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Sample records for cardiac triglyceride accumulation

  1. Mechanisms of intrahepatic triglyceride accumulation

    PubMed Central

    Ress, Claudia; Kaser, Susanne

    2016-01-01

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

  2. Triglycerides

    MedlinePlus

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

  3. Triglycerides

    MedlinePlus

    ... type of fat may raise the risk of coronary artery disease, especially in women. A blood test measures your triglycerides along with your cholesterol. Normal triglyceride levels are below 150. Levels above ...

  4. Early structural and metabolic cardiac remodelling in response to inducible adipose triglyceride lipase ablation

    PubMed Central

    Kienesberger, Petra C.; Pulinilkunnil, Thomas; Nagendran, Jeevan; Young, Martin E.; Bogner-Strauss, Juliane G.; Hackl, Hubert; Khadour, Rammy; Heydari, Emma; Haemmerle, Guenter; Zechner, Rudolf; Kershaw, Erin E.; Dyck, Jason R. B.

    2013-01-01

    Aims While chronic alterations in cardiac triacylglycerol (TAG) metabolism and accumulation are associated with cardiomyopathy, it is unclear whether TAG catabolizing enzymes such as adipose triglyceride lipase (ATGL) play a role in acquired cardiomyopathies. Importantly, germline deletion of ATGL leads to marked cardiac steatosis and heart failure in part through reducing peroxisome proliferator-activated receptor α (PPARα) activity and subsequent fatty acid oxidation (FAO). However, whether ATGL deficiency specifically in adult cardiomyocytes contributes to impaired PPARα activity, cardiac function, and metabolism is not known. Methods and results To study the effects of acquired cardiac ATGL deficiency on cardiac PPARα activity, function, and metabolism, we generated adult mice with tamoxifen-inducible cardiomyocyte-specific ATGL deficiency (icAtglKO). Within 4–6 weeks following ATGL ablation, icAtglKO mice had markedly increased myocardial TAG accumulation, fibrotic remodelling, and pathological hypertrophy. Echocardiographic analysis of hearts in vivo revealed that contractile function was moderately reduced in icAtglKO mice. Analysis of energy metabolism in ex vivo perfused working hearts showed diminished FAO rates which was not paralleled by markedly impaired PPARα target gene expression. Conclusions This study shows that acquired cardiomyocyte-specific ATGL deficiency in adult mice is sufficient to promote fibrotic and hypertrophic cardiomyopathy and impair myocardial FAO in the absence of markedly reduced PPARα signalling. PMID:23708736

  5. [Triglyceride deposit cardiomyovasculopathy].

    PubMed

    Hirano, Ken-Ichi

    2013-09-01

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

  6. Hypertriglyceridemic very low density lipoproteins induce triglyceride synthesis and accumulation in mouse peritoneal macrophages.

    PubMed

    Gianturco, S H; Bradley, W A; Gotto, A M; Morrisett, J D; Peavy, D L

    1982-07-01

    Triglyceride-rich lipoproteins may be responsible for the lipid accumulation in macrophages that can occur in hypertriglyceridemia. Chylomicrons and very low density lipoproteins (VLDL, total and with flotation constant [S(f)] 100-400) from fasting hypertriglyceridemic subjects induced a massive accumulation of oil red O-positive inclusions in unstimulated peritoneal macrophages. Cell viability was not affected. The predominant lipid that accumulated in cells exposed to hypertriglyceridemic VLDL was triglyceride. Hypertriglyceridemic VLDL stimulated the incorporation of [(14)C]oleate into cellular triglyceride up to ninefold in 16 h, but not into cholesteryl esters. Mass increase in cellular triglyceride was 38-fold. The stimulation of cellular triglyceride formation was dependent on time, temperature, and concentration of hypertriglyceridemic VLDL. By contrast, VLDL, low density, and high density lipoproteins from fasting normolipemic subjects had no significant effect on oleate incorporation into neutral lipids or on visible lipid accumulation.(125)I-Hypertriglyceridemic VLDL (S(f) 100-400) were degraded by macrophages in a dose-dependent manner, with 50 and 100% saturation observed at 3 and 24 mug protein/ml (2.5 and 20 nM), respectively. Hypertriglyceridemic VLDL inhibited the internalization and degradation of (125)I-hypertriglyceridemic VLDL (4 nM) by 50% at 3 nM. Cholesteryl ester-rich VLDL from cholesterol-fed rabbits gave 50% inhibition at 5 nM. Low density lipoproteins (LDL) inhibited by 10% at 5 nM and 40% at 47 nM. Acetyl LDL at 130 nM had no effect. We conclude that the massive triglyceride accumulation produced in macrophages by hypertriglyceridemic VLDL is a direct consequence of uptake via specific receptors that also recognize cholesteryl ester-rich VLDL and LDL but are distinct from the acetyl LDL receptor. Uptake of these triglyceride-rich lipoproteins by monocyte-macrophages in vivo may play a significant role in the pathophysiology of

  7. Role of the ubiquitin–proteasome system in cardiac dysfunction of adipose triglyceride lipase-deficient mice

    PubMed Central

    Mussbacher, Marion; Stessel, Heike; Wölkart, Gerald; Haemmerle, Guenter; Zechner, Rudolf; Mayer, Bernd; Schrammel, Astrid

    2014-01-01

    Systemic deletion of the gene encoding for adipose triglyceride lipase (ATGL) in mice leads to severe cardiac dysfunction due to massive accumulation of neutral lipids in cardiomyocytes. Recently, impaired peroxisome proliferator-activated receptor α (PPARα) signaling has been described to substantially contribute to the observed cardiac phenotype. Disturbances of the ubiquitin–proteasome system (UPS) have been implicated in numerous cardiac diseases including cardiomyopathy, ischemic heart disease, and heart failure. The objective of the present study was to investigate the potential role of UPS in cardiac ATGL deficiency. Our results demonstrate prominent accumulation of ubiquitinated proteins in hearts of ATGL-deficient mice, an effect that was abolished upon cardiomyocyte-directed overexpression of ATGL. In parallel, cardiac protein expression of the ubiquitin-activating enzyme E1a, which catalyzes the first step of the ubiquitination cascade, was significantly upregulated in ATGL-deficient hearts. Dysfunction of the UPS was accompanied by activation of NF-κB signaling. Moreover, the endoplasmic reticulum (ER)-resident chaperon protein disulfide isomerase was significantly upregulated in ATGL-deficient hearts. Chronic treatment of ATGL-deficient mice with the PPARα agonist Wy14,643 improved proteasomal function, prevented NF-κB activation and decreased oxidative stress. In summary, our data point to a hitherto unrecognized link between proteasomal function, PPARα signaling and cardiovascular disease. PMID:25285770

  8. Impact of Perturbed Pyruvate Metabolism on Adipocyte Triglyceride Accumulation

    PubMed Central

    Si, Yaguang; Shi, Hai; Lee, Kyongbum

    2009-01-01

    This study aimed to test the hypothesis that adipocyte TG accumulation could be altered by specifically perturbing pyruvate metabolism. We treated cultured 3T3-L1 adipocytes with chemical inhibitors of lactate dehydrogenase (LDH) and pyruvate carboxylase (PC), and characterized their global effects on intermediary metabolism using metabolic flux and isotopomer analysis. Inhibiting the enzymes over several days did not alter the adipocyte differentiation program as assessed by the expression levels of peroxisome proliferator-activated receptor-γ and glycerol-3-phosphate dehydrogenase. The main metabolic effects were to up-regulate intracellular lipolysis and decrease TG accumulation. Inhibiting PC also up-regulated glycolysis. Flux estimates indicated that the reduction in TG was due to decreased de novo fatty acid synthesis. Exogenous addition of free fatty acids dose-dependently increased the cellular TG level in the inhibitor-treated adipocytes, but not in untreated control cells. The results of this study support our hypothesis regarding the critical role of pyruvate reactions in TG synthesis. PMID:19683593

  9. 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

  10. Evaluation of inhibitory effect of phlorotannins from Ecklonia cava on triglyceride accumulation in adipocyte.

    PubMed

    Kim, Haejin; Kong, Chang-Suk; Lee, Jung Im; Kim, Hojun; Baek, Seungoh; Seo, Youngwan

    2013-09-11

    In the present study, a methanolic extract of Ecklonia cava and its solvent-partitioned fractions were evaluated for their antiadipogenic effect in 3T3-L1 adipocytes. One of them, the n-BuOH fraction, effectively reduced lipid accumulation and glucose consumption. In addition, the presence of the n-BuOH fraction in adipocytes suppressed the regulations of adipogenic transcription factors, PPARγ and SREBP1c, and adipogenic specific genes, FABP4, FABP1, FAS, LPL, HSL, and ACS1. Further purification of n-BuOH fractions led to the isolation of six phlorotannins (1-6). The six phlorotannins effectively suppressed triglyceride accumulation. Comparative analysis showed that lipid accumulation in adipocytes was dramatically attenuated in the presence of eckstolonol (4). PMID:23957842

  11. Silicon dioxide nanoparticles increase macrophage atherogenicity: Stimulation of cellular cytotoxicity, oxidative stress, and triglycerides accumulation.

    PubMed

    Petrick, Lauren; Rosenblat, Mira; Paland, Nicole; Aviram, Michael

    2016-06-01

    Nanoparticle research has focused on their toxicity in general, while increasing evidence points to additional specific adverse effects on atherosclerosis development. Arterial macrophage cholesterol and triglyceride (TG) accumulation and foam cell formation are the hallmark of early atherogenesis, leading to cardiovascular events. To investigate the in vitro atherogenic effects of silicon dioxide (SiO2 ), J774.1 cultured macrophages (murine cell line) were incubated with SiO2 nanoparticle (SP, d = 12 nm, 0-20 µg/mL), followed by cellular cytotoxicity, oxidative stress, TG and cholesterol metabolism analyses. A significant dose-dependent increase in oxidative stress (up to 164%), in cytotoxicity (up to 390% measured by lactate dehydrogenase (LDH) release), and in TG content (up to 63%) was observed in SiO2 exposed macrophages compared with control cells. A smaller increase in macrophage cholesterol mass (up to 22%) was noted. TG accumulation in macrophages was not due to a decrease in TG cell secretion or to an increased TG biosynthesis rate, but was the result of attenuated TG hydrolysis secondary to decreased lipase activity and both adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) protein expression (by 42 and 25%, respectively). Overall, SPs showed pro-atherogenic effects on macrophages as observed by cytotoxicity, increased oxidative stress and TG accumulation. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 713-723, 2016. PMID:25448404

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

    PubMed

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

    2014-01-01

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

  13. O-methylated theaflavins suppress the intracellular accumulation of triglycerides from terminally differentiated human visceral adipocytes.

    PubMed

    Tanaka, Yoshihisa; Kirita, Masanobu; Miyata, Satoshi; Abe, Yuko; Tagashira, Motoyuki; Kanda, Tomomasa; Maeda-Yamamoto, Mari

    2013-12-26

    A known O-methylated theaflavin, theaflavin 3-O-(3-O-methyl)gallate (3MeTF3G), and the new theaflavin 3-O-(3,5-di-O-methyl)gallate (3,5diMeTF3G) were synthesized via the O-methylation of theaflavin 3-O-gallate (TF3G). Both 3MeTF3G and 3,5diMeTF3G are more stable than TF3G at pH 7.5 in the order 3,5diMeTF3G > 3MeTF3G > TF3G. The inhibitory effects of these compounds on the intracellular accumulation of triglycerides from terminally differentiated human visceral adipocytes were investigated. Compound 3MeTF3G exhibited an inhibitory effect similar to that of TF3G at 3 μM and a slightly lower effect than that of TF3G at 10 μM. The result suggested that the degradants and oxidatively polymerized products of TF3G may also have inhibitory effects. For cells treated with 3,5diMeTF3G at 3 and 10 μM, intracellular triglyceride accumulation was dose dependent and significantly lower compared with that for other compounds. It was suggested that the higher effect of 3,5diMeTF3G was due to its higher stability and likely improved absorption owing to di-O-methylation. PMID:24308363

  14. 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

  15. 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

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

    SciTech Connect

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

    1990-03-01

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

  17. A new hexacyclic triterpene acid from the roots of Euscaphis japonica and its inhibitory activity on triglyceride accumulation.

    PubMed

    Li, Yan-Ci; Tian, Ke; Sun, Li-Juan; Long, Hui; Li, Lu-Jun; Wu, Zheng-Zhi

    2016-03-01

    A new taraxerene-type hexacyclic triterpene acid named (12R,13S)-3-methoxy-12,13-cyclo-taraxerene-2,14-diene-1-one-28-oic acid (1), together with a known compound 3,7-dihydroxy-5-octanolide (2), was isolated from the roots of Euscaphis japonica. The structure of new compound 1 was elucidated on the basis of NMR, HR-ESIMS and X-ray diffraction analysis. It showed promising inhibitory activity on oleic acid induced triglyceride accumulation on HepG2 cells. PMID:26828452

  18. A lipasin/Angptl8 monoclonal antibody lowers mouse serum triglycerides involving increased postprandial activity of the cardiac lipoprotein lipase

    PubMed Central

    Fu, Zhiyao; Abou-Samra, Abdul B.; Zhang, Ren

    2015-01-01

    Lipasin/Angptl8 is a feeding-induced hepatokine that regulates triglyceride (TAG) metabolism; its therapeutical potential, mechanism of action, and relation to the lipoprotein lipase (LPL), however, remain elusive. We generated five monoclonal lipasin antibodies, among which one lowered the serum TAG level when injected into mice, and the epitope was determined to be EIQVEE. Lipasin-deficient mice exhibited elevated postprandial activity of LPL in the heart and skeletal muscle, but not in white adipose tissue (WAT), suggesting that lipasin suppresses the activity of LPL specifically in cardiac and skeletal muscles. Consistently, mice injected with the effective antibody or with lipasin deficiency had increased postprandial cardiac LPL activity and lower TAG levels only in the fed state. These results suggest that lipasin acts, at least in part, in an endocrine manner. We propose the following model: feeding induces lipasin, activating the lipasin-Angptl3 pathway, which inhibits LPL in cardiac and skeletal muscles to direct circulating TAG to WAT for storage; conversely, fasting induces Angptl4, which inhibits LPL in WAT to direct circulating TAG to cardiac and skeletal muscles for oxidation. This model suggests a general mechanism by which TAG trafficking is coordinated by lipasin, Angptl3 and Angptl4 at different nutritional statuses. PMID:26687026

  19. Limited feeding of potassium nitrate for intracellular lipid and triglyceride accumulation of Nannochloris sp. UTEX LB1999.

    PubMed

    Takagi, M; Watanabe, K; Yamaberi, K; Yoshida, T

    2000-07-01

    Limited feeding of nitrate during culture of Nannochloris sp. UTEX LB1999 for intracellular lipid and triglyceride accumulation was investigated with the aim of obtaining cells superior for liquefaction into a fuel oil. The intracellular lipid contents and the percentage of triglycerides in the lipids of cells grown in a nitrogen-limited medium (0.9 mM KNO3) were 1.3 times as high as those grown in a modified NORO medium containing 2.0-9.9 mM KNO3. However, the cell concentration was too low for the practical production of fuel oil by high-pressure liquefaction of the cell mass. A single feeding of 0.9 mM nitrate after nitrate depletion during cultivation in a nitrate-limited medium increased the cell concentration to twice that obtained without such feeding, and the lipid content was maintained at a high level. The timing of nitrate feeding, i.e., whether it was given during the log phase (before nitrate depletion), the constant growth phase (just after the depletion), or the stationary phase (after the depletion), had negligible effect on the intracellular lipid content and percentage of triglycerides in the lipids. When 0.9 mM nitrate was intermittently fed ten times during the log phase in addition to the initial nitrate feed (0.9 mM), the cell concentration reached almost the same (2.16 g/l) and the intracellular lipid content and the percentage of triglycerides in the lipids increased from 31.0 to 50.9% and 26.0 to 47.6%, respectively, compared with those of cells cultured in a modified NORO medium containing 9.9 mM KNO3 without additional nitrate feeding. PMID:10952013

  20. Cyclic GMP signaling in cardiomyocytes modulates fatty acid trafficking and prevents triglyceride accumulation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    While the balance between carbohydrates and fatty acids for energy production appears to be crucial for cardiac homeostasis, much remains to be learned about the molecular mechanisms underlying this relationship. Given the reported benefits of cGMP signaling on the myocardium, we investigated the im...

  1. Enhanced acetyl-CoA production is associated with increased triglyceride accumulation in the green alga Chlorella desiccata

    PubMed Central

    Avidan, Omri; Brandis, Alexander; Rogachev, Ilana; Pick, Uri

    2015-01-01

    Triglycerides (TAGs) from microalgae can be utilized as food supplements and for biodiesel production, but little is known about the regulation of their biosynthesis. This work aimed to test the relationship between acetyl-CoA (Ac-CoA) levels and TAG biosynthesis in green algae under nitrogen deprivation. A novel, highly sensitive liquid chromatography mass spectrometry (LC-MS/MS) technique enabled us to determine the levels of Ac-CoA, malonyl-CoA, and unacetylated (free) CoA in green microalgae. A comparative study of three algal species that differ in TAG accumulation levels shows that during N starvation, Ac-CoA levels rapidly rise, preceding TAG accumulation in all tested species. The levels of Ac-CoA in the high TAG accumulator Chlorella desiccata exceed the levels in the moderate TAG accumulators Dunaliella tertiolecta and Chlamydomonas reinhardtii. Similarly, malonyl-CoA and free CoA levels also increase, but to lower extents. Calculated cellular concentrations of Ac-CoA are far lower than reported K mAc-CoA values of plastidic Ac-CoA carboxylase (ptACCase) in plants. Transcript level analysis of plastidic pyruvate dehydrogenase (ptPDH), the major chloroplastic Ac-CoA producer, revealed rapid induction in parallel with Ac-CoA accumulation in C. desiccata, but not in D. tertiolecta or C. reinhardtii. It is proposed that the capacity to accumulate high TAG levels in green algae critically depends on their ability to divert carbon flow towards Ac-CoA. This requires elevation of the chloroplastic CoA pool level and enhancement of Ac-CoA biosynthesis. These conclusions may have important implications for future genetic manipulation to enhance TAG biosynthesis in green algae. PMID:25922486

  2. Enhanced acetyl-CoA production is associated with increased triglyceride accumulation in the green alga Chlorella desiccata.

    PubMed

    Avidan, Omri; Brandis, Alexander; Rogachev, Ilana; Pick, Uri

    2015-07-01

    Triglycerides (TAGs) from microalgae can be utilized as food supplements and for biodiesel production, but little is known about the regulation of their biosynthesis. This work aimed to test the relationship between acetyl-CoA (Ac-CoA) levels and TAG biosynthesis in green algae under nitrogen deprivation. A novel, highly sensitive liquid chromatography mass spectrometry (LC-MS/MS) technique enabled us to determine the levels of Ac-CoA, malonyl-CoA, and unacetylated (free) CoA in green microalgae. A comparative study of three algal species that differ in TAG accumulation levels shows that during N starvation, Ac-CoA levels rapidly rise, preceding TAG accumulation in all tested species. The levels of Ac-CoA in the high TAG accumulator Chlorella desiccata exceed the levels in the moderate TAG accumulators Dunaliella tertiolecta and Chlamydomonas reinhardtii. Similarly, malonyl-CoA and free CoA levels also increase, but to lower extents. Calculated cellular concentrations of Ac-CoA are far lower than reported K mAc-CoA values of plastidic Ac-CoA carboxylase (ptACCase) in plants. Transcript level analysis of plastidic pyruvate dehydrogenase (ptPDH), the major chloroplastic Ac-CoA producer, revealed rapid induction in parallel with Ac-CoA accumulation in C. desiccata, but not in D. tertiolecta or C. reinhardtii. It is proposed that the capacity to accumulate high TAG levels in green algae critically depends on their ability to divert carbon flow towards Ac-CoA. This requires elevation of the chloroplastic CoA pool level and enhancement of Ac-CoA biosynthesis. These conclusions may have important implications for future genetic manipulation to enhance TAG biosynthesis in green algae. PMID:25922486

  3. Transient hypoxia reprograms differentiating adipocytes for enhanced insulin sensitivity and triglyceride accumulation

    PubMed Central

    Lu, Hongyun; Gao, Zhanguo; Zhao, Zhiyun; Weng, Jianping; Ye, Jianping

    2015-01-01

    Objective To investigate the impact of transient (2-4 h) hypoxia on metabolic reprogramming of adipocytes. Methods The impact of transient hypoxia on metabolic reprogramming was investigated in 3T3-L1 cells before and after differentiation. Glucose uptake, fatty acid oxidation, lipolysis, and mitochondria were examined to determine the hypoxia effects. Preadipocytes were exposed to transient hypoxia (4h/day) in the course of differentiation. Insulin sensitivity and TG accumulation was examined in the cells at the end of differentiation to determine the reprogramming effects. AMPK activity and gene expression were determined by quantitative RT-PCR and Western blotting in search for mechanism of the reprogramming. Results In acute response to hypoxia, adipocytes exhibited an increase in insulin-dependent and -independent glucose uptake. Fatty acid β-oxidation and pyruvate dehydrogenase (PDH) activity were decreased. Multiple exposures of differentiating adipocytes to transient hypoxia enhanced insulin signaling, TG accumulation, expression of antioxidant genes in differentiated adipocytes in the absence of hypoxia. The metabolic memory was associated with elevated AMPK activity and gene expression (GLUT1, PGC-1α, PPARγ, SREBP, NRF-1, ESRRα, LPL). The enhanced insulin sensitivity was blocked by an AMPK inhibitor. Conclusions Repeated exposure of differentiating adipocytes to transient hypoxia is able to reprogram the cells for increased TG accumulation and enhanced insulin sensitivity. The metabolic alterations were observed in post-differentiated cells under normoxia. The reprogramming involves AMPK activation and gene expression in the metabolic pathways in cytosol and mitochondria. PMID:26219415

  4. Exercise-induced lactate accumulation regulates intramuscular triglyceride metabolism via transforming growth factor-β1 mediated pathways.

    PubMed

    Nikooie, Rohollah; Samaneh, Sajadian

    2016-01-01

    The mechanism regulating the utilization of intramuscular triacylglycerol (IMTG) during high-intensity interval training (HIIT) and post-exercise recovery period remains elusive. In this study, the acute and long-term effects of HIIT on transforming growth factor beta 1 (TGF-β1) abundance in rat skeletal muscle and role of lactate and TGF-β1 in IMTG lipolysis during post-exercise recovery period were examined. TGF-β1 and Adipose triacylglycerol lipase (ATGL) abundance as well as total lipase activity in the gastrocnemius muscle significantly increased to a maximum value 10 h after acute bout of HIIT. Inhibition of TGF-β1 signaling by intramuscular injection of SB431542 30 min prior to the acute exercise attenuated ATGL abundance and total lipase activity in the gastrocnemius muscle in response to acute exercise. Intramuscular acute injection of lactate increased TGF-β1 and ATGL abundance in the gastrocnemius muscle and there were a significant increase in Muscle TGF-β1 and ATGL abundance after 5 weeks of HIIT/lactate treatment. These results indicate that exercise-induced lactate accumulation regulates intramuscular triglyceride metabolism via transforming growth factor-β1 mediated pathways during post-exercise recovery from strenuous exercise. PMID:26522131

  5. Triglyceride level

    MedlinePlus

    ... may also cause swelling of your pancreas (called pancreatitis). The triglyceride level is usually included in a ... lower triglyceride levels may be used to prevent pancreatitis for levels above 500 mg/dL Low triglyceride ...

  6. 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

  7. Regulation of G0/G1 Switch Gene 2 (G0S2) Protein Ubiquitination and Stability by Triglyceride Accumulation and ATGL Interaction

    PubMed Central

    Heckmann, Bradlee L.; Zhang, Xiaodong; Saarinen, Alicia M.; Liu, Jun

    2016-01-01

    Intracellular triglyceride (TG) hydrolysis or lipolysis is catalyzed by the key intracellular triglyceride hydrolase, adipose triglyceride lipase (ATGL). The G0/G1 Switch Gene 2 (G0S2) was recently identified as the major selective inhibitor of ATGL and its hydrolase function. Since G0S2 levels are dynamically linked and rapidly responsive to nutrient status or metabolic requirements, the identification of its regulation at the protein level is of significant value. Earlier evidence from our laboratory demonstrated that G0S2 is a short-lived protein degraded through the proteasomal pathway. However, little is currently known regarding the underlying mechanisms. In the current study we find that 1) protein degradation is initiated by K48-linked polyubiquitination of the lysine- 25 in G0S2; and 2) G0S2 protein is stabilized in response to ATGL expression and TG accumulation. Mutation of lysine-25 of G0S2 abolished ubiquitination and increased protein stability. More importantly, G0S2 was stabilized via different mechanisms in the presence of ATGL vs. in response to fatty acid (FA)-induced TG accumulation. Furthermore, G0S2 protein but not mRNA levels were reduced in the adipose tissue of ATGL-deficient mice, corroborating the involvement of ATGL in the stabilization of G0S2. Taken together our data illustrate for the first time a crucial multifaceted mechanism for the stabilization of G0S2 at the protein level. PMID:27248498

  8. Triglycerides Test

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Triglycerides Share this page: Was this page helpful? Also known as: TG; TRIG Formal name: Triglycerides Related tests: Cholesterol ; HDL Cholesterol ; LDL Cholesterol ; Direct ...

  9. Triglyceride level

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003493.htm Triglyceride level To use the sharing features on this page, please enable JavaScript. The triglyceride level is a blood test to measure the amount ...

  10. The activity of microsomal triglyceride transfer protein is essential for accumulation of triglyceride within microsomes in McA-RH7777 cells. A unified model for the assembly of very low density lipoproteins.

    PubMed

    Wang, Y; Tran, K; Yao, Z

    1999-09-24

    Previously, based on distinct requirement of microsomal triglyceride transfer protein (MTP) and kinetics of triglyceride (TG) utilization, we concluded that assembly of very low density lipoproteins (VLDL) containing B48 or B100 was achieved through different paths (Wang, Y. , McLeod, R. S., and Yao, Z. (1997) J. Biol. Chem. 272, 12272-12278). To test if the apparent dual mechanisms were accounted for by apolipoprotein B (apoB) length, we studied VLDL assembly using transfected cells expressing various apoB forms (e.g. B64, B72, B80, and B100). For each apoB, enlargement of lipoprotein to form VLDL via bulk TG incorporation was induced by exogenous oleate, which could be blocked by MTP inhibitor BMS-197636 treatment. While particle enlargement was readily demonstrable by density ultracentrifugation for B64- and B72-VLDL, it was not obvious for B80- and B100-VLDL unless the VLDL was further resolved by cumulative rate flotation into VLDL(1) (S(f) > 100) and VLDL(2) (S(f) 20-100). BMS-197636 diminished B100 secretion in a dose-dependent manner (0.05-0.5 microM) and also blocked the particle enlargement from small to large B100-lipoproteins. These results yield a unified model that can accommodate VLDL assembly with all apoB forms, which invalidates our previous conclusion. To gain a better understanding of the MTP action, we examined the effect of BMS-197636 on lipid and apoB synthesis during VLDL assembly. While BMS-197636 (0.2 microM) entirely abolished B100-VLDL(1) assembly/secretion, it did not affect B100 translation or translocation across the microsomal membrane, nor did it affect TG synthesis and cell TG mass. However, BMS-197636 drastically decreased accumulation of [(3)H]glycerol-labeled TG and TG mass within microsomal lumen. The decreased TG accumulation was not a result of impaired B100-VLDL assembly, because in cells treated with brefeldin A (0.2 microgram/ml), the assembly of B100-VLDL was blocked yet lumenal TG accumulation was normal. Thus, MTP plays

  11. The Mammalian “Obesogen” Tributyltin Targets Hepatic Triglyceride Accumulation and the Transcriptional Regulation of Lipid Metabolism in the Liver and Brain of Zebrafish

    PubMed Central

    Lyssimachou, Angeliki; Santos, Joana G.; André, Ana; Soares, Joana; Lima, Daniela; Guimarães, Laura; Almeida, C. Marisa R.; Teixeira, Catarina; Castro, L. Filipe C.; Santos, Miguel M.

    2015-01-01

    Recent findings indicate that different Endocrine Disrupting Chemicals (EDCs) interfere with lipid metabolic pathways in mammals and promote fat accumulation, a previously unknown site of action for these compounds. The antifoulant and environmental pollutant tributyltin (TBT), which causes imposex in gastropod snails, induces an “obesogenic” phenotype in mammals, through the activation of the nuclear receptors retinoid X receptor (RXR) and peroxisome proliferator-activated receptor gamma (PPARγ). In teleosts, the effects of TBT on the lipid metabolism are poorly understood, particularly following exposure to low, environmental concentrations. In this context, the present work shows that exposure of zebrafish to 10 and 50 ng/L of TBT (as Sn) from pre-hatch to 9 months of age alters the body weight, condition factor, hepatosomatic index and hepatic triglycerides in a gender and dose related manner. Furthermore, TBT modulated the transcription of key lipid regulating factors and enzymes involved in adipogenesis, lipogenesis, glucocorticoid metabolism, growth and development in the brain and liver of exposed fish, revealing sexual dimorphic effects in the latter. Overall, the present study shows that the model mammalian obesogen TBT interferes with triglyceride accumulation and the transcriptional regulation of lipid metabolism in zebrafish and indentifies the brain lipogenic transcription profile of fish as a new target of this compound. PMID:26633012

  12. Targeting acid sphingomyelinase reduces cardiac ceramide accumulation in the post-ischemic heart.

    PubMed

    Klevstig, Martina; Ståhlman, Marcus; Lundqvist, Annika; Scharin Täng, Margareta; Fogelstrand, Per; Adiels, Martin; Andersson, Linda; Kolesnick, Richard; Jeppsson, Anders; Borén, Jan; Levin, Malin C

    2016-04-01

    Ceramide accumulation is known to accompany acute myocardial ischemia, but its role in the pathogenesis of ischemic heart disease is unclear. In this study, we aimed to determine how ceramides accumulate in the ischemic heart and to determine if cardiac function following ischemia can be improved by reducing ceramide accumulation. To investigate the association between ceramide accumulation and heart function, we analyzed myocardial left ventricle biopsies from subjects with chronic ischemia and found that ceramide levels were higher in biopsies from subjects with reduced heart function. Ceramides are produced by either de novo synthesis or hydrolysis of sphingomyelin catalyzed by acid and/or neutral sphingomyelinase. We used cultured HL-1 cardiomyocytes to investigate these pathways and showed that acid sphingomyelinase activity rather than neutral sphingomyelinase activity or de novo sphingolipid synthesis was important for hypoxia-induced ceramide accumulation. We also used mice with a partial deficiency in acid sphingomyelinase (Smpd1(+/-) mice) to investigate if limiting ceramide accumulation under ischemic conditions would have a beneficial effect on heart function and survival. Although we showed that cardiac ceramide accumulation was reduced in Smpd1(+/-) mice 24h after an induced myocardial infarction, this reduction was not accompanied by an improvement in heart function or survival. Our findings show that accumulation of cardiac ceramides in the post-ischemic heart is mediated by acid sphingomyelinase. However, targeting ceramide accumulation in the ischemic heart may not be a beneficial treatment strategy. PMID:26930027

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

    PubMed

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

    2016-04-01

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

  14. The Associations Between Smoking Habits and Serum Triglyceride or Hemoglobin A1c Levels Differ According to Visceral Fat Accumulation

    PubMed Central

    Koda, Michiko; Kitamura, Itsuko; Okura, Tomohiro; Otsuka, Rei; Ando, Fujiko; Shimokata, Hiroshi

    2016-01-01

    Background Whether smokers and former smokers have worse lipid profiles or glucose levels than non-smokers remains unclear. Methods The subjects were 1152 Japanese males aged 42 to 81 years. The subjects were divided according to their smoking habits (nonsmokers, former smokers, and current smokers) and their visceral fat area (VFA) (<100 cm2 and ≥100 cm2). Results The serum triglyceride (TG) levels of 835 males were assessed. In the VFA ≥100 cm2 group, a significantly greater proportion of current smokers (47.3%) exhibited TG levels of ≥150 mg/dL compared with former smokers (36.4%) and non-smokers (18.8%). The difference in TG level distribution between former smokers and non-smokers was also significant. However, among the subjects with VFA of <100 cm2, the TG levels of the three smoking habit groups did not differ. The serum hemoglobin A1c (HbA1c) levels of 877 males were also assessed. In the VFA <100 cm2 group, significantly higher proportions of current smokers (17.9%) and former smokers (14.9%) demonstrated HbA1c levels of ≥5.6% compared with non-smokers (6.3%). In contrast, in the VFA ≥100 cm2 group, significantly fewer former smokers displayed HbA1c levels of ≥5.6% compared with non-smokers and current smokers. Furthermore, the interaction between smoking habits and VFA was associated with the subjects’ TG and HbA1c concentrations, and the associations of TG and HbA1c concentrations and smoking habits varied according to VFA. Conclusions Both smoking habits and VFA exhibited associations with TG and HbA1c concentrations. The associations between smoking habits and these parameters differed according to VFA. PMID:26616395

  15. Resolvin D1 reduces ER stress-induced apoptosis and triglyceride accumulation through JNK pathway in HepG2 cells.

    PubMed

    Jung, Tae Woo; Hwang, Hwan-Jin; Hong, Ho Cheol; Choi, Hae Yoon; Yoo, Hye Jin; Baik, Sei Hyun; Choi, Kyung Mook

    2014-06-25

    Research has indicated that stress on the endoplasmic reticulum (ER) of a cell affects the pathogenesis of metabolic disorders such as obesity, type 2 diabetes mellitus, and non-alcoholic fatty liver disease (NAFLD). Resolvins, a novel family derived from ω-3 polyunsaturated fatty acids, have anti-inflammatory and insulin sensitizing properties, and it has been suggested that they play a role in the amelioration of obesity-related metabolic dysfunctions. This study showed that pretreatment with resolvin D1 (RvD1) attenuated ER stress-induced apoptosis and also decreased caspase 3 activity in HepG2 cells. Furthermore, RvD1 significantly decreased tunicamycin-induced triglycerides accumulation as well as SREBP-1 expression. However, tunicamycin-induced ER stress markers were not significantly affected by RvD1 treatment. Moreover, RvD1 treatment did not affect the tunicamycin-induced expression of chaperones that assist protein folding in the ER. These results suggest that RvD1-conferred cellular protection may occur downstream of the ER stress. This was supported by the finding that RvD1 significantly inhibited tunicamycin-induced c-Jun N-terminal kinase (JNK) expression, although P38 and ERK1/2 phosphorylation were not affected. In addition, anisomycin, a JNK activator, increased caspase 3 activity and apoptosis as well as triglycerides accumulation and SREBP1 expression, and RvD1 treatment reversed these changes. In conclusion, RvD1 attenuated ER stress-induced hepatic steatosis and apoptosis via the JNK-mediated pathway. This study may provide insight into a novel underlying mechanism and a strategy for treating NAFLD. PMID:24784707

  16. Role of Endothelial AADC in Cardiac Synthesis of Serotonin and Nitrates Accumulation

    PubMed Central

    Rouzaud-Laborde, Charlotte; Hanoun, Naïma; Baysal, Ipek; Rech, Jean-Simon; Mias, Céline; Calise, Denis; Sicard, Pierre; Frugier, Céline; Seguelas, Marie-Helène; Parini, Angelo; Pizzinat, Nathalie

    2012-01-01

    Serotonin (5-HT) regulates different cardiac functions by acting directly on cardiomyocytes, fibroblasts and endothelial cells. Today, it is widely accepted that activated platelets represent a major source of 5-HT. In contrast, a supposed production of 5-HT in the heart is still controversial. To address this issue, we investigated the expression and localization of 5-HT synthesizing enzyme tryptophan hydroxylase (TPH) and L-aromatic amino acid decarboxylase (AADC) in the heart. We also evaluated their involvement in cardiac production of 5-HT. TPH1 was weakly expressed in mouse and rat heart and appeared restricted to mast cells. Degranulation of mast cells by compound 48/80 did not modify 5-HT cardiac content in mice. Western blots and immunolabelling experiments showed an abundant expression of AADC in the mouse and rat heart and its co-localization with endothelial cells. Incubation of cardiac homogenate with the AADC substrate (5-hydroxy-L-tryptophan) 5-HTP or intraperitoneal injection of 5-HTP in mice significantly increased cardiac 5-HT. These effects were prevented by the AADC inhibitor benserazide. Finally, 5-HTP administration in mice increased phosphorylation of aortic nitric oxide synthase 3 at Ser (1177) as well as accumulation of nitrates in cardiac tissue. This suggests that the increase in 5-HT production by AADC leads to activation of endothelial and cardiac nitric oxide pathway. These data show that endothelial AADC plays an important role in cardiac synthesis of 5-HT and possibly in 5-HT-dependent regulation of nitric oxide generation. PMID:22829864

  17. Role of endothelial AADC in cardiac synthesis of serotonin and nitrates accumulation.

    PubMed

    Rouzaud-Laborde, Charlotte; Hanoun, Naïma; Baysal, Ipek; Rech, Jean-Simon; Mias, Céline; Calise, Denis; Sicard, Pierre; Frugier, Céline; Seguelas, Marie-Helène; Parini, Angelo; Pizzinat, Nathalie

    2012-01-01

    Serotonin (5-HT) regulates different cardiac functions by acting directly on cardiomyocytes, fibroblasts and endothelial cells. Today, it is widely accepted that activated platelets represent a major source of 5-HT. In contrast, a supposed production of 5-HT in the heart is still controversial. To address this issue, we investigated the expression and localization of 5-HT synthesizing enzyme tryptophan hydroxylase (TPH) and L-aromatic amino acid decarboxylase (AADC) in the heart. We also evaluated their involvement in cardiac production of 5-HT. TPH1 was weakly expressed in mouse and rat heart and appeared restricted to mast cells. Degranulation of mast cells by compound 48/80 did not modify 5-HT cardiac content in mice. Western blots and immunolabelling experiments showed an abundant expression of AADC in the mouse and rat heart and its co-localization with endothelial cells. Incubation of cardiac homogenate with the AADC substrate (5-hydroxy-L-tryptophan) 5-HTP or intraperitoneal injection of 5-HTP in mice significantly increased cardiac 5-HT. These effects were prevented by the AADC inhibitor benserazide. Finally, 5-HTP administration in mice increased phosphorylation of aortic nitric oxide synthase 3 at Ser (1177) as well as accumulation of nitrates in cardiac tissue. This suggests that the increase in 5-HT production by AADC leads to activation of endothelial and cardiac nitric oxide pathway. These data show that endothelial AADC plays an important role in cardiac synthesis of 5-HT and possibly in 5-HT-dependent regulation of nitric oxide generation. PMID:22829864

  18. Consumption of sucrose from infancy increases the visceral fat accumulation, concentration of triglycerides, insulin and leptin, and generates abnormalities in the adrenal gland.

    PubMed

    Díaz-Aguila, Yadira; Castelán, Francisco; Cuevas, Estela; Zambrano, Elena; Martínez-Gómez, Margarita; Muñoz, Alvaro; Rodríguez-Antolín, Jorge; Nicolás-Toledo, Leticia

    2016-03-01

    Consumption of sugar-sweetened beverages promotes the development of metabolic syndrome (MetS) and type 2 diabetes mellitus in humans. One factor related to the appearance of MetS components is the dysfunction of the adrenal gland. In fact, the experimental generation of hyperglycemia has been associated with morphological and microvascular changes in the adrenal glands of rats. We hypothesized that high sucrose consumption from infancy promotes histological disruption of the adrenal glands associated with the appearance of metabolic syndrome indicators. Male Wistar rats were separated at weaning (21 days old) into two groups: free access to tap water (control group, C) or 30 % sucrose diluted in water (sugar-fed group). After 12 weeks, high sucrose consumption promoted an increase in visceral fat accumulation, adipose cell number, and insulin resistance. Also, a rise in the concentration of triglycerides, very low-density lipoprotein, insulin and leptin was observed. In control rats, a histomorphometric asymmetry between the right and left adrenal glands was found. In the sugar-fed group, sucrose consumption produced a major change in adrenal gland asymmetry. No changes in corticosterone serum level were observed in either group. Our results suggest that a high sucrose liquid-diet from early life alters the morphology of adrenocortical zones, leading to MetS indicators. PMID:25834995

  19. The Relationship of Ectopic Lipid Accumulation to Cardiac and Vascular Function in Obesity and Metabolic Syndrome

    PubMed Central

    Ruberg, Frederick L.; Chen, Zhongjing; Hua, Ning; Bigornia, Sherman; Guo, Zifang; Hallock, Kevin; Jara, Hernan; LaValley, Michael; Phinikaridou, Alkystis; Qiao, Ye; Viereck, Jason; Apovian, Caroline M.; Hamilton, James A.

    2010-01-01

    Storage of lipid in ectopic depots outside of abdominal visceral and subcutaneous stores, including within the pericardium and liver, has been associated with obesity, insulin resistance, and cardiovascular risk. We sought to determine whether anatomically distinct ectopic depots were physiologically correlated and site-specific effects upon cardiovascular function could be identified. Obese subjects (n = 28) with metabolic syndrome but without known atherosclerotic disease and healthy controls (n = 18) underwent magnetic resonance imaging (MRI) and proton MR spectroscopy (MRS) to quantify pericardial and periaortic lipid volumes, cardiac function, aortic compliance, and intrahepatic lipid content. Fasting plasma lipoproteins, glucose, insulin, and free-fatty acids were measured. Pericardial and intrahepatic (P < 0.01) and periaortic (P < 0.05) lipid volumes were increased in obese subjects vs. controls and were strongly and positively correlated (P ≤ 0.01) but independent of BMI (P = NS) among obese subjects. Intrahepatic lipid was associated with insulin resistance (P < 0.01) and triglycerides (P < 0.05), whereas pericardial and periaortic lipid were not (P = NS). Periaortic and pericardial lipid positively correlated to free-fatty acids (P ≤ 0.01) and negatively correlated to high-density lipoprotein (HDL) cholesterol (P < 0.05). Pericardial lipid negatively correlated to cardiac output (P = 0.03) and stroke volume (P = 0.01) but not to left ventricular ejection fraction (P = 0.46). None of the ectopic depots correlated to aortic compliance. In conclusion, ectopic storage of lipid in anatomically distinct depots appeared tightly correlated but independent of body size. Site-specific functional abnormalities were observed for pericardial but not periaortic lipid. These findings underscore the utility of MRI to assess individual differences in ectopic lipid that are not predictable from BMI. PMID:19875992

  20. Inactivation of Plin4 downregulates Plin5 and reduces cardiac lipid accumulation in mice.

    PubMed

    Chen, Weiqin; Chang, Benny; Wu, Xinyu; Li, Lan; Sleeman, Mark; Chan, Lawrence

    2013-04-01

    Plin4 is a lipid droplet protein (LDP) found predominantly in white adipose tissue (WAT). The Plin4 gene is immediately downstream of the Plin5 gene; the two genes exhibit distinct though overlapping tissue expression patterns. Plin4 is absent in brown adipose tissue (BAT) and liver and expressed at low levels in heart and skeletal muscle, whereas Plin5 is highly expressed in these oxidative tissues but at a low level in WAT. The physiological role of Plin4 remains unclear. We have generated Plin4(-/-) mice by gene targeting. Loss of Plin4 has no effect on body weight or composition or on adipose mass or development. However, the triacylglycerol (TAG) content in heart, but not other oxidative tissues such as BAT, soleus muscle, and liver, is markedly reduced in Plin4(-/-) mice. The heart of Plin4(-/-) mice displays reduced Plin5 mRNA and protein levels (by ~38 and 87%, respectively, vs. wild-type) but unchanged mRNA levels of other perilipin family genes (Plin2 and Plin3) or genes involved in glucose and lipid metabolism. Despite reduced cardiac TAG level, both young and aged Plin4(-/-) mice maintain normal heart function as wild-type mice, as measured by echocardiography. Interestingly, Plin4 deficiency prevents the lipid accumulation in the heart that normally occurs after a prolonged (48-h) fast. It also protects the heart from cardiac steatosis induced by high-fat diet or when Plin4(-/-) mice are bred into Lep(-/-) obese background. In conclusion, inactivation of Plin4 downregulates Plin5 and reduces cardiac lipid accumulation in mice. PMID:23423172

  1. β3 Integrin in Cardiac Fibroblast Is Critical for Extracellular Matrix Accumulation during Pressure Overload Hypertrophy in Mouse

    PubMed Central

    Balasubramanian, Sundaravadivel; Quinones, Lakeya; Kasiganesan, Harinath; Zhang, Yuhua; Pleasant, Dorea L.; Sundararaj, Kamala P.; Zile, Michael R.; Bradshaw, Amy D.; Kuppuswamy, Dhandapani

    2012-01-01

    The adhesion receptor β3 integrin regulates diverse cellular functions in various tissues. As β3 integrin has been implicated in extracellular matrix (ECM) remodeling, we sought to explore the role of β3 integrin in cardiac fibrosis by using wild type (WT) and β3 integrin null (β3−/−) mice for in vivo pressure overload (PO) and in vitro primary cardiac fibroblast phenotypic studies. Compared to WT mice, β3−/− mice upon pressure overload hypertrophy for 4 wk by transverse aortic constriction (TAC) showed a substantially reduced accumulation of interstitial fibronectin and collagen. Moreover, pressure overloaded LV from β3−/− mice exhibited reduced levels of both fibroblast proliferation and fibroblast-specific protein-1 (FSP1) expression in early time points of PO. To test if the observed impairment of ECM accumulation in β3−/− mice was due to compromised cardiac fibroblast function, we analyzed primary cardiac fibroblasts from WT and β3−/− mice for adhesion to ECM proteins, cell spreading, proliferation, and migration in response to platelet derived growth factor-BB (PDGF, a growth factor known to promote fibrosis) stimulation. Our results showed that β3−/− cardiac fibroblasts exhibited a significant reduction in cell-matrix adhesion, cell spreading, proliferation and migration. In addition, the activation of PDGF receptor associated tyrosine kinase and non-receptor tyrosine kinase Pyk2, upon PDGF stimulation were impaired in β3−/− cells. Adenoviral expression of a dominant negative form of Pyk2 (Y402F) resulted in reduced accumulation of fibronectin. These results indicate that β3 integrin-mediated Pyk2 signaling in cardiac fibroblasts plays a critical role in PO-induced cardiac fibrosis. PMID:22984613

  2. Fatty Heart, Cardiac Damage, and Inflammation

    PubMed Central

    Guzzardi, Maria A.; Iozzo, Patricia

    2011-01-01

    Type 2 diabetes and obesity are associated with systemic inflammation, generalized enlargement of fat depots, and uncontrolled release of fatty acids (FA) into the circulation. These features support the occurrence of cardiac adiposity, which is characterized by an increase in intramyocardial triglyceride content and an enlargement of the volume of fat surrounding the heart and vessels. Both events may initially serve as protective mechanisms to portion energy, but their excessive expansion can lead to myocardial damage and heart disease. FA overload promotes FA oxidation and the accumulation of triglycerides and metabolic intermediates, which can impair calcium signaling, β-oxidation, and glucose utilization. This leads to damaged mitochondrial function and increased production of reactive oxygen species, pro-apoptotic, and inflammatory molecules, and finally to myocardial inflammation and dysfunction. Triglyceride accumulation is associated with left ventricular hypertrophy and dysfunction. The enlargement of epicardial fat in patients with metabolic disorders, and coronary artery disease, is associated with the release of proinflammatory and proatherogenic cytokines to the subtending tissues. In this review, we examine the evidence supporting a causal relationship linking FA overload and cardiac dysfunction. Also, we disentangle the separate roles of FA oxidation and triglyceride accumulation in causing cardiac damage. Finally, we focus on the mechanisms of inflammation development in the fatty heart, before summarizing the available evidence in humans. Current literature confirms the dual (protective and detrimental) role of cardiac fat, and suggests prospective studies to establish the pathogenetic (when and how) and possible prognostic value of this potential biomarker in humans. PMID:22262077

  3. Triglyceride Metabolism and Hepatic Diseases.

    PubMed

    Fernandez-Mejia, Emptyyn Y

    2013-09-11

    Triglycerides participate in key metabolic functions such as energy storage, thermal insulation and as deposit for essential and non-essential fatty acids that can be used as precursors for the synthesis of structural and functional phospholipids. The liver is a central organ in the regulation of triglyceride metabolism, and it participates in triglyceride synthesis, export, uptake and oxidation. The metabolic syndrome and associated diseases are among the main concerns of public health worldwide. One of the metabolic syndrome components is impaired triglyceride metabolism. Diseases associated with the metabolic syndrome promote the appearance of hepatic alterations e.g., non-alcoholic steatosis, steatohepatitis, fibrosis, cirrhosis and cancer. In this article, we review the molecular actions involved in impaired triglyceride metabolism and its association with hepatic diseases. We discuss mechanisms that reconcile the chronic inflammation and insulin resistance, and new concepts on the role of intestinal micro-flora permeability and proliferation in fatty liver etiology. We also describe the participation of oxidative stress in the progression of events leading from steatosis to steatohepatitis and fibrosis. Finally, we provide information regarding the mechanisms that link fatty acid accumulation during steatosis with changes in growth factors and cytokines that lead to the development of neoplasticcells. One of the main medical concerns vis-à-vishepatic diseases is the lack of symptoms at the onset of the illness and, as result, its late diagnosis. The understandings of the molecular mechanisms that underlie hepatic diseases could help design strategies towards establishing markers for their accurate and timely diagnosis. PMID:24032513

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

    PubMed

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

    2014-01-10

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

  5. Induction of a reversible cardiac lipidosis by a dietary long-chain fatty acid (erucic acid). Relationship to lipid accumulation in border zones of myocardial infarcts.

    PubMed Central

    Chien, K. R.; Bellary, A.; Nicar, M.; Mukherjee, A.; Buja, L. M.

    1983-01-01

    Previous studies have demonstrated that cardiac myocytes in the border zone of acute myocardial infarction become markedly overloaded with neutral lipid during the transition from reversible to irreversible injury. To examine directly the role of these changes in neutral lipid metabolism in the development of irreversible cellular injury and associated increases in tissue Ca2+ content, the authors fed rats large amounts of a fatty acid (erucic acid) that is poorly oxidized by the heart and that subsequently accumulates as neutral lipid. Rats fed a high erucic acid (C22:1) diet in the form of 20% rapeseed oil for 3-5 days had a fourfold increase in triglyceride (49.5 +/- 3.8 SEM mg/g wet wt versus 13.6 +/- 13, n = 4) and a 60% increase in long-chain acyl CoA content (166.0 +/- 21.9 versus 91.5 +/- 9.0 nM/g wet wt, n = 4), compared with controls. However, there was no change in long-chain acyl carnitine or total phospholipid content. Histochemical studies showed accumulation of numerous lipid droplets in the myocytes, and electron microscopy revealed localization of lipid vesicles in direct contact with mitochondria, thus mimicking the lipid-laden cells in the border zone regions of acute myocardial infarcts. The acute lipidosis was reversible with either continued feeding of erucic acid for several weeks or conversion to a normal diet. It was not associated with an increased tissue Ca2+ content, nor with cell necrosis. However, continued erucic acid intake for 3 months was associated with focal myocardial degeneration and loss of myocytes. These results suggest that acute increases in neutral lipids, as found in the border zone of acute myocardial infarction, may not be the cause of progression to irreversible damage during acute myocardial injury, but that the persistent presence of similar lipid material over months may result in focal myocardial degeneration. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:6859230

  6. Host-Derived Smooth Muscle Cells Accumulate in Cardiac Allografts: Role of Inflammation and Monocyte Chemoattractant Protein 1

    PubMed Central

    Bojakowski, Krzysztof; Soin, Joanna; Nozynski, Jerzy; Zakliczynski, Michal; Gaciong, Zbigniew; Zembala, Marian; Söderberg-Nauclér, Cecilia

    2009-01-01

    Transplant arteriosclerosis is characterized by inflammation and intimal thickening caused by accumulation of smooth muscle cells (SMCs) both from donor and recipient. We assessed the relationship between clinical factors and the presence of host-derived SMCs in 124 myocardial biopsies from 26 consecutive patients who received hearts from opposite-sex donors. Clinical and demographic information was obtained from the patients' medical records. Host-derived SMCs accounted for 3.35±2.3% of cells in arterioles (range, 0.08–12.51%). As shown by linear regression analysis, an increased number of SMCs was associated with rejection grade (mean, 1.41±1.03, p = 0.034) and the number of leukocytes (19.1±12.7 per 20 high-power fields, p = 0.01). The accumulation of host-derived SMCs was associated with an increased number of leukocytes in the allografts. In vitro, monocyte chemoattractant protein 1 (MCP-1) released from leukocytes was crucial for SMC migration. After heart allotransplantion, mice treated with MCP-1-specific antibodies had significantly fewer host-derived SMCs in the grafts than mice treated with isotypic antibody controls. We conclude that the number of host-derived SMCs in human cardiac allografts is associated with the rejection grade and that MCP-1 may play pivotal role in recruiting host-derived SMCs into cardiac allografts. PMID:19142231

  7. A cardiac mitochondrial cAMP signaling pathway regulates calcium accumulation, permeability transition and cell death

    PubMed Central

    Wang, Z; Liu, D; Varin, A; Nicolas, V; Courilleau, D; Mateo, P; Caubere, C; Rouet, P; Gomez, A-M; Vandecasteele, G; Fischmeister, R; Brenner, C

    2016-01-01

    Although cardiac cytosolic cyclic 3′,5′-adenosine monophosphate (cAMP) regulates multiple processes, such as beating, contractility, metabolism and apoptosis, little is known yet on the role of this second messenger within cardiac mitochondria. Using cellular and subcellular approaches, we demonstrate here the local expression of several actors of cAMP signaling within cardiac mitochondria, namely a truncated form of soluble AC (sACt) and the exchange protein directly activated by cAMP 1 (Epac1), and show a protective role for sACt against cell death, apoptosis as well as necrosis in primary cardiomyocytes. Upon stimulation with bicarbonate (HCO3−) and Ca2+, sACt produces cAMP, which in turn stimulates oxygen consumption, increases the mitochondrial membrane potential (ΔΨm) and ATP production. cAMP is rate limiting for matrix Ca2+ entry via Epac1 and the mitochondrial calcium uniporter and, as a consequence, prevents mitochondrial permeability transition (MPT). The mitochondrial cAMP effects involve neither protein kinase A, Epac2 nor the mitochondrial Na+/Ca2+ exchanger. In addition, in mitochondria isolated from failing rat hearts, stimulation of the mitochondrial cAMP pathway by HCO3− rescued the sensitization of mitochondria to Ca2+-induced MPT. Thus, our study identifies a link between mitochondrial cAMP, mitochondrial metabolism and cell death in the heart, which is independent of cytosolic cAMP signaling. Our results might have implications for therapeutic prevention of cell death in cardiac pathologies. PMID:27100892

  8. Azelnidipine prevents cardiac dysfunction in streptozotocin-diabetic rats by reducing intracellular calcium accumulation, oxidative stress and apoptosis

    PubMed Central

    2011-01-01

    Background Numerous evidences suggest that diabetic heart is characterized by compromised ventricular contraction and prolonged relaxation attributable to multiple causative factors including calcium accumulation, oxidative stress and apoptosis. Therapeutic interventions to prevent calcium accumulation and oxidative stress could be therefore helpful in improving the cardiac function under diabetic condition. Methods This study was designed to examine the effect of long-acting calcium channel blocker (CCB), Azelnidipine (AZL) on contractile dysfunction, intracellular calcium (Ca2+) cycling proteins, stress-activated signaling molecules and apoptosis on cardiomyocytes in diabetes. Adult male Wistar rats were made diabetic by a single intraperitoneal (IP) injection of streptozotocin (STZ). Contractile functions were traced from live diabetic rats to isolated individual cardiomyocytes including peak shortening (PS), time-to-PS (TPS), time-to-relengthening (TR90), maximal velocity of shortening/relengthening (± dL/dt) and intracellular Ca2+ fluorescence. Results Diabetic heart showed significantly depressed PS, ± dL/dt, prolonged TPS, TR90 and intracellular Ca2+ clearing and showed an elevated resting intracellular Ca2+. AZL itself exhibited little effect on myocyte mechanics but it significantly alleviated STZ-induced myocyte contractile dysfunction. Diabetes increased the levels of superoxide, enhanced expression of the cardiac damage markers like troponin I, p67phox NADPH oxidase subunit, restored the levels of the mitochondrial superoxide dismutase (Mn-SOD), calcium regulatory proteins RyR2 and SERCA2a, and suppressed the levels of the anti-apoptotic Bcl-2 protein. All of these STZ-induced alterations were reconciled by AZL treatment. Conclusion Collectively, the data suggest beneficial effect of AZL in diabetic cardiomyopathy via altering intracellular Ca2+ handling proteins and preventing apoptosis by its antioxidant property. PMID:22054019

  9. Polymerized and functionalized triglycerides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant oils are useful sustainable raw materials for the development of new chemical products. As part of our research emphasis in sustainability and green polymer chemistry, we have explored a new method for polymerizing epoxidized triglycerides with the use of fluorosulfonic acid. Depending on the ...

  10. Magnolia extract (BL153) protection of heart from lipid accumulation caused cardiac oxidative damage, inflammation, and cell death in high-fat diet fed mice.

    PubMed

    Sun, Weixia; Zhang, Zhiguo; Chen, Qiang; Yin, Xia; Fu, Yaowen; Zheng, Yang; Cai, Lu; Kim, Ki-Soo; Kim, Ki Ho; Tan, Yi; Kim, Young Heui

    2014-01-01

    Magnolia as an herbal material obtained from Magnolia officinalis has been found to play an important role in anti-inflammation, antioxidative stress, and antiapoptosis. This study was designed to investigate the effect of Magnolia extract (BL153) on obesity-associated lipid accumulation, inflammation, oxidative stress, and apoptosis in the heart. C57BL/6 mice were fed a low- (10 kcal% fat) or high-fat (60 kcal% fat) diet for 24 weeks to induce obesity. These mice fed with high-fat diet (HFD) were given a gavage of vehicle, 2.5, 5, or 10 mg/kg body weight BL153 daily. The three doses of BL153 treatment slightly ameliorated insulin resistance without decrease of body weight gain induced by HFD feeding. BL153 at 10 mg/kg slightly attenuated a mild cardiac hypertrophy and dysfunction induced by HFD feeding. Both 5 mg/kg and 10 mg/kg of BL153 treatment significantly inhibited cardiac lipid accumulation measured by Oil Red O staining and improved cardiac inflammation and oxidative stress by downregulating ICAM-1, TNF-α, PAI-1, 3-NT, and 4-HNE. TUNEL staining showed that BL153 treatment also ameliorated apoptosis induced by mitochondrial caspase-3 independent cell death pathway. This study demonstrates that BL153 attenuates HFD-associated cardiac damage through prevention of HFD-induced cardiac lipid accumulation, inflammation, oxidative stress, and apoptosis. PMID:24693333

  11. Endothelial dysfunction in adipose triglyceride lipase deficiency.

    PubMed

    Schrammel, Astrid; Mussbacher, Marion; Wölkart, Gerald; Stessel, Heike; Pail, Karoline; Winkler, Sarah; Schweiger, Martina; Haemmerle, Guenter; Al Zoughbi, Wael; Höfler, Gerald; Lametschwandtner, Alois; Zechner, Rudolf; Mayer, Bernd

    2014-06-01

    Systemic knockout of adipose triglyceride lipase (ATGL), the pivotal enzyme of triglyceride lipolysis, results in a murine phenotype that is characterized by progredient cardiac steatosis and severe heart failure. Since cardiac and vascular dysfunction have been closely related in numerous studies we investigated endothelium-dependent and -independent vessel function of ATGL knockout mice. Aortic relaxation studies and Langendorff perfusion experiments of isolated hearts showed that ATGL knockout mice suffer from pronounced micro- and macrovascular endothelial dysfunction. Experiments with agonists directly targeting vascular smooth muscle cells revealed the functional integrity of the smooth muscle cell layer. Loss of vascular reactivity was restored ~50% upon treatment of ATGL knockout mice with the PPARα agonist Wy14,643, indicating that this phenomenon is partly a consequence of impaired cardiac contractility. Biochemical analysis revealed that aortic endothelial NO synthase expression and activity were significantly reduced in ATGL deficiency. Enzyme activity was fully restored in ATGL mice treated with the PPARα agonist. Biochemical analysis of perivascular adipose tissue demonstrated that ATGL knockout mice suffer from perivascular inflammatory oxidative stress which occurs independent of cardiac dysfunction and might contribute to vascular defects. Our results reveal a hitherto unrecognized link between disturbed lipid metabolism, obesity and cardiovascular disease. PMID:24657704

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

    SciTech Connect

    Hirano, Ken-ichi; Tanaka, Tatsuya; Ikeda, Yoshihiko; Yamaguchi, Satoshi; Zaima, Nobuhiro; Kobayashi, Kazuhiro; Sakata, Yasuhiko; and others

    2014-01-10

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

  13. Salacia oblonga root improves cardiac lipid metabolism in Zucker diabetic fatty rats: Modulation of cardiac PPAR-{alpha}-mediated transcription of fatty acid metabolic genes

    SciTech Connect

    Huang, Tom H.-W.; Yang Qinglin; Harada, Masaki; Uberai, Jasna; Radford, Jane; Li, George Q.; Yamahara, Johji; Roufogalis, Basil D.; Li Yuhao . E-mail: yuhao@pharm.usyd.edu.au

    2006-01-15

    Excess cardiac triglyceride accumulation in diabetes and obesity induces lipotoxicity, which predisposes the myocytes to death. On the other hand, increased cardiac fatty acid (FA) oxidation plays a role in the development of myocardial dysfunction in diabetes. PPAR-{alpha} plays an important role in maintaining homeostasis of lipid metabolism. We have previously demonstrated that the extract from Salacia oblonga root (SOE), an Ayurvedic anti-diabetic and anti-obesity medicine, improves hyperlipidemia in Zucker diabetic fatty (ZDF) rats (a genetic model of type 2 diabetes and obesity) and possesses PPAR-{alpha} activating properties. Here we demonstrate that chronic oral administration of SOE reduces cardiac triglyceride and FA contents and decreases the Oil red O-stained area in the myocardium of ZDF rats, which parallels the effects on plasma triglyceride and FA levels. Furthermore, the treatment suppressed cardiac overexpression of both FA transporter protein-1 mRNA and protein in ZDF rats, suggesting inhibition of increased cardiac FA uptake as the basis for decreased cardiac FA levels. Additionally, the treatment also inhibited overexpression in ZDF rat heart of PPAR-{alpha} mRNA and protein and carnitine palmitoyltransferase-1, acyl-CoA oxidase and 5'-AMP-activated protein kinase mRNAs and restored the downregulated acetyl-CoA carboxylase mRNA. These results suggest that SOE inhibits cardiac FA oxidation in ZDF rats. Thus, our findings suggest that improvement by SOE of excess cardiac lipid accumulation and increased cardiac FA oxidation in diabetes and obesity occurs by reduction of cardiac FA uptake, thereby modulating cardiac PPAR-{alpha}-mediated FA metabolic gene transcription.

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

    PubMed Central

    Qasem, Rani J.; Li, Jing; Tang, Hee Man; Browne, Veron; Mendez, Claudia; Yablonski, Elizabeth; Pontiggia, Laura; D’mello, Anil P.

    2015-01-01

    We have previously demonstrated that protein restriction throughout gestation and lactation reduced liver triglyceride content in adult rat offspring. The mechanism(s) mediating the decrease in liver triglyceride content are not understood. The objective 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 sacrificed 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 CoA dehydrogenase activity within the mitochondrial matrix, expression of nuclear peroxisome proliferator activated receptor-α, and plasma levels of β-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. Since 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

  15. 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-α, and plasma levels of β-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

  16. Hepatic diseases related to triglyceride metabolism.

    PubMed

    Aguilera-Méndez, Asdrubal; Álvarez-Delgado, Carolina; Hernández-Godinez, Daniel; Fernandez-Mejia, Cristina

    2013-10-01

    Triglycerides participate in key metabolic functions such as energy storage, thermal insulation and as deposit for essential and non-essential fatty acids that can be used as precursors for the synthesis of structural and functional phospholipids. The liver is a central organ in the regulation of triglyceride metabolism, and it participates in triglyceride synthesis, export, uptake and oxidation. The metabolic syndrome and associated diseases are among the main concerns of public health worldwide. One of the metabolic syndrome components is impaired triglyceride metabolism. Diseases associated with the metabolic syndrome promote the appearance of hepatic alterations e.g., non-alcoholic steatosis, steatohepatitis, fibrosis, cirrhosis and cancer. In this article, we review the molecular actions involved in impaired triglyceride metabolism and its association with hepatic diseases. We discuss mechanisms that reconcile the chronic inflammation and insulin resistance, and new concepts on the role of intestinal micro-flora permeability and proliferation in fatty liver etiology. We also describe the participation of oxidative stress in the progression of events leading from steatosis to steatohepatitis and fibrosis. Finally, we provide information regarding the mechanisms that link fatty acid accumulation during steatosis with changes in growth factors and cytokines that lead to the development of neoplastic cells. One of the main medical concerns vis-a-vis hepatic diseases is the lack of symptoms at the onset of the illness and, as result, its late diagnosis. The understandings of the molecular mechanisms that underlie hepatic diseases could help design strategies towards establishing markers for their accurate and timely diagnosis. PMID:24059726

  17. Triglycerides and Cardiovascular Disease: FAQ

    MedlinePlus

    ... lifestyle change with their patients. For improved metabolic health and protection to the heart and blood vessels, the American Heart Association now recommends an optimum fasting triglyceride level of 100 mg/dL. This puts ...

  18. Novel polymeric materials from triglycerides

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Triglycerides are good platforms for new polymeric products that can substitute for petroleum-based materials. As part of our research emphasis in sustainability and green polymer chemistry, we have explored a number of reactions in efforts to produce a wide range of value-added products. In this ...

  19. Cardiac-specific overexpression of perilipin 5 provokes severe cardiac steatosis via the formation of a lipolytic barrier[S

    PubMed Central

    Pollak, Nina M.; Schweiger, Martina; Jaeger, Doris; Kolb, Dagmar; Kumari, Manju; Schreiber, Renate; Kolleritsch, Stephanie; Markolin, Philipp; Grabner, Gernot F.; Heier, Christoph; Zierler, Kathrin A.; Rülicke, Thomas; Zimmermann, Robert; Lass, Achim; Zechner, Rudolf; Haemmerle, Guenter

    2013-01-01

    Cardiac triacylglycerol (TG) catabolism critically depends on the TG hydrolytic activity of adipose triglyceride lipase (ATGL). Perilipin 5 (Plin5) is expressed in cardiac muscle (CM) and has been shown to interact with ATGL and its coactivator comparative gene identification-58 (CGI-58). Furthermore, ectopic Plin5 expression increases cellular TG content and Plin5-deficient mice exhibit reduced cardiac TG levels. In this study we show that mice with cardiac muscle-specific overexpression of perilipin 5 (CM-Plin5) massively accumulate TG in CM, which is accompanied by moderately reduced fatty acid (FA) oxidizing gene expression levels. Cardiac lipid droplet (LD) preparations from CM of CM-Plin5 mice showed reduced ATGL- and hormone-sensitive lipase-mediated TG mobilization implying that Plin5 overexpression restricts cardiac lipolysis via the formation of a lipolytic barrier. To test this hypothesis, we analyzed TG hydrolytic activities in preparations of Plin5-, ATGL-, and CGI-58-transfected cells. In vitro ATGL-mediated TG hydrolysis of an artificial micellar TG substrate was not inhibited by the presence of Plin5, whereas Plin5-coated LDs were resistant toward ATGL-mediated TG catabolism. These findings strongly suggest that Plin5 functions as a lipolytic barrier to protect the cardiac TG pool from uncontrolled TG mobilization and the excessive release of free FAs. PMID:23345410

  20. [Residual risk: The roles of triglycerides and high density lipoproteins].

    PubMed

    Grammer, Tanja; Kleber, Marcus; Silbernagel, Günther; Scharnagl, Hubert; März, Winfried

    2016-06-01

    In clinical trials, the reduction of LDL-cholesterol (LDL-C) with statins reduces the incidence rate of cardiovascular events by approximately one third. This means, that a sizeable "residual risk" remains. Besides high lipoprotein (a), disorders in the metabolism of triglyceride-rich lipoproteins and high density liproteins have been implicated as effectors of the residual risk. Both lipoprotein parameters correlate inversely with each other. Therefore, the etiological contributions of triglycerides and / or of HDL for developing cardiovascular disease can hardly be estimated from either observational studies or from intervention studies. The largely disappointing results of intervention studies with inhibitors of the cholesteryl ester transfer protein and in particular the available set of genetically-epidemiological studies suggest that in the last decade, the importance of HDL cholesterol has been overvalued, while the importance of triglycerides has been underestimated. High triglycerides not always atherogenic, but only if they are associated with the accumulation relatively cholesterol-enriched, incompletely catabolized remnants of chylomicrons and very low density lipoproteins (familial type III hyperlipidemia, metabolic syndrome, diabetes mellitus). The normalization of the concentration of triglycerides and remnants by inhibiting the expression of apolipoprotein C3 is hence a new, promising therapeutic target. PMID:27305303

  1. Mobilization of stored triglycerides from macrophages as free fatty acids.

    PubMed

    von Hodenberg, E; Khoo, J C; Jensen, D; Witztum, J L; Steinberg, D

    1984-01-01

    Because many or most lipid-laden foam cells in atheromas and in xanthomas derive from macrophages, it is important to understand how they accumulate lipids and how they can divest themselves of lipids. The mobilization of stored triglycerides from macrophages was studied in cell cultures. Mouse resident peritoneal macrophages and J774 macrophages increased their triglyceride content six- to tenfold during a 24-hour incubation with free fatty acids complexed to albumin. Subsequent incubation in fresh medium containing free fatty acid-poor albumin was accompanied by a fall in cell triglyceride content (50% in 20 hours) and a corresponding increase in medium-free fatty acid. Release of free fatty acid was linear as a function of time, provided fresh medium was added hourly. When medium was not changed, release rates fell off rapidly, probably due to re-uptake of released free fatty acid. Chloroquine did not affect the rate of free fatty acid release. The results suggest that macrophages-foam cells can reduce their triglyceride stores via the action of a nonlysosomal (presumably cytoplasmic) neutral triglyceride lipase. PMID:6508637

  2. The pathophysiological role of oxidized cholesterols in epicardial fat accumulation and cardiac dysfunction: a study in swine fed a high caloric diet with an inhibitor of intestinal cholesterol absorption, ezetimibe.

    PubMed

    Shimabukuro, Michio; Okawa, Chinami; Yamada, Hirotsugu; Yanagi, Shuhei; Uematsu, Etsuko; Sugasawa, Noriko; Kurobe, Hirotsugu; Hirata, Yoichiro; Kim-Kaneyama, Joo-Ri; Lei, Xiao-Feng; Takao, Shoichiro; Tanaka, Yasutake; Fukuda, Daiju; Yagi, Shusuke; Soeki, Takeshi; Kitagawa, Tetsuya; Masuzaki, Hiroaki; Sato, Masao; Sata, Masataka

    2016-09-01

    Oxidized cholesterols (oxycholesterols) in food have been recognized as strong atherogenic components, but their tissue distributions and roles in cardiovascular diseases remain unclear. To investigate whether accumulation of oxycholesterols is linked to cardiac morphology and function, and whether reduction of oxycholesterols can improve cardiac performance, domestic male swine were randomized to a control diet (C), high caloric diet (HCD) or HCD+Ezetimibe, an inhibitor of intestinal cholesterol absorption, group (HCD+E) and evaluated for: (1) distribution of oxycholesterol components in serum and tissues, (2) levels of oxycholesterol-related enzymes, (3) paracardial and epicardial coronary fat thickness, and (4) cardiac performance. Ezetimibe treatment for 8weeks attenuated increases in oxycholesterols in the HCD group almost completely in liver, but reduced only levels of 4β-hydroxycholesterol in left ventricular (LV) myocardium. Ezetimibe treatment altered the expression of genes for cholesterol and fatty acid metabolism and decreased the expression of CYP3A46, which catabolizes cholesterol to 4β-hydroxycholesterol, strongly in liver. An increase in epicardial fat thickness and impaired cardiac performance in the HCD group were improved by ezetimibe treatment, and the improvement was closely related to the reduction in levels of 4β-hydroxycholesterol in LV myocardium. In conclusion, an increase in oxycholesterols in the HCD group was closely related to cardiac hypertrophy and dysfunction, as well as an increase in epicardial fat thickness. Ezetimibe may directly reduce oxycholesterol in liver and LV myocardium, and improve cardiac morphology and function. PMID:27416363

  3. Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: role of lowering circulating lipids.

    PubMed

    Huang, Tom Hsun-Wei; Peng, Gang; Kota, Bhavani Prasad; Li, George Qian; Yamahara, Johji; Roufogalis, Basil D; Li, Yuhao

    2005-07-01

    Excess triglyceride (TG) accumulation and increased fatty acid (FA) oxidation in the diabetic heart contribute to cardiac dysfunction. Punica granatum flower (PGF) is a traditional antidiabetic medicine. Here, we investigated the effects and mechanisms of action of PGF extract on abnormal cardiac lipid metabolism both in vivo and in vitro. Long-term oral administration of PGF extract (500 mg kg(-1)) reduced cardiac TG content, accompanied by a decrease in plasma levels of TG and total cholesterol in Zucker diabetic fatty (ZDF) rats, indicating improvement by PGF extract of abnormal cardiac TG accumulation and hyperlipidemia in this diabetic model. Treatment of ZDF rats with PGF extract lowered plasma FA levels. Furthermore, the treatment suppressed cardiac overexpression of mRNAs encoding for FA transport protein, peroxisome proliferator-activated receptor (PPAR)-alpha, carnitine palmitoyltransferase-1, acyl-CoA oxidase and 5'-AMP-activated protein kinase alpha2, and restored downregulated cardiac acetyl-CoA carboxylase mRNA expression in ZDF rats, whereas it showed little effect in Zucker lean rats. The results suggest that PGF extract inhibits increased cardiac FA uptake and oxidation in the diabetic condition. PGF extract and its component oleanolic acid enhanced PPAR-alpha luciferase reporter gene activity in human embryonic kidney 293 cells, and this effect was completely suppressed by a selective PPAR-alpha antagonist MK-886, consistent with the presence of PPAR-alpha activator activity in the extract and this component. Our findings suggest that PGF extract improves abnormal cardiac lipid metabolism in ZDF rats by activating PPAR-alpha and thereby lowering circulating lipid and inhibiting its cardiac uptake. PMID:15880139

  4. The interplay of protein kinase A and perilipin 5 regulates cardiac lipolysis.

    PubMed

    Pollak, Nina M; Jaeger, Doris; Kolleritsch, Stephanie; Zimmermann, Robert; Zechner, Rudolf; Lass, Achim; Haemmerle, Guenter

    2015-01-16

    Defective lipolysis in mice lacking adipose triglyceride lipase provokes severe cardiac steatosis and heart dysfunction, markedly shortening life span. Similarly, cardiac muscle (CM)-specific Plin5 overexpression (CM-Plin5) leads to severe triglyceride (TG) accumulation in cardiomyocytes via impairing TG breakdown. Interestingly, cardiac steatosis due to overexpression of Plin5 is compatible with normal heart function and life span indicating a more moderate impact of Plin5 overexpression on cardiac lipolysis and energy metabolism. We hypothesized that cardiac Plin5 overexpression does not constantly impair cardiac lipolysis. In line with this assumption, TG levels decreased in CM of fasted compared with nonfasted CM-Plin5 mice indicating that fasting may lead to a diminished barrier function of Plin5. Recent studies demonstrated that Plin5 is phosphorylated, and activation of adenylyl cyclase leads to phosphorylation of Plin5, suggesting that Plin5 is a substrate for PKA. Furthermore, any significance of Plin5 phosphorylation by PKA in the regulation of TG mobilization from lipid droplets (LDs) is unknown. Here, we show that the lipolytic barrier of Plin5-enriched LDs, either prepared from cardiac tissue of CM-Plin5 mice or Plin5-transfected cells, is abrogated by incubation with PKA. Notably, PKA-induced lipolysis of LDs enriched with Plin5 carrying a single mutation at serine 155 (PlinS155A) of the putative PKA phosphorylation site was substantially impaired revealing a critical role for PKA in Plin5-regulated lipolysis. The strong increase in protein levels of phosphorylated PKA in CM of Plin5 transgenic mice may partially restore fatty acid release from Plin5-enriched LDs, rendering these hearts compatible with normal heart function despite massive steatosis. PMID:25418045

  5. Fructose impairs glucose-induced hepatic triglyceride synthesis

    PubMed Central

    2011-01-01

    Obesity, type 2 diabetes and hyperlipidemia frequently coexist and are associated with significantly increased morbidity and mortality. Consumption of refined carbohydrate and particularly fructose has increased significantly in recent years and has paralled the increased incidence of obesity and diabetes. Human and animal studies have demonstrated that high dietary fructose intake positively correlates with increased dyslipidemia, insulin resistance, and hypertension. Metabolism of fructose occurs primarily in the liver and high fructose flux leads to enhanced hepatic triglyceride accumulation (hepatic steatosis). This results in impaired glucose and lipid metabolism and increased proinflammatory cytokine expression. Here we demonstrate that fructose alters glucose-stimulated expression of activated acetyl CoA carboxylase (ACC), pSer hormone sensitive lipase (pSerHSL) and adipose triglyceride lipase (ATGL) in hepatic HepG2 or primary hepatic cell cultures in vitro. This was associated with increased de novo triglyceride synthesis in vitro and hepatic steatosis in vivo in fructose- versus glucose-fed and standard-diet fed mice. These studies provide novel insight into the mechanisms involved in fructose-mediated hepatic hypertriglyceridemia and identify fructose-uptake as a new potential therapeutic target for lipid-associated diseases. PMID:21261970

  6. Inhibition of hepatic triglyceride formation by clofibrate

    PubMed Central

    Adams, Larry L.; Webb, William W.; Fallon, Harold J.

    1971-01-01

    The effect of clofibrate (CPIB) on hepatic glycerolipid formation has been studied in vivo and in vitro in the rat. Feeding 0.25% CPIB in laboratory chow significantly reduced serum triglyceride levels by 6 hr and concomitantly decreased the rate of glycerol-14C incorporation into hepatic and serum glycerides, in vivo. These changes persisted for at least 14 days. A similar decrease in serum triglyceride and glycerol incorporation into hepatic glycerides was observed in rats fed high glucose diets containing 0.25% CPIB. Serum glycerol was reduced by feeding CPIB for 14 days. The formation of diglyceride and triglyceride from 14C-sn-glycerol-3-P by rat liver homogenates was inhibited by addition of 1-40 mM CPIB to the reaction mixture. These results suggest that CPIB reduces hepatic glycerolipid synthesis, possibly by inhibition of one or more reactions in the esterification of sn-glycerol-3-P. This change may account for the early fall in serum triglyceride. At later time periods, serum glycerol levels fall and in some experiments, hepatic triglyceride content increases. Therefore, it is likely that additional metabolic alterations may contribute to the sustained hypotriglyceridemic effects of CPIB. PMID:5096518

  7. 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.

  8. Cardiac Rehabilitation

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Cardiac Rehabilitation? Cardiac rehabilitation (rehab) is a medically supervised program ... be designed to meet your needs. The Cardiac Rehabilitation Team Cardiac rehab involves a long-term commitment ...

  9. Heat-killed Lactobacillus Reuteri GMNL-263 Prevents Epididymal Fat Accumulation and Cardiac Injury in High-Calorie Diet-Fed Rats

    PubMed Central

    Liao, Po-Hsiang; Kuo, Wei-Wen; Hsieh, Dennis Jine-Yuan; Yeh, Yu-Lan; Day, Cecilia-Hsuan; Chen, Ya-Hui; Chang, Sheng-Huang; Padma, V. Vijaya; Chen, Yi-Hsing; Huang, Chih-Yang

    2016-01-01

    High-calorie diet-induced obesity leads to cardiomyocyte dysfunction and apoptosis. Impaired regulation of epididymal fat content in obese patients has been known to increase the risk of cardiac injury. In our study, a lactic acid bacteria, Lactobacillus reuteri GMNL-263, was evaluated for its potential to reduce body weight and body fat ratio and to prevent heart injury in rats with high-fat diet-induced obesity. Lactic acid bacteria supplementation restored the cardiac function and decreased the physiological changes in the heart of the obese rats. In addition, the Fas/Fas-associated protein pathway-induced caspase 3/e Poly polymerase mediated apoptosis in the cardiomyocytes of the obese rats was reversed in the Lr263-treated rats. These results reveal that fed with Lr-263 reduces body fat ratio, inhibits caspase 3-mediated apoptosis and restores cardiac function in obese rats through recovery of ejection fraction and fractional shortening. Our results indicated that the administration of Lr263 lactic acid bacteria can significantly down-regulate body fat and prevent cardiomyocyte injury in obese rats. PMID:27499689

  10. Heat-killed Lactobacillus Reuteri GMNL-263 Prevents Epididymal Fat Accumulation and Cardiac Injury in High-Calorie Diet-Fed Rats.

    PubMed

    Liao, Po-Hsiang; Kuo, Wei-Wen; Hsieh, Dennis Jine-Yuan; Yeh, Yu-Lan; Day, Cecilia-Hsuan; Chen, Ya-Hui; Chang, Sheng-Huang; Padma, V Vijaya; Chen, Yi-Hsing; Huang, Chih-Yang

    2016-01-01

    High-calorie diet-induced obesity leads to cardiomyocyte dysfunction and apoptosis. Impaired regulation of epididymal fat content in obese patients has been known to increase the risk of cardiac injury. In our study, a lactic acid bacteria, Lactobacillus reuteri GMNL-263, was evaluated for its potential to reduce body weight and body fat ratio and to prevent heart injury in rats with high-fat diet-induced obesity. Lactic acid bacteria supplementation restored the cardiac function and decreased the physiological changes in the heart of the obese rats. In addition, the Fas/Fas-associated protein pathway-induced caspase 3/e Poly polymerase mediated apoptosis in the cardiomyocytes of the obese rats was reversed in the Lr263-treated rats. These results reveal that fed with Lr-263 reduces body fat ratio, inhibits caspase 3-mediated apoptosis and restores cardiac function in obese rats through recovery of ejection fraction and fractional shortening. Our results indicated that the administration of Lr263 lactic acid bacteria can significantly down-regulate body fat and prevent cardiomyocyte injury in obese rats. PMID:27499689

  11. Modified triglyceride oil through reactions with phenyltriazolinedione

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  12. Polymerization of epoxidized triglycerides with fluorosulfonic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of triglycerides as agri-based renewable raw materials for the development of new products is highly desirable in view of uncertain future petroleum prices. A new method of polymerizing epoxidized soybean oil has been devised with the use of fluorosulfonic acid. Depending on the reaction con...

  13. Acute exposure to 2,4-dinitrophenol alters zebrafish swimming performance and whole body triglyceride levels.

    PubMed

    Marit, Jordan S; Weber, Lynn P

    2011-06-01

    While swimming endurance (critical swimming speed or U(crit)) and lipid stores have both been reported to acutely decrease after exposure to a variety of toxicants, the relationship between these endpoints has not been clearly established. In order to examine these relationships, adult zebrafish (Danio rerio) were aqueously exposed to solvent control (ethanol) or two nominal concentrations of 2,4-dinitrophenol (DNP), a mitochondrial electron transport chain uncoupler, for a 24-h period. Following exposure, fish were placed in a swim tunnel in clean water for swimming testing or euthanized immediately without testing, followed by analysis of whole body triglyceride levels. U(crit) decreased in both the 6 mg/L and 12 mg/L DNP groups, with 12 mg/L approaching the LC₅₀. A decrease in tail beat frequency was observed without a significant change in tail beat amplitude. In contrast, triglyceride levels were elevated in a concentration-dependent manner in the DNP exposure groups, but only in fish subjected to swimming tests. This increase in triglyceride stores may be due to a direct interference of DNP on lipid catabolism as well as increased triglyceride production when zebrafish were subjected to the co-stressors of swimming and toxicant exposure. Future studies should be directed at determining how acute DNP exposure combines with swimming to cause alterations in triglyceride accumulation. PMID:21406246

  14. GPIHBP1 and Plasma Triglyceride Metabolism.

    PubMed

    Fong, Loren G; Young, Stephen G; Beigneux, Anne P; Bensadoun, André; Oberer, Monika; Jiang, Haibo; Ploug, Michael

    2016-07-01

    GPIHBP1, a GPI-anchored protein in capillary endothelial cells, is crucial for the lipolytic processing of triglyceride-rich lipoproteins (TRLs). GPIHBP1 shuttles lipoprotein lipase (LPL) to its site of action in the capillary lumen and is essential for the margination of TRLs along capillaries - such that lipolytic processing can proceed. GPIHBP1 also reduces the unfolding of the LPL catalytic domain, thereby stabilizing LPL catalytic activity. Many different GPIHBP1 mutations have been identified in patients with severe hypertriglyceridemia (chylomicronemia), the majority of which interfere with folding of the protein and abolish its capacity to bind and transport LPL. The discovery of GPIHBP1 has substantially revised our understanding of intravascular triglyceride metabolism but has also raised many new questions for future research. PMID:27185325

  15. Miniaturization of EISCAP sensor for triglyceride detection.

    PubMed

    Vemulachedu, Hareesh; Fernandez, Renny Edwin; Bhattacharya, Enakshi; Chadha, Anju

    2009-12-01

    In this paper we discuss the fabrication and characterization of miniaturized triglyceride biosensors on crystalline silicon and porous silicon (PS) substrates. The sensors are miniaturized Electrolyte Insulator Semiconductor Capacitors (mini-EISCAPs), which primarily sense the pH variation of the electrolyte used. The lipase enzyme, which catalyses the hydrolysis of triglycerides, was immobilized on the sensor surface. Triglyceride solutions introduced into the enzyme immobilized sensor produced butyric acid which causes the change in pH of the electrolyte. Miniaturized EISCAP sensors were fabricated using bulk micromachining technique and have silicon nitride as the pH sensitive dielectric layer. The sensors are cubical pits of dimensions 1,500 microm x 1,500 microm x 100 microm which can hold an electrolyte volume of 0.1 microl. The pH changes in the solution can be sensed through the EISCAP sensors by monitoring the flatband voltage shift in the Capacitance-Voltage (C-V) characteristics taken during the course of the reaction. The reaction rate is found to be quite high in the miniature cells when compared to the sensors of bigger dimensions. PMID:18649048

  16. 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)

  17. Cardiac Catheterization

    MedlinePlus

    ... from the NHLBI on Twitter. What Is Cardiac Catheterization? Cardiac catheterization (KATH-eh-ter-ih-ZA-shun) is a ... disease. Doctors also can use ultrasound during cardiac catheterization to see blockages in the coronary arteries. Ultrasound ...

  18. Accumulate repeat accumulate codes

    NASA Technical Reports Server (NTRS)

    Abbasfar, Aliazam; Divsalar, Dariush; Yao, Kung

    2004-01-01

    In this paper we propose an innovative channel coding scheme called 'Accumulate Repeat Accumulate codes' (ARA). This class of codes can be viewed as serial turbo-like codes, or as a subclass of Low Density Parity Check (LDPC) codes, thus belief propagation can be used for iterative decoding of ARA codes on a graph. The structure of encoder for this class can be viewed as precoded Repeat Accumulate (RA) code or as precoded Irregular Repeat Accumulate (IRA) code, where simply an accumulator is chosen as a precoder. Thus ARA codes have simple, and very fast encoder structure when they representing LDPC codes. Based on density evolution for LDPC codes through some examples for ARA codes, we show that for maximum variable node degree 5 a minimum bit SNR as low as 0.08 dB from channel capacity for rate 1/2 can be achieved as the block size goes to infinity. Thus based on fixed low maximum variable node degree, its threshold outperforms not only the RA and IRA codes but also the best known LDPC codes with the dame maximum node degree. Furthermore by puncturing the accumulators any desired high rate codes close to code rate 1 can be obtained with thresholds that stay close to the channel capacity thresholds uniformly. Iterative decoding simulation results are provided. The ARA codes also have projected graph or protograph representation that allows for high speed decoder implementation.

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

    EPA Science Inventory

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

  20. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  1. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  2. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  3. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  4. Punicalagin, an active component in pomegranate, ameliorates cardiac mitochondrial impairment in obese rats via AMPK activation

    PubMed Central

    Cao, Ke; Xu, Jie; Pu, Wenjun; Dong, Zhizhong; Sun, Lei; Zang, Weijin; Gao, Feng; Zhang, Yong; Feng, Zhihui; Liu, Jiankang

    2015-01-01

    Obesity is associated with an increasing prevalence of cardiovascular diseases and metabolic syndrome. It is of paramount importance to reduce obesity-associated cardiac dysfunction and impaired energy metabolism. In this study, the activation of the AMP-activated protein kinase (AMPK) pathway by punicalagin (PU), a major ellagitannin in pomegranate was investigated in the heart of a rat obesity model. In male SD rats, eight-week administration of 150 mg/kg pomegranate extract (PE) containing 40% punicalagin sufficiently prevented high-fat diet (HFD)-induced obesity associated accumulation of cardiac triglyceride and cholesterol as well as myocardial damage. Concomitantly, the AMPK pathway was activated, which may account for prevention of mitochondrial loss via upregulating mitochondrial biogenesis and amelioration of oxidative stress via enhancing phase II enzymes in the hearts of HFD rats. Together with the normalized expression of uncoupling proteins and mitochondrial dynamic regulators, PE significantly prevented HFD-induced cardiac ATP loss. Through in vitro cultures, we showed that punicalagin was the predominant component that activated AMPK by quickly decreasing the cellular ATP/ADP ratio specifically in cardiomyocytes. Our findings demonstrated that punicalagin, the major active component in PE, could modulate mitochondria and phase II enzymes through AMPK pathway to prevent HFD-induced cardiac metabolic disorders. PMID:26369619

  5. MK2 Deletion in Mice Prevents Diabetes-Induced Perturbations in Lipid Metabolism and Cardiac Dysfunction.

    PubMed

    Ruiz, Matthieu; Coderre, Lise; Lachance, Dominic; Houde, Valérie; Martel, Cécile; Thompson Legault, Julie; Gillis, Marc-Antoine; Bouchard, Bertrand; Daneault, Caroline; Carpentier, André C; Gaestel, Matthias; Allen, Bruce G; Des Rosiers, Christine

    2016-02-01

    Heart disease remains a major complication of diabetes, and the identification of new therapeutic targets is essential. This study investigates the role of the protein kinase MK2, a p38 mitogen-activated protein kinase downstream target, in the development of diabetes-induced cardiomyopathy. Diabetes was induced in control (MK2(+/+)) and MK2-null (MK2(-/-)) mice using repeated injections of a low dose of streptozotocin (STZ). This protocol generated in MK2(+/+) mice a model of diabetes characterized by a 50% decrease in plasma insulin, hyperglycemia, and insulin resistance (IR), as well as major contractile dysfunction, which was associated with alterations in proteins involved in calcium handling. While MK2(-/-)-STZ mice remained hyperglycemic, they showed improved IR and none of the cardiac functional or molecular alterations. Further analyses highlighted marked lipid perturbations in MK2(+/+)-STZ mice, which encompass increased 1) circulating levels of free fatty acid, ketone bodies, and long-chain acylcarnitines and 2) cardiac triglyceride accumulation and ex vivo palmitate β-oxidation. MK2(-/-)-STZ mice were also protected against all these diabetes-induced lipid alterations. Our results demonstrate the benefits of MK2 deletion on diabetes-induced cardiac molecular and lipid metabolic changes, as well as contractile dysfunction. As a result, MK2 represents a new potential therapeutic target to prevent diabetes-induced cardiac dysfunction. PMID:26558681

  6. 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

  7. 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

  8. Conjugation to Poly(amidoamine) Dendrimers and Pulmonary Delivery Reduce Cardiac Accumulation and Enhance Antitumor Activity of Doxorubicin in Lung Metastasis.

    PubMed

    Zhong, Qian; Bielski, Elizabeth R; Rodrigues, Leonan S; Brown, Matthew R; Reineke, Joshua J; da Rocha, Sandro R P

    2016-07-01

    Lung is one of the most common sites to which almost all other primary tumors metastasize. The major challenges in the chemotherapy of lung metastases include the low drug concentration found in the tumors and high systemic toxicity upon systemic administration. In this study, we combine local lung delivery and the use of nanocarrier-based systems for improving pharmacokinetics and biodistribution of the therapeutics to fight lung metastases. We investigate the impact of the conjugation of doxorubicin (DOX) to carboxyl-terminated poly(amidoamine) dendrimers (PAMAM) through a bond that allows for intracellular-triggered release, and the effect of pulmonary delivery of the dendrimer-DOX conjugate in decreasing tumor burden in a lung metastasis model. The results show a dramatic increase in efficacy of DOX treatment of the melanoma (B16-F10) lung metastasis mouse model upon pulmonary administration of the drug, as indicated by decreased tumor burden (lung weight) and increased survival rates of the animals (male C57BL/6) when compared to iv delivery. Conjugation of DOX further increased the therapeutic efficacy upon lung delivery as indicated by the smaller number of nodules observed in the lungs when compared to free DOX. These results are in agreement with the biodistribution characteristics of the DOX upon pulmonary delivery, which showed a longer lung accumulation/retention compared to iv administration. The distribution of DOX to the heart tissue is also significantly decreased upon pulmonary administration, and further decreased upon conjugation. The results show, therefore, that pulmonary administration of DOX combined to conjugation to PAMAM dendrimer through an intracellular labile bond is a potential strategy to enhance the therapeutic efficacy and decrease systemic toxicity of DOX. PMID:27253493

  9. Functional Cardiac Lipolysis in Mice Critically Depends on Comparative Gene Identification-58*

    PubMed Central

    Zierler, Kathrin A.; Jaeger, Doris; Pollak, Nina M.; Eder, Sandra; Rechberger, Gerald N.; Radner, Franz P. W.; Woelkart, Gerald; Kolb, Dagmar; Schmidt, Albrecht; Kumari, Manju; Preiss-Landl, Karina; Pieske, Burkert; Mayer, Bernd; Zimmermann, Robert; Lass, Achim; Zechner, Rudolf; Haemmerle, Guenter

    2013-01-01

    Efficient catabolism of cellular triacylglycerol (TG) stores requires the TG hydrolytic activity of adipose triglyceride lipase (ATGL). The presence of comparative gene identification-58 (CGI-58) strongly increased ATGL-mediated TG catabolism in cell culture experiments. Mutations in the genes coding for ATGL or CGI-58 in humans cause neutral lipid storage disease characterized by TG accumulation in multiple tissues. ATGL gene mutations cause a severe phenotype especially in cardiac muscle leading to cardiomyopathy that can be lethal. In contrast, CGI-58 gene mutations provoke severe ichthyosis and hepatosteatosis in humans and mice, whereas the role of CGI-58 in muscle energy metabolism is less understood. Here we show that mice lacking CGI-58 exclusively in muscle (CGI-58KOM) developed severe cardiac steatosis and cardiomyopathy linked to impaired TG catabolism and mitochondrial fatty acid oxidation. The marked increase in ATGL protein levels in cardiac muscle of CGI-58KOM mice was unable to compensate the lack of CGI-58. The addition of recombinant CGI-58 to cardiac lysates of CGI-58KOM mice completely reconstituted TG hydrolytic activities. In skeletal muscle, the lack of CGI-58 similarly provoked TG accumulation. The addition of recombinant CGI-58 increased TG hydrolytic activities in control and CGI-58KOM tissue lysates, elucidating the limiting role of CGI-58 in skeletal muscle TG catabolism. Finally, muscle CGI-58 deficiency affected whole body energy homeostasis, which is caused by impaired muscle TG catabolism and increased cardiac glucose uptake. In summary, this study demonstrates that functional muscle lipolysis depends on both CGI-58 and ATGL. PMID:23413028

  10. A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis.

    PubMed

    He, Shaoqing; McPhaul, Christopher; Li, John Zhong; Garuti, Rita; Kinch, Lisa; Grishin, Nick V; Cohen, Jonathan C; Hobbs, Helen H

    2010-02-26

    Obesity and insulin resistance are associated with deposition of triglycerides in tissues other than adipose tissue. Previously, we showed that a missense mutation (I148M) in PNPLA3 (patatin-like phospholipase domain-containing 3 protein) is associated with increased hepatic triglyceride content in humans. Here we examined the effect of the I148M substitution on the enzymatic activity and cellular location of PNPLA3. Structural modeling predicted that the substitution of methionine for isoleucine at residue 148 would restrict access of substrate to the catalytic serine at residue 47. In vitro assays using recombinant PNPLA3 partially purified from Sf9 cells confirmed that the wild type enzyme hydrolyzes emulsified triglyceride and that the I148M substitution abolishes this activity. Expression of PNPLA3-I148M, but not wild type PNPLA3, in cultured hepatocytes or in the livers of mice increased cellular triglyceride content. Cell fractionation studies revealed that approximately 90% of wild type PNPLA3 partitioned between membranes and lipid droplets; substitution of isoleucine for methionine at position 148 did not alter the subcellular distribution of the protein. These data are consistent with PNPLA3-I148M promoting triglyceride accumulation by limiting triglyceride hydrolysis. PMID:20034933

  11. Inflammatory stress exacerbates the progression of cardiac fibrosis in high-fat-fed apolipoprotein E knockout mice via endothelial-mesenchymal transition.

    PubMed

    Ma, Kun Ling; Liu, Jing; Ni, Jie; Zhang, Yang; Lv, Lin Li; Tang, Ri Ning; Ni, Hai Feng; Ruan, Xiong Zhong; Liu, Bi Cheng

    2013-01-01

    Background Chronic inflammation plays a crucial role in the progression of cardiac fibrosis. This study investigated whether inflammation exacerbated the progression of cardiac fibrosis in high-fat-fed apolipoprotein E knockout (ApoE KO) mice via endothelial-mesenchymal transition (EndMT). Methods Twenty-four male ApoE KO mice were divided into normal chow diet (Control), high-fat diet (HFD), or high-fat diet plus 10% casein injection (inflamed) groups for 8 weeks. The body weight of ApoE KO mice was measured at each week. The lipid profile and serum amyloid A (SAA) levels were examined using clinical biochemistry and enzyme-linked immunosorbent assays, respectively. Cardiac lipid and collagen accumulation was visualised with haematoxylin-eosin (HE) and Masson's trichrome staining. EndMT-related molecule expression was examined by immunohistochemistry and Western blotting. Results SAA levels were increased in the inflamed group compared with the HFD and control groups, suggesting that inflammation was successfully induced. There were no differences in body weight among three groups at each week. Interestingly, inflammation significantly reduced serum total cholesterol, triglyceride, and low-density lipoprotein (LDL) levels compared with the HFD mice. However, both foam cell formation in cardiac blood vessels and cardiac collagen deposition were increased in the inflamed group, as demonstrated by HE and Masson trichrome staining. Furthermore, inflammation reduced protein expression of CD31 and increased protein expression of alpha-smooth muscle actin (α-SMA) and collagen I, which contribute to cardiac EndMT. Conclusions Inflammatory stress exacerbates the progression of cardiac fibrosis in high-fat-fed ApoE KO mice via EndMT, suggesting that hyperlipidaemia and inflammation act synergistically to redistribute plasma lipids to cardiac tissues and accelerate the progression of cardiac fibrosis. PMID:23471419

  12. Inborn errors of cytoplasmic triglyceride metabolism.

    PubMed

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

    2015-01-01

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

  13. 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

  14. Multi-modal contributions to detoxification of acute pharmacotoxicity by a triglyceride micro-emulsion

    PubMed Central

    Fettiplace, Michael R; Lis, Kinga; Ripper, Richard; Kowal, Katarzyna; Pichurko, Adrian; Vitello, Dominic; Rubinstein, Israel; Schwartz, David; Akpa, Belinda S; Weinberg, Guy

    2014-01-01

    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

  15. Black-white differences in postprandial triglyceride response and postheparin lipoprotein lipase and hepatic triglyceride lipase among young men.

    PubMed

    Friday, K E; Srinivasan, S R; Elkasabany, A; Dong, C; Wattigney, W A; Dalferes, E; Berenson, G S

    1999-06-01

    Black-white differences in serum triglycerides and high-density lipoprotein (HDL) cholesterol concentrations are known. However, the metabolic basis for these differences is not clear. This study determined the magnitude of postprandial triglyceride concentrations, lipoprotein lipase and hepatic triglyceride lipase activities in postheparin plasma, and serum lipid and lipoprotein cholesterol concentrations in healthy young adult black men (n = 22) and white men (n = 28). Postprandial triglyceride concentrations were measured at 2, 3, 4, 5, 6, and 8 hours after a standardized test meal. Serum lipid and lipoprotein cholesterol concentrations were similar between the races in this study sample. However, incremental (above basal) increases in triglycerides were significantly greater in white men versus black men at 2 hours (P = .01) and tended to be greater at 3 hours (P = .12) and 4 hours (P = .06) after the fat load. In a multivariate analysis that included age, race, apolipoprotein E (apoE) genotype, fasting triglycerides, obesity measures, alcohol intake, and cigarette use, fasting triglycerides (P = .04) and, to a lesser extent, race (P = .07) were associated independently with the 2-hour incremental increase in triglycerides. The incremental triglyceride response correlated inversely with HDL cholesterol in both whites (r = -.38, P = .04) and blacks (r = -.59, P = .004). Lipoprotein lipase activity was higher (P = .049) and hepatic triglyceride lipase activity lower (P = .0001) in black men compared with white men; racial differences persisted after adjusting for the covariates. While lipoprotein lipase activity tended to associate inversely with the postprandial triglyceride concentration in both races, hepatic triglyceride lipase activity tended to correlate positively in whites and inversely in blacks. These results suggest that compared with whites, blacks may have an efficient lipid-clearing mechanism that could explain the black-white differences in

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

    SciTech Connect

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

    1997-07-01

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

  17. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Triglyceride test system. 862.1705 Section 862.1705 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1705 Triglyceride test system....

  18. Accumulate-Repeat-Accumulate-Accumulate-Codes

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush; Dolinar, Sam; Thorpe, Jeremy

    2004-01-01

    Inspired by recently proposed Accumulate-Repeat-Accumulate (ARA) codes [15], in this paper we propose a channel coding scheme called Accumulate-Repeat-Accumulate-Accumulate (ARAA) codes. These codes can be seen as serial turbo-like codes or as a subclass of Low Density Parity Check (LDPC) codes, and they have a projected graph or protograph representation; this allows for a high-speed iterative decoder implementation using belief propagation. An ARAA code can be viewed as a precoded Repeat-and-Accumulate (RA) code with puncturing in concatenation with another accumulator, where simply an accumulator is chosen as the precoder; thus ARAA codes have a very fast encoder structure. Using density evolution on their associated protographs, we find examples of rate-lJ2 ARAA codes with maximum variable node degree 4 for which a minimum bit-SNR as low as 0.21 dB from the channel capacity limit can be achieved as the block size goes to infinity. Such a low threshold cannot be achieved by RA or Irregular RA (IRA) or unstructured irregular LDPC codes with the same constraint on the maximum variable node degree. Furthermore by puncturing the accumulators we can construct families of higher rate ARAA codes with thresholds that stay close to their respective channel capacity thresholds uniformly. Iterative decoding simulation results show comparable performance with the best-known LDPC codes but with very low error floor even at moderate block sizes.

  19. Direct binding of triglyceride to fat storage-inducing transmembrane proteins 1 and 2 is important for lipid droplet formation.

    PubMed

    Gross, David A; Zhan, Chenyang; Silver, David L

    2011-12-01

    The process of lipid droplet (LD) formation is an evolutionarily conserved process among all eukaryotes and plays an important role in both cellular physiology and disease. Recently, fat storage-inducing transmembrane proteins 1 and 2 (FIT1/FITM1 and FIT2/FITM2) were discovered as an evolutionarily conserved family of proteins involved in fat storage. In mammals, FIT1 is expressed primarily in skeletal muscle and FIT2 is expressed primarily in adipose, raising the possibility that FIT1 and FIT2 have unique functions. These proteins are exclusively localized to the endoplasmic reticulum (ER) and mediate triglyceride-rich LD accumulation when overexpressed in cells, mouse liver, or muscle. Unlike the ER-resident diacylglycerol O-acyltransferase family of triglyceride-synthesizing enzymes, FITs do not synthesize triglyceride, but rather partition triglyceride into LDs. The mechanism by which FIT proteins mediate this process has not been determined. A simple hypothesis was tested that FIT proteins bind to triglyceride to mediate LD formation. Here, it is shown that FIT proteins purified in detergent micelles directly bind triolein with specificity and saturation-binding kinetics. A FIT2 gain-of-function mutant that formed larger LDs, FLL(157-9)AAA, showed increased binding to triolein relative to wild-type FIT2, whereas FIT1 and a FIT2 partial loss-of-function mutant, N80A, had significantly lower triolein binding and produced smaller LDs. In summary, FIT proteins are transmembrane domain-containing proteins shown to bind triglyceride. These findings indicate that FITs have a unique biochemical mechanism in mediating LD formation and implicates triglyceride binding as important for FIT-mediated LD formation. PMID:22106267

  20. Accumulate-Repeat-Accumulate-Accumulate Codes

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush; Dolinar, Samuel; Thorpe, Jeremy

    2007-01-01

    Accumulate-repeat-accumulate-accumulate (ARAA) codes have been proposed, inspired by the recently proposed accumulate-repeat-accumulate (ARA) codes. These are error-correcting codes suitable for use in a variety of wireless data-communication systems that include noisy channels. ARAA codes can be regarded as serial turbolike codes or as a subclass of low-density parity-check (LDPC) codes, and, like ARA codes they have projected graph or protograph representations; these characteristics make it possible to design high-speed iterative decoders that utilize belief-propagation algorithms. The objective in proposing ARAA codes as a subclass of ARA codes was to enhance the error-floor performance of ARA codes while maintaining simple encoding structures and low maximum variable node degree.

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

    PubMed Central

    Lambert, Jennifer E.; Parks, Elizabeth J.

    2012-01-01

    Triglyceride Metabolism and Disease. PMID:22281699

  2. Comparative gene identification-58/α/β hydrolase domain 5: more than just an adipose triglyceride lipase activator?

    PubMed Central

    Zierler, Kathrin A.; Zechner, Rudolf; Haemmerle, Guenter

    2014-01-01

    Purpose of review Comparative gene identification-58 (CGI-58) is a lipid droplet-associated protein that controls intracellular triglyceride levels by its ability to activate adipose triglyceride lipase (ATGL). Additionally, CGI-58 was described to exhibit lysophosphatidic acid acyl transferase (LPAAT) activity. This review focuses on the significance of CGI-58 in energy metabolism in adipose and nonadipose tissue. Recent findings Recent studies with transgenic and CGI-58-deficient mouse strains underscored the importance of CGI-58 as a regulator of intracellular energy homeostasis by modulating ATGL-driven triglyceride hydrolysis. In accordance with this function, mice and humans that lack CGI-58 accumulate triglyceride in multiple tissues. Additionally, CGI-58-deficient mice develop an ATGL-independent severe skin barrier defect and die soon after birth. Although the premature death prevented a phenotypical characterization of adult global CGI-58 knockout mice, the characterization of mice with tissue-specific CGI-58 deficiency revealed new insights into its role in neutral lipid and energy metabolism. Concerning the ATGL-independent function of CGI-58, a recently identified LPAAT activity for CGI-58 was shown to be involved in the generation of signaling molecules regulating inflammatory processes and insulin action. Summary Although the function of CGI-58 in the catabolism of cellular triglyceride depots via ATGL is well established, further studies are required to consolidate the function of CGI-58 as LPAAT and to clarify the involvement of CGI-58 in the metabolism of skin lipids. PMID:24565921

  3. Role of Cardiac MRI in Diabetes

    PubMed Central

    Shah, Ravi V.; Abbasi, Siddique A.; Kwong, Raymond Y.

    2014-01-01

    Diabetes and insulin resistance have a variety of detrimental effects on cardiovascular health and outcomes. Cardiac magnetic resonance offers a non-invasive means to obtain many layers of information at a tissue level, including fibrosis, edema, intramyocardial motion, triglyceride content, and myocardial energetics. The role of cardiovascular magnetic resonance is particularly important in the evaluation of recognized and unrecognized coronary artery disease. In this review, we address the current state-of-the-art in cardiac magnetic resonance imaging – for both clinical and investigational use – as it applies to diabetic cardiovascular disease. PMID:24430012

  4. Carnitine Palmitoyltransferase-1b (CPT1b) Deficiency Aggravates Pressure-Overload-Induced Cardiac Hypertrophy due to Lipotoxicity

    PubMed Central

    He, Lan; Kim, Teayoun; Long, Qinqiang; Liu, Jian; Wang, Peiyong; Zhou, Yiqun; Ding, Yishu; Prasain, Jeevan; Wood, Philip A.; Yang, Qinglin

    2012-01-01

    Background Carnitine palmitoyltransferase 1(CPT1) is a rate-limiting step of mitochondrial β-oxidation by controlling the mitochondrial uptake of long-chain acyl-CoAs. The muscle isoform, CPT1b, is the predominant isoform expressed in the heart. It has been suggested that inhibiting CPT-1 activity by specific CPT-1 inhibitors exerts protective effects against cardiac hypertrophy and heart failure. However, clinical and animal studies have shown mixed results, thereby posting concerns on the safety of this class of drugs. Preclinical studies using genetically modified animal models should provide a better understanding of targeting CPT1 in order to evaluate it as a safe and effective therapeutic approach. Methods and Results Heterozygous CPT1b knockout mice (CPT1b+/−) were subjected to transverse aorta constriction (TAC)-induced pressure-overload. These mice showed overtly normal cardiac structure/function under the basal condition. Under a severe pressure-overload condition induced by two weeks of transverse aorta constriction (TAC), CPT1b+/− mice were susceptible to premature death with congestive heart failure. Under a milder pressure-overload condition, CPT1b+/− mice exhibited exacerbated cardiac hypertrophy and remodeling compared with that in wild-type littermates. There were more pronounced impairments of cardiac contraction with greater eccentric cardiac hypertrophy in CPT1b+/− than in controlled mice. Moreover, the CPT1b+/− heart exhibited exacerbated mitochondrial abnormalities and myocardial lipid accumulation with elevated triglycerides and ceramide content, leading to greater cardiomyocytes apoptosis. Conclusions We conclude that CPT1b deficiency can cause lipotoxicity in the heart under pathological stress, leading to exacerbation of cardiac pathology. Therefore, caution should be applied in the clinical use of CPT-1 inhibitors. PMID:22932257

  5. Patient Guide to the Assessment and Treatment of Hypertriglyceridemia (High Triglycerides)

    MedlinePlus

    Assessment and Treatment of Hypertriglyceridemia (High Triglycerides) A Patient’s Guide Having high levels of triglycerides, or hypertriglyceridemia , is a common problem. Triglycerides are fats in the blood (also called ...

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

    PubMed Central

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

    2015-01-01

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

  7. Redox Control of Cardiac Excitability

    PubMed Central

    Aggarwal, Nitin T.

    2013-01-01

    Abstract Reactive oxygen species (ROS) have been associated with various human diseases, and considerable attention has been paid to investigate their physiological effects. Various ROS are synthesized in the mitochondria and accumulate in the cytoplasm if the cellular antioxidant defense mechanism fails. The critical balance of this ROS synthesis and antioxidant defense systems is termed the redox system of the cell. Various cardiovascular diseases have also been affected by redox to different degrees. ROS have been indicated as both detrimental and protective, via different cellular pathways, for cardiac myocyte functions, electrophysiology, and pharmacology. Mostly, the ROS functions depend on the type and amount of ROS synthesized. While the literature clearly indicates ROS effects on cardiac contractility, their effects on cardiac excitability are relatively under appreciated. Cardiac excitability depends on the functions of various cardiac sarcolemal or mitochondrial ion channels carrying various depolarizing or repolarizing currents that also maintain cellular ionic homeostasis. ROS alter the functions of these ion channels to various degrees to determine excitability by affecting the cellular resting potential and the morphology of the cardiac action potential. Thus, redox balance regulates cardiac excitability, and under pathological regulation, may alter action potential propagation to cause arrhythmia. Understanding how redox affects cellular excitability may lead to potential prophylaxis or treatment for various arrhythmias. This review will focus on the studies of redox and cardiac excitation. Antioxid. Redox Signal. 18, 432–468. PMID:22897788

  8. Cardiac metastases

    PubMed Central

    Bussani, R; De‐Giorgio, F; Abbate, A; Silvestri, F

    2007-01-01

    Tumours metastatic to the heart (cardiac metastases) are among the least known and highly debated issues in oncology, and few systematic studies are devoted to this topic. Although primary cardiac tumours are extremely uncommon (various postmortem studies report rates between 0.001% and 0.28%), secondary tumours are not, and at least in theory, the heart can be metastasised by any malignant neoplasm able to spread to distant sites. In general, cardiac metastases are considered to be rare; however, when sought for, the incidence seems to be not as low as expected, ranging from 2.3% and 18.3%. Although no malignant tumours are known that diffuse preferentially to the heart, some do involve the heart more often than others—for example, melanoma and mediastinal primary tumours. This paper attempts to review the pathophysiology of cardiac metastatic disease, epidemiology and clinical presentation of cardiac metastases, and pathological characterisation of the lesions. PMID:17098886

  9. 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, PPARα 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

  10. Cardiac Lymphoma.

    PubMed

    Jeudy, Jean; Burke, Allen P; Frazier, Aletta Ann

    2016-07-01

    Lymphoma of the heart and pericardium may develop in up to 25% of patients with disseminated nodal disease, but primary cardiac lymphoma is rare. The majority are diffuse large B-cell lymphomas, which arise in immunocompetent older individuals, men twice as often as women. Subsets are found in immunocompromised patients, including those with HIV-AIDS or allograft recipients. Cardiac lymphomas tend to arise in the wall of the right heart, especially right atrium, with contiguous infiltration of epicardium and pericardium. Pericardial implants and effusions are common. The disease is often multifocal in the heart, but cardiac valves are usually spared. PMID:27265603

  11. Fibroblast growth factor 21 is induced upon cardiac stress and alters cardiac lipid homeostasis

    PubMed Central

    Brahma, Manoja K.; Adam, Rene C.; Pollak, Nina M.; Jaeger, Doris; Zierler, Kathrin A.; Pöcher, Nadja; Schreiber, Renate; Romauch, Matthias; Moustafa, Tarek; Eder, Sandra; Ruelicke, Thomas; Preiss-Landl, Karina; Lass, Achim; Zechner, Rudolf; Haemmerle, Guenter

    2014-01-01

    Fibroblast growth factor 21 (FGF21) is a PPARα-regulated gene elucidated in the liver of PPARα-deficient mice or PPARα agonist-treated mice. Mice globally lacking adipose triglyceride lipase (ATGL) exhibit a marked defect in TG catabolism associated with impaired PPARα-activated gene expression in the heart and liver, including a drastic reduction in hepatic FGF21 mRNA expression. Here we show that FGF21 mRNA expression is markedly increased in the heart of ATGL-deficient mice accompanied by elevated expression of endoplasmic reticulum (ER) stress markers, which can be reversed by reconstitution of ATGL expression in cardiac muscle. In line with this assumption, the induction of ER stress increases FGF21 mRNA expression in H9C2 cardiomyotubes. Cardiac FGF21 expression was also induced upon fasting of healthy mice, implicating a role of FGF21 in cardiac energy metabolism. To address this question, we generated and characterized mice with cardiac-specific overexpression of FGF21 (CM-Fgf21). FGF21 was efficiently secreted from cardiomyocytes of CM-Fgf21 mice, which moderately affected cardiac TG homeostasis, indicating a role for FGF21 in cardiac energy metabolism. Together, our results show that FGF21 expression is activated upon cardiac ER stress linked to defective lipolysis and that a persistent increase in circulating FGF21 levels interferes with cardiac and whole body energy homeostasis. PMID:25176985

  12. Cardiac rehabilitation

    MedlinePlus

    ... 123-210. Thomas PD. Exercise-Based, Comprehensive Cardiac Rehabilitation. In: Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine . 9th ed. Philadelphia, PA: Saunders Elsevier; 2011: ...

  13. Cardiac rehabilitation

    MedlinePlus

    ... goal of cardiac rehab is to: Improve your cardiovascular function Improve your overall health and quality of ... E, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine . 10th ed. Philadelphia, PA: Elsevier Saunders; 2015: ...

  14. Cardiac arrest

    MedlinePlus

    ... treatment for cardiac arrest. It is a medical device that gives an electrical shock to the heart. The shock can get the heart beating normally again. Small, portable defibrillators are often available in public areas for ...

  15. Cardiac amyloidosis

    MedlinePlus

    ... the way electrical signals move through the heart (conduction system). This can lead to abnormal heart beats ( ... due to medication) Sick sinus syndrome Symptomatic cardiac conduction system disease (arrhythmias related to abnormal conduction of ...

  16. Cardiac Sarcoidosis

    MedlinePlus

    ... is Cardiac Sarcoidosis? Sarcoidosis is a poorly understood disease that commonly affects the lungs. It can also involve the lymph nodes, liver, spleen, eyes, skin, bones, salivary glands and heart. ...

  17. Mesenchymal stem cells and cardiac repair

    PubMed Central

    Nesselmann, Catharina; Ma, Nan; Bieback, Karen; Wagner, Wolfgang; Ho, Anthony; Konttinen, Yrjö T; Zhang, Hao; Hinescu, Mihail E; Steinhoff, Gustav

    2008-01-01

    Accumulating clinical and experimental evidence indicates that mesenchymal stem cells (MSCs) are promising cell types in the treatment of cardiac dysfunction. They may trigger production of reparative growth factors, replace damaged cells and create an environment that favours endogenous cardiac repair. However, identifying mechanisms which regulate the role of MSCs in cardiac repair is still at work. To achieve the maximal clinical benefits, ex vivo manipulation can further enhance MSC therapeutic potential. This review focuses on the mechanism of MSCs in cardiac repair, with emphasis on ex vivo manipulation. PMID:18684237

  18. 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. PMID:25848301

  19. The ANGPTL3-4-8 model, a molecular mechanism for triglyceride trafficking

    PubMed Central

    Zhang, Ren

    2016-01-01

    Lipoprotein lipase (LPL) is a rate-limiting enzyme for hydrolysing circulating triglycerides (TG) into free fatty acids that are taken up by peripheral tissues. Postprandial LPL activity rises in white adipose tissue (WAT), but declines in the heart and skeletal muscle, thereby directing circulating TG to WAT for storage; the reverse is true during fasting. However, the mechanism for the tissue-specific regulation of LPL activity during the fed–fast cycle has been elusive. Recent identification of lipasin/angiopoietin-like 8 (Angptl8), a feeding-induced hepatokine, together with Angptl3 and Angptl4, provides intriguing, yet puzzling, insights, because all the three Angptl members are LPL inhibitors, and the deficiency (overexpression) of any one causes hypotriglyceridaemia (hypertriglyceridaemia). Then, why does nature need all of the three? Our recent data that Angptl8 negatively regulates LPL activity specifically in cardiac and skeletal muscles suggest an Angptl3-4-8 model: feeding induces Angptl8, activating the Angptl8–Angptl3 pathway, which inhibits LPL in cardiac and skeletal muscles, thereby making circulating TG available for uptake by WAT, in which LPL activity is elevated owing to diminished Angptl4; the reverse is true during fasting, which suppresses Angptl8 but induces Angptl4, thereby directing TG to muscles. The model suggests a general framework for how TG trafficking is regulated. PMID:27053679

  20. Cardiac Sarcoidosis.

    PubMed

    Birnie, David H; Nery, Pablo B; Ha, Andrew C; Beanlands, Rob S B

    2016-07-26

    Clinically manifest cardiac involvement occurs in perhaps 5% of patients with sarcoidosis. The 3 principal manifestations of cardiac sarcoidosis (CS) are conduction abnormalities, ventricular arrhythmias, and heart failure. An estimated 20% to 25% of patients with pulmonary/systemic sarcoidosis have asymptomatic cardiac involvement (clinically silent disease). In 2014, the first international guideline for the diagnosis and management of CS was published. In patients with clinically manifest CS, the extent of left ventricular dysfunction seems to be the most important predictor of prognosis. There is controversy in published reports as to the outcome of patients with clinically silent CS. Despite a paucity of data, immunosuppression therapy (primarily with corticosteroids) has been advocated for the treatment of clinically manifest CS. Device therapy, primarily with implantable cardioverter-defibrillators, is often recommended for patients with clinically manifest disease. PMID:27443438

  1. New approaches to target microsomal triglyceride transfer protein

    PubMed Central

    Hussain, M.M.; Bakillah, Ahmed

    2009-01-01

    Purpose of review Microsomal triglyceride transfer protein (MTP), a chaperone for the biosynthesis of apolipoprotein B lipoproteins and CD1d, is a therapeutic candidate to decrease plasma lipids and to diminish inflammation. MTP inhibition increases plasma transaminases and tissue lipids, and therefore new approaches are needed to avoid them. Recent findings Inositol requiring enzyme 1β has been identified as a novel intestine-specific regulator of MTP. A new function of MTP in cholesterol ester biosynthesis has been reported. The importance of the phospholipid transfer activity of MTP in the lipidation of apolipoprotein B and CD1d has been indicated. Diurnal variations in MTP expression and its induction by food availability have been observed. On the basis of these and other findings, we propose that upregulation of inositol requiring enzyme 1β, a combined reduction of cellular free cholesterol or triglyceride or both and MTP activity, specific inhibition of phospholipid or triglyceride transfer activities, and targeting of apolipoprotein B–-MTP protein–protein interactions might be pursued to avoid some of the side effects associated with the inhibition of triglyceride transfer activity of MTP. We further speculate that short-lived MTP antagonists may be useful in controlling plasma and tissue lipids and in avoiding steatosis. Summary We have highlighted the importance of addressing the causal relationship between MTP inhibition and aberrant elevations in plasma liver enzymes. The proposed approaches may show that MTP targeting is a viable approach to lower plasma lipids. PMID:18957879

  2. Mechanisms of triglyceride metabolism in patients with bile acid diarrhea.

    PubMed

    Sagar, Nidhi Midhu; McFarlane, Michael; Nwokolo, Chuka; Bardhan, Karna Dev; Arasaradnam, Ramesh Pulendran

    2016-08-14

    Bile acids (BAs) are essential for the absorption of lipids. BA synthesis is inhibited through intestinal farnesoid X receptor (FXR) activity. BA sequestration is known to influence BA metabolism and control serum lipid concentrations. Animal data has demonstrated a regulatory role for the FXR in triglyceride metabolism. FXR inhibits hepatic lipogenesis by inhibiting the expression of sterol regulatory element binding protein 1c via small heterodimer primer activity. Conversely, FXR promotes free fatty acids oxidation by inducing the expression of peroxisome proliferator-activated receptor α. FXR can reduce the expression of microsomal triglyceride transfer protein, which regulates the assembly of very low-density lipoproteins (VLDL). FXR activation in turn promotes the clearance of circulating triglycerides by inducing apolipoprotein C-II, very low-density lipoproteins receptor (VLDL-R) and the expression of Syndecan-1 together with the repression of apolipoprotein C-III, which increases lipoprotein lipase activity. There is currently minimal clinical data on triglyceride metabolism in patients with bile acid diarrhoea (BAD). Emerging data suggests that a third of patients with BAD have hypertriglyceridemia. Further research is required to establish the risk of hypertriglyceridaemia in patients with BAD and elicit the mechanisms behind this, allowing for targeted treatment. PMID:27570415

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

    PubMed Central

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

    2010-01-01

    Unhealthy lipid levels are among the leading controllable risk factors for coronary heart disease. To identify the psychological factors associated with dyslipidemia, this study investigates the personality correlates of cholesterol (total, LDL, and HDL) and triglycerides. A community-based sample (N=5,532) from Sardinia, Italy, had their cholesterol and triglyceride levels assessed and completed a comprehensive personality questionnaire, the NEO-PI-R. All analyses controlled for age, sex, BMI, smoking, drinking, hypertension, and diabetes. Low Conscientiousness and traits related to impulsivity were associated with lower HDL cholesterol and higher triglycerides. Compared to the lowest 10%, those who scored in top 10% on Impulsivity had a 2.5 times greater risk of exceeding the clinical threshold for elevated triglycerides (OR=2.51, CI=1.56–4.07). In addition, sex moderated the association between trait depression (a component of Neuroticism) and HDL cholesterol, such that trait depression was associated with lower levels of HDL cholesterol in women but not men. When considering the connection between personality and health, unhealthy lipid profiles may be one intermediate biomarker between personality and morbidity and mortality. PMID:20109519

  4. 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

  5. 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...

  6. Infectious Complication Following Midface Reconstruction With Calcified Triglyceride.

    PubMed

    Cooper, Sarah E; Durairaj, Vikram D; Ramakrishnan, Vijay R

    2015-01-01

    This case report describes an infectious complication related to the use of calcified triglyceride (Kryptonite Bone Cement) in post-traumatic midface reconstruction. Ultimately, the infected material required removal, and the facial deformity was repaired with subsequent procedures. The literature suggests that bone cement products should be used with caution when in contact with the paranasal sinuses. PMID:24901377

  7. Mechanisms of triglyceride metabolism in patients with bile acid diarrhea

    PubMed Central

    Sagar, Nidhi Midhu; McFarlane, Michael; Nwokolo, Chuka; Bardhan, Karna Dev; Arasaradnam, Ramesh Pulendran

    2016-01-01

    Bile acids (BAs) are essential for the absorption of lipids. BA synthesis is inhibited through intestinal farnesoid X receptor (FXR) activity. BA sequestration is known to influence BA metabolism and control serum lipid concentrations. Animal data has demonstrated a regulatory role for the FXR in triglyceride metabolism. FXR inhibits hepatic lipogenesis by inhibiting the expression of sterol regulatory element binding protein 1c via small heterodimer primer activity. Conversely, FXR promotes free fatty acids oxidation by inducing the expression of peroxisome proliferator-activated receptor α. FXR can reduce the expression of microsomal triglyceride transfer protein, which regulates the assembly of very low-density lipoproteins (VLDL). FXR activation in turn promotes the clearance of circulating triglycerides by inducing apolipoprotein C-II, very low-density lipoproteins receptor (VLDL-R) and the expression of Syndecan-1 together with the repression of apolipoprotein C-III, which increases lipoprotein lipase activity. There is currently minimal clinical data on triglyceride metabolism in patients with bile acid diarrhoea (BAD). Emerging data suggests that a third of patients with BAD have hypertriglyceridemia. Further research is required to establish the risk of hypertriglyceridaemia in patients with BAD and elicit the mechanisms behind this, allowing for targeted treatment. PMID:27570415

  8. Triglyceride in plasma: prospective effects on microcirculatory functions.

    PubMed

    Maeda, Nobuji; Cicha, Iwona; Tateishi, Norihiko; Suzuki, Yoji

    2006-01-01

    The effect of triglyceride in plasma on RBC aggregation was examined, and the prospective influence on the flow of RBCs in microcirculation and the O2 release was discussed. To minimize the individual differences, blood samples were collected from one subject 2 hrs after high-fat and low fat meals. Triglyceride content in plasma was measured by an enzymatic method, and the rate of rouleaux formation was measured with a low shear rheoscope. The rate of rouleaux formation was increased with the increase of triglyceride concentration. Our previous findings suggested some functional impairment in microcirculation. (1) The enhanced RBC aggregation tends to reduce flow resistance in arterioles, but results in inhomogeneous flow of RBCs in capillaries. (2) The sclerotic change of microvessels alters flow behavior of RBCs, and thereby flow resistance is increased. (3) The enhanced RBC aggregation reduces O2 release from RBCs flowing in microvessels. In conclusion, high triglyceride level in plasma not only changes flow behavior of RBCs in microcirculation and thus increases flow resistance, but also prevents homogeneous tissue oxygenation. PMID:16543655

  9. Enhancement of red blood cell aggregation by plasma triglycerides.

    PubMed

    Cicha, I; Suzuki, Y; Tateishi, N; Maeda, N

    2001-01-01

    The effects of plasma triglycerides level on human red blood cells (RBCs) indices, hematological parameters, RBCs aggregation velocity and whole blood viscosity were studied at 2 hours after high-fat or low-fat meal. Proteins, triglycerides and cholesterol levels of plasma were analysed. The RBCs rouleaux formation rate was measured in 70% autologous plasma (with 30% phosphate-buffered saline, PBS) or 1 g/dl dextran T70 solution (with 4 g/dl bovine serum albumin) in PBS, using a low-shear rheoscope. The results were grouped according to triglycerides content in plasma. No significant difference in whole blood viscosity, hematological parameters, RBC indices, protein and cholesterol content was observed between high-fat and low-fat blood samples. There was a significant increase in rouleaux formation rate of samples with high triglyceride levels, when measured in 70% autologous plasma, but it was not significant in dextran T70 containing medium. In conclusion, the results obtained suggest that alteration of plasma lipid levels as well as possible changes in the cell membrane lipid composition lead to enhanced RBC aggregation. PMID:11564913

  10. Boysenberry Polyphenols Suppressed Elevation of Plasma Triglyceride Levels in Rats.

    PubMed

    Mineo, Shigeru; Noguchi, Akane; Nagakura, Yuta; Kobori, Kinji; Ohta, Tatsuo; Sakaguchi, Ei; Ichiyanagi, Takashi

    2015-01-01

    Boysenberry, a hybrid Rubus berry, is mainly cultivated in New Zealand. We previously reported that consumption of boysenberry juice (BBJ) exhibited anti-obesity effects in high-fat feeding rats. In this study, we focused on the suppressive effect of BBJ and its fraction on triglyceride absorption from the gastrointestinal tract. BBJ effectively inhibited pancreatic lipase activity in vitro, and was separated into four fractions (Fr1, Fr2, Fr3 and Fr4) by HP-20 column chromatography. Among all the fractions, Fr3, the ellagic acid-rich fraction, showed the most potent inhibition against pancreatic lipase in vitro with Fr2, the anthocyanin-rich fraction, second. Authentic ellagic acid equivalent in Fr3 showed poor activity against pancreatic lipase. Then, each fraction was orally administered with corn oil to rats fitted with a jugular catheter to examine the effects of each fraction on plasma triglyceride levels. Both Fr2 and Fr3 effectively suppressed the plasma triglyceride level elevation at a dose of 1,000 mg/kg body weight. These findings demonstrated that BBJ contains chemical components which inhibit triglyceride absorption from the gastrointestinal tract. PMID:26440637

  11. Cardiac sarcoidosis

    PubMed Central

    Smedema, J.P.; Zondervan, P.E.; van Hagen, P.; ten Cate, F.J.; Bresser, P.; Doubell, A.F.; Pattynama, P.; Hoogsteden, H.C.; Balk, A.H.M.M.

    2002-01-01

    Sarcoidosis is a multi-system granulomatous disorder of unknown aetiology. Symptomatic cardiac involvement occurs in approximately 5% of patients. The prevalence of sarcoidosis in the Netherlands is unknown, but estimated to be approximately 20 per 100,000 population (3200 patients). We report on five patients who presented with different manifestations of cardiac sarcoidosis, and give a brief review on the current management of this condition. Magnetic Resonance Imaging (MRI) can be of great help in diagnosing this condition as well as in the follow-up of the response to therapy. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6 PMID:25696121

  12. [Cardiac rehabilitation after myocardial infarction].

    PubMed

    Ghannem, M; Ghannem, L; Ghannem, L

    2015-12-01

    Although the proofs of the benefits of cardiac rehabilitation accumulate, many patients are not sent to rehabilitation units, especially younger and very elderly patients. As the length of stay in acute care units decreases, rehabilitation offers more time to fully assess the patients' conditions and needs. Meta-analyses of randomised trials suggest that mortality can be improved by as much as 20-30%. In addition, rehabilitation helps managing risk factors, including hyperlipidemia, diabetes, smoking and sedentary behaviours. Physical training also helps improving exercise capacity. Because of all of these effects, cardiac rehabilitation for post-myocardial infarction patients has been given a class IA recommendation in current guidelines. PMID:26548984

  13. Accumulate Repeat Accumulate Coded Modulation

    NASA Technical Reports Server (NTRS)

    Abbasfar, Aliazam; Divsalar, Dariush; Yao, Kung

    2004-01-01

    In this paper we propose an innovative coded modulation scheme called 'Accumulate Repeat Accumulate Coded Modulation' (ARA coded modulation). This class of codes can be viewed as serial turbo-like codes, or as a subclass of Low Density Parity Check (LDPC) codes that are combined with high level modulation. Thus at the decoder belief propagation can be used for iterative decoding of ARA coded modulation on a graph, provided a demapper transforms the received in-phase and quadrature samples to reliability of the bits.

  14. Aging and Cardiac Fibrosis

    PubMed Central

    Biernacka, Anna; Frangogiannis, Nikolaos G

    2011-01-01

    The aging heart is characterized by morphological and structural changes that lead to its functional decline and are associated with diminished ability to meet increased demand. Extensive evidence, derived from both clinical and experimental studies suggests that the aging heart undergoes fibrotic remodeling. Age-dependent accumulation of collagen in the heart leads to progressive increase in ventricular stiffness and impaired diastolic function. Increased mechanical load, due to reduced arterial compliance, and direct senescence-associated fibrogenic actions appear to be implicated in the pathogenesis of cardiac fibrosis in the elderly. Evolving evidence suggests that activation of several distinct molecular pathways may contribute to age-related fibrotic cardiac remodeling. Reactive oxygen species, chemokine-mediated recruitment of mononuclear cells and fibroblast progenitors, transforming growth factor (TGF)-β activation, endothelin-1 and angiotensin II signaling mediate interstitial and perivascular fibrosis in the senescent heart. Reduced collagen degradation may be more important than increased de novo synthesis in the pathogenesis of aging-associated fibrosis. In contrast to the baseline activation of fibrogenic pathways in the senescent heart, aging is associated with an impaired reparative response to cardiac injury and defective activation of reparative fibroblasts in response to growth factors. Because these reparative defects result in defective scar formation, senescent hearts are prone to adverse dilative remodeling following myocardial infarction. Understanding the pathogenesis of interstitial fibrosis in the aging heart and dissecting the mechanisms responsible for age-associated healing defects following cardiac injury are critical in order to design new strategies for prevention of adverse remodeling and heart failure in elderly patients. PMID:21837283

  15. The hereditary spastic paraplegia-related enzyme DDHD2 is a principal brain triglyceride lipase.

    PubMed

    Inloes, Jordon M; Hsu, Ku-Lung; Dix, Melissa M; Viader, Andreu; Masuda, Kim; Takei, Thais; Wood, Malcolm R; Cravatt, Benjamin F

    2014-10-14

    Complex hereditary spastic paraplegia (HSP) is a genetic disorder that causes lower limb spasticity and weakness and intellectual disability. Deleterious mutations in the poorly characterized serine hydrolase DDHD2 are a causative basis for recessive complex HSP. DDHD2 exhibits phospholipase activity in vitro, but its endogenous substrates and biochemical functions remain unknown. Here, we report the development of DDHD2(-/-) mice and a selective, in vivo-active DDHD2 inhibitor and their use in combination with mass spectrometry-based lipidomics to discover that DDHD2 regulates brain triglycerides (triacylglycerols, or TAGs). DDHD2(-/-) mice show age-dependent TAG elevations in the central nervous system, but not in several peripheral tissues. Large lipid droplets accumulated in DDHD2(-/-) brains and were localized primarily to the intracellular compartments of neurons. These metabolic changes were accompanied by impairments in motor and cognitive function. Recombinant DDHD2 displays TAG hydrolase activity, and TAGs accumulated in the brains of wild-type mice treated subchronically with a selective DDHD2 inhibitor. These findings, taken together, indicate that the central nervous system possesses a specialized pathway for metabolizing TAGs, disruption of which leads to massive lipid accumulation in neurons and complex HSP syndrome. PMID:25267624

  16. Fate of oxidized triglycerides during refining of seed oils.

    PubMed

    Gomes, Tommaso; Caponio, Francesco; Delcuratolo, Debora

    2003-07-30

    The evolution of oxidized triglycerides (ox-TG) during industrial refining was studied in soybean, sunflower, peanut, and corn oils. The analytical techniques used were silica gel column chromatography and high-performance size exclusion chromatography. The decrease in ox-TG during refining (42.3% on average) was accompanied by an increase in triglyceride oligopolymers (TGP). The inverse correlation between the two lipid groups suggests that the decrease in ox-TG during refining was due in part to the occurrence of polymerization reactions. An inverse correlation was also found between the percentage sum of ox-TG + TGP and percent TGP, indicating that a part of the ox-TG also underwent degradation or transformation reactions. On average, almost 58% of the ox-TG remained unchanged during refining and, of the rest, about half was involved in polymerization reactions and half in degradation or transformation reactions. PMID:14705891

  17. Triglyceride-Rich Lipoproteins and Remnants: Targets for Therapy?

    PubMed

    Dallinga-Thie, Geesje M; Kroon, Jeffrey; Borén, Jan; Chapman, M John

    2016-07-01

    It is now evident that elevated circulating levels of triglycerides in the non-fasting state, a marker for triglyceride (TG)-rich remnant particles, are associated with increased risk of premature cardiovascular disease (CVD). Recent findings from basic and clinical studies have begun to elucidate the mechanisms that contribute to the atherogenicity of these apoB-containing particles. Here, we review current knowledge of the formation, intravascular remodelling and catabolism of TG-rich lipoproteins and highlight (i) the pivotal players involved in this process, including lipoprotein lipase, glycosylphosphatidylinositol HDL binding protein 1 (GPIHBP1), apolipoprotein (apo) C-II, apoC-III, angiopoietin-like protein (ANGPTL) 3, 4 and 8, apoA-V and cholesteryl ester transfer protein; (ii) key determinants of triglyceride (TG) levels and notably rates of production of very-low-density lipoprotein 1 (VLDL1) particles; and (iii) the mechanisms which underlie the atherogenicity of remnant particles. Finally, we emphasise the polygenic nature of moderate hypertriglyceridemia and briefly discuss modalities for its clinical management. Several new therapeutic strategies to attenuate hypertriglyceridemia have appeared recently, among which those targeted to apoC-III appear to hold considerable promise. PMID:27216847

  18. α-Lipoic acid as a triglyceride-lowering nutraceutical.

    PubMed

    Pashaj, Anjeza; Xia, Mengna; Moreau, Régis

    2015-12-01

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

  19. Cardiac optogenetics

    PubMed Central

    2013-01-01

    Optogenetics is an emerging technology for optical interrogation and control of biological function with high specificity and high spatiotemporal resolution. Mammalian cells and tissues can be sensitized to respond to light by a relatively simple and well-tolerated genetic modification using microbial opsins (light-gated ion channels and pumps). These can achieve fast and specific excitatory or inhibitory response, offering distinct advantages over traditional pharmacological or electrical means of perturbation. Since the first demonstrations of utility in mammalian cells (neurons) in 2005, optogenetics has spurred immense research activity and has inspired numerous applications for dissection of neural circuitry and understanding of brain function in health and disease, applications ranging from in vitro to work in behaving animals. Only recently (since 2010), the field has extended to cardiac applications with less than a dozen publications to date. In consideration of the early phase of work on cardiac optogenetics and the impact of the technique in understanding another excitable tissue, the brain, this review is largely a perspective of possibilities in the heart. It covers the basic principles of operation of light-sensitive ion channels and pumps, the available tools and ongoing efforts in optimizing them, overview of neuroscience use, as well as cardiac-specific questions of implementation and ideas for best use of this emerging technology in the heart. PMID:23457014

  20. Cardiac Surgery

    PubMed Central

    Weisse, Allen B.

    2011-01-01

    Well into the first decades of the 20th century, medical opinion held that any surgical attempts to treat heart disease were not only misguided, but unethical. Despite such reservations, innovative surgeons showed that heart wounds could be successfully repaired. Then, extracardiac procedures were performed to correct patent ductus arteriosus, coarctation of the aorta, and tetralogy of Fallot. Direct surgery on the heart was accomplished with closed commissurotomy for mitral stenosis. The introduction of the heart-lung machine and cardiopulmonary bypass enabled the surgical treatment of other congenital and acquired heart diseases. Advances in aortic surgery paralleled these successes. The development of coronary artery bypass grafting greatly aided the treatment of coronary heart disease. Cardiac transplantation, attempts to use the total artificial heart, and the application of ventricular assist devices have brought us to the present day. Although progress in the field of cardiovascular surgery appears to have slowed when compared with the halcyon times of the past, substantial challenges still face cardiac surgeons. It can only be hoped that sufficient resources and incentive can carry the triumphs of the 20th century into the 21st. This review covers past developments and future opportunities in cardiac surgery. PMID:22163121

  1. [Cardiac involvement in Fabry's disease].

    PubMed

    Weidemann, Frank; Breunig, Frank

    2008-03-15

    Fabry's disease is a rare X-linked lysosomal storage disorder leading to an accumulation of globotriaosylceramides in the lysosomes of all tissues. The disease is characterized by a progressive involvement of important vital organs like the kidneys, the cerebrovascular system and the heart. Within the scope of this article an overview of Fabry's cardiomyopathy, the necessary cardiac diagnostic tests and, in addition, the new concept of enzyme replacement therapy is given. PMID:18344066

  2. Comparison of the pharmacological profiles of murine antisense oligonucleotides targeting apolipoprotein B and microsomal triglyceride transfer protein.

    PubMed

    Lee, Richard G; Fu, Wuxia; Graham, Mark J; Mullick, Adam E; Sipe, Donna; Gattis, Danielle; Bell, Thomas A; Booten, Sheri; Crooke, Rosanne M

    2013-03-01

    Therapeutic agents that suppress apolipoprotein B (apoB) and microsomal triglyceride transfer protein (MTP) levels/activity are being developed in the clinic to benefit patients who are unable to reach target LDL-C levels with maximally tolerated lipid-lowering drugs. To compare and contrast the metabolic consequences of reducing these targets, murine-specific apoB or MTP antisense oligonucleotides (ASOs) were administered to chow-fed and high fat-fed C57BL/6 or to chow-fed and Western diet-fed LDLr⁻/⁻ mice for periods ranging from 2 to 12 weeks, and detailed analyses of various factors affecting fatty acid metabolism were performed. Administration of these drugs significantly reduced target hepatic mRNA and protein, leading to similar reductions in hepatic VLDL/triglyceride secretion. MTP ASO treatment consistently led to increases in hepatic triglyceride accumulation and biomarkers of hepatotoxicity relative to apoB ASO due in part to enhanced expression of peroxisome proliferator activated receptor γ target genes and the inability to reduce hepatic fatty acid synthesis. Thus, although both drugs effectively lowered LDL-C levels in mice, the apoB ASO produced a more positive liver safety profile. PMID:23220583

  3. Triglyceride-Rich Lipoproteins Modulate the Distribution and Extravasation of Ly6C/Gr1(low) Monocytes.

    PubMed

    Saja, Maha F; Baudino, Lucie; Jackson, William D; Cook, H Terence; Malik, Talat H; Fossati-Jimack, Liliane; Ruseva, Marieta; Pickering, Matthew C; Woollard, Kevin J; Botto, Marina

    2015-09-22

    Monocytes are heterogeneous effector cells involved in the maintenance and restoration of tissue integrity. However, their response to hyperlipidemia remains poorly understood. Here, we report that in the presence of elevated levels of triglyceride-rich lipoproteins, induced by administration of poloxamer 407, the blood numbers of non-classical Ly6C/Gr1(low) monocytes drop, while the number of bone marrow progenitors remains similar. We observed an increased crawling and retention of the Gr1(low) monocytes at the endothelial interface and a marked accumulation of CD68(+) macrophages in several organs. Hypertriglyceridemia was accompanied by an increased expression of tissue, and plasma CCL4 and blood Gr1(low) monocyte depletion involved a pertussis-toxin-sensitive receptor axis. Collectively, these findings demonstrate that a triglyceride-rich environment can alter blood monocyte distribution, promoting the extravasation of Gr1(low) cells. The behavior of these cells in response to dyslipidemia highlights the significant impact that high levels of triglyceride-rich lipoproteins may have on innate immune cells. PMID:26344769

  4. Experimentally caused proliferation of lysosomes in cultured BHK cells involving an increase of biphosphatidic acids and triglycerides.

    PubMed

    Brotherus, J; Niinioja, T; Sandelin, K; Renkonen, O

    1977-05-01

    When cultured hamster fibroblasts (BHK 21 cells) were incubated in a synthetic serum-free medium up to 4 days, they developed signs of a progressive proliferation of lysosomes. The cells became filled with vacuoles that contained polymorphic debris and showed acid phosphatase activity. The specific activities of acid protease and acid phosphatase in the cell cultures increased three- to fourfold. The process was accompanied by a marked decrease in the contents of protein, deoxyribonucleic acid, and total phospholipids of the cultures. The concentration of lysobisphosphatidic acid increased during the incubation from about 1.5% to 3-6% of the cellular phospholipids. The concentrations of two related lipids, bisphosphatidic acid and semilysobisphosphatidic acid also increased substantially. The triglyceride content of the cells increased several fold, whereas the concentration of phosphatidylcholine decreased markedly. Lysobisphosphatidic acid did not increase upon induction of vacuolization by exogenous sucrose, nor when there was an accumulation of triglyceride due to addition of oleic acid to the growth medium. These findings suggest that the formation of the bisphosphatidic acids may be specifically linked to the autolysis of the phospholipids of the cellular membranes and the formation of triglycerides associated with this process. PMID:864326

  5. AMP-Activated Kinase Regulates Lipid Droplet Localization and Stability of Adipose Triglyceride Lipase in C. elegans Dauer Larvae

    PubMed Central

    Xie, Meng; Roy, Richard

    2015-01-01

    Animals have developed diverse mechanisms to adapt to their changing environment. Like many organisms the free-living nematode C. elegans can alternate between a reproductive mode or a diapause-like "dauer" stage during larval development to circumvent harsh environmental conditions. The master metabolic regulator AMP-activated protein kinase (AMPK) is critical for survival during the dauer stage, where it phosphorylates adipose triglyceride lipase (ATGL-1) at multiple sites to block lipid hydrolysis and ultimately protect the cellular triglyceride-based energy depot from rapid depletion. However, how the AMPK-mediated phosphorylation affects the function of ATGL-1 has not been characterised at the molecular level. Here we show that AMPK phosphorylation leads to the generation of 14-3-3 binding sites on ATGL-1, which are recognized by the C. elegans 14-3-3 protein orthologue PAR-5. Physical interaction of ATGL-1 with PAR-5 results in sequestration of ATGL-1 away from the lipid droplets and eventual proteasome-mediated degradation. In addition, we also show that the major AMPK phosphorylation site on ATGL-1, Ser 303, is required for both modification of its lipid droplet localization and its degradation. Our data provide mechanistic insight as to how AMPK functions to enhance survival through its ability to protect the accumulated triglyceride deposits from rapid hydrolysis to preserve the energy stores during periods of extended environmental duress. PMID:26098762

  6. 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...

  7. Competitive effects of long-chain-triglyceride emulsion on the metabolism of medium-chain-triglyceride emulsions.

    PubMed

    Cotter, R; Johnson, R C; Young, S K; Lin, L I; Rowe, W B

    1989-10-01

    This study was conducted to assess the potential metabolic competitive interactions of intravenous medium-chain-triglyceride (MCT) and long-chain-triglyceride (LCT) lipid emulsions. To assess this competition increasing concentrations of LCT emulsion were added to an intravenous dose of MCT emulsion of 3.0 g/kg body wt up to a maximum dose of 3.0 g LCTs/kg body wt. Blood samples were assessed for competitive interactions by analyzing the following metabolites: glucose, insulin, lactate, pyruvate, ketones (acetoacetate, beta-hydroxybutyrate), elimination of triglycerides, and free fatty acids. Evaluation of the data showed a strong competitive interaction between the MCT and LCT emulsions. This competition was evident as soon as LCTs were added to the MCT infusions and appeared to favor LCTs for removal and metabolism over MCTs. This appears to indicate that there is a peripheral, strong affinity site for LCT removal and metabolism and a shared peripheral site and specific visceral site for MCT removal and metabolism. PMID:2679038

  8. Parenteral use of medium-chain triglycerides: a reappraisal.

    PubMed

    Ulrich, H; Pastores, S M; Katz, D P; Kvetan, V

    1996-04-01

    Over the last two decades, the clinical use of intravenous fat emulsions for the nutritional support of hospitalized patients has become routine. During this time long-chain triglycerides (LCT) derived from soybean and/or safflower oils were the exclusive lipid source for these emulsions, providing both a safe calorically dense alternative to dextrose and essential fatty acids needed for biologic membranes and the maintenance of immune function. During the past decade, the availability of novel experimental triglycerides for parenteral use has generated interest in the use of these substrates for nutritional and metabolic support. Medium-chain triglycerides (MCT), long advocated as a superior substrate for parenteral use, possess many unique physiochemical and metabolic properties that make them theoretically advantageous over their LCT counterparts. Although not yet approved in the United States, preparations containing MCT have been widely available in Europe. Intravenous MCT preparations, either as physical mixtures or structured lipids, have been used clinically in patients with immunosuppresion, critical illness, liver and pulmonary disease and in premature infants. Despite great promise, the clinical data comparing the efficacy of MCT-based lipid emulsions to their LCT counterparts has been equivocal. This may be due in part to the limited nature of the published clinical trials. Measures of efficacy for parenteral or enteral nutritional products has taken on new meaning, in light of the reported experience using immunomodulatory nutrients. Current concerns about cost of medical care and resource use warrant careful deliberation about the utility of any new and expensive therapy. Until clinical data can fulfill expectations derived from animal studies, it is difficult to advocate the general use of MCT-based lipid emulsions. Future clinical studies with MCT-based emulsions should have clear outcome objectives sufficient to prove their theorized metabolic

  9. The medium chain triglyceride diet and intractable epilepsy.

    PubMed Central

    Sills, M A; Forsythe, W I; Haidukewych, D; MacDonald, A; Robinson, M

    1986-01-01

    Fifty children with drug resistant epilepsy were treated with the Medium Chain Triglyceride (MCT) Emulsion diet. Eight achieved complete control of seizures (four without anticonvulsant drugs), and with the addition of anticonvulsants four had seizures reduced in frequency by 90% and 10 by 50-90%. The best results were obtained with astatic myoclonic and absence seizures, but control of seizures was improved in four children with tonic-clonic and three with complex partial seizures. Food given at the same time as MCT helped to reduce side effects, and an extra dose of MCT before bedtime improved control of nocturnal seizures. PMID:3101615

  10. 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

  11. Cardiac rehabilitation.

    PubMed

    Ehsani, A A

    1984-02-01

    Exercise training is a major, and the most important, component of cardiac rehabilitation. Besides providing psychological benefits and promoting a "sense of well being," it elicits a number of adaptations in patients with ischemic heart disease. Among the clinically important adaptations are changes in the trained skeletal muscles and autonomic nervous system, resulting not only in increased maximum exercise capacity but also a slower heart rate and, at times, a lower systolic blood pressure during submaximal exercise. The reduction in the rate pressure product decreases myocardial O2 demand at any given submaximal exercise intensity and may thus alleviate myocardial ischemia and angina in patients with coronary artery disease. These adaptive responses occur even with a relatively modest exercise intensity. Although short-term exercise training of moderate intensity has not been reported to result in improvement in left ventricular performance, recent data suggest that exercise training of higher intensity and longer duration (12 months or longer) than has conventionally been used in cardiac rehabilitation programs may favorably affect the heart. This is characterized by improvements in left ventricular function, diminished electrocardiographic criteria of myocardial ischemia and increased stroke volume during exercise. Modest weight reduction accompanies regularly performed prolonged exercise training. It is important, however, to recognize that high-intensity exercise programs are suitable for only some patients with coronary artery disease who are stable and should be used only under strict medical supervision. PMID:6400004

  12. Treatment of cardiomyopathy and rhabdomyolysis in long-chain fat oxidation disorders using an anaplerotic odd-chain triglyceride

    PubMed Central

    Roe, Charles R.; Sweetman, Lawrence; Roe, Diane S.; David, France; Brunengraber, Henri

    2002-01-01

    The current dietary treatment of long-chain fatty acid oxidation defects (high carbohydrate with medium-even-chain triglycerides and reduced amounts of long-chain fats) fails, in many cases, to prevent cardiomyopathy, rhabdomyolysis, and muscle weakness. We hypothesized that the apparent defect in energy production results from a depletion of the catalytic intermediates of the citric acid cycle via leakage through cell membranes (cataplerosis). We further hypothesized that replacing dietary medium-even-chain fatty acids (precursors of acetyl-CoA) by medium-odd-chain fatty acids (precursors of acetyl-CoA and anaplerotic propionyl-CoA) would restore energy production and improve cardiac and skeletal muscle function. We fed subjects with long-chain defects a controlled diet in which the fat component was switched from medium-even-chain triglycerides to triheptanoin. In three patients with very-long-chain acyl-CoA dehydrogenase deficiency, this treatment led rapidly to clinical improvement that included the permanent disappearance of chronic cardiomyopathy, rhabdomyolysis, and muscle weakness (for more than 2 years in one child), and of rhabdomyolysis and weakness in the others. There was no evidence of propionyl overload in these patients. The treatment has been well tolerated for up to 26 months and opens new avenues for the management of patients with mitochondrial fat oxidation disorders. PMID:12122118

  13. Treatment of cardiomyopathy and rhabdomyolysis in long-chain fat oxidation disorders using an anaplerotic odd-chain triglyceride.

    PubMed

    Roe, Charles R; Sweetman, Lawrence; Roe, Diane S; David, France; Brunengraber, Henri

    2002-07-01

    The current dietary treatment of long-chain fatty acid oxidation defects (high carbohydrate with medium-even-chain triglycerides and reduced amounts of long-chain fats) fails, in many cases, to prevent cardiomyopathy, rhabdomyolysis, and muscle weakness. We hypothesized that the apparent defect in energy production results from a depletion of the catalytic intermediates of the citric acid cycle via leakage through cell membranes (cataplerosis). We further hypothesized that replacing dietary medium-even-chain fatty acids (precursors of acetyl-CoA) by medium-odd-chain fatty acids (precursors of acetyl-CoA and anaplerotic propionyl-CoA) would restore energy production and improve cardiac and skeletal muscle function. We fed subjects with long-chain defects a controlled diet in which the fat component was switched from medium-even-chain triglycerides to triheptanoin. In three patients with very-long-chain acyl-CoA dehydrogenase deficiency, this treatment led rapidly to clinical improvement that included the permanent disappearance of chronic cardiomyopathy, rhabdomyolysis, and muscle weakness (for more than 2 years in one child), and of rhabdomyolysis and weakness in the others. There was no evidence of propionyl overload in these patients. The treatment has been well tolerated for up to 26 months and opens new avenues for the management of patients with mitochondrial fat oxidation disorders. PMID:12122118

  14. 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

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

    SciTech Connect

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

    2013-01-15

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

  16. Decoding the Cardiac Message

    PubMed Central

    Dorn, Gerald W

    2012-01-01

    This review reflects and expands upon the contents of the author’s presentation at The Thomas W. Smith Memorial Lecture at AHA Scientific Sessions, 2011. “Decoding the cardiac message” refers to accumulating results from ongoing microRNA research that is altering longstanding concepts of the mechanisms for, and consequences of, messenger RNA (mRNA) regulation in the heart. First, I provide a brief historical perspective of the field of molecular genetics, touching upon seminal research that paved the way for modern molecular cardiovascular research and helped establish the foundation for current concepts of mRNA regulation in the heart. I follow with some interesting details about the specific research that led to the discovery and appreciation of microRNAs as highly conserved pivotal regulators of RNA expression and translation. Finally, I provide a personal viewpoint as to how agnostic genome-wide techniques for measuring microRNAs, their mRNA targets, and their protein products can be applied in an integrated multi-systems approach to uncover direct and indirect effects of microRNAs. Experimental designs integrating next-generation sequencing and global proteomics have the potential to address unanswered questions regarding microRNA-mRNA interactions in cardiac disease, how disease alters mRNA targeting by specific microRNAs, and how mutational and polymorphic nucleotide variation in microRNAs can affect end-organ function and stress-response. PMID:22383710

  17. Effects of phorbol 12-myristate 13-acetate on triglyceride and cholesteryl ester synthesis in cultured coronary smooth muscle cells and macrophages.

    PubMed

    Moinat, M; Chevey, J M; Muzzin, P; Giacobino, J P; Kossovsky, M

    1990-02-01

    In cultured pig coronary smooth muscle cells phorbol 12-myristate 13-acetate (PMA) stimulated the conversion of [4-14C]cholesterol into cholesteryl esters and the incorporation of [2-3H]glycerol into triglycerides 6.4- and 4.5-fold, respectively. The maximal effects occurred after 3 h of treatment and there was a return to basal values after 72 h. In the presence of 400 microM oleic acid, PMA stimulated the conversion of [4-14C]cholesterol into cholesteryl esters and that of [2-3H]glycerol into triglycerides 5.3- and 2.3-fold, respectively. The stimulatory effects were more sustained (still significant after 72 h) and their maxima were delayed (peaks after 24 h). PMA was also found to increase 2-fold the amount of triglyceride that accumulated in the cells in the presence of oleic acid after 24 h. In macrophages IC-21, the effects of PMA were observed only in the presence of oleic acid. They consisted of a 1.9-fold stimulation in the conversion of [4-14C]cholesterol into cholesteryl esters after 72 h and of a 1.7-fold stimulation in the incorporation of [2-3H]glycerol into triglycerides after 24 h. PMA also increased the amount of triglyceride that accumulated in the cells 1.9-fold after 72 h. It is concluded that PMA, and possibly growth factors, may promote lipid storage in smooth muscle cells and that fatty acids favor long lasting effects of PMA in smooth muscle cells and are necessary for any effect of PMA in macrophages. PMID:2324651

  18. Empagliflozin Protects against Diet-Induced NLRP-3 Inflammasome Activation and Lipid Accumulation.

    PubMed

    Benetti, Elisa; Mastrocola, Raffaella; Vitarelli, Giovanna; Cutrin, Juan Carlos; Nigro, Debora; Chiazza, Fausto; Mayoux, Eric; Collino, Massimo; Fantozzi, Roberto

    2016-10-01

    The aim of this study was to evaluate the effects of chronic treatment with empagliflozin, a potent and selective sodium glucose cotransporter-2 inhibitor, in a murine model of diet-induced obesity and insulin resistance, focusing on drug effects on body weight reduction and nucleotide-binding domain, leucine-rich repeat containing protein (NLRP)-3 inflammasome activation, which have never been investigated to date. Male C57BL/6 mice were fed control or a high fat-high sugar (HFHS) diet for 4 months. Over the last 2 months, subsets of animals were treated with empagliflozin (1-10 mg/kg) added to the diet. Empagliflozin evoked body weight reduction (P < 0.001 for the highest dose) and positive effects on fasting glycemia and homeostasis model assessment of insulin resistance. In addition, the drug was able to reduce renal tubular damage and liver triglycerides level in a dose-dependent manner. Interestingly, empagliflozin also decreased cardiac lipid accumulation. Moreover, diet-induced activation of NLRP-3 in kidney and liver (not observed in the heart) was dose-dependently attenuated by empagliflozin. Our results clearly demonstrate the ability of empagliflozin to counteract the deleterious effects evoked by chronic exposure to HFHS diet. Most notably, empagliflozin treatment was associated with NLRP-3 inflammasome signaling modulation, suggesting that this inhibition may contribute to the drug therapeutic effects. PMID:27440421

  19. Pleiotropic Analysis of Lung Cancer and Blood Triglycerides.

    PubMed

    Zuber, Verena; Marconett, Crystal N; Shi, Jianxin; Hua, Xing; Wheeler, William; Yang, Chenchen; Song, Lei; Dale, Anders M; Laplana, Marina; Risch, Angela; Witoelar, Aree; Thompson, Wesley K; Schork, Andrew J; Bettella, Francesco; Wang, Yunpeng; Djurovic, Srdjan; Zhou, Beiyun; Borok, Zea; van der Heijden, Henricus F M; de Graaf, Jacqueline; Swinkels, Dorine; Aben, Katja K; McKay, James; Hung, Rayjean J; Bikeböller, Heike; Stevens, Victoria L; Albanes, Demetrius; Caporaso, Neil E; Han, Younghun; Wei, Yongyue; Panadero, Maria Angeles; Mayordomo, Jose I; Christiani, David C; Kiemeney, Lambertus; Andreassen, Ole A; Houlston, Richard; Amos, Christopher I; Chatterjee, Nilanjan; Laird-Offringa, Ite A; Mills, Ian G; Landi, Maria Teresa

    2016-12-01

    Epidemiologically related traits may share genetic risk factors, and pleiotropic analysis could identify individual loci associated with these traits. Because of their shared epidemiological associations, we conducted pleiotropic analysis of genome-wide association studies of lung cancer (12 160 lung cancer case patients and 16 838 control subjects) and cardiovascular disease risk factors (blood lipids from 188 577 subjects, type 2 diabetes from 148 821 subjects, body mass index from 123 865 subjects, and smoking phenotypes from 74 053 subjects). We found that 6p22.1 (rs6904596, ZNF184) was associated with both lung cancer (P = 5.50x10(-6)) and blood triglycerides (P = 1.39x10(-5)). We replicated the association in 6097 lung cancer case patients and 204 657 control subjects (P = 2.40 × 10(-4)) and in 71 113 subjects with triglycerides data (P = .01). rs6904596 reached genome-wide significance in lung cancer meta-analysis (odds ratio = 1.15, 95% confidence interval = 1.10 to 1.21 ,: Pcombined = 5.20x10(-9)). The large sample size provided by the lipid GWAS data and the shared genetic risk factors between the two traits contributed to the uncovering of a hitherto unidentified genetic locus for lung cancer. PMID:27565901

  20. PCSK9 and triglyceride-rich lipoprotein metabolism

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  2. Medium-chain triglyceride and n-3 polyunsaturated fatty acid-containing emulsions in intravenous nutrition.

    PubMed

    Chan, S; McCowen, K C; Bistrian, B

    1998-03-01

    Medium-chain triglycerides and n-3 polyunsaturated fatty acid emulsions as a physical mixture have attracted increasing interest for use in parenteral nutrition and may play an important role in the development of structured triglycerides in a future generation of new lipids. Over the past two decades, the clinical use of intravenous emulsion for the nutritional support of hospitalized patients has relied exclusively on long-chain triglycerides providing both a safe, calorically dense alternative to dextrose and a source of essential fatty acids needed for biological membranes and maintenance of the immune function. During the past decade, the development of new triglycerides (medium- and long-chain triglyceride emulsions and structured triglyceride emulsions) for parenteral use have provided useful advances and opportunities to enhance nutritional and metabolic support. Medium-chain triglycerides and n-3 polyunsaturated fatty acid emulsions possess unique physical, chemical, and metabolic properties that make them theoretically advantageous over the conventional long-chain triglycerides. The physical mixture of medium- and long-chain triglycerides have been used clinically in patients with critical illness, liver disease, immunosuppression, pulmonary disease, and in premature infants, with good tolerance and the avoidance of some of the problems encountered with long-chain triglycerides alone. PMID:10565343

  3. Imaging of cardiac sarcoidosis.

    PubMed

    Erthal, Fernanda; Juneau, Daniel; Lim, Siok P; Dwivedi, Girish; Nery, Pablo B; Birnie, David; Beanlands, Rob S

    2016-09-01

    Sarcoidosis is a multisystem inflammatory disease. Cardiac involvement is described in up to 50% of the cases. The disease spectrum is wide and cardiac manifestations ranges from being asymptomatic to heart failure, arrhythmias and sudden cardiac death. The diagnosis of cardiac sarcoidosis can be challenging due to its non-specific nature and the focal involvement of the heart. In this review, we discuss the utility of a stepwise approach with multimodality cardiac imaging in the diagnosis and management of CS. PMID:27225318

  4. Cardiac lipin 1 expression is regulated by the peroxisome proliferator activated receptor γ coactivator 1α/estrogen related receptor axis.

    PubMed

    Mitra, Mayurranjan S; Schilling, Joel D; Wang, Xiaowei; Jay, Patrick Y; Huss, Janice M; Su, Xiong; Finck, Brian N

    2011-07-01

    Lipin family proteins (lipin 1, 2, and 3) are bifunctional intracellular proteins that regulate metabolism by acting as coregulators of DNA-bound transcription factors and also dephosphorylate phosphatidate to form diacylglycerol [phosphatidate phosphohydrolase activity] in the triglyceride synthesis pathway. Herein, we report that lipin 1 is enriched in heart and that hearts of mice lacking lipin 1 (fld mice) exhibit accumulation of phosphatidate. We also demonstrate that the expression of the gene encoding lipin 1 (Lpin1) is under the control of the estrogen-related receptors (ERRs) and their coactivator the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). PGC-1α, ERRα, or ERRγ overexpression increased Lpin1 transcription in cultured ventricular myocytes and the ERRs were associated with response elements in the first intron of the Lpin1 gene. Concomitant RNAi-mediated knockdown of ERRα and ERRγ abrogated the induction of lipin 1 expression by PGC-1α overexpression. Consistent with these data, 3-fold overexpression of PGC-1α in intact myocardium of transgenic mice increased cardiac lipin 1 and ERRα/γ expression. Similarly, injection of the β2-adrenergic agonist clenbuterol induced PGC-1α and lipin 1 expression, and the induction in lipin 1 after clenbuterol occurred in a PGC-1α-dependent manner. In contrast, expression of PGC-1α, ERRα, ERRγ, and lipin 1 was down-regulated in failing heart. Cardiac phosphatidic acid phosphohydrolase activity was also diminished, while cardiac phosphatidate content was increased, in failing heart. Collectively, these data suggest that lipin 1 is the principal lipin protein in the myocardium and is regulated in response to physiologic and pathologic stimuli that impact cardiac metabolism. PMID:21549711

  5. Cardiac lipin 1 expression is regulated by the peroxisome proliferator activated receptor γ coactivator 1α/estrogen related receptor axis

    PubMed Central

    Mitra, Mayurranjan S.; Schilling, Joel D.; Wang, Xiaowei; Jay, Patrick Y.; Huss, Janice M.; Su, Xiong; Finck, Brian N.

    2011-01-01

    Lipin family proteins (lipin 1, 2, and 3) are bifunctional intracellular proteins that regulate metabolism by acting as coregulators of DNA-bound transcription factors and also dephosphorylate phosphatidate to form diacylglycerol [phosphatidate phosphohydrolase activity] in the triglyceride synthesis pathway. Herein, we report that lipin 1 is enriched in heart and that hearts of mice lacking lipin 1 (fld mice) exhibit accumulation of phosphatidate. We also demonstrate that the expression of the gene encoding lipin 1 (Lpin1) is under the control of the estrogen-related receptors (ERRs) and their coactivator the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). PGC-1α, ERRα, or ERRγ overexpression increased Lpin1 transcription in cultured ventricular myocytes and the ERRs were associated with response elements in the first intron of the Lpin1 gene. Concomitant RNAi-mediated knockdown of ERRα and ERRγ abrogated the induction of lipin 1 expression by PGC-1α overexpression. Consistent with these data, 3-fold overexpression of PGC-1α in intact myocardium of transgenic mice increased cardiac lipin 1 and ERRα/γ expression. Similarly, injection of the β2-adrenergic agonist clenbuterol induced PGC-1α and lipin 1 expression, and the induction in lipin 1 after clenbuterol occurred in a PGC-1α-dependent manner. In contrast, expression of PGC-1α, ERRα, ERRγ, and lipin 1 was down-regulated in failing heart. Cardiac phosphatidic acid phosphohydrolase activity was also diminished, while cardiac phosphatidate content was increased, in failing heart. Collectively, these data suggest that lipin 1 is the principal lipin protein in the myocardium and is regulated in response to physiologic and pathologic stimuli that impact cardiac metabolism. PMID:21549711

  6. Palmitate Diet-induced Loss of Cardiac Caveolin-3: A Novel Mechanism for Lipid-induced Contractile Dysfunction

    PubMed Central

    Knowles, Catherine J.; Cebova, Martina; Pinz, Ilka M.

    2013-01-01

    Obesity is associated with an increased risk of cardiomyopathy, and mechanisms linking the underlying risk and dietary factors are not well understood. We tested the hypothesis that dietary intake of saturated fat increases the levels of sphingolipids, namely ceramide and sphingomyelin in cardiac cell membranes that disrupt caveolae, specialized membrane micro-domains and important for cellular signaling. C57BL/6 mice were fed two high-fat diets: palmitate diet (21% total fat, 47% is palmitate), and MCT diet (21% medium-chain triglycerides, no palmitate). We established that high-palmitate feeding for 12 weeks leads to 40% and 50% increases in ceramide and sphingomyelin, respectively, in cellular membranes. Concomitant with sphingolipid accumulation, we observed a 40% reduction in systolic contractile performance. To explore the relationship of increased sphingolipids with caveolins, we analyzed caveolin protein levels and intracellular localization in isolated cardiomyocytes. In normal cardiomyocytes, caveolin-1 and caveolin-3 co-localize at the plasma membrane and the T-tubule system. However, mice maintained on palmitate lost 80% of caveolin-3, mainly from the T-tubule system. Mice maintained on MCT diet had a 90% reduction in caveolin-1. These data show that caveolin isoforms are sensitive to the lipid environment. These data are further supported by similar findings in human cardiac tissue samples from non-obese, obese, non-obese cardiomyopathic, and obese cardiomyopathic patients. To further elucidate the contractile dysfunction associated with the loss of caveolin-3, we determined the localization of the ryanodine receptor and found lower expression and loss of the striated appearance of this protein. We suggest that palmitate-induced loss of caveolin-3 results in cardiac contractile dysfunction via a defect in calcium-induced calcium release. PMID:23585895

  7. Nitro-Oleic Acid Reduces J774A.1 Macrophage Oxidative Status and Triglyceride Mass: Involvement of Paraoxonase2 and Triglyceride Metabolizing Enzymes.

    PubMed

    Rosenblat, Mira; Rom, Oren; Volkova, Nina; Aviram, Michael

    2016-08-01

    Nitro-fatty acids possess anti-atherogenic properties, but their effects on macrophage oxidative status and lipid metabolism that play important roles in atherosclerosis development are unclear. This study compared the effects of nitro-oleic acid (OLA-NO2) with those of native oleic acid (OLA) on intracellular reactive oxygen species (ROS) generation, anti-oxidants and metabolism of triglycerides and cholesterol in J774A.1 macrophages. Upon incubating the cells with physiological concentrations of OLA-NO2 (0-1 µM) or with equivalent levels of OLA, ROS levels measured by 2, 7-dichlorofluorescein diacetate, decreased dose-dependently, but the anti-oxidative effects of OLA-NO2 were significantly augmented. Copper ion addition increased ROS generation in OLA treated macrophages without affecting OLA-NO2 treated cells. These effects could be attributed to elevated glutathione levels and to increased activity and expression of paraoxonase2 that were observed in OLA-NO2 vs OLA treated cells. Beneficial effects on triglyceride metabolism were noted in OLA-NO2 vs OLA treated macrophages in which cellular triglycerides were reduced due to attenuated biosynthesis and accelerated hydrolysis of triglycerides. Accordingly, OLA-NO2 treated cells demonstrated down-regulation of diacylglycerol acyltransferase1, the key enzyme in triglyceride biosynthesis, and increased expression of hormone-sensitive lipase and adipose triglyceride lipase that regulate triglyceride hydrolysis. Finally, OLA-NO2 vs OLA treatment resulted in modest but significant beneficial effects on macrophage cholesterol metabolism, reducing cholesterol biosynthesis rate and low density lipoprotein influx into the cells, while increasing high density lipoprotein-mediated cholesterol efflux from the macrophages. Collectively, compared with OLA, OLA-NO2 modestly but significantly reduces macrophage oxidative status and cellular triglyceride content via modulation of cellular anti-oxidants and triglyceride

  8. Improved triglyceride transesterification by circular permuted Candida antarctica lipase B.

    PubMed

    Yu, Ying; Lutz, Stefan

    2010-01-01

    Lipases represent a versatile class of biocatalysts with numerous potential applications in industry including the production of biodiesel via enzyme-catalyzed transesterification. In this article, we have investigated the performance of cp283, a variant of Candida antarctica lipase B (CALB) engineered by circular permutation, with a series of esters, as well as pure and complex triglycerides. In comparison with wild-type CALB, the permutated enzyme showed consistently higher catalytic activity (2.6- to 9-fold) for trans and interesterification of the different substrates with 1-butanol and ethyl acetate as acyl acceptors. Differences in the observed rates for wild-type CALB and cp283 are believe to be related to changes in the rate-determining step of the catalytic cycle as a result of circular permutation. PMID:19609971

  9. Therapeutic Targets of Triglyceride Metabolism as Informed by Human Genetics.

    PubMed

    Bauer, Robert C; Khetarpal, Sumeet A; Hand, Nicholas J; Rader, Daniel J

    2016-04-01

    Human genetics has contributed to the development of multiple drugs to treat hyperlipidemia and coronary artery disease (CAD), most recently including antibodies targeting PCSK9 to reduce LDL cholesterol. Despite these successes, a large burden of CAD remains. Genetic and epidemiological studies have suggested that circulating triglyceride (TG)-rich lipoproteins (TRLs) are a causal risk factor for CAD, presenting an opportunity for novel therapeutic strategies. We discuss recent unbiased human genetics testing, including genome-wide association studies (GWAS) and whole-genome or -exome sequencing, that have identified the lipoprotein lipase (LPL) and hepatic lipogenesis pathways as important mechanisms in the regulation of circulating TRLs. Further strengthening the causal relationship between TRLs and CAD, findings such as these may provide novel targets for much-needed potential therapeutic interventions. PMID:26988439

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

    SciTech Connect

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

    1990-02-26

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

  11. Blood Triglycerides Levels and Dietary Carbohydrate Indices in Healthy Koreans

    PubMed Central

    Kang, Ji Yeon

    2016-01-01

    Objectives: Previous studies have obtained conflicting findings regarding possible associations between indices measuring carbohydrate intake and dyslipidemia, which is an established risk factor of coronary heart disease. In the present study, we examined cross-sectional associations between carbohydrate indices, including the dietary glycemic index (GI), glycemic load (GL), total amount of carbohydrates, and the percentage of energy from carbohydrates, and a range of blood lipid parameters. Methods: This study included 1530 participants (554 men and 976 women) from 246 families within the Healthy Twin Study. We analyzed the associations using a generalized linear mixed model to control for familial relationships. Results: Levels of the Apo B were inversely associated with dietary GI, GL, and the amount of carbohydrate intake for men, but these relationships were not significant when fat-adjusted values of the carbohydrate indices were used. Triglyceride levels were positively associated with dietary GI and GL in women, and this pattern was more notable in overweight participants (body mass index [BMI] ≥25 kg/m2). However, total, low-density lipoprotein and high-density lipoprotein cholesterol levels were not significantly related with carbohydrate intake overall. Conclusions: Of the blood lipid parameters we investigated, only triglyceride levels were positively related with dietary carbohydrate indices among women participants in the Healthy Twin Study, with an interactive role observed for BMI. However, these associations were not observed in men, suggesting that the association between blood lipid levels and carbohydrate intake depends on the type of lipid, specific carbohydrate indices, gender, and BMI. PMID:27255074

  12. In vitro effect of insulin and adrenaline on lung triglyceride-lipase activity in rats.

    PubMed

    Hadjiivanova, N; Koumanov, K; Georgiev, G

    1976-01-01

    The in vitro effect of insulin and adrenaline on the activity of lung triglyceride-lipases (alkaline and acid) has been investigated. Insulin inhibited strongly both triglyceride-lipases. Only caffein almost eliminated the inhibitory action of insulin, while adrenaline and dibutyryl cyclic adenosine monophosphate did not exhibit such an effect. It was assumed that the inhibition of lung triglyceride-lipases by insulin was effected through the activation of phosphodiesterases. On the other hand since adrenaline markedly activated lung triglyceride-lipases, this action was assumed to be carried out via the activation of lung adenylate cyclase and the increase of cyclic adenosine monophosphate. PMID:189868

  13. Cardiac perception and cardiac control. A review.

    PubMed

    Carroll, D

    1977-12-01

    The evidence regarding specific cardiac perception and discrimination, and its relationship to voluntary cardiac control, is critically reviewed. Studies are considered in three sections, depending on the method used to assess cardiac perception: questionnaire assessment, discrimination procedures, and heartbeat tracking. The heartbeat tracking procedure would appear to suffer least from interpretative difficulties. Recommendations are made regarding the style of analysis used to assess heartbeat perception in such tracking tasks. PMID:348240

  14. Anatomical relationship between traditional acupuncture point ST 36 and Omura's ST 36 (True ST 36) with their therapeutic effects: 1) inhibition of cancer cell division by markedly lowering cancer cell telomere while increasing normal cell telomere, 2) improving circulatory disturbances, with reduction of abnormal increase in high triglyceride, L-homocystein, CRP, or cardiac troponin I & T in blood by the stimulation of Omura's ST 36--Part 1.

    PubMed

    Omura, Yoshiaki; Chen, Yemeng; Lu, Dominic P; Shimotsura, Yasuhiro; Ohki, Motomu; Duvvi, Harsha

    2007-01-01

    for cardio-vascular diseases with hypertriglyceridemia, hyperglycemia, high L-homocystein, and CRP, high cardiac Troponim I & T, and some hypertension. These beneficial effects were accompanied by euphoria, & relaxation with increased alpha waves in EEG. Thus Omura's ST 36 stimulation is a safe, effective and highly desirable supplemental treatment. In addition to manual stimulation, similar beneficial effects can be induced by finger tip stmulation (without any needle) or with electroacupuncture stimulation, (+) Qi Gong energy stored paper and (+) solar energy stored paper which often resulted in significant clinical improvement. PMID:18077937

  15. Assessment of Myocardial Triglyceride Oxidation with PET and 11C-Palmitate

    PubMed Central

    Kisrieva-Ware, Zulfia; Coggan, Andrew R.; Sharp, Terry L.; Dence, Carmen S.; Gropler, Robert J.; Herrero, Pilar

    2010-01-01

    Background The goal of this study was to test whether myocardial triglyceride (TG) turnover including oxidation of TG-derived fatty acids could be assessed with PET and 11C-palmitate. Methods and Results 26 dogs were studied fasted (FAST), during Intralipid infusion (IL), during a hyperinsulinemic-euglycemic clamp without (HIEG) or with Intralipid infusion (HIEG+IL). 11C-palmitate was injected, and 45 min were allowed for labeling of myocardial TG pool. 3-D PET data were then acquired for 60 min, with first 15 min at baseline followed by 45 min during cardiac work stimulated with constant infusion of either phenylephrine (FAST, n=6; IL, n=6; HIEG+IL, n=6) or dobutamine (FAST, n=4; HIEG, n=4). Myocardial 11C washout during adrenergic stimulation (AS) was fitted to a mono-exponential function (Km(PET)). To determine the source of this 11C clearance, Km(PET) was compared to direct coronary sinus-arterial measurements of total 11C activity, 11C-palmitate, and 11CO2. Before AS, PET curves in all groups were flat indicating absence of net clearance of 11C activity from heart. In both FAST groups, AS resulted in negligible net 11C activity and 11CO2 production higher than net 11C-palmitate uptake. AS with phenylephrine resulted in net myocardial uptake of total 11C activity and 11C-palmitate in IL and HIEG+IL, and 11CO2 production lower than 11C-palmitate uptake. In contrast, AS with dobutamine in HIEG resulted in net clearance of all 11C metabolites (total 11C activity, 11C-palmitate and 11CO2) with 11CO2 contributing 66% to endogenous FA oxidation. AS resulted in significant Km(PET) in all groups, except HIEG+IL. However, positive correlation between Km(PET) and 11CO2 was observed only in HIEG (R2=0.83, P=0.09). Conclusions This is the first study to demonstrate that using PET and pre-labeling of intracardiac TG pool with 11C-palmitate, noninvasive assessment of myocardial TG use is feasible under metabolic conditions that favor endogenous TG use such as increased

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

    SciTech Connect

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

    1991-03-11

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

  17. 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

  18. Differential Benefit of Statin in Secondary Prevention of Acute Myocardial Infarction according to the Level of Triglyceride and High Density Lipoprotein Cholesterol

    PubMed Central

    Kim, Kyung Hwan; Kim, Cheol Hwan; Ahn, Youngkeun; Kim, Young Jo; Cho, Myeong Chan; Kim, Wan; Kim, Jong Jin

    2016-01-01

    Background and Objectives The differential benefit of statin according to the state of dyslipidemia has been sparsely investigated. We sought to address the efficacy of statin in secondary prevention of myocardial infarction (MI) according to the level of triglyceride and high density lipoprotein cholesterol (HDL-C) on admission. Subjects and Methods Acute MI patients (24653) were enrolled and the total patients were divided according to level of triglyceride and HDL-C on admission: group A (HDL-C≥40 mg/dL and triglyceride<150 mg/dL; n=11819), group B (HDL-C≥40 mg/dL and triglyceride≥150 mg/dL; n=3329), group C (HDL-C<40 mg/dL and triglyceride<150 mg/dL; n=6062), and group D (HDL-C<40 mg/dL & triglyceride≥150 mg/dL; n=3443). We evaluated the differential efficacy of statin according to the presence or absence of component of dyslipidemia. The primary end points were major adverse cardiac events (MACE) for 2 years. Results Statin therapy significantly reduced the risk of MACE in group A (hazard ratio=0.676; 95% confidence interval: 0.582-0.785; p<0.001). However, the efficacy of statin was not prominent in groups B, C, or D. In a propensity-matched population, the result was similar. In particular, the benefit of statin in group A was different compared with group D (interaction p=0.042) Conclusion The benefit of statin in patients with MI was different according to the presence or absence of dyslipidemia. In particular, because of the insufficient benefit of statin in patients with MI and dyslipidemia, a different lipid-lowering strategy is necessary in these patients. PMID:27275169

  19. Triglyceride-rich lipoproteins inhibit cholesterol efflux to apolipoprotein (apo) A1 from human macrophage foam cells.

    PubMed

    Palmer, Anna M; Murphy, Nuala; Graham, Annette

    2004-03-01

    High circulating levels of triglyceride-rich lipoproteins (TGRL) represent an independent risk factor for coronary artery disease. Here, we show that TGRL inhibit the efflux of cholesterol from 'foam cell' macrophages to lipid-poor apolipoprotein (apo) A1, and may thereby inhibit arterial reverse cholesterol transport and promote the formation of atherosclerotic lesions. Human (THP-1) monocyte-derived macrophages were pre-incubated (48 h) with acetylated low-density lipoprotein (AcLDL) to provide a foam cell model of cholesterol efflux to apoA1. Pre-incubation of macrophage 'foam cells' with TGRL (0-200 microg/ml, 0-24 h) inhibited the efflux of exogenously radiolabelled ([3H]), endogenously synthesised ([14C]) and cellular cholesterol mass to lipid-poor apoA1, but not control medium, during a (subsequent) efflux period. This inhibition is dependent upon the length of prior exposure to, and concentration of, TGRL employed, but is independent of changes in intracellular triglyceride accumulation or turnover of the cholesteryl ester pool. Despite the negative impact of TGRL on cholesterol efflux, major proteins involved in this process--namely apoE, ABCA1, SR-B1 and caveolin-1--were unaffected by TGRL pre-incubation, suggesting that exposure to these lipoproteins inhibits an alternate, and possibly novel, anti-atherogenic pathway. PMID:15177121

  20. Cardiac ferroportin regulates cellular iron homeostasis and is important for cardiac function.

    PubMed

    Lakhal-Littleton, Samira; Wolna, Magda; Carr, Carolyn A; Miller, Jack J J; Christian, Helen C; Ball, Vicky; Santos, Ana; Diaz, Rebeca; Biggs, Daniel; Stillion, Richard; Holdship, Philip; Larner, Fiona; Tyler, Damian J; Clarke, Kieran; Davies, Benjamin; Robbins, Peter A

    2015-03-10

    Iron is essential to the cell. Both iron deficiency and overload impinge negatively on cardiac health. Thus, effective iron homeostasis is important for cardiac function. Ferroportin (FPN), the only known mammalian iron-exporting protein, plays an essential role in iron homeostasis at the systemic level. It increases systemic iron availability by releasing iron from the cells of the duodenum, spleen, and liver, the sites of iron absorption, recycling, and storage respectively. However, FPN is also found in tissues with no known role in systemic iron handling, such as the heart, where its function remains unknown. To explore this function, we generated mice with a cardiomyocyte-specific deletion of Fpn. We show that these animals have severely impaired cardiac function, with a median survival of 22 wk, despite otherwise unaltered systemic iron status. We then compared their phenotype with that of ubiquitous hepcidin knockouts, a recognized model of the iron-loading disease hemochromatosis. The phenotype of the hepcidin knockouts was far milder, with normal survival up to 12 mo, despite far greater iron loading in the hearts. Histological examination demonstrated that, although cardiac iron accumulates within the cardiomyocytes of Fpn knockouts, it accumulates predominantly in other cell types in the hepcidin knockouts. We conclude, first, that cardiomyocyte FPN is essential for intracellular iron homeostasis and, second, that the site of deposition of iron within the heart determines the severity with which it affects cardiac function. Both findings have significant implications for the assessment and treatment of cardiac complications of iron dysregulation. PMID:25713362

  1. Cardiac ferroportin regulates cellular iron homeostasis and is important for cardiac function

    PubMed Central

    Lakhal-Littleton, Samira; Wolna, Magda; Carr, Carolyn A.; Miller, Jack J. J.; Christian, Helen C.; Ball, Vicky; Santos, Ana; Diaz, Rebeca; Biggs, Daniel; Stillion, Richard; Holdship, Philip; Clarke, Kieran; Davies, Benjamin; Robbins, Peter A.

    2015-01-01

    Iron is essential to the cell. Both iron deficiency and overload impinge negatively on cardiac health. Thus, effective iron homeostasis is important for cardiac function. Ferroportin (FPN), the only known mammalian iron-exporting protein, plays an essential role in iron homeostasis at the systemic level. It increases systemic iron availability by releasing iron from the cells of the duodenum, spleen, and liver, the sites of iron absorption, recycling, and storage respectively. However, FPN is also found in tissues with no known role in systemic iron handling, such as the heart, where its function remains unknown. To explore this function, we generated mice with a cardiomyocyte-specific deletion of Fpn. We show that these animals have severely impaired cardiac function, with a median survival of 22 wk, despite otherwise unaltered systemic iron status. We then compared their phenotype with that of ubiquitous hepcidin knockouts, a recognized model of the iron-loading disease hemochromatosis. The phenotype of the hepcidin knockouts was far milder, with normal survival up to 12 mo, despite far greater iron loading in the hearts. Histological examination demonstrated that, although cardiac iron accumulates within the cardiomyocytes of Fpn knockouts, it accumulates predominantly in other cell types in the hepcidin knockouts. We conclude, first, that cardiomyocyte FPN is essential for intracellular iron homeostasis and, second, that the site of deposition of iron within the heart determines the severity with which it affects cardiac function. Both findings have significant implications for the assessment and treatment of cardiac complications of iron dysregulation. PMID:25713362

  2. What Is Cardiac Rehabilitation?

    MedlinePlus

    ANSWERS by heart Treatments + Tests What Is Cardiac Rehabilitation? A cardiac rehabilitation (rehab) program takes place in a hospital or ... special help in making lifestyle changes. During your rehabilitation program you’ll… • Have a medical evaluation to ...

  3. Sudden Cardiac Arrest

    MedlinePlus

    ... from American Heart Association Aneurysms and Dissections Angina Arrhythmia Bundle Branch Block Cardiomyopathy Carotid Artery Disease Chronic ... terms: SCA, sudden cardiac death (SCD), sudden death, arrhythmias, ... ventricular fibrillation, defibrillator, automatic cardiac defibrillator ( ...

  4. Cardiac conduction system

    MedlinePlus Videos and Cool Tools

    ... cardiac muscle cells in the walls of the heart that send signals to the heart muscle causing it to contract. The main components ... the cardiac conduction system’s electrical activity in the heart.

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

    PubMed Central

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

    2013-01-01

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

  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, Ayşe; Den Hertog, Heleen M; Donnelly, Louise A; Ehret, Georg B; Esko, Tõnu; Feitosa, Mary F; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M; Freitag, Daniel F; Gurdasani, Deepti; Heikkilä, Kauko; Hyppönen, Elina; Isaacs, Aaron; Jackson, Anne U; Johansson, 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; Stančáková, Alena; Stirrups, Kathleen; Swift, Amy J; Tiret, Laurence; Uitterlinden, Andre G; van Pelt, L Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F; Young, Elizabeth H; Zhao, Jing Hua; Adair, Linda S; Arveiler, Dominique; Assimes, Themistocles L; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O; Boomsma, Dorret I; Borecki, Ingrid B; Bornstein, Stefan R; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C; Chen, Yii-Der Ida; Collins, Francis S; Cooper, Richard S; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B; Ferrières, Jean; Ferrucci, Luigi; Freimer, Nelson B; Gieger, Christian; Groop, Leif C; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B; Hingorani, Aroon; Hirschhorn, Joel N; Hofman, Albert; Hovingh, G Kees; Hsiung, Chao Agnes; Humphries, Steve E; Hunt, Steven C; Hveem, Kristian; Iribarren, Carlos; Järvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kaprio, Jaakko; Kesäniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S; Koudstaal, Peter J; Krauss, Ronald M; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O; Laakso, Markku; Lakka, Timo A; Lind, Lars; Lindgren, Cecilia M; Martin, Nicholas G; März, Winfried; McCarthy, Mark I; McKenzie, Colin A; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D; Munroe, Patricia B; Njølstad, Inger; Pedersen, Nancy L; Power, Chris; Pramstaller, Peter P; Price, Jackie F; Psaty, Bruce M; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K; Saramies, Jouko; Schwarz, Peter E H; Sheu, Wayne H-H; Shuldiner, Alan R; Siegbahn, Agneta; Spector, Tim D; Stefansson, Kari; Strachan, David P; Tayo, Bamidele O; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J; Whitfield, John B; Wolffenbuttel, Bruce H R; Altshuler, David; Ordovas, Jose M; Boerwinkle, Eric; Palmer, Colin N A; Thorsteinsdottir, Unnur; Chasman, Daniel I; Rotter, Jerome I; Franks, Paul W; Ripatti, Samuli; Cupples, L Adrienne; Sandhu, Manjinder S; Rich, Stephen S; Boehnke, Michael; Deloukas, Panos; Mohlke, Karen L; Ingelsson, Erik; Abecasis, Goncalo R; Daly, Mark J; Neale, Benjamin M; Kathiresan, Sekar

    2013-11-01

    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. Effect of Amphiphiles on the Rheology of Triglyceride Networks

    NASA Astrophysics Data System (ADS)

    Seth, Jyoti

    2014-11-01

    Networks of aggregated crystallites form the structural backbone of many products from the food, cosmetic and pharmaceutical industries. Such materials are generally formulated by cooling a saturated solution to yield the desired solid fraction. Crystal nucleation and growth followed by aggregation leads to formation of a space percolating fractal-network. It is understood that microstructural hierarchy and particle-particle interactions determine material behavior during processing, storage and use. In this talk, rheology of suspensions of triglycerides (TAG, like tristearin) will be explored. TAGs exhibit a rich assortment of polymorphs and form suspensions that are evidently sensitive to surface modifying additives like surfactants and polymers. Here, a theoretical framework will be presented for suspensions containing TAG crystals interacting via pairwise potentials. The work builds on existing models of fractal aggregates to understand microstructure and its correlation with material rheology. Effect of amphiphilic additives is derived through variation of particle-particle interactions. Theoretical predictions for storage modulus will be compared against experimental observations and data from the literature and micro structural predictions against microscopy. Such a theory may serve as a step towards predicting short and long-term behavior of aggregated suspensions formulated via crystallization.

  8. Drug solubilisation in lipid nanoparticles containing high melting point triglycerides.

    PubMed

    Wasutrasawat, Prawarisa; Al-Obaidi, Hisham; Gaisford, Simon; Lawrence, M Jayne; Warisnoicharoen, Warangkana

    2013-11-01

    The effect of lipid (either the triglyceride trilaurin or tripalmitin, melting points of 43 and 64 °C, respectively) on the properties of lipid nanoparticles (LN) stabilised by the surfactant, polyoxyethylene-10-oleyl ether (C18:1E10) at a temperature of 22 °C, has been determined. LN were prepared by heating lipid, surfactant and water to 70 °C and cooling to ambient temperature with constant stirring. While lipid type influenced LN formation in that trilaurin-containing LN formed over the greatest range of compositions, phase inversion studies suggested that both lipids formed a core within the LN while light scattering studies indicated that the size of both types of LN varied with lipid concentration: in an approximately linear fashion for clear or opalescent LN and exponentially for cloudy LN. Additionally, both types of preformed LN exhibited an increase in solubilisation capacity of the hydrophobic drug, testosterone propionate compared to C18:1E10 micelles, although the trilaurin-containing LN exhibited the greatest increase. Differential scanning calorimetry studies demonstrated that trilaurin formed a 'fluid-like' core and therefore liquefied-lipid nanoparticles, which allowed dissolution of testosterone propionate in the lipid core. In contrast, tripalmitin was present in a 'solid-like' state forming solid lipid nanoparticles which did not allow testosterone propionate dissolution in the core. PMID:23688806

  9. Cardiac Biomarkers: a Focus on Cardiac Regeneration

    PubMed Central

    Forough, Reza; Scarcello, Catherine; Perkins, Matthew

    2011-01-01

    Historically, biomarkers have been used in two major ways to maintain and improve better health status: first, for diagnostic purposes, and second, as specific targets to treat various diseases. A new era in treatment and even cure for the some diseases using reprograming of somatic cells is about to be born. In this approach, scientists are successfully taking human skin cells (previously considered terminally-differentiated cells) and re-programming them into functional cardiac myocytes and other cell types in vitro. A cell reprograming approach for treatment of cardiovascular diseases will revolutionize the field of medicine and significantly expand the human lifetime. Availability of a comprehensive catalogue for cardiac biomarkers is necessary for developing cell reprograming modalities to treat cardiac diseases, as well as for determining the progress of reprogrammed cells as they become cardiac cells. In this review, we present a comprehensive survey of the cardiac biomarkers currently known. PMID:23074366

  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. Temperature independence of the composition of triglyceride fatty acids synthesized de novo by the mosquito.

    PubMed

    Van Handel, E

    1966-01-01

    The hypothesis that depot fat is more unsaturated when it is synthesized at lower temperatures was tested in the mosquito. Female mosquitoes (Aedes sollicitans) were starved until no triglycerides remained. A single dose of sugar was fed and the mosquitoes were maintained at different temperatures. Approximately the same amount of triglyceride was synthesized per mosquito at each temperature, although at different rates. Mosquitoes maintained at low temperatures did not synthesize more unsaturated triglycerides than those at higher temperatures: the fatty acid composition was essentially the same from 10 to 35 degrees. The triglycerides synthesized from sugar contained no poly-unsaturated fatty acids. Total amounts and composition of phospholipid fatty acids remained unaltered during sugar feeding. When deprived of food, the mosquitoes catabolized triglyceride fatty acids randomly; cold-exposure did not cause selective retention or utilization of any individual fatty acid. PMID:4378885

  12. Biological determinants of aldosterone-induced cardiac fibrosis in rats.

    PubMed

    Robert, V; Silvestre, J S; Charlemagne, D; Sabri, A; Trouvé, P; Wassef, M; Swynghedauw, B; Delcayre, C

    1995-12-01

    To determine the events leading to cardiac fibrosis in aldosterone-salt hypertensive rats, we studied protein and mRNA accumulation of procollagens I and III for 60 days. After 3 and 7 days of treatment systolic pressure was normal, and no histological or biochemical changes were seen in rat hearts. At day 15 arterial pressure was raised (+40%) and left ventricular hypertrophy was +15%. Cardiac examination after hemalun-eosin staining and immunolabeling with anticollagen I and III antibodies showed no structural alterations, but an 83% increase in right ventricular type III procollagen mRNA levels was found. At 30 and 60 days we found progressive cardiac fibrosis, with inflammatory cells, myocyte necrosis, and elevation of both types I and III procollagen mRNA levels in both ventricles. To determine whether aldosterone had effects on Na,K-ATPase that might lead to ionic disturbances and induce myocyte necrosis, we studied the major cardiac Na,K-ATPase isoform genes. Although Na,K-ATPase alpha 1- and beta 1-subunit mRNA levels were elevated in kidney at day 1, neither of these cardiac transcripts nor the specific alpha 2 isoform was altered between 1 and 15 days. These results show that accumulation of procollagen mRNAs occurs before collagen deposition. Cardiac alterations are late and not preceded by changes in Na,K-ATPase cardiac gene expression, precluding a direct modulation of cardiac collagen synthesis and Na,K-ATPase by aldosterone. PMID:7490157

  13. Cardiac steatosis and left ventricular function in men with metabolic syndrome

    PubMed Central

    2013-01-01

    Background Ectopic accumulation of fat accompanies visceral obesity with detrimental effects. Lipid oversupply to cardiomyocytes leads to cardiac steatosis, and in animal studies lipotoxicity has been associated with impaired left ventricular (LV) function. In humans, studies have yielded inconclusive results. The aim of the study was to evaluate the role of epicardial, pericardial and myocardial fat depots on LV structure and function in male subjects with metabolic syndrome (MetS). Methods A study population of 37 men with MetS and 38 men without MetS underwent cardiovascular magnetic resonance and proton magnetic spectroscopy at 1.5 T to assess LV function, epicardial and pericardial fat area and myocardial triglyceride (TG) content. Results All three fat deposits were greater in the MetS than in the control group (p <0.001). LV diastolic dysfunction was associated with MetS as measured by absolute (471 mL/s vs. 667 mL/s, p = 0.002) and normalized (3.37 s-1 vs. 3.75 s-1, p = 0.02) LV early diastolic peak filling rate and the ratio of early diastole (68% vs. 78%, p = 0.001). The amount of epicardial and pericardial fat correlated inversely with LV diastolic function. However, myocardial TG content was not independently associated with LV diastolic dysfunction. Conclusions In MetS, accumulation of epicardial and pericardial fat is linked to the severity of structural and functional alterations of the heart. The role of increased intramyocardial TG in MetS is more complex and merits further study. PMID:24228979

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

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

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

  15. Insulin Cannot Induce Adipogenic Differentiation in Primary Cardiac Cultures.

    PubMed

    Parameswaran, Sreejit; Sharma, Rajendra K

    2016-09-01

    Cardiac tissue contains a heterogeneous population of cardiomyocytes and nonmyocyte population especially fibroblasts. Fibroblast differentiation into adipogenic lineage is important for fat accumulation around the heart which is important in cardiac pathology. The differentiation in fibroblast has been observed both spontaneously and due to increased insulin stimulation. The present study aims to observe the effect of insulin in adipogenic differentiation of cardiac cells present in primary murine cardiomyocyte cultures. Oil Red O (ORO) staining has been used for observing the lipid accumulations formed due to adipogenic differentiation in murine cardiomyocyte cultures. The accumulated lipids were quantified by ORO assay and normalized using protein estimation. The lipid accumulation in cardiac cultures did not increase in presence of insulin. However, addition of other growth factors like insulin-like growth factor 1 and epidermal growth factor promoted adipogenic differentiation even in the presence of insulin and other inhibitory molecules such as vitamins. Lipid accumulation also increased in cells grown in media without insulin after an initial exposure to insulin-containing growth media. The current study adds to the existing knowledge that the insulin by itself cannot induce adipogenic induction in the cardiac cultures. The data have significance in the understanding of cardiovascular health especially in diabetic patients. PMID:27574386

  16. Cardiac gated ventilation

    SciTech Connect

    Hanson, C.W. III; Hoffman, E.A.

    1995-12-31

    There are several theoretic advantages to synchronizing positive pressure breaths with the cardiac cycle, including the potential for improving distribution of pulmonary and myocardial blood flow and enhancing cardiac output. The authors evaluated the effects of synchronizing respiration to the cardiac cycle using a programmable ventilator and electron beam CT (EBCT) scanning. The hearts of anesthetized dogs were imaged during cardiac gated respiration with a 50 msec scan aperture. Multi slice, short axis, dynamic image data sets spanning the apex to base of the left ventricle were evaluated to determine the volume of the left ventricular chamber at end-diastole and end-systole during apnea, systolic and diastolic cardiac gating. The authors observed an increase in cardiac output of up to 30% with inspiration gated to the systolic phase of the cardiac cycle in a non-failing model of the heart.

  17. Cardiac gated ventilation

    NASA Astrophysics Data System (ADS)

    Hanson, C. William, III; Hoffman, Eric A.

    1995-05-01

    There are several theoretic advantages to synchronizing positive pressure breaths with the cardiac cycle, including the potential for improving distribution of pulmonary and myocardial blood flow and enhancing cardiac output. We evaluated the effects of synchronizing respiration to the cardiac cycle using a programmable ventilator and electron beam CT (EBCT) scanning. The hearts of anesthetized dogs were imaged during cardiac gated respiration with a 50msec scan aperture. Multislice, short axis, dynamic image data sets spanning the apex to base of the left ventricle were evaluated to determine the volume of the left ventricular chamber at end-diastole and end-systole during apnea, systolic and diastolic cardiac gating. We observed an increase in cardiac output of up to 30% with inspiration gated to the systolic phase of the cardiac cycle in a nonfailing model of the heart.

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

    PubMed Central

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

    2015-01-01

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

  19. MicroRNA-192* impairs adipocyte triglyceride storage.

    PubMed

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

    2016-04-01

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

  20. Validity of a portable glucose, total cholesterol, and triglycerides multi-analyzer in adults.

    PubMed

    Coqueiro, Raildo da Silva; Santos, Mateus Carmo; Neto, João de Souza Leal; Queiroz, Bruno Morbeck de; Brügger, Nelson Augusto Jardim; Barbosa, Aline Rodrigues

    2014-07-01

    This study investigated the accuracy and precision of the Accutrend Plus system to determine blood glucose, total cholesterol, and plasma triglycerides in adults and evaluated its efficiency in measuring these blood variables. The sample consisted of 53 subjects (≥ 18 years). For blood variable laboratory determination, venous blood samples were collected and processed in a Labmax 240 analyzer. To measure blood variables with the Accutrend Plus system, samples of capillary blood were collected. In the analysis, the following tests were included: Wilcoxon and Student's t-tests for paired samples, Lin's concordance coefficient, Bland-Altman method, receiver operating characteristic curve, McNemar test, and k statistics. The results show that the Accutrend Plus system provided significantly higher values (p ≤ .05) of glucose and triglycerides but not of total cholesterol (p > .05) as compared to the values determined in the laboratory. However, the system showed good reproducibility (Lin's coefficient: glucose = .958, triglycerides = .992, total cholesterol = .940) and high concordance with the laboratory method (Lin's coefficient: glucose = .952, triglycerides = .990, total cholesterol = .944) and high sensitivity (glucose = 80.0%, triglycerides = 90.5%, total cholesterol = 84.4%) and specificity (glucose = 100.0%, triglycerides = 96.9%, total cholesterol = 95.2%) in the discrimination of high values of the three blood variables analyzed. It could be concluded that despite the tendency to overestimate glucose and triglyceride levels, a portable multi-analyzer is a valid alternative for the monitoring of metabolic disorders and cardiovascular risk factors. PMID:23871994

  1. Obese yeast: triglyceride lipolysis is functionally conserved from mammals to yeast.

    PubMed

    Kurat, Christoph F; Natter, Klaus; Petschnigg, Julia; Wolinski, Heimo; Scheuringer, Kim; Scholz, Harald; Zimmermann, Robert; Leber, Regina; Zechner, Rudolf; Kohlwein, Sepp D

    2006-01-01

    Storage and degradation of triglycerides are essential processes to ensure energy homeostasis and availability of precursors for membrane lipid synthesis. Recent evidence suggests that an emerging class of enzymes containing a conserved patatin domain are centrally important players in lipid degradation. Here we describe the identification and characterization of a major triglyceride lipase of the adipose triglyceride lipase/Brummer family, Tgl4, in the yeast Saccharomyces cerevisiae. Elimination of Tgl4 in a tgl3 background led to fat yeast, rendering growing cells unable to degrade triglycerides. Tgl4 and Tgl3 lipases localized to lipid droplets, independent of each other. Serine 315 in the GXSXG lipase active site consensus sequence of the patatin domain of Tgl4 is essential for catalytic activity. Mouse adipose triglyceride lipase (which also contains a patatin domain but is otherwise highly divergent in primary structure from any yeast protein) localized to lipid droplets when expressed in yeast, and significantly restored triglyceride breakdown in tgl4 mutants in vivo. Our data identify yeast Tgl4 as a functional ortholog of mammalian adipose triglyceride lipase. PMID:16267052

  2. Effects of dietary triglycerides on rheological properties of human red blood cells (abstract).

    PubMed

    Cicha, I; Suzuki, Y; Tateishi, N; Maeda, N

    2004-01-01

    Atherogenic diets rich in saturated fat and cholesterol influence the blood viscosity and red blood cell (RBC) aggregability, the parameters associated with increased risk of circulatory disorders. However, little is known about the effect of triglycerides, which are the major dietary lipid form in humans, on blood rheology. Therefore, we studied the effects of postprandial plasma triglyceride levels on human RBC indices, hematological parameters, RBCs aggregation velocity and whole blood viscosity. For this purpose, whole blood was collected 2 hours after high-fat or low-fat meal. Proteins, triglycerides and cholesterol levels of plasma were analysed, and RBCs rouleaux formation rate was measured in 70% autologous plasma using a low-shear rheoscope. There were no significant differences in hematological parameters, RBC indices, whole blood viscosity, plasma protein and cholesterol content between high-fat and low-fat blood samples. However, a significant increase in rouleaux formation rate was observed in samples with high postprandial triglyceride levels, when compared with low-triglyceride samples. Plasma triglyceride levels correlated significantly with rouleaux formation rate. In conclusion, these results suggest that diet-dependent alterations of plasma triglyceride levels as well as possible changes in the cell membrane lipid composition lead to RBC hyperaggregability. PMID:15258358

  3. Evaluation of the effects of various factors on the serum triglyceride level in young adults.

    PubMed

    Yamasaki, R; Miyoshi, T; Imaki, M; Nakamura, T

    1994-06-01

    The life style of young adults has been receiving attention with a view to its improvement to preventing coronary heart diseases (CHD) in later life. In this study, for determining the influence of different life styles on the serum triglyceride level, we carried out surveys and laboratory studies on the relationships of the nutritional intake, physical activity, and cigarette smoking and alcohol consumption of young adults with their serum triglyceride levels. The nutritional survey indicated a significant correlation between the serum triglyceride level and carbohydrate intake (p < 0.01). In the survey of physical activity, a significant inverse correlation was found between the energy expenditure per kg body weight and the serum triglyceride level (p < 0.05). No significant relationship was found of smoking or drinking with the serum triglyceride level. The body mass index was found to have effects on both the serum triglyceride and total cholesterol levels. Of the factors examined, carbohydrate intake and energy expenditure per kg body weight had the greatest effects on the serum triglyceride level. Considering the trend for young people to consume large quantities of carbonated drinks, in which most of carbohydrate is sucrose, we tested the affect of a high carbohydrate diet on one group of subjects and found that it caused a significant increase in the serum triglyceride level (p < 0.05). Another group for whom a mild exercise regimen was prescribed showed slight, but not significant decrease in the serum triglyceride level. These results suggest that at least optimal nutrition and physical activity including weight control during adolescence are important for preventing CHD. PMID:7940529

  4. 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

  5. Stimulating endogenous cardiac repair

    PubMed Central

    Finan, Amanda; Richard, Sylvain

    2015-01-01

    The healthy adult heart has a low turnover of cardiac myocytes. The renewal capacity, however, is augmented after cardiac injury. Participants in cardiac regeneration include cardiac myocytes themselves, cardiac progenitor cells, and peripheral stem cells, particularly from the bone marrow compartment. Cardiac progenitor cells and bone marrow stem cells are augmented after cardiac injury, migrate to the myocardium, and support regeneration. Depletion studies of these populations have demonstrated their necessary role in cardiac repair. However, the potential of these cells to completely regenerate the heart is limited. Efforts are now being focused on ways to augment these natural pathways to improve cardiac healing, primarily after ischemic injury but in other cardiac pathologies as well. Cell and gene therapy or pharmacological interventions are proposed mechanisms. Cell therapy has demonstrated modest results and has passed into clinical trials. However, the beneficial effects of cell therapy have primarily been their ability to produce paracrine effects on the cardiac tissue and recruit endogenous stem cell populations as opposed to direct cardiac regeneration. Gene therapy efforts have focused on prolonging or reactivating natural signaling pathways. Positive results have been demonstrated to activate the endogenous stem cell populations and are currently being tested in clinical trials. A potential new avenue may be to refine pharmacological treatments that are currently in place in the clinic. Evidence is mounting that drugs such as statins or beta blockers may alter endogenous stem cell activity. Understanding the effects of these drugs on stem cell repair while keeping in mind their primary function may strike a balance in myocardial healing. To maximize endogenous cardiac regeneration, a combination of these approaches could ameliorate the overall repair process to incorporate the participation of multiple cellular players. PMID:26484341

  6. Uric acid or 1-methyl uric acid in the urinary bladder increases serum glucose, insulin, true triglyceride, and total cholesterol levels in Wistar rats.

    PubMed

    Balasubramanian, T

    2003-10-01

    In animals deprived of food for a long period, a drop in the fat mass below 5% of the total body mass results in an increase in blood glucocorticoids and uric acid levels, followed by foraging activity. Since the glucocorticoids increase the uric acid excretion, an increase in the level of uric acid in the bladder urine could be the signal for this feeding behaviour and subsequent fat storage. Accumulation of fat is associated with hyperglycaemia, hyperinsulinaemia, hyperlipidaemia, and hypercholesterolaemia as seen in the metabolic syndrome or hibernation. It is hypothesized that uric acid or its structurally related compound, 1-methyl uric acid (one of the metabolites of the methyl xanthines namely caffeine, theophylline, and theobromine present in coffee, tea, cocoa, and some drugs), can act on the urinary bladder mucosa and increases the blood glucose, insulin, triglyceride, and cholesterol levels. In rats, perfusion of the urinary bladder with saturated aqueous solution of uric acid or 1-methyl uric acid results in a significant increase in the serum levels of glucose, insulin, true triglyceride, and total cholesterol in comparison with perfusion of the bladder with distilled water at 20, 40, and 80 min. The uric acid or the 1-methyl uric acid acts on the urinary bladder mucosa and increases the serum glucose, insulin, true triglyceride, and total cholesterol levels. PMID:15241498

  7. Cardiac Innervation and Sudden Cardiac Death

    PubMed Central

    Fukuda, Keiichi; Kanazawa, Hideaki; Aizawa, Yoshiyasu; Ardell, Jeffrey L.; Shivkumar, Kalyanam

    2015-01-01

    Afferent and efferent cardiac neurotransmission via the cardiac nerves intricately modulates nearly all physiological functions of the heart (chronotropy, dromotropy, lusitropy and inotropy). Afferent information from the heart is transmitted to higher levels of the nervous system for processing (intrinsic cardiac nervous system, extracardiac-intrathoracic ganglia, spinal cord, brain stem and higher centers) which ultimately results in efferent cardiomotor neural impulses (via the sympathetic and parasympathetic nerves). This system forms interacting feedback loops that provide physiological stability for maintaining normal rhythm and life-sustaining circulation. This system also ensures that there is fine-tuned regulation of sympathetic-parasympathetic balance in the heart under normal and stressed states in the short (beat to beat), intermediate (minutes-hours) and long term (days-years). This important neurovisceral /autonomic nervous system also plays a major role in the pathophysiology and progression of heart disease, including heart failure and arrhythmias leading to sudden cardiac death (SCD). Transdifferentiation of neurons in heart failure, functional denervation, cardiac and extra-cardiac neural remodeling have also been identified and characterized during the progression of disease. Recent advances in understanding the cellular and molecular processes governing innervation and the functional control of the myocardium in health and disease provides a rational mechanistic basis for development of neuraxial therapies for preventing SCD and other arrhythmias. Advances in cellular, molecular, and bioengineering realms have underscored the emergence of this area as an important avenue of scientific inquiry and therapeutic intervention. PMID:26044253

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  10. Camphene, a Plant-Derived Monoterpene, Reduces Plasma Cholesterol and Triglycerides in Hyperlipidemic Rats Independently of HMG-CoA Reductase Activity

    PubMed Central

    Vallianou, Ioanna; Peroulis, Nikolaos; Pantazis, Panayotis; Hadzopoulou-Cladaras, Margarita

    2011-01-01

    Background Central to the pathology of coronary heart disease is the accumulation of lipids, cholesterol and triglycerides, within the intima of arterial blood vessels. The search for drugs to treat dislipidemia, remains a major pharmaceutical focus. In this study, we evaluated the hypolipidemic properties of the essential oil from Chios mastic gum (MGO). Methodology/Principal Findings The hypolipidemic effect of MGO was investigated in naïve as well as in rats susceptible to detergent-induced hyperlipidemia. Serum cholesterol and triglycerides were determined using commercial kits. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase activity was measured in HepG2 cell extracts using a radioactive assay; cellular cholesterol and cholesterol esters were assessed using gas chromatography. MGO administration into naïve rats resulted in a dose-dependent reduction in the constitutive synthesis of serum cholesterol and triglycerides. In hyperlipidemic rats, MGO treatment had also a strong hypolipidemic effect. By testing various components of MGO, we show for the first time that the hypolipidemic action is associated with camphene. Administration of camphene at a dose of 30 µg/gr of body weight in hyperlipidemic rats resulted in a 54.5% reduction of total cholesterol (p<0.001), 54% of Low Density Lipoprotein (LDL)-cholesterol (p<0.001) and 34.5% of triglycerides (p<0.001). Treatment of HepG2 cells with camphene led to a decrease in cellular cholesterol content to the same extend as mevinolin, a known HMG-CoA reductase inhibitor. The hypolipidemic action of camphene is independent of HMG-CoA reductase activity, suggesting that its hypocholesterolemic and hypotriglyceridemic effects are associated with a mechanism of action different than that of statins. Conclusions Given the critical role that the control of hyperlipidemia plays in cardiovascular disease, the results of our study provide insights into the use of camphene as an alternative lipid lowering agent

  11. Metabolic Effects of n-3 PUFA as Phospholipids Are Superior to Triglycerides in Mice Fed a High-Fat Diet: Possible Role of Endocannabinoids

    PubMed Central

    Rossmeisl, Martin; Macek Jilkova, Zuzana; Kuda, Ondrej; Jelenik, Tomas; Medrikova, Dasa; Stankova, Barbora; Kristinsson, Björn; Haraldsson, Gudmundur G.; Svensen, Harald; Stoknes, Iren; Sjövall, Peter; Magnusson, Ylva; Balvers, Michiel G. J.; Verhoeckx, Kitty C. M.; Tvrzicka, Eva; Bryhn, Morten; Kopecky, Jan

    2012-01-01

    Background n-3 polyunsaturated fatty acids, namely docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), reduce the risk of cardiovascular disease and can ameliorate many of obesity-associated disorders. We hypothesised that the latter effect will be more pronounced when DHA/EPA is supplemented as phospholipids rather than as triglycerides. Methodology/Principal Findings In a ‘prevention study’, C57BL/6J mice were fed for 9 weeks on either a corn oil-based high-fat obesogenic diet (cHF; lipids ∼35% wt/wt), or cHF-based diets in which corn oil was partially replaced by DHA/EPA, admixed either as phospholipids or triglycerides from marine fish. The reversal of obesity was studied in mice subjected to the preceding cHF-feeding for 4 months. DHA/EPA administered as phospholipids prevented glucose intolerance and tended to reduce obesity better than triglycerides. Lipemia and hepatosteatosis were suppressed more in response to dietary phospholipids, in correlation with better bioavailability of DHA and EPA, and a higher DHA accumulation in the liver, white adipose tissue (WAT), and muscle phospholipids. In dietary obese mice, both DHA/EPA concentrates prevented a further weight gain, reduced plasma lipid levels to a similar extent, and tended to improve glucose tolerance. Importantly, only the phospholipid form reduced plasma insulin and adipocyte hypertrophy, while being more effective in reducing hepatic steatosis and low-grade inflammation of WAT. These beneficial effects were correlated with changes of endocannabinoid metabolome in WAT, where phospholipids reduced 2-arachidonoylglycerol, and were more effective in increasing anti-inflammatory lipids such as N-docosahexaenoylethanolamine. Conclusions/Significance Compared with triglycerides, dietary DHA/EPA administered as phospholipids are superior in preserving a healthy metabolic profile under obesogenic conditions, possibly reflecting better bioavalability and improved modulation of the

  12. The impact of exams anxiety on the level of triglycerides in university female students.

    PubMed

    Maimanee, Tahia A

    2010-04-01

    Anxiety affects the level of blood fats such as the triglycerides according to several studies conducted in various conditions causing anxiety as exam for the university students. The health experts suggested that the anxiety works to stimulate the autonomic nervous system which in turn leads to the appearance of a group of physiologic symptoms. The current study showed the changes happened in the triglycerides' levels in the female university students before and after exams at the intermediate anxiety level compared to other high and low levels of anxiety. In addition, there was a difference in triglycerides' levels in female students of college of Science before and after exam. This difference did not appear in case of other colleges. The exam type had an impact as the significant difference appeared in the triglycerides' levels during the periodical tests and these differences did not appear in the final exam. PMID:20503603

  13. 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.

  14. Lapacho tea (Tabebuia impetiginosa) extract inhibits pancreatic lipase and delays postprandial triglyceride increase in rats.

    PubMed

    Kiage-Mokua, Beatrice Nyanchama; Roos, Nils; Schrezenmeir, Jürgen

    2012-12-01

    Earlier work in our laboratory indicated that ethanolic extracts of Tabebuia impetiginosa, Arctium lappa L., Calendula officinalis, Helianthus annuus, Linum usitatissimum and L. propolis, inhibit pancreatic lipase in vitro. In a follow-up study we assessed their effects on plasma triglycerides in rats fed on a fatty meal. Extracts, orlistat or only ethanol were given orally to the rats together with the test meal and the rate of increase of postprandial triglycerides was assessed over 4 h. Clearing of the triglycerides from the blood compartment was abolished by inhibiting lipoprotein lipase with Triton WR-1339. Our results showed that out of all the extracts, the bark of Tabebuia impetiginosa led to a significant delay in the postprandial increase of plasma triglycerides. However, lapachol, which is contained in the bark of Tabebuia impetiginosa and soluble in ethanol, had no lipase inhibitory effect in vitro and hence this substance did not seem to mediate the pertinent effect. PMID:22431070

  15. 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...

  16. Cardiac fibrosis and down regulation of GLUT4 in experimental diabetic cardiomyopathy are ameliorated by chronic exposures to intermittent altitude

    PubMed Central

    Faramoushi, Mahdi; Amir Sasan, Ramin; Sari Sarraf, Vahid; Karimi, Pouran

    2016-01-01

    Introduction: Chronic intermittent hypoxia is considered as a preconditioning status in cardiovascular health to inducing resistance to the low oxygen supply. Diabetic cardiomyopathy leads to inability of the heart to effective circulation of blood preventing of consequent tissue damages so; the aim of this study was elucidation of effect of chronic exposure to hypoxia on Cardiac fibrosis and expression of GLUT4 in experimental diabetic cardiomyopathy. Methods: A total number of 30 rats were randomly divided into three groups; 1: Normoxia control group (NN, n = 10). 2: Normoxia diabetic group (ND, n = 10) that took fat diet for 2 weeks then were injected by streptozotocin (37 mg/kg) and 3: Hypoxia diabetic group (HD, n = 10): that were exposed to chronic intermittent hypoxia (CIH) (altitude ≈3400 m, 14% oxygen for 8 weeks). After hypoxia challenge, plasma metabolic parameters including: fasting blood glucose (FBS), triglyceride (TG) and total cholesterol (TC) were measured by colorimetric assay. Cardiac expression of GLUT4 protein and cardiac collagen accumulation were determined in the excised left ventricle by western blotting, and Masson trichrome staining respectively. Results: Based on resultant data, FBS, TG and TC were significantly (P < 0.05) decreased in HD vs. ND. Homeostasis Model Assessment (HOMA) were also significantly attenuated after exposed to CIH in HD group compared to ND group (P < 0.05). Significant increase in packed cell volume and hemoglobin concentration was observed in HD group compared to ND group (P < 0.05). Comparison of heart wet weight between three groups showed a significant difference (P < 0.05) with lower amount in HD and ND versus NN. Myocardial fibrosis was significantly more pronounced in ND when compared to NN. Eight weeks exposure to hypoxia ameliorated this increase in HD group. Intermittent hypoxia significantly increased GLUT4 protein expression in HD compared to ND group (P < 0.05). Conclusion: Data suggested that CIH

  17. Inhibition of apolipoprotein B and triglyceride secretion in human hepatoma cells (HepG2).

    PubMed

    Haghpassand, M; Wilder, D; Moberly, J B

    1996-07-01

    Apolipoprotein B (apoB), the major protein component of triglyceride-rich lipoproteins, is assembled into a lipoprotein particle via a complex, multistep process. Recent studies indicate that triglyceride-rich lipoprotein assembly requires the activity of the heterodimeric protein, microsomal triglyceride transfer protein (MTP). We identified a novel inhibitor of apolipoprotein B secretion using the human hepatoma cell line, HepG2. CP-10447, a derivative of the hypnotic drug methaqualone (Quaalude), inhibited apoB secretion from HepG2 cells with an IC50 of approximately 5 microM. CP-10447 also inhibited apoB secretion from Caco-2 cells, a model of intestinal lipoprotein production. In experiments using [3H]glycerol as a precursor for triglyceride synthesis, CP-10447 (20 microM) inhibited radiolabeled triglyceride secretion by approximately 83% (P < 0.0001) in HepG2 cells and 76% (P < 0.05) in Caco-2 cells with no effect on radiolabel incorporation into cellular triglyceride, indicating that CP-10447 inhibited triglyceride secretion without affecting triglyceride synthesis. RNA solution hybridization assay indicated that CP-10447 did not affect apoB or apoA-I mRNA levels. Pulse-chase experiments in HepG2 cells confirmed that CP-10447 inhibited the secretion of apoB (not its synthesis) without affecting secretion of total proteins or albumin and suggested that CP-10447 stimulates the early intracellular degradation of apoB in the endoplasmic reticulum (ER). Further studies demonstrated that CP-10447 is a potent inhibitor of human liver microsomal triglyceride transfer activity (IC50 approximately 1.7 microM) in an in vitro assay containing artificial liposomes and partially purified human MTP. These data suggest that CP-10447 may inhibit apoB and triglyceride secretion by inhibiting MTP activity and stimulating the early ER degradation of apoB. CP-10447 should provide a useful tool for further study of the mechanisms of apoB secretion and triglyceride

  18. Marketing cardiac CT programs.

    PubMed

    Scott, Jason

    2010-01-01

    There are two components of cardiac CT discussed in this article: coronary artery calcium scoring (CACS) and coronary computed tomography angiography (CCTA).The distinctive advantages of each CT examination are outlined. In order to ensure a successful cardiac CT program, it is imperative that imaging facilities market their cardiac CT practices effectively in order to gain a competitive advantage in this valuable market share. If patients receive quality care by competent individuals, they are more likely to recommend the facility's cardiac CT program. Satisfied patients will also be more willing to come back for any further testing. PMID:22276376

  19. 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.

  20. Serum Triglyceride Level: A Predictor of Complications and Outcomes in Acute Pancreatitis?

    PubMed Central

    Tariq, Hassan; Gaduputi, Vinaya; Peralta, Richard; Abbas, Naeem; Nayudu, Suresh Kumar; Thet, Phyo; Zaw, Tin; Hui, Shirley; Chilimuri, Sridhar

    2016-01-01

    Aim. To study serum triglyceride level as a predictor of complications and outcomes in acute pancreatitis. Methods. In this retrospective observational study, 582 patients admitted with acute pancreatitis, who had serum triglyceride levels measured within the first 24 hours, were divided into two groups. The study group consisted of patients with a triglyceride level ≥2.26 mmol/L (group 2) and the control group consisted of triglyceride level of <2.26 mmol/L (group 1). We collected data for baseline demographics, laboratory values, incidence of complications (local and systemic), admission to the intensive care unit (ICU), ICU length of stay, length of total hospital stay, and death in the two groups. Results. A triglyceride level of ≥2.26 mmol/L was found to be an independent predictor of developing altered mental status (p: 0.004), pancreatic necrosis (p: 0.001), acute respiratory distress syndrome (p: 0001), systemic Inflammatory response syndrome (p: 0.001), acute kidney injury (p: 0.001), hospital length of stay (LOS) (p: 0.002), admission to intensive care unit (ICU) (p: 0.002), and ICU LOS (p: 0.003). Conclusion. A triglyceride level of ≥2.26 mmol/L on admission in acute pancreatitis is an independent predictor of developing local and systemic complications, hospital LOS, admission to ICU, and ICU LOS.

  1. Apolipoprotein E promotes lipid accumulation and differentiation in human adipocytes

    SciTech Connect

    Lasrich, Dorothee; Bartelt, Alexander; Grewal, Thomas; Heeren, Joerg

    2015-09-10

    Several studies in mice indicate a role for apolipoprotein E (APOE) in lipid accumulation and adipogenic differentiation in adipose tissue. However, little is yet known if APOE functions in a similar manner in human adipocytes. This prompted us to compare lipid loading and expression of adipocyte differentiation markers in APOE-deficient and control adipocytes using the differentiated human mesenchymal stem cell line hMSC-Tert as well as primary human and mouse adipocytes as model systems. Differentiated hMSC-Tert were stably transduced with or without siRNA targeting APOE while murine adipocytes were isolated from wild type and Apoe knockout mice. Human APOE knockdown hMSC-Tert adipocytes accumulated markedly less triglycerides compared to control cells. This correlated with strongly decreased gene expression levels of adipocyte markers such as adiponectin (ADIPOQ) and fatty acid binding protein 4 (FABP4) as well as the key transcription factor driving adipocyte differentiation, peroxisome proliferator activator receptor gamma (PPARG), in particular the PPARG2 isoform. Similarly, differentiation of murine Apoe-deficient adipocytes was characterized by reduced gene expression of Adipoq, Fabp4 and Pparg. Interestingly, incubation of APOE-deficient hMSC-Tert adipocytes with conditioned media from APOE3-overexpressing adipocytes or APOE-containing Very Low Density Lipoprotein (VLDL) partially restored triglyceride accumulation, but were unable to induce adipocyte differentiation, as judged by expression of adipocyte markers. Taken together, depletion of endogenous APOE in human adipocytes severely impairs lipid accumulation, which is associated with an inability to initiate differentiation. - Highlights: • Immortalized human mesenchymal stem cells were used to study adipocyte development. • Knockdown of endogenous APOE lead to impaired lipid accumulation and adipogenesis. • APOE supplementation partially restored lipid accumulation but not differentiation.

  2. Association of Lipid Accumulation Product with Cardio-Metabolic Risk Factors in Postmenopausal Women.

    PubMed

    Namazi Shabestari, Alireza; Asadi, Mojgan; Jouyandeh, Zahra; Qorbani, Mostafa; Kelishadi, Roya

    2016-06-01

    The lipid accumulation product is a novel, safe and inexpensive index of central lipid over accumulation based on waist circumference and fasting concentration of circulating triglycerides. This study was designed to investigate the ability of lipid accumulation product to predict Cardio-metabolic risk factors in postmenopausal women. In this Cross-sectional study, 264 postmenopausal women by using convenience sampling method were selected from menopause clinic in Tehran. Cardio-metabolic risk factors were measured, and lipid accumulation product (waist-58×triglycerides [nmol/L]) was calculated. Optimal cut-off point of lipid accumulation product for predicting metabolic syndrome was estimated by ROC (Receiver-operating characteristic) curve analysis. Metabolic syndrome was diagnosed in 41.2% of subjects. Optimal cut-off point of lipid accumulation product for predicting metabolic syndrome was 47.63 (sensitivity:75%; specificity:77.9%). High lipid accumulation product increases risk of all Cardio-metabolic risk factors except overweight, high Total Cholesterol, high Low Density Lipoprotein Cholesterol and high Fasting Blood Sugar in postmenopausal women. Our findings show that lipid accumulation product is associated with metabolic syndrome and some Cardio-metabolic risk factors Also lipid accumulation product may have been a useful tool for predicting cardiovascular disease and metabolic syndrome risk in postmenopausal women. PMID:27306343

  3. Cardiac sarcoidosis demonstrated by Tl-201 and Ga-67 SPECT imaging

    SciTech Connect

    Taki, J.; Nakajima, K.; Bunko, H.; Ohguchi, M.; Tonami, N.; Hisada, K. )

    1990-09-01

    Ga-67 and Tl-201 SPECT was performed to evaluate cardiac sarcoidosis in a 15-year-old boy. Tl-201 SPECT imaging showed decreased uptake in the inferior to lateral wall and Ga-67 accumulation in the area of decreased Tl-201 uptake. These findings suggested cardiac sarcoidosis, and cardiac biopsy confirmed this diagnosis. After corticosteroid therapy, myocardial uptake of Ga-67 disappeared and myocardial TI-201 uptake became more homogeneous.

  4. Blunt cardiac rupture.

    PubMed

    Martin, T D; Flynn, T C; Rowlands, B J; Ward, R E; Fischer, R P

    1984-04-01

    Blunt injury to the heart ranges from contusion to disruption. This report comprises 14 patients seen during a 6-year period with cardiac rupture secondary to blunt trauma. Eight patients were injured in automobile accidents, two patients were injured in auto-pedestrian accidents, two were kicked in the chest by ungulates, and two sustained falls. Cardiac tamponade was suspected in ten patients. Five patients presented with prehospital cardiac arrest or arrested shortly after arrival. All underwent emergency department thoracotomy without survival. Two patients expired in the operating room during attempted cardiac repair; both had significant extracardiac injury. Seven patients survived, three had right atrial injuries, three had right ventricular injuries, and one had a left atrial injury. Cardiopulmonary bypass was not required for repair of the surviving patients. There were no significant complications from the cardiac repair. The history of significant force dispersed over a relatively small area of the precordium as in a kicking injury from an animal or steering wheel impact should alert the physician to possible cardiac rupture. Cardiac rupture should be considered in patients who present with signs of cardiac tamponade or persistent thoracic bleeding after blunt trauma. PMID:6708151

  5. Sudden Cardiac Death

    PubMed Central

    Weinberg, Marc

    1978-01-01

    Over the past decade, there has been a significant decrease in the hospital mortality of patients with coronary artery disease. However, sudden cardiac death, which accounts for the majority of deaths from coronary artery disease, hasbeen little affected. This report reviews the pathology, electrophysiology, demographics and clinical presentation of sudden cardiac death. Emergency care and possible preventative measures are examined. PMID:356435

  6. Myocardial Fat Accumulation Is Independent of Measures of Insulin Sensitivity

    PubMed Central

    Noureldin, Radwa; Ouwerkerk, Ronald; Liu, Elizabeth Y.; Madan, Ritu; Abel, Brent S.; Mullins, Katherine; Walter, Mary F.; Skarulis, Monica C.; Gharib, Ahmed M.

    2015-01-01

    Background: Myocardial steatosis, an independent predictor of diastolic dysfunction, is frequently present in type 2 diabetes mellitus. High free fatty acid flux, hyperglycemia, and hyperinsulinemia may play a role in myocardial steatosis. There are no prior studies examining the relationship between insulin sensitivity (antilipolytic and glucose disposal actions of insulin) and cardiac steatosis. Objective: Using a cross-sectional study design of individuals with and without metabolic syndrome (MetSyn), we examined the relationships between cardiac steatosis and the sensitivity of the antilipolytic and glucose disposal actions of insulin. Methods: Pericardial fat (PF) volume, intramyocardial and hepatic fat (MF and HF) content, visceral fat (VF) and sc fat content were assessed by magnetic resonance imaging in 77 subjects (49 without MetSyn and 28 with MetSyn). In a subset of the larger cohort (n = 52), peripheral insulin sensitivity index (SI) and adipocyte insulin sensitivity (Adipo-SI) were determined from an insulin-modified frequently sampled iv glucose tolerance test. The Quantitative Insulin Sensitivity Check Index was used as a surrogate for hepatic insulin sensitivity. Results: Individuals with the MetSyn had significantly higher body mass index, total body fat, and MF, PF, HF, and VF content. HF and VF, but not MF, were negatively correlated with the Quantitative Insulin Sensitivity Check Index, Adipo-SI, and SI. Stepwise regression revealed that waist circumference and serum triglyceride levels independently predicted MF and PF, respectively. Adipo-SI and serum triglyceride levels independently predict HF. Conclusion: Myocardial steatosis is unrelated to hepatic, adipocyte, or peripheral insulin sensitivity. Although it is frequently observed in insulin-resistant subjects, further studies are necessary to identify and delineate pathogenic mechanisms that differentially affect cardiac and hepatic steatosis. PMID:26020762

  7. Cardiac Hegemony of Senescence.

    PubMed

    Siddiqi, Sailay; Sussman, Mark A

    2013-12-01

    Cardiac senescence and age-related disease development have gained general attention and recognition in the past decades due to increased accessibility and quality of health care. The advancement in global civilization is complementary to concerns regarding population aging and development of chronic degenerative diseases. Cardiac degeneration has been rigorously studied. The molecular mechanisms of cardiac senescence are on multiple cellular levels and hold a multilayer complexity level, thereby hampering development of unambiguous treatment protocols. In particular, the synergistic exchange of the senescence phenotype through a senescence secretome between myocytes and stem cells appears complicated and is of great future therapeutic value. The current review article will highlight hallmarks of senescence, cardiac myocyte and stem cell senescence, and the mutual exchange of senescent secretome. Future cardiac cell therapy approaches require a comprehensive understanding of myocardial senescence to improve therapeutic efficiency as well as efficacy. PMID:24349878

  8. Cardiac Hegemony of Senescence

    PubMed Central

    Siddiqi, Sailay; Sussman, Mark A.

    2013-01-01

    Cardiac senescence and age-related disease development have gained general attention and recognition in the past decades due to increased accessibility and quality of health care. The advancement in global civilization is complementary to concerns regarding population aging and development of chronic degenerative diseases. Cardiac degeneration has been rigorously studied. The molecular mechanisms of cardiac senescence are on multiple cellular levels and hold a multilayer complexity level, thereby hampering development of unambiguous treatment protocols. In particular, the synergistic exchange of the senescence phenotype through a senescence secretome between myocytes and stem cells appears complicated and is of great future therapeutic value. The current review article will highlight hallmarks of senescence, cardiac myocyte and stem cell senescence, and the mutual exchange of senescent secretome. Future cardiac cell therapy approaches require a comprehensive understanding of myocardial senescence to improve therapeutic efficiency as well as efficacy. PMID:24349878

  9. Cardiac NO signalling in the metabolic syndrome

    PubMed Central

    Pechánová, O; Varga, Z V; Cebová, M; Giricz, Z; Pacher, P; Ferdinandy, P

    2015-01-01

    It is well documented that metabolic syndrome (i.e. a group of risk factors, such as abdominal obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides and low cholesterol level in high-density lipoprotein), which raises the risk for heart disease and diabetes, is associated with increased reactive oxygen and nitrogen species (ROS/RNS) generation. ROS/RNS can modulate cardiac NO signalling and trigger various adaptive changes in NOS and antioxidant enzyme expressions/activities. While initially these changes may represent protective mechanisms in metabolic syndrome, later with more prolonged oxidative, nitrosative and nitrative stress, these are often exhausted, eventually favouring myocardial RNS generation and decreased NO bioavailability. The increased oxidative and nitrative stress also impairs the NO-soluble guanylate cyclase (sGC) signalling pathway, limiting the ability of NO to exert its fundamental signalling roles in the heart. Enhanced ROS/RNS generation in the presence of risk factors also facilitates activation of redox-dependent transcriptional factors such as NF-κB, promoting myocardial expression of various pro-inflammatory mediators, and eventually the development of cardiac dysfunction and remodelling. While the dysregulation of NO signalling may interfere with the therapeutic efficacy of conventional drugs used in the management of metabolic syndrome, the modulation of NO signalling may also be responsible for the therapeutic benefits of already proven or recently developed treatment approaches, such as ACE inhibitors, certain β-blockers, and sGC activators. Better understanding of the above-mentioned pathological processes may ultimately lead to more successful therapeutic approaches to overcome metabolic syndrome and its pathological consequences in cardiac NO signalling. Linked Articles This article is part of a themed section on Pharmacology of the Gasotransmitters. To view the other articles in this

  10. [Cardiac evaluation before non-cardiac surgery].

    PubMed

    Menzenbach, Jan; Boehm, Olaf

    2016-07-01

    Before non-cardiac surgery, evaluation of cardiac function is no frequent part of surgical treatment. European societies of anesthesiology and cardiology published consensus-guidelines in 2014 to present a reasonable approach for preoperative evaluation. This paper intends to differentiate the composite of perioperative risk and to display the guidelines methodical approach to handle it. Features to identify patients at risk from an ageing population with comorbidities, are the classification of surgical risk, functional capacity and risk indices. Application of diagnostic means, should be used adjusted to this risk estimation. Cardiac biomarkers are useful to discover risk of complications or mortality, that cannot be assessed by clinical signs. After preoperative optimization and perioperative cardiac protection, the observation of the postoperative period remains, to prohibit complications or even death. In consideration of limited resources of intensive care department, postoperative ward rounds beyond intensive care units are considered to be an appropriate instrument to avoid or recognize complications early to reduce postoperative mortality. PMID:27479258

  11. Cardiac oxidative stress in a mouse model of neutral lipid storage disease☆

    PubMed Central

    Schrammel, Astrid; Mussbacher, Marion; Winkler, Sarah; Haemmerle, Guenter; Stessel, Heike; Wölkart, Gerald; Zechner, Rudolf; Mayer, Bernd

    2013-01-01

    Cardiac oxidative stress has been implicated in the pathogenesis of hypertrophy, cardiomyopathy and heart failure. Systemic deletion of the gene encoding adipose triglyceride lipase (ATGL), the enzyme that catalyzes the rate-limiting step of triglyceride lipolysis, results in a phenotype characterized by severe steatotic cardiac dysfunction. The objective of the present study was to investigate a potential role of oxidative stress in cardiac ATGL deficiency. Hearts of mice with global ATGL knockout were compared to those of mice with cardiomyocyte-restricted overexpression of ATGL and to those of wildtype littermates. Our results demonstrate that oxidative stress, measured as lucigenin chemiluminescence, was increased ~ 6-fold in ATGL-deficient hearts. In parallel, cytosolic NADPH oxidase subunits p67phox and p47phox were upregulated 4–5-fold at the protein level. Moreover, a prominent upregulation of different inflammatory markers (tumor necrosis factor α, monocyte chemotactant protein-1, interleukin 6, and galectin-3) was observed in those hearts. Both the oxidative and inflammatory responses were abolished upon cardiomyocyte-restricted overexpression of ATGL. Investigating the effect of oxidative and inflammatory stress on nitric oxide/cGMP signal transduction we observed a ~ 2.5-fold upregulation of soluble guanylate cyclase activity and a ~ 2-fold increase in cardiac tetrahydrobiopterin levels. Systemic treatment of ATGL-deficient mice with the superoxide dismutase mimetic Mn(III)tetrakis (4-benzoic acid) porphyrin did not ameliorate but rather aggravated cardiac oxidative stress. Our data suggest that oxidative and inflammatory stress seems involved in lipotoxic heart disease. Upregulation of soluble guanylate cyclase and cardiac tetrahydrobiopterin might be regarded as counterregulatory mechanisms in cardiac ATGL deficiency. PMID:23867907

  12. Naturally occurring cardiac glycosides.

    PubMed

    Radford, D J; Gillies, A D; Hinds, J A; Duffy, P

    1986-05-12

    Cardiac glycoside poisoning from the ingestion of plants, particularly of oleanders, occurs with reasonable frequency in tropical and subtropical areas. We have assessed a variety of plant specimens for their cardiac glycoside content by means of radioimmunoassays with antibodies that differ in their specificity for cardiac glycosides. Significant amounts of immunoreactive cardiac glycoside were found to be present in the ornamental shrubs: yellow oleander (Thevetia peruviana); oleander (Nerium oleander); wintersweet (Carissa spectabilis); bushman's poison (Carissa acokanthera); sea-mango (Cerbera manghas); and frangipani (Plumeria rubra); and in the milkweeds: redheaded cotton-bush (Asclepias curassavica); balloon cotton (Asclepias fruiticosa); king's crown (Calotropis procera); and rubber vine (Cryptostegia grandifolia). The venom gland of the cane toad (Bufo marinus) also contained large quantities of cardiac glycosides. The competitive immunoassay method permits the rapid screening of specimens that are suspected to contain cardiac glycosides. Awareness of the existence of these plant and animal toxins and their dangers allows them to be avoided and poisoning prevented. The method is also useful for the confirmation of the presence of cardiac glycosides in serum in cases of poisoning. PMID:3086679

  13. [Cardiac Rehabilitation 2015].

    PubMed

    Hoffmann, Andreas

    2015-11-25

    The goals of cardiac rehabilitation are (re-)conditioning and secondary prevention in patients with heart disease or an elevated cardiovascular risk profile. Rehabilitation is based on motivation through education, on adapted physical activity, instruction of relaxation techniques, psychological support and optimized medication. It is performed preferably in groups either in outpatient or inpatient settings. The Swiss working group on cardiac rehabilitation provides a network of institutions with regular quality auditing. Positive effects of rehabilitation programs on mortality and morbidity have been established by numerous studies. Although a majority of patients after cardiac surgery are being referred to rehabilitation, these services are notoriously underused after catheter procedures. PMID:26602848

  14. Insulin therapy in burn patients does not contribute to hepatic triglyceride production.

    PubMed Central

    Aarsland, A; Chinkes, D L; Sakurai, Y; Nguyen, T T; Herndon, D N; Wolfe, R R

    1998-01-01

    Lipid kinetics were studied in six severely burned patients who were treated with a high dose of exogenous insulin plus glucose to promote protein metabolism. The patients were 20+/-2-yr-old (SD) with 63+/-8% total body surface area burned. They were studied in a randomized order (a) in the fed state on the seventh day of a control period (C) of continuous high-carbohydrate enteral feeding alone, and (b) on the seventh day of enteral feeding plus exogenous insulin (200 pmol/h = 28 U/h) with extra glucose given as needed to avoid hypoglycemia (I+G). Despite a glucose delivery rate approximately 100% in excess of energy requirements, the following lipid parameters were unchanged: (a) total hepatic VLDL triglyceride (TG) secretion rate (0.165+/-0.138 [C] vs. 0.154+/- 0.138 mmol/kg . d-1 [I+G]), (b) plasma TG concentration (1.58+/-0.66 [C] vs. 1. 36+/-0.41 mmol/liter [I+G]), and (c) plasma VLDL TG concentration (0. 68+/-0.79 [C] vs. 0.67+/- 0.63 mmol/liter [I+G]). Instead, the high-carbohydrate delivery in conjunction with insulin therapy increased the proportion of de novo-synthesized palmitate in VLDL TG from 13+/-5% (C) to 34+/-14% (I+G), with a corresponding decreased amount of palmitate from lipolysis. In association with the doubling of the secretion rate of de novo-synthesized fatty acid (FA) in VLDL TG during insulin therapy (P > 0.5), the relative amount of palmitate and stearate increased from 35+/-5 to 44+/-8% and 4+/-1 to 7+/-2%, respectively, in VLDL TG, while the relative concentration of oleate and linoleate decreased from 43+/-5 to 37+/-6% and 8+/-4% to 2+/-2%, respectively. A 15-fold increase in plasma insulin concentration did not change the rate of release of FA into plasma (8.22+/-2.86 [C] vs. 8.72+/-6.68 mmol/kg.d-1 [I+G]. The peripheral release of FA represents a far greater potential for hepatic lipid accumulation in burn patients than the endogenous hepatic fat synthesis, even during excessive carbohydrate intake in conjunction with insulin

  15. Lysophosphatidylcholine (LPC) metabolism and cardiac arrhythmias

    SciTech Connect

    Giffin, D.M.; Man, R.Y.K.; Arthur, G.; Choy, P.C.

    1986-05-01

    The effect of LPC in the production of cardiac arrhythmias in isolated mammalian hearts has been well-documented. Cardiac arrhythmias are initiated by the accumulation of the lysolipid in the cardiac membrane. When isolated rat hearts were perfused in 10 ..mu..M LPC for 10 min, severe arrhythmias were observed in all experiments. In isolated guinea pig hearts that were perfused under identical conditions, the development of severe arrhythmias was never observed, and mild arrhythmias were produced in less than 50% of the hearts used. When the hearts of both species were perfused with (/sup 14/C-palmitate)-LPC, the labellings found in the microsomal fractions (expressed in mg protein) were similar. However, a higher amount of labelled LPC (2-fold) was found in rat heart microsomes, whereas a higher amount of labelled fatty acid was located in the guinea pig heart microsomes. Determination of lysophospholipase activities in these microsomal fractions revealed that the specific activity of the enzyme was much higher in the guinea pig heart than the rat heart. The authors conclude that the differential effect of LPC-induced arrhythmias between the rat and guinea pig heart may be a direct result of the lysophospholipase activities in these hearts. The ability to catabolize LPC more rapidly in the guinea pig heart may decrease the accumulation of LPC in the membrane, and hence, reduce the production of arrhythmias.

  16. Fast carry accumulator design

    NASA Technical Reports Server (NTRS)

    Mastin, W. C.

    1971-01-01

    Simple iterative accumulator combined with gated-carry, carry-completion detection, and skip-carry circuits produces three accumulators with decreased carry propagation times. Devices are used in machine control, measurement equipment, and computer applications to increase speed of binary addition. NAND gates are used in combining network.

  17. Cardiac sarcoidosis - silent destroyer.

    PubMed

    Martusewicz-Boros, Magdalena M; Piotrowska-Kownacka, Dorota; Wiatr, Elżbieta; Roszkowski-Śliż, Kazimierz

    2016-01-01

    We report a case of histologically proven pulmonary sarcoidosis and cardiac involvement in a 53-year old woman with progression leading to the heart failure documented in cardiovascular magnetic resonsnce studies. PMID:27537722

  18. Cardiac glycoside overdose

    MedlinePlus

    ... found in the leaves of the digitalis (foxglove) plant. This plant is the original source of this medicine. People ... Digitoxin (Crystodigin) Digoxin (Lanoxicaps, Lanoxin) Besides the foxglove plant, cardiac glycosides also occur naturally in plants such ...

  19. Cardiac conduction system

    MedlinePlus Videos and Cool Tools

    ... signals to the heart muscle causing it to contract. The main components of the cardiac conduction system ... the sequence by causing the atrial muscles to contract. From there, the signal travels to the AV ...

  20. Nonfasting triglycerides and risk of cardiovascular death in men and women from the Norwegian Counties Study

    PubMed Central

    Veierød, M. B.; Tverdal, A.; Pedersen, J. I.; Selmer, R.

    2010-01-01

    The association between nonfasting triglycerides and cardiovascular disease (CVD) has recently been actualized. The aim of the present study was to investigate nonfasting triglycerides as a predictor of CVD mortality in men and women. A total of 86,261 participants in the Norwegian Counties Study 1974–2007, initially aged 20–50 years and free of CVD were included. We estimated hazard ratios (HRs) for deaths from CVD, ischemic heart disease (IHD), stroke and all causes by level of nonfasting triglycerides. Mean follow-up was 27.0 years. A total of 9,528 men died (3,620 from CVD, 2,408 IHD, 543 stroke), and totally 5,267 women died (1,296 CVD, 626 IHD, 360 stroke). After adjustment for CVD risk factors other than HDL-cholesterol, the HRs (95% CI) per 1 mmol/l increase in nonfasting triglycerides were 1.16 (1.13–1.20), 1.20 (1.14–1.27), 1.26 (1.19–1.34) and 1.09 (0.96–1.23) for all cause mortality, CVD, IHD, and stroke mortality in women. Corresponding figures in men were 1.03 (1.01–1.04), 1.03 (1.00–1.05), 1.03 (1.00–1.06) and 0.99 (0.92–1.07). In a subsample where HDL-cholesterol was measured (n = 40,144), the association between CVD mortality and triglycerides observed in women disappeared after adjustment for HDL-cholesterol. In a model including the Framingham CHD risk score the effect of triglycerides disappeared in both men and women. In conclusion, nonfasting triglycerides were associated with increased risk of CVD death for both women and men. Adjustment for major cardiovascular risk factors, however, attenuated the effect. Nonfasting triglycerides added no predictive information on CVD mortality beyond the Framingham CHD risk score in men and women. PMID:20890636

  1. Ranolazine in Cardiac Arrhythmia.

    PubMed

    Saad, Marwan; Mahmoud, Ahmed; Elgendy, Islam Y; Richard Conti, C

    2016-03-01

    Ranolazine utilization in the management of refractory angina has been established by multiple randomized clinical studies. However, there is growing evidence showing an evolving role in the field of cardiac arrhythmias. Multiple experimental and clinical studies have evaluated the role of ranolazine in prevention and management of atrial fibrillation, with ongoing studies on its role in ventricular arrhythmias. In this review, we will discuss the pharmacological, experimental, and clinical evidence behind ranolazine use in the management of various cardiac arrhythmias. PMID:26459200

  2. Cardiac rehabilitation in Germany.

    PubMed

    Karoff, Marthin; Held, Klaus; Bjarnason-Wehrens, Birna

    2007-02-01

    The purpose of this review is to give an overview of the rehabilitation measures provided for cardiac patients in Germany and to outline its legal basis and outcomes. In Germany the cardiac rehabilitation system is different from rehabilitation measures in other European countries. Cardiac rehabilitation in Germany since 1885 is based on specific laws and the regulations of insurance providers. Cardiac rehabilitation has predominantly been offered as an inpatient service, but has recently been complemented by outpatient services. A general agreement on the different indications for offering these two services has yet to be reached. Cardiac rehabilitation is mainly offered after an acute cardiac event and bypass surgery. It is also indicated in severe heart failure and special cases of percutaneous coronary intervention. Most patients are men (>65%) and the age at which events occur is increasing. The benefits obtained during the 3-4 weeks after an acute event, and confirmed in numerous studies, are often later lost under 'usual care' conditions. Many attempts have been made by rehabilitation institutions to improve this deficit by providing intensive aftercare. One instrument set up to achieve this is the nationwide institution currently comprising more than 6000 heart groups with approximately 120000 outpatients. After coronary artery bypass grafting or acute coronary syndrome cardiac rehabilitation can usually be started within 10 days. The multidisciplinary rehabilitation team consists of cardiologists, psychologists, exercise therapists, social workers, nutritionists and nurses. The positive effects of cardiac rehabilitation are also important economically, for example, for the improvement of secondary prevention and vocational integration. PMID:17301623

  3. Cardiac imaging in adults

    SciTech Connect

    Jaffe, C.C.

    1987-01-01

    This book approaches adult cardiac disease from the correlative imaging perspective. It includes chest X-rays and angiographs, 2-dimensional echocardiograms with explanatory diagrams for clarity, plus details on digital radiology, nuclear medicine techniques, CT and MRI. It also covers the normal heart, valvular heart disease, myocardial disease, pericardial disease, bacterial endocarditis, aortic aneurysm, cardiac tumors, and congenital heart disease of the adult. It points out those aspects where one imaging technique has significant superiority.

  4. Cardiac Munchausen's syndrome.

    PubMed Central

    Dickinson, E J; Evans, T R

    1987-01-01

    Ten years' experience of cardiac Munchausen's syndrome in the Cardiac Care Unit of an Inner London teaching hospital is reported. Thirty-six admissions in this category were identified and analysed, and 4 typical cases are described. The common presenting complaints, recurring features and the relationship with other forms of Munchausen's syndrome are discussed, as are possible strategies available to deal with this clinical entity. PMID:3694601

  5. Lean heart: Role of leptin in cardiac hypertrophy and metabolism.

    PubMed

    Hall, Michael E; Harmancey, Romain; Stec, David E

    2015-09-26

    Leptin is an adipokine that has been linked with the cardiovascular complications resulting from obesity such as hypertension and heart disease. Obese patients have high levels of circulating leptin due to increased fat mass. Clinical and population studies have correlated high levels of circulating leptin with the development of cardiac hypertrophy in obesity. Leptin has also been demonstrated to increase the growth of cultured cardiomyocytes. However, several animal studies of obese leptin deficient mice have not supported a role for leptin in promoting cardiac hypertrophy so the role of leptin in this pathological process remains unclear. Leptin is also an important hormone in the regulation of cardiac metabolism where it supports oxidation of glucose and fatty acids. In addition, leptin plays a critical role in protecting the heart from excess lipid accumulation and the formation of toxic lipids in obesity a condition known as cardiac lipotoxicity. This paper focuses on the data supporting and refuting leptin's role in promoting cardiac hypertrophy as well as its important role in the regulation of cardiac metabolism and protection against cardiac lipotoxicity. PMID:26413228

  6. Lean heart: Role of leptin in cardiac hypertrophy and metabolism

    PubMed Central

    Hall, Michael E; Harmancey, Romain; Stec, David E

    2015-01-01

    Leptin is an adipokine that has been linked with the cardiovascular complications resulting from obesity such as hypertension and heart disease. Obese patients have high levels of circulating leptin due to increased fat mass. Clinical and population studies have correlated high levels of circulating leptin with the development of cardiac hypertrophy in obesity. Leptin has also been demonstrated to increase the growth of cultured cardiomyocytes. However, several animal studies of obese leptin deficient mice have not supported a role for leptin in promoting cardiac hypertrophy so the role of leptin in this pathological process remains unclear. Leptin is also an important hormone in the regulation of cardiac metabolism where it supports oxidation of glucose and fatty acids. In addition, leptin plays a critical role in protecting the heart from excess lipid accumulation and the formation of toxic lipids in obesity a condition known as cardiac lipotoxicity. This paper focuses on the data supporting and refuting leptin’s role in promoting cardiac hypertrophy as well as its important role in the regulation of cardiac metabolism and protection against cardiac lipotoxicity. PMID:26413228

  7. Cardiac Applications of Optogenetics

    PubMed Central

    Ambrosi, Christina M.; Klimas, Aleksandra; Yu, Jinzhu; Entcheva, Emilia

    2014-01-01

    In complex multicellular systems, such as the brain or the heart, the ability to selectively perturb and observe the response of individual components at the cellular level and with millisecond resolution in time, is essential for mechanistic understanding of function. Optogenetics uses genetic encoding of light sensitivity (by the expression of microbial opsins) to provide such capabilities for manipulation, recording, and control by light with cell specificity and high spatiotemporal resolution. As an optical approach, it is inherently scalable for remote and parallel interrogation of biological function at the tissue level; with implantable miniaturized devices, the technique is uniquely suitable for in vivo tracking of function, as illustrated by numerous applications in the brain. Its expansion into the cardiac area has been slow. Here, using examples from published research and original data, we focus on optogenetics applications to cardiac electrophysiology, specifically dealing with the ability to manipulate membrane voltage by light with implications for cardiac pacing, cardioversion, cell communication, and arrhythmia research, in general. We discuss gene and cell delivery methods of inscribing light sensitivity in cardiac tissue, functionality of the light-sensitive ion channels within different types of cardiac cells, utility in probing electrical coupling between different cell types, approaches and design solutions to all-optical electrophysiology by the combination of optogenetic sensors and actuators, and specific challenges in moving towards in vivo cardiac optogenetics. PMID:25035999

  8. Cardiac MRI of acute coronary syndrome.

    PubMed

    Akerem Khan, Shamruz; Khan, Shamruz Akarem; Williamson, Eric E; Foley, Thomas A; Cullen, Ethany L; Young, Phillip M; Araoz, Philip A

    2013-05-01

    Acute coronary syndrome (ACS) is a major cause of morbidity and mortality worldwide. New serological biomarkers, such as troponins, have improved the diagnosis of ACS; however, the diagnosis of ACS can still be difficult as there is marked heterogeneity in its presentation and significant overlap with other disorders presenting with chest pain. Evidence is accumulating that cardiac MRI provides information that can aid the detection and differential diagnosis of ACS, guide clinical decision-making and improve risk-stratification after an event. In this review, we present the relevant cardiac MRI techniques that can be used to detect ACS accurately, provide differential diagnosis, identify the sequelae of ACS, and determine prognostication after ACS. PMID:23668741

  9. Direct Cardiac Reprogramming: Advances in Cardiac Regeneration

    PubMed Central

    Chen, Olivia; Qian, Li

    2015-01-01

    Heart disease is one of the lead causes of death worldwide. Many forms of heart disease, including myocardial infarction and pressure-loading cardiomyopathies, result in irreversible cardiomyocyte death. Activated fibroblasts respond to cardiac injury by forming scar tissue, but ultimately this response fails to restore cardiac function. Unfortunately, the human heart has little regenerative ability and long-term outcomes following acute coronary events often include chronic and end-stage heart failure. Building upon years of research aimed at restoring functional cardiomyocytes, recent advances have been made in the direct reprogramming of fibroblasts toward a cardiomyocyte cell fate both in vitro and in vivo. Several experiments show functional improvements in mouse models of myocardial infarction following in situ generation of cardiomyocyte-like cells from endogenous fibroblasts. Though many of these studies are in an early stage, this nascent technology holds promise for future applications in regenerative medicine. In this review, we discuss the history, progress, methods, challenges, and future directions of direct cardiac reprogramming. PMID:26176012

  10. Effect of medium/ω-6 long chain triglyceride-based emulsion on leucocyte death and inflammatory gene expression

    PubMed Central

    Cury-Boaventura, M F; Gorjão, R; Martins de Lima, T; Fiamoncini, J; Godoy, A B P; Deschamphs, F C; Soriano, F G; Curi, R

    2011-01-01

    Lipid emulsion (LE) containing medium/ω-6 long chain triglyceride-based emulsion (MCT/ω-6 LCT LE) has been recommended in the place of ω-6 LCT-based emulsion to prevent impairment of immune function. The impact of MCT/ω-6 LCT LE on lymphocyte and neutrophil death and expression of genes related to inflammation was investigated. Seven volunteers were recruited and infusion of MCT/ω-6 LCT LE was performed for 6 h. Four volunteers received saline and no change was found. Blood samples were collected before, immediately afterwards and 18 h after LE infusion. Lymphocytes and neutrophils were studied immediately after isolation and after 24 and 48 h in culture. The following determinations were carried out: plasma-free fatty acids, triacylglycerol and cholesterol concentrations, plasma fatty acid composition, neutral lipid accumulation in lymphocytes and neutrophils, signs of lymphocyte and neutrophil death and lymphocyte expression of genes related to inflammation. MCT/ω-6 LCT LE induced lymphocyte and neutrophil death. The mechanism for MCT/ω-6 LCT LE-dependent induction of leucocyte death may involve changes in neutral lipid content and modulation of expression of genes related to cell death, proteolysis, cell signalling, inflammatory response, oxidative stress and transcription. PMID:21682721