and lowered the production of A?42, attenuated memory deficits, and reduced A? plaque formation and inflammation in Tg2576 transgenic animals. In summary, these data suggest that ?-secretase modulation with EVP-0015962 represents a viable therapeutic alternative for disease modification in Alzheimer’s disease. PMID:23249765

  11. Sodium/myo-Inositol Transporters: Substrate Transport Requirements and Regional Brain Expression in the TgCRND8 Mouse Model of Amyloid Pathology

    PubMed Central

    Fenili, Daniela; Weng, Ying-Qi; Aubert, Isabelle; Nitz, Mark; McLaurin, JoAnne

    2011-01-01

    Inositol stereoisomers, myo- and scyllo-inositol, are known to enter the brain and are significantly elevated following oral administration. Elevations in brain inositol levels occur across a concentration gradient as a result of active transport from the periphery. There are two sodium/myo-inositol transporters (SMIT1, SMIT2) that may be responsible for regulating brain inositol levels. The goals of this study were to determine the effects of aging and Alzheimer's disease (AD)-like amyloid pathology on transporter expression, to compare regional expression and to analyze substrate requirements of the inositol transporters. QPCR was used to examine expression of the two transporters in the cortex, hippocampus and cerebellum of TgCRND8 mice, a mouse model of amyloid pathology, in comparison to non-transgenic littermates. In addition, we examined the structural features of inositol required for active transport, utilizing a cell-based competitive uptake assay. Disease pathology did not alter transporter expression in the cortex or hippocampus (p>0.005), with only minimal effects of aging observed in the cerebellum (SMIT1: F2,26?=?12.62; p?=?0.0002; SMIT2: F2,26?=?8.71; p?=?0.0015). Overall, brain SMIT1 levels were higher than SMIT2, however, regional differences were observed. For SMIT1, at 4 and 6 months cerebellar SMIT1 levels were significantly higher than cortical and hippocampal levels (p<0.05). For SMIT2, at all three ages both cortical and cerebellar SMIT2 levels were significantly higher than hippocampal levels (p<0.05) and at 4 and 6 months of age, cerebellar SMIT2 levels were also significantly higher than cortical levels (p<0.05). Inositol transporter levels are stably expressed as a function of age, and expression is unaltered with disease pathology in the TgCRND8 mouse. Given the fact that scyllo-inositol is currently in clinical trials for the treatment of AD, the stable expression of inositol transporters regardless of disease pathology is an important finding. PMID:21887366

  12. Central and Peripheral Administration of Antisense Oligonucleotide Targeting Amyloid Precursor Protein Improves Learning and Memory and Reduces Neuroinflammatory Cytokines in Tg2576 (APPswe) Mice

    PubMed Central

    Farr, Susan A.; Erickson, Michelle A.; Niehoff, Michael L.; Banks, William A.; Morley, John E.

    2014-01-01

    Alzheimer’s disease (AD) is a progressive neurodegenerative disease. The World Health Organization estimates that there are currently 18 million people worldwide living with AD and that number is expected to double by early 2025. Currently, there are no therapies to stop or reverse the symptoms of AD. We have developed an antisense oligonucleotide (OL-1) against the amyloid betaprotein precursor (A?PP) that can decrease A?PP expression and amyloid beta protein (A?) production. This antisense rapidly crosses the blood-brain barrier, reverses learning and memory impairments, reduces oxidative stress and restores brain-to-blood efflux of A? in SAMP8 mice. In the current study, we examined the effects of this A?PP antisense in the Tg2576 mouse model of AD. The Tg2576 overproduces human A?, develops age-related learning and memory deficits, and exhibits oxidative damage in the brain. First, we administered the A?PP antisense centrally into the lateral ventricle 3 times at 2 week intervals. Seventy-two hours after the third injection, we tested learning and memory in T-maze foot shock avoidance. In the second study, we injected the mice with A?PP antisense 3 times at two week intervals via the tail vein. Seventy-two hours later, we tested learning and memory T-maze foot shock avoidance, novel object recognition and elevated plus maze. At the end of behavioral testing, mice were sacrificed and brain tissue was collected for evaluation of A?PP, A?, and expression of cytokines and chemokines. A?PP antisense administered centrally improved acquisition and retention of T-maze foot shock avoidance. A?PP antisense administered via tail vein improved learning and memory in both T-maze foot shock avoidance and novel object-place recognition. In the elevated plus maze the mice which received OL-1 A?PP antisense spent less time in the open arms and had fewer entries into the open arms indicating reduced disinhibitation. Biochemical analyses reveal significant reduction of A?PP signal and a reduction of measures of neuroinflammation. The current findings support the therapeutic potential of OL-1 A?PP antisense. PMID:24577464

  13. Elevated A beta and apolipoprotein E in A betaPP transgenic mice and its relationship to amyloid accumulation in Alzheimer's disease.

    PubMed Central

    Kuo, Y. M.; Crawford, F.; Mullan, M.; Kokjohn, T. A.; Emmerling, M. R.; Weller, R. O.; Roher, A. E.

    2000-01-01

    BACKGROUND: Amyloid-beta (A beta) accumulates in plaques and as cerebral amyloid angiopathy (CAA) in the brains of both Alzheimer's disease (AD) patients and transgenic A betaPPswe/tg2576 (tg2576) mice. Increasingly, evidence in humans and mice shows this process to be modulated by apolipoprotein E (apoE). MATERIALS AND METHODS: To explore this relationship, we measured apoE and A beta levels in brains of tg2576 mice and controls at intervals between 2 and 20 months. In addition, A beta concentrations in plasma and muscle of these animals were also quantified. RESULTS: Quite strikingly, we found that the amount of tg2576 mice brain apoE was elevated by an average of 45%, relative to the control mice from 2 months on. The level of brain apoE soared after 14 months to almost 60% greater than the level found in control mice. A beta concentrations in brains before 9 months were less than 2 ng/mg of protein, but by 14 months concentrations rose to 8.7 ng/mg, and by 20 months to 47 ng/mg. In plasma, we noted that the levels of A beta in tg2576 mice declined from above 30 ng/ml prior to 12 months to 14 ng/ml by 14 months. Histology showed that A beta plaques and CAA began to be discernible in the tg2576 mice at about 9 and 20 months of age, respectively. CONCLUSIONS: ApoE was immunocytochemically detected in neuritic plaques that were positive for thioflavine-S. We suggest that the elevation of brain apoE in tg2576 mice participates in an age-related dysregulation of A beta clearance and signals the start of A beta sequestration during the time of cognitive dysfunction. PMID:10952022

  14. Elevation leads to altruistic behavior

    E-print Network

    Schnall, Simone; Roper, Jean; Fessler, Daniel M. T.

    2010-01-01

    of an emotion are key to understand- ing its origins, functions, or social consequences (e.g., Frijda, 1987; Lazarus, 1991; Nesse, 1990; Russell, 1991; Tooby & Cosmides, 2008). However, to date, there is only limited evi- dence that elevation affects prosocial... not test whether elevation affects altruism across divergent contexts, motivating helping outside of contexts that juxtapose compassion and group-based prejudice, or whether elevation motivates helping above and beyond the effect of general posi- tive...

  15. A Hardware Implementation of a Coherent SOQPSK-TG Demodulator for FEC Applications

    E-print Network

    Rea Zanabria, Gino

    2011-03-31

    , it is in conflict with traditional CPM notation. In strict CPM terms, 4 we really have h = 1=4 and i 2f 2;0;2g when the data alphabet is ternary (M = 3). The phase pulse q(t) is defined as q(t) , 8 >>> >>> >> >>> : 0; t< 0 Z t 0 f( )d ; 0 tTG(t), frequency pulse q...

  16. TG, DTA, FTIR and Raman spectral analysis of Zn a \\/Mg b ammonium sulfate mixed crystals

    Microsoft Academic Search

    G. Madhurambal; S. C. Mojumdar; S. Hariharan; P. Ramasamy

    2004-01-01

    To understand the structural and thermal properties of the mixed crystals, thermogravimetric (TG) and differential thermal\\u000a analysis (DTA), and FTIR and Raman spectral studies were carried out for the mixed crystals of Zna\\/Mgb ammonium sulfate of composition namely 'a' (fraction by mass of salt Zn[NH4]2[SO4]26H2O to the total salt (both Zn[NH4]2[SO4]26H2O, Mg[NH4]2[SO4]26H2O or it can be explained as ZnaMgb[NH4]2[SO4]26H2O, a

  17. Elevated temperature biaxial fatigue

    NASA Technical Reports Server (NTRS)

    Jordan, E. H.

    1985-01-01

    A 3 year experimental program for studying elevated temperature biaxial fatigue of a nickel based alloy Hastelloy-X has been completed. A new high temperature fatigue test facility with unique capabilities has been developed. Effort was directed toward understanding multiaxial fatigue and correlating the experimental data to the existing theories of fatigue failure. The difficult task of predicting fatigue lives for nonproportional loading was used as an ultimate test for various life prediction methods being considered. The primary means of reaching improved understanding were through several critical nonproportional loading experiments. The direction of cracking observed on failed specimens was also recorded and used to guide the development of the theory. Cyclic deformation responses were permanently recorded digitally during each test. It was discovered that the cracking mode switched from primarily cracking on the maximum shear planes at room temperature to cracking on the maximum normal strain planes at 649 C. In contrast to some other metals, loading path in nonproportional loading had little effect on fatigue lives. Strain rate had a small effect on fatigue lives at 649 C. Of the various correlating parameters the modified plastic work and octahedral shear stress were the most successful.

  18. Suppression of the Tg-Confinement Effect in Thin Polymer Films by the Presence of an Anti-Plasticizer

    NASA Astrophysics Data System (ADS)

    Kim, Soyoung; Mundra, Manish; Roth, Connie; Torkelson, John

    2008-03-01

    The effect of film thickness on the glass transition temperature (Tg) of poly(vinyl acetate) supported on silica was studied via ellipsometry for films that were in the bone-dry state and also with several weight percent water sorbed into the film. The presence of water resulted in a decrease of the Tg of bulk poly(vinyl acetate) films but an increase in the density of the films. This combination of effects indicates that water acts as an anti-plasticizer in poly(vinyl acetate). We demonstrate that the bone-dry poly(vinyl acetate) films exhibit a significant reduction in Tg with decreasing film thickness below about 50 nm. In contrast, the poly(vinyl acetate films) containing several weight percent water exhibited no reduction in Tg relative to bulk Tg with decreasing film thickness down to a thickness of about 10 nm. These results are in accord with recent theoretical analysis (Riggelman et al., PRL 97, 045502 (2006)) indicating that the presence of anti-plasticizers leads to a suppression of confinement effects on the behavior of polymer films and indicate that caution should be employed when studying confinement effects in polymer systems that may sorb significant levels of water from the atmosphere.

  19. Hydroxylamine-doping effect on the Tg of 160 K for water confined in silica-gel nanopores.

    PubMed

    Nagoe, A; Oguni, M

    2013-11-20

    The glass transition behavior of hydroxylamine (HA) aqueous solutions in bulk and confined in silica-gel nanopores with average width of 1.1 nm was studied by means of differential scanning calorimetry measurements and adiabatic calorimetry. The glass transition temperature (Tg) of the confined solution with high HA mole-fraction (xHA) was essentially the same as the value of the bulk. This suggests that the nano-size confinement affects the Tg of HA aqueous solution little. Meanwhile, the bulk solution with xHA < 0.3 revealed partial crystallization on cooling and, on the other hand, the confined solution with the same xHA did not crystallize. The Tg of the xHA = 0.076 confined solution was 174 K which is higher than the value of 160 K for pure water confined in the same silica-gel pores. This demonstrates that HA doping leads to no abrupt Tg-decrease, unlike doping of all the other second components reported so far, suggesting that HA is set neatly in a hydrogen-bond network formed by water molecules. We discuss the xHA dependence of Tg for the HA aqueous solutions from a viewpoint related to peculiar phase-behavior of pure water. Considering that the xHA = 0.076 aqueous solution revealed no anomaly compared with pure water, it was recognized as corresponding to the high-temperature phase of pure water. PMID:24162332

  20. Liver-specific loss of lipin-1-mediated phosphatidic acid phosphatase activity does not mitigate intrahepatic TG accumulation in mice.

    PubMed

    Schweitzer, George G; Chen, Zhouji; Gan, Connie; McCommis, Kyle S; Soufi, Nisreen; Chrast, Roman; Mitra, Mayurranjan S; Yang, Kui; Gross, Richard W; Finck, Brian N

    2015-04-01

    Lipin proteins (lipin 1, 2, and 3) regulate glycerolipid homeostasis by acting as phosphatidic acid phosphohydrolase (PAP) enzymes in the TG synthesis pathway and by regulating DNA-bound transcription factors to control gene transcription. Hepatic PAP activity could contribute to hepatic fat accumulation in response to physiological and pathophysiological stimuli. To examine the role of lipin 1 in regulating hepatic lipid metabolism, we generated mice that are deficient in lipin-1-encoded PAP activity in a liver-specific manner (Alb-Lpin1(-/-) mice). This allele of lipin 1 was still able to transcriptionally regulate the expression of its target genes encoding fatty acid oxidation enzymes, and the expression of these genes was not affected in Alb-Lpin1(-/-) mouse liver. Hepatic PAP activity was significantly reduced in mice with liver-specific lipin 1 deficiency. However, hepatocytes from Alb-Lpin1(-/-) mice had normal rates of TG synthesis, and steady-state hepatic TG levels were unaffected under fed and fasted conditions. Furthermore, Alb-Lpin1(-/-) mice were not protected from intrahepatic accumulation of diacylglyerol and TG after chronic feeding of a diet rich in fat and fructose. Collectively, these data demonstrate that marked deficits in hepatic PAP activity do not impair TG synthesis and accumulation under acute or chronic conditions of lipid overload. PMID:25722343

  1. Inheritance of rare functional GCKR variants and their contribution to triglyceride levels in families

    PubMed Central

    Rees, Matthew G.; Raimondo, Anne; Wang, Jian; Ban, Matthew R.; Davis, Mindy I.; Barrett, Amy; Ranft, Jessica; Jagdhuhn, David; Waterstradt, Rica; Baltrusch, Simone; Simeonov, Anton; Collins, Francis S.; Hegele, Robert A.; Gloyn, Anna L.

    2014-01-01

    Significant resources have been invested in sequencing studies to investigate the role of rare variants in complex disease etiology. However, the diagnostic interpretation of individual rare variants remains a major challenge, and may require accurate variant functional classification and the collection of large numbers of variant carriers. Utilizing sequence data from 458 individuals with hypertriglyceridemia and 333 controls with normal plasma triglyceride levels, we investigated these issues using GCKR, encoding glucokinase regulatory protein. Eighteen rare non-synonymous GCKR variants identified in these 791 individuals were comprehensively characterized by a range of biochemical and cell biological assays, including a novel high-throughput-screening-based approach capable of measuring all variant proteins simultaneously. Functionally deleterious variants were collectively associated with hypertriglyceridemia, but a range of in silico prediction algorithms showed little consistency between algorithms and poor agreement with functional data. We extended our study by obtaining sequence data on family members; however, functional variants did not co-segregate with triglyceride levels. Therefore, despite evidence for their collective functional and clinical relevance, our results emphasize the low predictive value of rare GCKR variants in individuals and the complex heritability of lipid traits. PMID:24879641

  2. Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion.

    PubMed

    Fettiplace, Michael R; Lis, Kinga; Ripper, Richard; Kowal, Katarzyna; Pichurko, Adrian; Vitello, Dominic; Rubinstein, Israel; Schwartz, David; Akpa, Belinda S; Weinberg, Guy

    2015-01-28

    Triglyceride micro-emulsions such as Intralipid® have been used to reverse cardiac toxicity induced by a number of drugs but reservations about their broad-spectrum applicability remain because of the poorly understood mechanism of action. Herein we report an integrated mechanism of reversal of bupivacaine toxicity that includes both transient drug scavenging and a cardiotonic effect that couple to accelerate movement of the toxin away from sites of toxicity. We thus propose a multi-modal therapeutic paradigm for colloidal bio-detoxification whereby a micro-emulsion both improves cardiac output and rapidly ferries the drug away from organs subject to toxicity. In vivo and in silico models of toxicity were combined to test the contribution of individual mechanisms and reveal the multi-modal role played by the cardiotonic and scavenging actions of the triglyceride suspension. These results suggest a method to predict which drug toxicities are most amenable to treatment and inform the design of next-generation therapeutics for drug overdose. PMID:25483426

  3. Investigation of some characteristics of polyhydroxy milkweed triglycerides and their acylated derivatives in relation to lubricity.

    PubMed

    Harry-O'kuru, Rogers E; Biresaw, Girma; Cermak, Steven C; Gordon, Sherald H; Vermillion, Karl

    2011-05-11

    Most industrial lubricants are derived from nonrenewable petroleum-based sources. As useful as these lubricants are, their unintended consequences are the pollution of the Earth's environment as a result of the slow degradation of the spent materials. Native seed oils, on the other hand, are renewable and are also biodegradable in the environment, but these oils often suffer a drawback in having lower thermal stability and a shorter shelf life because of the intrinsic -C?C- unsaturation in their structures. This drawback can be overcome, yet the inherent biodegradative property retained, by appropriate derivatization of the oil. Pursuant to this, this study investigated derivatized polyhydroxy milkweed oil to assess its suitability as lubricant. The milkweed plant is a member of the Asclepiadaceae, a family with many genera including the common milkweeds, Asclepias syriaca L., Asclepias speciosa L., Asclepias tuberosa L., etc. The seeds of these species contain mainly C-18 triglycerides that are highly unsaturated, 92%. The olefinic character of this oil has been chemically modified by generating polyhydroxy triglycerides (HMWO) that show high viscosity and excellent moisturizing characteristics. In this work, HMWO have been chemically modified by esterifying their hydroxyl groups with acyl groups of various chain lengths (C2-C5). The results of investigation into the effect of the acyl derivatives' chemical structure on kinematic and dynamic viscosity, oxidation stability, cold-flow (pour point, cloud point) properties, coefficient of friction, wear, and elastohydrodynamic film thickness are discussed. PMID:21428293

  4. Human lactation: maternal transfer of dietary triglycerides labeled with stable isotopes

    SciTech Connect

    Hachey, D.L.; Thomas, M.R.; Emken, E.A.; Garza, C.; Brown-Booth, L.; Adlof, R.O.; Klein, P.D.

    1987-10-01

    A stable isotope tracer method was utilized to measure quantitatively the secretion of diet-derived fatty acids (FA) into human milk. A mixture of (/sup 2/H6)tripalmitin, (/sup 2/H18)-triolein, and (/sup 2/H12)trilinolein was administered to three healthy, lactating women 22 to 30 years of age. Milk and blood samples were collected sequentially for 72 hr. The FA composition and concentration of total plasma, lipoprotein, and milk triglycerides were determined by gas-liquid chromatography (GLC) and the isotopic enrichment was determined by gas-liquid chromatography-mass spectrometry (GLC-MS). There were no statistically significant differences in mammary secretion of the individual fats, either by a single individual or between subjects. The mean secretion of fat by one breast was 5.11 +/- 1.26% of the dose (CV = 25%). There was a significant 6.0-hr delay between peak occurrence of the tracer in plasma and its occurrence in milk. The lipids are transported to the mammary gland primarily by the chylomicron and very low density lipoprotein triglycerides.

  5. GCG-rich tea catechins are effective in lowering cholesterol and triglyceride concentrations in hyperlipidemic rats.

    PubMed

    Lee, Sang Min; Kim, Chae Wook; Kim, Jung Kee; Shin, Hyun Jung; Baik, Joo Hyun

    2008-05-01

    The (-)-gallocatechin gallate (GCG) concentration in some tea beverages can account for as much as 50% of the total catechins, as a result of sterilization. The present study aims to examine the effects of GCG-rich tea catechins on hyperlipidemic rats and the mechanisms associated with regulating cholesterol metabolism in the liver. By performing heat epimerization of (-)-epigallocatechin gallate (EGCG), we manufactured a mixture of catechins that had a GCG content of approximately 50% (w/w). In sucrose-rich diet-induced hyperlipidemic rats, the GCG-rich tea catechins exhibited strong activity in reducing plasma cholesterol and triglyceride concentrations. Furthermore, the hepatic cholesterol and triglyceride concentrations that had increased as a result of the sucrose-rich diet were reduced due to GCG-rich tea catechins consumption. In order to investigate the hyperlipidemic mechanism of GCG-rich tea catechins, we examined the hepatic expressions of LDL receptor and HMG-CoA reductase in hyperlipidemic rats. We further evaluated the action of purified GCG on LDL receptor activity, which is a key contributor to the regulation of cholesterol concentrations. We found that purified GCG increased LDL receptor protein level and activity to a greater extent than EGCG. In conclusion, our study indicates that GCG-rich tea catechins in tea beverages may be effective in preventing hyperlipidemia by lowering plasma and hepatic cholesterol concentrations. PMID:18365267

  6. Digital analysis of hepatic sections in mice accurately quantitates triglycerides and selected properties of lipid droplets

    PubMed Central

    Ge, Fengxia; Lobdell, Harrison; Zhou, Shengli; Hu, Chunguang; Berk, Paul D

    2010-01-01

    We describe a method for the histologic evaluation of lipid accumulation in the livers of various mouse models of hepatic steatosis based on quantitative digital analysis of Oil Red O (ORO) accumulation in fresh-frozen hepatic sections. The process involves two principal steps: identification and digital photographic imaging of areas appropriate for analysis, followed by digital determination of the fraction of the identified area (Area Fraction) exhibiting ORO staining. The Area Fraction, designated the Digital Steatosis Score, is a valuable aspect of the histologic assessment of the liver, especially in various forms of alcoholic and non-alcoholic liver diseases. The method is rapid, requiring ~3 min per specimen, and highly reproducible, avoiding the inevitably subjective, semi-quantitative evaluation of lipid content inherent in visual steatosis scoring systems. In normal mice and in six different mouse models of fatty liver, the Area Fraction was highly correlated with hepatic triglyceride content (P < 0.01). The coefficient of variation of repeated determinations of the Area Fraction by two different observers was ±6.4%. If made available in clinical settings rapid, accurate quantitation of liver triglycerides by this method could be very useful in specific conditions such as assessment of donor livers for transplantation. PMID:20975077

  7. Digital analysis of hepatic sections in mice accurately quantitates triglycerides and selected properties of lipid droplets.

    PubMed

    Ge, Fengxia; Lobdell, Harrison; Zhou, Shengli; Hu, Chunguang; Berk, Paul D

    2010-11-01

    We describe a method for the histologic evaluation of lipid accumulation in the livers of various mouse models of hepatic steatosis based on quantitative digital analysis of Oil Red O (ORO) accumulation in fresh-frozen hepatic sections. The process involves two principal steps: identification and digital photographic imaging of areas appropriate for analysis, followed by digital determination of the fraction of the identified area (Area Fraction) exhibiting ORO staining. The Area Fraction, designated the Digital Steatosis Score, is a valuable aspect of the histologic assessment of the liver, especially in various forms of alcoholic and non-alcoholic liver diseases. The method is rapid, requiring ?3 min per specimen, and highly reproducible, avoiding the inevitably subjective, semi-quantitative evaluation of lipid content inherent in visual steatosis scoring systems. In normal mice and in six different mouse models of fatty liver, the Area Fraction was highly correlated with hepatic triglyceride content (P < 0.01). The coefficient of variation of repeated determinations of the Area Fraction by two different observers was ±6.4%. If made available in clinical settings, rapid, accurate quantitation of liver triglycerides by this method could be very useful in specific conditions such as assessment of donor livers for transplantation. PMID:20975077

  8. Alterations of hippocampal glucose metabolism by even versus uneven medium chain triglycerides

    PubMed Central

    McDonald, Tanya S; Tan, Kah Ni; Hodson, Mark P; Borges, Karin

    2014-01-01

    Medium chain triglycerides (MCTs) are used to treat neurologic disorders with metabolic impairments, including childhood epilepsy and early Alzheimer's disease. However, the metabolic effects of MCTs in the brain are still unclear. Here, we studied the effects of feeding even and uneven MCTs on brain glucose metabolism in the mouse. Adult mice were fed 35% (calories) of trioctanoin or triheptanoin (the triglycerides of octanoate or heptanoate, respectively) or a matching control diet for 3 weeks. Enzymatic assays and targeted metabolomics by liquid chromatography tandem mass spectrometry were used to quantify metabolites in extracts from the hippocampal formations (HFs). Both oils increased the levels of ?-hydroxybutyrate, but no other significant metabolic alterations were observed after triheptanoin feeding. The levels of glucose 6-phosphate and fructose 6-phosphate were increased in the HF of mice fed trioctanoin, whereas levels of metabolites further downstream in the glycolytic pathway and the pentose phosphate pathway were reduced. This indicates that trioctanoin reduces glucose utilization because of a decrease in phosphofructokinase activity. Trioctanoin and triheptanoin showed similar anticonvulsant effects in the 6?Hz seizure model, but it remains unknown to what extent the anticonvulsant mechanism(s) are shared. In conclusion, triheptanoin unlike trioctanoin appears to not alter glucose metabolism in the healthy brain. PMID:24169853

  9. Alterations of hippocampal glucose metabolism by even versus uneven medium chain triglycerides.

    PubMed

    McDonald, Tanya S; Tan, Kah Ni; Hodson, Mark P; Borges, Karin

    2014-01-01

    Medium chain triglycerides (MCTs) are used to treat neurologic disorders with metabolic impairments, including childhood epilepsy and early Alzheimer's disease. However, the metabolic effects of MCTs in the brain are still unclear. Here, we studied the effects of feeding even and uneven MCTs on brain glucose metabolism in the mouse. Adult mice were fed 35% (calories) of trioctanoin or triheptanoin (the triglycerides of octanoate or heptanoate, respectively) or a matching control diet for 3 weeks. Enzymatic assays and targeted metabolomics by liquid chromatography tandem mass spectrometry were used to quantify metabolites in extracts from the hippocampal formations (HFs). Both oils increased the levels of ?-hydroxybutyrate, but no other significant metabolic alterations were observed after triheptanoin feeding. The levels of glucose 6-phosphate and fructose 6-phosphate were increased in the HF of mice fed trioctanoin, whereas levels of metabolites further downstream in the glycolytic pathway and the pentose phosphate pathway were reduced. This indicates that trioctanoin reduces glucose utilization because of a decrease in phosphofructokinase activity. Trioctanoin and triheptanoin showed similar anticonvulsant effects in the 6?Hz seizure model, but it remains unknown to what extent the anticonvulsant mechanism(s) are shared. In conclusion, triheptanoin unlike trioctanoin appears to not alter glucose metabolism in the healthy brain. PMID:24169853

  10. Pro- and Antioxidative Effect of ?-Tocopherol on Edible Oils, Triglycerides and Fatty Acids.

    PubMed

    Jerzykiewicz, Maria; Cwiel?g-Piasecka, Irmina; Jezierski, Adam

    2013-06-01

    Using advanced electron paramagnetic resonance techniques (EPR), oxidation of crude vegetable oils and their components (fatty acids and triglycerides) by radicals generated from hydrogen peroxide was investigated. The correlation rotational times were determined allowing us to characterize radicals formed during edible oils oxidation. Additionally (1)H- and (14)N-hyperfine coupling constants differentiate the fatty acids dependently on their unsaturation. The acids with a higher number of unsaturated bonds exhibit higher AN values of PBN/·lipid adduct. The waste oil with high free fatty acids content underwent the oxidation reaction more efficiently, however due to saturation and the high content of the fatty acids the carbon-centered radicals formed (upon hydrogen peroxide radicals) and their PBN (N-tert-butyl-?-phenylnitrone) adducts were less stable. The antioxidant effect was dependent on the amount of ?-tocopherol added. In small amounts of up to 0.35 mg/1 g of fatty acid or triglyceride, it inhibited the creation of PBN/·lipid adducts while with higher amounts it intensified adduct formation. The ?-tocopherol (AT) addition influence was also studied as spin scavenging dependence and indicated that any addition of the antioxidant in the investigated samples led to free radical scavenging and the effect increased with the increase in AT content. PMID:23710072

  11. Using the Tg(nrd:egfp)/albino Zebrafish Line to Characterize In Vivo Expression of neurod

    PubMed Central

    Thomas, Jennifer L.; Ochocinska, Margaret J.; Hitchcock, Peter F.; Thummel, Ryan

    2012-01-01

    In this study, we used a newly-created transgenic zebrafish, Tg(nrd:egfp)/albino, to further characterize the expression of neurod in the developing and adult retina and to determine neurod expression during adult photoreceptor regeneration. We also provide observations regarding the expression of neurod in a variety of other tissues. In this line, EGFP is found in cells of the developing and adult retina, pineal gland, cerebellum, olfactory bulbs, midbrain, hindbrain, neural tube, lateral line, inner ear, pancreas, gut, and fin. Using immunohistochemistry and in situ hybridization, we compare the expression of the nrd:egfp transgene to that of endogenous neurod and to known retinal cell types. Consistent with previous data based on in situ hybridizations, we show that during retinal development, the nrd:egfp transgene is not expressed in proliferating retinal neuroepithelium, and is expressed in a subset of retinal neurons. In contrast to previous studies, nrd:egfp is gradually re-expressed in all rod photoreceptors. During photoreceptor regeneration in adult zebrafish, in situ hybridization reveals that neurod is not expressed in Müller glial-derived neuronal progenitors, but is expressed in photoreceptor progenitors as they migrate to the outer nuclear layer and differentiate into new rod photoreceptors. During photoreceptor regeneration, expression of the nrd:egfp matches that of neurod. We conclude that Tg(nrd:egfp)/albino is a good representation of endogenous neurod expression, is a useful tool to visualize neurod expression in a variety of tissues and will aid investigating the fundamental processes that govern photoreceptor regeneration in adults. PMID:22235264

  12. 180 degree view of Building 7 elevations, illustrating rear elevation ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    180 degree view of Building 7 elevations, illustrating rear elevation of two story unit type with one story step-down on street side. View facing east - Harbor Hills Housing Project, One & Two Story Townhouse Type, 26607 Western Avenue, Lomita, Los Angeles County, CA

  13. 180 degree view of Building 7 elevations, illustrating front elevation ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    180 degree view of Building 7 elevations, illustrating front elevation of two story unit type with one story step-down on street side. View facing west - Harbor Hills Housing Project, One & Two Story Townhouse Type, 26607 Western Avenue, Lomita, Los Angeles County, CA

  14. 34. Coal Fuel Elevator (diagonal in foreground), Fuel Elevator (left), ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    34. Coal Fuel Elevator (diagonal in foreground), Fuel Elevator (left), Fuel Storage Bins (center), and Power Plant (far center), and Retail Coal Storage Bins (right) Photograph taken by George Harven - Huber Coal Breaker, 101 South Main Street, Ashley, Luzerne County, PA

  15. 35. Coal Fuel Elevator (diagonal in center), Fuel Elevator (left), ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    35. Coal Fuel Elevator (diagonal in center), Fuel Elevator (left), Fuel Storage Bins (center), and Power Plant (far center), and Retail Coal Storage Bins (right) Photograph taken by George Harven - Huber Coal Breaker, 101 South Main Street, Ashley, Luzerne County, PA

  16. Niemann-Pick disease type C2 protein induces triglyceride accumulation in silkworm and mammalian cell lines.

    PubMed

    Adachi, Tatsuo; Ishii, Kenichi; Matsumoto, Yasuhiko; Hayashi, Yohei; Hamamoto, Hiroshi; Sekimizu, Kazuhisa

    2014-04-01

    Silkworm haemolymph induced both the cessation of growth and an increase in triglyceride (triacylglycerol) storage in BmN4 cells. We purified the growth inhibitory factor from the silkworm haemolymph and identified this protein as the Bombyx mori PP (promoting protein), an orthologue of NPC2 (Niemann-Pick disease type C2) protein. Recombinant silkworm NPC2 inhibited cellular proliferation and increased triglyceride accumulation in BmN4 cells. Injection of either the recombinant protein or antiserum of NPC2 into living silkworms increased or decreased respectively triglyceride levels in the fat body. A mutation that depletes the cholesterol-binding capacity did not abolish the activity of NPC2. We further revealed that NPC2 induced the phosphorylation of AMPK (AMP-activated protein kinase) and that an AMPK inhibitor suppressed NPC2-dependent triglyceride accumulation. These findings suggest that NPC2 induces triglyceride accumulation via the activation of AMPK independently of its cholesterol-binding capacity in the silkworm. PMID:24438076

  17. Competition between substrate-mediated ?-? stacking and surface-mediated T(g) depression in ultrathin conjugated polymer films.

    PubMed

    Wang, Tao; Pearson, Andrew J; Dunbar, Alan D F; Staniec, Paul A; Watters, Darren C; Coles, David; Yi, Hunan; Iraqi, Ahmed; Lidzey, David G; Jones, Richard A L

    2012-12-01

    We report surface and interface effects in dynamics and chain conformation in the thin film of conjugated polymer PCDTBT. To probe dynamic anomalies, we measure the glass transition temperature (T(g)) of PCDTBT films as a function of thickness, and find that there is a significant depression in T(g) for films less than 100 nm thick; a result qualitatively similar to that observed in many other polymer film systems. However, for films less than 40 nm, the T(g) converges to a constant value of 20 K below its bulk value. Grazing incidence X-ray diffraction shows depth-dependent molecular organization that is associated with the unusual thickness-dependent dynamics. PMID:23239269

  18. Capillary GC of triglycerides in fats and oils using a high temperature phenylmethylsilicone stationary phase. Part II. The analysis of chocolate fats

    Microsoft Academic Search

    E. Geeraerta; P. Sandrab

    1987-01-01

    The analyses of the fats and oils used in the chocolate industry are reported. Triglyceride mixtures are directly injected\\u000a on an FSOT column coated with a phenylmethylsilicone gum stationary phase. On phenylmethylsilicone phase, besides a carbon\\u000a number separation, the triglycerides are separated according to the different combinations of saturated and unsaturated fatty\\u000a acids in the triglycerides. Cocoa butters of different

  19. Cotinine halts the advance of Alzheimer's disease-like pathology and associated depressive-like behavior in Tg6799 mice

    PubMed Central

    Patel, Sagar; Grizzell, J. Alex; Holmes, Rosalee; Zeitlin, Ross; Solomon, Rosalynn; Sutton, Thomas L.; Rohani, Adeeb; Charry, Laura C.; Iarkov, Alexandre; Mori, Takashi; Echeverria Moran, Valentina

    2014-01-01

    Alzheimer's disease (AD) is associated with cognitive and non-cognitive symptoms for which there are currently no effective therapies. We have previously reported that cotinine, a natural product obtained from tobacco leaves, prevented memory loss and diminished amyloid-? (A?) plaque pathology in transgenic 6799 mice (Tg6799 mice) when treated prior to the development of the pathology. We have also shown that cotinine reduces depressive-like behavior in normal and chronically stressed C57BL/6 mice. Here, we extend our previous studies by investigating the effects of cotinine on the progression of AD-like pathology, depressive-like behavior, and the mechanisms underlying its beneficial effects in Tg6799 mice when left untreated until after a more advanced stage of the disease's development. The results show that vehicle-treated Tg6799 mice displayed an accentuated loss of working memory and an abundant A? plaque pathology that were accompanied by higher levels of depressive-like behavior as compared to control littermates. By contrast, prolonged daily cotinine treatment to Tg6799 mice, withheld until after a mid-level progression of AD-like pathology, reduced A? levels/plaques and depressive-like behavior. Moreover, this treatment paradigm dramatically improved working memory as compared to control littermates. The beneficial effects of cotinine were accompanied by an increase in the expression of the active form of protein kinase B and the postsynaptic density protein 95 in the hippocampi and frontal cortices of Tg6799 mice. This suggests that cotinine halts the progression of AD-like pathology while reducing depressive-like behavior by stimulating signaling pathways supporting synaptic plasticity in Tg6799 mice. The potential use of cotinine to treat cognitive and non-cognitive symptoms of AD is discussed. PMID:25100990

  20. Space Station tethered elevator system

    NASA Technical Reports Server (NTRS)

    Haddock, Michael H.; Anderson, Loren A.; Hosterman, K.; Decresie, E.; Miranda, P.; Hamilton, R.

    1989-01-01

    The optimized conceptual engineering design of a space station tethered elevator is presented. The tethered elevator is an unmanned, mobile structure which operates on a ten-kilometer tether spanning the distance between Space Station Freedom and a platform. Its capabilities include providing access to residual gravity levels, remote servicing, and transportation to any point along a tether. The report discusses the potential uses, parameters, and evolution of the spacecraft design. Emphasis is placed on the elevator's structural configuration and three major subsystem designs. First, the design of elevator robotics used to aid in elevator operations and tethered experimentation is presented. Second, the design of drive mechanisms used to propel the vehicle is discussed. Third, the design of an onboard self-sufficient power generation and transmission system is addressed.

  1. Apolipoprotein AV Accelerates Plasma Hydrolysis OfTriglyceride-Rich Lipoproteins By Interaction With Proteoglycan BoundLipoprotein Lipase

    SciTech Connect

    Merkel, Martin; Loeffler, Britta; Kluger, Malte; Fabig, Nathalie; Geppert, Gesa; Pennacchio, Len A.; Laatsch, Alexander; Heeren, Joerg

    2005-02-22

    Apolipoprotein A5 (APOA5) is associated with differences intriglyceride levels and familial combined hyperlipidemia. In genetically engineered mice, apoAV plasma levels are inversely correlated with plasmatriglycerides. To elucidate the mechanism by which apoAV influences plasma triglycerides, metabolic studies and in vitro assays resembling physiological conditions were performed. In hAPOA5 transgenic mice(hAPOA5tr), catabolism of chylomicrons and VLDL was accelerated due to a faster plasma hydrolysis of triglycerides by lipoprotein lipase (LPL).Hepatic VLDL and intestinal chylomicron production were not affected. The functional interplay between apoAV and LPL was further investigated by crossbreeding a human LPL transgene with the apoa5 knockout, and the hAPOA5tr to an LPL deficient background. Increased LPL activity completely normalized hypertriglyceridemia of apoa5 deficient mice,however, over expression of human apoAV modulated triglyceride levels only slightly when LPL was reduced. To reflect the physiological situation in which LPL is bound to cell surface proteoglycans, we examined hydrolysis in the presence or absence of proteoglycans. Without proteoglycans, apoAV derived either from triglyceride-rich lipoproteins, hAPOA5tr HDL, or a recombinant source did not alter the LPL hydrolysis rate. In the presence of proteoglycans, however, apoAV led to a significant and dose-dependent increase in LPL mediated hydrolysis of VLDL triglycerides. These results were confirmed in cell culture using a proteoglycan-deficient cell line.A direct interaction between LPL and apoAV was found by ligand blotting.It is proposed, that apoAV reduces triglyceride levels by guiding VLDL and chylomicrons to proteoglycans bound LPL for lipolysis.

  2. Central and peripheral administration of antisense oligonucleotide targeting amyloid-? protein precursor improves learning and memory and reduces neuroinflammatory cytokines in Tg2576 (A?PPswe) mice.

    PubMed

    Farr, Susan A; Erickson, Michelle A; Niehoff, Michael L; Banks, William A; Morley, John E

    2014-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease. Currently, there are no therapies to stop or reverse the symptoms of AD. We have developed an antisense oligonucleotide (OL-1) against the amyloid-? protein precursor (A?PP) that can decrease A?PP expression and amyloid-? protein (A?) production. This antisense rapidly crosses the blood-brain barrier, reverses learning and memory impairments, reduces oxidative stress, and restores brain-to-blood efflux of A? in SAMP8 mice. Here, we examined the effects of this A?PP antisense in the Tg2576 mouse model of AD. We administered the OL-1 antisense into the lateral ventricle 3 times at 2week intervals. Seventy-two hours after the third injection, we tested learning and memory in T-maze foot shock avoidance. In the second study, we injected the mice with OL-1 antisense 3 times at 2-week intervals via the tail vein. Seventy-two hours later, we tested learning and memory T-maze, novel object recognition, and elevated plus maze. At the end of behavioral testing, brain tissue was collected. OL-1 antisense administered centrally improved acquisition and retention of T-maze foot shock avoidance. OL-1 antisense administered via tail vein improved learning and memory in both T-maze foot shock avoidance and novel object-place recognition. In the elevated plus maze, the mice which received OL-1 antisense spent less time in the open arms and had fewer entries into the open arms indicating reduced disinhibitation. Biochemical analyses reveal significant reduction of A?PP signal and a reduction of measures of neuroinflammation. The current findings support the therapeutic potential of OL-1 A?PP antisense. PMID:24577464

  3. [Medium-chain triglycerides--useful energy carriers in parenteral nutrition].

    PubMed

    Wolfram, G

    1989-04-14

    The use of medium-chain triglycerides (MCT) in lipid malabsorption and lipoproteinlipase deficiency is well established. It is known from experiments in animals and humans that after parenteral administration MCT are rapidly hydrolyzed by lipoprotein lipase in plasma. The liberated medium-chain fatty acids are taken up independently of carnitine by mitochondria and oxidized to CO2 in extrahepatic tissues more rapidly than long-chain fatty acids. Medium-chain fatty acids are ketogenic, and consequently both medium-chain fatty acids and ketones are carnitine-independent energy carriers for different tissues. By simultaneously infusing glucose the risk of ketoacidosis can be minimizes. MCT in parenteral nutrition is a substrate which provides high-density energy without problems regarding osmolality or renal losses and with less interference to the reticulohistiocytes of the immune system. On the basis of these metabolic and functional properties MCT represent a valuable additional energy source in total parenteral nutrition. PMID:2499124

  4. Kinetic analysis of free-radical reactions in the low-temperature autoxidation of triglycerides

    SciTech Connect

    Zhu, Jingmin; Sevilla, M.D. (Oakland Univ., Rochester, MI (USA))

    1990-02-22

    The kinetics of the low-temperature autoxidation of triglycerides has been investigated by electron spin resonance spectroscopy. After initial radical production, four reaction stages are found in the overall autoxidation of unsaturated lipids: (1) formation of peroxyl radicals by addition of molecular oxygen to the initial carbon radicals, (2) consumption of oxygen in the autoxidation cycle, (3) decay of the lipid peroxyl radical into allylic and pentadienyl radicals, and (4) recombination of the carbon-centered radicals. Peroxyl radical decay in saturated lipids follows second-order kinetics with an apparent activation energy of ca. 50 kJ/mol. The authors find that, for polyunsaturated lipids, even at quite low temperatures (120 K), the autoxidation process occurs readily and must be considered in the storage of biological samples.

  5. Small-molecule diffusion through polycrystalline triglyceride networks quantified using fluorescence recovery after photobleaching.

    PubMed

    Marty, Stéphanie; Schroeder, Melanie; Baker, Kenneth W; Mazzanti, Gianfranco; Marangoni, Alejandro G

    2009-08-01

    Fluorescence recovery after photobleaching (FRAP) has been used to quantify Nile red diffusion through five different triglyceride crystal networks composed of pure peanut oil (PeO), pure chemically interesterified fully hydrogenated palm oil (IHPO), two blends of PeO and IHPO blended in different mass ratios (70:30 and 30:70%, w/w), and pure cocoa butter. Calculated components from FRAP experiments (effective diffusion coefficient (D(eff)) and mobile fraction (Mr)) were correlated with crystal network structural characteristics (crystalline mass fraction and permeability coefficient) and illustrated that D(eff) can be predicted using this tool. Higher-permeability coefficients found for higher fractal dimensions, lower volume fraction of solids, and larger average particle sizes were significantly correlated to higher D(eff). PMID:19400565

  6. Comprehensive Experiment—Clinical Biochemistry: Determination of Blood Glucose and Triglycerides in Normal and Diabetic Rats

    PubMed Central

    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 standard clinical biochemistry exercise. The students are not only exposed to techniques and equipment but are also inspired to think more about the biochemical mechanisms of diseases. When linked with lecture topics about the metabolism of carbohydrates and lipids, the students obtain a better understanding of the relevance of abnormal metabolism in relation to diseases. Such understanding provides a solid foundation for the medical students' future research and for other clinical applications. PMID:25521692

  7. Comprehensive experiment-clinical biochemistry: determination of blood glucose and triglycerides in normal and diabetic rats.

    PubMed

    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 standard clinical biochemistry exercise. The students are not only exposed to techniques and equipment but are also inspired to think more about the biochemical mechanisms of diseases. When linked with lecture topics about the metabolism of carbohydrates and lipids, the students obtain a better understanding of the relevance of abnormal metabolism in relation to diseases. Such understanding provides a solid foundation for the medical students' future research and for other clinical applications. PMID:25521692

  8. Fractal character of triglyceride spherulites is a consequence of nucleation kinetics

    NASA Astrophysics Data System (ADS)

    Marangoni, Alejandro G.; Ollivon, Michel

    2007-07-01

    Multicomponent triglyceride mixtures crystallize from the melt to form polycrystalline clusters, or spherulites, under low undercooling. Using polarized light microscopy and image analysis, we show that spherulite diameter scales with the mass fraction of solids in a power law fashion, with a characteristic fractal dimension ( D = 1.71) whose value was in close agreement with image analysis results ( D = 1.73). This suggests that the internal spatial distribution of mass within these spherulites is fractal in nature. Based on these findings, and former work by our group [A.G. Marangoni, S.E. McGauley, Cryst. Growth Des. 3 (2003) 95-108; H.D. Batte, A.G. Marangoni, Cryst. Growth Des. 5 (2005) 1703-1705], we then derive a relationship between spherulite diameter and the free energy of nucleation.

  9. Determination of Free Fatty Acids and Triglycerides by Gas Chromatography Using Selective Esterification Reactions

    SciTech Connect

    Kail, Brian W.; Link, Dirk D.; Morreale, Bryan D

    2012-11-01

    A method for selectively determining both free fatty acids (FFA) and triacylglycerides (TAGs) in biological oils was investigated and optimized using gas chromatography after esterification of the target species to their corresponding fatty acid methyl esters (FAMEs). The method used acid catalyzed esterification in methanolic solutions under conditions of varying severity to achieve complete conversion of more reactive FFAs while preserving the concentration of TAGs. Complete conversion of both free acids and glycerides to corresponding FAMEs was found to require more rigorous reaction conditions involving heating to 120°C for up to 2 h. Method validation was provided using gas chromatography–flame ionization detection, gas chromatography–mass spectrometry, and liquid chromatography–mass spectrometry. The method improves on existing methods because it allows the total esterified lipid to be broken down by FAMEs contributed by FFA compared to FAMEs from both FFA and TAGs. Single and mixed-component solutions of pure fatty acids and triglycerides, as well as a sesame oil sample to simulate a complex biological oil, were used to optimize the methodologies. Key parameters that were investigated included: HCl-to-oil ratio, temperature and reaction time. Pure free fatty acids were found to esterify under reasonably mild conditions (10 min at 50°C with a 2.1:1 HCl to fatty acid ratio) with 97.6 ± 2.3% recovery as FAMEs, while triglycerides were largely unaffected under these reaction conditions. The optimized protocol demonstrated that it is possible to use esterification reactions to selectively determine the free acid content, total lipid content, and hence, glyceride content in biological oils. This protocol also allows gas chromatography analysis of FAMEs as a more ideal analyte than glyceride species in their native state.

  10. Supported phosphate and carbonate salts for heterogeneous catalysis of triglycerides to fatty acid methyl esters

    NASA Astrophysics Data System (ADS)

    Britton, Stephanie Lynne

    Fatty acid methyl esters made from vegetable oil, or biodiesel, have been identified as a substitute for diesel derived from crude oil. Biodiesel is currently made using a homogeneous base catalyst to perform the transesterification of triglycerides with methanol to generate fatty acid methyl esters (FAME). The use of a homogeneous catalyst necessitates additional purification of the product and byproducts before sale, and the catalyst is consumed and discarded. The development of a heterogeneous basic catalyst for the production of FAME is desirable. Tribasic phosphate salts and dibasic carbonate salts are active for the production of FAME but generally operate as homogeneous catalysts. Supporting these phosphate and carbonate salts on mesoporous MCM-41, microporous silica gel, and nonporous a-alumina proved successful to greater or lesser degrees depending on the identity of the support and pretreatment of the support. Although these salts were supported and were active for the production of FAME from canola oil, they proved to be operating as homogeneous catalysts due to leaching of the active species off the surface of the support. Further investigation of the active species present in the tribasic phosphate catalysts identified the active support as orthophosphate, and NMR studies revealed the phosphorus to be present as orthophosphate and diphosphate in varying proportions in each catalyst. Evaluation of the acid-washing support pretreatment process revealed that the exposure of the support to acid plays a large role in the development of activity on the surface of the catalyst, but manipulation of these parameters did not prevent leaching of the active site off the surface of the catalyst. Alternate methods of support pretreatment were no more effective in preventing leaching. Tribasic phosphate supported on silica gel is not effective as a heterogeneous catalyst for FAME production from triglycerides because of the lack of stability of the phosphate on the support. The support is not stable under the reaction conditions, and alternatives should be explored to develop a heterogeneous base catalyst for the production of FAME.

  11. Molecular cloning, expression, and hormonal regulation of the chicken microsomal triglyceride transfer protein.

    PubMed

    Ivessa, N Erwin; Rehberg, Edward; Kienzle, Bernadette; Seif, Fridolin; Hermann, Robert; Hermann, Marcela; Schneider, Wolfgang J; Gordon, David A

    2013-07-01

    During an egg-laying cycle, oviparous animals transfer massive amounts of triglycerides, the major lipid component of very low density lipoprotein (VLDL), from the liver to the developing oocytes. A major stimulus for this process is the rise in estrogen associated with the onset of an egg-laying cycle. In mammals, the microsomal triglyceride transfer protein (MTP) is required for VLDL assembly and secretion. To enable studies to determine if MTP plays a role in basal and estrogen-stimulated VLDL assembly and secretion in an oviparous vertebrate, we have cloned and sequenced the chicken MTP cDNA. This cDNA encodes a protein of 893 amino acids with an N-terminal signal sequence. The primary sequence of chicken MTP is, on average, 65% identical to that of mammalian homologs, and 23% identical to the Drosophila melanogaster protein. We have obtained a clone of chicken embryo fibroblast cells that stably express the avian MTP cDNA and show that these cells display MTP activity as measured by the transfer of a fluorescently labeled neutral lipid. As in mammals, chicken MTP is localized to the endoplasmic reticulum as revealed by indirect immunofluorescence and by the fact that its N-linked oligosaccharide moiety remains sensitive to endoglycosidase H. Endogenous, enzymatically active MTP is also expressed in an estrogen receptor-expressing chicken hepatoma cell line that secretes apolipoprotein B-containing lipoproteins. In this cell line and in vivo, the expression and activity of MTP are not influenced by estrogen. Therefore, up-regulation of MTP in the liver is not required for the increased VLDL assembly during egg production in the chicken. This indicates that MTP is not rate-limiting, even for the massive estrogen-induced secretion of VLDL accompanying an egg-laying cycle. PMID:23542778

  12. Moral elevation can induce nursing.

    PubMed

    Silvers, Jennifer A; Haidt, Jonathan

    2008-04-01

    There is little extant research on the psychological or physiological response to witnessing good deeds. The authors call the emotional reaction to virtue "moral elevation" and the authors examined its effects on mother-infant dyads. Breastfeeding women who watched a morally elevating video were more likely to nurse their infants and were marginally more likely to hug them, compared to women who watched an equally enjoyable comedy video. Both of these effects suggest that moral elevation may involve the release of oxytocin, a hormone associated with lactation and affiliation. PMID:18410202

  13. Elevation Derivatives for National Applications

    USGS Publications Warehouse

    U.S. Geological Survey

    2005-01-01

    The Elevation Derivatives for National Applications (EDNA) project is a multi-agency effort to develop standard topographically derived layers for use in hydrologic and environmental modeling. The EDNA takes advantage of the seamless and filtered characteristics for the National Elevation Dataset (NED) to create a hydrologically conditioned Digital Elevation Model (DEM) useful for modeling applications. The goals of the project are to create a hydrologically conditioned DEM and systematically extract a set of standard derivatives that can be used to facilitate data integration with other U.S. Geological Survey (USGS) framework data sets such as the National Hydrography Dataset (NHD) and the Watershed Boundaries Dataset (WBD).

  14. Slowly and rapidly digested fat emulsions are equally satiating but their triglycerides are differentially absorbed and metabolized in humans.

    PubMed

    Keogh, Jennifer B; Wooster, Tim J; Golding, Matthew; Day, Li; Otto, Bärbel; Clifton, Peter M

    2011-05-01

    Little is known about the effect of dietary fat emulsion microstructure on plasma TG concentrations, satiety hormones, and food intake. The aim of this study was to structure dietary fat to slow digestion and flatten postprandial plasma TG concentrations but not increase food intake. Emulsions were stabilized by egg lecithin (control), sodium sterol lactylate, or sodium caseinate/monoglyceride (CasMag) with either liquid oil or a liquid oil/solid fat mixture. In a randomized, double-blind, crossover design, 4 emulsions containing 30 g of fat in a 350-mL preload were consumed by 10 men and 10 women (BMI = 25.1 ± 2.8 kg/m(2); age = 58.8 ± 4.8 y). Pre- and postprandial plasma TG, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide YY (PYY) concentrations and food intake were measured. In a second experiment in a subset of the participants (n = 8, 4 men and 4 women), (13)C-labeled mixed TG was incorporated into 2 different emulsions and breath (13)C was measured over 6 h. In the first experiment, the postprandial rise in plasma TG concentrations following the CasMag-stabilized emulsion containing 30% solid fat was lower than all other emulsions at 90 and 120 min (P < 0.05). Plasma CCK (P < 0.0001), GLP-1 (P < 0.01), and PYY (P < 0.001) concentrations were also reduced following this emulsion compared with control. Food intake at a test meal, eaten 3 h after the preload, did not differ among the emulsions. In the second experiment, when measured by the (13)C breath test, 25% of the TG in the CasMag emulsion was absorbed and metabolized compared with control. In conclusion, fat can be structured to decrease its effect on plasma TG concentrations without increasing food intake. PMID:21411612

  15. control group. In HDL2, a low CE level and a high amount of UC, TG and PL were

    E-print Network

    Boyer, Edmond

    - ciations between serum lipid levels (triglyc- erides, HDL-cholesterol) and restriction fragment length for women and26.4 kg/m2 for men. Diabetic patients or patients using drugs known to modify serum lipid (spontaneous diet or hypocaloric diet). In conclusion, the serum TG and VLDL levels differed in obese people

  16. Relation of Swelling and Tg Depression to the Apparent Free Volume of a Particle-Filled Epoxy-based Adhesive

    NSDL National Science Digital Library

    Chiang, M. Y.

    2003-01-01

    The effect of hygrothermal aging on a particle-filled, epoxy-based adhesive was studied using a gravimetric sorption technique. This study has explored moisture sorption characteristics as well as the associated behaviors of swelling and the depression of the glass transition temperature (Tg). We observed that the diffusion of water in this adhesive has a non-Fickian behavior, and the depression of Tg proceeds to a definite value that is independent of the final equilibrium water content of the system. Our observations suggest that water diffuses into the polymer in a dualsorption mode, in which water resides in two populations. In one population, water is considered to occupy apparent free volume of the adhesive, and the second population water infiltrates polymer structure and forms hydrogenbonded clusters. Our results show that hygrothermal aging temperature and swelling do not alter the apparent free volume of this adhesive. We conclude that the constant value of Tg depression at saturation implies that only water in the apparent free volume is responsible for the Tg depression, whereas the swelling proceeds through the formation of hydrogen bonds in the adhesive.

  17. Measurement of tg? and C of single-phase electrical apparatus with capacitive insulation under operating voltage

    Microsoft Academic Search

    G. Zhu; J. Wang

    1988-01-01

    The authors describe a method of measuring tg? (loss tangent) and C (capacitance) of a single-phase apparatus with capacitive insulation by using an ordinary Schering bridge which takes the secondary voltage of a same-phase power transformer as the voltage of the standard arm and suppresses interference. Examples are given to illustrate how to analyze the results of measurement. The proposed

  18. TG containing stearic acid, synthesized from coconut oil, exhibit lipidemic effects in rats similar to those of cocoa butter.

    PubMed

    Rao, Reena; Lokesh, Belur R

    2003-09-01

    Lipase-catalyzed interesterification was used to prepare structured TG from coconut oil TG by partially replacing some of the atherogenic saturated FA with stearic acid, which is known to have a neutral effect on lipid levels in the body. The level of stearic acid was increased from 4% in the native coconut oil to 40% in the structured lipids, with most of the stearic acid being incorporated into the sn-1 and sn-3 positions of TG. When structured lipids were fed to rats at a 10% level for a period of 60 d, a 15% decrease in total cholesterol and a 23% decrease in LDL cholesterol levels in the serum were observed when compared to those fed coconut oil. Similarly, the total and free cholesterol levels in the livers of the rats fed structured lipids were lowered by 31 and 36%, respectively, when compared to those fed coconut oil. The TG levels in the serum and in the liver showed decreases of 14 and 30%, respectively, in animals fed structured lipids. Rats fed cocoa butter and structured lipids having a similar amount of stearic acid had similar lipid levels in the serum and liver. These studies indicated that the atherogenic potential of coconut oil lipids can be reduced significantly by enriching them with stearic acid. This also changed the physical properties of coconut oil closer to those of cocoa butter as determined by DSC. PMID:14584598

  19. Vogan-Zuckerman , $GL(n, R)$ $G$ $GL(n, R)$ Cartan involution $g$ }$arrow {}^{t}g^{-1}$

    E-print Network

    Kobayashi, Toshiyuki

    ­ Vogan-Zuckerman , ( ) 1. $GL(n, R)$ $G$ $GL(n, R)$ Cartan involution $g$ }$arrow {}^{t}g^{-1}$ $G$ (2.5) $G/H$ $B$ $G$ , , $G$ , , $-3/]-$ #12;: 1.7 2. , , , ( ) Vogan , , Borcl-Weil 8 $0$ Zuckerman Zuckerman , , Zuckerman Sclunid, Wong ( 17) , - $\\iota j$ orbit method $G$ Ad: $Garrow GL(\\mathfrak{g})$ Ad

  20. Carbazole dendronised triphenylamines as solution processed high Tg amorphous hole-transporting materials for organic electroluminescent devices.

    PubMed

    Moonsin, Preecha; Prachumrak, Narid; Rattanawan, Ratanawalee; Keawin, Tinnagon; Jungsuttiwong, Siriporn; Sudyoadsuk, Taweesak; Promarak, Vinich

    2012-04-01

    Carbazole dendrimers up to 4th generation were synthesized. They showed significantly high T(g), amorphous and stable electrochemical properties, and great potential as solution processed hole-transporting materials for OLEDs. Alq3-based green devices exhibited high luminance efficiency and CIE coordinates of 4.45 cd A(-1) and (0.29, 0.53), respectively. PMID:22301677

  1. CHF5074 restores visual memory ability and pre-synaptic cortical acetylcholine release in pre-plaque Tg2576 mice.

    PubMed

    Giuliani, Alessandro; Beggiato, Sarah; Baldassarro, Vito A; Mangano, Chiara; Giardino, Luciana; Imbimbo, Bruno P; Antonelli, Tiziana; Calzà, Laura; Ferraro, Luca

    2013-03-01

    CHF5074, a new microglial modulator, attenuates memory deficit in Alzheimer's disease transgenic mice. In this study, the effect of an acute or subacute CHF5074 treatment on in vivo novel object recognition test and on [³H]Acetylcholine (ACh) and GABA release in pre-plaque (7-month-old) Tg2576 mice have been compared with those induced by the ?-secretase inhibitor LY450139 (semagacestat). Vehicle-treated Tg2576 mice displayed an impairment of recognition memory compared with wild-type animals. This impairment was recovered in transgenic animals acutely treated with CHF5074 (30 mg/kg), while LY450139 (1, 3, 10 mg/kg) was ineffective. In frontal cortex synaptosomes from vehicle-treated Tg2576 mice, K?-evoked [³H]ACh release was lower than that measured in wild-type mice. This reduction was absent in transgenic animals subacutely treated with CHF5074 (30 mg/kg daily for 8 days), while it was slightly, not significantly, amplified by LY450139 (3 mg/kg daily for 8 days). There were no differences between the groups on spontaneous [³H]ACh release as well as spontaneous and K?-evoked GABA release. These results suggest that CHF5074 has beneficial effects on visual memory and cortical cholinergic dysfunctions in pre-plaque Tg2576 mice. Together with previous findings, these data suggest that CHF5074 could be a possible candidate for early Alzheimer's disease therapeutic regimens. PMID:23278303

  2. Effect of rice-expressed amyloid ? in the Tg2576 Alzheimer's disease transgenic mouse model.

    PubMed

    Nojima, Jun; Maeda, Azusa; Aoki, Sho; Suo, Satoshi; Yanagihara, Dai; Watanabe, Yuichiro; Yoshida, Taiji; Ishiura, Shoichi

    2011-08-26

    One of the main hallmarks of Alzheimer's disease (AD) is senile plaques composed of amyloid ? (A?). We developed a new edible vaccine: rice expressing GFP-A?42. In a previous report, we described the production of anti-A? antibodies in B6 mice fed A? rice mixed with cholera toxin B subunit (CTB). In this report, we investigated whether A? rice had therapeutic effects in the Tg2576 AD model mice. The anti-A? antibody titer was increased and levels of intracerebral A? (soluble and insoluble) and serum A? decreased. Because the value of IgG1/IgG2a in the A? feeding group was >1, immunization via A? rice may induce a non-inflammatory Th2 reaction. We also found that the A? vaccine improved memory, as assessed in a Y-maze test. The number of arm entries in the Y-maze test was lower in the A? feeding group than in the control group. These results suggest that the new edible vaccine A? rice may have therapeutic effects in AD. PMID:21726591

  3. Tg(Afp-GFP) Expression Marks Primitive and Definitive Endoderm Lineages during Mouse Development

    PubMed Central

    Kwon, Gloria S.; Fraser, Stuart T.; Eakin, Guy S.; Mangano, Michael; Isern, Joan; Sahr, Kenneth E.; Hadjantonakis, Anna-Katerina; Baron, Margaret H.

    2007-01-01

    Alpha-fetoprotein (Afp) is the most abundant serum protein in the developing embryo. It is secreted by the visceral endoderm, its derivative yolk sac endoderm, fetal liver hepatocytes, and the developing gut epithelium. The abundance of this protein suggested that Afp gene regulatory elements might serve to effectively drive reporter gene expression in developing endodermal tissues. To this end, we generated transgenic mouse lines Tg(Afp-GFP) using an Afp promoter/enhancer to drive expression of green fluorescent protein (GFP). Bright GFP fluorescence allowed the visualization, in real time, of visceral endoderm, yolk sac endoderm, fetal liver hepatocytes, and the epithelium of the gut and pancreas. Comparison of the localization of green fluorescence with that of endogenous Afp transcripts and protein indicated that the regulatory elements used to generate these mouse lines directed transgene expression in what appeared to be all Afp-expressing cells of the embryo, but only in a subset of fetal liver cells. The bright GFP signal permitted flow cytometric analysis of fetal liver hepatocytes. These mice represent a valuable resource for live imaging as well as identification, quantitation and isolation of cells from the primitive and definitive endoderm lineages of the developing mouse embryo. PMID:16708394

  4. Ruthenium Red Colorimetric and Birefringent Staining of Amyloid-? Aggregates in Vitro and in Tg2576 Mice

    PubMed Central

    2012-01-01

    Alzheimer’s disease (AD) is a devastating neurodegenerative disease most notably characterized by the misfolding of amyloid-? (A?) into fibrils and its accumulation into plaques. In this Article, we utilize the affinity of A? fibrils to bind metal cations and subsequently imprint their chirality to bound molecules to develop novel imaging compounds for staining A? aggregates. Here, we investigate the cationic dye ruthenium red (ammoniated ruthenium oxychloride) that binds calcium-binding proteins, as a labeling agent for A? deposits. Ruthenium red stained amyloid plaques red under light microscopy, and exhibited birefringence under crossed polarizers when bound to A? plaques in brain tissue sections from the Tg2576 mouse model of AD. Staining of A? plaques was confirmed via staining of the same sections with the fluorescent amyloid binding dye Thioflavin S. In addition, it was confirmed that divalent cations such as calcium displace ruthenium red, consistent with a mechanism of binding by electrostatic interaction. We further characterized the interaction of ruthenium red with synthetic A? fibrils using independent biophysical techniques. Ruthenium red exhibited birefringence and induced circular dichroic bands at 540 nm upon binding to A? fibrils due to induced chirality. Thus, the chirality and cation binding properties of A? aggregates could be capitalized for the development of novel amyloid labeling methods, adding to the arsenal of AD imaging techniques and diagnostic tools. PMID:23509974

  5. Study of glass transition temperature (Tg) of novel stress-sensitive composites using molecular dynamic simulation

    NASA Astrophysics Data System (ADS)

    Koo, B.; Liu, Y.; Zou, J.; Chattopadhyay, A.; Dai, L. L.

    2014-09-01

    This study investigates the glass transition temperature (Tg) of novel stress-sensitive composites capable of detecting a damage precursor using molecular dynamics (MD) simulations. The molecular structures of a cross-linked epoxy network (which consist of epoxy resin, hardener and stress-sensitive material) have been simulated and experimentally validated. The chemical constituents of the molecular structures are di-glycidyl ether of bisphenol F (DGEBF: epoxy resin), di-ethylene tri-amine (DETA: hardener) and tris-(cinnamoyloxymethyl)-ethane (TCE: stress-sensitive material). The cross-linking degree is varied by manipulating the number of covalent bonds through tuning a cutoff distance between activated DGEBF and DETA during the non-equilibrium MD simulation. A relationship between the cross-linking degree and Tgs has been studied numerically. In order to validate a proposed MD simulation framework, MD-predicted Tgs of materials used in this study have been compared to the experimental results obtained by the differential scanning calorimetry (DSC). Two molecular models have been constructed for comparative study: (i) neat epoxy (epoxy resin with hardener) and (ii) smart polymer (neat epoxy with stress-sensitive material). The predicted Tgs show close agreement with the DSC results.

  6. Ruthenium red colorimetric and birefringent staining of amyloid-? aggregates in vitro and in Tg2576 mice.

    PubMed

    Cook, Nathan P; Archer, Clarissa M; Fawver, Janelle N; Schall, Hayley E; Rodriguez-Rivera, Jennifer; Dineley, Kelly T; Martí, Angel A; Murray, Ian V J

    2013-03-20

    Alzheimer's disease (AD) is a devastating neurodegenerative disease most notably characterized by the misfolding of amyloid-? (A?) into fibrils and its accumulation into plaques. In this Article, we utilize the affinity of A? fibrils to bind metal cations and subsequently imprint their chirality to bound molecules to develop novel imaging compounds for staining A? aggregates. Here, we investigate the cationic dye ruthenium red (ammoniated ruthenium oxychloride) that binds calcium-binding proteins, as a labeling agent for A? deposits. Ruthenium red stained amyloid plaques red under light microscopy, and exhibited birefringence under crossed polarizers when bound to A? plaques in brain tissue sections from the Tg2576 mouse model of AD. Staining of A? plaques was confirmed via staining of the same sections with the fluorescent amyloid binding dye Thioflavin S. In addition, it was confirmed that divalent cations such as calcium displace ruthenium red, consistent with a mechanism of binding by electrostatic interaction. We further characterized the interaction of ruthenium red with synthetic A? fibrils using independent biophysical techniques. Ruthenium red exhibited birefringence and induced circular dichroic bands at 540 nm upon binding to A? fibrils due to induced chirality. Thus, the chirality and cation binding properties of A? aggregates could be capitalized for the development of novel amyloid labeling methods, adding to the arsenal of AD imaging techniques and diagnostic tools. PMID:23509974

  7. TG and DSC studies of natural and artificial aging of polypropylene

    NASA Astrophysics Data System (ADS)

    Rjeb, M.; Labzour, A.; Rjeb, A.; Sayouri, S.; Claire, Y.; Périchaud, A.

    2005-12-01

    We study the evolution of thermal degradation of samples of polypropylene (PP), during their aging for two periods of 60 and 80 days. The study, using thermogravimetric analysis (TG) and differential scanning calorimetric (DSC) analyses, focused on two types of aging: the natural one under the impact of the solar environment and the artificial one which was carried out by exposing the sample to radiations of a 100 W commercial lamp. The comparative study of these two types of aging shows that the thermal degradation of the PP increases as a function of time of aging. Indeed, for a same duration, this thermal degradation is more important in the artificial aging case than it is in the natural one and is an increasing function of aging. The prolonged and continuous thermal effect produced by the lamp, in the case of the artificial aging, weakened the polymer and implies very important acceleration of the process of degradation. The results obtained during heating and cooling of the samples, using the DSC, show an evolution of the phase transition temperatures and the corresponding enthalpies of melting and crystallization.

  8. TG-MS study of the thermo-oxidative behavior of plastic automobile shredder residues.

    PubMed

    Guo, Qingjie; Zhang, Xuan; Li, Chao; Liu, Xinmin; Li, Jinhui

    2012-03-30

    Automobile shredder residues (ASR) are materials that are rejected in the metal recovery process for end-of-life vehicles (ELV). These residues are composed of such materials as plastics, foams, glasses, rubbers, textiles, remaining metals and soils. ASR disposal is a difficult task, due to increasingly restrictive re-use policies. The pyrolytic reuse of ASR is one important option for energy recovery. The gas release behavior of pyrolyzed ASR was measured using a TG-MS apparatus, and this thermo-oxidative process was observed under different N(2)/O(2) volume ratios. The final weight/initial residue weight ratio for pyrolyzed ASR decreased from 43.4% to 10.1% with increasing oxygen concentrations. The production rates of hydrogen, methane and carbon dioxide also varied with different N(2)/O(2) volume ratios. The maximum emission of hydrogen and methane occurred when the thermo-oxidative atmosphere was entirely N(2). Temperature had a positive impact on hydrogen production, and the methane emission ratio reached a peak at the second shoulder of the devolatilization stage during which stage organic polymers were emitted. A peculiar characteristic of ASR is its content of nitrogen. The effects of ASR nitrogen content on N(2)O and NO(X) emissions were investigated in detail. NH(3) was the dominant nitrogen species that was released during ASR pyrolysis. N(2)O is highly temperature-sensitive and decomposes to N(2) at temperatures greater than 900°C. PMID:22316686

  9. Effects of mitiglinide on glucose-induced insulin release into the portal vein and fat-induced triglyceride elevation in prediabetic and diabetic OLETF rats

    Microsoft Academic Search

    Y. Mori; K. Ojima; Y. Fujimori; I. Aoyagi; H. Kusama; Y. Yamazaki; S. Kojima; N. Shibata; Y. Itoh; N. Tajima

    2006-01-01

    Objective: The effect of single-dose mitiglinide on glucose and lipid metabolism was examined in OLETF rats with spontaneous\\u000a type 2 diabetes in which the early insulin response following glucose challenge is known to diminish over time and become\\u000a lost with aging. Methods: (1) With catheters inserted into the portal veins, 12-wk-old prediabetic OLETF rats were given an\\u000a OGTT of 1g\\/kg

  10. Effect of soybean leci-vita product on serum lipids and fatty acid composition in patients with elevated serum cholesterol and triglyceride levels

    Microsoft Academic Search

    Danijela Risti? Medi?; Vanja Risti?; Vesna Tepši?; Marija Rani?; Gordana Risti?; Ilona Estelecki

    2003-01-01

    The study was designed to examine the effects of soybean Leci-Vita, product rich in polyunsaturated phospholipids (with 7% lecithin, 17% soy protein) on serum lipids and serum and erythrocyte phospholipid fatty acid composition in patients with different types of hyperlipidemia. 106 patients with isolated hypertriglyceridemia (IHTG), combined hyperlipidemia (CHL) and isolated hypercholesterolemia (IHCH), aged 40-70 years, were given 20g of

  11. Cholesterol, Oxysterol, Triglyceride, and Coenzyme Q Homeostasis in ALS. Evidence against the Hypothesis That Elevated 27-Hydroxycholesterol Is a Pathogenic Factor

    PubMed Central

    Wuolikainen, Anna; Acimovic, Jure; Lövgren-Sandblom, Anita; Parini, Paolo; Andersen, Peter M.; Björkhem, Ingemar

    2014-01-01

    High plasma levels of cholesterol have been suggested to be neuroprotective for the degenerative disease amyotrophic lateral sclerosis (ALS) and to be associated with increased survival time. The gene encoding cholesterol 27-hydroxylase, CYP27A1, was recently identified as a susceptibility gene for sporadic ALS. A product of this enzyme is 27-hydroxycholesterol. We investigated plasma samples from 52 ALS patients and 40 control subjects (spouses) regarding cholesterol homeostasis, lipid profiles, and coenzyme Q. Eleven of the patients carried mutations in C9orf72 and seven in SOD1. Plasma levels of 27-hydroxycholesterol were significantly lower in male patients with ALS than in controls. It was not possible to link the reduced levels to any specific mutation, and there was no significant correlation between 27-hydroxycholesterol and survival. With normalization for diet using the spouses, a correlation was found between survival and total cholesterol, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, and coenzyme Q. We conclude that cholesterol, 24S-hydroxycholesterol, 25-hydroxycholesterol, 27-hydroxycholesterol and lipid profiles in plasma are of limited prognostic value in individual ALS patients. PMID:25415378

  12. The effects of the ? -glucosidase inhibitor BAY g 5421 (Acarbose) on meal-stimulated elevations of circulating glucose, insulin, and triglyceride levels in man

    Microsoft Academic Search

    I. Hillebrand; K. Boehme; G. Frank; H. Fink; P. Berchtold

    1979-01-01

    Summary In blind studies the effects of a newa-glucosidase inhibitor (BAY g 5421) were tested in normal weight and overweight male volunteers after oral application of 75, 150, or 300 mg of BAY g 5421 or placebo per os before three standardized main meals of one day. Before and three hours after each meal blood glucose, serum insulin, and serum

  13. Ospemifene and 4-Hydroxyospemifene Effectively Prevent and Treat Breast Cancer in the MTag.Tg Transgenic Mouse Model

    PubMed Central

    Burich, Rebekah A.; McCall, Jamie L.; Mehta, Neelima R.; Greenberg, Brittany E.; Bell, Katie E.; Griffey, Stephen M.; DeGregorio, Michael W.; Wurz, Gregory T.

    2011-01-01

    Objective Ospemifene, a new drug indicated for the treatment of vulvovaginal atrophy, has completed Phase III clinical trials. A condition affecting millions of women worldwide, vulvovaginal atrophy has long been treated with estrogen therapy. Estrogen treatment carries with it risks of thromboembolism, endometrial proliferative effects, and breast cancer promotion. In this study, we test the effects of three dosing levels of ospemifene in both the prevention and treatment of breast cancer in the MTag.Tg mouse model. Methods The polyomavirus middle-T transgenic mouse model (MTag.Tg), which produces synchronized, multifocal mammary tumors in the immunologically intact C57BL/6 background, was used to examine the impact of ospemifene treatment. First, a cell line derived from an MTag.Tg mouse tumor (Mtag 34) was treated in vitro with ospemifene and its major metabolite, 4-OH ospemifene. MTag.Tg mice were treated daily by gavage with three different doses of ospemifene (5, 25, and 50 mg/kg) before or after the development of mammary tumors. Survival and tumor development results were used to determine the effect of ospemifene treatment on mammary tumors in both the preventive and treatment settings. Results Tumors and the MTag 34 cell line were positive for estrogen receptor expression. The MTag 34 line was not stimulated by ospemifene or its major, active metabolite 4-OH ospemifene in vitro. Ospemifene increased survival time and exerted an antitumor effect on the development and growth of estrogen receptor positive mammary tumors in the MTag.Tg mouse model at the 50 mg/kg dose. Levels of ospemifene and 4-OH ospemifene in both the tumors and plasma of mice confirmed dosing. Ospemifene did not exert an estrogenic effect in the breast tissue at doses equivalent to human dosing. Conclusions Ospemifene prevents and treats estrogen receptor positive MTag.Tg mammary tumors in this immune intact mouse model in a dose-dependent fashion. Ospemifene drug levels in the plasma of treated mice were comparable to those found in humans. Combined with our previous data, ospemifene does not appear to pose a breast cancer risk in animals, and slows cancer development and progression in the MTag.Tg model. PMID:21926925

  14. ConcepTest: Elevated Terraces

    NSDL National Science Digital Library

    A series of elevated terraces (former wave-cut platforms) along an active plate boundary coast is evidence for ______________. a. Sea level rise b. Uplift of continental crust c. Subsidence (sinking) of crust

  15. Early induction of interleukin-6 mRNA in the hippocampus and cortex of APPsw transgenic mice Tg2576.

    PubMed

    Tehranian, R; Hasanvan, H; Iverfeldt, K; Post, C; Schultzberg, M

    2001-03-23

    The neuropathological changes in Alzheimer's disease (AD) include the occurrence of activated microglia and astrocytes. Activated microglia expressing interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) immunoreactivity have been observed in close vicinity of the amyloid plaques in post-mortem tissue from AD patients. In order to further analyze the inflammatory process in relation to amyloidosis, we have studied the levels of markers for inflammation in the brain of Tg(HuAPP695K670N/M671L)2576 transgenic mice (Tg2576) that express high levels of human beta-amyloid precursor protein with the Swedish double mutation and develop prominent AD type neuropathology. The mRNA levels for IL-1beta, IL-1beta-converting enzyme (ICE/caspase-1) and IL-6 were analyzed by semi-quantitative reverse transcription-polymerase chain reaction in the cerebral cortex, hippocampus and cerebellum from Tg2576 and wild type (wt) mice. The levels of mRNA for IL-1beta and caspase-1 were not significantly increased in either young (4 months) or aged (18 months) Tg2576 mice as compared to the age-matched wt mice. However, we observed an increase in IL-6 mRNA levels in the hippocampus and cortex of both 4- and 18-month-old transgenic mice as compared to wt mice. The increase in IL-6 mRNA levels in Tg2576 animals thus occurs before amyloid plaques can be detected (9-10 months). This would indicate that IL-6 mRNA induction is an early event in a beta-amyloid-induced immune response cascade or that it may be involved in the amyloidosis. PMID:11239715

  16. Cognitive and emotional profiles of aged Alzheimer's disease (3×TgAD) mice: effects of environmental enrichment and sexual dimorphism.

    PubMed

    Blázquez, Gloria; Cañete, Toni; Tobeña, Adolf; Giménez-Llort, Lydia; Fernández-Teruel, Alberto

    2014-07-15

    Alzheimer's disease is a neurodegenerative disorder associated with age which represents the most common cause of dementia. It is characterized by an accelerated memory loss compared to normal aging, and deterioration of other cognitive abilities that interfere with mood, reason, judgment and language. The main neuropathological hallmarks of the disorder are ?-amyloid (?A) plaques and neurofibrillary Tau tangles. Triple transgenic 3×TgAD mouse model develops ?A and Tau pathologies in a progressive manner, with a specific temporal and anatomic profile mimicking the pattern that takes place in the human brain with AD, and showing cognitive alterations characteristic of the disease. Environmental enrichment treatment in mice induces behavioral and emotional reactivity changes, including cognitive improvements in some AD-related transgenic mice. The present work intended to characterize the behavioral profile of 3×TgAD mice at advanced stages of neuropathological development (12 and 15 months of age) and to investigate whether environmental enrichment administered during adulthood was able to modify some of their behavioral and cognitive alterations. Results show that, at advanced stages of the disease 3×TgAD mice show deficits of spatial learning acquisition, as well as short-term and working memory deficits, while displaying increased levels of anxiety/fearfulness and normal sensorimotor functions. 3×TgAD mice also show sexual dimorphism, as reflected by increased cognitive deficits in females and increased levels of novelty-induced behavioral inhibition in males. Environmental enrichment exerts some slight positive effects, by mainly improving the initial acquisition of the spatial learning and working memory in 12-month-old 3×TgAD mice. Such effects vary depending on the gender. PMID:24746486

  17. Association between ADIPOQ +45T>G Polymorphism and Type 2 Diabetes: A Systematic Review and Meta-Analysis

    PubMed Central

    Fan, Yaofu; Wang, Kun; Xu, Shuhang; Chen, Guofang; Di, Hongjie; Cao, Meng; Liu, Chao

    2014-01-01

    Recently, a number of studies have reported the association between the single nucleotide polymorphisms (SNPs) +45T>G polymorphism in the adiponectin (ADIPOQ) gene and type 2 diabetes mellitus (T2DM) risk, though the results are inconsistent. In order to obtain a more precise estimation of the relationship, a meta-analysis was performed. In this current study, the Medline, Embase, Pubmed, ISI Web of Knowledge, Ovid, Science Citation Index Expanded Database, Wanfang Database, and China National Knowledge Infrastructure were searched for eligible studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of association. Forty-five publications were included in the final meta-analysis with 9986 T2DM patients and 16,222 controls for ADIPOQ +45T>G polymorphism according to our inclusion and exclusion criteria. The +45T>G polymorphism was associated with an overall significantly increased risk of T2DM (G vs. T: OR = 1.18, 95% CI = 1.06–1.32; The dominant model: OR = 1.18, 95% CI = 1.03–1.33; The recessive model: OR = 1.47, 95% CI = 1.20–1.78; The homozygous model: OR = 1.62, 95% CI = 1.25–2.09; Except the heterozygous model: OR = 1.11, 95% CI = 0.98–1.24). Subgroup analysis revealed a significant association between the +45T>G polymorphism and T2D in an Asian population. Thus, this meta-analysis indicates that the G allele of the ADIPOQ +45T>G polymorphisms associated with a significantly increased risk of T2DM in the Asian population. PMID:25561226

  18. Developmental, hormonal, and nutritional regulation of expression of porcine adipose tissue triglyceride lipase (pATGL) gene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adipose triglyceride lipase (ATGL) is a newly identified lipase. We report for the first time the porcine ATGL sequence and characterize ATGL gene and protein expression in vitro and in vivo. Adult pig tissue expresses ATGL at high levels in the white adipose and muscle tissue relative to other te...

  19. Fatty Acid and Triglyceride Composition of Milk Fat from Lactating Holstein Cows in Response to Supplemental Canola Oil

    Microsoft Academic Search

    E. J. DePeters; J. B. German; S. J. Taylor; S. T. Essex; H. Perez-Monti

    2001-01-01

    The objective was to determine the influence of di- etary lipid on total and sn-2 fatty acid composition and triglyceride structure of milk fat in lactating Holstein cows. Five primiparous Holstein cows surgically fitted with ruminal and duodenal cannulas were used in a 4 × 5 incomplete Latin square. All cows received a basal diet. Treatments consisted of a basal

  20. Triglyceride Blisters in Lipid Bilayers: Implications for Lipid Droplet Biogenesis and the Mobile Lipid Signal in Cancer Cell Membranes

    Microsoft Academic Search

    Himanshu Khandelia; Lars Duelund; Kirsi I. Pakkanen; John H. Ipsen; Darren R. Flower

    2010-01-01

    Triglycerides have a limited solubility, around 3%, in phosphatidylcholine lipid bilayers. Using millisecond-scale course grained molecular dynamics simulations, we show that the model lipid bilayer can accommodate a higher concentration of triolein (TO) than earlier anticipated, by sequestering triolein molecules to the bilayer center in the form of a disordered, isotropic, mobile neutral lipid aggregate, at least 17 nm in