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Sample records for medium chain triglycerides

  1. Medium Chain Triglycerides in Paediatric Practice

    PubMed Central

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

    1970-01-01

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

  2. 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

  3. 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

  4. A comparison of medium-chain and long-chain triglycerides in surgical patients.

    PubMed

    Jiang, Z M; Zhang, S Y; Wang, X R; Yang, N F; Zhu, Y; Wilmore, D

    1993-02-01

    Available lipid emulsions made from soybean or safflower oil are classified as long-chain triglycerides (LCT). In contrast, medium-chain triglyceride (MCT) emulsions have different physical properties and are metabolized by other biochemical pathways. To compare the differences between these two fat emulsions, the authors studied 12 surgical patients and 6 volunteers. These subjects were randomly assigned to receive parenteral nutrition with MCT or LCT emulsion. Measurement of arterial and venous concentration differences across the forearm demonstrated that muscle utilization was significantly improved with MCT administration. There was also a trend toward improved nitrogen balance in the MCT group, and less weight loss in the postoperative period also was observed in this group. During the fat clearance test, the serum ketone concentrations were significantly higher in the MCT than the LCT group. The improvement in nitrogen retention may be associated with increasing ketone and insulin levels. Fat emulsions containing 50% MCT are safe for use in parenteral nutrition and may provide an alternate fuel that improves protein metabolism. PMID:8439215

  5. Physico-chemical characteristics of burfi prepared by using medium chain triglyceride rich margarines.

    PubMed

    Tiwari, Shipra; Chetana, Ramakrishna; Puttaraju, Shashikala; Khatoon, Sakina

    2014-01-01

    Medium chain triglyceride rich margarines were prepared using palm, coconut oil blends in the ratio of 80:20 (Margarine 1) and 60:40 (Margarine 2). The margarines were used to prepare burfi and compared with products prepared using commercial margarine, ghee and butter. The physicochemical characteristics such as texture, color, free fatty acid, peroxide value, saponification value, unsaponifiable matter and fatty acid composition of oils, fats and margarines were carried out. Results showed that 11.0 and 21.9% of medium chain triglycerides were present in margarine 1 and 2 respectively. The texture, colour, moisture content, peroxide value and sensory evaluation were carried out for the burfi samples. Laboratory prepared margarines improved the textural quality of burfi compared to commercial margarine, ghee and butter. The sensory analyses of the burfi samples revealed that burfi prepared from margarine 1 was more acceptable compared to commercial margarine.

  6. Physico-chemical characteristics of burfi prepared by using medium chain triglyceride rich margarines.

    PubMed

    Tiwari, Shipra; Chetana, Ramakrishna; Puttaraju, Shashikala; Khatoon, Sakina

    2014-01-01

    Medium chain triglyceride rich margarines were prepared using palm, coconut oil blends in the ratio of 80:20 (Margarine 1) and 60:40 (Margarine 2). The margarines were used to prepare burfi and compared with products prepared using commercial margarine, ghee and butter. The physicochemical characteristics such as texture, color, free fatty acid, peroxide value, saponification value, unsaponifiable matter and fatty acid composition of oils, fats and margarines were carried out. Results showed that 11.0 and 21.9% of medium chain triglycerides were present in margarine 1 and 2 respectively. The texture, colour, moisture content, peroxide value and sensory evaluation were carried out for the burfi samples. Laboratory prepared margarines improved the textural quality of burfi compared to commercial margarine, ghee and butter. The sensory analyses of the burfi samples revealed that burfi prepared from margarine 1 was more acceptable compared to commercial margarine. PMID:24426059

  7. [Absorption of medium chain triglycerides in patients with blind loop syndrome].

    PubMed

    Pereira Filho, R A; Sevá-Pereira, A; de Magalhães, A F

    1988-01-01

    Absorption of medium chain triglycerides (MCT) was estimated in 10 patients with stagnant loop syndrome (SLS). Six patients had steatorrhea due to gastrojejunal anastomosis and 4 due to diabetic neuropathy. The diagnosis of SLS was confirmed by antibiotic therapeutic test after exclusion of other causes of malabsorption syndrome. Each patient was submitted to 2 types of diet during one week each, differing only in the type of added lipid. In the diet with long chain triglycerides (LCT), soy oil and butter were added. In the diet, with medium chain triglycerides, only MCT oil from babaçu was added. The excretion of lipid was determined in the feces in the last 3 days of each diet. The results showed that the medium fecal lipid excretion was 48.6 (sd = 19.8) g/d in the LCT diet and 26.6 (sd = 13.8) g/d in the MCT [d = 22.0; s(d) = 3.10; t = 7.10; p less than 0.001], which indicates that in patients with SLS, MCT diet was better absorbed than LCT diet. It is suggested that MCT oil may be used as a caloric source during nutritional recovery in SLS.

  8. Effect of medium-chain triglycerides on calbindin-D9k expression in the intestine.

    PubMed

    Devlin, A; Innis, S M; Wall, K; Krisinger, J

    1996-05-01

    These studies determined the effect of the saturated fat source in infant formula on the expression of calbindin-D9k (CaBP-9k). Piglets were fed from birth to 8 d with milk or formula containing saturated fatty acids as medium-chain triglycerides (MCT), coconut oil, palm oil (Palm 1), or synthesized triglycerides with 16:0 directed to the sn-2 position (Palm 2). Levels of intestinal CaBP-9k mRNA were significantly (P < 0.01) higher in piglets fed formula with MCT than in piglets fed the other formula or milk; and higher in piglets fed the Palm-1 than in piglets fed Palm-2 formula. This is the first evidence that MCT alter piglet intestinal CaBP-9k mRNA. PMID:8727649

  9. Medium chain triglycerides for treatment of spontaneous, neonatal chylothorax. Lipid analysis of the chyle.

    PubMed

    Peitersen, B; Jacobsen, B

    1977-01-01

    Volume and contents of lipid and protein in the pleural fluid from a three weeks old girl with spontaneous chylothorax were studied (a) during parenteral, nonfatty nutrition and later (b) during administration of a formula (Biosorbin) containing medium chain triglycerides (MCT). The pleural fluid production could not be correlated to the treatment employed but suddenly ceased after 20 days management. Triglyceride and total esterified fatty acid concentrations in pleural fluid were high on admission when feeded with human milk, and chylomicrons and other lipoproteins were present in the chyle. During parenteral treatment a pronounced decrease in pleural fluid concentrations of triglyceride and total fatty acids occurred concomitant with a disappearance of the chylomicrons. During the following MCT diet a pronounced increase in triglyceride and total fatty acids concentrations appeared and the chylomicrons reappeared in the chyle. The cholesterol and phospholipid concentrations in the pleural fluid showed only small changes during the different treatments. No significant changes in protein and albumin concentrations of chyle were observed. It is concluded, that administration of the Biosorbin MCT formula, containing 871/2% of the fat as MCT, seems without value ih the treatment of spontaneous, neonatal chylothorax.

  10. Selective deuteration for molecular insights into the digestion of medium chain triglycerides.

    PubMed

    Salentinig, Stefan; Yepuri, Nageshwar Rao; Hawley, Adrian; Boyd, Ben J; Gilbert, Elliot; Darwish, Tamim A

    2015-09-01

    Medium chain triglycerides (MCTs) are a unique form of dietary fat that have a wide range of health benefits. They are molecules with a glycerol backbone esterified with medium chain (6-12 carbon atoms) fatty acids on the two outer (sn-1 and sn-3) and the middle (sn-2) positions. During lipid digestion in the gastrointestinal tract, pancreatic lipase stereoselectively hydrolyses the ester bonds of these triglycerides on the sn-1 and sn-3 positions resulting in sn-2 monoglyceride and fatty acids as major products. However, the sn-2 monoglycerides are thermodynamically less stable than their sn-1/3 counterparts. Isomerization or fatty acid migration from the sn-2 monoglyceride to sn-1/3 monoglyceride may occur spontaneously and would lead to glycerol and fatty acid as final products. Here, tricaprin (C10) with selectively deuterated fatty acid chains was used for the first time to monitor chain migration and the stereoselectivity of the pancreatic lipase-catalyzed hydrolysis of ester bonds. The intermediate and final digestion products were studied using NMR and mass spectrometry under biologically relevant conditions. The hydrolysis of the sn-2 monocaprin to glycerol and capric acid did not occur within biologically relevant timescales and fatty acid migration occurs only in limited amounts as a result of the presence of undigested diglyceride species over long periods of time in the digestion medium. The slow kinetics for the exchange of the sn-2 fatty acid chain and the stereoselectivity of pancreatic lipase on MCTs is relevant for industrial processes that involve enzymatic interesterification and the production of high-value products such as specific structured triacylglycerols, confectionery fats and nutritional products. PMID:26151129

  11. Selective deuteration for molecular insights into the digestion of medium chain triglycerides.

    PubMed

    Salentinig, Stefan; Yepuri, Nageshwar Rao; Hawley, Adrian; Boyd, Ben J; Gilbert, Elliot; Darwish, Tamim A

    2015-09-01

    Medium chain triglycerides (MCTs) are a unique form of dietary fat that have a wide range of health benefits. They are molecules with a glycerol backbone esterified with medium chain (6-12 carbon atoms) fatty acids on the two outer (sn-1 and sn-3) and the middle (sn-2) positions. During lipid digestion in the gastrointestinal tract, pancreatic lipase stereoselectively hydrolyses the ester bonds of these triglycerides on the sn-1 and sn-3 positions resulting in sn-2 monoglyceride and fatty acids as major products. However, the sn-2 monoglycerides are thermodynamically less stable than their sn-1/3 counterparts. Isomerization or fatty acid migration from the sn-2 monoglyceride to sn-1/3 monoglyceride may occur spontaneously and would lead to glycerol and fatty acid as final products. Here, tricaprin (C10) with selectively deuterated fatty acid chains was used for the first time to monitor chain migration and the stereoselectivity of the pancreatic lipase-catalyzed hydrolysis of ester bonds. The intermediate and final digestion products were studied using NMR and mass spectrometry under biologically relevant conditions. The hydrolysis of the sn-2 monocaprin to glycerol and capric acid did not occur within biologically relevant timescales and fatty acid migration occurs only in limited amounts as a result of the presence of undigested diglyceride species over long periods of time in the digestion medium. The slow kinetics for the exchange of the sn-2 fatty acid chain and the stereoselectivity of pancreatic lipase on MCTs is relevant for industrial processes that involve enzymatic interesterification and the production of high-value products such as specific structured triacylglycerols, confectionery fats and nutritional products.

  12. Medium-chain triglycerides/long-chain triglycerides versus long-chain triglycerides in treatment of cancer patients with major body mass loss. Survival in patients with refractory cachexia

    PubMed Central

    Kruszewski, Wiesław J.; Szajewski, Mariusz; Ciesielski, Maciej; Sobczak, Ewa; Czerepko, Maksymilian; Łysiak-Szydłowska, Wiesława

    2016-01-01

    Introduction Currently there are no established guidelines regarding the use of long-chain triglycerides (LCT) vs. medium-chain triglycerides medium-chain triglycerides (MCT)/long-chain triglycerides (LCT) in total parenteral nutrition (TPN). Severe malnutrition of patients with refractory cachexia (RC) often causes their disqualification from invasive methods of treatment thus decreasing their quality of life and survival time. Aim To compare the changes in nutritional state of patients with RC receiving PN with LCT and LCT/MCT lipid emulsions and to assess the influence of enteral nutrition on their survival time. Material and methods The study group comprised of 50 patients (23 female, 27 male) with a median age of 66 years. Refractory cachexia was diagnosed in them due to dysphagia secondary to solid tumours causing obstruction of the gastrointestinal tract (GT). All patients were qualified for surgical gastrostomy due to contraindications to percutaneous endoscopic gastrostomy. The patients were randomly assigned into one of two groups and perioperatively received either LCT or LCT/MCT. Blood samples were collected four times and tested for: total protein, albumin, prealbumin, and C-reactive protein concentration. Patients received Home Enteral Nutrition after discharge from hospital. Results Changes in nutritional status parameters were similar among patients receiving lipid emulsions LCT vs. MCT/LCT in TPN for 11 days. The mean survival time of all patients operated to gain enteral access to nutrition was 192 ±268 days, and the median survival was 98 days. Conclusions Regarding the short-term TPN, the results of the study do not demonstrate any superiority of MCT/LCT lipid emulsions over LCT, or vice versa. The inability to eat significantly accelerates unintended body mass loss among patients with RC. Disqualification from invasive treatment options deprives some patients of the benefits they might have obtained from the surgical access to GT and enteral

  13. Long- and medium-chain triglycerides during parenteral nutrition in critically ill patients.

    PubMed

    Delafosse, B; Viale, J P; Pachiaudi, C; Normand, S; Goudable, J; Bouffard, Y; Annat, G; Bertrand, O

    1997-04-01

    Due to their special metabolic pathway, medium-chain triglycerides (MCT) have been claimed to be oxidized more extensively, compared with long-chain triglycerides (LCT), when administered as a parenteral nutritional support. This enhanced lipid oxidation rate of MCT emulsions could be particularly disclosed in hyperglycemic and hyperinsulinemic conditions. In an attempt to further elucidate this question, we measured substrate oxidation rates in critically ill patients liable to experience such metabolic conditions, that is to say postoperative patients after esophageal resection receiving 1.5 times their measured energy expenditure (n = 12) or after liver transplantation (n = 8). These patients received either LCT or MCT-LCT emulsions. The metabolic measurements were performed simultaneously by two methods, namely indirect calorimetry and isotopic methods based on natural abundance of nutrients. Although both groups of patients were hyperglycemic and hyperinsulinemic, the measured carbohydrate and lipid oxidation rates were not different with whatever type of lipid was administered. The MCT-LCT emulsions did not offer clear-cut advantages over LCT emulsions in critically ill patients when lipid energetic fate was considered. PMID:9142873

  14. Biobased Fat Mimicking Molecular Structuring Agents for Medium-Chain Triglycerides (MCTs) and Other Edible Oils.

    PubMed

    Silverman, Julian R; John, George

    2015-12-01

    To develop sustainable value-added materials from biomass, novel small-molecule sugar ester gelators were synthesized using biocatalysis. The facile one-step regiospecific coupling of the pro-antioxidant raspberry ketone glucoside and unsaturated or saturated long- and medium-chain fatty acids provides a simple approach to tailor the structure and self-assembly of the amphiphilic product. These low molecular weight molecules demonstrated the ability to self-assemble in a variety of solvents and exhibited supergelation, with a minimum gelation concentration of 0.25 wt %, in numerous organic solvents, as well as in a range of natural edible oils, specifically a relatively unstudied group of liquids: natural medium-chain triglyceride oils, notably coconut oil. Spectroscopic analysis details the gelator structure as well as the intermolecular noncovalent interactions, which allow for gelation. X-ray diffraction studies indicate fatty acid chain packing of gelators is similar to that of natural fats, signifying the crystalline nature may lead to desirable textural properties and mouthfeel.

  15. Biobased Fat Mimicking Molecular Structuring Agents for Medium-Chain Triglycerides (MCTs) and Other Edible Oils.

    PubMed

    Silverman, Julian R; John, George

    2015-12-01

    To develop sustainable value-added materials from biomass, novel small-molecule sugar ester gelators were synthesized using biocatalysis. The facile one-step regiospecific coupling of the pro-antioxidant raspberry ketone glucoside and unsaturated or saturated long- and medium-chain fatty acids provides a simple approach to tailor the structure and self-assembly of the amphiphilic product. These low molecular weight molecules demonstrated the ability to self-assemble in a variety of solvents and exhibited supergelation, with a minimum gelation concentration of 0.25 wt %, in numerous organic solvents, as well as in a range of natural edible oils, specifically a relatively unstudied group of liquids: natural medium-chain triglyceride oils, notably coconut oil. Spectroscopic analysis details the gelator structure as well as the intermolecular noncovalent interactions, which allow for gelation. X-ray diffraction studies indicate fatty acid chain packing of gelators is similar to that of natural fats, signifying the crystalline nature may lead to desirable textural properties and mouthfeel. PMID:26624525

  16. Management of spontaneous congenital chylothorax: oral medium-chain triglycerides versus total parenteral nutrition.

    PubMed

    Fernández Alvarez, J R; Kalache, K D; Graŭel, E L

    1999-01-01

    The aim of this article is to compare total parenteral nutrition (TPN) with oral medium-chain triglycerides-diets (MCT) in the management of spontaneous congenital chylothorax. We analyzed retrospectively the charts of 6 patients seen in our tertiary care center and of 11 comparable patients from the literature. All neonates were symptomatic at birth; 15 had bilateral chylothorax. In the neonates who received mainly TPN (n = 9), the chylothorax resolved significantly (p < 0.05) earlier (mean 10 days, SE 1) than in the others, who received mainly MCT (n = 8) (mean 23 days, SE 4). The mean chyle loss was not significantly different between the 2 groups. Our results suggest that TPN is more effective than oral MCT in the treatment of spontaneous congenital chylothorax. These results support the data of Peitersen et al, who reported that most of the positive results with MCT were achieved in postoperative chylothorax of the newborn.

  17. Alterations of hippocampal glucose metabolism by even versus uneven medium chain triglycerides

    PubMed Central

    McDonald, Tanya S; Tan, Kah Ni; Hodson, Mark P; Borges, Karin

    2014-01-01

    Medium chain triglycerides (MCTs) are used to treat neurologic disorders with metabolic impairments, including childhood epilepsy and early Alzheimer's disease. However, the metabolic effects of MCTs in the brain are still unclear. Here, we studied the effects of feeding even and uneven MCTs on brain glucose metabolism in the mouse. Adult mice were fed 35% (calories) of trioctanoin or triheptanoin (the triglycerides of octanoate or heptanoate, respectively) or a matching control diet for 3 weeks. Enzymatic assays and targeted metabolomics by liquid chromatography tandem mass spectrometry were used to quantify metabolites in extracts from the hippocampal formations (HFs). Both oils increased the levels of β-hydroxybutyrate, but no other significant metabolic alterations were observed after triheptanoin feeding. The levels of glucose 6-phosphate and fructose 6-phosphate were increased in the HF of mice fed trioctanoin, whereas levels of metabolites further downstream in the glycolytic pathway and the pentose phosphate pathway were reduced. This indicates that trioctanoin reduces glucose utilization because of a decrease in phosphofructokinase activity. Trioctanoin and triheptanoin showed similar anticonvulsant effects in the 6 Hz seizure model, but it remains unknown to what extent the anticonvulsant mechanism(s) are shared. In conclusion, triheptanoin unlike trioctanoin appears to not alter glucose metabolism in the healthy brain. PMID:24169853

  18. Creatine, arginine alpha-ketoglutarate, amino acids, and medium-chain triglycerides and endurance and performance.

    PubMed

    Little, Jonathan P; Forbes, Scott C; Candow, Darren G; Cornish, Stephen M; Chilibeck, Philip D

    2008-10-01

    Creatine (Cr) supplementation increases muscle mass, strength, and power. Arginine a-ketoglutarate (A-AKG) is a precursor for nitric oxide production and has the potential to improve blood flow and nutrient delivery (i.e., Cr) to muscles. This study compared a commercial dietary supplement of Cr, A-AKG, glutamine, taurine, branched-chain amino acids, and medium-chain triglycerides with Cr alone or placebo on exercise performance and body composition. Thirty-five men (approximately 23 yr) were randomized to Cr + A-AKG (0.1 g . kg(-1) . d(-1) Cr + 0.075 g . kg(-1) . d(-1)A-AKG, n = 12), Cr (0.1 g . kg(-1) . d(-1), n = 11), or placebo (1 g . kg(-1) . d(-1) sucrose, n = 12) for 10 d. Body composition, muscle endurance (bench press), and peak and average power (Wingate tests) were measured before and after supplementation. Bench-press repetitions over 3 sets increased with Cr + A-AKG (30.9 +/- 6.6 +/- 34.9 +/- 8.7 reps; p < .01) and Cr (27.6 +/- 5.9 +/- 31.0 +/- 7.6 reps; p < .01), with no change for placebo (26.8 +/- 5.0 +/- 27.1 +/- 6.3 reps). Peak power significantly increased in Cr + A-AKG (741 +/- 112 +/- 794 +/- 92 W; p < .01), with no changes in Cr (722 +/- 138 +/- 730 +/- 144 W) and placebo (696 +/- 63 +/- 705 +/- 77 W). There were no differences in average power between groups over time. Only the Cr-only group increased total body mass (79.9 +/- 13.0 +/- 81.1 +/- 13.8 kg; p < .01), with no significant changes in lean-tissue or fat mass. These results suggest that Cr alone and in combination with A-AKG improves upper body muscle endurance, and Cr + A-AKG supplementation improves peak power output on repeated Wingate tests. PMID:19033611

  19. Triheptanoin - a medium chain triglyceride with odd chain fatty acids: a new anaplerotic anticonvulsant treatment?

    PubMed Central

    Borges, Karin; Sonnewald, Ursula

    2012-01-01

    The triglyceride of heptanoate (C7 fatty acid), triheptanoin, is a tasteless oil used to treat rare metabolic disorders in USA and France. Heptanoate is metabolized by β-oxidation to provide propionyl-CoA, which after carboxylation can produce succinyl-CoA, resulting in anaplerosis – the refilling of the tricarboxylic acid cycle. Heptanoate is also metabolized by the liver to the “C5 ketones”, β-ketopentanoate and/or β-hydroxypentanoate, which are released into the blood and thought to enter the brain via monocarboxylate transporters. Oral triheptanoin has recently been discovered to be reproducibly anticonvulsant in acute and chronic mouse seizures models. However, current knowledge on alterations of brain metabolism after triheptanoin administration and anaplerosis via propionyl-CoA carboxylation in the brain is limited. This review outlines triheptanoin’s unique anticonvulsant profile and its clinical potential for the treatment of medically refractory epilepsy. Anaplerosis as a therapeutic approach for the treatment of epilepsy is discussed. More research is needed to elucidate the anticonvulsant mechanism of triheptanoin and to reveal its clinical potential for the treatment of epilepsy and other disorders of the brain. PMID:21855298

  20. The Addition of Medium-Chain Triglycerides to a Purified Fish Oil Based Diet Alters Inflammatory Profiles in Mice

    PubMed Central

    Carlson, SJ; Nandivada, P; Chang, MI; Mitchell, PD; O’Loughlin, A; Cowan, E; Gura, KM; Nose, V; Bistrian, B; Puder, M

    2014-01-01

    Objective Parenteral nutrition associated liver disease (PNALD) is a deadly complication of long term parenteral nutrition (PN) use in infants. Fish oil-based lipid emulsion has been shown in recent years to effectively treat PNALD. Alternative fat sources free of essential fatty acids have recently been investigated for health benefits related to decreased inflammatory response. We hypothesized that the addition of medium-chain triglycerides (MCT) to a purified fish oil-based diet would decrease the response to inflammatory challenge in mice, while allowing for sufficient growth and development. Materials/Methods Six groups of ten adult male C57/Bl6 mice were pair-fed different dietary treatments for a period of twelve weeks, varying only in fat source (percent calories by weight): 10.84% soybean oil (SOY), 10% coconut oil (HCO), 10% medium-chain triglycerides (MCT), 3% purified fish oil (PFO), 3% purified fish oil with 3% medium-chain triglycerides (50:50 MCT:PFO) and 3% purified fish oil with 7.59% medium-chain triglycerides (70:30 MCT:PFO). An endotoxin challenge was administered to half of the animals in each group at the completion of dietary treatment. Results All groups demonstrated normal growth throughout the study period. Groups fed MCT and HCO diets demonstrated biochemical essential fatty acid deficiency and decreased IL-6 and TNF-α response to endotoxin challenge. Groups containing PFO had increased inflammatory response to endotoxin challenge, and the addition of MCT to PFO mitigated this inflammatory response. Conclusion These results suggest that the addition of MCT to PFO formulations may decrease the host response to inflammatory challenge, which may pose potential for optimized PN formulations. Inclusion of MCT in lipid emulsions given with PN formulations may be of use in therapeutic interventions for disease states resulting from chronic inflammation. PMID:25458829

  1. Effect of medium- and long-chain triglyceride infusion on lipoprotein and hepatic lipase in healthy subjects.

    PubMed

    Nordenström, J; Neeser, G; Olivecrona, T; Wahren, J

    1991-12-01

    Plasma lipolytic activity and hydrolysis of intravenous fat were studied in six healthy subjects during infusion of a long-chain triglyceride (LCT) fat emulsion (Intralipid 20%) or of a medium-chain triglyceride (MCT)/LCT emulsion (Lipofundin MCT 20%). The fat emulsions were infused continuously at a rate of 0.17 g triglyceride kg-1 body weight (BW)h-1 for 6 h in random order at 7-day intervals. A continuous infusion of glucose (0.18 g kg-1 BW h-1) was administered for a period of 7 h and was started 1 h before the lipid infusion. Infusions of both types of fat increased plasma triglyceride (TG), free fatty acid (FFA) and lipoprotein lipase (LPL) levels and steady-state values were present during the 3rd to 5th h of infusion. MCT/LCT infusion resulted in higher plasma levels at steady-state of TG (3.63 +/- 0.45 [SEM] vs 2.73 +/- 0.45 mmol l-1; P less than 0.05), FFA (1.05 +/- 0.08 vs 0.54 +/- 0.04 mmol l-1; P less than 0.01) and LPL (4.6 +/- 0.6 vs 2.6 +/- 0.5 mU ml-1; P less than 0.05) in comparison with LCT administration. There was a positive correlation between plasma LPL activity and TG concentration (r = 0.77; P less than 0.001) when data for the two infusions were combined. Although the same amount of fat was infused on a weight basis, the molar infusion rate was 40% higher with MCT/LCT than with LCT infusion, due to differences in molecular weights (634 vs 885 Da).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1778219

  2. Adherence of medium-chain fatty acids to feeding tubes of premature infants fed formula fortified with medium-chain triglyceride.

    PubMed

    Mehta, N R; Hamosh, M; Bitman, J; Wood, D L

    1991-10-01

    Adherence of medium-chain triglyceride (MCT) oil to feeding tubes during gavage feeding of Enfamil formula was quantitated. Infants were fed similar volumes of either unfortified formula (n = 11) or MCT oil-fortified formula (0.5 ml/oz); either the MCT oil was mixed with the formula before feeding (n = 11) or the MCT oil was delivered into the feeding tube and then was followed by formula (n = 11). The fat residue in the feeding sets was quantitated by gravimetry, and individual fatty acids were characterized by gas-liquid chromatography. The data show that only trace amounts of lipid (0.23 +/- 0.04%) adhered to feeding sets during feeding of unfortified formula. Significantly more lipid (p less than 0.0005) adhered when formula was fortified with MCT oil, and the method of feeding greatly affected lipid adherence, i.e., 1.52 +/- 0.21% when the MCT oil was followed by formula versus 10.20 +/- 1.76% when the MCT oil was mixed with formula before feeding. Analysis of the fat residue of fortified formula showed that greater than 90% was composed of C8:0 and C10:0, the major fatty acid components of MCT oil. We suggest that care be exercised when fortifying infant formula with MCT oil.

  3. Cognition and Synaptic-Plasticity Related Changes in Aged Rats Supplemented with 8- and 10-Carbon Medium Chain Triglycerides

    PubMed Central

    Wang, Dongmei; Mitchell, Ellen S.

    2016-01-01

    Brain glucose hypometabolism is a common feature of Alzheimer’s disease (AD). Previous studies have shown that cognition is improved by providing AD patients with an alternate energy source: ketones derived from either ketogenic diet or supplementation with medium chain triglycerides (MCT). Recently, data on the neuroprotective capacity of MCT-derived medium chain fatty acids (MCFA) suggest 8-carbon and 10-carbon MCFA may have cognition-enhancing properties which are not related to ketone production. We investigated the effect of 8 week treatment with MCT8, MCT10 or sunflower oil supplementation (5% by weight of chow diet) in 21 month old Wistar rats. Both MCT diets increased ketones plasma similarly compared to control diet, but MCT diets did not increase ketones in the brain. Treatment with MCT10, but not MCT8, significantly improved novel object recognition memory compared to control diet, while social recognition increased in both MCT groups. MCT8 and MCT10 diets decreased weight compared to control diet, where MCFA plasma levels were higher in MCT10 groups than in MCT8 groups. Both MCT diets increased IRS-1 (612) phosphorylation and decreased S6K phosphorylation (240/244) but only MCT10 increased Akt phosphorylation (473). MCT8 supplementation increased synaptophysin, but not PSD-95, in contrast MCT10 had no effect on either synaptic marker. Expression of Ube3a, which controls synaptic stability, was increased by both MCT diets. Cortex transcription via qPCR showed that immediate early genes related to synaptic plasticity (arc, plk3, junb, egr2, nr4a1) were downregulated by both MCT diets while MCT8 additionally down-regulated fosb and egr1 but upregulated grin1 and gba2. These results demonstrate that treatment of 8- and 10-carbon length MCTs in aged rats have slight differential effects on synaptic stability, protein synthesis and behavior that may be independent of brain ketone levels. PMID:27517611

  4. Cognition and Synaptic-Plasticity Related Changes in Aged Rats Supplemented with 8- and 10-Carbon Medium Chain Triglycerides.

    PubMed

    Wang, Dongmei; Mitchell, Ellen S

    2016-01-01

    Brain glucose hypometabolism is a common feature of Alzheimer's disease (AD). Previous studies have shown that cognition is improved by providing AD patients with an alternate energy source: ketones derived from either ketogenic diet or supplementation with medium chain triglycerides (MCT). Recently, data on the neuroprotective capacity of MCT-derived medium chain fatty acids (MCFA) suggest 8-carbon and 10-carbon MCFA may have cognition-enhancing properties which are not related to ketone production. We investigated the effect of 8 week treatment with MCT8, MCT10 or sunflower oil supplementation (5% by weight of chow diet) in 21 month old Wistar rats. Both MCT diets increased ketones plasma similarly compared to control diet, but MCT diets did not increase ketones in the brain. Treatment with MCT10, but not MCT8, significantly improved novel object recognition memory compared to control diet, while social recognition increased in both MCT groups. MCT8 and MCT10 diets decreased weight compared to control diet, where MCFA plasma levels were higher in MCT10 groups than in MCT8 groups. Both MCT diets increased IRS-1 (612) phosphorylation and decreased S6K phosphorylation (240/244) but only MCT10 increased Akt phosphorylation (473). MCT8 supplementation increased synaptophysin, but not PSD-95, in contrast MCT10 had no effect on either synaptic marker. Expression of Ube3a, which controls synaptic stability, was increased by both MCT diets. Cortex transcription via qPCR showed that immediate early genes related to synaptic plasticity (arc, plk3, junb, egr2, nr4a1) were downregulated by both MCT diets while MCT8 additionally down-regulated fosb and egr1 but upregulated grin1 and gba2. These results demonstrate that treatment of 8- and 10-carbon length MCTs in aged rats have slight differential effects on synaptic stability, protein synthesis and behavior that may be independent of brain ketone levels. PMID:27517611

  5. Gut Microbiota and Metabolic Health: The Potential Beneficial Effects of a Medium Chain Triglyceride Diet in Obese Individuals.

    PubMed

    Rial, Sabri Ahmed; Karelis, Antony D; Bergeron, Karl-F; Mounier, Catherine

    2016-01-01

    Obesity and associated metabolic complications, such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), are in constant increase around the world. While most obese patients show several metabolic and biometric abnormalities and comorbidities, a subgroup of patients representing 3% to 57% of obese adults, depending on the diagnosis criteria, remains metabolically healthy. Among many other factors, the gut microbiota is now identified as a determining factor in the pathogenesis of metabolically unhealthy obese (MUHO) individuals and in obesity-related diseases such as endotoxemia, intestinal and systemic inflammation, as well as insulin resistance. Interestingly, recent studies suggest that an optimal healthy-like gut microbiota structure may contribute to the metabolically healthy obese (MHO) phenotype. Here, we describe how dietary medium chain triglycerides (MCT), previously found to promote lipid catabolism, energy expenditure and weight loss, can ameliorate metabolic health via their capacity to improve both intestinal ecosystem and permeability. MCT-enriched diets could therefore be used to manage metabolic diseases through modification of gut microbiota. PMID:27187452

  6. Medium chain triglyceride (MCT) rich, paclitaxel loaded self nanoemulsifying preconcentrate (PSNP): a safe and efficacious alternative to Taxol.

    PubMed

    Patel, Ketan; Patil, Anand; Mehta, Miten; Gota, Vikram; Vavia, Pradeep

    2013-12-01

    The current work was aimed to develop Medium Chain Triglyceride (MCT) rich self nanoemulsifying preconcentrate of paclitaxel (PTX) for parenteral delivery. Very high concentrations of Cremophor EL and ethanol in Taxol have rendered patients to severe side effects. Years of extensive research on development of cost effective and safer vehicle for PTX, have failed to provide a promising replacement for Taxol. MCT was selected as oil owing to its parenteral acceptability, high solubilization capacity and multiple therapeutic benefits in cancer cachexia. PTX precipitation kinetics and reported toxicity profile of Kolliphor HS15 has favored its selection for PTX Self Nanoemulsifying Preconcentrate (PSNP). Presence of 30% free PEG in Kolliphor HS15 (PEG-15-hydroxystearate) restricts its miscibility with MCT, imposing significant challenge in development of MCT rich self nanoemulsifying preconcentrate. Removal of PEG layer from oil-surfactant mixture facilitated the formulation of PSNP with 51% w/w MCT. PSNP exhibited better precipitation kinetic profile, higher PTX loading with negligible hemolysis and histamine release compared to Taxol. PSNP was bioequivalent to Taxol, though V(d) and MRT was significantly higher than Taxol. PSNP showed distinctly better profile in inhibiting tumor growth and maintaining body weight with significantly higher % survival. Thus, PSNP can be a safer vehicle with potential clinical benefits.

  7. [Protein-losing enteropathy with systemic lupus erythematosus effectively treated with octreotide and medium chain triglyceride diet: A case report].

    PubMed

    Kubo, Makoto; Uchida, Kousuke; Nakashima, Tadaaki; Oda, Seiko; Nakamura, Tomomi; Hashimoto, Shinichi; Watada, Toshiko; Nakamura, Hiroshi; Araki, Jun; Matsuzaki, Masunori; Yano, Masafumi

    2015-01-01

    In January 2009, a 62-year-old man presented with diarrhea, leg edema, and thrombopenia and was admitted to our hospital. The past medical history revealed Sjögren's syndrome and autoimmune hepatitis for which he had been administered prednisolone. On admission, a laboratory examination revealed massive hypoalbuminemia and high levels of C-reactive protein and platelet-associated IgG. Anti-double stranded DNA and anti-Sm antibodies were negative. Analysis of the bone marrow aspirate and Tc-99m albumin scintigraphy findings suggested autoimmune thrombocytopenic purpura (AITP) and protein-losing enteropathy (PLE), respectively. We diagnosed him as SLE, because past immunoserological testing had showed positivity for anti-double stranded DNA antibody and LE cells. Methylprednisolone pulse therapy and intravenous immunoglobulin therapy were ineffective. Rituximab was ineffective against PLE but was effective against AITP. Cyclosporine and Cyclophosphamide were ineffective against PLE. Subcutaneous injection of 200-μg octreotide daily and a medium chain triglyceride (MCT) diet was effective against PLE, and the patient's condition dramatically improved. The effectiveness of octreotide treatment and an MCT diet in the treatment of PLE with SLE is discussed. PMID:26725864

  8. Gut Microbiota and Metabolic Health: The Potential Beneficial Effects of a Medium Chain Triglyceride Diet in Obese Individuals

    PubMed Central

    Rial, Sabri Ahmed; Karelis, Antony D.; Bergeron, Karl-F.; Mounier, Catherine

    2016-01-01

    Obesity and associated metabolic complications, such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), are in constant increase around the world. While most obese patients show several metabolic and biometric abnormalities and comorbidities, a subgroup of patients representing 3% to 57% of obese adults, depending on the diagnosis criteria, remains metabolically healthy. Among many other factors, the gut microbiota is now identified as a determining factor in the pathogenesis of metabolically unhealthy obese (MUHO) individuals and in obesity-related diseases such as endotoxemia, intestinal and systemic inflammation, as well as insulin resistance. Interestingly, recent studies suggest that an optimal healthy-like gut microbiota structure may contribute to the metabolically healthy obese (MHO) phenotype. Here, we describe how dietary medium chain triglycerides (MCT), previously found to promote lipid catabolism, energy expenditure and weight loss, can ameliorate metabolic health via their capacity to improve both intestinal ecosystem and permeability. MCT-enriched diets could therefore be used to manage metabolic diseases through modification of gut microbiota. PMID:27187452

  9. Causes of reduced survival of neonatal pigs by medium-chain triglycerides: blood metabolite and behavioral activity approaches.

    PubMed

    Lin, C L; Chiang, S H; Lee, H F

    1995-07-01

    Two experiments were conducted to investigate the causes of the failure of orally dosed medium-chain triglycerides (MCT) in improving the survival of neonatal pigs. In Exp. 1, four litters consisting of 24 unsuckled neonatal pigs were either dosed with 6 mL/kg BW.75 of MCT or the dosing process was mimicked by inserting and withdrawing the feeding tube at 10 and 18 h after birth. Blood beta-hydroxybutyrate concentration was increased (P < .06) and the depletion of liver glycogen was reduced (P < .05) by MCT. Plasma octanoate (C8) concentration peaked at 1 h and was minimized at 4 to 8 h after each MCT dosage; decanoate (C10) concentration increased (P < .001) gradually after each dosage. Activity of pigs was decreased (P < .01) by MCT. In Exp. 2, 94 litters consisting of 887 neonatal pigs were dosed with either 6 mL/kg BW.75 of MCT, coconut oil (CO), or saline at 10 to 14 and 20 to 28 h after birth. Milk intake (P < .05) and weight gain were reduced (P < .01) in 1- to 2-d-old pigs dosed with MCT compared with intake and gain of pigs dosed with saline. Mortality of large pigs (> 1 kg) was increased (P < .05) but mortality of small pigs (< 1 kg) was not affected by MCT. Mortality of small pigs was reduced (P < .05) but mortality of large pigs (> 1 kg) was not affected by CO. Standing, walking, and suckling behaviors of pigs were not affected by MCT or CO. Coma was evident in 9.7% of pigs dosed with MCT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7592086

  10. Medium-chain triglycerides and conjugated linoleic acids in beverage form increase satiety and reduce food intake in humans.

    PubMed

    Coleman, Hannah; Quinn, Paul; Clegg, Miriam E

    2016-06-01

    Both developed and developing countries are seeing increasing trends of obesity in people young and old. It is thought that satiety may play a role in the prevention of obesity by increasing satiety and reducing energy intake. We hypothesized that medium-chain triglycerides (MCT) would increase satiety and decrease food intake compared with conjugated linoleic acid (CLA) and a control oil. Nineteen healthy participants were tested on 3 separate occasions, where they consumed a beverage test breakfast containing (1) vegetable oil (control), (2) CLA, or (3) MCT. Participants self-requested an ad libitum sandwich buffet lunch. Time between meals, satiety from visual analog scales, energy intake at lunch, and intake for the rest of the day using weighed food diaries were measured. The results indicated that the time until a meal request was significantly different between the 3 meals (P=.016); however, there were no differences in intakes at the ad libitum lunch (P>.05). The CLA breakfast generated the greatest delay in meal time request. There was a difference between the control lipid compared with both the CLA and MCT for energy intake over the remainder of the test day and for total energy intake on the test day (P<.001 for both), with the CLA and MCT resulting in a lower intake than the control throughout the day. There were no significant differences in satiety from visual analog scale scores (P>.05). Both CLA and MCT increased satiety and reduced energy intake, indicating a potential role in aiding the maintenance of energy balance. PMID:27188898

  11. Importance of nutritional status in recovery from acute cholecystitis: benefit from enteral nutrition supplementation including medium chain triglycerides.

    PubMed

    Nomura, Yukinobu; Inui, Kazuo; Yoshino, Junji; Wakabayashi, Takao; Okushima, Kazumu; Kobayashi, Takashi; Miyoshi, Hironao; Nakamura, Yuta

    2007-09-01

    This study was undertaken to clarify the importance of nutritional status in patients with acute cholecystitis, and also evaluate whether they benefited from enteral nutrition supplementation, including medium-chain triglycerides (MCT), during the convalescent stage. Patients with acute cholecystitis admitted to our hospital between April 1994 and March 2002 were classified into a poor nutrition group (n=40; total serum protein<5.0 g/dl) or a fair nutrition group (n=71; >5.0 g/dl). Patients with poor nutrition were significantly more elderly than those with fair nutrition, and had significantly higher serum C-reactive protein (CRP) concentrations. The two groups did not differ significantly with respect to other laboratory data, gender distribution, or medical treatment. We supplemented ordinary meals with enteral nutrition including MCT in 16 patients during the convalescent stage (MCT group). We compared their length of hospital stay and days required to recovery to pre-admission functional status for activities of daily living (ADL) with the same intervals in 16 patients without supplementation (non-MCT group) selected to match for age, gender, and fair or poor nutritional status from among 111 patients. Hospitalizations were significantly longer in the poor nutrition group (43.0+/-2.2 days) than in the fair nutrition group (27.0+/-8.2 days). Significantly more days were required to recover ADL status in the poor nutrition group (12.0+/-7.2 days) than in the fair group (9.4+/-5.2 days). Hospitalizations were significantly shorter in the MCT group (20.1+/-15 days) than in the non-MCT group (35.4+/-12.8 days). Significantly fewer days were required to recover ADL status in the MCT group (10.9+/-7 days) than in the non-MCT group (13.1+/-6.8 days). Administration of enteral nutrition including MCT during convalescence from acute cholecystitis thus appears to promote functional recovery shorten hospital stay.

  12. Medium-chain triglycerides and conjugated linoleic acids in beverage form increase satiety and reduce food intake in humans.

    PubMed

    Coleman, Hannah; Quinn, Paul; Clegg, Miriam E

    2016-06-01

    Both developed and developing countries are seeing increasing trends of obesity in people young and old. It is thought that satiety may play a role in the prevention of obesity by increasing satiety and reducing energy intake. We hypothesized that medium-chain triglycerides (MCT) would increase satiety and decrease food intake compared with conjugated linoleic acid (CLA) and a control oil. Nineteen healthy participants were tested on 3 separate occasions, where they consumed a beverage test breakfast containing (1) vegetable oil (control), (2) CLA, or (3) MCT. Participants self-requested an ad libitum sandwich buffet lunch. Time between meals, satiety from visual analog scales, energy intake at lunch, and intake for the rest of the day using weighed food diaries were measured. The results indicated that the time until a meal request was significantly different between the 3 meals (P=.016); however, there were no differences in intakes at the ad libitum lunch (P>.05). The CLA breakfast generated the greatest delay in meal time request. There was a difference between the control lipid compared with both the CLA and MCT for energy intake over the remainder of the test day and for total energy intake on the test day (P<.001 for both), with the CLA and MCT resulting in a lower intake than the control throughout the day. There were no significant differences in satiety from visual analog scale scores (P>.05). Both CLA and MCT increased satiety and reduced energy intake, indicating a potential role in aiding the maintenance of energy balance.

  13. Sexual dimorphism of lipid metabolism in very long-chain acyl-CoA dehydrogenase deficient (VLCAD-/-) mice in response to medium-chain triglycerides (MCT).

    PubMed

    Tucci, Sara; Flögel, Ulrich; Spiekerkoetter, Ute

    2015-07-01

    Medium-chain triglycerides (MCT) are widely applied in the treatment of long-chain fatty acid oxidation disorders. Previously it was shown that long-term MCT supplementation strongly affects lipid metabolism in mice. We here investigate sex-specific effects in mice with very-long-chain-acyl-CoA dehydrogenase (VLCAD) deficiency in response to a long-term MCT modified diet. We quantified blood lipids, acylcarnitines, glucose, insulin and free fatty acids, as well as tissue triglycerides in the liver and skeletal muscle under a control and an MCT diet over 1 year. In addition, visceral and hepatic fat content and muscular intramyocellular lipids (IMCL) were assessed by in vivo(1)H magnetic resonance spectroscopy (MRS) techniques. The long-term application of an MCT diet induced a marked alteration of glucose homeostasis. However, only VLCAD-/- female mice developed a severe metabolic syndrome characterized by marked insulin resistance, dyslipidemia, severe hepatic and visceral steatosis, whereas VLCAD-/- males seemed to be protected and only presented with milder insulin resistance. Moreover, the highly saturated MCT diet is associated with a decreased hepatic stearoyl-CoA desaturase 1 (SCD1) activity in females aggravating the harmful effects of a saturated MCT diet. Long-term MCT supplementation deeply affects lipid metabolism in a sexual dimorphic manner resulting in a severe metabolic syndrome only in female mice. These findings are striking since the first signs of insulin resistance already occur in female VLCAD-/- mice during their reproductive period. How these metabolic adaptations are finally regulated needs to be determined. More important, the relevance of these findings for humans under these dietary modifications needs to be investigated. PMID:25887160

  14. Sexual dimorphism of lipid metabolism in very long-chain acyl-CoA dehydrogenase deficient (VLCAD-/-) mice in response to medium-chain triglycerides (MCT).

    PubMed

    Tucci, Sara; Flögel, Ulrich; Spiekerkoetter, Ute

    2015-07-01

    Medium-chain triglycerides (MCT) are widely applied in the treatment of long-chain fatty acid oxidation disorders. Previously it was shown that long-term MCT supplementation strongly affects lipid metabolism in mice. We here investigate sex-specific effects in mice with very-long-chain-acyl-CoA dehydrogenase (VLCAD) deficiency in response to a long-term MCT modified diet. We quantified blood lipids, acylcarnitines, glucose, insulin and free fatty acids, as well as tissue triglycerides in the liver and skeletal muscle under a control and an MCT diet over 1 year. In addition, visceral and hepatic fat content and muscular intramyocellular lipids (IMCL) were assessed by in vivo(1)H magnetic resonance spectroscopy (MRS) techniques. The long-term application of an MCT diet induced a marked alteration of glucose homeostasis. However, only VLCAD-/- female mice developed a severe metabolic syndrome characterized by marked insulin resistance, dyslipidemia, severe hepatic and visceral steatosis, whereas VLCAD-/- males seemed to be protected and only presented with milder insulin resistance. Moreover, the highly saturated MCT diet is associated with a decreased hepatic stearoyl-CoA desaturase 1 (SCD1) activity in females aggravating the harmful effects of a saturated MCT diet. Long-term MCT supplementation deeply affects lipid metabolism in a sexual dimorphic manner resulting in a severe metabolic syndrome only in female mice. These findings are striking since the first signs of insulin resistance already occur in female VLCAD-/- mice during their reproductive period. How these metabolic adaptations are finally regulated needs to be determined. More important, the relevance of these findings for humans under these dietary modifications needs to be investigated.

  15. Effect of Medium-chain Triglyceride (MCT) on Growth Performance, Nutrient Digestibility, Blood Characteristics in Weanling Pigs

    PubMed Central

    Hong, S. M.; Hwang, J. H.; Kim, I. H.

    2012-01-01

    One hundred and twenty weanling pigs in experiment 1 (Exp. 1) (6.91±0.99 kg; 21 d of age) and Exp. 2 (10.20±1.09 kg; 28 d of age) were used in two 42-d and 35-d experiments to evaluate the effect of medium-chain-triglyceride (MCT) on growth performance, apparent total tract digestibility (ATTD) of nutrients and blood profile. In both of Exp. 1 and Exp. 2, the same dietary treatments were utilized as follows : i) negative control (NC), ii) positive control (PC), NC+antibiotics (40 mg/kg Tiamulin, 110 mg/kg Tylosin, and 10 mg/kg Enramycin, iii) MCT3, NC+0.32% (phase 1, 2 and 3) MCT, and iv) MCT5, NC+0.55% (phase 1), 0.32% (phase 2 and 3) MCT. In Exp. 1, the pigs fed MCT5 diets had higher (p<0.05) ADG compared to NC treatment during the first 2 wk. From d 15 to 28, the ATTD of energy was improved (p<0.05) by MCT3 compared to the PC treatment. No effect has been observed on the blood profiles [red blood cell (RBC), white blood cell (WBC), immunoglobulin-G (IgG), lymphocyte concentration] measured in this study. In Exp. 2, the ADG were increased (p<0.05) by the MCT5 treatment than the PC treatment from d 0 to 14. Pigs fed PC treatment diet had lower ADFI (p<0.05) and better FCR (p<0.05) than NC treatment, whereas no differences were shown between MCT treatments and NC or PC treatment from d 15 to 35 and overall phase. The ATTD of DM and nitrogen were improved (p<0.05) by the effect of MCT5 related to the NC and PC treatment at the end of 2nd and 5th wk. The pigs fed MCT3 had higher (p<0.05) energy digestibility than PC treatment. No effects were seen in the blood profiles we measured (WBC, RBC, lymphocyte and immunoglobulin-G). In conclusion, the addition of MCT in the weanling pigs diet can improve the ADG and digestibility during the earlier period (first 2 wks), but had little effect on the blood characteristics. PMID:25049656

  16. Dietary medium- or long-chain triglycerides improve body condition of lean-genotype sows and increase suckling pig growth.

    PubMed

    Gatlin, L Averette; Odle, J; Soede, J; Hansent, J A

    2002-01-01

    In a field trial conducted on a commercial swine farm, lean-genotype sows (n = 485) were fed diets containing 0 or 10% supplemental fat as either medium-chain triglyceride or choice white grease from d 90 of gestation until weaning (15.5 d). Effects on standard sow and litter production traits were examined together with assessment of sow body condition using live ultrasound. Daily feed intake during lactation was 10% higher in sows consuming diets without added fat (7.2 vs 6.5 kg; P < 0.01); however, lactation ME (23.9 Mcal/d) and digestible lysine (54 g/d) intakes were unaffected (P > 0.10). Sows supplemented with fat were 4 kg heavier on d 109 of gestation (220 vs 224 kg; P < or = 0.01), 1 d after farrowing (210 vs 214 kg; P < or = 0.01), and at weaning (210 vs 214 kg; P < or = 0.01). Expressed as overall gain, this amounted to a 23% increase (0.66 vs 0.86 kg/d; P < or = 0.01) and was accompanied by a 49% increase in backfat (0.82 vs 1.68 mm; P < or = 0.03) from d 90 to farrowing. Changes in sow weight (-0.01 kg/d) and backfat (+4.2 mm) over lactation were minimal and were not affected by fat supplementation (P > or = 0.10). Longissimus muscle area at weaning was slightly greater (44.96 vs 46.2 cm2) in sows consuming fat than in control sows (P < or = 0.05), but changes in longissimus muscle area were not significant from d 90 to weaning (P > or = 0.10). Gestation length, pigs born alive, average birth weight, survival (d 3 to weaning), and days to estrus were not affected by diet (P > 0.10). However, supplemental fat increased pig ADG (192 vs 203 g/d; P < 0.01) and average pig weaning weight (4.3 vs 4.5 kg) at 15.5 d (P < or = 0.02). No differences between the two fat sources were detected. This large-scale study demonstrated that supplemental fat during gestation and lactation effectively improved sow condition and improved suckling pig performance without affecting energy intake during lactation, implying improved efficiency of sow energy utilization.

  17. Medium chain triglycerides dose-dependently prevent liver pathology in a rat model of non-alcoholic fatty liver disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Metabolic syndrome is often accompanied by development of hepatic steatosis and less frequently by nonalcoholic fatty liver disease (NAFLD) leading to nonalcoholic steatohepatitis (NASH). Replacement of corn oil with medium chain triacylglycerols (MCT) in the diets of alcohol-fed rats has been show...

  18. Lauric acid-rich medium-chain triglycerides can substitute for other oils in cooking applications and may have limited pathogenicity

    PubMed Central

    McCarty, Mark F; DiNicolantonio, James J

    2016-01-01

    Recently, medium-chain triglycerides (MCTs) containing a large fraction of lauric acid (LA) (C12)—about 30%—have been introduced commercially for use in salad oils and in cooking applications. As compared to the long-chain fatty acids found in other cooking oils, the medium-chain fats in MCTs are far less likely to be stored in adipose tissue, do not give rise to ‘ectopic fat’ metabolites that promote insulin resistance and inflammation, and may be less likely to activate macrophages. When ingested, medium-chain fatty acids are rapidly oxidised in hepatic mitochondria; the resulting glut of acetyl-coenzyme A drives ketone body production and also provokes a thermogenic response. Hence, studies in animals and humans indicate that MCT ingestion is less obesogenic than comparable intakes of longer chain oils. Although LA tends to raise serum cholesterol, it has a more substantial impact on high density lipoprotein (HDL) than low density lipoprotein (LDL) in this regard, such that the ratio of total cholesterol to HDL cholesterol decreases. LA constitutes about 50% of the fatty acid content of coconut oil; south Asian and Oceanic societies which use coconut oil as their primary source of dietary fat tend to be at low cardiovascular risk. Since ketone bodies can exert neuroprotective effects, the moderate ketosis induced by regular MCT ingestion may have neuroprotective potential. As compared to traditional MCTs featuring C6–C10, laurate-rich MCTs are more feasible for use in moderate-temperature frying and tend to produce a lower but more sustained pattern of blood ketone elevation owing to the more gradual hepatic oxidation of ingested laurate. PMID:27547436

  19. Lauric acid-rich medium-chain triglycerides can substitute for other oils in cooking applications and may have limited pathogenicity.

    PubMed

    McCarty, Mark F; DiNicolantonio, James J

    2016-01-01

    Recently, medium-chain triglycerides (MCTs) containing a large fraction of lauric acid (LA) (C12)-about 30%-have been introduced commercially for use in salad oils and in cooking applications. As compared to the long-chain fatty acids found in other cooking oils, the medium-chain fats in MCTs are far less likely to be stored in adipose tissue, do not give rise to 'ectopic fat' metabolites that promote insulin resistance and inflammation, and may be less likely to activate macrophages. When ingested, medium-chain fatty acids are rapidly oxidised in hepatic mitochondria; the resulting glut of acetyl-coenzyme A drives ketone body production and also provokes a thermogenic response. Hence, studies in animals and humans indicate that MCT ingestion is less obesogenic than comparable intakes of longer chain oils. Although LA tends to raise serum cholesterol, it has a more substantial impact on high density lipoprotein (HDL) than low density lipoprotein (LDL) in this regard, such that the ratio of total cholesterol to HDL cholesterol decreases. LA constitutes about 50% of the fatty acid content of coconut oil; south Asian and Oceanic societies which use coconut oil as their primary source of dietary fat tend to be at low cardiovascular risk. Since ketone bodies can exert neuroprotective effects, the moderate ketosis induced by regular MCT ingestion may have neuroprotective potential. As compared to traditional MCTs featuring C6-C10, laurate-rich MCTs are more feasible for use in moderate-temperature frying and tend to produce a lower but more sustained pattern of blood ketone elevation owing to the more gradual hepatic oxidation of ingested laurate. PMID:27547436

  20. Evaluation of resveratrol, green tea extract, curcumin, oxaloacetic acid, and medium-chain triglyceride oil on life span of genetically heterogeneous mice.

    PubMed

    Strong, Randy; Miller, Richard A; Astle, Clinton M; Baur, Joseph A; de Cabo, Rafael; Fernandez, Elizabeth; Guo, Wen; Javors, Martin; Kirkland, James L; Nelson, James F; Sinclair, David A; Teter, Bruce; Williams, David; Zaveri, Nurulain; Nadon, Nancy L; Harrison, David E

    2013-01-01

    The National Institute on Aging Interventions Testing Program (ITP) was established to evaluate agents that are hypothesized to increase life span and/or health span in genetically heterogeneous mice. Each compound is tested in parallel at three test sites. It is the goal of the ITP to publish all results, negative or positive. We report here on the results of lifelong treatment of mice, beginning at 4 months of age, with each of five agents, that is, green tea extract (GTE), curcumin, oxaloacetic acid, medium-chain triglyceride oil, and resveratrol, on the life span of genetically heterogeneous mice. Each agent was administered beginning at 4 months of age. None of these five agents had a statistically significant effect on life span of male or female mice, by log-rank test, at the concentrations tested, although a secondary analysis suggested that GTE might diminish the risk of midlife deaths in females only.

  1. Medium-chain triglycerides promote macrophage reverse cholesterol transport and improve atherosclerosis in ApoE-deficient mice fed a high-fat diet.

    PubMed

    Zhang, Xinsheng; Zhang, Yong; Liu, Yinghua; Wang, Jin; Xu, Qing; Yu, Xiaoming; Yang, Xueyan; Liu, Zhao; Xue, Changyong

    2016-09-01

    We previously observed that medium-chain triglycerides (MCTs) could reduce body fat mass and improve the metabolism of cholesterol. We hypothesized that MCTs can improve atherosclerosis by promoting the reverse cholesterol transport (RCT) process. Therefore, the objective of this study was to investigate the roles of MCTs in macrophage RCT and the progression of atherosclerosis. To test this hypothesis, 30 4-week-old ApoE-deficient (ApoE(-/-)) mice were randomly divided into 2 groups and fed a diet of 2% MCTs or long-chain triglycerides (LCTs) for 16 weeks. Ten age- and sex-matched C57BL/6J mice were fed a diet of 2% LCTs as the control. Macrophage-to-feces RCT was assessed in vivo by intraperitoneal injection of RAW 264.7 macrophages containing (3)H-labeled cholesterol, and atherosclerotic plaques were measured. The mRNA and protein expressions were determined by reverse transcriptase polymerase chain reaction and Western blot analyses, respectively. There was a greater decrease in body fat mass, atherosclerotic plaques, and an improvement in serum lipid profiles. In addition, the MCT mice group showed an increase in (3)H-tracer in the feces and a decrease in the liver. Significantly higher levels of mRNA and protein expression of hepatic ATP-binding cassette transporter A1, ATP-binding cassette transporter G5, cholesterol 7α-hydroxylase, and intestinal ATP-binding cassette transporter G8, as well as lower levels of expression of intestinal Niemann-Pick C1-like 1, were found in the MCT group. These results suggest that MCTs could obviously promote macrophage RCT and improve atherosclerosis in ApoE(-/-) mice, indicating that MCTs have the potential to prevent cardiovascular disease. PMID:27632916

  2. The effects of feeding medium-chain triglycerides on the growth, insulin responsiveness, and body composition of Holstein calves from birth to 85 kg of body weight.

    PubMed

    Mills, J K; Ross, D A; Van Amburgh, M E

    2010-09-01

    The objective of this study was to determine the effects of feeding calves isocaloric, isonitrogenous diets that varied in the amount and type of fatty acids on growth, response to an insulin challenge, and body composition. Thirty-six calves were assigned to a randomized block design with 3 dietary treatments, 10 calves per treatment, and a baseline group of 6 calves. Three different milk-replacer-based diets were designed to deliver less than 2% of the lipid as medium-chain triglycerides (control; diet contained no added medium-chain triglycerides), 32% medium-chain triglycerides primarily as caprylate (CAP oil), and 32% of fatty acids primarily as laurate from coconut oil (CCO). Calves were offered 0.28 Mcal of intake energy/kg of body weight (BW)0.75 from d 1 to 7 and 0.32 Mcal of intake energy/kg of BW0.75 adjusted weekly for BW from d 8 to harvest. Dry matter, intake energy, crude protein, and fat intakes were 53.7 kg, 281.8 Mcal, 14.6 kg, and 13.0 kg; 56.6 kg, 297.2 Mcal, 15.8 kg, and 14.2 kg; and 53.8 kg, 280.4 Mcal, 15.4 kg, and 13.3 kg for the control, CAP oil, and CCO treatments, respectively. Dry matter, energy, protein, and fat intakes did not differ among treatments. At approximately 65 kg of BW, 5 calves per treatment were given an insulin challenge. After the challenge the decrease in plasma glucose concentration was greater for the calves fed the CAP oil diet compared with those fed the control and CCO diets. Calves were harvested at approximately 88 kg of BW. Empty body gains were 0.92, 0.79, and 0.87 kg/d for control-, CAP oil-, and CCO-fed calves, respectively, and the gains of the CAP oil-fed calves were less than those of the control-fed calves. Empty body crude protein, ash, and water were not different among treatments. Empty body retained energy and fat tended to be 5.6 and 8.7% greater for calves consuming the CCO diet than for those fed the control diet. The livers of calves consuming the CCO diet were 330 g heavier and contained 15% more

  3. Further investigations of enhancing effect of medium-chain triglycerides on d-alpha-tocopherol acetate absorption from lecithin-dispersed preparations in rat small intestine.

    PubMed

    Fukui, E; Tabuchi, H; Kurosaki, Y; Nakayama, T; Kimura, T

    1989-12-01

    The effect of medium-chain triglycerides (MCTG) in lecithin-dispersed d-alpha-tocopherol acetate (VEA) preparation on intestinal absorption of VEA was investigated in rats using the in situ loop experiment. When VEA preparations containing soybean phosphatidylcholine (PC) and various amounts of MCTG were administered, the amount of VEA absorbed in 2 h was not significantly different among them. However, the amounts of total VE, sum of VEA and d-alpha-tocopherol (VE), remaining in the luminal fluid and the intestinal tissue were dependent on the MCTG content. Total VE remaining in the intestinal tissue after the administration of a VEA/PC/MCTG (5/16/1 by weight) preparation was nearly twice of VEA/PC (5/16) preparation, although the effect of MCTG varied with the increase or decrease in the MCTG content. Moreover, the increased tissue accumulation of total VE by the VEA/PC/MCTG (5/16/1) preparation resulted in an increase in the plasma VE concentration after the removal of the luminal fluid. No effect of pretreatment with PC/MCTG (1/1) dispersion on the tissue accumulation of total VE from VEA/PC (5/16) preparation was observed. Furthermore, the plasma concentration of VE from VEA and/or VE taken up in the tissue from the VEA/PC preparation was not increased by the treatment with the PC/MCTG dispersion. These results suggest that MCTG should coexist in the luminal VEA preparation to enhance the mucosal uptake. A similar enhancing effect was also observed by the addition of the metabolite of MCTG, a medium-chain fatty acid.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Medium-chain triglycerides and monounsaturated fatty acids potentiate the beneficial effects of fish oil on selected cardiovascular risk factors in rats.

    PubMed

    Kondreddy, Vijay Kumar Reddy; Anikisetty, Maheswaraiah; Naidu, Kamatham Akhilender

    2016-02-01

    Fish oil (FO) rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is known to reduce the risk of cardiovascular diseases (CVDs). Little information is known regarding the influence of lipid composition in the background diet on the modulatory effect of FO supplementation on CVDs. The present study was designed to investigate the influence of various background dietary lipids and FO on selected cardiovascular risk factors in rats. Adult Wistar rats were fed semisynthetic diet with FO at 1.0% or 2.0% along with other lipids, namely, medium-chain triacylglycerols (MCTs), monounsaturated fatty acids (MUFAs), n-6 polyunsaturated fatty acids (PUFAs) and n-3 PUFAs, for 5 weeks. Some of the potent CVD risk factors were estimated in the rats. FO at 1.0% and 2.0% has significantly reduced serum lipid peroxides, total cholesterol, triglycerides (TAGs), tumor necrosis factor-α, interleukin-6 and C-reactive protein; liver and adipose TAG and cholesterol levels in MCT, MUFA and n-6 PUFA diet groups. Notably, these alterations were comparatively higher in 1.0% FO-substituted MCT and MUFA diet groups. Interestingly, feeding of FO along with n-3 PUFAs did not show additive effect in attenuation of these factors. Serum liver EPA and DHA levels were remarkably elevated in rats fed FO-enriched MCT or MUFA diets. Our results suggest that MCTs or MUFAs in the background diet might promote the beneficial effects of FO on CVDs. PMID:26878786

  5. Medium-chain triglyceride as an alternative of in-feed colistin sulfate to improve growth performance and intestinal microbial environment in newly weaned pigs.

    PubMed

    Yen, Hung-Che; Lai, Wei-Kang; Lin, Chuan-Shun; Chiang, Shu-Hsing

    2015-01-01

    Five hundred and twenty-eight newly weaned pigs were given four treatments, with eight replicates per treatment. Sixteen to 18 pigs were assigned per replicate and were fed diets supplemented with 0 or 3% medium-chain triglyceride (MCT) and 0 or 40 ppm colistin sulfate (CS) in a 2 × 2 factorial arrangement for 2 weeks. The results showed that dietary supplementation with MCT improved the gain-to-feed ratio during days 3-7 and in the overall period (P < 0.05). Dietary supplementation with MCT decreased coliforms counts (C) in colon and rectum content (P < 0.05). Dietary supplementation with CS decreased C and lactic acid bacteria plus C counts (L + C) in cecum (P < 0.05), and C, L + C (P < 0.01) and ratio of L and C (P < 0.05) in colon and rectum contents. The lack of interactions between MCT and CS indicates different modes of action and additive effects between the two supplementations. In conclusion, supplementation with MCT in diet with or without CS could improve the intestinal microbial environment and the feed utilization efficiency of newly weaned pigs.

  6. Medium-chain triglycerides and monounsaturated fatty acids potentiate the beneficial effects of fish oil on selected cardiovascular risk factors in rats.

    PubMed

    Kondreddy, Vijay Kumar Reddy; Anikisetty, Maheswaraiah; Naidu, Kamatham Akhilender

    2016-02-01

    Fish oil (FO) rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is known to reduce the risk of cardiovascular diseases (CVDs). Little information is known regarding the influence of lipid composition in the background diet on the modulatory effect of FO supplementation on CVDs. The present study was designed to investigate the influence of various background dietary lipids and FO on selected cardiovascular risk factors in rats. Adult Wistar rats were fed semisynthetic diet with FO at 1.0% or 2.0% along with other lipids, namely, medium-chain triacylglycerols (MCTs), monounsaturated fatty acids (MUFAs), n-6 polyunsaturated fatty acids (PUFAs) and n-3 PUFAs, for 5 weeks. Some of the potent CVD risk factors were estimated in the rats. FO at 1.0% and 2.0% has significantly reduced serum lipid peroxides, total cholesterol, triglycerides (TAGs), tumor necrosis factor-α, interleukin-6 and C-reactive protein; liver and adipose TAG and cholesterol levels in MCT, MUFA and n-6 PUFA diet groups. Notably, these alterations were comparatively higher in 1.0% FO-substituted MCT and MUFA diet groups. Interestingly, feeding of FO along with n-3 PUFAs did not show additive effect in attenuation of these factors. Serum liver EPA and DHA levels were remarkably elevated in rats fed FO-enriched MCT or MUFA diets. Our results suggest that MCTs or MUFAs in the background diet might promote the beneficial effects of FO on CVDs.

  7. Fat-soluble vitamins and plasma and erythrocyte membrane fatty acids in chylothorax pediatric patients receiving a medium-chain triglyceride-rich diet

    PubMed Central

    Densupsoontorn, Narumon; Jirapinyo, Pipop; Tirapongporn, Hathaichanok; Wongarn, Renu; Chotipanang, Kwanjai; Phuangphan, Phakkanan; Chongviriyaphan, Nalinee

    2014-01-01

    Post-operative chylothorax can be cured by a medium-chain triglyceride (MCT)-rich diet. However, there is concern that an MCT-rich diet results in clinical and biochemical deficiencies in fat-soluble vitamins and fatty acids. We compared fat-soluble vitamins status and fatty acids status before and after administration of an MCT-rich diet. Nine children with congenital heart disease developed chylothorax after cardiac surgery. Blood samples were drawn from each subject twice, first prior to administration of an MCT-rich diet and secondly when the chylothorax was clinically cured and the MCT diet discontinued. Both blood samples were analyzed for retinol and 25-hydroxy vitamin D concentrations, the ratio of α-tocopherol to total lipids (α-TE/TL), coagulogram, and the fatty acid composition in plasma and erythrocyte membrane phospholipids. In spite of a decrease in the α-TE/TL ratio (3.78 ± 0.89 vs 2.36 ± 0.44 mg/g, p<0.05), this decrease did not reach the deficiency cut-off level. Linoleic acid in both plasma and erythrocyte membrane lipids decreased significantly (25.25 ± 8.06 vs 14.25 ± 2.88%, and 11.19 ± 2.15 vs 6.89 ± 2.45%, respectively). Administration of an MCT-rich diet for treatment of postoperative chylothorax caused a reduction in vitamin E status and linoleic acid, but without any symptoms of deficiency. PMID:25411522

  8. Enhancing effect of medium-chain triglycerides on intestinal absorption of d-alpha-tocopherol acetate from lecithin-dispersed preparations in the rat.

    PubMed

    Fukui, E; Kurohara, H; Kageyu, A; Kurosaki, Y; Nakayama, T; Kimura, T

    1989-02-01

    The effect of formulations of lecithin-dispersed preparation on the absorption of d-alpha-tocopherol acetate (VEA) from the small intestine was investigated in rats. When lecithin-dispersed preparations containing VEA or polysorbate 80 (PS-80)-solubilized solution of VEA were intraduodenally administered, VEA was hydrolyzed to d-alpha-tocopherol (VE) and was not detected in the plasma nor in the thoracic lymph. The maximum plasma concentration (Cmax) of VE after the intraduodenal administration of a preparation consisting of VEA, soybean phosphatidylcholine (PC) and medium-chain triglycerides (MCTG) (VEA/PC/MCTG, 5/16/1 by weight) was highest among the VEA preparations, and PS-80-solubilized solution gave the lowest Cmax. AUC of VE up to 24 h was also increased by the addition of MCTG to VEA/PC preparation. In the thoracic duct-fistula rat, the transport of VE into the thoracic lymph was increased by the administration of the VEA/PC/MCTG preparation significantly more than the VEA/PC preparation; the cumulative amounts of VE recovered in the thoracic lymph up to 24 h were 23.2 +/- 0.5% and 10.9 +/- 1.5% of dose, respectively. The plasma concentration of VE was not increased in the thoracic duct-fistula rat even after the intraduodenal administration of VEA preparations, suggesting that VE is not transported directly to the systemic circulation, but by way of the lymphatic route. The lymphatic transport of VE following the intraduodenal administration of VEA/PC/MCTG preparation was markedly diminished by the simultaneous administration of Pluronic L-81 emulsion, an inhibitor of chylomicron formation. It is suggested that the chylomicron is essential to the lymphatic transport of VE from VEA preparations.

  9. 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 ...

  10. 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

  11. The rapid hydrolysis and efficient absorption of triglycerides with octanoic acid in the 1 and 3 positions and long-chain fatty acid in the 2 position.

    PubMed

    Jandacek, R J; Whiteside, J A; Holcombe, B N; Volpenhein, R A; Taulbee, J D

    1987-05-01

    We describe rapid hydrolysis of triglycerides with medium-chain fatty acids in the 1 and 3 positions and a long-chain fatty acid in the 2 position. The triglycerides, 2-linoleoyl-1,3-dioctanoyl glycerol (8L8) and 2-oleoyl-1,3-dioctanoyl glycerol, hydrolyzed more rapidly than triglycerides comprising all long-chain fatty acids. The in vitro hydrolysis rate of 8L8 was similar to that of a medium-chain triglyceride of octanoic and decanoic acids in random positions. From intestinal recovery of 14C 45 min after injection into the isolated, irrigated loop of the small intestine of an anesthetized rat, the amount of 2-[1-14C]linoleoyl-1,3-dioctanoyl glycerol absorbed was greater than 2 1/2 times that of its long-chain analog, 2-[1-14C]linoleoyl-1,3-dioleoyl glycerol. These data support the ease of hydrolysis and absorption of 1,3-dioctanoyl triglycerides with long-chain fatty acids in the 2 position.

  12. Autoxidation of medium chain length polyhydroxyalkanoate.

    PubMed

    Schmid, Manfred; Ritter, Axel; Grubelnik, Andreas; Zinn, Manfred

    2007-02-01

    Polyhydroxyalkanoates (PHAs) are a class of biopolymers that are currently the subject of intensive research for various applications (packaging, consumer products, medical applications, etc.). It is known from synthetic polymers that all plastic materials show more or less pronounced autoxidation (aging induced by UV radiation, temperature, heavy metal ions, etc.). There is less knowledge as yet regarding the autoxidation behavior of biopolymers. The autoxidative behavior of medium chain length poly[(R)-3-hydroxyalkanoate] (mcl-PHA) was therefore investigated. mcl-PHA (co)polymers with amounts of 0, 10, 50, and 75 mol % of olefinic side chains with terminal double bonds were tempered at 60 degrees C in air for 3 months. After 1, 2, 4, 8, and 12 weeks, samples were removed and analyzed for changes in chemical and physical properties by sol-gel analysis (Soxhlet extraction), size exclusion chromatography (SEC), infrared analysis (IR), and gas chromatography/flame ionization detection (GC/FID). It became apparent that the content of double bonds greatly influences the autoxidation of mcl-PHA. A low amount of unsaturated moiety (0 and 10 mol %) resulted in chain scission, whereas samples with 50 and 75 mol % olefinic side chains showed cross-linking and became insoluble after a few weeks. Kinetic data of oxidation behavior were investigated by performing isothermal DSC experiments at elevated temperatures. The kinetic data combined with the experiment enabled the gelation time to be predicted and the shelf-life of mcl-PHA to be estimated. Because of the detected sensitivity of mcl-PHA regarding autoxidation, it is recommended that these biopolymers should be stored cold (at least -5 degrees C) and in an inert gas atmosphere or stabilized by suitable additives (antioxidants).

  13. [The medium chain fat acids. Content in food. Physiology, characteristics of metabolism and application in clinical practice].

    PubMed

    Arkhipovskiĭ, A V; Titov, V N

    2013-06-01

    It is rational, according to biology laws and purposes for which cells use fatty acids, to distinguish between saturated (without double bonds in chain), monoene (with one bond), unsaturated (with 2 and 3 double bonds) and polyene (with 4, 5 and 6 double bonds) acids. The saturated and monoene fatty acids are mainly the substratum for oxygenation and working out of energy by cells. The unsaturated fatty acids are the substratum for formation of membranes. The polyene fatty acids are the predecessors of synthesis of eicosanoids and aminophosphotides. With subject to characteristics of metabolism and transfer in vivo, the fatty acids are subdivided into short chain C4 - C8 and medium chain C-10 - C-14 fatty acids. The etherification occurs with glycerin into "short" triglycerides which are not bounded with apoproteins. The long chain fatty acids form "long" triglycerides which in enterocytes are structured by apoprotein B-48 into composition of chylomicrons. It is possible to validly consider that difference in outflow from enterocytes to veins of portal system (which includes veins of omentum) of medium chain fatty acids in the form of short triglycerides can directly input into pathogenesis of syndrome of isolated omental obesity and metabolic syndrome. The another input into the mentioned conditions is the secretion through ductus thoracicus into large veins of greater systemic circulation of long chain fatty acids in the form of triglycerides in the content of chylomicrons. The omental obesity is the only specific symptom of metabolic syndrome.

  14. Positional specificity of gastric hydrolysis of long-chain n-3 polyunsaturated fatty acids of seal milk triglycerides.

    PubMed

    Iverson, S J; Sampugna, J; Oftedal, O T

    1992-11-01

    Long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) of marine oils are important dietary components for both infants and adults, and are incorporated into milks following maternal dietary intake. However, little is known about the hydrolysis of these PUFA from milk triglycerides (TG) by lipases in suckling young. Seals, like humans, possess gastric lipase; however, the milk lipids of seals and sea lions are almost devoid of the readily hydrolyzable medium-chain fatty acids, and are characterized by a large percentage (10-30%) of n-3 PUFA. Gastric hydrolysis of milk lipids was studied in vivo in suckling pups of three species (the California sea lion, the harp seal and the hooded seal) in order to elucidate the actions and specificity of gastric lipases on milk TG in relation to fatty acid composition and TG structure. Regardless of milk fat content (31-61% fat) or extent of gastric hydrolysis (10-56%), the same fatty acids were preferentially released in all three species, as determined by their relative enrichment in the free fatty acid (FFA) fraction. In addition to 16:1 and 18:0, these were the PUFA of 18 carbons and longer, except for 22:6n-3. Levels of 20:5n-3 were most notably enriched in FFA, at up to five times that found in the TG. Although 22:6n-3 was apparently also released from the TG (reduced in the diglyceride), it was also notably reduced in FFA.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. [THE DETECTION OF CONTENT OF DIAGNOSTICALLY SIGNIFICANT FATTY ACIDS AND INDIVIDUAL TRIGLYCERIDES IN BIOLOGICAL MEDIUMS BASED ON INFRARED SPECTROMETRY].

    PubMed

    Kalinin, A V; Krasheninnikov, V N; Sviridov, A P; Titov, V N

    2015-11-01

    The content of clinically important fatty acids and individual triglycerides in food and biological mediums are traditionally detected by gas and fluid chromatography in various methodical modifications. The techniques are hard-to-get in laboratories of clinical biochemistry. The study was carried out to develop procedures and equipment for operative quantitative detection of concentration of fatty acids, primarily palmitic saturated fatty acid and oleic mono unsaturated fatty acid. Also detection was applied to sums ofpolyenoic (eicosapentaenoic and docosahexaenoic acid) fatty acids in biological mediums (cod-liver oil, tissues, blood plasma) using spectrometers of short-range infrared band of different types: with Fourier transform, diffraction and combined scattering. The evidences of reliable and reproducible quantitative detection offatty acids were received on the basis of technique of calibration (regression) by projection on latent structures using standard samples of mixtures of oils and fats. The evaluation is implemented concerning possibility of separate detection of content of palmitic and oleic triglycerides in mediums with presence of water The choice of technical conditions and mode of application of certain types of infrared spectrometers and techniques of their calibration is substantiated PMID:26999859

  16. Medium-chain fatty acids undergo elongation before {beta}-oxidation in fibroblasts

    SciTech Connect

    Jones, Patricia M. . E-mail: Patti.Jones@childrens.com; Butt, Yasmeen; Messmer, Bette; Boriak, Richard; Bennett, Michael J.

    2006-07-21

    Although mitochondrial fatty acid {beta}-oxidation (FAO) is considered to be well understood, further elucidation of the pathway continues through evaluation of patients with FAO defects. The FAO pathway can be examined by measuring the 3-hydroxy-fatty acid (3-OHFA) intermediates. We present a unique finding in the study of this pathway: the addition of medium-chain fatty acids to the culture media of fibroblasts results in generation of 3-OHFAs which are two carbons longer than the precursor substrate. Cultured skin fibroblasts from normal and LCHAD-deficient individuals were grown in media supplemented with various chain-length fatty acids. The cell-free medium was analyzed for 3-OHFAs by stable-isotope dilution gas-chromatography/mass-spectrometry. Our finding suggests that a novel carbon chain-length elongation process precedes the oxidation of medium-chain fatty acids. This previously undescribed metabolic step may have important implications for the metabolism of medium-chain triglycerides, components in the dietary treatment of a number of disorders.

  17. Difference in Hepatic Metabolism of Long- and Medium-Chain Fatty Acids: the Role of Fatty Acid Chain Length in the Production of the Alcoholic Fatty Liver*

    PubMed Central

    Lieber, Charles S.; Lefèvre, André; Spritz, Norton; Feinman, Lawrence; DeCarli, Leonore M.

    1967-01-01

    Replacement of dietary triglycerides containing long-chain fatty acids (LCFA) by triglycerides containing medium-chain fatty acids (MCFA) markedly reduced the capacity of alcohol to produce fatty liver in rats. After 24 days of ethanol and MCFA, the increase in hepatic triglycerides was only 3 times that of controls, whereas an 8-fold rise was observed after ethanol and LCFA. The triglyceride fatty acids that accumulated in the liver after feeding of ethanol with MCFA contained only a small percentage of the MCFA; their composition also differed strikingly from that of adipose lipids. To study the mechanism of the reduction in steatosis, we compared oxidation to CO2 and incorporation into esterified lipids of 14C-labeled chylomicrons or palmitate-14C (representing LCFA), and of octanoate-14C (as MCFA) in liver slices and isolated perfused livers, in the presence or absence of ethanol. Ethanol depressed the oxidation of all substrates to CO2; MCFA, however, was much more oxidized and reciprocally much less esterified than LCFA, with a 100-fold difference in the ratio of esterified lipid-14C to 14CO2. Furthermore, in hepatic microsomal fractions incubated with α-glycerophosphate, octanoate was much less esterified than palmitate. This propensity of MCFA to oxidation rather than esterification represents a likely explanation for the reduction in alcoholic steatosis upon replacement of dietary LCFA by MCFA. PMID:6036539

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

    PubMed

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

    1996-03-01

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

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

    PubMed

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

    2015-06-01

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

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

    PubMed

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

    2015-06-01

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

  1. Perturbation and age-related changes in the fatty acid pattern of soleus muscle phospholipids and triglycerides in rats depleted in long-chain polyunsaturated omega3 fatty acids.

    PubMed

    Malaisse, Willy J; Portois, Laurence; Sener, Abdullah; Carpentier, Yvon A

    2007-12-01

    Altered D-glucose metabolism prevails in the soleus muscle of rats depleted in long-chain polyunsaturated omega3 fatty acids (omega3). In these animals, the prior intravenous injection of an omega3-rich medium-chain triglyceride:fish oil emulsion (omega3-FO rats), as compared to that of an omega3-poor medium-chain triglyceride:olive oil emulsion (omega3-OO rats), may either correct or aggravate selected metabolic variables. This study deals with the fatty acid pattern of soleus phospholipids and triglycerides in control animals versus omega3-depleted rats not injected with any lipid emulsion (omega3-NI rats) and in omega3-OO versus omega3-FO rats. In each group of omega3-depleted rats, age-related changes were also monitored. The omega3-depleted rats displayed low long-chain polyunsaturated omega3 fatty acid content, facilitated metabolism of long-chain polyunsaturated omega6 fatty acids, and increased Delta9-desaturase activity. Both the age-related changes in lipid variables and those attributable to the prior intravenous injection of the omega3-rich lipid emulsion consisted either in a move towards normalization or in the opposite direction, i.e. towards aggravation of the defect found in the omega3-depleted rats. Emphasis is placed, therefore, on the unusual situation found in the soleus muscle of omega3-depleted rats, in which both lipid and metabolic variables may be either favourably or adversely affected by the same environmental factor(s). PMID:17982700

  2. 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 ...

  3. Carbon chain abundance in the diffuse interstellar medium.

    PubMed

    Allamandola, L J; Hudgins, D M; Bauschlicher, C W; Langhoff, S R

    1999-12-10

    Thanks to the mid-IR sensitivities of the ISO and IRTS orbiting spectrometers it is now possible to search the diffuse interstellar medium for heretofore inaccessible molecular emission. In view of the recent strong case for the presence of C(7-) (Kirkwood et al. 1998, Tulej et al. 1998),and the fact that carbon chains possess prominent infrared active modes in a very clean portion of the interstellar spectrum, we have analyzed the IRTS spectrum of the diffuse interstellar medium for the infrared signatures of these species. Theoretical and experimental infrared band frequencies and absolute intensities of many different carbon chain species are presented. These include cyanopolyynes, neutral and anionic linear carbon molecules, and neutral and ionized, even-numbered, hydrogenated carbon chains. We show that--as a family--these species have abundances in the diffuse ISM on the order of 10(-10) with respect to hydrogen, values consistent with their abundances in dense molecular clouds. Assuming an average length of 10 C atoms per C-chain implies that roughly a millionth of the cosmically available carbon is in the form of carbon chains and that carbon chains can account for a few percent of the visible to near-IR diffuse interstellar band (DIB) total equivalent width (not DIB number).

  4. Short- and medium-chain fatty acids in energy metabolism: the cellular perspective.

    PubMed

    Schönfeld, Peter; Wojtczak, Lech

    2016-06-01

    Short- and medium-chain fatty acids (SCFAs and MCFAs), independently of their cellular signaling functions, are important substrates of the energy metabolism and anabolic processes in mammals. SCFAs are mostly generated by colonic bacteria and are predominantly metabolized by enterocytes and liver, whereas MCFAs arise mostly from dietary triglycerides, among them milk and dairy products. A common feature of SCFAs and MCFAs is their carnitine-independent uptake and intramitochondrial activation to acyl-CoA thioesters. Contrary to long-chain fatty acids, the cellular metabolism of SCFAs and MCFAs depends to a lesser extent on fatty acid-binding proteins. SCFAs and MCFAs modulate tissue metabolism of carbohydrates and lipids, as manifested by a mostly inhibitory effect on glycolysis and stimulation of lipogenesis or gluconeogenesis. SCFAs and MCFAs exert no or only weak protonophoric and lytic activities in mitochondria and do not significantly impair the electron transport in the respiratory chain. SCFAs and MCFAs modulate mitochondrial energy production by two mechanisms: they provide reducing equivalents to the respiratory chain and partly decrease efficacy of oxidative ATP synthesis. PMID:27080715

  5. 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 ...

  6. Pharmacokinetics and pharmacodynamics of a new reformulated microemulsion and the long-chain triglyceride emulsion of propofol in beagle dogs

    PubMed Central

    Lee, S-H; Ghim, J-L; Song, M-H; Choi, H-G; Choi, B-M; Lee, H-M; Lee, E-K; Roh, Y-J; Noh, G-J

    2009-01-01

    Background and purpose: Microemulsion propofol was developed to eliminate lipid solvent-related adverse events of long-chain triglyceride emulsion (LCT) propofol. We compared dose proportionality, pharmacokinetic and pharmacodynamic characteristics of both formulations. Experimental approach: The study was a randomized, two-period and crossover design with 7-day wash-out period. Microemulsion and LCT propofol were administered by zero-order infusion (0.75, 1.00 and 1.25 mg·kg−1·min−1) for 20 min in 30 beagle dogs (male/female = 5/5 for each rate). Arterial samples were collected at preset intervals. The electroencephalographic approximate entropy (ApEn) was used as a measure of propofol effect. Dose proportionality, pharmacokinetic and pharmacodynamic bioequivalence were evaluated by non-compartmental analyses. Population analysis was performed using nonlinear mixed effects modelling. Key results: Both formulations showed dose proportionality at the applied dose range. The ratios of geometric means of AUClast and AUCinf between both formulations were acceptable for bioequivalence, whereas that of Cmax was not. The pharmacodynamic bioequivalence was indicated by the arithmetic means of AAC (areas above the ApEn time curves) and E0 (baseline ApEn)–Emax (maximally decreased ApEn) between both formulations. The pharmacokinetics of both formulations were best described by three compartment models. Body weight was a significant covariate for V1 of both formulations and sex for k21 of microemulsion propofol. The blood-brain equilibration rate constants (ke0, min−1) were 0.476 and 0.696 for microemulsion and LCT propofol respectively. Conclusions and implications: Microemulsion propofol was pharmacodynamically bioequivalent to LCT propofol although pharmacokinetic bioequivalence was incomplete, and demonstrated linear pharmacokinetics at the applied dose ranges. PMID:19925493

  7. Engineered biosynthesis of medium-chain esters in Escherichia coli.

    PubMed

    Tai, Yi-Shu; Xiong, Mingyong; Zhang, Kechun

    2015-01-01

    Medium-chain esters such as isobutyl acetate (IBAc) and isoamyl acetate (IAAc) are high-volume solvents, flavors and fragrances. In this work, we engineered synthetic metabolic pathways in Escherichia coli for the total biosynthesis of IBAc and IAAc directly from glucose. Our pathways harnessed the power of natural amino acid biosynthesis. In particular, the native valine and leucine pathways in E. coli were utilized to supply the precursors. Then alcohol acyltransferases from various organisms were investigated on their capability to catalyze esterification reactions. It was discovered that ATF1 from Saccharomyces cerevisiae was the best enzyme for the formation of both IBAc and IAAc in E. coli. In vitro biochemical characterization of ATF1 confirmed the fermentation results and provided rational guidance for future enzyme engineering. We also performed strain improvement by removing byproduct pathways (Δldh, ΔpoxB, Δpta) and increased the production of both target chemicals. Then the best IBAc producing strain was used for scale-up fermentation in a 1.3-L benchtop bioreactor. 36g/L of IBAc was produced after 72h fermentation. This work demonstrates the feasibility of total biosynthesis of medium-chain esters as renewable chemicals. PMID:25447641

  8. Site-specific saturation mutagenesis on residues 132 and 450 of Candida rugosa LIP2 enhances catalytic efficiency and alters substrate specificity in various chain lengths of triglycerides and esters.

    PubMed

    Yen, Chih-Chung; Malmis, Conmar C; Lee, Guan-Chiun; Lee, Li-Chiun; Shaw, Jei-Fu

    2010-10-27

    The catalytic versatility of recombinant Candida rugosa LIP2 has been known to have potential applications in industry. In this study, site-specific saturation mutagenesis on residues L132 and G450 of recombinant LIP2 has been employed to investigate the impact of both residues on substrate specificity of LIP2. Point mutations on L132 and G450 were done separately using mutagenic degenerate primer sets containing 32 codons to generate two libraries of mutants in Pichia pastoris . Replacements of amino acid on these mutants were identified as L132A, L132I, G450S, and G450A. In lipase activity assay, L132A and L132I mutants showed a shift of preference from short- to medium-chain triglyceride, whereas G450S and G450A mutants retained preferences as compared to wild-type LIP2. Among mutants, G450A has the highest activity on tributyrin. However, hydrolysis of p-nitrophenyl (p-NP) esters with L132A, L132I, and G450S did not show differences of preferences over medium- to long-chain esters except in G450A, which prefers only medium-chain ester as compared to wild-type LIP2. All mutants showed an enhanced catalytic activity and higher optimal temperature and pH stability as compared to wild-type LIP2.

  9. Effect of long-chain triglyceride lipid emulsion on bupivacaine-induced changes in electrophysiological parameters of rabbit Purkinje cells.

    PubMed

    Lemoine, Sandrine; Rouet, René; Manrique, Alain; Hanouz, Jean-Luc

    2014-10-01

    Lipid emulsions are used in the reversal of local anesthetic toxicity. The aim of this study was to investigate the cellular electrophysiological effects of long-chain triglyceride lipid emulsion (LCTE) on cardiac action potential characteristics and conduction disturbances induced by bupivacaine. Purkinje fibers were dissected from the left ventricle of New Zealand white rabbit hearts and superfused with either Tyrode's solution during 30 min (control group), with bupivacaine 10(-6) M, 10(-5) M, and 5.10(-5) M alone, or in the presence of LCTE 0.5%, in addition, LCTE at 0.1%, 0.5%, and 1% was perfused alone. Electrophysiological parameters were recorded using the conventional microelectrode technique (37 °C, 1 Hz frequency). Bupivacaine 5.10(-5) M-induced conduction blocks (8/8 preparations): LCTE 0.5% suppressed the bupivacaine 5.10(-5) M-induced conduction blocks (1/8 preparations). Exposure to bupivacaine 10(-6) M, 10(-5) M, and 5.10(-5) M resulted in a significant decrease in the maximal rate of depolarization (Vmax) (respectively, 25%, 55%, 75%; P < 0.002 vs. control group). In the presence of LCTE 0.5%, bupivacaine 10(-6) M did not significantly decreased Vmax (13%; P = 0.10 vs. control group). The decrease in Vmax resulting from bupivacaine 10(-5) M alone was significantly less in the presence of LCTE 0.5% (P < 0.01 vs. bupivacaine 10(-5) M alone). Exposure to bupivacaine 10(-6) M, 10(-5) M, and 5.10(-5) M alone or in the presence of LCTE 0.5% resulted in a significant decrease in action potential duration measured at 50% and 90% repolarization (APD50 and APD90; P < 0.01 vs. control group). LCTE inhibited the Purkinje fibers conduction blocks induced by bupivacaine. Moreover, LCTE 0.5% attenuates the decrease in Vmax induced by bupivacaine 10(-6) M and 10(-5) M.

  10. Fish Oil Supplementation Alters the Plasma Lipidomic Profile and Increases Long-Chain PUFAs of Phospholipids and Triglycerides in Healthy Subjects

    PubMed Central

    Ottestad, Inger; Hassani, Sahar; Borge, Grethe I.; Kohler, Achim; Vogt, Gjermund; Hyötyläinen, Tuulia; Orešič, Matej; Brønner, Kirsti W.; Holven, Kirsten B.; Ulven, Stine M.; Myhrstad, Mari C. W.

    2012-01-01

    Background While beneficial health effects of fish and fish oil consumption are well documented, the incorporation of n-3 polyunsaturated fatty acids in plasma lipid classes is not completely understood. The aim of this study was to investigate the effect of fish oil supplementation on the plasma lipidomic profile in healthy subjects. Methodology/Principal Findings In a double-blinded randomized controlled parallel-group study, healthy subjects received capsules containing either 8 g/d of fish oil (FO) (1.6 g/d EPA+DHA) (n = 16) or 8 g/d of high oleic sunflower oil (HOSO) (n = 17) for seven weeks. During the first three weeks of intervention, the subjects completed a fully controlled diet period. BMI and total serum triglycerides, total-, LDL- and HDL-cholesterol were unchanged during the intervention period. Lipidomic analyses were performed using Ultra Performance Liquid Chromatography (UPLC) coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (QTOFMS), where 568 lipids were detected and 260 identified. Both t-tests and Multi-Block Partial Least Square Regression (MBPLSR) analysis were performed for analysing differences between the intervention groups. The intervention groups were well separated by the lipidomic data after three weeks of intervention. Several lipid classes such as phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine, sphingomyelin, phosphatidylserine, phosphatidylglycerol, and triglycerides contributed strongly to this separation. Twenty-three lipids were significantly decreased (FDR<0.05) in the FO group after three weeks compared with the HOSO group, whereas fifty-one were increased including selected phospholipids and triglycerides of long-chain polyunsaturated fatty acids. After seven weeks of intervention the two intervention groups showed similar grouping. Conclusions/Significance In healthy subjects, fish oil supplementation alters lipid metabolism and increases the proportion of

  11. Genetics Home Reference: medium-chain acyl-CoA dehydrogenase deficiency

    MedlinePlus

    ... down (metabolize) a group of fats called medium-chain fatty acids. These fatty acids are found in foods and the body's fat tissues. Fatty acids are a major source of energy for the heart and muscles. During periods of fasting, ... of this enzyme, medium-chain fatty acids are not metabolized properly. As a ...

  12. Medium-chain fatty acids inhibit mitochondrial metabolism in astrocytes promoting astrocyte-neuron lactate and ketone body shuttle systems.

    PubMed

    Thevenet, Jonathan; De Marchi, Umberto; Domingo, Jaime Santo; Christinat, Nicolas; Bultot, Laurent; Lefebvre, Gregory; Sakamoto, Kei; Descombes, Patrick; Masoodi, Mojgan; Wiederkehr, Andreas

    2016-05-01

    Medium-chain triglycerides have been used as part of a ketogenic diet effective in reducing epileptic episodes. The health benefits of the derived medium-chain fatty acids (MCFAs) are thought to result from the stimulation of liver ketogenesis providing fuel for the brain. We tested whether MCFAs have direct effects on energy metabolism in induced pluripotent stem cell-derived human astrocytes and neurons. Using single-cell imaging, we observed an acute pronounced reduction of the mitochondrial electrical potential and a concomitant drop of the NAD(P)H signal in astrocytes, but not in neurons. Despite the observed effects on mitochondrial function, MCFAs did not lower intracellular ATP levels or activate the energy sensor AMP-activated protein kinase. ATP concentrations in astrocytes were unaltered, even when blocking the respiratory chain, suggesting compensation through accelerated glycolysis. The MCFA decanoic acid (300 μM) promoted glycolysis and augmented lactate formation by 49.6%. The shorter fatty acid octanoic acid (300 μM) did not affect glycolysis but increased the rates of astrocyte ketogenesis 2.17-fold compared with that of control cells. MCFAs may have brain health benefits through the modulation of astrocyte metabolism leading to activation of shuttle systems that provide fuel to neighboring neurons in the form of lactate and ketone bodies.-Thevenet, J., De Marchi, U., Santo Domingo, J., Christinat, N., Bultot, L., Lefebvre, G., Sakamoto, K., Descombes, P., Masoodi, M., Wiederkehr, A. Medium-chain fatty acids inhibit mitochondrial metabolism in astrocytes promoting astrocyte-neuron lactate and ketone body shuttle systems.

  13. Medium-chain fatty acids inhibit mitochondrial metabolism in astrocytes promoting astrocyte-neuron lactate and ketone body shuttle systems.

    PubMed

    Thevenet, Jonathan; De Marchi, Umberto; Domingo, Jaime Santo; Christinat, Nicolas; Bultot, Laurent; Lefebvre, Gregory; Sakamoto, Kei; Descombes, Patrick; Masoodi, Mojgan; Wiederkehr, Andreas

    2016-05-01

    Medium-chain triglycerides have been used as part of a ketogenic diet effective in reducing epileptic episodes. The health benefits of the derived medium-chain fatty acids (MCFAs) are thought to result from the stimulation of liver ketogenesis providing fuel for the brain. We tested whether MCFAs have direct effects on energy metabolism in induced pluripotent stem cell-derived human astrocytes and neurons. Using single-cell imaging, we observed an acute pronounced reduction of the mitochondrial electrical potential and a concomitant drop of the NAD(P)H signal in astrocytes, but not in neurons. Despite the observed effects on mitochondrial function, MCFAs did not lower intracellular ATP levels or activate the energy sensor AMP-activated protein kinase. ATP concentrations in astrocytes were unaltered, even when blocking the respiratory chain, suggesting compensation through accelerated glycolysis. The MCFA decanoic acid (300 μM) promoted glycolysis and augmented lactate formation by 49.6%. The shorter fatty acid octanoic acid (300 μM) did not affect glycolysis but increased the rates of astrocyte ketogenesis 2.17-fold compared with that of control cells. MCFAs may have brain health benefits through the modulation of astrocyte metabolism leading to activation of shuttle systems that provide fuel to neighboring neurons in the form of lactate and ketone bodies.-Thevenet, J., De Marchi, U., Santo Domingo, J., Christinat, N., Bultot, L., Lefebvre, G., Sakamoto, K., Descombes, P., Masoodi, M., Wiederkehr, A. Medium-chain fatty acids inhibit mitochondrial metabolism in astrocytes promoting astrocyte-neuron lactate and ketone body shuttle systems. PMID:26839375

  14. Medium-chain and short-chain dehydrogenases/reductases in retinoid metabolism

    PubMed Central

    Parés, X.; Farrés, J.; Kedishvili, N.; Duester, G.

    2009-01-01

    Retinoic acid (RA), the most active retinoid, is synthesized in two steps from retinol. The first step, oxidation of retinol to retinaldehyde, is catalyzed by cytosolic alcohol dehydrogenases (ADHs) of the medium-chain dehydrogenase/reductase (MDR) superfamily and microsomal retinol dehydrogenases (RDHs) of the short-chain dehydrogenase/reductase (SDR) superfamily. The second step, oxidation of retinaldehyde to RA, is catalyzed by several aldehyde dehydrogenases. ADH1 and ADH2 are the major MDR enzymes in liver retinol detoxification, while ADH3 (less active) and ADH4 (most active) participate in RA generation in tissues. Several NAD+- and NADP+-dependent SDRs are retinoid active. Their in vivo contribution has been demonstrated in the visual cycle (RDH5, RDH12), adult retinoid homeostasis (RDH1) and embryogenesis (RDH10). Km values for most retinoid-active ADHs and RDHs are close to 1 μM or lower, suggesting that they participate physiologically in retinol/retinaldehyde interconversion. Probably none of these enzymes uses retinoids bound to cellular retinol-binding protein, but only free retinoids. The large number of enzymes involved in the two directions of this step, also including aldoketo reductases, suggests that retinaldehyde levels are strictly regulated. PMID:19011747

  15. An insight on acyl migration in solvent-free ethanolysis of model triglycerides using Novozym 435.

    PubMed

    Sánchez, Daniel Alberto; Tonetto, Gabriela Marta; Ferreira, María Luján

    2016-02-20

    In this work, the ethanolysis of triglycerides catalyzed by immobilized lipase was studied, focusing on the secondary reaction of acyl migration. The catalytic tests were performed in a solvent-free reaction medium using Novozym 435 as biocatalyst. The selected experimental variables were biocatalyst loading (5-20mg), reaction time (30-90min), and chain length of the fatty acids in triglycerides with and without unsaturation (short (triacetin), medium (tricaprylin) and long (tripalmitin/triolein)). The formation of 2-monoglyceride by ethanolysis of triglycerides was favored by long reaction times and large biocatalyst loading with saturated short- to medium-chain triglycerides. In the case of long-chain triglycerides, the formation of this monoglyceride was widely limited by acyl migration. In turn, acyl migration increased the yield of ethyl esters and minimized the content of monoglycerides and diglycerides. Thus, the enzymatic synthesis of biodiesel was favored by long-chain triglycerides (which favor the acyl migration), long reaction times and large biocatalyst loading. The conversion of acylglycerides made from long-chain fatty acids with unsaturation was relatively low due to limitations in their access to the active site of the lipase. PMID:26795690

  16. Effects of medium-chain fatty acids on performance, carcass characteristics, blood biochemical parameters and immune response in Japanese quail.

    PubMed

    Saeidi, E; Shokrollahi, B; Karimi, K; Amiri-Andi, M

    2016-06-01

    This study had the aim of evaluating the effects of medium-chain fatty acids (MCFA) on performance, carcass characteristics, some blood parameters and antibody titre against sheep red blood cells (SRBC) in quail. A total of 240 quail chicks were allotted to 4 treatments consisting of respectively 0, 1, 2 and 4 g/kg dietary MCFA. There were no significant differences in body weight, feed intake and feed conversion ratio among treatments at different stages of the experiment. MCFAs had no significant effect on breast, thigh, liver, spleen and bursa of Fabricius weight ratios. However, the relative weight of abdominal fat significantly decreased in quail receiving 0.2 and 0.4 MCFA as compared to other treatments. Concentrations of low-density lipoprotein-cholesterol (LDL), triglycerides and total cholesterol were decreased and high-density lipoprotein (HDL)-cholesterol was increased in quail chicks receiving MCFA compared with control quail chicks. The concentrations of SRBC antibody were not statistically different among treatments. It is concluded that MCFA significantly decreased LDL, triglycerides, cholesterol and abdominal fat and increased HDL in quail chicks. PMID:27074264

  17. Long-term biopermanence of ceramides, cholesteryl esters, and ether-linked triglycerides with very-long-chain PUFA in the cadmium-damaged testis.

    PubMed

    Zanetti, Samanta R; Aveldaño, Marta I

    2014-01-01

    Cadmium is known to harm rat testis by causing the dose-dependent apoptotic or necrotic death of seminiferous epithelium cells. Here we investigated how this affects the lipids with long-chain (C18-C22) and very-long-chain (C24-C32) polyunsaturated fatty acids (VLCPUFA) typical of spermatogenic and Sertoli cells. A severe acute inflammatory reaction resulted from the massive necrotic death of these cells two days after a single high (4mg/kg) dose of CdCl2. This led to the conversion of most testicular glycerophospholipids to diradylglycerols (DRG) and free fatty acids (FFA) and of most sphingomyelins to ceramides (Cer). By day 30 the testis weight had decreased three-fold. The DRG and FFA had been metabolized but, unexpectedly, ceramides persisted. Also slow to disappear were VLCPUFA-containing triacylglycerols from former germ cells and ether-linked triglycerides and cholesteryl esters (CE) from former Sertoli cells. Similar results were observed 30 and 45days after administering repeated small non pro-inflammatory CdCl2 doses (1mg/kg). At day 30 after both treatments, an amorphous material replaced the original seminiferous tubules and the interstitium was populated by macrophages. Species of CE and ether-linked triglycerides containing fatty acids other than VLCPUFA steadily accumulated in the irreversibly damaged testis, a manifestation of the activity of these cells. The long-term permanence of original VLCPUFA-containing neutral lipids, especially ceramides, indicates that these phagocytes were slow to clear out the acellular material contained in seminiferous tubules, pointing to a form of silent chronic inflammation as an additional outcome of the multifactorial commotion caused in the testis by experimentally administered cadmium. PMID:24120575

  18. Exceptionally elevated triglyceride in severe lipemia retinalis

    PubMed Central

    Yin, Han Y; Warman, Roberto; Suh, Edward H; Cheng, Anny MS

    2016-01-01

    Purpose To report a case of successful treatment for severe lipemia retinalis with extreme severe hypertriglyceridemia (sHTG). Design Observational case report. Observations A 6-week-old infant with severe lipemia retinalis manifested diffuse creamy retinal vessels complicated with vulvar xanthomas. Extreme sHTG with 185-folds of the normal level was reported. Chromosome microarray and lipid gene sequencing confirmed a homozygous lipoprotein lipase gene coding mutation. Results Under strict adherence to a high medium-chain triglycerides formula and discontinuation of breast milk, the lipemia retinalis and vulval lesions resolved along with a stable plasma lipid level throughout the follow-up period of 6 months. Conclusion Strict adherence to a low-fat diet without breast milk appears to be effective in treating infants with severe lipemia retinalis associated with exceptionally high triglycerides. PMID:27799830

  19. De novo fatty acid biosynthesis and elongation in very long-chain acyl-CoA dehydrogenase-deficient mice supplemented with odd or even medium-chain fatty acids.

    PubMed

    Tucci, Sara; Behringer, Sidney; Spiekerkoetter, Ute

    2015-11-01

    An even medium-chain triglyceride (MCT)-based diet is the mainstay of treatment in very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD). Previous studies with magnetic resonance spectroscopy have shown an impact of MCT on the average fatty acid chain length in abdominal fat. We therefore assume that medium-chain fatty acids (MCFAs) are elongated and accumulate in tissue as long-chain fatty acids. In this study, we explored the hepatic effects of long-term supplementation with MCT or triheptanoin, an odd-chain C7-based triglyceride, in wild-type and VLCAD-deficient (VLCAD(-/-) ) mice after 1 year of supplementation as compared with a control diet. The de novo biosynthesis and elongation of fatty acids, and peroxisomal β-oxidation, were quantified by RT-PCR. This was followed by a comprehensive analysis of hepatic and cardiac fatty acid profiles by GC-MS. Long-term application of even and odd MCFAs strongly induced de novo biosynthesis and elongation of fatty acids in both wild-type and VLCAD(-/-) mice, leading to an alteration of the hepatic fatty acid profiles. We detected de novo-synthesized and elongated fatty acids, such as heptadecenoic acid (C17:1n9), eicosanoic acid (C20:1n9), erucic acid (C22:1n9), and mead acid (C20:3n9), that were otherwise completely absent in mice under control conditions. In parallel, the content of monounsaturated fatty acids was massively increased. Furthermore, we observed strong upregulation of peroxisomal β-oxidation in VLCAD(-/-) mice, especially when they were fed an MCT diet. Our data raise the question of whether long-term MCFA supplementation represents the most efficient treatment in the long term. Studies on the hepatic toxicity of triheptanoin are still ongoing.

  20. De novo fatty acid biosynthesis and elongation in very long-chain acyl-CoA dehydrogenase-deficient mice supplemented with odd or even medium-chain fatty acids.

    PubMed

    Tucci, Sara; Behringer, Sidney; Spiekerkoetter, Ute

    2015-11-01

    An even medium-chain triglyceride (MCT)-based diet is the mainstay of treatment in very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD). Previous studies with magnetic resonance spectroscopy have shown an impact of MCT on the average fatty acid chain length in abdominal fat. We therefore assume that medium-chain fatty acids (MCFAs) are elongated and accumulate in tissue as long-chain fatty acids. In this study, we explored the hepatic effects of long-term supplementation with MCT or triheptanoin, an odd-chain C7-based triglyceride, in wild-type and VLCAD-deficient (VLCAD(-/-) ) mice after 1 year of supplementation as compared with a control diet. The de novo biosynthesis and elongation of fatty acids, and peroxisomal β-oxidation, were quantified by RT-PCR. This was followed by a comprehensive analysis of hepatic and cardiac fatty acid profiles by GC-MS. Long-term application of even and odd MCFAs strongly induced de novo biosynthesis and elongation of fatty acids in both wild-type and VLCAD(-/-) mice, leading to an alteration of the hepatic fatty acid profiles. We detected de novo-synthesized and elongated fatty acids, such as heptadecenoic acid (C17:1n9), eicosanoic acid (C20:1n9), erucic acid (C22:1n9), and mead acid (C20:3n9), that were otherwise completely absent in mice under control conditions. In parallel, the content of monounsaturated fatty acids was massively increased. Furthermore, we observed strong upregulation of peroxisomal β-oxidation in VLCAD(-/-) mice, especially when they were fed an MCT diet. Our data raise the question of whether long-term MCFA supplementation represents the most efficient treatment in the long term. Studies on the hepatic toxicity of triheptanoin are still ongoing. PMID:26284828

  1. Medium chain triglycerides dose-dependently prevent liver pathology in a rat model of nonalcoholic fatty liver disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity is often associated with a cluster of increased health risks collectively known as "Metabolic Syndrome" (MS). MS is often accompanied by development of fatty liver. Sometimes fatty liver results in damage leading to reduced liver function, and need for a transplant. This condition is known...

  2. Fatty acid biosynthesis redirected to medium chains in transgenic oilseed plants

    SciTech Connect

    Voelker, T.A.; Worrell, A.C.; Anderson, L.; Bleibaum, J.; Fan, C.; Hawkins, D.J.; Radke, S.E.; Davies, H.M. )

    1992-07-03

    Medium-chain fatty acids (FAs), found in storage lipids of certain plants, are an important renewable resource. Seeds of undomesticated California bay accumulate laurate (12:0), and a 12:0-acyl-carrier protein thioesterase (BTE) has been purified from this tissue. Sequencing of BTE enabled the cloning of a complementary DNA coding for a plastid-targeted preprotein. Expression of the complementary DNA in the seeds of Arabidopsis thaliana resulted in BTE activity, and medium chains accumulated at the expense of long-chain ({ge}16) FAs. Laurate became the most abundant FA species and was deposited in the storage triacylglycerols. These results demonstrate a mechanism for medium-chain FA synthesis in plants.

  3. Biosynthesis and Elongation of Short- and Medium-Chain-Length Fatty Acids

    PubMed Central

    van der Hoeven, Rutger S.; Steffens, John C.

    2000-01-01

    Short- and medium-chain-length fatty acids (FAs) are important constituents of a wide array of natural products. Branched and straight short-chain-length FAs originate from branched chain amino acid metabolism, and serve as primers for elongation in FA synthase-like reactions. However, a recent model proposes that the one-carbon extension reactions that utilize 2-oxo-3-methylbutyric acid in leucine biosynthesis also catalyze a repetitive one-carbon elongation of short-chain primers to medium-chain-length FAs. The existence of such a mechanism would require a novel form of regulation to control carbon flux between amino acid and FA biosynthesis. A critical re-analysis of the data used to support this pathway fails to support the hypothesis for FA elongation by one-carbon extension cycles of α-ketoacids. Therefore, we tested the hypothesis experimentally using criteria that distinguish between one- and two-carbon elongation mechanisms: (a) isotopomer patterns in terminal carbon atom pairs of branched and straight FAs resulting from differential labeling with [13C]acetate; (b) [13C]threonine labeling patterns in odd- and even chain length FAs; and (c) differential sensitivity of elongation reactions to inhibition by cerulenin. All three criteria indicated that biosynthesis of medium-chain length FAs is mediated primarily by FA synthase-like reactions. PMID:10631271

  4. Efficient odd straight medium chain free fatty acid production by metabolically engineered Escherichia coli.

    PubMed

    Wu, Hui; San, Ka-Yiu

    2014-11-01

    Free fatty acids (FFAs) can be used as precursors for the production of biofuels or chemicals. Different composition of FFAs will be useful for further modification of the biofuel/biochemical quality. Microbial biosynthesis of even chain FFAs can be achieved by introducing an acyl-acyl carrier protein thioesterase gene into E. coli. In this study, odd straight medium chain FFAs production was investigated by using metabolic engineered E. coli carrying acyl-ACP thioesterase (TE, Ricinus communis), propionyl-CoA synthase (Salmonella enterica), and β-ketoacyl-acyl carrier protein synthase III (four different sources) with supplement of extracellular propionate. By using these metabolically engineered E. coli, significant quantity of C13 and C15 odd straight-chain FFAs could be produced from glucose and propionate. The highest concentration of total odd straight chain FFAs attained was 1205 mg/L by the strain HWK201 (pXZ18, pBHE2), and 85% of the odd straight chain FFAs was C15. However, the highest percentage of odd straight chain FFAs was achieved by the strain HWK201 (pXZ18, pBHE3) of 83.2% at 48 h. This strategy was also applied successfully in strains carrying different TE, such as the medium length acyl-ACP thioesterase gene from Umbellularia californica. C11 and C13 became the major odd straight-chain FFAs.

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

    PubMed Central

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

    2011-01-01

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

  6. Pathway Compartmentalization in Peroxisome of Saccharomyces cerevisiae to Produce Versatile Medium Chain Fatty Alcohols.

    PubMed

    Sheng, Jiayuan; Stevens, Joseph; Feng, Xueyang

    2016-01-01

    Fatty alcohols are value-added chemicals and important components of a variety of industries, which have a >3 billion-dollar global market annually. Long chain fatty alcohols (>C12) are mainly used in surfactants, lubricants, detergents, pharmaceuticals and cosmetics while medium chain fatty alcohols (C6-C12) could be used as diesel-like biofuels. Microbial production of fatty alcohols from renewable feedstock stands as a promising strategy to enable sustainable supply of fatty alcohols. In this study, we report, for the first time, that medium chain fatty alcohols could be produced in yeast via targeted expression of a fatty acyl-CoA reductase (TaFAR) in the peroxisome of Saccharomyces cerevisiae. By tagging TaFAR enzyme with peroxisomal targeting signal peptides, the TaFAR could be compartmentalized into the matrix of the peroxisome to hijack the medium chain fatty acyl-CoA generated from the beta-oxidation pathway and convert them to versatile medium chain fatty alcohols (C10 &C12). The overexpression of genes encoding PEX7 and acetyl-CoA carboxylase further improved fatty alcohol production by 1.4-fold. After medium optimization in fed-batch fermentation using glucose as the sole carbon source, fatty alcohols were produced at 1.3 g/L, including 6.9% 1-decanol, 27.5% 1-dodecanol, 2.9% 1-tetradecanol and 62.7% 1-hexadecanol. This work revealed that peroxisome could be engineered as a compartmentalized organelle for producing fatty acid-derived chemicals in S. cerevisiae. PMID:27230732

  7. Pathway Compartmentalization in Peroxisome of Saccharomyces cerevisiae to Produce Versatile Medium Chain Fatty Alcohols

    PubMed Central

    Sheng, Jiayuan; Stevens, Joseph; Feng, Xueyang

    2016-01-01

    Fatty alcohols are value-added chemicals and important components of a variety of industries, which have a >3 billion-dollar global market annually. Long chain fatty alcohols (>C12) are mainly used in surfactants, lubricants, detergents, pharmaceuticals and cosmetics while medium chain fatty alcohols (C6–C12) could be used as diesel-like biofuels. Microbial production of fatty alcohols from renewable feedstock stands as a promising strategy to enable sustainable supply of fatty alcohols. In this study, we report, for the first time, that medium chain fatty alcohols could be produced in yeast via targeted expression of a fatty acyl-CoA reductase (TaFAR) in the peroxisome of Saccharomyces cerevisiae. By tagging TaFAR enzyme with peroxisomal targeting signal peptides, the TaFAR could be compartmentalized into the matrix of the peroxisome to hijack the medium chain fatty acyl-CoA generated from the beta-oxidation pathway and convert them to versatile medium chain fatty alcohols (C10 & C12). The overexpression of genes encoding PEX7 and acetyl-CoA carboxylase further improved fatty alcohol production by 1.4-fold. After medium optimization in fed-batch fermentation using glucose as the sole carbon source, fatty alcohols were produced at 1.3 g/L, including 6.9% 1-decanol, 27.5% 1-dodecanol, 2.9% 1-tetradecanol and 62.7% 1-hexadecanol. This work revealed that peroxisome could be engineered as a compartmentalized organelle for producing fatty acid-derived chemicals in S. cerevisiae. PMID:27230732

  8. Short- and medium-chain fatty acids exhibit antimicrobial activity for oral microorganisms

    PubMed Central

    Huang, Chifu B.; Altimova, Yelena; Myers, Taylor M.; Ebersole, Jeffrey L.

    2011-01-01

    Objectives This study assessed the antibacterial activity of short-, medium-, and long-chain fatty acids against various oral microorganisms. Methods The short-chain fatty acids [formic acid (C1), acetic acid (C2), propionic acid (C3), butyric acid (C4), isobutyric acid (C4), isovaleric acid (C5), hexanoic acid (C6)], medium-chain fatty acids [octanoic acid (C8), capric acid (C10), lauric acid (12)], and long-chain fatty acids [myristic acid (C14), palmitic acid (C16)], were investigated for antimicrobial activity against Streptococcus mutans, S. gordonii, S. sanguis, Candida albicans, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, and Porphyromonas gingivalis. Results The data demonstrated that the fatty acids exhibited patterns of inhibition against oral bacteria with some specificity that appeared related more to the bacterial species that the general structural characteristics of the microorganism. As a group the fatty acids were much less effective against C. albicans than the oral bacteria, with effectiveness limited to hexanoic, octanoic, and lauric acids. Formic acid, capric, and lauric acids were broadly inhibitory for the bacteria. Interestingly, fatty acids that are produced at metabolic end-products by a number of these bacteria, were specifically inactive against the producing species, while substantially inhibiting the growth of other oral microorganisms. Conclusions The results indicate that the antimicrobial activity of short-chain fatty acids (SCFAs), medium-chain fatty acids (MCFAs), long-chain fatty acids (LCFAs) could influence the microbial ecology in the oral cavity via at least 2 potential pathways. First, the agents delivered exogenously as therapeutic adjuncts could be packaged to enhance a microbial-regulatory environment in the subgingival sulcus. Second, it would be the intrinsic nature of these fatty acid inhibitors in contributing to the characteristics of the microbial biofilms, their evolution, and emergence of

  9. Chain length determination of prenyltransferases: both heteromeric subunits of medium-chain (E)-prenyl diphosphate synthase are involved in the product chain length determination.

    PubMed

    Zhang, Y W; Li, X Y; Koyama, T

    2000-10-17

    Among prenyltransferases, medium-chain (E)-prenyl diphosphate synthases are unusual because of their heterodimeric structures. The larger subunit has highly conserved regions typical of (E)-prenyltransferases. The smaller one has recently been shown to be involved in the binding of allylic substrate as well as determining the chain length of the reaction product [Zhang, Y.-W., et al. (1999) Biochemistry 38, 14638-14643]. To better understand the product chain length determination mechanism of these enzymes, several amino acid residues in the larger subunits of Micrococcus luteus B-P 26 hexaprenyl diphosphate synthase and Bacillus subtilis heptaprenyl diphosphate synthase were selected for substitutions by site-directed mutagenesis and examined by combination with the corresponding wild-type or mutated smaller subunits. Replacement of the Ala at the fifth position upstream to the first Asp-rich motif with bulky amino acids in both larger subunits resulted in shortening the chain lengths of the major products, and a double combination of mutant subunits of the heptaprenyl diphosphate synthase, I-D97A/II-A79F, yielded exclusively geranylgeranyl diphosphate. However, the combination of a mutant subunit and the wild-type, I-Y103S/II-WT or I-WT/II-I76G, produced a C(40) prenyl diphosphate, and the double combination of the mutants, I-Y103S/II-I76G, gave a reaction product with longer prenyl chain up to C(50). These results suggest that medium-chain (E)-prenyl diphosphate synthases take a novel mode for the product chain length determination, in which both subunits cooperatively participate in maintaining and determining the product specificity of each enzyme.

  10. Draft Genome Sequence of Medium-Chain-Length Polyhydroxyalkanoate-Producing Pseudomonas putida Strain LS46.

    PubMed

    Sharma, Parveen K; Fu, Jilagamazhi; Zhang, Xiangli; Fristensky, Brian W; Davenport, Karen; Chain, Patrick S G; Sparling, Richard; Levin, David B

    2013-04-18

    We describe the draft genome sequence of Pseudomonas putida strain LS46, a novel isolate that synthesizes medium-chain-length polyhydroxyalkanoates. The draft genome of P. putida LS46 consists of approximately 5.86 million bp, with a G+C content of 61.69%. A total of 5,316 annotated genes and 5,219 coding sequences (CDS) were identified.

  11. [Progress on the biosynthesis of medium-chain-length polyhydroxyalkanoates by microorganisms].

    PubMed

    Yan, Q; Li, Y; Chen, J; Du, G C

    2001-09-01

    Polyhydroxylkanoates(PHAs) are a class of polyesters produced as reserve materials by a large number of microorganisms under metabolic stress. The most fascinating feature of PHAs is its degradability, and which is supposed to take place of the traditional plastics made from petroleum in the future. PHAs are divided into two classes: short-chain-length PHAs(scl-PHAs) and medium-chain-length PHAs. mcl-PHAs is more welcome owing to its more wide crystallinity and higher extension to break than scl-PHAs, especially when some kind of new functional groups were incorporated into the side chain of the polyester. Since Psedumonas oleovorans is the most typical microorganism to produce mcl-PHAs, here the author summarized how P. oleovorans synthesize the mcl-PHAs and the production of mcl-PHAs by fermentation and give some of the idea about the future research of this field. PMID:11797205

  12. A Review of Supply Chain Collaboration Practices for Small and Medium-sized Manufacturers

    NASA Astrophysics Data System (ADS)

    Wee, SY; Thoo, AC; Z, Sulaiman; FM, Muharam

    2016-05-01

    For the decades, organizations have endeavored to look for external sources for opportunities to achieve efficient and responsive supply chain with their partners especially for small and medium manufacturers (SMM). In this scenario, supply chain collaboration (SCC) is an interaction between supply chain members with the purpose of utilizes the knowledge and resources of customers and suppliers, and integrates the flows of products and information in order to achieve a common goal and obtain mutual benefit. The essential SCC dimensions for SMMs comprised of information sharing, joint knowledge creation, joint decision making, goal congruence and incentive sharing. The successful implementation of SCC can give SMMs an edge over their competitors. This paper aims to introduce a review of SCC practices for SMM. Overall, the findings provide managerial insights for the SMM in SCC implementation owing to resource scarcity and the need to draw SCC in order to ensure a sustainable competitive advantage.

  13. Calculation of Physicochemical Properties for Short- and Medium-Chain Chlorinated Paraffins

    NASA Astrophysics Data System (ADS)

    Glüge, Juliane; Bogdal, Christian; Scheringer, Martin; Buser, Andreas M.; Hungerbühler, Konrad

    2013-06-01

    Short- and medium-chain chlorinated paraffins are potential PBT chemicals (persistent, bioaccumulative, toxic) and short-chain chlorinated paraffins are under review for inclusion in the UNEP Stockholm Convention on Persistent Organic Pollutants. Despite their high production volume of more than one million metric tonnes per year, only few data on their physicochemical properties are available. We calculated subcooled-liquid vapor pressure, subcooled-liquid solubility in water and octanol, Henry's law constant for water and octanol, as well as the octanol-water partition coefficient with the property calculation methods COSMOtherm, SPARC, and EPI Suite™, and compared the results to experimental data from the literature. For all properties, good or very good agreement between calculated and measured data was obtained for COSMOtherm; results from SPARC were in good agreement with the measured data except for subcooled-liquid water solubility, whereas EPI Suite™ showed the largest discrepancies for all properties. After critical evaluation of the three property calculation methods, a final set of recommended property data for short- and medium-chain chlorinated paraffins was derived. The calculated property data show interesting relationships with chlorine content and carbon chain length. Increasing chlorine content does not cause pronounced changes in water solubility and octanol-water partition coefficient (KOW) as long as it is below 55%. Increasing carbon chain length leads to strong increases in KOW and corresponding decreases in subcooled-liquid water solubility. The present data set can be used in further studies to assess the environmental fate and human exposure of this relevant compound class.

  14. An improved method for determining medium- and long-chain FAMEs using gas chromatography.

    PubMed

    Xu, Zhidong; Harvey, Kevin; Pavlina, Thomas; Dutot, Guy; Zaloga, Gary; Siddiqui, Rafat

    2010-02-01

    The existing protocols for analyzing fatty acid methyl esters (FAMEs) using a one-step acetyl chloride (AC) catalyzed transesterification and extraction procedure cannot accurately determine the medium- and long-chain fatty acids simultaneously in clinical (enteral, parenteral) formulations. For example: (1) addition of AC at room temperature generates an exothermic reaction that often results in loss of sample and possible injury to the analyst; (2) certain polyunsaturated fatty acids (PUFAs) are less stable at elevated temperatures during the transesterification and contribute to the over-estimation of the C16:0 and C18:1 fatty acids; and (3) the flame-ionization detector (FID) response varies depending on the carbon chain length of the fatty acids, that consequently impacts the underestimation of medium-chain fatty acid (C6-C10) recoveries. To overcome these deficiencies and accurately determine FAMEs, we have developed an improved one-step transesterification method that employs the addition of AC in tubes kept on a dry ice bath, the transesterification at room temperature, and the data analysis using relative response factors. Using this modified protocol, we determined the fatty acid composition of lipid emulsions (Omegaven and Lipidem) on a Shimadzu GC2010 gas chromatography (GC) system using a capillary GC column (Zebron ZB-WAX plus, 30 m, 0.25 mm ID, 0.25 microm). Our data suggest that the improved method can be easily used to accurately determine fatty acids (C6-C24) in functional foods and lipid emulsions. PMID:20082149

  15. An improved method for determining medium- and long-chain FAMEs using gas chromatography.

    PubMed

    Xu, Zhidong; Harvey, Kevin; Pavlina, Thomas; Dutot, Guy; Zaloga, Gary; Siddiqui, Rafat

    2010-02-01

    The existing protocols for analyzing fatty acid methyl esters (FAMEs) using a one-step acetyl chloride (AC) catalyzed transesterification and extraction procedure cannot accurately determine the medium- and long-chain fatty acids simultaneously in clinical (enteral, parenteral) formulations. For example: (1) addition of AC at room temperature generates an exothermic reaction that often results in loss of sample and possible injury to the analyst; (2) certain polyunsaturated fatty acids (PUFAs) are less stable at elevated temperatures during the transesterification and contribute to the over-estimation of the C16:0 and C18:1 fatty acids; and (3) the flame-ionization detector (FID) response varies depending on the carbon chain length of the fatty acids, that consequently impacts the underestimation of medium-chain fatty acid (C6-C10) recoveries. To overcome these deficiencies and accurately determine FAMEs, we have developed an improved one-step transesterification method that employs the addition of AC in tubes kept on a dry ice bath, the transesterification at room temperature, and the data analysis using relative response factors. Using this modified protocol, we determined the fatty acid composition of lipid emulsions (Omegaven and Lipidem) on a Shimadzu GC2010 gas chromatography (GC) system using a capillary GC column (Zebron ZB-WAX plus, 30 m, 0.25 mm ID, 0.25 microm). Our data suggest that the improved method can be easily used to accurately determine fatty acids (C6-C24) in functional foods and lipid emulsions.

  16. Numerical simulation of the transport of a radionuclide chain in a rock medium.

    PubMed

    Sen, Soubhadra; Srinivas, C V; Baskaran, R; Venkatraman, B

    2015-03-01

    For the safe disposal of High Level Waste (HLW), a common practice is to bury the sealed container called canister containing the concentrated and vitrified waste deep inside the earth surface within a rocky medium. In the event of an accidental breach of such a canister, the sealed waste may come in contact of pore water. If this happens, then the parent nuclides present in the HLW and their daughters generated by the radioactive decay reaction start migrating through the surrounding rock medium due to the combined effect of advection and diffusion. The accurate estimation of the transport of such a chain through a rock is important for radiological safety. Here, we report a finite difference based numerical simulation to address the issue. To simplify the problem, we consider the rock to be a collection of identical parallel fractures separated by porous matrices of equal width with a source at one end. A Forward Time and Centered Space (FTCS) finite difference scheme is implemented to solve the set of coupled partial differential equations that govern the transport mechanism. The scheme is validated using the methods available in the literature and subsequently it is applied to estimate the time dependent buildup of the active elements of a chain. Two independent chains each with three members are considered for simulation to address the safety related issues. PMID:25574608

  17. [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.

  18. Radiation crosslinking of a bacterial medium-chain-length poly(hydroxyalkanoate) elastomer from tallow.

    PubMed

    Ashby, R D; Cromwick, A M; Foglia, T A

    1998-07-01

    Pseudomonas resinovorans produces a medium-chain-length poly(hydroxyalkanoate) (MCL-PHA) copolymer when grown on tallow (PHA-tal). This polymer had a repeat unit composition ranging from C4 to C14 with some mono-unsaturation in the C12 and C14 alkyl side chains. Thermal analysis indicated that the polymer was semi-crystalline with a melting temperature (T(m)) of 43.5 +/- 0.2 degrees C and a glass transition temperature (Tg) of -43.4 +/- 2.0 degrees C. The presence of unsaturated side chains allowed crosslinking by gamma-irradiation. Irradiated polymer films had decreased solubility in organic solvents that indicated an increase in the crosslinking density within the film matrix. The addition of linseed oil to the gamma-irradiated film matrix enhanced polymer recovery while minimizing chain scission. Linseed oil also caused a decrease in the enthalpy of fusion (delta Hm) of the films (by an average of 60%) as well as enhanced mineralization. The effects of crosslinking on the mechanical properties and biodegradability of the polymer were determined. Radiation had no effect on the storage modulus (E') of the polymer. However, radiation doses of 25 and 50 kGy did increase the Young modulus of the polymer by 129 and 114%, and the tensile strength of the polymer by 76 and 35%, respectively. Finally, the formation of a higher crosslink density within the polymer matrix decreased the biodegradability of the PHA films.

  19. Radiation crosslinking of a bacterial medium-chain-length poly(hydroxyalkanoate) elastomer from tallow.

    PubMed

    Ashby, R D; Cromwick, A M; Foglia, T A

    1998-07-01

    Pseudomonas resinovorans produces a medium-chain-length poly(hydroxyalkanoate) (MCL-PHA) copolymer when grown on tallow (PHA-tal). This polymer had a repeat unit composition ranging from C4 to C14 with some mono-unsaturation in the C12 and C14 alkyl side chains. Thermal analysis indicated that the polymer was semi-crystalline with a melting temperature (T(m)) of 43.5 +/- 0.2 degrees C and a glass transition temperature (Tg) of -43.4 +/- 2.0 degrees C. The presence of unsaturated side chains allowed crosslinking by gamma-irradiation. Irradiated polymer films had decreased solubility in organic solvents that indicated an increase in the crosslinking density within the film matrix. The addition of linseed oil to the gamma-irradiated film matrix enhanced polymer recovery while minimizing chain scission. Linseed oil also caused a decrease in the enthalpy of fusion (delta Hm) of the films (by an average of 60%) as well as enhanced mineralization. The effects of crosslinking on the mechanical properties and biodegradability of the polymer were determined. Radiation had no effect on the storage modulus (E') of the polymer. However, radiation doses of 25 and 50 kGy did increase the Young modulus of the polymer by 129 and 114%, and the tensile strength of the polymer by 76 and 35%, respectively. Finally, the formation of a higher crosslink density within the polymer matrix decreased the biodegradability of the PHA films. PMID:9644597

  20. Microbial biosynthesis of medium-chain 1-alkenes by a nonheme iron oxidase.

    PubMed

    Rui, Zhe; Li, Xin; Zhu, Xuejun; Liu, Joyce; Domigan, Bonnie; Barr, Ian; Cate, Jamie H D; Zhang, Wenjun

    2014-12-23

    Aliphatic medium-chain 1-alkenes (MCAEs, ∼10 carbons) are "drop-in" compatible next-generation fuels and precursors to commodity chemicals. Mass production of MCAEs from renewable resources holds promise for mitigating dependence on fossil hydrocarbons. An MCAE, such as 1-undecene, is naturally produced by Pseudomonas as a semivolatile metabolite through an unknown biosynthetic pathway. We describe here the discovery of a single gene conserved in Pseudomonas responsible for 1-undecene biosynthesis. The encoded enzyme is able to convert medium-chain fatty acids (C10-C14) into their corresponding terminal olefins using an oxygen-activating, nonheme iron-dependent mechanism. Both biochemical and X-ray crystal structural analyses suggest an unusual mechanism of β-hydrogen abstraction during fatty acid substrate activation. Our discovery unveils previously unidentified chemistry in the nonheme Fe(II) enzyme family, provides an opportunity to explore the biology of 1-undecene in Pseudomonas, and paves the way for tailored bioconversion of renewable raw materials to MCAE-based biofuels and chemical commodities.

  1. Exploring medium-chain-length polyhydroxyalkanoates production in the engineered yeast Yarrowia lipolytica.

    PubMed

    Gao, Cuijuan; Qi, Qingsheng; Madzak, Catherine; Lin, Carol Sze Ki

    2015-09-01

    Medium-chain-length polyhydroxyalkanoates (mcl-PHAs) are a large class of biopolymers that have attracted extensive attention as renewable and biodegradable bio-plastics. They are naturally synthesized via fatty acid de novo biosynthesis pathway or β-oxidation pathway from Pseudomonads. The unconventional yeast Yarrowia lipolytica has excellent lipid/fatty acid catabolism and anabolism capacity depending of the mode of culture. Nevertheless, it cannot naturally synthesize PHA, as it does not express an intrinsic PHA synthase. Here, we constructed a genetically modified strain of Y. lipolytica by heterologously expressing PhaC1 gene from P. aeruginosa PAO1 with a PTS1 peroxisomal signal. When in single copy, the codon optimized PhaC1 allowed the synthesis of 0.205 % DCW of PHA after 72 h cultivation in YNBD medium containing 0.1 % oleic acid. By using a multi-copy integration strategy, PHA content increased to 2.84 % DCW when the concentration of oleic acid in YNBD was 1.0 %. Furthermore, when the recombinant yeast was grown in the medium containing triolein, PHA accumulated up to 5.0 % DCW with as high as 21.9 g/L DCW, which represented 1.11 g/L in the culture. Our results demonstrated the potential use of Y. lipolytica as a promising microbial cell factory for PHA production using food waste, which contains lipids and other essential nutrients. PMID:26153503

  2. Exploring medium-chain-length polyhydroxyalkanoates production in the engineered yeast Yarrowia lipolytica.

    PubMed

    Gao, Cuijuan; Qi, Qingsheng; Madzak, Catherine; Lin, Carol Sze Ki

    2015-09-01

    Medium-chain-length polyhydroxyalkanoates (mcl-PHAs) are a large class of biopolymers that have attracted extensive attention as renewable and biodegradable bio-plastics. They are naturally synthesized via fatty acid de novo biosynthesis pathway or β-oxidation pathway from Pseudomonads. The unconventional yeast Yarrowia lipolytica has excellent lipid/fatty acid catabolism and anabolism capacity depending of the mode of culture. Nevertheless, it cannot naturally synthesize PHA, as it does not express an intrinsic PHA synthase. Here, we constructed a genetically modified strain of Y. lipolytica by heterologously expressing PhaC1 gene from P. aeruginosa PAO1 with a PTS1 peroxisomal signal. When in single copy, the codon optimized PhaC1 allowed the synthesis of 0.205 % DCW of PHA after 72 h cultivation in YNBD medium containing 0.1 % oleic acid. By using a multi-copy integration strategy, PHA content increased to 2.84 % DCW when the concentration of oleic acid in YNBD was 1.0 %. Furthermore, when the recombinant yeast was grown in the medium containing triolein, PHA accumulated up to 5.0 % DCW with as high as 21.9 g/L DCW, which represented 1.11 g/L in the culture. Our results demonstrated the potential use of Y. lipolytica as a promising microbial cell factory for PHA production using food waste, which contains lipids and other essential nutrients.

  3. Medium-chain sugar amphiphiles: a new family of healthy vegetable oil structuring agents.

    PubMed

    Jadhav, Swapnil R; Hwang, Hyeondo; Huang, Qingrong; John, George

    2013-12-11

    Vegetable oils are frequently structured to enhance their organoleptic and mechanical properties. This is usually achieved by increasing the net amount of saturated and/or trans fatty acids in the oil. With the risk of coronary heart diseases associated with these fatty acids, the food industry is looking for better alternatives. In this context, the medium-chain dialkanoates of low-calorie sugars (sugar alcohol dioctanoates) are investigated as a healthy alternative structuring agent. Precursors of sugar amphiphiles, being FDA-approved GRAS materials, exhibited high cell viability at a concentration ~50 μg/mL. They readily formed nanoscale multilayered structures in an oil matrix to form a coherent network at low concentrations (1-3 wt %/v), which immobilized a wide range of oils (canola, soybean, and grapeseed oils). The structuring efficiency of sugar amphiphiles was computed in terms of mechanical, thermal, and structural properties and found to be a function of its type and concentration.

  4. Medium chain fatty acid ethyl esters - activation of antimicrobial effects by Malassezia enzymes.

    PubMed

    Mayser, Peter

    2015-04-01

    Free medium and short chain fatty acids are known to have broad antimicrobial activity. However, their practical use in topical therapy is limited by their intensive smell and acidity. Surprisingly, a nearly identical antimicrobial effect was found with the ethyl ester derivatives of these fatty acids, but only against Malassezia (M.) yeast, not against Candida spp. Obviously, these esters are hydrolysed by M. enzymes, thus generating a selective activation of antimicrobial activity especially in areas well populated with these yeast ('targeting'). Octanoic acid ethyl ester (CAS 106-32-1) was found to be most suitable. In an agar dilution test, the minimal inhibitory concentrations against M. globosa, M. pachydermatis and M. sympodialis, respectively, ranged between ~5 and 10 mmol l(-1) after 10 days of incubation. The effect started immediately and was not delayed by other lipid sources applied simultaneously. Based on these data, fatty acid monoesters may represent a new therapeutic concept in M.-associated diseases. PMID:25676074

  5. Microextraction method of medium and long chain fatty acids from milk.

    PubMed

    Añorve-Morga, Javier; Castañeda-Ovando, Araceli; Cepeda-Saez, Alberto; Archibold, Armando Durant; Jaimez-Ordaz, Judith; Contreras-López, Elizabeth; González-Olivares, Luis Guillermo; Rodríguez-Rodríguez, José Luis

    2015-04-01

    The aim of this research was to develop a method for microextraction and quantification of long and medium chain fatty acids from milk. The proposed method was carried out on three steps: (1) lipids extraction from 10 μL of whole or skimmed milk containing omega-3 fatty acids (FAs) during 12, 24, 48, 72 and 96 h, in 2 mL chloroform: methanol mixture (2:1); (2) acid methylation of FAs; and (3) quantification of FAs methyl esters by gas chromatography. Using this method, the percentage recovery of FAs was higher (67% for whole and 85% for skimmed milk) compared with AOAC method 905.02 recovery (49% and 83%, respectively). Good reproducibility and repeatability (<3%) were obtained. The method developed can be useful for researching and in routine quality control. Additionally, it is simpler, faster and cheaper than the reference procedure since it requires minimum sample and solvents volume as well as fewer steps.

  6. Crystallization and its effect on the mechanical properties of a medium chain length polyhydroxyalkanoate.

    PubMed

    Larrañaga, A; Fernández, J; Vega, A; Etxeberria, A; Ronchel, C; Adrio, J L; Sarasua, J R

    2014-11-01

    Medium chain length polyhydroxyalkanoates (mcl-PHAs) could play a role in the growing demand for highly elastic and biodegradable materials in the medical field. In this study, a poly(3-hydroxyoctanoate-co-3-hydroxyhexanoate) (P(3HO-co-3HH)) was first fully characterized in terms of molecular weight, microstructural chain parameters and chemical structure by means of gel permeation chromatography (GPC), nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR). As determined by NMR, the synthesized polymer contained 94.3% and 5.7% molar content of 3-hydroxyoctanoate and 3-hydroxyhexanoate, respectively. Since mechanical properties are closely related to thermal history, the effect of crystallization on tensile properties was also investigated in the present study. Three crystallization temperatures were selected (0, 23 and 37°C), the conclusion reached is that the maximum crystallization rate for this copolymer was achieved at 0°C. On the other hand, evolution of tensile properties of P(3HO-co-3HH) films stored at room temperature demonstrated that, as crystallization occurred toward the equilibrium state, the polymer underwent a stiffening process. In this sense, secant modulus and tensile strength increased respectively from 8.3 ± 1.0 MPa and 6.4 ± 0.8 MPa after 1 day stored at room temperature to 36.2 ± 3.3 MPa and 16.3 ± 2.1 MPa after 16 weeks.

  7. Absorption enhancement of rectally infused cefoxitin by medium chain monoglycerides in conscious rats.

    PubMed

    Watanabe, Y; van Hoogdalem, E J; de Boer, A G; Breimer, D D

    1988-10-01

    The enhancing effect of the medium chain monoglycerides glyceryl-1-monoctanoate (GMO), glyceryl-1-monodecanoate (GMD), and glyceryl-1-monododecanoate (GMDD) on rectal absorption of the cephalosporin antibiotic cefoxitin [(6R,7S)-3-hydroxymethyl)-7-methoxy-8-oxo-7-[2-(2-thienyl)acetamido]-5- thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid carbamate (ester)] was investigated in unanesthetized rats. Rectal infusion of 3 mg of cefoxitin sodium without monoglyceride resulted in a mean bioavailability of 31 +/- 18% and a mean residence time (MRT) of 134 +/- 44 min. Coadministration with 53% (w/w) GMO significantly enhanced cefoxitin absorption, resulting in a mean bioavailability of 84 +/- 11% and a mean MRT of 75 +/- 8 min. In a lower concentration, GMD (13% w/w) also significantly promoted cefoxitin bioavailability to 68 +/- 14% and reduced MRT to 70 +/- 11 min. With GMDD only, a trend of increasing bioavailability with increasing monoglyceride concentration was observed, which may be explained by its limited aqueous solubility. Concerning the action of GMO and GMD, the longer monoglyceride is, in terms of effective concentration, more potent in enhancing the extent and rate of cefoxitin absorption. However, a further increase in chain length results in a loss of effect, indicating that the effect of monoglycerides on drug absorption may be determined by their intrinsic absorption enhancing action and solubility.

  8. Characterization of a Novel Subgroup of Extracellular Medium-Chain-Length Polyhydroxyalkanoate Depolymerases from Actinobacteria

    PubMed Central

    Gangoiti, Joana; Santos, Marta; Prieto, María Auxiliadora; de la Mata, Isabel; Llama, María J.

    2012-01-01

    Nineteen medium-chain-length (mcl) poly(3-hydroxyalkanoate) (PHA)-degrading microorganisms were isolated from natural sources. From them, seven Gram-positive and three Gram-negative bacteria were identified. The ability of these microorganisms to hydrolyze other biodegradable plastics, such as short-chain-length (scl) PHA, poly(ε-caprolactone) (PCL), poly(ethylene succinate) (PES), and poly(l-lactide) (PLA), has been studied. On the basis of the great ability to degrade different polyesters, Streptomyces roseolus SL3 was selected, and its extracellular depolymerase was biochemically characterized. The enzyme consisted of one polypeptide chain of 28 kDa with a pI value of 5.2. Its maximum activity was observed at pH 9.5 with chromogenic substrates. The purified enzyme hydrolyzed mcl PHA and PCL but not scl PHA, PES, and PLA. Moreover, the mcl PHA depolymerase can hydrolyze various substrates for esterases, such as tributyrin and p-nitrophenyl (pNP)-alkanoates, with its maximum activity being measured with pNP-octanoate. Interestingly, when poly(3-hydroxyoctanoate-co-3-hydroxyhexanoate [11%]) was used as the substrate, the main hydrolysis product was the monomer (R)-3-hydroxyoctanoate. In addition, the genes of several Actinobacteria strains, including S. roseolus SL3, were identified on the basis of the peptide de novo sequencing of the Streptomyces venezuelae SO1 mcl PHA depolymerase by tandem mass spectrometry. These enzymes did not show significant similarity to mcl PHA depolymerases characterized previously. Our results suggest that these distinct enzymes might represent a new subgroup of mcl PHA depolymerases. PMID:22865072

  9. Medium-chain fatty acid reduces lipid accumulation by regulating expression of lipid-sensing genes in human liver cells with steatosis.

    PubMed

    Wang, Baogui; Fu, Jing; Li, Lumin; Gong, Deming; Wen, Xuefang; Yu, Ping; Zeng, Zheling

    2016-01-01

    Accumulation of lipids in the liver can lead to cell dysfunction and steatosis, an important factor in pathogenesis causing non-alcoholic fatty liver disease. The mechanisms related to lipid deposition in the liver, however, remain poorly understood. This study was aimed to investigate the effects of medium-chain fatty acid (MCFA) on the lipolysis and expression of lipid-sensing genes in human liver cells with steatosis. A cellular steatosis model, which is suitable to experimentally investigate the impact of fat accumulation in the liver, was established in human normal liver cells (LO2 cells) with a mixture of free fatty acids (oleate/palmitate, 2:1) at 200 μm for 24 h incubation. MCFA was found to down-regulate expression of liver X receptor-α, sterol regulatory element binding protein-1, acetyl-CoA carboxylase, fatty acid synthase, CD 36 and lipoprotein lipase in this cellular model, and have positive effects on adipose triglyceride lipase and hormone-sensitive lipase. These results suggest that MCFA may reduce lipid accumulation by regulating key lipid-sensing genes in human liver cells with steatosis. PMID:26932533

  10. Evidence for involvement of medium chain acyl-CoA dehydrogenase in the metabolism of phenylbutyrate

    PubMed Central

    Kormanik, Kaitlyn; Kang, Heejung; Cuebas, Dean; Vockley, Jerry; Mohsen, Al-Walid

    2012-01-01

    Sodium phenylbutyrate is used for treating urea cycle disorders, providing an alternative for ammonia excretion. Following conversion to its CoA ester, phenylbutyryl-CoA is postulated to undergo one round of β-oxidation to phenylacetyl-CoA, the active metabolite. Molecular modeling suggests that medium chain acyl-CoA dehydrogenase (MCAD; EC 1.3.99.3), a key enzyme in straight chain fatty acid β-oxidation, could utilize phenylbutyryl-CoA as substrate. Moreover, phenylpropionyl-CoA has been shown to be a substrate for MCAD and its intermediates accumulate in patients with MCAD deficiency. We have examined the involvement of MCAD and other acyl-CoA dehydrogenases (ACADs) in the metabolism of phenylbutyryl-CoA. Anaerobic titration of purified recombinant human MCAD with phenylbutyryl-CoA caused changes in the MCAD spectrum that are similar to those induced by octanoyl-CoA, its bona fide substrate, and unique to the development of the charge transfer ternary complex. The calculated apparent dissociation constant (KD app) for these substrates was 2.16 μM and 0.12 μM, respectively. The MCAD reductive and oxidative half reactions were monitored using the electron transfer flavoprotein (ETF) fluorescence reduction assay. The catalytic efficiency and the Km for phenylbutyryl-CoA were 0.2 mM−1· sec−1 and 5.3 μM compared to 4.0 mM−1· sec−1 and 2.8 μM for octanoyl-CoA. Extracts of wild type and MCAD-deficient lymphoblast cells were tested for the ability to reduce ETF using phenylbutyryl-CoA as substrate. While ETF reduction activity was detected in extracts of wild type cells, it was undetectable in extracts of cells deficient in MCAD. The results are consistent with MCAD playing a key role in phenylbutyrate metabolism. PMID:23141465

  11. Degradation of medium-chain-length polyhydroxyalkanoates in tropical forest and mangrove soils.

    PubMed

    Lim, Siew-Ping; Gan, Seng-Neon; Tan, Irene K P

    2005-07-01

    Bacterial polyhydroxyalkanoates (PHAs) are perceived to be a suitable alternative to petrochemical plastics because they have similar material properties, are environmentally degradable, and are produced from renewable resources. In this study, the in situ degradation of medium-chain-length PHA (PHAMCL) films in tropical forest and mangrove soils was assessed. The PHAMCL was produced by Pseudomonas putida PGA1 using saponified palm kernel oil (SPKO) as the carbon source. After 112 d of burial, there was 16.7% reduction in gross weight of the films buried in acidic forest soil (FS), 3.0% in the ones buried in alkaline forest soil by the side of a stream (FSst) and 4.5% in those buried in mangrove soil (MS). There was a slight decrease in molecular weight for the films buried in FS but not for the films buried in FSst and in MS. However, no changes were observed for the melting temperature, glass transition temperature, monomer compositions, structure, and functional group analyses of the films from any of the burial sites during the test period. This means that the integral properties of the films were maintained during that period and degradation was by surface erosion. Scanning electron microscopy of the films from the three sites revealed holes on the film surfaces which could be attributed to attack by microorganisms and bigger organisms such as detritivores. For comparison purposes, films of polyhydroxybutyrate (PHB), a short-chain-length PHA, and polyethylene (PE) were buried together with the PHAMCL films in all three sites. The PHB films disintegrated completely in MS and lost 73.5% of their initial weight in FSst, but only 4.6% in FS suggesting that water movement played a major role in breaking up the brittle PHB films. The PE films did not register any weight loss in any of the test sites. PMID:16014996

  12. cDNA cloning of rat and human medium chain acyl-CoA dehydrogenase (MCAD)

    SciTech Connect

    Matsubara, Y.; Kraus, J.P.; Rosenberg, L.E.; Tanaka, K.

    1986-05-01

    MCAD is one of three mitochondrial flavoenzymes which catalyze the first step in the ..beta..-oxidation of straight chain fatty acids. It is a tetramer with a subunit Mr of 45 kDa. MCAD is synthesized in the cytosol as a 49 kDa precursor polypeptide (pMCAD), imported into mitochondria, and cleaved to the mature form. Genetic deficiency of MCAD causes recurrent episodes of hypoglycemic coma accompanied by medium chain dicarboxylic aciduria. Employing a novel approach, the authors now report isolation of partial rat and human cDNA clones encoding pMCAD. mRNA encoding pMCAD was purified to near homogeneity by polysome immunoadsorption using polyclonal monospecific antibody. Single-stranded (/sup 32/P)labeled cDNA probe was synthesized using the enriched mRNA as template, and was used to screen directly 16,000 colonies from a total rat liver cDNA library constructed in pBR322. One clone (600 bp) was detected by in situ hybridization. Hybrid-selected translation with this cDNA yielded a 49 kDa polypeptide indistinguishable in size from rat pMCAD and immunoprecipitable with anti-MCAD antibody. Using the rat cDNA as probe, 43,000 colonies from a human liver cDNA library were screened. Four identical positive clones (400 bp) were isolated and positively identified by hybrid-selected translation and immunoprecipitation. The sizes of rat and human mRNAs encoding pMCAD were 2.2 kb and 2.4 kb, respectively, as determined by Northern blotting.

  13. A medium-chain fatty acid as an alternative energy source in mouse preimplantation development.

    PubMed

    Yamada, Mitsutoshi; Takanashi, Kazumi; Hamatani, Toshio; Hirayama, Akiyoshi; Akutsu, Hidenori; Fukunaga, Tomoko; Ogawa, Seiji; Sugawara, Kana; Shinoda, Kosaku; Soga, Tomoyoshi; Umezawa, Akihiro; Kuji, Naoaki; Yoshimura, Yasunori; Tomita, Masaru

    2012-01-01

    To further optimize the culturing of preimplantation embryos, we undertook metabolomic analysis of relevant culture media using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). We detected 28 metabolites: 23 embryo-excreted metabolites including 16 amino acids and 5 media-derived metabolites (e.g., octanoate, a medium-chain fatty acid (MCFA)). Due to the lack of information on MCFAs in mammalian preimplantation development, this study examined octanoate as a potential alternative energy source for preimplantation embryo cultures. No embryos survived in culture media lacking FAs, pyruvate, and glucose, but supplementation of octanoate rescued the embryonic development. Immunoblotting showed significant expression of acyl-CoA dehydrogenase and hydroxyacyl-CoA dehydrogenase, important enzymes for ß-oxidation of MCFAs, in preimplantation embryo. Furthermore, CE-TOFMS traced [1-(13)C(8)] octanoate added to the culture media into intermediate metabolites of the TCA cycle via ß-oxidation in mitochondria. These results are the first demonstration that octanoate could provide an efficient alternative energy source throughout preimplantation development.

  14. Antimicrobial effects of virgin coconut oil and its medium-chain fatty acids on Clostridium difficile.

    PubMed

    Shilling, Michael; Matt, Laurie; Rubin, Evelyn; Visitacion, Mark Paul; Haller, Nairmeen A; Grey, Scott F; Woolverton, Christopher J

    2013-12-01

    Clostridium difficile is the leading cause of hospital-acquired antibiotic-associated diarrhea worldwide; in addition, the proliferation of antibiotic-resistant C. difficile is becoming a significant problem. Virgin coconut oil (VCO) has been shown previously to have the antimicrobial activity. This study evaluates the lipid components of VCO for the control of C. difficile. VCO and its most active individual fatty acids were tested to evaluate their antimicrobial effect on C. difficile in vitro. The data indicate that exposure to lauric acid (C12) was the most inhibitory to growth (P<.001), as determined by a reduction in colony-forming units per milliliter. Capric acid (C10) and caprylic acid (C8) were inhibitory to growth, but to a lesser degree. VCO did not inhibit the growth of C. difficile; however, growth was inhibited when bacterial cells were exposed to 0.15-1.2% lipolyzed coconut oil. Transmission electron microscopy (TEM) showed the disruption of both the cell membrane and the cytoplasm of cells exposed to 2 mg/mL of lauric acid. Changes in bacterial cell membrane integrity were additionally confirmed for VCO and select fatty acids using Live/Dead staining. This study demonstrates the growth inhibition of C. difficile mediated by medium-chain fatty acids derived from VCO.

  15. Preparation and characterization of nanoliposomes entrapping medium-chain fatty acids and vitamin C by lyophilization.

    PubMed

    Yang, Shuibing; Liu, Chengmei; Liu, Wei; Yu, Haixia; Zheng, Huijuan; Zhou, Wei; Hu, Yaqin

    2013-01-01

    The complex nanoliposomes encapsulating both a hydrophilic drug vitamin C (vit C) and hydrophobic drug medium-chain fatty acids (MCFAs) was prepared by combining double emulsion method with dynamic high pressure microfluidization. The complex nanoliposomes was further freeze-dried under -86 °C for 48 h with sucrose at the sucrose/lipids ratio of 2:1(w/w) in order to enhance its stability. The freeze-dried complex nanoliposomes under the suitable conditions exhibited high entrapment efficiency of MCFAs (44.26 ± 3.34)%, relatively high entrapment efficiency of vit C (62.25 ± 3.43)%, low average size diameter (110.4 ± 7.28) nm and good storage stability at 4 °C for 60 days with slight changes in mean particle diameter and drug entrapment efficiencies. The results of transmission electron microscopy of freeze-dried complex nanoliposomes also showed that the freeze-dried samples with sucrose were stable without great increase in their particle sizes and without destroying their spherical shape. The results indicated that sucrose presented well protection effects in MCFAs-vit C complex nanoliposomes, suggesting the possibility of further usage in commercial liposomes. PMID:24084723

  16. A medium-chain fatty acid as an alternative energy source in mouse preimplantation development

    PubMed Central

    Yamada, Mitsutoshi; Takanashi, Kazumi; Hamatani, Toshio; Hirayama, Akiyoshi; Akutsu, Hidenori; Fukunaga, Tomoko; Ogawa, Seiji; Sugawara, Kana; Shinoda, Kosaku; Soga, Tomoyoshi; Umezawa, Akihiro; Kuji, Naoaki; Yoshimura, Yasunori; Tomita, Masaru

    2012-01-01

    To further optimize the culturing of preimplantation embryos, we undertook metabolomic analysis of relevant culture media using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). We detected 28 metabolites: 23 embryo-excreted metabolites including 16 amino acids and 5 media-derived metabolites (e.g., octanoate, a medium-chain fatty acid (MCFA)). Due to the lack of information on MCFAs in mammalian preimplantation development, this study examined octanoate as a potential alternative energy source for preimplantation embryo cultures. No embryos survived in culture media lacking FAs, pyruvate, and glucose, but supplementation of octanoate rescued the embryonic development. Immunoblotting showed significant expression of acyl-CoA dehydrogenase and hydroxyacyl-CoA dehydrogenase, important enzymes for ß-oxidation of MCFAs, in preimplantation embryo. Furthermore, CE-TOFMS traced [1-13C8] octanoate added to the culture media into intermediate metabolites of the TCA cycle via ß-oxidation in mitochondria. These results are the first demonstration that octanoate could provide an efficient alternative energy source throughout preimplantation development. PMID:23226596

  17. Medium-chain Fatty Acid-sensing Receptor, GPR84, Is a Proinflammatory Receptor

    PubMed Central

    Suzuki, Masakatsu; Takaishi, Sachiko; Nagasaki, Miyuki; Onozawa, Yoshiko; Iino, Ikue; Maeda, Hiroaki; Komai, Tomoaki; Oda, Tomiichiro

    2013-01-01

    G protein-coupled receptor 84 (GPR84) is a putative receptor for medium-chain fatty acids (MCFAs), whose pathophysiological roles have not yet been clarified. Here, we show that GPR84 was activated by MCFAs with the hydroxyl group at the 2- or 3-position more effectively than nonhydroxylated MCFAs. We also identified a surrogate agonist, 6-n-octylaminouracil (6-OAU), for GPR84. These potential ligands and the surrogate agonist, 6-OAU, stimulated [35S]GTP binding and accumulated phosphoinositides in a GPR84-dependent manner. The surrogate agonist, 6-OAU, internalized GPR84-EGFP from the cell surface. Both the potential ligands and 6-OAU elicited chemotaxis of human polymorphonuclear leukocytes (PMNs) and macrophages and amplified LPS-stimulated production of the proinflammatory cytokine IL-8 from PMNs and TNFα from macrophages. Furthermore, the intravenous injection of 6-OAU raised the blood CXCL1 level in rats, and the inoculation of 6-OAU into the rat air pouch accumulated PMNs and macrophages in the site. Our results indicate a proinflammatory role of GPR84, suggesting that the receptor may be a novel target to treat chronic low grade inflammation associated-disease. PMID:23449982

  18. Role of Conserved Glycine in Zinc-dependent Medium Chain Dehydrogenase/Reductase Superfamily*

    PubMed Central

    Tiwari, Manish Kumar; Singh, Raushan Kumar; Singh, Ranjitha; Jeya, Marimuthu; Zhao, Huimin; Lee, Jung-Kul

    2012-01-01

    The medium-chain dehydrogenase/reductase (MDR) superfamily consists of a large group of enzymes with a broad range of activities. Members of this superfamily are currently the subject of intensive investigation, but many aspects, including the zinc dependence of MDR superfamily proteins, have not yet have been adequately investigated. Using a density functional theory-based screening strategy, we have identified a strictly conserved glycine residue (Gly) in the zinc-dependent MDR superfamily. To elucidate the role of this conserved Gly in MDR, we carried out a comprehensive structural, functional, and computational analysis of four MDR enzymes through a series of studies including site-directed mutagenesis, isothermal titration calorimetry, electron paramagnetic resonance (EPR), quantum mechanics, and molecular mechanics analysis. Gly substitution by other amino acids posed a significant threat to the metal binding affinity and activity of MDR superfamily enzymes. Mutagenesis at the conserved Gly resulted in alterations in the coordination of the catalytic zinc ion, with concomitant changes in metal-ligand bond length, bond angle, and the affinity (Kd) toward the zinc ion. The Gly mutants also showed different spectroscopic properties in EPR compared with those of the wild type, indicating that the binding geometries of the zinc to the zinc binding ligands were changed by the mutation. The present results demonstrate that the conserved Gly in the GHE motif plays a role in maintaining the metal binding affinity and the electronic state of the catalytic zinc ion during catalysis of the MDR superfamily enzymes. PMID:22500022

  19. The n-3 long-chain PUFAs modulate the impact of the GCKR Pro446Leu polymorphism on triglycerides in adolescents[S

    PubMed Central

    Rousseaux, Julien; Duhamel, Alain; Dumont, Julie; Dallongeville, Jean; Molnar, Denes; Widhalm, Kurt; Manios, Yannis; Sjöström, Michael; Kafatos, Anthony; Breidenassel, Christina; Gonzales-Gross, Marcela; Cuenca-Garcia, Magdalena; Censi, Laura; Ascensión, Marcos; De Henauw, Stefaan; Moreno, Luis A.; Meirhaeghe, Aline; Gottrand, Frédéric

    2015-01-01

    Dietary n-3 long-chain PUFAs (LC-PUFAs) are associated with improvement in the parameters of the metabolic syndrome (MetS). Glucokinase regulatory protein (GCKR) is a key protein regulating intracellular glucose disposal. Our aim was to investigate: i) the relationship between the GCKR rs1260326 (Pro446Leu) polymorphism and parameters of the MetS; and ii) a potential influence of n-3 and n-6 LC-PUFA levels on this relationship in the HELENA study (1,155 European adolescents). Linear regression analyses were performed to study the association between rs1260326 and the outcomes of interest. Interactions between rs1260326 and LC-PUFA levels on outcomes were explored. The T allele of rs1260326 was associated with higher serum TG concentrations compared with the C allele. In contrast to n-6 LC-PUFA levels, a significant interaction (P = 0.01) between rs1260326 and total n-3 LC-PUFA levels on serum TG concentrations was observed. After stratification on the n-3 LC-PUFA median values, the association between rs1260326 and TG concentration was significant only in the group with high n-3 LC-PUFA levels. In conclusion, this is the first evidence that n-3 LC-PUFAs may modulate the impact of the GCKR rs1260326 polymorphism on TG concentrations in adolescents. Several molecular mechanisms, in link with glucose uptake, could explain these findings. PMID:26136510

  20. The n-3 long-chain PUFAs modulate the impact of the GCKR Pro446Leu polymorphism on triglycerides in adolescents.

    PubMed

    Rousseaux, Julien; Duhamel, Alain; Dumont, Julie; Dallongeville, Jean; Molnar, Denes; Widhalm, Kurt; Manios, Yannis; Sjöström, Michael; Kafatos, Anthony; Breidenassel, Christina; Gonzales-Gross, Marcela; Cuenca-Garcia, Magdalena; Censi, Laura; Ascensión, Marcos; De Henauw, Stefaan; Moreno, Luis A; Meirhaeghe, Aline; Gottrand, Frédéric

    2015-09-01

    Dietary n-3 long-chain PUFAs (LC-PUFAs) are associated with improvement in the parameters of the metabolic syndrome (MetS). Glucokinase regulatory protein (GCKR) is a key protein regulating intracellular glucose disposal. Our aim was to investigate: i) the relationship between the GCKR rs1260326 (Pro446Leu) polymorphism and parameters of the MetS; and ii) a potential influence of n-3 and n-6 LC-PUFA levels on this relationship in the HELENA study (1,155 European adolescents). Linear regression analyses were performed to study the association between rs1260326 and the outcomes of interest. Interactions between rs1260326 and LC-PUFA levels on outcomes were explored. The T allele of rs1260326 was associated with higher serum TG concentrations compared with the C allele. In contrast to n-6 LC-PUFA levels, a significant interaction (P = 0.01) between rs1260326 and total n-3 LC-PUFA levels on serum TG concentrations was observed. After stratification on the n-3 LC-PUFA median values, the association between rs1260326 and TG concentration was significant only in the group with high n-3 LC-PUFA levels. In conclusion, this is the first evidence that n-3 LC-PUFAs may modulate the impact of the GCKR rs1260326 polymorphism on TG concentrations in adolescents. Several molecular mechanisms, in link with glucose uptake, could explain these findings.

  1. The n-3 long-chain PUFAs modulate the impact of the GCKR Pro446Leu polymorphism on triglycerides in adolescents.

    PubMed

    Rousseaux, Julien; Duhamel, Alain; Dumont, Julie; Dallongeville, Jean; Molnar, Denes; Widhalm, Kurt; Manios, Yannis; Sjöström, Michael; Kafatos, Anthony; Breidenassel, Christina; Gonzales-Gross, Marcela; Cuenca-Garcia, Magdalena; Censi, Laura; Ascensión, Marcos; De Henauw, Stefaan; Moreno, Luis A; Meirhaeghe, Aline; Gottrand, Frédéric

    2015-09-01

    Dietary n-3 long-chain PUFAs (LC-PUFAs) are associated with improvement in the parameters of the metabolic syndrome (MetS). Glucokinase regulatory protein (GCKR) is a key protein regulating intracellular glucose disposal. Our aim was to investigate: i) the relationship between the GCKR rs1260326 (Pro446Leu) polymorphism and parameters of the MetS; and ii) a potential influence of n-3 and n-6 LC-PUFA levels on this relationship in the HELENA study (1,155 European adolescents). Linear regression analyses were performed to study the association between rs1260326 and the outcomes of interest. Interactions between rs1260326 and LC-PUFA levels on outcomes were explored. The T allele of rs1260326 was associated with higher serum TG concentrations compared with the C allele. In contrast to n-6 LC-PUFA levels, a significant interaction (P = 0.01) between rs1260326 and total n-3 LC-PUFA levels on serum TG concentrations was observed. After stratification on the n-3 LC-PUFA median values, the association between rs1260326 and TG concentration was significant only in the group with high n-3 LC-PUFA levels. In conclusion, this is the first evidence that n-3 LC-PUFAs may modulate the impact of the GCKR rs1260326 polymorphism on TG concentrations in adolescents. Several molecular mechanisms, in link with glucose uptake, could explain these findings. PMID:26136510

  2. Preparation and evaluation of easy energy supply property of medium-chain fatty acids liposomes.

    PubMed

    Liu, Weilin; Liu, Wei; Liu, Chengmei; Liu, Jianhua; Zheng, Huijuan; Yang, Shuibing; Su, Jiahong

    2011-01-01

    To develop an easy-energy-supply agent, medium-chain fatty acids (MCFAs) liposomes were prepared by thin-layer dispersion, freeze-thawing and dynamic high pressure microfluidization (DHPM)-freeze-thawing methods. Results showed that MCFAs nanoliposomes obtained by the novel method (DHPM-freeze-thawing) exhibited a smaller size (72.6 ± 4.9 nm), narrower size distribution (PDI = 0.175 ± 0.005), higher zeta potential (-41.27 ± 1.16 mV) and entrapment efficiency (45.9 ± 6.0%) compared to the other two methods. In the weight-loaded swimming test of the mice, the high-dose group of MCFAs nanoliposomes indicated a significantly longer swimming time (105 ± 31 min, p < 0.05), a lower serum urea nitrogen (839.5 ± 111.9 mg/L, p < 0.05) and blood lactic acid (5.7 ± 1.0 mmol/L, p ≤ 0.001), and a higher hepatic glycogen (15.0 ± 3.6 mg/g, p ≤ 0.001) than those of the control group (53 ± 13 min, 1153.6 ± 102.5 mg/L, 12.5 ± 1.9 mmol/L and 8.8 ± 3.3 mg/g, respectively). However, no significant difference was found between the high-dose group and MCFAs group. The results suggested that MCFAs nanoliposomes could be used as a potential easy-energy-supply agent. PMID:21970656

  3. Production of medium chain length polyhydroxyalkanoate in metabolic flux optimized Pseudomonas putida

    PubMed Central

    2014-01-01

    Background Pseudomnas putida is a natural producer of medium chain length polyhydroxyalkanoates (mcl-PHA), a polymeric precursor of bioplastics. A two-fold increase of mcl-PHA production via inactivation of the glucose dehydrogenase gene gcd, limiting the metabolic flux towards side products like gluconate was achieved before. Here, we investigated the overproduction of enzymes catalyzing limiting steps of mcl-PHA precursor formation. Results A genome-based in silico model for P. putida KT2440 metabolism was employed to identify potential genetic targets to be engineered for the improvement of mcl-PHA production using glucose as sole carbon source. Here, overproduction of pyruvate dehydrogenase subunit AcoA in the P. putida KT2440 wild type and the Δgcd mutant strains led to an increase of PHA production. In controlled bioreactor batch fermentations PHA production was increased by 33% in the acoA overexpressing wild type and 121% in the acoA overexpressing Δgcd strain in comparison to P. putida KT2440. Overexpression of pgl-encoding 6-phosphoglucolactonase did not influence PHA production. Transcriptome analyses of engineered PHA producing P. putida in comparison to its parental strains revealed the induction of genes encoding glucose 6-phosphate dehydrogenase and pyruvate dehydrogenase. In addition, NADPH seems to be quantitatively consumed for efficient PHA synthesis, since a direct relationship between low levels of NADPH and high concentrations of the biopolymer were observed. In contrast, intracellular levels of NADH were found increased in PHA producing organisms. Conclusion Production of mcl-PHAs was enhanced in P. putida when grown on glucose via overproduction of a pyruvate dehydrogenase subunit (AcoA) in combination with a deletion of the glucose dehydrogenase (gcd) gene as predicted by in silico elementary flux mode analysis. PMID:24948031

  4. Production and characterization of medium-chain-length polyhydroxyalkanoates by Pseudomonas mosselii TO7.

    PubMed

    Chen, Yi-Jr; Huang, Yan-Chia; Lee, Chia-Yin

    2014-08-01

    The polyhydroxyalkanoate (PHA) production and growth of Pseudomonas mosselii TO7, a newly isolated Pseudomonas species from the wastewater of a vegetable oil manufacturing facility, was analyzed. Phenotypic analysis and phylogenetic analysis of the 16S rRNA gene revealed that it is closely related to Pseudomonas mosselii. In the presence of palm kernel and soybean oils, P. mosselii TO7 produced up to 50% cell dry weight (CDW) medium-chain-length (MCL) PHAs comprising high poly(3-hydroxyoctanoate) (P(3HO)) content; P(3HO) content increased to 45% CDW when grown in octanoate using a single-step culture process. The PHA monomer was identified by (13)C nuclear magnetic resonance spectroscopy. The average molecular weight and polydispersity index of PHA were 218.30 ± 31.73 and 2.21 ± 0.18, respectively. The PHA produced by P. mosselii TO7 in the presence of palm kernel oil had two melting temperature (Tm) values of 37.2°C and 55.7°C with melting enthalpy (ΔHm) values of 51.09 J g(-1) and 26.57 J g(-1), respectively. Inhibition analyses using acrylic and 2-bromooctanoic acids revealed β-oxidation as the primary pathway for MCL-PHA biosynthesis using octanoic acid. Moreover, Pseudomonas putida GPp104 PHA(-), harboring the PHA synthase genes of P. mosselii (phaC1pm and phaC2pm) was used for heterologous expression, which demonstrated that phaC1pm is the main PHA synthesis enzyme, and 3-hydroxyoctanoyl-CoA is its major substrate. This was the first report of a P. mosselii TO7 isolate producing high-yield P(3HO) through utilization of plant oils.

  5. Knocking out the MFE-2 gene of Candida bombicola leads to improved medium-chain sophorolipid production.

    PubMed

    Van Bogaert, Inge N A; Sabirova, Julia; Develter, Dirk; Soetaert, Wim; Vandamme, Erick J

    2009-06-01

    The nonpathogenic yeast Candida bombicola synthesizes sophorolipids. These biosurfactants are composed of the disaccharide sophorose linked to a long-chain hydroxy fatty acid and have potential applications in the food, pharmaceutical, cosmetic and cleaning industries. In order to expand the range of application, a shift of the fatty acid moiety towards medium-chain lengths would be recommendable. However, the synthesis of medium-chain sophorolipids by C. bombicola is a challenging objective. First of all, these sophorolipids can only be obtained by fermentations on unconventional carbon sources, which often have a toxic effect on the cells. Furthermore, medium-chain substrates are partially metabolized in the beta-oxidation pathway. In order to redirect unconventional substrates towards sophorolipid synthesis, the beta-oxidation pathway was blocked on the genome level by knocking out the multifunctional enzyme type 2 (MFE-2) gene. The total gene sequence of the C. bombicola MFE-2 (6033 bp) was cloned (GenBank accession number EU371724), and the obtained nucleotide sequence was used to construct a knock-out cassette. Several knock-out mutants with the correct geno- and phenotype were evaluated in a fermentation on 1-dodecanol. All mutants showed a 1.7-2.9 times higher production of sophorolipids, indicating that in those strains the substrate is redirected towards the sophorolipid synthesis.

  6. Enhancement of oral bioavailability of d-alpha-tocopherol acetate by lecithin-dispersed aqueous preparation containing medium-chain triglycerides in rats.

    PubMed

    Kimura, T; Fukui, E; Kageyu, A; Kurohara, H; Kurosaki, Y; Nakayama, T; Morita, Y; Shibusawa, K; Ohsawa, S; Takeda, Y

    1989-02-01

    In order to evaluate oral dosage forms of d-alpha-tocopherol acetate (VEA), d-alpha-tocopherol (VE) concentration in the plasma was examined following oral administration of three VEA preparations; lecithin-dispersed aqueous preparation, polysorbate 80 (PS-80)-solubilized aqueous solution and soybean oil solution. The lecithin-dispersed preparation gave the highest Cmax and the largest AUC0-24h, while Tmax was delayed. In the thoracic duct fistula rat, no increase in VE plasma concentration was observed after intraduodenal administration of lecithin-dispersed VEA preparation via the lymphatic route. The delayed Tmax and prolonged VE plasma concentration obtained with the lecithin-dispersed preparation in comparison with PS-80-solubilized aqueous solution could be explained by the different route of absorption.

  7. Development of paclitaxel-loaded liposomal nanocarrier stabilized by triglyceride incorporation

    PubMed Central

    Hong, Soon-Seok; Choi, Ju Yeon; Kim, Jong Oh; Lee, Mi-Kyung; Kim, So Hee; Lim, Soo-Jeong

    2016-01-01

    Studies have highlighted the challenge of developing injectable liposomes as a paclitaxel (PTX) carrier, a challenge attributable to the limitations in liposomal stability caused by PTX loading. Poor stability of PTX-loaded liposomes is caused by PTX-triggered aggregation or fusion of liposomal membranes and is exacerbated in the presence of PEGylated lipid. In the present study, the effect of triglyceride incorporation on the stability of PTX-loaded/PEGylated liposomes was explored. Incorporation of a medium chain triglyceride Captex 300 into saturated phosphatidylcholine (PC)-based liposomes (1,2-dimyristoyl-sn-glycero-3-phosphocholine [DMPC]:cholesterol [CHOL]:N-(Carbonyl-methoxypolyethyleneglycol 2000)-1, 2-distearoyl-sn-glycero-3-phospho-ethanolamine [PE-PEG]), produced a fine, homogeneous, and membrane-filterable PTX-loaded liposomes fulfilling the requirement of an injectable lipid formulation. Triglyceride incorporation also greatly inhibited the time-dependent leakage of PTX from saturated PC-based liposomes, which appears to be mediated by the inhibition of liposome fusion. In contrast, triglyceride incorporation induced the destabilization and PTX leakage of unsaturated PC-based liposomes, indicating the opposite effect of triglyceride depending on the fluidity status of PC constituting the liposomal membrane. PTX release profile and the in vitro and in vivo anticancer efficacy of triglyceride-incorporated DMPC:CHOL:PE-PEG liposomes were similar to Taxol® while the toxicity of liposomal PTX was significantly lower than that of Taxol. Taken together, triglyceride incorporation provided an injectable PTX formulation by functioning as a formulation stabilizer of PEGylated/saturated PC-based liposomes.

  8. Development of paclitaxel-loaded liposomal nanocarrier stabilized by triglyceride incorporation

    PubMed Central

    Hong, Soon-Seok; Choi, Ju Yeon; Kim, Jong Oh; Lee, Mi-Kyung; Kim, So Hee; Lim, Soo-Jeong

    2016-01-01

    Studies have highlighted the challenge of developing injectable liposomes as a paclitaxel (PTX) carrier, a challenge attributable to the limitations in liposomal stability caused by PTX loading. Poor stability of PTX-loaded liposomes is caused by PTX-triggered aggregation or fusion of liposomal membranes and is exacerbated in the presence of PEGylated lipid. In the present study, the effect of triglyceride incorporation on the stability of PTX-loaded/PEGylated liposomes was explored. Incorporation of a medium chain triglyceride Captex 300 into saturated phosphatidylcholine (PC)-based liposomes (1,2-dimyristoyl-sn-glycero-3-phosphocholine [DMPC]:cholesterol [CHOL]:N-(Carbonyl-methoxypolyethyleneglycol 2000)-1, 2-distearoyl-sn-glycero-3-phospho-ethanolamine [PE-PEG]), produced a fine, homogeneous, and membrane-filterable PTX-loaded liposomes fulfilling the requirement of an injectable lipid formulation. Triglyceride incorporation also greatly inhibited the time-dependent leakage of PTX from saturated PC-based liposomes, which appears to be mediated by the inhibition of liposome fusion. In contrast, triglyceride incorporation induced the destabilization and PTX leakage of unsaturated PC-based liposomes, indicating the opposite effect of triglyceride depending on the fluidity status of PC constituting the liposomal membrane. PTX release profile and the in vitro and in vivo anticancer efficacy of triglyceride-incorporated DMPC:CHOL:PE-PEG liposomes were similar to Taxol® while the toxicity of liposomal PTX was significantly lower than that of Taxol. Taken together, triglyceride incorporation provided an injectable PTX formulation by functioning as a formulation stabilizer of PEGylated/saturated PC-based liposomes. PMID:27660440

  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. Medium-chain chlorinated paraffins (MCCPs): a review of bioaccumulation potential in the aquatic environment.

    PubMed

    Thompson, Roy; Vaughan, Martin

    2014-01-01

    Chlorinated paraffins (CPs) are high molecular weight organochlorine compounds that have been used in a variety of industrial applications for many years. Medium-chain chlorinated paraffins (MCCPs) (CAS 85535-85-9; Alkanes, C14-17 , chloro) are currently under investigation as potential persistent bioaccumulative toxic (PBT) compounds. In this article, the bioaccumulation potential of MCCPs is assessed using a tiered framework proposed after a recent Society of Environmental Toxicology and Chemistry (SETAC) Pellston Workshop in 2008. The framework proposes the use of physicochemical properties and modeling assessment, bioconcentration/bioaccumulation (BCF/BAF) assessment, biomagnification (BMF) assessment, and trophic magnification factor (TMF) assessment. It is hoped that use of this framework could harmonize and improve the efficiency and effectiveness of the chemical substance evaluation screening process for PBT properties. When applied to MCCPs, the following conclusions were made: empirical physiochemical data is available negating the use of models; laboratory BCFs range from 1000 to 15 000 (growth-corrected lipid normalized values) for 2 MCCP structures; field BAFs were an order of magnitude higher than the trigger criterion for "B status possible"; although results may not meet acceptance criteria for field studies, laboratory-derived BMFs for a number of C14-17 chlorinated alkanes were less than the trigger value of 1 (based on whole-body concentrations) whereas field-derived BMFs were less than 1 (based on lipid corrected values [generally used for field data] excluding one measure for sculpin, [Cottus cognatus]-Diporeia that was based on only one detectable sample); and finally, TMFs were less than the trigger criterion value of 1, which are considered the most convincing evidence for bioaccumulative properties of a compound and the "Gold Standard" measure of bioaccumulation. This article also discusses the uncertainties surrounding the published data

  11. Gut triglyceride production.

    PubMed

    Pan, Xiaoyue; Hussain, M Mahmood

    2012-05-01

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

  12. Medium-chain versus long-chain triacylglycerol emulsion hydrolysis by lipoprotein lipase and hepatic lipase: Implications for the mechanisms of lipase action

    SciTech Connect

    Deckelbaum, R.J. ); Hamilton, J.A.; Butbul, E.; Gutman, A. ); Moser, A. ); Bengtsson-Olivecrona, G.; Olivecrona, T. ); Carpentier, Y.A. )

    1990-02-06

    To explore how enzyme affinities and enzyme activities regulate hydrolysis of water-insoluble substrates, the authors compared hydrolysis of phospholipid-stabilized emulsions of medium-chain (MCT) versus long-chain triacylglycerols (LCT). Because substrate solubility at the emulsion surface might modulate rates of hydrolysis, the ability of egg yolk phosphatidylcholine to solubilize MCT was examined by NMR spectroscopy. Chemical shift measurements showed that 11 mol % of ({sup 13}C)carbonyl enriched trioctanoin was incorporated into phospholipid vesicles as a surface component. Line widths of trioctanoin surface peaks were half that of LCT, and relaxation times, T{sub 1}, were also shorter for trioctanoin, showing greater mobility for MCT in phospholipid. In assessing the effects of these differences in solubility on lipolysis, they found that both purified bovine milk lipoprotein lipase and human hepatic lipase hydrolyzed MCT at rates at least 2-fold higher than for LCT. Differences in affinity were also demonstrated in mixed incubations where increasing amounts of LCT emulsion resulted in decreased hydrolysis of MCT emulsions. These results suggest that despite lower enzyme affinity for MCT emulsions, shorter chain triacylglycerols are more readily hydrolyzed by lipoprotein and hepatic lipases than long-chain triacylglycerols because of greater MCT solubility and mobility at the emulsion-water interface.

  13. Poly(ethylene glycol)-mediated molar mass control of short-chain- and medium-chain-length poly(hydroxyalkanoates) from Pseudomonas oleovorans.

    PubMed

    Ashby, R D; Solaiman, D K Y; Foglia, T A

    2002-10-01

    Three strains of Pseudomonas oleovorans, a well known poly(hydroxyalkanoate) (PHA) producer, were tested for the ability to control PHA molar mass and end group structure by addition of poly(ethylene glycol) (PEG) to the fermentation medium. Each strain of P. oleovorans - NRRL B-14682 (B-14682), NRRL B-14683 (B-14683), and NRRL B-778 (B-778) - synthesized a different type of PHA from oleic acid when cultured under identical growth conditions. Strain B-14682 produced poly(3-hydroxybutyrate) (PHB), while B-14683 synthesized a medium-chain-length PHA ( mcl-PHA) with a repeat unit composition ranging from C4 to C14 and some mono-unsaturation in the C14 alkyl side chains. Strain B-778 synthesized a mixture of PHB (95 mol%) and mcl-PHA (5 mol%). The addition of 0.5% (v/v) PEG (M(n) =200 g/mol, PEG-200) to the fermentation broth of strains B-14682 and B-778 resulted in chain termination through esterification at the carboxyl terminus of the PHB with PEG chain segments, thus reducing the molar mass by 54% and 23%, respectively. The molar mass of the mcl-PHA produced by strains B-14683 and B-778 also showed a 34% and 47% reduction in the presence of PEG-200, respectively, but no evidence of esterification was present. PEG-400 (M(n) =400 g/mol) had a reduced effect on PHA molar mass. In fact, the molar masses of the mcl-PHA derived from strain B-14683 and both the PHB and mcl-PHA from B-778 were unchanged by PEG-400. In contrast, the PHB produced by B-14682 showed a 35% reduction in molar mass in the presence of PEG-400. PMID:12382057

  14. Analytical solution to the diffusion, sorption and decay chain equation in a saturated porous medium between two reservoirs.

    PubMed

    Guzman, Juan; Maximov, Serguei; Escarela-Perez, Rafael; López-García, Irvin; Moranchel, Mario

    2015-01-01

    The diffusion and distribution coefficients are important parameters in the design of barrier systems used in radioactive repositories. These coefficients can be determined using a two-reservoir configuration, where a saturated porous medium is allocated between two reservoirs filled by stagnant water. One of the reservoirs contains a high concentration of radioisotopes. The goal of this work is to obtain an analytical solution for the concentration of all radioisotopes in the decay chain of a two-reservoir configuration. The analytical solution must be obtained by taking into account the diffusion and sorption processes. Concepts such as overvalued concentration, diffusion and decay factors are employed to this end. It is analytically proven that a factor of the solution is identical for all chains (considering a time scaling factor), if certain parameters do not change. In addition, it is proven that the concentration sensitivity, due to the distribution coefficient variation, depends of the porous medium thickness, which is practically insensitive for small porous medium thicknesses. The analytical solution for the radioisotope concentration is compared with experimental and numerical results available in literature.

  15. Fatty acid oxidation and its impact on response of spontaneously hypertensive rat hearts to an adrenergic stress: benefits of a medium-chain fatty acid.

    PubMed

    Labarthe, François; Khairallah, Maya; Bouchard, Bertrand; Stanley, William C; Des Rosiers, Christine

    2005-03-01

    The spontaneously hypertensive rat (SHR) is a model of cardiomyopathy characterized by a restricted use of exogenous long-chain fatty acid (LCFA) for energy production. The aims of the present study were to document the functional and metabolic response of the SHR heart under conditions of increased energy demand and the effects of a medium-chain fatty acid (MCFA; octanoate) supplementation in this situation. Hearts were perfused ex vivo in a working mode with physiological concentrations of substrates and hormones and subjected to an adrenergic stimulation (epinephrine, 10 microM). (13)C-labeled substrates were used to assess substrate selection for energy production. Compared with control Wistar rat hearts, SHR hearts showed an impaired response to the adrenergic stimulation as reflected by 1) a smaller increase in contractility and developed pressure, 2) a faster decline in the aortic flow, and 3) greater cardiac tissue damage (lactate dehydrogenase release: 1,577 +/- 118 vs. 825 +/- 44 mU/min, P < 0.01). At the metabolic level, SHR hearts presented 1) a reduced exogenous LCFA contribution to the citric acid cycle flux (16 +/- 1 vs. 44 +/- 4%, P < 0.001) and an enhanced contribution of endogenous substrates (20 +/- 4 vs. 1 +/- 4%, P < 0.01); and 2) an increased lactate production from glycolysis, with a greater lactate-to-pyruvate production ratio. Addition of 0.2 mM octanoate reduced lactate dehydrogenase release (1,145 +/- 155 vs. 1,890 +/- 89 mU/min, P < 0.001) and increased exogenous fatty acid contribution to energy metabolism (23.7 +/- 1.3 vs. 15.8 +/- 0.8%, P < 0.01), which was accompanied by an equivalent decrease in unlabeled endogenous substrate contribution, possibly triglycerides (11.6 +/- 1.5 vs. 19.0 +/- 1.2%, P < 0.01). Taken altogether, these results demonstrate that the SHR heart shows an impaired capacity to withstand an acute adrenergic stress, which can be improved by increasing the contribution of exogenous fatty acid oxidation to energy

  16. Engineering Escherichia coli for odd straight medium chain free fatty acid production.

    PubMed

    Wu, Hui; San, Ka-Yiu

    2014-10-01

    Microbial biosynthesis of free fatty acids (FFAs) can be achieved by introducing an acyl-acyl carrier protein thioesterase gene into Escherichia coli. The engineered E. coli usually produced even chain FFAs. In this study, propionyl-CoA synthetase (prpE) from Salmonella enterica was overexpressed in two efficient even chain FFAs producers, ML103 (pXZM12) carrying the acyl-ACP thioesterase gene from Umbellularia californica and ML103 (pXZ18) carrying the acyl-ACP thioesterase gene from Ricinus communis combined with supplement of extracellular propionate. With these metabolically engineered E. coli, the odd straight chain FFAs, undecanoic acid (C11:0), tridecanoic acid (C13:0), and pentadecanoic acid (C15:0) were produced from glucose and propionate. The highest total odd straight chain FFAs produced by ML103 (pXZM12, pBAD-prpE) reached 276 mg/l with a ratio of 23.43 % of the total FFAs. In ML103 (pXZ18, pBAD-prpE), the highest total odd straight chain FFAs accumulated to 297 mg/l, and the ratio reached 17.68 % of the total FFAs. Due to the different substrate specificity of the acyl-ACP thioesterases, the major odd straight chain FFA components of ML103 (pXZM12, pBAD-prpE) were undecanoic acid and tridecanoic acid, while the ML103 (pXZ18, pBAD-prpE) preferred pentadecanoic acid. PMID:25030454

  17. Medium chain and behenic acid incorporated structured lipids from sal, mango and kokum fats by lipase acidolysis.

    PubMed

    Bebarta, Biranchi; M, Jhansi; Kotasthane, Pranitha; Sunkireddy, Yella Reddy

    2013-01-15

    Medium chain (MC) and behenic fatty acids were incorporated into kokum, sal and mango fats using 1,3-specific lipase catalysed acidolysis. The incorporation of fatty acids increased with increase in concentration of fatty acids and duration of reaction. The order of incorporation of fatty acids was C22:0>C10:0>C8:0, to the extent of 53%, 42.5%, 35.8%, respectively, after 16 h, using kokum as substrate. The same trend was observed with sal or mango fats as substrates though the percentages incorporated were different. The modified products with higher contents of MC were liquids with no solid fats, even at 0°C, and which showed low cloud point due to an increase in triacylglycerols containing lower chain fatty acids. The modified products after incorporating both MC and C22:0 showed long melting ranges and were suitable for use in bakery, confectionery, etc. as vanaspati substitutes.

  18. Characterization of medium-chain triacylglycerol (MCT)-enriched seed oil from Cinnamomum camphora (Lauraceae) and its oxidative stability.

    PubMed

    Hu, Jiang-Ning; Zhang, Bing; Zhu, Xue-Mei; Li, Jing; Fan, Ya-Wei; Liu, Rong; Tang, Liang; Lee, Ki-Teak; Deng, Ze-Yuan

    2011-05-11

    Medium-chain triacylglycerol (MCT)-enriched oil was extracted by supercritical fluid extraction of carbon dioxide (SFE-CO(2)) from Cinnamomum camphora seeds. The SFE-CO(2) process was optimized using the Box-Behnken design (BBD). The maximum oil yield (42.82%) was obtained under the optimal SFE-CO(2) conditions: extraction pressure, 21.16 MPa; extraction temperature, 45.67 °C; and extraction time, 2.38 h. Subsequently, the physicochemical characteristics, fatty acid composition, triacylglycerol (TAG) composition, tocopherol content, and DSC profile as well as oxidative stabilities of C. camphora seed oil (CCSO) were studied. Results showed that CCSO contained two major medium-chain fatty acids, capric acid (53.27%) and lauric acid (39.93%). The predominant TAG species in CCSO was LaCC/CLaC (ECN 32, 79.29%). Meanwhile, it can be found that CCSO had much higher oxidative stabilities than coconut oil due to the higher content of tocopherols in CCSO (α-tocopherol, 8.67 ± 0.51 mg/100 g; γ-tocopherol, 22.6 ± 1.02 mg/100 g; δ-tocopherol, 8.38 ± 0.47 mg/100 g). Conclusively, CCSO with such a high level of MCTs and high oxidative stabilities could be potentially applied in special food for specific persons such as weak patients and overweight persons because oils enriched in MCTs can be rapidly absorbed into body to provide energy without fat accumulation.

  19. Effects of Long-Chain and Medium-Chain Fatty Acids on Apoptosis and Oxidative Stress in Human Liver Cells with Steatosis.

    PubMed

    Wang, Baogui; Li, Lumin; Fu, Jing; Yu, Ping; Gong, Deming; Zeng, Cheng; Zeng, Zheling

    2016-03-01

    Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity-related metabolic complications, which caused by excess energy intake and physical inactivity apart from genetic defects. The mechanisms that promote disease progression from NAFLD to further liver injury are still unclear. We hypothesize that the progression involved "2nd hit" is strongly influenced by the type of fatty acids in diets. Flow cytometric analysis showed that medium-chain fatty acid (MCFA) markedly decreased the percentage of late apoptotic and necrotic cells compared with long-chain fatty acid (LCFA), and MCFA inhibited the activities of caspase-3 and -9 in human liver cells with steatosis. Western blot analysis found that the levels of inflammatory markers (interleukin [IL]-6, IL-1-β, and tumor necrosis factor-α) were substantially reduced by MCFA compared with LCFA. Proteomic analysis further showed that LCFA inhibited the expression of antioxidant enzymes, and increased the expression of proteins associated with oxidative stress. It was found that LCFA (palmitate), not MCFA induced apoptosis, oxidative stress and chronic inflammatory responses in the hepatic cells with steatosis. In conclusion, reasonable selection of dietary fats has potential to translate therapeutically by ameliorating disease progression in patients with NAFLD.

  20. Second-generation functionalized medium-chain-length polyhydroxyalkanoates: the gateway to high-value bioplastic applications.

    PubMed

    Tortajada, Marta; da Silva, Luiziana Ferreira; Prieto, María Auxiliadora

    2013-03-01

    Polyhydroxyalkanoates (PHAs) are biodegradable biocompatible polyesters, which accumulate as granules in the cytoplasm of many bacteria under unbalanced growth conditions. Medium-chain-length PHAs (mcl-PHAs), characterized by C6-C14 branched monomer chains and typically produced by Pseudomonas species, are promising thermoelastomers, as they can be further modified by introducing functional groups in the side chains. Functionalized PHAs are obtained either by feeding structurally related substrates processed through the beta-oxidation pathway, or using specific strains able to transform sugars or glycerol into unsaturated PHA by de novo fatty-acid biosynthesis. Functionalized mcl-PHAs provide modified mechanical and thermal properties, and consequently have new processing requirements and highly diverse potential applications in emergent fields such as biomedicine. However, process development and sample availability are limited due to the toxicity of some precursors and still low productivity, which hinder investigation. Conversely, improved mutant strains designed through systems biology approaches and cofeeding with low-cost substrates may contribute to the widespread application of these biopolymers. This review focuses on recent developments in the production of functionalized mcl-PHAs, placing particular emphasis on strain and bioprocess design for cost-effective production.

  1. Second-generation functionalized medium-chain-length polyhydroxyalkanoates: the gateway to high-value bioplastic applications.

    PubMed

    Tortajada, Marta; da Silva, Luiziana Ferreira; Prieto, María Auxiliadora

    2013-03-01

    Polyhydroxyalkanoates (PHAs) are biodegradable biocompatible polyesters, which accumulate as granules in the cytoplasm of many bacteria under unbalanced growth conditions. Medium-chain-length PHAs (mcl-PHAs), characterized by C6-C14 branched monomer chains and typically produced by Pseudomonas species, are promising thermoelastomers, as they can be further modified by introducing functional groups in the side chains. Functionalized PHAs are obtained either by feeding structurally related substrates processed through the beta-oxidation pathway, or using specific strains able to transform sugars or glycerol into unsaturated PHA by de novo fatty-acid biosynthesis. Functionalized mcl-PHAs provide modified mechanical and thermal properties, and consequently have new processing requirements and highly diverse potential applications in emergent fields such as biomedicine. However, process development and sample availability are limited due to the toxicity of some precursors and still low productivity, which hinder investigation. Conversely, improved mutant strains designed through systems biology approaches and cofeeding with low-cost substrates may contribute to the widespread application of these biopolymers. This review focuses on recent developments in the production of functionalized mcl-PHAs, placing particular emphasis on strain and bioprocess design for cost-effective production. PMID:24151777

  2. Production of medium chain length fatty alcohols from glucose in Escherichia coli

    PubMed Central

    Youngquist, J. Tyler; Schumacher, Martin H.; Rose, Joshua P.; Raines, Thomas C.; Politz, Mark C.; Copeland, Matthew F.; Pfleger, Brian F.

    2013-01-01

    Metabolic engineering offers the opportunity to produce a wide range of commodity chemicals that are currently derived from petroleum or other non-renewable resources. Microbial synthesis of fatty alcohols is an attractive process because it can control the distribution of chain lengths and utilize low cost fermentation substrates. Specifically, primary alcohols with chain lengths of 12 to 14 carbons have many uses in the production of detergents, surfactants, and personal care products. The current challenge is to produce these compounds at titers and yields that would make them economically competitive. Here, we demonstrate a metabolic engineering strategy for producing fatty alcohols from glucose. To produce a high level of 1-dodecanol and 1-tetradecanol, an acyl-ACP thioesterase (BTE), an acyl-CoA ligase (FadD), and an acyl-CoA/aldehyde reductase (MAACR) were overexpressed in an engineered strain of Escherichia coli. Yields were improved by balancing expression levels of each gene, using a fed-batch cultivation strategy, and adding a solvent to the culture for extracting the product from cells. Using these strategies, a titer of over 1.6 g/L fatty alcohol with a yield of over 0.13 g fatty alcohol / g carbon source was achieved. These are the highest reported yield of fatty alcohols produced from glucose in E. coli. PMID:24141053

  3. Continuous measurement of galactolipid hydrolysis by pancreatic lipolytic enzymes using the pH-stat technique and a medium chain monogalactosyl diglyceride as substrate.

    PubMed

    Amara, Sawsan; Lafont, Dominique; Fiorentino, Brice; Boullanger, Paul; Carrière, Frédéric; De Caro, Alain

    2009-10-01

    Galactolipids are the main lipids from plants and galactolipases play a major role in their metabolism. These enzymes were however poorly studied so far and only few assays have been developed. A specific and continuous galactolipase assay using synthetic medium chain monogalactosyl diacylglycerol (MGDG) as substrate was developed using the pH-stat technique and recombinant human (rHPLRP2) and guinea pig (rGPLRP2) pancreatic lipase-related protein 2 as model enzymes. PLRP2s are the main enzymes involved in the digestion of galactolipids in the gastrointestinal tract. Monogalactosyl di-octanoylglycerol was mixed with bile salt solutions by sonication to form a micellar substrate before launching the assay. The nature of the bile salt and the bile salt to MGDG ratio were found to significantly affect the rate of MGDG hydrolysis by rHPLRP2 and rGPLRP2. The maximum galactolipase activity of both enzymes was recorded with sodium deoxycholate (NaDC) and at a NaDC to MGDG ratio of 1.33 and at basic pH values (8.0-9.0). The maximum rates of hydrolysis were obtained using a MGDG concentration of 10(-2) M and calcium chloride was found to be not necessary to obtain the maximum of activity. Under these conditions, the maximum turnovers of rGPLRP2 and rHPLRP2 on mixed NaDC/MGDG micelles were found to be 8000+/-500 and 2800+/-60 micromol/min/mg (U/mg), respectively. These activities are in the same order of magnitude as the activities on triglycerides of lipases and they are the highest specific activities ever reported for galactolipases. For the sake of comparison, the hydrolysis of mixed bile salt/MGDG micelles was also tested using other pancreatic lipolytic enzymes and only native and recombinant human carboxyl ester hydrolase were found to display significant but lower activities (240+/-17 and 432+/-62 U/mg, respectively) on MGDG.

  4. Medium-chain fatty acid binding to albumin and transfer to phospholipid bilayers

    SciTech Connect

    Hamilton, J.A. )

    1989-04-01

    Temperature-dependent (5-42{degree}C) {sup 13}C NMR spectra of albumin complexes with 90% isotopically substituted (1-{sup 13}C)octanoic or (1-{sup 13}C)decanoic acids showed a single peak at >30{degree}C but three peaks at lower temperatures. The chemical-shift differences result from different ionic and/or hydrogen-bonding interactions between amino acid side chains and the fatty acid carboxyl carbon. Rapid exchange of fatty acid among binding sites obscures these sites at temperatures >30{degree}C. Rate constants for exchange at 33{degree}C were 350 sec{sup {minus}1} for octanoate and 20 sec {sup {minus}1} for decanoate. Temperature-dependent data for octanoate showed an activation energy of 2 kcal/mol for exchange. Spectra of albumin complexes with the 12-carbon saturated fatty acid, lauric acid, had several narrow laurate carboxyl peaks at 35{degree}C, indicating longer lifetimes in the different binding sites. Fatty acid exchange between albumin and model membranes (phosphatidylcholine bilayers) occurred on a time scale comparable to that for exchange among albumin binding sites, following the order octanoate > decanoate > laurate. The equilibrium distribution of fatty acid between lipid bilayers and protein was measured directly from NMR spectra. Decreasing pH increased the relative affinity of fatty acid for the lipid bilayer. The results predict that the relative affinity of octanoic acid for albumin and membranes will be similar to that of long-chain fatty acids, but the rate of equilibration will be {approx} 10{sup 4} faster for octanoic acid.

  5. Phase equilibriums, self-assembly and interactions in two-, three- and four medium-chain length component systems.

    PubMed

    Rosenholm, Jarl B

    2014-03-01

    The Scandinavian surface (surfactant) and colloid science owes much of its success to Per Ekwall and Björn Lindman. In this review the main topics shared by their research groups at Åbo Akademi University in Finland and at Lund University in Sweden are described. The nature of surface active substances (cosolvents, co-surfactants and surfactants) and microemulsions are evaluated. It is shown that the properties of medium-chain length surfactants differ dramatically from long-chain surfactants. The phase equilibriums of binary systems are related to the phase equilibriums of ternary and quaternary systems referred to as microemulsions or more recently also as nanoemulsions. A distinction is made between hydrotrope liquids, detergentless microemulsions, surfactant mixture systems and microemulsions. Three component systems are assembled to "true" quaternary microemulsions. An exceptionally comprehensive network of thermodynamic parameters describing molecular site exchange and micelle formation are derived and related mutually. Gibbs free energy, enthalpy, entropy, volume, heat capacity, expansivity and compressibility can be used to illustrate the degree of aggregation cooperativity and to evaluate whether micelle formation is of a first-, second- or intermediate order phase transition. Theoretical simulations and experimental results show that the associate structures of medium-chain length surfactants are quite open and may be deformed due to small aggregation numbers. The self-assembly occurs over a number of distinct steps at a series of experimentally detectable critical concentrations. Despite the low aggregation tendency their phase behavior equals those of long-chain homologs in surfactant mixture and microemulsion systems. A number of models describing the self-assembly are reviewed. Nuclear magnetic resonance (shift, relaxation rate and diffusion), Laser Raman and infrared spectroscopies were chosen as key instruments for molecular interaction

  6. Markov chain formalism for generalized radiative transfer in a plane-parallel medium, accounting for polarization

    NASA Astrophysics Data System (ADS)

    Xu, Feng; Davis, Anthony B.; Diner, David J.

    2016-11-01

    A Markov chain formalism is developed for computing the transport of polarized radiation according to Generalized Radiative Transfer (GRT) theory, which was developed recently to account for unresolved random fluctuations of scattering particle density and can also be applied to unresolved spectral variability of gaseous absorption as an improvement over the standard correlated-k method. Using Gamma distribution to describe the probability density function of the extinction or absorption coefficient, a shape parameter a that quantifies the variability is introduced, defined as the mean extinction or absorption coefficient squared divided by its variance. It controls the decay rate of a power-law transmission that replaces the usual exponential Beer-Lambert-Bouguer law. Exponential transmission, hence classic RT, is recovered when a→∞. The new approach is verified to high accuracy against numerical benchmark results obtained with a custom Monte Carlo method. For a<∞, angular reciprocity is violated to a degree that increases with the spatial variability, as observed for finite portions of real-world cloudy scenes. While the degree of linear polarization in liquid water cloudbows, supernumerary bows, and glories is affected by spatial heterogeneity, the positions in scattering angle of these features are relatively unchanged. As a result, a single-scattering model based on the assumption of subpixel homogeneity can still be used to derive droplet size distributions from polarimetric measurements of extended stratocumulus clouds.

  7. Effect of medium-chain fatty acids in mould ripened cheese on the growth of Listeria monocytogenes.

    PubMed

    Kinderlerer, J L; Matthias, H E; Finner, P

    1996-11-01

    Listeria monocytogenes and List. innocua were isolated from commercial soft ripened and blue-veined cheeses manufactured in France, mainly from Brie cheese made from unpasteurized milk. Five isolates were List. monocytogenes serotype 1/2 and two were List. innocua. Examination of Bleu d'Auvergne cheese with the cryoscanning electron microscope showed that many conidia spores were present in the blue veins in close contact with the cheese surface. There were few conidia spores in the Brie, mostly on the outside of the cheese but not in contact with the surface. High concentrations of free dodecanoic (lauric) acid (1.77-2.50 g/kg cheese) and tetradecanoic (myristic) acid (2.54-6.38 g/kg cheese) were found in the veins of the blue cheese, but concentrations in the white regions were much lower. Free lauric and myristic acids were not detected in the Brie cheeses. There was no difference in the overall fatty acid composition of the fat in the surface ripened and blue-veined cheeses, although higher concentrations of free medium-chain fatty acids were found in a blue cheese compared with a surface ripened cheese. The pH and fat content were higher in regions with obvious fungal growth, the blue veins of Fourme d'Ambert and the rind of Brie. Free lauric acid dissolved in butteroil inhibited multiplication in broth at pH 7.0 of a test strain of List. monocytogenes isolated from Bleu d'Auvergne. Some inhibition was seen with hexanoic, octanoic, decanoic and tetradecanoic acids. We suggest that the presence of localized concentrations of free medium-chain fatty acids (dissolved in the fat) in the blue veins of blue mould ripened cheese could act as natural preservatives and inhibit the growth of listerias in conditions where (if present), one would otherwise expect them to grow.

  8. Medium-chain acyl-CoA deficiency: outlines from newborn screening, in silico predictions, and molecular studies.

    PubMed

    Catarzi, Serena; Caciotti, Anna; Thusberg, Janita; Tonin, Rodolfo; Malvagia, Sabrina; la Marca, Giancarlo; Pasquini, Elisabetta; Cavicchi, Catia; Ferri, Lorenzo; Donati, Maria A; Baronio, Federico; Guerrini, Renzo; Mooney, Sean D; Morrone, Amelia

    2013-01-01

    Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a disorder of fatty acid oxidation characterized by hypoglycemic crisis under fasting or during stress conditions, leading to lethargy, seizures, brain damage, or even death. Biochemical acylcarnitines data obtained through newborn screening by liquid chromatography-tandem mass spectrometry (LC-MS/MS) were confirmed by molecular analysis of the medium-chain acyl-CoA dehydrogenase (ACADM) gene. Out of 324.000 newborns screened, we identified 14 MCADD patients, in whom, by molecular analysis, we found a new nonsense c.823G>T (p.Gly275∗) and two new missense mutations: c.253G>C (p.Gly85Arg) and c.356T>A (p.Val119Asp). Bioinformatics predictions based on both phylogenetic conservation and functional/structural software were used to characterize the new identified variants. Our findings confirm the rising incidence of MCADD whose existence is increasingly recognized due to the efficacy of an expanded newborn screening panel by LC-MS/MS making possible early specific therapies that can prevent possible crises in at-risk infants. We noticed that the "common" p.Lys329Glu mutation only accounted for 32% of the defective alleles, while, in clinically diagnosed patients, this mutation accounted for 90% of defective alleles. Unclassified variants (UVs or VUSs) are especially critical when considering screening programs. The functional and pathogenic characterization of genetic variants presented here is required to predict their medical consequences in newborns. PMID:24294134

  9. Comparative functional analysis of human medium-chain dehydrogenases, short-chain dehydrogenases/reductases and aldo-keto reductases with retinoids

    PubMed Central

    Gallego, Oriol; Belyaeva, Olga V.; Porté, Sergio; Ruiz, F. Xavier; Stetsenko, Anton V.; Shabrova, Elena V.; Kostereva, Natalia V.; Farrés, Jaume; Parés, Xavier; Kedishvili, Natalia Y.

    2006-01-01

    Retinoic acid biosynthesis in vertebrates occurs in two consecutive steps: the oxidation of retinol to retinaldehyde followed by the oxidation of retinaldehyde to retinoic acid. Enzymes of the MDR (medium-chain dehydrogenase/reductase), SDR (short-chain dehydrogenase/reductase) and AKR (aldo-keto reductase) superfamilies have been reported to catalyse the conversion between retinol and retinaldehyde. Estimation of the relative contribution of enzymes of each type was difficult since kinetics were performed with different methodologies, but SDRs would supposedly play a major role because of their low Km values, and because they were found to be active with retinol bound to CRBPI (cellular retinol binding protein type I). In the present study we employed detergent-free assays and HPLC-based methodology to characterize side-by-side the retinoid-converting activities of human MDR [ADH (alcohol dehydrogenase) 1B2 and ADH4), SDR (RoDH (retinol dehydrogenase)-4 and RDH11] and AKR (AKR1B1 and AKR1B10) enzymes. Our results demonstrate that none of the enzymes, including the SDR members, are active with CRBPI-bound retinoids, which questions the previously suggested role of CRBPI as a retinol supplier in the retinoic acid synthesis pathway. The members of all three superfamilies exhibit similar and low Km values for retinoids (0.12–1.1 μM), whilst they strongly differ in their kcat values, which range from 0.35 min−1 for AKR1B1 to 302 min−1 for ADH4. ADHs appear to be more effective retinol dehydrogenases than SDRs because of their higher kcat values, whereas RDH11 and AKR1B10 are efficient retinaldehyde reductases. Cell culture studies support a role for RoDH-4 as a retinol dehydrogenase and for AKR1B1 as a retinaldehyde reductase in vivo. PMID:16787387

  10. Solubilisation of different medium chain esters in zwitterionic surfactant solutions--effects on phase behaviour and structure.

    PubMed

    Barth, A; Prévost, S; Popig, J; Dzionara, M; Hedicke, G; Gradzielski, M

    2011-12-01

    We studied the effect of solubilisation of methyl esters with different chains of medium length into the binary surfactant system tetradecyldimethylamine oxide/water at constant surfactant concentration of 200 mM. As esters we employed valeric, capronic, enanthic, and pelargonic methyl ester, thereby decreasing the polarity. Always a phase sequence L(1)-L(α)-L(1) is observed with increasing ester concentration, where the L(α)-phase increases in extent and goes to much lower temperatures with increasing chain length of the ester. Viscosity measurements show a maximum at intermediate concentrations of additive that is independent of the type of ester. From SANS measurements detailed information about the structural changes occurring during the rod-to-sphere transition in the system of the shortest additive is deduced, which proceeds first through a pronounced rod growth. Interestingly, for the different esters an almost constant value of the volumic solubilisation capacity is observed, in agreement with the relatively constant interfacial tension. For the different esters no effect on the radius and the area requirement at the amphiphilic interface is observed at the solubilisation boundary. The microemulsions present here are spherical aggregates where the ester is partitioned between core and shell. From the SANS and interfacial tension data the effective bending constants of the surfactant monolayers were deduced and they show that the extension of the L(α)-phase is directly related to a corresponding increase in the bending constants of the surfactant/ester monolayers.

  11. Effects of dietary medium-chain triacylglycerol on mRNA level of gluconeogenic enzymes in malnourished rats.

    PubMed

    Kojima, Keiichi; Kasai, Michio

    2008-12-01

    We have reported previously that dietary medium-chain triacylglycerol (MCT) improved serum albumin concentration and protein balance in malnourished rats. To clarify the mechanisms for this effect of MCT, hepatic messenger RNA levels of gluconeogenic enzymes, pyruvate dehydrogenase (PDH) and alanine aminotransferase (ALT) were measured in rats fed low-protein diets containing either MCT or isocaloric long-chain triacylglycerol (LCT) for 2 wk. The serum albumin concentration in rats fed the MCT diet was significantly higher compared with those fed the LCT diet. Serum free fatty acids and ketone body fraction were higher in rats fed MCT compared with those fed the LCT diet. The hepatic mRNA level of PDH was significantly lower in rats fed MCT than those fed LCT. But, there was no significant difference between the two groups in mRNA of gluconeogenic enzymes or ALT. These results suggest that ketone bodies, which are an alternative energy source and might spare blood glucose, increase by MCT feeding, and the reason for the PEM (protein-energy malnutrition)-improving effect of MCT is not caused by suppression of gluconeogenesis.

  12. Medium chain fatty acids are selective peroxisome proliferator activated receptor (PPAR) γ activators and pan-PPAR partial agonists.

    PubMed

    Liberato, Marcelo Vizoná; Nascimento, Alessandro S; Ayers, Steven D; Lin, Jean Z; Cvoro, Aleksandra; Silveira, Rodrigo L; Martínez, Leandro; Souza, Paulo C T; Saidemberg, Daniel; Deng, Tuo; Amato, Angela Angelica; Togashi, Marie; Hsueh, Willa A; Phillips, Kevin; Palma, Mário Sérgio; Neves, Francisco A R; Skaf, Munir S; Webb, Paul; Polikarpov, Igor

    2012-01-01

    Thiazolidinediones (TZDs) act through peroxisome proliferator activated receptor (PPAR) γ to increase insulin sensitivity in type 2 diabetes (T2DM), but deleterious effects of these ligands mean that selective modulators with improved clinical profiles are needed. We obtained a crystal structure of PPARγ ligand binding domain (LBD) and found that the ligand binding pocket (LBP) is occupied by bacterial medium chain fatty acids (MCFAs). We verified that MCFAs (C8-C10) bind the PPARγ LBD in vitro and showed that they are low-potency partial agonists that display assay-specific actions relative to TZDs; they act as very weak partial agonists in transfections with PPARγ LBD, stronger partial agonists with full length PPARγ and exhibit full blockade of PPARγ phosphorylation by cyclin-dependent kinase 5 (cdk5), linked to reversal of adipose tissue insulin resistance. MCFAs that bind PPARγ also antagonize TZD-dependent adipogenesis in vitro. X-ray structure B-factor analysis and molecular dynamics (MD) simulations suggest that MCFAs weakly stabilize C-terminal activation helix (H) 12 relative to TZDs and this effect is highly dependent on chain length. By contrast, MCFAs preferentially stabilize the H2-H3/β-sheet region and the helix (H) 11-H12 loop relative to TZDs and we propose that MCFA assay-specific actions are linked to their unique binding mode and suggest that it may be possible to identify selective PPARγ modulators with useful clinical profiles among natural products.

  13. Synthesis of short-/medium-chain-length poly(hydroxyalkanoate) blends by mixed culture fermentation of glycerol.

    PubMed

    Ashby, Richard D; Solaiman, Daniel K Y; Foglia, Thomas A

    2005-01-01

    Glycerol was used as a substrate in the bio-production of poly(hydroxyalkanoates) (PHAs) in an effort to establish an alternative outlet for glycerol and produce value-added products. Pseudomonas oleovorans NRRL B-14682 and Pseudomonas corrugata 388 grew and synthesized poly(3-hydroxybutyrate) (P3HB) and medium-chain-length PHA (mcl-PHA) consisting primarily of 3-hydroxydecanoic acid (C(10:0); 44 +/- 2 mol %) and 3-hydroxydodecenoic acid (C(12:1); 31 +/- 2 mol %), respectively, from glycerol at concentrations up to 5% (v/v). Cellular productivity maximized at 40% for P. oleovorans in 5% (v/v) glycerol and 20% for P. corrugata in 2% (v/v) glycerol after 72 h. Increasing the glycerol media concentration from 1% to 5% (v/v) caused a 61% and 72% reduction in the molar mass (M(n)) of the P3HB and mcl-PHA polymers, respectively. Proton-NMR analysis of the glycerol-derived P3HB revealed that the M(n) decrease was the result of esterification of glycerol onto the polymer in a chain terminating position. However, no evidence of glycerol-based chain termination was present in the mcl-PHA. The growth patterns of P. oleovorans and P. corrugata on glycerol permitted their use as mixed cultures to produce natural blends of P3HB and mcl-PHA. By incorporating a staggered inoculation pattern and varying the duration of the fermentations, P3HB/mcl-PHA ratios were achieved that varied from 34:66 to 96:4. PMID:16004451

  14. Intake of small-to-medium-chain saturated fatty acids is associated with peripheral leukocyte telomere length in postmenopausal women.

    PubMed

    Song, Yan; You, Nai-Chieh Y; Song, Yiqing; Kang, Mo K; Hou, Lifang; Wallace, Robert; Eaton, Charles B; Tinker, Lesley F; Liu, Simin

    2013-06-01

    Dietary factors, including dietary fat, may affect the biological aging process, as reflected by the shortening of telomere length (TL), by affecting levels of oxidative stress and inflammatory responses. We examined the direct relations of total and types of dietary fats and fat-rich foods to peripheral leukocyte TL. In 4029 apparently healthy postmenopausal women who participated in the Women's Health Initiative, intakes of total fat, individual fatty acids, and fat-rich foods were assessed by a questionnaire. TL was measured by quantitative polymerase chain reaction. Intake of short-to-medium-chain saturated fatty acids (SMSFAs; aliphatic tails of ≤ 12 carbons) was inversely associated with TL. Compared with participants in other quartiles of SMSFA intake, women who were in the highest quartile (median: 1.29% of energy) had shorter TLs [mean: 4.00 kb (95% CI: 3.89, 4.11 kb)], whereas women in the lowest quartile of intake (median: 0.29% of energy) had longer TLs [mean: 4.13 kb (95% CI: 4.03, 4.24 kb); P-trend = 0.046]. Except for lauric acid, all other individual SMSFAs were inversely associated with TL (P < 0.05). In isoenergetic substitution models, the substitution of 1% of energy from SMSFAs with any other energy source was associated with 119 bp longer TLs (95% CI: 21, 216 bp). Intakes of nonskim milk, butter, and whole-milk cheese (major sources of SMSFAs) were all inversely associated with TL. No significant associations were found with long-chain saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids. In conclusion, we found that higher intakes of SMSFAs and SMSFA-rich foods were associated with shorter peripheral leukocyte TL among postmenopausal women. These findings suggest the potential roles of SMSFAs in the rate of biological aging.

  15. Determination and comparison of how the chain number and chain length of a lipid affects its interactions with a phospholipid at an air/water interface.

    PubMed

    Ngyugen, Hang; McNamee, Cathy E

    2014-06-01

    We determined how the number of chains in a lipid and its chain length affects its interactions with a phospholipid model membrane, and whether the number of chains or the chain length of lipids affects their interactions with the phospholipids more. This was achieved by using a Langmuir trough and a fluorescence microscope to study the interactions of mono-, di-, and triglycerides with a phospholipid monolayer at an air/water interface. The effect of the number of chains in a lipid on its interactions with phospholipids at air/water interfaces was shown by surface pressure-area per molecule isotherms and their thermodynamic analysis to worsen as the number of alkyl chains was increased to be greater than one. An increase in the packing density decreased the mixing ability of the lipids with the phospholipids, resulting in the formation of aggregates in the mixed monolayer. The aggregation was explained by the intermolecular hydrophobic and van der Waals attractions between the lipid molecules. Fluorescence microscopy revealed partial mixing without aggregation for monoglycerides, but the presence of lipid aggregation for diglycerides and triglycerides. The effect of decreasing the chain length of triglycerides from a long chain to a medium chain caused the interactions of the lipids with the phospholipid molecules at the air/water interface to significantly improve. Decreasing the chain length of monoglycerides from a long chain to a medium chain worsened their interaction with the phospholipid molecules. The effect of decreasing the triglyceride chain length on their interactions with phospholipids was much greater than the effect of decreasing the number of alkyl chains in the lipid.

  16. Molecular Characterization of the Elaeis guineensis Medium-Chain Fatty Acid Diacylglycerol Acyltransferase DGAT1-1 by Heterologous Expression in Yarrowia lipolytica

    PubMed Central

    Aymé, Laure; Jolivet, Pascale; Nicaud, Jean-Marc; Chardot, Thierry

    2015-01-01

    Diacylglycerol acyltransferases (DGAT) are involved in the acylation of sn-1,2-diacylglycerol. Palm kernel oil, extracted from Elaeis guineensis (oil palm) seeds, has a high content of medium-chain fatty acids mainly lauric acid (C12:0). A putative E. guineensis diacylglycerol acyltransferase gene (EgDGAT1-1) is expressed at the onset of lauric acid accumulation in the seed endosperm suggesting that it is a determinant of medium-chain triacylglycerol storage. To test this hypothesis, we thoroughly characterized EgDGAT1-1 activity through functional complementation of a Yarrowia lipolytica mutant strain devoid of neutral lipids. EgDGAT1-1 expression is sufficient to restore triacylglycerol accumulation in neosynthesized lipid droplets. A comparative functional study with Arabidopsis thaliana DGAT1 highlighted contrasting substrate specificities when the recombinant yeast was cultured in lauric acid supplemented medium. The EgDGAT1-1 expressing strain preferentially accumulated medium-chain triacylglycerols whereas AtDGAT1 expression induced long-chain triacylglycerol storage in Y. lipolytica. EgDGAT1-1 localized to the endoplasmic reticulum where TAG biosynthesis takes place. Reestablishing neutral lipid accumulation in the Y. lipolytica mutant strain did not induce major reorganization of the yeast microsomal proteome. Overall, our findings demonstrate that EgDGAT1-1 is an endoplasmic reticulum DGAT with preference for medium-chain fatty acid substrates, in line with its physiological role in palm kernel. The characterized EgDGAT1-1 could be used to promote medium-chain triacylglycerol accumulation in microbial-produced oil for industrial chemicals and cosmetics. PMID:26581109

  17. Molecular Characterization of the Elaeis guineensis Medium-Chain Fatty Acid Diacylglycerol Acyltransferase DGAT1-1 by Heterologous Expression in Yarrowia lipolytica.

    PubMed

    Aymé, Laure; Jolivet, Pascale; Nicaud, Jean-Marc; Chardot, Thierry

    2015-01-01

    Diacylglycerol acyltransferases (DGAT) are involved in the acylation of sn-1,2-diacylglycerol. Palm kernel oil, extracted from Elaeis guineensis (oil palm) seeds, has a high content of medium-chain fatty acids mainly lauric acid (C12:0). A putative E. guineensis diacylglycerol acyltransferase gene (EgDGAT1-1) is expressed at the onset of lauric acid accumulation in the seed endosperm suggesting that it is a determinant of medium-chain triacylglycerol storage. To test this hypothesis, we thoroughly characterized EgDGAT1-1 activity through functional complementation of a Yarrowia lipolytica mutant strain devoid of neutral lipids. EgDGAT1-1 expression is sufficient to restore triacylglycerol accumulation in neosynthesized lipid droplets. A comparative functional study with Arabidopsis thaliana DGAT1 highlighted contrasting substrate specificities when the recombinant yeast was cultured in lauric acid supplemented medium. The EgDGAT1-1 expressing strain preferentially accumulated medium-chain triacylglycerols whereas AtDGAT1 expression induced long-chain triacylglycerol storage in Y. lipolytica. EgDGAT1-1 localized to the endoplasmic reticulum where TAG biosynthesis takes place. Reestablishing neutral lipid accumulation in the Y. lipolytica mutant strain did not induce major reorganization of the yeast microsomal proteome. Overall, our findings demonstrate that EgDGAT1-1 is an endoplasmic reticulum DGAT with preference for medium-chain fatty acid substrates, in line with its physiological role in palm kernel. The characterized EgDGAT1-1 could be used to promote medium-chain triacylglycerol accumulation in microbial-produced oil for industrial chemicals and cosmetics.

  18. Molecular Characterization of the Elaeis guineensis Medium-Chain Fatty Acid Diacylglycerol Acyltransferase DGAT1-1 by Heterologous Expression in Yarrowia lipolytica.

    PubMed

    Aymé, Laure; Jolivet, Pascale; Nicaud, Jean-Marc; Chardot, Thierry

    2015-01-01

    Diacylglycerol acyltransferases (DGAT) are involved in the acylation of sn-1,2-diacylglycerol. Palm kernel oil, extracted from Elaeis guineensis (oil palm) seeds, has a high content of medium-chain fatty acids mainly lauric acid (C12:0). A putative E. guineensis diacylglycerol acyltransferase gene (EgDGAT1-1) is expressed at the onset of lauric acid accumulation in the seed endosperm suggesting that it is a determinant of medium-chain triacylglycerol storage. To test this hypothesis, we thoroughly characterized EgDGAT1-1 activity through functional complementation of a Yarrowia lipolytica mutant strain devoid of neutral lipids. EgDGAT1-1 expression is sufficient to restore triacylglycerol accumulation in neosynthesized lipid droplets. A comparative functional study with Arabidopsis thaliana DGAT1 highlighted contrasting substrate specificities when the recombinant yeast was cultured in lauric acid supplemented medium. The EgDGAT1-1 expressing strain preferentially accumulated medium-chain triacylglycerols whereas AtDGAT1 expression induced long-chain triacylglycerol storage in Y. lipolytica. EgDGAT1-1 localized to the endoplasmic reticulum where TAG biosynthesis takes place. Reestablishing neutral lipid accumulation in the Y. lipolytica mutant strain did not induce major reorganization of the yeast microsomal proteome. Overall, our findings demonstrate that EgDGAT1-1 is an endoplasmic reticulum DGAT with preference for medium-chain fatty acid substrates, in line with its physiological role in palm kernel. The characterized EgDGAT1-1 could be used to promote medium-chain triacylglycerol accumulation in microbial-produced oil for industrial chemicals and cosmetics. PMID:26581109

  19. Analytic study of the chain dark decomposition reaction of iodides - atomic iodine donors - in the active medium of a pulsed chemical oxygen-iodine laser: 1. Criteria for the development of the branching chain dark decomposition reaction of iodides

    SciTech Connect

    Andreeva, Tamara L; Kuznetsova, S V; Maslov, Aleksandr I; Sorokin, Vadim N

    2009-02-28

    The scheme of chemical processes proceeding in the active medium of a pulsed chemical oxygen-iodine laser (COIL) is analysed. Based on the analysis performed, the complete system of differential equations corresponding to this scheme is replaced by a simplified system of equations describing in dimensionless variables the chain dark decomposition of iodides - atomic iodine donors, in the COIL active medium. The procedure solving this system is described, the basic parameters determining the development of the chain reaction are found and its specific time intervals are determined. The initial stage of the reaction is analysed and criteria for the development of the branching chain decomposition reaction of iodide in the COIL active medium are determined. (active media)

  20. Biosynthesis of medium chain length poly(3-hydroxyalkanoates) (mcl-PHAs) by Comamonas testosteroni during cultivation on vegetable oils.

    PubMed

    Thakor, Nehal; Trivedi, Ujjval; Patel, K C

    2005-11-01

    Comamonas testosteroni has been studied for its ability to synthesize and accumulate medium chain length poly(3-hydroxyalkanoates) (mcl-PHAs) during cultivation on vegetable oils available in the local market. Castor seed oil, coconut oil, mustard oil, cotton seed oil, groundnut oil, olive oil and sesame oil were supplemented in the mineral medium as a sole source of carbon for growth and PHAs accumulation. The composition of PHAs was analysed by a coupled gas chromatography/mass spectroscopy (GC/MS). PHAs contained C6 to C14 3-hydroxy acids, with a strong presence of 3-hydroxyoctanoate when coconut oil, mustard oil, cotton seed oil and groundnut oil were supplied. 3-hydroxydecanoate was incorporated at higher concentrations when castor seed oil, olive oil and sesame oil were the substrates. Purified PHAs samples were characterized by Fourier Transform Infrared (FTIR) and 13C NMR analysis. During cultivation on various vegetable oils, C. testosteroni accumulated PHAs up to 78.5-87.5% of the cellular dry material (CDM). The efficiency of the culture to convert oil to PHAs ranged from 53.1% to 58.3% for different vegetable oils. Further more, the composition of the PHAs formed was not found to be substrate dependent as PHAs obtained from C. testosteroni during growth on variety of vegetable oils showed similar compositions; 3-hydroxyoctanoic acid and/or 3-hydroxydecanoic acid being always predominant. The polymerizing system of C. testosteroni showed higher preference for C8 and C10 monomers as longer and smaller monomers were incorporated less efficiently. PMID:16084364

  1. Biosynthesis of medium chain length poly(3-hydroxyalkanoates) (mcl-PHAs) by Comamonas testosteroni during cultivation on vegetable oils.

    PubMed

    Thakor, Nehal; Trivedi, Ujjval; Patel, K C

    2005-11-01

    Comamonas testosteroni has been studied for its ability to synthesize and accumulate medium chain length poly(3-hydroxyalkanoates) (mcl-PHAs) during cultivation on vegetable oils available in the local market. Castor seed oil, coconut oil, mustard oil, cotton seed oil, groundnut oil, olive oil and sesame oil were supplemented in the mineral medium as a sole source of carbon for growth and PHAs accumulation. The composition of PHAs was analysed by a coupled gas chromatography/mass spectroscopy (GC/MS). PHAs contained C6 to C14 3-hydroxy acids, with a strong presence of 3-hydroxyoctanoate when coconut oil, mustard oil, cotton seed oil and groundnut oil were supplied. 3-hydroxydecanoate was incorporated at higher concentrations when castor seed oil, olive oil and sesame oil were the substrates. Purified PHAs samples were characterized by Fourier Transform Infrared (FTIR) and 13C NMR analysis. During cultivation on various vegetable oils, C. testosteroni accumulated PHAs up to 78.5-87.5% of the cellular dry material (CDM). The efficiency of the culture to convert oil to PHAs ranged from 53.1% to 58.3% for different vegetable oils. Further more, the composition of the PHAs formed was not found to be substrate dependent as PHAs obtained from C. testosteroni during growth on variety of vegetable oils showed similar compositions; 3-hydroxyoctanoic acid and/or 3-hydroxydecanoic acid being always predominant. The polymerizing system of C. testosteroni showed higher preference for C8 and C10 monomers as longer and smaller monomers were incorporated less efficiently.

  2. Production of medium-chain volatile fatty acids by mixed ruminal microorganisms is enhanced by ethanol in co-culture with Clostridium kluyveri

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fermentative production of medium-chain (C5-C8) volatile fatty acids by the carboxylate platform has several potential advantages as a route to biofuel precursors. However, its practicality is limited by the relatively slow synthesis of these acids from shorter precursors (C2-C4) that accumulate dur...

  3. A late Golgi sorting function for Saccharomyces cerevisiae Apm1p, but not for Apm2p, a second yeast clathrin AP medium chain-related protein.

    PubMed Central

    Stepp, J D; Pellicena-Palle, A; Hamilton, S; Kirchhausen, T; Lemmon, S K

    1995-01-01

    Mammalian clathrin-associated protein (AP) complexes, AP-1 (trans-Golgi network) and AP-2 (plasma membrane), are composed of two large subunits of 91-107 kDa, one medium chain (mu) of 47-50 kDa and one small chain (sigma) of 17-19 kDa. Two yeast genes, APM1 and APM2, have been identified that encode proteins related to AP mu chains. APM1, whose sequence was reported previously, codes for a protein of 54 kDa that has greatest similarity to the mammalian 47-kDa mu 1 chain of AP-1. APM2 encodes an AP medium chain-related protein of 605 amino acids (predicted molecular weight of 70 kDa) that is only 30-33% identical to the other family members. In yeast containing a normal clathrin heavy chain gene (CHC1), disruptions of the APM genes, singly or in combination, had no detectable phenotypic consequences. However, deletion of APM1 greatly enhanced the temperature-sensitive growth phenotype and the alpha-factor processing defect displayed by cells carrying a temperature-sensitive allele of the clathrin heavy chain gene. In contrast, deletion of APM2 caused no synthetic phenotypes with clathrin mutants. Biochemical analysis indicated that Apm1p and Apm2p are components of distinct high molecular weight complexes. Apm1p, Apm2p, and clathrin cofractionated in a discrete vesicle population, and the association of Apm1p with the vesicles was disrupted in CHC1 deletion strains. These results suggest that Apm1p is a component of an AP-1-like complex that participates with clathrin in sorting at the trans-Golgi in yeast. We propose that Apm2p represents a new class of AP-medium chain-related proteins that may be involved in a nonclathrin-mediated vesicular transport process in eukaryotic cells. Images PMID:7749194

  4. Inhibition of Salmonella typhimurium by medium-chain fatty acids in an in vitro simulation of the porcine cecum.

    PubMed

    Messens, Winy; Goris, Johan; Dierick, Noël; Herman, Lieve; Heyndrickx, Marc

    2010-02-24

    Salmonella typhimurium was responsible for more than half of the reported cases of human salmonellosis in Belgium in 2007 and was the predominant serovar isolated from slaughter pig carcasses. To lower the Salmonella contamination of pork meat, measures can be taken at the primary production level, e.g. by reducing the shedding of Salmonella through the use of feed additives such as medium-chain fatty acids (MCFAs). An in vitro continuous culture system, simulating the porcine cecum, was developed for investigating the effect of MCFAs (sodium caproate, sodium caprylate and sodium caprinate) on the pig intestinal microbial community. The system was monitored by plating on selective media, PCR-DGGE and HPLC analysis of fermentation products. An inoculated S. typhimurium strain could be maintained by the system at a population size of about 5 log(10)cfu/mL. By the addition of 15 mM caprylate, significant reductions of coliforms and Salmonella counts by 4.69 log(10) units (95% confidence interval: 4.19-5.18) could be achieved, while other bacterial populations were clearly less affected. This concentration seems economically feasible in pig feed, provided that the substance can reach the cecum without being absorbed. Thus, caprylate, for example in the form of encapsulated beads or as triacylglycerol oil, might have potential as a Salmonella-reducing additive in pig feed. PMID:19709819

  5. Evaluation of medium-chain-length polyhydroxyalkanoate production by Pseudomonas putida LS46 using biodiesel by-product streams.

    PubMed

    Fu, Jilagamazhi; Sharma, Umesh; Sparling, Richard; Cicek, Nazim; Levin, David B

    2014-07-01

    Medium-chain-length polyhydroxyalkanoate (mcl-PHA) production by Pseudomonas putida LS46 was analyzed in shake-flask-based batch reactions, using pure chemical-grade glycerol (PG), biodiesel-derived "waste" glycerol (WG), and biodiesel-derived "waste" free fatty acids (WFA). Cell growth, substrate consumption, mcl-PHA accumulation within the cells, and the monomer composition of the synthesized biopolymers were monitored. The patterns of mcl-PHA synthesis in P. putida LS46 cells grown on PG and WG were similar but differed from that of cells grown with WFA. Polymer accumulation in glycerol-based cultures was stimulated by nitrogen limitation and plateaued after 48 h in both PG and WG cultures, with a total accumulation of 17.9% cell dry mass and 16.3% cell dry mass, respectively. In contrast, mcl-PHA synthesis was independent of nitrogen concentration in P. putida LS46 cells cultured with WFA, which accumulated to 29% cell dry mass. In all cases, the mcl-PHAs synthesized consisted primarily of 3-hydroxyoctanoate (C(8)) and 3-hydroxydecanoate (C(10)). WG and WFA supported similar or greater cell growth and mcl-PHA accumulation than PG under the experimental conditions used. These results suggest that biodiesel by-product streams could be used as low-cost carbon sources for sustainable mcl-PHA production.

  6. Antibacterial study of the medium chain fatty acids and their 1-monoglycerides: individual effects and synergistic relationships.

    PubMed

    Batovska, Daniela I; Todorova, Iva T; Tsvetkova, Iva V; Najdenski, Hristo M

    2009-01-01

    The antibacterial activity of the medium chain fatty acids and their 1-monoglycerides was evaluated towards several Gram-positive strains belonging to the genera Staphylococcus, Corynebacterium, Bacillus, Listeria and Streptococcus. The 1-monoglycerides were more active than the fatty acids with monolaurin being the most active compound. Interesting effects were observed when the streptococcal strain Streptococcus pyogenes was used as a test microorganism. First, blocking of the hydroxyl groups of the glycerol moiety of monolaurin led to a compound with remarkable antibacterial activity (MIC, 3.9 microg/ml). Secondly, synergistic relationships were observed between monolaurin and monocaprin as well as between monolaurin and the poorly active lauric acid when their two component mixtures were examined. The mixtures in which one of the components was 2-fold more predominant than the other one were much more active than the pure components taken individually. Moreover, the presence of the components in ratio 1:1 was disadvantageous. Synergistic relationships were also found between monolaurin and monomyristin towards Staphylococcus aureus 209 when monomyristin was in the same quantity as monolaurin or in shortage. PMID:19469285

  7. A medium-chain fatty acid receptor Gpr84 in zebrafish: expression pattern and roles in immune regulation.

    PubMed

    Huang, Qiaoyan; Feng, Dong; Liu, Kai; Wang, Peng; Xiao, Hongyan; Wang, Ying; Zhang, Shicui; Liu, Zhenhui

    2014-08-01

    Gpr84 was recently identified as a receptor for medium-chain fatty acids, but its functions remain to be clarified. We reported the identification of a zebrafish Gpr84 homologue (zGpr84), which has a higher gene expression in the tissues of intestine, heart and liver. During embryogenesis, zGpr84 is maternally expressed and a significant increase is observed at segmentation period, and it is mainly restricted to the head region, pectoral fins, branchial arches, intestine and lateral line neuromast. Fasting or treatment with lipopolysaccharide (LPS) can induce significant up-regulation of zGpr84. We further demonstrated that zGpr84 is involved in the accumulation of lipid droplets in cells. Moreover, undecanoic acid (UA) can amplify LPS induced production of the proinflammatory cytokine IL-12 p40 through zGpr84, supporting the proposal that Gpr84 may play a role in directly linking fatty acid metabolism to immunological regulation. The resulting data in fish lay a foundation for a comprehensive exploration of the functions and evolution of Gpr84.

  8. Inhibition of Salmonella typhimurium by medium-chain fatty acids in an in vitro simulation of the porcine cecum.

    PubMed

    Messens, Winy; Goris, Johan; Dierick, Noël; Herman, Lieve; Heyndrickx, Marc

    2010-02-24

    Salmonella typhimurium was responsible for more than half of the reported cases of human salmonellosis in Belgium in 2007 and was the predominant serovar isolated from slaughter pig carcasses. To lower the Salmonella contamination of pork meat, measures can be taken at the primary production level, e.g. by reducing the shedding of Salmonella through the use of feed additives such as medium-chain fatty acids (MCFAs). An in vitro continuous culture system, simulating the porcine cecum, was developed for investigating the effect of MCFAs (sodium caproate, sodium caprylate and sodium caprinate) on the pig intestinal microbial community. The system was monitored by plating on selective media, PCR-DGGE and HPLC analysis of fermentation products. An inoculated S. typhimurium strain could be maintained by the system at a population size of about 5 log(10)cfu/mL. By the addition of 15 mM caprylate, significant reductions of coliforms and Salmonella counts by 4.69 log(10) units (95% confidence interval: 4.19-5.18) could be achieved, while other bacterial populations were clearly less affected. This concentration seems economically feasible in pig feed, provided that the substance can reach the cecum without being absorbed. Thus, caprylate, for example in the form of encapsulated beads or as triacylglycerol oil, might have potential as a Salmonella-reducing additive in pig feed.

  9. Biosynthesis of medium-chain-length poly(3-hydroxyalkanoates) by volatile aromatic hydrocarbons-degrading Pseudomonas fulva TY16.

    PubMed

    Ni, Yu-Yang; Kim, Do Young; Chung, Moon Gyu; Lee, Sun Hee; Park, Ho-Yong; Rhee, Young Ha

    2010-11-01

    Pseudomonas fulva TY16 biosynthesized medium-chain-length poly(3-hydroxyalkanoates) (MCL-PHAs) containing unsaturated 3-hydroxydodecenoate unit (approximately 8-9%) when grown with volatile aromatic compounds including benzene, toluene, and ethylbenzene as sole carbon substrate. In particular, when cultivated using a continuous feeding system designed to supply toluene at a flow rate of 0.42gL(-1)h(-1) into a 7-L jar fermentor, the growth of the organism reached up to approximately 3.87gL(-1) after the 48h fed-batch fermentation, representing an accumulated cellular MCL-PHA of 58.9% by weight. The obtained MCL-PHA was a copolyester primarily consisting of 3-hydroxydecanoate (55.2%) and 3-hydroxyoctanoate (26.8%) with minor constituents being 3-hydroxyhexanoate (3.7%), 3-hydroxydodecenoate (8.2%), and 3-hydroxydodecanoate (6.1%). The present results suggest that P. fulva TY16 is a promising candidate for the biotechnological conversion of toxic petrochemical wastes to valuable biopolymers.

  10. Fruit pomace and waste frying oil as sustainable resources for the bioproduction of medium-chain-length polyhydroxyalkanoates.

    PubMed

    Follonier, Stéphanie; Goyder, Miriam S; Silvestri, Anne-Claire; Crelier, Simon; Kalman, Franka; Riesen, Roland; Zinn, Manfred

    2014-11-01

    Medium-chain-length polyhydroxyalkanoates (mcl-PHAs) are biobased and biodegradable alternatives to petrol-derived polymers, whose break-through has been prevented by high production cost. Therefore we investigated whether wastes from the food industry (nine types of fruit pomace including apricots, cherries and grapes, and waste frying oil) could replace the costly sugars and fatty acids typically used as carbon substrates for the bacterial fermentations. A selection of enzyme preparations was tested for converting the residual polysaccharides from the pomaces into fermentable monosaccharides. From the pomace of apricots, cherries and Solaris grapes, 47, 49 and 106gL(-1) glucose were recovered, respectively. Solaris grapes had the highest sugar content whereas apricots contained the fewest growth inhibitors. These two pomaces were assessed for their suitability to produce mcl-PHA in bioreactor. A 2-step fermentation was established with Pseudomonas resinovorans, hydrolyzed pomace as growth substrate and WFO as mcl-PHA precursor. Solaris grapes proved to be a very promising growth substrate, resulting in the production of 21.3gPHA(Lpomace)(-1) compared to 1.4g PHA (L pomace)(-1) for apricots. Finally, capillary zone electrophoresis analyses allowed monitoring of sugar and organic acid uptake during the fermentation on apricots, which led to the discovery of reverse diauxie in P. resinovorans.

  11. Pulsed feeding strategy is more favorable to medium-chain-length polyhydroxyalkanoates production from waste rapeseed oil.

    PubMed

    Możejko, Justyna; Ciesielski, Slawomir

    2014-01-01

    This article presents the results of production and characterization of medium-chain-length polyhydroxyalkanoates (mcl-PHAs) using Pseudomonas sp. Gl01. Studies have been carried out to find suitable feeding strategies for mcl-PHAs production and, for the first time, to investigate in-depth the properties of biopolyesters obtained under controlled conditions with waste rapeseed oil as a substrate. Up to 44% mcl-PHAs of cell dry weight was produced at 41 h of biofermentor culture by employing pulsed feeding of waste rapeseed oil. GC analysis showed a polymer composition with monomer length of C6 to C12 with C8 and C10 as the principal monomers. The monomeric structure of the extracted polyesters did not depend on the cultivation time and the feeding strategy. Molecular weight of the mcl-PHAs was found to be ranging from 57 to 154 kDa. Thermal analyses showed the obtained mcl-polyhydroxyalkanaotes to be semi-crystalline biopolymer with promising thermal stability, having a glass transition temperature of -38 to -50°C.

  12. Role of medium-chain fatty acids in the emulsification mechanistics of self-micro-emulsifying lipid formulations

    PubMed Central

    Hasan, Naser M.Y.

    2014-01-01

    Purpose The objective of the present study was to design and develop stable o/w microemulsions comprising Miglyol 812, Imwitor 988 and Tagat TO as a non ionic surfactant. This was based on particle size measurements and phase behavior studies. The empirical role of incorporating medium-chain mono/di-glycerides in the lipid matrix in the mechanistic processes of emulsification was also established in various simulating physiological conditions. Methods The efficiency of self-emulsification was evaluated under conditions of varying key compositions in the lipid mixtures; oil, cosurfactant and surfactant. Droplet diameter was measured using laser diffraction and light scattering techniques. Equilibrium phase studies were performed and phase boundaries were determined for the lipid–water systems. Results Microemulsion systems were produced from blends of Miglyol 812, Imwitor 988 and Tagat TO. An optimized formulation consisted of {Miglyol 812/Imwitor 988} and Tagat TO spontaneously self-emulsified in water producing dispersions with droplet diameters of ∼50 nm. Phase equilibrium diagrams have revealed significant enhancement in the water-solubilized region (L2) without any presence of liquid crystalline materials. Conclusions Potential SMEDDS formulations for the bioavailability enhancement of poorly water-soluble compounds were developed by mixing blends of {Miglyol 812/Imwitor 988} and Tagat TO as a non-ionic surfactant. ‘Diffusion and stranding’ appears to be the dominant mechanism of emulsification. PMID:25561872

  13. Effect of medium-chain glycerides (MGK) on the intestinal absorption and the hepatobiliary transport of bromthymol blue.

    PubMed

    Higaki, K; Kishimoto, I; Komatsu, H; Hashida, M; Sezaki, H

    1986-06-01

    The effect of medium chain glyceride (MGK) emulsion on the intestinal absorption and the biliary excretion of bromthymol blue (BTB) was investigated in rats. Extensive tissue accumulation of BTB was reduced when BTB was administered with MGK emulsion formulation. HCO-100, an emulsifier, was also important for the decrease in the tissue accumulation of BTB. The ratios of absorption percent to tissue accumulation percent and to free fraction, not contained in the droplet of emulsion, in MGK emulsion were much greater than that of the control. Pretreatment with BTB-free emulsion reduced BTB absorption under the control, although tissue accumulation was not affected. The absorption appeared to decrease with increase in the time of pretreatment. The effect of leaving treatment after pretreatment on the absorption of BTB was also investigated. With the increase in leaving time after pretreatment, reduced absorption tended to resume to the level of control. The change in monocaprylate content from 54 to 60% in MGK made a difference in BTB absorption and it was suggested that monocaprylate content in MGK was one of the significant factors of MGK emulsion on drug absorption. Bile recovery study was simultaneously carried out with an in situ recirculation experiment. The recovery of BTB into bile tended to decrease. The ratio of recovery percent of BTB into bile to the absorption percent of BTB also decreased extensively, which is possibly another effect of MGK on drug disposition. PMID:3761141

  14. Dietary Medium Chain Fatty Acid Supplementation Leads to Reduced VLDL Lipolysis and Uptake Rates in Comparison to Linoleic Acid Supplementation

    PubMed Central

    van Schalkwijk, Daniël B.; Pasman, Wilrike J.; Hendriks, Henk F. J.; Verheij, Elwin R.; Rubingh, Carina M.; van Bochove, Kees; Vaes, Wouter H. J.; Adiels, Martin; Freidig, Andreas P.; de Graaf, Albert A.

    2014-01-01

    Dietary medium chain fatty acids (MCFA) and linoleic acid follow different metabolic routes, and linoleic acid activates PPAR receptors. Both these mechanisms may modify lipoprotein and fatty acid metabolism after dietary intervention. Our objective was to investigate how dietary MCFA and linoleic acid supplementation and body fat distribution affect the fasting lipoprotein subclass profile, lipoprotein kinetics, and postprandial fatty acid kinetics. In a randomized double blind cross-over trial, 12 male subjects (age 51±7 years; BMI 28.5±0.8 kg/m2), were divided into 2 groups according to waist-hip ratio. They were supplemented with 60 grams/day MCFA (mainly C8:0, C10:0) or linoleic acid for three weeks, with a wash-out period of six weeks in between. Lipoprotein subclasses were measured using HPLC. Lipoprotein and fatty acid metabolism were studied using a combination of several stable isotope tracers. Lipoprotein and tracer data were analyzed using computational modeling. Lipoprotein subclass concentrations in the VLDL and LDL range were significantly higher after MCFA than after linoleic acid intervention. In addition, LDL subclass concentrations were higher in lower body obese individuals. Differences in VLDL metabolism were found to occur in lipoprotein lipolysis and uptake, not production; MCFAs were elongated intensively, in contrast to linoleic acid. Dietary MCFA supplementation led to a less favorable lipoprotein profile than linoleic acid supplementation. These differences were not due to elevated VLDL production, but rather to lower lipolysis and uptake rates. PMID:25049048

  15. In vitro antioxidant assay of medium chain fatty acid rich rice bran oil in comparison to native rice bran oil.

    PubMed

    Sengupta, Avery; Ghosh, Mahua; Bhattacharyya, D K

    2015-08-01

    The study aimed to evaluate the in vitro antioxidant activity of medium chain fatty acid (MCFA) rich-rice bran oils in comparison with native rice bran oil. Different in vitro methods were used to evaluate the free radical scavenging activity, metal chelation activity, reducing acitivity, ABTS radical scavenging activity, thiobarbituric acid (TBA) value and so on at different concentrations of the oils such as 10-100 μg/mL. Inhibition of lipid peroxidation was evaluated measuring thiobarbituric acid responsive substance (TBARS) and conjugated diene formation. All the oils showed potent antioxidant activity at 100 μg/mL concentration. TBARS formation and conjugated diene formation was lower with MCFA rich oils i.e. the inhibition of lipid peroxidation was more in MCFA rich oils than original rice bran oil. Caprylic acid rich rice bran oil showed maximum antioxidant activity in comparison to capric- and lauric acid rich rice bran oils. Overall the MCFA rich rice bran oils showed to be more potent antioxidant than rice bran oil due to their lower unsaturated fatty acid content. PMID:26243941

  16. Broad-range and binary-range acyl-acyl-carrier protein thioesterases suggest an alternative mechanism for medium-chain production in seeds.

    PubMed

    Voelker, T A; Jones, A; Cranmer, A M; Davies, H M; Knutzon, D S

    1997-06-01

    In the current model of medium-chain (C8-14) fatty acid biosynthesis in seeds, specialized FatB acyl-acyl-carrier-protein (ACP) thioesterases are responsible for the production of medium chains. We have isolated and characterized FatB cDNAs from the maturing seeds of elm (Ulmus americana) and nutmeg (Myristica fragrans), which accumulate predominantly caprate (10:0)- and myristate (14:0)-containing oils, respectively. In neither species were we able to find cDNAs encoding enzymes specialized for these chain lengths. Nutmeg FatB hydrolyses C14-18 substrates in vitro and expression in Brassica napus seeds leads to an oil enriched in C14-18 saturates. Elm FatB1 displays a binary specificity: one activity is centered on 10:0-ACP, and a second is centered on palmitate (16:0)-ACP. After expression in B. napus seeds the oil is enriched in C10-18 saturates, predominantly 16:0, 14:0, and 10:0. The composition of free fatty acids produced by elm FatB1 in Escherichia coli shifts from C14-16 to mostly C8-10 by increasing the rate of chain termination by this enzyme. These results suggest the existence of an alternative mechanism used in the evolution of medium-chain production, a model of which is presented. PMID:9193098

  17. Self-diffusion in molecular liquids: Medium-chain n-alkanes and coenzyme Q10 studied by quasielastic neutron scattering

    NASA Astrophysics Data System (ADS)

    Smuda, Christoph; Busch, Sebastian; Gemmecker, Gerd; Unruh, Tobias

    2008-07-01

    A systematic time-of-flight quasielastic neutron scattering (TOF-QENS) study on diffusion of n-alkanes in a melt is presented for the first time. As another example of a medium-chain molecule, coenzyme Q10 is investigated in the same way. The data were evaluated both in the frequency and in the time domain. TOF-QENS data can be satisfactorily described by different models, and it turned out that the determined diffusion coefficients are largely independent of the applied model. The derived diffusion coefficients are compared with values measured by pulsed-field gradient nuclear magnetic resonance (PFG-NMR). With increasing chain length, an increasing difference between the TOF-QENS diffusion coefficient and the PFG-NMR diffusion coefficient is observed. This discrepancy in the diffusion coefficients is most likely due to a change of the diffusion mechanism on a nanometer length scale for molecules of medium-chain length.

  18. Extraction of medium chain fatty acids from organic municipal waste and subsequent production of bio-based fuels.

    PubMed

    Kannengiesser, Jan; Sakaguchi-Söder, Kaori; Mrukwia, Timo; Jager, Johannes; Schebek, Liselotte

    2016-01-01

    This paper provides an overview on investigations for a new technology to generate bio-based fuel additives from bio-waste. The investigations are taking place at the composting plant in Darmstadt-Kranichstein (Germany). The aim is to explore the potential of bio-waste as feedstock in producing different bio-based products (or bio-based fuels). For this investigation, a facultative anaerobic process is to be integrated into the normal aerobic waste treatment process for composting. The bio-waste is to be treated in four steps to produce biofuels. The first step is the facultative anaerobic treatment of the waste in a rotting box namely percolate to generate a fatty-acid rich liquid fraction. The Hydrolysis takes place in the rotting box during the waste treatment. The organic compounds are then dissolved and transferred into the waste liquid phase. Browne et al. (2013) describes the hydrolysis as an enzymatically degradation of high solid substrates to soluble products which are further degraded to volatile fatty acids (VFA). This is confirmed by analytical tests done on the liquid fraction. After the percolation, volatile and medium chain fatty acids are found in the liquid phase. Concentrations of fatty acids between 8.0 and 31.5 were detected depending on the nature of the input material. In the second step, a fermentation process will be initiated to produce additional fatty acids. Existing microorganism mass is activated to degrade the organic components that are still remaining in the percolate. After fermentation the quantity of fatty acids in four investigated reactors increased 3-5 times. While fermentation mainly non-polar fatty acids (pentanoic to octanoic acid) are build. Next to the fermentation process, a chain-elongation step is arranged by adding ethanol to the fatty acid rich percolate. While these investigations a chain-elongation of mainly fatty acids with pair numbers of carbon atoms (acetate, butanoic and hexanoic acid) are demonstrated. After

  19. Extraction of medium chain fatty acids from organic municipal waste and subsequent production of bio-based fuels.

    PubMed

    Kannengiesser, Jan; Sakaguchi-Söder, Kaori; Mrukwia, Timo; Jager, Johannes; Schebek, Liselotte

    2016-01-01

    This paper provides an overview on investigations for a new technology to generate bio-based fuel additives from bio-waste. The investigations are taking place at the composting plant in Darmstadt-Kranichstein (Germany). The aim is to explore the potential of bio-waste as feedstock in producing different bio-based products (or bio-based fuels). For this investigation, a facultative anaerobic process is to be integrated into the normal aerobic waste treatment process for composting. The bio-waste is to be treated in four steps to produce biofuels. The first step is the facultative anaerobic treatment of the waste in a rotting box namely percolate to generate a fatty-acid rich liquid fraction. The Hydrolysis takes place in the rotting box during the waste treatment. The organic compounds are then dissolved and transferred into the waste liquid phase. Browne et al. (2013) describes the hydrolysis as an enzymatically degradation of high solid substrates to soluble products which are further degraded to volatile fatty acids (VFA). This is confirmed by analytical tests done on the liquid fraction. After the percolation, volatile and medium chain fatty acids are found in the liquid phase. Concentrations of fatty acids between 8.0 and 31.5 were detected depending on the nature of the input material. In the second step, a fermentation process will be initiated to produce additional fatty acids. Existing microorganism mass is activated to degrade the organic components that are still remaining in the percolate. After fermentation the quantity of fatty acids in four investigated reactors increased 3-5 times. While fermentation mainly non-polar fatty acids (pentanoic to octanoic acid) are build. Next to the fermentation process, a chain-elongation step is arranged by adding ethanol to the fatty acid rich percolate. While these investigations a chain-elongation of mainly fatty acids with pair numbers of carbon atoms (acetate, butanoic and hexanoic acid) are demonstrated. After

  20. Subdivision of the MDR superfamily of medium-chain dehydrogenases/reductases through iterative hidden Markov model refinement

    PubMed Central

    2010-01-01

    Background The Medium-chain Dehydrogenases/Reductases (MDR) form a protein superfamily whose size and complexity defeats traditional means of subclassification; it currently has over 15000 members in the databases, the pairwise sequence identity is typically around 25%, there are members from all kingdoms of life, the chain-lengths vary as does the oligomericity, and the members are partaking in a multitude of biological processes. There are profile hidden Markov models (HMMs) available for detecting MDR superfamily members, but none for determining which MDR family each protein belongs to. The current torrential influx of new sequence data enables elucidation of more and more protein families, and at an increasingly fine granularity. However, gathering good quality training data usually requires manual attention by experts and has therefore been the rate limiting step for expanding the number of available models. Results We have developed an automated algorithm for HMM refinement that produces stable and reliable models for protein families. This algorithm uses relationships found in data to generate confident seed sets. Using this algorithm we have produced HMMs for 86 distinct MDR families and 34 of their subfamilies which can be used in automated annotation of new sequences. We find that MDR forms with 2 Zn2+ ions in general are dehydrogenases, while MDR forms with no Zn2+ in general are reductases. Furthermore, in Bacteria MDRs without Zn2+ are more frequent than those with Zn2+, while the opposite is true for eukaryotic MDRs, indicating that Zn2+ has been recruited into the MDR superfamily after the initial life kingdom separations. We have also developed a web site http://mdr-enzymes.org that provides textual and numeric search against various characterised MDR family properties, as well as sequence scan functions for reliable classification of novel MDR sequences. Conclusions Our method of refinement can be readily applied to create stable and reliable HMMs

  1. Two-stage continuous process development for the production of medium-chain-length poly(3-hydroxyalkanoates).

    PubMed

    Jung, K; Hazenberg, W; Prieto, M; Witholt, B

    2001-01-01

    Pseudomonas oleovorans forms medium-chain-length poly(3-hydroxyalkanoate) (PHA) most effectively at growth rates below the maximum specific growth rate. Under adequate conditions, PHA accumulates in inclusion bodies in cells up to levels higher than half of the cell mass, which is a time-consuming process. For PHA production, a two-stage continuous cultivation system with two fermentors connected in series is a potentially useful system. It offers production of cells at a specific growth rate in a first compartment at conditions that lead cells to generate PHA at higher rates in a second compartment, with a relatively long residence time. In such a system, dilution rates of 0.21 h(-1) in the first fermentor (D(1)) and 0.16 h(-1) in the second fermentor (D(2)) were found to yield the highest volumetric PHA productivity. Transient-state experiments allowed investigation of D(1) and D(2) over a wide dilution rate range at high resolution in time-saving experiments. Furthermore, the influence of temperature, pH, nutrient limitation, and carbon source on PHA productivity was investigated and results similar to optimum conditions in single-stage chemostat cultivations of P. oleovorans were found. With all culture parameters optimized, a volumetric PHA productivity of 1.06 g L(-1) h(-1) was determined. Under these conditions, P. oleovorans cells contained 63% (dry weight) PHA in the effluent of the second fermentor. This is the highest PHA productivity and PHA content reported thus far for P. oleovorans cultures grown on alkanes. PMID:11084589

  2. The conversion of BTEX compounds by single and defined mixed cultures to medium-chain-length polyhydroxyalkanoate.

    PubMed

    Nikodinovic, Jasmina; Kenny, Shane T; Babu, Ramesh P; Woods, Trevor; Blau, Werner J; O'Connor, Kevin E

    2008-09-01

    Here, we report the use of petrochemical aromatic hydrocarbons as a feedstock for the biotechnological conversion into valuable biodegradable plastic polymers--polyhydroxyalkanoates (PHAs). We assessed the ability of the known Pseudomonas putida species that are able to utilize benzene, toluene, ethylbenzene, p-xylene (BTEX) compounds as a sole carbon and energy source for their ability to produce PHA from the single substrates. P. putida F1 is able to accumulate medium-chain-length (mcl) PHA when supplied with toluene, benzene, or ethylbenzene. P. putida mt-2 accumulates mcl-PHA when supplied with toluene or p-xylene. The highest level of PHA accumulated by cultures in shake flask was 26% cell dry weight for P. putida mt-2 supplied with p-xylene. A synthetic mixture of benzene, toluene, ethylbenzene, p-xylene, and styrene (BTEXS) which mimics the aromatic fraction of mixed plastic pyrolysis oil was supplied to a defined mixed culture of P. putida F1, mt-2, and CA-3 in the shake flasks and fermentation experiments. PHA was accumulated to 24% and to 36% of the cell dry weight of the shake flask and fermentation grown cultures respectively. In addition a three-fold higher cell density was achieved with the mixed culture grown in the bioreactor compared to shake flask experiments. A run in the 5-l fermentor resulted in the utilization of 59.6 g (67.5 ml) of the BTEXS mixture and the production of 6 g of mcl-PHA. The monomer composition of PHA accumulated by the mixed culture was the same as that accumulated by single strains supplied with single substrates with 3-hydroxydecanoic acid occurring as the predominant monomer. The purified polymer was partially crystalline with an average molecular weight of 86.9 kDa. It has a thermal degradation temperature of 350 degrees C and a glass transition temperature of -48.5 degrees C.

  3. Production and clearance of plasma triacylglycerols in ponies fed diets containing either medium-chain triacylglycerols or soya bean oil.

    PubMed

    Hallebeek, J M; Beynen, A C

    2003-06-01

    The hypothesis was tested that feeding ponies a diet containing medium-chain triacylglcyerols (MCT) instead of soya bean oil causes an increase in the production of plasma triacylglycerols, which, under steady-state conditions, is associated with an increased clearance of triacylglycerols. Six ponies were fed rations containing either MCT or an isoenergetic amount of soya bean oil according to a cross-over design. The concentration of MCT in the total dietary dry matter was about 13%. When the ponies were fed the diets for 3 weeks, plasma triacylglycerol concentrations were 0.42 +/- 0.09 and 0.17 +/- 0.03 mmol/l (mean +/- SE, n = 6; p < 0.05) for the MCT and soya bean-oil treatment, respectively. Plasma triacylglycerol production was assessed using the Triton method and clearance with the use of Intralipid(R) infusion. Plasma triacylglycerol production was 2.91 +/- 0.88 and 0.50 +/- 0.14 micromol/l.min (means +/- SE, n = 4; p < 0.05) for the diets containing MCT and soya bean oil, respectively. It is suggested that the calculated rates of triacylglycerol production are underestimated, the deviation being greatest when the ponies were fed the ration of soya bean oil. Triacylglycerol clearance rates were calculated on the basis of group mean values for both the fractional clearance rate and the baseline levels of plasma triacylglycerols; the values were 4.28 and 3.52 micromol/l.min for MCT and soya bean oil feeding, respectively. The mean, absolute clearance rates as based on those found in individual ponies did not show an increase when the diet with MCT was fed. Nevertheless, it is concluded that the data obtained support our hypothesis.

  4. Structurally divergent lysophosphatidic acid acyltransferases with high selectivity for saturated medium chain fatty acids from Cuphea seeds.

    PubMed

    Kim, Hae Jin; Silva, Jillian E; Iskandarov, Umidjon; Andersson, Mariette; Cahoon, Rebecca E; Mockaitis, Keithanne; Cahoon, Edgar B

    2015-12-01

    Lysophosphatidic acid acyltransferase (LPAT) catalyzes acylation of the sn-2 position on lysophosphatidic acid by an acyl CoA substrate to produce the phosphatidic acid precursor of polar glycerolipids and triacylglycerols (TAGs). In the case of TAGs, this reaction is typically catalyzed by an LPAT2 from microsomal LPAT class A that has high specificity for C18 fatty acids containing Δ9 unsaturation. Because of this specificity, the occurrence of saturated fatty acids in the TAG sn-2 position is infrequent in seed oils. To identify LPATs with variant substrate specificities, deep transcriptomic mining was performed on seeds of two Cuphea species producing TAGs that are highly enriched in saturated C8 and C10 fatty acids. From these analyses, cDNAs for seven previously unreported LPATs were identified, including cDNAs from Cuphea viscosissima (CvLPAT2) and Cuphea avigera var. pulcherrima (CpuLPAT2a) encoding microsomal, seed-specific class A LPAT2s and a cDNA from C. avigera var. pulcherrima (CpuLPATB) encoding a microsomal, seed-specific LPAT from the bacterial-type class B. The activities of these enzymes were characterized in Camelina sativa by seed-specific co-expression with cDNAs for various Cuphea FatB acyl-acyl carrier protein thioesterases (FatB) that produce a variety of saturated medium-chain fatty acids. CvLPAT2 and CpuLPAT2a expression resulted in accumulation of 10:0 fatty acids in the Camelina sativa TAG sn-2 position, indicating a 10:0 CoA specificity that has not been previously described for plant LPATs. CpuLPATB expression generated TAGs with 14:0 at the sn-2 position, but not 10:0. Identification of these LPATs provides tools for understanding the structural basis of LPAT substrate specificity and for generating altered oil functionalities.

  5. Effects of medium-chain fatty acids on the structure and immune response of IPEC-J2 cells.

    PubMed

    Martínez-Vallespín, B; Vahjen, W; Zentek, J

    2016-10-01

    Medium-chain fatty acids (MCFAs) have been suggested as an alternative to the use of antibiotics in animal nutrition with promising results. First, we studied the sensitivity of Salmonella Enteritidis and an enteropathogenic Escherichia coli strain against caprylic (C8), capric (C10) and lauric (C12) acids. A porcine in vitro model using the porcine cell line IPEC-J2 was used to test the effects of MCFAs on structural and immunological traits without and with a concomitant challenge with E. coli or S. Enteritidis. The three MCFAs exerted an inhibitory effect on bacterial growth, stronger for C12 than C8 or C10, S. Enteritidis being more sensitive than the E. coli strain. Flow cytometry showed a numeric concentration dependent increase in the adhesion of E. coli or S. Enteritidis to IPEC-J2 cells. Measurement of transepithelial electrical resistance after bacterial challenge showed negative effects of all MCFAs on IPEC-J2 cells at the highest concentrations. Immune parameters were affected by C8, since a concentration dependent effect starting at 5 mM was observed for mRNA expression of IL-6 and TLR-4 (up-regulated) and IL-8 (down-regulated). TLR-4 was up-regulated with C10 at 2 and 5 mM. The three MCFAs affected also the epithelial morphology through down-regulation of Occludin and up-regulation of Claudin-4 expression. In conclusion, the three MCFAs under study influenced bacterial growth rates and modified the gene expression to a different degree in the cell line IPEC-J2 but the effect on the morphological structure and response of the cells after bacterial challenge could not be assessed. Although these tests show a prior estimation of MCFAs effects in intestinal epithelium, in vivo confirmation is still needed. PMID:27553650

  6. 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 ...

  7. Enzymes involved in triglyceride hydrolysis.

    PubMed

    Taskinen, M R; Kuusi, T

    1987-08-01

    The lipolytic enzymes LPL and HL play important roles in the metabolism of lipoproteins and participate in lipoprotein interconversions. LPL was originally recognized to be the key enzyme in the hydrolysis of chylomicrons and triglyceride, but it also turned out to be one determinant of HDL concentration in plasma. When LPL activity is high, chylomicrons and VLDL are rapidly removed from circulation and a concomitant rise of the HDL2 occurs. In contrast, low LPL activity impedes the removal of triglyceride-rich particles, resulting in the elevation of serum triglycerides and a decrease of HDL (HDL2). Concordant changes of this kind in LPL and HDL2 are induced by many physiological and pathological perturbations. Finally, the operation of LPL is also essential for the conversion of VLDL to LDL. This apparently clear-cut role of LPL in lipoprotein interconversions is contrasted with the enigmatic actions of HL. The enzyme was originally thought to participate in the catalyses of chylomicron and VLDL remnants generated in the LPL reaction. However, substantial in vitro and in vivo data indicate that HL is a key enzyme in the degradation of plasma HDL (HDL2) in a manner which opposes LPL. A scheme is presented for the complementary actions of the two enzymes in plasma HDL metabolism. In addition, recent studies have attributed a role to HL in the catabolism of triglyceride-rich lipoproteins, particularly those containing apo E. However, this function becomes clinically important only under conditions where the capacity of the LPL-mediated removal system is exceeded. Such a situation may arise when the input of triglyceride-rich particles (chylomicrons and/or VLDL) is excessive or LPL activity is decreased or absent.

  8. Optimisation of stir-bar sorptive extraction (SBSE), targeting medium and long-chain free fatty acids in cooked ham exudates.

    PubMed

    Benet, Iu; Ibañez, Carles; Guàrdia, Maria Dolors; Solà, Josep; Arnau, Jacint; Roura, Eugeni

    2015-10-15

    The purpose of our research was to optimise the extraction conditions of the stir-bar sorptive extraction (SBSE) targeting the identification of lipid compounds particularly medium and long-chain free fatty acids in cooked cured pork ham exudates. The analytical conditions of extraction (including sample volume, extraction time, stirring speed, pH and dilution of the sample) were checked using the Simplex method approach. As a result of the SBSE optimisation, improved detection limits and linear ranges for hexanoic, heptanoic, octanoic, nonanoic, decanoic, dodecanoic and tetradecanoic fatty acids were obtained. When comparing results with those obtained by the commonly used SPME methodology, optimisation of SBSE achieved better results for volatile compounds of low volatility, such as medium and long-chain free fatty acids, whereas compounds with high volatility and polarity were only detected by SPME. SBSE also confirmed its potential as a tool to help identify undesirable contaminants/residues in meat products. PMID:25952843

  9. Optimisation of stir-bar sorptive extraction (SBSE), targeting medium and long-chain free fatty acids in cooked ham exudates.

    PubMed

    Benet, Iu; Ibañez, Carles; Guàrdia, Maria Dolors; Solà, Josep; Arnau, Jacint; Roura, Eugeni

    2015-10-15

    The purpose of our research was to optimise the extraction conditions of the stir-bar sorptive extraction (SBSE) targeting the identification of lipid compounds particularly medium and long-chain free fatty acids in cooked cured pork ham exudates. The analytical conditions of extraction (including sample volume, extraction time, stirring speed, pH and dilution of the sample) were checked using the Simplex method approach. As a result of the SBSE optimisation, improved detection limits and linear ranges for hexanoic, heptanoic, octanoic, nonanoic, decanoic, dodecanoic and tetradecanoic fatty acids were obtained. When comparing results with those obtained by the commonly used SPME methodology, optimisation of SBSE achieved better results for volatile compounds of low volatility, such as medium and long-chain free fatty acids, whereas compounds with high volatility and polarity were only detected by SPME. SBSE also confirmed its potential as a tool to help identify undesirable contaminants/residues in meat products.

  10. Glucose/lipid mixed substrates as a means of controlling the properties of medium chain length poly(hydroxyalkanoates).

    PubMed

    Ashby, R D; Solaiman, D K; Foglia, T A; Liu, C K

    2001-01-01

    Glucose-triacylglycerol (TAG) mixed substrates were used to modulate the physical and mechanical properties of medium-chain-length poly(hydroxyalkanoates) (mcl-PHAs). Pseudomonas resinovorans NRRL B-2649 grew and produced mcl-PHAs on glucose and TAGs (coconut oil, C; soybean oil, S) after 24 h in a shake flask culture. However, with the exception of coconut oil, maximum cell productivity was not reached in any of the cultures until 72 h post-inoculation. Here, 50:50 mixtures of glucose and coconut oil (glc/C) or glucose and soybean oil (glc/S) resulted in intermediate cell productivities with a maximum of 57% and 48% of the CDW at 72 h, respectively. In addition, mixed substrates resulted in mcl-PHAs with compositions that varied slightly over time. PHA-glc/C and PHA-glc/S were composed of 7 mol % and 8 mol % 3-hydroxydodecenoic acid (C(12:1)), respectively at 72 h. These concentrations were intermediate to the C(12:1) concentration of PHA-glc and respective PHA-TAG. Also, significant amounts of 3-hydroxytetradecanoic acid (C(14:0)), 3-hydroxytetradecenoic acid (C(14:1)), and 3-hydroxytetradecadienoic acid (C(14:2)) were present in PHA-glc/C and PHA-glc/S, which were derived from the respective TAG, as glucose resulted in almost no C(14:)(X) monomers. The molar masses of each of the polymers remained relatively constant between 24 and 96 h. At 72 h, the number-average molar masses (M(n)) of PHA-glc/C and PHA-glc/S were 178,000 and 163,000 g/mol, respectively, which were also intermediate to the M(n) of PHA-glc (225,000 g/mol) and the respective PHA-TAG (PHA-C = 153,000 g/mol; PHA-S = 75,000 g/mol). These physical differences caused variations in the mechanical properties of mcl-PHA films, thus providing a new and effective method of modifying their properties.

  11. A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy.

    PubMed

    Law, Tsz Hong; Davies, Emma S S; Pan, Yuanlong; Zanghi, Brian; Want, Elizabeth; Volk, Holger A

    2015-11-14

    Despite appropriate antiepileptic drug treatment, approximately one-third of humans and dogs with epilepsy continue experiencing seizures, emphasising the importance for new treatment strategies to improve the quality of life of people or dogs with epilepsy. A 6-month prospective, randomised, double-blinded, placebo-controlled cross-over dietary trial was designed to compare a ketogenic medium-chain TAG diet (MCTD) with a standardised placebo diet in chronically antiepileptic drug-treated dogs with idiopathic epilepsy. Dogs were fed either MCTD or placebo diet for 3 months followed by a subsequent respective switch of diet for a further 3 months. Seizure frequency, clinical and laboratory data were collected and evaluated for twenty-one dogs completing the study. Seizure frequency was significantly lower when dogs were fed the MCTD (2·31/month, 0-9·89/month) in comparison with the placebo diet (2·67/month, 0·33-22·92/month, P=0·020); three dogs achieved seizure freedom, seven additional dogs had ≥50 % reduction in seizure frequency, five had an overall <50 % reduction in seizures (38·87 %, 35·68-43·27 %) and six showed no response. Seizure day frequency were also significantly lower when dogs were fed the MCTD (1·63/month, 0-7·58/month) in comparison with the placebo diet (1·69/month, 0·33-13·82/month, P=0·022). Consumption of the MCTD also resulted in significant elevation of blood β-hydroxybutyrate concentrations in comparison with placebo diet (0·041 (sd 0·004) v. 0·031 (sd 0·016) mmol/l, P=0·028). There were no significant changes in serum concentrations of glucose (P=0·903), phenobarbital (P=0·422), potassium bromide (P=0·404) and weight (P=0·300) between diet groups. In conclusion, the data show antiepileptic properties associated with ketogenic diets and provide evidence for the efficacy of the MCTD used in this study as a therapeutic option for epilepsy treatment.

  12. A randomised trial of a medium-chain TAG diet as treatment for dogs with idiopathic epilepsy.

    PubMed

    Law, Tsz Hong; Davies, Emma S S; Pan, Yuanlong; Zanghi, Brian; Want, Elizabeth; Volk, Holger A

    2015-11-14

    Despite appropriate antiepileptic drug treatment, approximately one-third of humans and dogs with epilepsy continue experiencing seizures, emphasising the importance for new treatment strategies to improve the quality of life of people or dogs with epilepsy. A 6-month prospective, randomised, double-blinded, placebo-controlled cross-over dietary trial was designed to compare a ketogenic medium-chain TAG diet (MCTD) with a standardised placebo diet in chronically antiepileptic drug-treated dogs with idiopathic epilepsy. Dogs were fed either MCTD or placebo diet for 3 months followed by a subsequent respective switch of diet for a further 3 months. Seizure frequency, clinical and laboratory data were collected and evaluated for twenty-one dogs completing the study. Seizure frequency was significantly lower when dogs were fed the MCTD (2·31/month, 0-9·89/month) in comparison with the placebo diet (2·67/month, 0·33-22·92/month, P=0·020); three dogs achieved seizure freedom, seven additional dogs had ≥50 % reduction in seizure frequency, five had an overall <50 % reduction in seizures (38·87 %, 35·68-43·27 %) and six showed no response. Seizure day frequency were also significantly lower when dogs were fed the MCTD (1·63/month, 0-7·58/month) in comparison with the placebo diet (1·69/month, 0·33-13·82/month, P=0·022). Consumption of the MCTD also resulted in significant elevation of blood β-hydroxybutyrate concentrations in comparison with placebo diet (0·041 (sd 0·004) v. 0·031 (sd 0·016) mmol/l, P=0·028). There were no significant changes in serum concentrations of glucose (P=0·903), phenobarbital (P=0·422), potassium bromide (P=0·404) and weight (P=0·300) between diet groups. In conclusion, the data show antiepileptic properties associated with ketogenic diets and provide evidence for the efficacy of the MCTD used in this study as a therapeutic option for epilepsy treatment. PMID:26337751

  13. The combined use of whole Cuphea seeds containing medium chain fatty acids and an exogenous lipase in piglet nutrition.

    PubMed

    Dierick, N A; Decuypere, J A; Degeyter, I

    2003-02-01

    In search for an alternative for nutritional antimicrobials in piglet feeding, the effects of adding whole Cuphea seeds, as a natural source of medium chain fatty acids (MCFA), with known antimicrobial effects, and an exogenous lipase to a weaner diet were studied. The foregut flora, the gut morphology, some digestive parameters and the zootechnical performance of weaned piglets were investigated. Thirty newly weaned piglets, initial weight 7.0 +/- 0.4 kg, were divided according to litter, sex and weight in two groups (control diet; Cuphea + lipase diet). The Cuphea seeds (lanceolata and ignea) (50 g kg(-1)) were substituted for soybean oil (15 g kg(-1)), Alphacell (25 g kg(-1)) and soy protein isolate (10 g kg(-1)) in the control diet. Also 500 mg kg(-1) microbial lipase was added to the Cuphea diet. The piglets were weighted individually on days 0, 3. 7, 14 and 16. Feed intake was recorded per pen during days 0 to 3, 3 to 7, 7 to 14 and 14 to 16. On day 7 five piglets of each experimental group were euthanized for counting the gastric and small intestinal gut flora and for gut morphology at two sites of the small intestine (proximal, distal). The results indicate a trend towards improved performances parameters by feeding Cuphea + lipase. The enzymic released MCFA (1.7 g kg(-1) fresh gastric contents) tended to decrease the number of Coliforms in the proximal small intestine, but increased the number in the stomach and distal small intestine. With Culphea, the number of Streptococci was significantly lower in small intestine, but not in the stomach, while the number of Lactobacilli was significantly lower in the distal small intestine and tended to be lower in the stomach and proximal small intestine. No differences between the diets were noted for the total anaerobic microbial load in the stomach or in the gut. Feeding Cuphea + lipase resulted in a significantly greater villus height (distal small intestine) and a lesser crypt depth (proximal and distal small

  14. Newborn screening for medium-chain acyl-CoA dehydrogenase deficiency: regional experience and high incidence of carnitine deficiency

    PubMed Central

    2013-01-01

    Background Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common inherited defect in the mitochondrial fatty acid oxidation pathway, resulting in significant morbidity and mortality in undiagnosed patients. Newborn screening (NBS) has considerably improved MCADD outcome, but the risk of complication remains in some patients. The aim of this study was to evaluate the relationship between genotype, biochemical parameters and clinical data at diagnosis and during follow-up, in order to optimize monitoring of these patients. Methods We carried out a multicenter study in southwest Europe, of MCADD patients detected by NBS. Evaluated NBS data included free carnitine (C0) and the acylcarnitines C8, C10, C10:1 together with C8/C2 and C8/C10 ratios, clinical presentation parameters and genotype, in 45 patients. Follow-up data included C0 levels, duration of carnitine supplementation and occurrence of metabolic crises. Results C8/C2 ratio and C8 were the most accurate biomarkers of MCADD in NBS. We found a high number of patients homozygous for the prevalent c.985A > G mutation (75%). Moreover, in these patients C8, C8/C10 and C8/C2 were higher than in patients with other genotypes, while median value of C0 was significantly lower (23 μmol/L vs 36 μmol/L). The average follow-up period was 43 months. To keep carnitine levels within the normal range, carnitine supplementation was required in 82% of patients, and for a longer period in patients homozygotes for the c.985A>G mutation than in patients with other genotypes (average 31 vs 18 months). Even with treatment, median C0 levels remained lower in homozygous patients than in those with other genotypes (14 μmol/L vs 22 μmol/L). Two patients died and another three suffered a metabolic crisis, all of whom were homozygous for the c.985 A>G mutation. Conclusions Our data show a direct association between homozygosity for c.985A>G and lower carnitine values at diagnosis, and a higher dose of carnitine

  15. Medium-chain plasma acylcarnitines, ketone levels, cognition, and gray matter volumes in healthy elderly, mildly cognitively impaired, or Alzheimer's disease subjects.

    PubMed

    Ciavardelli, Domenico; Piras, Fabrizio; Consalvo, Ada; Rossi, Claudia; Zucchelli, Mirco; Di Ilio, Carmine; Frazzini, Valerio; Caltagirone, Carlo; Spalletta, Gianfranco; Sensi, Stefano L

    2016-07-01

    Aging, amyloid deposition, and tau-related pathology are key contributors to the onset and progression of Alzheimer's disease (AD). However, AD is also associated with brain hypometabolism and deficits of mitochondrial bioenergetics. Plasma acylcarnitines (ACCs) are indirect indices of altered fatty acid beta-oxidation, and ketogenesis has been found to be decreased on aging. Furthermore, in elderly subjects, alterations in plasma levels of specific ACCs have been suggested to predict conversion to mild cognitive impairment (MCI) or AD. In this study, we assayed plasma profiles of ACCs in a cohort of healthy elderly control, MCI subjects, and AD patients. Compared with healthy controls or MCI subjects, AD patients showed significant lower plasma levels of several medium-chain ACCs. Furthermore, in AD patients, these lower concentrations were associated with lower prefrontal gray matter volumes and the presence of cognitive impairment. Interestingly, lower levels of medium-chain ACCs were also found to be associated with lower plasma levels of 2-hydroxybutyric acid. Overall, these findings suggest that altered metabolism of medium-chain ACCs and impaired ketogenesis can be metabolic features of AD. PMID:27255810

  16. Medium-chain plasma acylcarnitines, ketone levels, cognition, and gray matter volumes in healthy elderly, mildly cognitively impaired, or Alzheimer's disease subjects.

    PubMed

    Ciavardelli, Domenico; Piras, Fabrizio; Consalvo, Ada; Rossi, Claudia; Zucchelli, Mirco; Di Ilio, Carmine; Frazzini, Valerio; Caltagirone, Carlo; Spalletta, Gianfranco; Sensi, Stefano L

    2016-07-01

    Aging, amyloid deposition, and tau-related pathology are key contributors to the onset and progression of Alzheimer's disease (AD). However, AD is also associated with brain hypometabolism and deficits of mitochondrial bioenergetics. Plasma acylcarnitines (ACCs) are indirect indices of altered fatty acid beta-oxidation, and ketogenesis has been found to be decreased on aging. Furthermore, in elderly subjects, alterations in plasma levels of specific ACCs have been suggested to predict conversion to mild cognitive impairment (MCI) or AD. In this study, we assayed plasma profiles of ACCs in a cohort of healthy elderly control, MCI subjects, and AD patients. Compared with healthy controls or MCI subjects, AD patients showed significant lower plasma levels of several medium-chain ACCs. Furthermore, in AD patients, these lower concentrations were associated with lower prefrontal gray matter volumes and the presence of cognitive impairment. Interestingly, lower levels of medium-chain ACCs were also found to be associated with lower plasma levels of 2-hydroxybutyric acid. Overall, these findings suggest that altered metabolism of medium-chain ACCs and impaired ketogenesis can be metabolic features of AD.

  17. Acyl CoA profiles of transgenic plants that accumulate medium-chain fatty acids indicate inefficient storage lipid synthesis in developing oilseeds.

    PubMed

    Larson, Tony R; Edgell, Teresa; Byrne, James; Dehesh, Katayoon; Graham, Ian A

    2002-11-01

    Several Brassica napus lines transformed with genes responsible for the synthesis of medium- or long-chain fatty acids were examined to determine limiting factor(s) for the subsequent accumulation of these fatty acids in seed lipids. Examination of a decanoic acid (10:0) accumulating line revealed a disproportionately high concentration of 10:0 CoA during seed development compared to long-chain acyl CoAs isolated from the same tissues, suggesting that poor incorporation of 10:0 CoA into seed lipids limits 10:0 fatty acid accumulation. This relationship was also seen for dodecanoyl (12:0) CoA and fatty acid in a high 12:0 line, but not for octadecanoic (18:0) CoA and fatty acid in a high 18:0 line. Comparison of 10:0 CoA and fatty acid proportions from seeds at different developmental stages for transgenic B. napus and Cuphea hookeriana, the source plant for the medium-chain thioesterase and 3-ketoacyl-ACP synthase transgenes, revealed that C. hookeriana incorporates 10:0 CoA into seed lipids more efficiently than transgenic B. napus. Furthermore, beta-oxidation and glyoxylate cycle activities were not increased above wild type levels during seed development in the 8:0/10:0 line, suggesting that lipid catabolism was not being induced in response to the elevated 10:0 CoA concentrations. Taken together, these data suggest that transgenic plants that are engineered to synthesize medium-chain fatty acids may lack the necessary mechanisms, such as specific acyltransferases, to incorporate these fatty acids efficiently into seed lipids.

  18. Characterization of alkylphenol degradation gene cluster in Pseudomonas putida MT4 and evidence of oxidation of alkylphenols and alkylcatechols with medium-length alkyl chain.

    PubMed

    Takeo, Masahiro; Prabu, Subbuswamy K; Kitamura, Chitoshi; Hirai, Makoto; Takahashi, Hana; Kato, Dai-Ichiro; Negoro, Seiji

    2006-10-01

    Alkylphenols (APs) are ubiquitous contaminants in aquatic environments and have endocrine disrupting and toxic effects on aquatic organisms. To investigate biodegradation mechanisms of APs, an AP degradation gene cluster was cloned from a butylphenol (BP)-degrading bacterium, Pseudomonas putida MT4. The gene cluster consisted of 13 genes named bupBA1A2A3A4A5A6CEHIFG. From the nucleotide sequences, bupA1A2A3A4A5A6 were predicted to encode a multicomponent phenol hydroxylase (PH), whereas bupBCEHIFG were expected to encode meta-cleavage pathway enzymes. A partial sequence of a putative NtrC-type regulatory gene, bupR, was also found upstream of the gene bupB. This result indicates that APs can be initially oxidized into alkylcatechols (ACs), followed by the meta-cleavage of the aromatic rings. To confirm this pathway, AP degradation tests were carried out using the recombinant P. putida KT2440 harboring the PH genes (bupA1A2A3A4A5A6). The recombinant strain oxidized 4-n-APs with an alkyl chain of up to C7 (< or = C7) efficiently and also several BPs including those with an alkyl chain with some degree of branching. Therefore, it was found that PH had a broad substrate specificity for APs with a medium-length alkyl chain (C3-C7). Moreover, the cell extract of a recombinant Escherichia coli harboring bupB (a catechol 2,3-dioxygenase gene) converted 4-n-ACs with an alkyl chain of < or = C9 into yellow meta-cleavage products with a maximum absorbance at 379 nm, indicating that the second step enzyme in this pathway is also responsible for the degradation of ACs with a medium-length alkyl chain. These results suggest that MT4 is a very useful strain in the biodegradation of a wide range of APs with a medium-length alkyl chain, which known nonylphenol-degrading Sphingomonas strains have never degraded. PMID:17116584

  19. 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

  20. The Medium-Chain Dehydrogenase/Reductase Engineering Database: A systematic analysis of a diverse protein family to understand sequence–structure–function relationship

    PubMed Central

    Knoll, Michael; Pleiss, Jürgen

    2008-01-01

    The Medium-Chain Dehydrogenase/Reductase Engineering Database (MDRED, http://www.mdred.uni-stuttgart.de) has been established to serve as an analysis tool for a systematic investigation of sequence–structure–function relationships. It includes sequence and structure information of 2684 and 42 medium-chain dehydrogenases/reductases (MDRs), respectively. Although MDRs are very diverse in sequence, they have a conserved tertiary structure. MDRs are assigned to 199 homologous families and 29 superfamilies. For each family, annotated multiple sequence alignments are provided, and functionally relevant residues are annotated. Twenty-five superfamilies were classified as zinc-containing MDRs, four as non-zinc-containing MDRs. For the zinc-containing MDRs, three subclasses were identified by systematic analysis of a variable loop region, the quaternary structure determining loop (QSDL): the class of short, medium, and long QSDL, which include 11, 3, and 5 superfamilies, respectively. The length of the QSDL is predictive for tetramer (short QSDL) and dimer (long QSDL) formation. The class of medium QSDL includes both tetrameric and dimeric MDRs. The shape of the substrate-binding site is highly conserved in all zinc-containing MDRs with the exception of two variable regions, the substrate recognition sites (SRS): two residues located on the QSDL (SRS1) and, for the class of long QSDL, one residue located in the catalytic domain (SRS2). The MDRED is the first online-accessible resource of MDRs that integrates information on sequence, structure, and function. Annotation of functionally relevant residues assist the understanding of sequence–structure–function relationships. Thus, the MDRED serves as a valuable tool to identify potential hotspots for engineering properties such as substrate specificity. PMID:18614751

  1. Transmural triglycerides in acute myocardial ischaemia.

    PubMed

    Jesmok, G J; Warltier, D C; Gross, G J; Hardman, H F

    1978-11-01

    The effect of coronary artery occlusion on endogenous triglycerides of left ventricular subepicardium and subendocardium was studied in the open-chest anaesthetised dog. Under control conditions, the subepicardium was found to have a greater concentration of triglycerides than the subendocardium. Thirty minutes after acute coronary artery occlusion there was a decrease followed by a steady increase at 60, 120, and 240 min in subepicardial triglycerides of the ischaemic region. No change in triglycerides in the subendocardium of normal or ischaemic regions was observed. The initial decrease of subepicardial triglycerides in the ischaemic region was blocked by administration of propranolol or bevantolol (CI-775; a specific beta 1 antagonist) given 30 min before occlusion. It is concluded that the effect of coronary artery ligation on transmural endogenous triglycerides is biphasic with an initial period of increased mobilisation followed by a period of increased deposition.

  2. YfcX Enables Medium-Chain-Length Poly(3-Hydroxyalkanoate) Formation from Fatty Acids in Recombinant Escherichia coli fadB Strains

    PubMed Central

    Snell, Kristi D.; Feng, Feng; Zhong, Luhua; Martin, David; Madison, Lara L.

    2002-01-01

    Expression of Escherichia coli open reading frame yfcX is shown to be required for medium-chain-length polyhydroxyalkanoate (PHAMCL) formation from fatty acids in an E. coli fadB mutant. The open reading frame encodes a protein, YfcX, with significant similarity to the large subunit of multifunctional β-oxidation enzymes. E. coli fadB strains modified to contain an inactivated copy of yfcX and to express a medium-chain-length synthase are unable to form PHAMCLs when grown in the presence of fatty acids. Plasmid-based expression of yfcX in the FadB− YfcX− PhaC+ strain restores polymer formation. YfcX is shown to be a multifunctional enzyme that minimally encodes hydratase and dehydrogenase activities. The gene encoding YfcX is located downstream from yfcY, a gene encoding thiolase activity. Results of insertional inactivation studies and enzyme activity analyses suggest a role for yfcX in PHA monomer unit formation in recombinant E. coli fadB mutant strains. Further studies are required to determine the natural role of YfcX in the metabolism of E. coli. PMID:12270828

  3. Improvement of medium chain fatty acid content and antimicrobial activity of coconut oil via solid-state fermentation using a Malaysian Geotrichum candidum.

    PubMed

    Khoramnia, Anahita; Ebrahimpour, Afshin; Ghanbari, Raheleh; Ajdari, Zahra; Lai, Oi-Ming

    2013-01-01

    Coconut oil is a rich source of beneficial medium chain fatty acids (MCFAs) particularly lauric acid. In this study, the oil was modified into a value-added product using direct modification of substrate through fermentation (DIMOSFER) method. A coconut-based and coconut-oil-added solid-state cultivation using a Malaysian lipolytic Geotrichum candidum was used to convert the coconut oil into MCFAs-rich oil. Chemical characteristics of the modified coconut oils (MCOs) considering total medium chain glyceride esters were compared to those of the normal coconut oil using ELSD-RP-HPLC. Optimum amount of coconut oil hydrolysis was achieved at 29% moisture content and 10.14% oil content after 9 days of incubation, where the quantitative amounts of the modified coconut oil and MCFA were 0.330 mL/g of solid media (76.5% bioconversion) and 0.175 mL/g of solid media (53% of the MCO), respectively. MCOs demonstrated improved antibacterial activity mostly due to the presence of free lauric acid. The highest MCFAs-rich coconut oil revealed as much as 90% and 80% antibacterial activities against Staphylococcus aureus and Escherichia coli, respectively. The results of the study showed that DIMOSFER by a local lipolytic G. candidum can be used to produce MCFAs as natural, effective, and safe antimicrobial agent. The produced MCOs and MCFAs could be further applied in food and pharmaceutical industries.

  4. Improvement of Medium Chain Fatty Acid Content and Antimicrobial Activity of Coconut Oil via Solid-State Fermentation Using a Malaysian Geotrichum candidum

    PubMed Central

    Khoramnia, Anahita; Ebrahimpour, Afshin; Ghanbari, Raheleh; Ajdari, Zahra; Lai, Oi-Ming

    2013-01-01

    Coconut oil is a rich source of beneficial medium chain fatty acids (MCFAs) particularly lauric acid. In this study, the oil was modified into a value-added product using direct modification of substrate through fermentation (DIMOSFER) method. A coconut-based and coconut-oil-added solid-state cultivation using a Malaysian lipolytic Geotrichum candidum was used to convert the coconut oil into MCFAs-rich oil. Chemical characteristics of the modified coconut oils (MCOs) considering total medium chain glyceride esters were compared to those of the normal coconut oil using ELSD-RP-HPLC. Optimum amount of coconut oil hydrolysis was achieved at 29% moisture content and 10.14% oil content after 9 days of incubation, where the quantitative amounts of the modified coconut oil and MCFA were 0.330 mL/g of solid media (76.5% bioconversion) and 0.175 mL/g of solid media (53% of the MCO), respectively. MCOs demonstrated improved antibacterial activity mostly due to the presence of free lauric acid. The highest MCFAs-rich coconut oil revealed as much as 90% and 80% antibacterial activities against Staphylococcus aureus and Escherichia coli, respectively. The results of the study showed that DIMOSFER by a local lipolytic G. candidum can be used to produce MCFAs as natural, effective, and safe antimicrobial agent. The produced MCOs and MCFAs could be further applied in food and pharmaceutical industries. PMID:23971051

  5. Synthesis of polyhydroxyalkanoates from glucose that contain medium-chain-length monomers via the reversed fatty acid β-oxidation cycle in Escherichia coli.

    PubMed

    Zhuang, Qianqian; Wang, Qian; Liang, Quanfeng; Qi, Qingsheng

    2014-07-01

    Polyhydroxyalkanoates that contain the medium-chain-length monomers (mcl-PHAs) have a wide range of applications owing to their superior physical and mechanical properties. A challenge to synthesize such mcl-PHAs from unrelated and renewable sources is exploiting the efficient metabolic pathways that lead to the formation of precursor (R)-3-hydroxyacyl-CoA. Here, by engineering the reversed fatty acid β-oxidation cycle, we were able to synthesize mcl-PHAs in Escherichia coli directly from glucose. After deletion of the major thioesterases, the engineered E. coli produced 6.62wt% of cell dry weight mcl-PHA heteropolymers. Furthermore, when a low-substrate-specificity PHA synthase from Pseudomonas stutzeri 1317 was employed, recombinant E. coli synthesized 12.10wt% of cell dry weight scl-mcl PHA copolymers, of which 21.18mol% was 3-hydroxybutyrate and 78.82mol% was medium-chain-length monomers. The reversed fatty acid β-oxidation cycle offered an efficient metabolic pathway for mcl-PHA biosynthesis in E. coli and can be further optimized.

  6. Integrated engineering of β-oxidation reversal and ω-oxidation pathways for the synthesis of medium chain ω-functionalized carboxylic acids.

    PubMed

    Clomburg, James M; Blankschien, Matthew D; Vick, Jacob E; Chou, Alexander; Kim, Seohyoung; Gonzalez, Ramon

    2015-03-01

    An engineered reversal of the β-oxidation cycle was exploited to demonstrate its utility for the synthesis of medium chain (6-10-carbons) ω-hydroxyacids and dicarboxylic acids from glycerol as the only carbon source. A redesigned β-oxidation reversal facilitated the production of medium chain carboxylic acids, which were converted to ω-hydroxyacids and dicarboxylic acids by the action of an engineered ω-oxidation pathway. The selection of a key thiolase (bktB) and thioesterase (ydiI) in combination with previously established core β-oxidation reversal enzymes, as well as the development of chromosomal expression systems for the independent control of pathway enzymes, enabled the generation of C6-C10 carboxylic acids and provided a platform for vector based independent expression of ω-functionalization enzymes. Using this approach, the expression of the Pseudomonas putida alkane monooxygenase system, encoded by alkBGT, in combination with all β-oxidation reversal enzymes resulted in the production of 6-hydroxyhexanoic acid, 8-hydroxyoctanoic acid, and 10-hydroxydecanoic acid. Following identification and characterization of potential alcohol and aldehyde dehydrogenases, chnD and chnE from Acinetobacter sp. strain SE19 were expressed in conjunction with alkBGT to demonstrate the synthesis of the C6-C10 dicarboxylic acids, adipic acid, suberic acid, and sebacic acid. The potential of a β-oxidation cycle with ω-oxidation termination pathways was further demonstrated through the production of greater than 0.8 g/L C6-C10 ω-hydroxyacids or about 0.5 g/L dicarboxylic acids of the same chain lengths from glycerol (an unrelated carbon source) using minimal media.

  7. Abundances of Triacylglycerol Positional Isomers and Enantiomers Comprised of a Dipalmitoylglycerol Backbone and Short- or Medium-chain Fatty Acids in Bovine Milk Fat.

    PubMed

    Nagai, Toshiharu; Watanabe, Natsuko; Yoshinaga, Kazuaki; Mizobe, Hoyo; Kojima, Koichi; Kuroda, Ikuma; Odanaka, Yuki; Saito, Tadao; Beppu, Fumiaki; Gotoh, Naohiro

    2015-01-01

    Bovine milk fat (BMF) is composed of triacylglycerols (TAG) rich in palmitic acid (P), oleic acid (O), and short-chain or medium-chain fatty acids (SCFAs or MCFAs). The composition and binding positions of the fatty acids on the glycerol backbone determine their physical and nutritional properties. SCFAs and MCFAs are known to characteristically bind to the sn-3 position of the TAGs in BMF; however, there are very few non-destructive analyses of TAG enantiomers binding the fatty acids at this position. We previously reported a method to resolve the enantiomers of TAGs, binding both long-chain saturated fatty acid and unsaturated fatty acid at the sn-1 and 3 positions, in palm oil, fish oil, and marine mammal oil using chiral HPLC. Here, we further developed a method to resolve several TAG enantiomers containing a dipalmitoyl (PP) glycerol backbone and one SCFA (or MCFA) in BMF. We revealed that the predominant TAG structure in BMF was homochiral, such as 1,2-dipalmitoyl-3-butyroyl-sn-glycerol. This is the first quantitative determination of many TAG enantiomers, which bind to a SCFA or MCFA, in BMF was evaluated simultaneously. Furthermore, the results indicated that the amount ratios of the positional isomers and enantiomers of TAGs consisting of a dipalmitoyl (PP) glycerol backbone and SCFA (or MCFA), resembled the whole TAG structures containing the other diacylglycerol backbones consisting of P, O, myristic acid, and/or stearic acid in BMF. PMID:26329769

  8. Engineering Escherichia coli for Conversion of Glucose to Medium-Chain ω-Hydroxy Fatty Acids and α,ω-Dicarboxylic Acids.

    PubMed

    Bowen, Christopher H; Bonin, Jeff; Kogler, Anna; Barba-Ostria, Carlos; Zhang, Fuzhong

    2016-03-18

    In search of sustainable approaches to plastics production, many efforts have been made to engineer microbial conversions of renewable feedstock to short-chain (C2-C8) bifunctional polymer precursors (e.g., succinic acid, cadaverine, 1,4-butanediol). Less attention has been given to medium-chain (C12-C14) monomers such as ω-hydroxy fatty acids (ω-OHFAs) and α,ω-dicarboxylic acids (α,ω-DCAs), which are precursors to high performance polyesters and polyamides. Here we engineer a complete microbial conversion of glucose to C12 and C14 ω-OHFAs and α,ω-DCAs, with precise control of product chain length. Using an expanded bioinformatics approach, we screen a wide range of enzymes across phyla to identify combinations that yield complete conversion of intermediates to product α,ω-DCAs. Finally, through optimization of culture conditions, we enhance production titer of C12 α,ω-DCA to nearly 600 mg/L. Our results indicate potential for this microbial factory to enable commercially relevant, renewable production of C12 α,ω-DCA-a valuable precursor to the high-performance plastic, nylon-6,12. PMID:26669968

  9. The synthesis of n-caproate from lactate: a new efficient process for medium-chain carboxylates production

    PubMed Central

    Zhu, Xiaoyu; Tao, Yong; Liang, Cheng; Li, Xiangzhen; Wei, Na; Zhang, Wenjie; Zhou, Yan; Yang, Yanfei; Bo, Tao

    2015-01-01

    A unique microbiome that metabolizes lactate rather than ethanol for n-caproate production was obtained from a fermentation pit used for the production of Chinese strong-flavour liquor (CSFL). The microbiome was able to produce n-caproate at concentrations as high as 23.41 g/L at a maximum rate of 2.97 g/L/d in batch trials without in-line extraction. Compared with previous work using ethanol as the electron donor, the n-caproate concentration increased by 82.89%. High-throughput sequencing analysis showed that the microbiome was dominated by a Clostridium cluster IV, which accounted for 79.07% of total reads. A new process for n-caproate production was proposed, lactate oxidation coupled to chain elongation, which revealed new insight into the well-studied lactate conversion and carbon chain elongation. In addition, these findings indicated a new synthesis mechanism of n-caproate in CSFL. We believe that this efficient process will provide a promising opportunity for the innovation of waste recovery as well as for n-caproate biosynthesis. PMID:26403516

  10. Biosynthesis and genomic analysis of medium-chain hydrocarbon production by the endophytic fungal isolate Nigrograna mackinonnii E5202H

    PubMed Central

    Shaw, Jeffery J; Spakowicz, Daniel J; Dalal, Rahul S; Davis, Jared H; Lehr, Nina A; Dunican, Brian F; Orellana, Esteban A; Narváez-Trujillo, Alexandra; Strobel, Scott A

    2015-01-01

    An endophytic fungus was isolated that produces a series of volatile natural products, including terpenes and odd chain polyenes. Phylogenetic analysis of the isolate using five loci suggests that it is closely related to Nigrograna mackinnonii CBS 674.75. The main component of the polyene series was purified and identified as (3E,5E,7E)-nona-1,3,5,7-tetraene (NTE), a novel natural product. Non-oxygenated hydrocarbons of this chain length are uncommon and desirable as gasoline-surrogate biofuels. The biosynthetic pathway for NTE production was explored using metabolic labeling and GCMS. Two-carbon incorporation 13C acetate suggests that it is derived from a polyketide synthase (PKS) followed by decarboxylation. There are several known mechanisms for such decarboxylation, though none have been discovered in fungi. Towards identifying the PKS responsible for the production of NTE, the genome of N. mackinnonii E5202H (ATCC SD-6839) was sequenced and assembled. Of the 32 PKSs present in the genome, 17 are predicted to contain sufficient domains for the production of NTE. These results exemplify the capacity of endophytic fungi to produce novel natural products that may have many uses, such as biologically derived fuels and commodity chemicals. PMID:25672844

  11. Carbon-limited fed-batch production of medium-chain-length polyhydroxyalkanoates by a phaZ-knockout strain of Pseudomonas putida KT2440.

    PubMed

    Vo, Minh Tri; Ko, Kenton; Ramsay, Bruce

    2015-04-01

    A medium-chain-length poly-3-hydroxyalkanote (MCL-PHA) depolymerase knockout mutant of Pseudomonas putida KT2440 was produced by double homologous recombination. A carbon-limited shake-flask study confirmed that depolymerase activity was eliminated. Lysis of both mutant and wild-type strains occurred under these conditions. In carbon-limited, fed-batch culture, the yield of unsaturated monomers from unsaturated substrate averaged only 0.62 mol mol(-1) for the phaZ minus strain compared to 0.72 mol mol(-1) for the wild type. The mutant strain also produced more CO2 and less residual biomass from the same amount of carbon substrate. However, most results indicated that elimination of PHA depolymerase activity had little impact on the overall yield of biomass and PHA.

  12. Theoretical studies of salt-bridge formation by amino acid side chains in low and medium polarity environments.

    PubMed

    Nagy, Peter I; Erhardt, Paul W

    2010-12-16

    Salt-bridge formation between Asp/Glu···Lys and Asp/Glu···Arg side chains has been studied by model systems including formic and acetic acids as proton donors and methylamine, guanidine, and methylguanidine as proton acceptors. Calculations have been performed up to the CCSD(T)(CBS)//MP2/aug-cc-pvtz level with formic acid proton donors. Complexes formed with acetic acid were studied at the CCSD(T)/aug-cc-pvdz//MP2/aug-cc-pvdz level. Protein environments of low and moderate polarity were mimicked by a continuum solvent with dielectric constants (ε) set to 5 and 15, respectively. Free energy differences, ΔG(tot), were calculated for the neutral, hydrogen-bonded form and for the tautomeric ion pair. These values predict that a salt bridge is not favored for the Asp/Glu···Lys pair, even in an environment with ε as large as 15. In contrast, the Asp/Glu···Arg salt bridge is feasible even in an environment with ε = 5. Charge transfers for the complexes were calculated on the basis of CHELPG and AIM charges.

  13. Equilibrium and dynamical properties of polymer chains in random medium filled with randomly distributed nano-sized fillers.

    PubMed

    Li, Chao-Yang; Luo, Meng-Bo; Huang, Jian-Hua; Li, Hong

    2015-12-21

    The effect of randomly distributed nano-sized fillers on the equilibrium and dynamical properties of linear polymers is studied by using off-lattice Monte Carlo simulation. Lennard-Jones interactions between polymers and fillers are considered. Results show that the statistical dimensions and dynamical diffusion of polymer are dependent on the polymer-filler interaction strength εpf. The mean square radius of gyration 〈RG(2)〉 shows a minimum at a critical polymer-filler interaction εpf*. The value of εpf* decreases with the increase in the polymer length or the concentration of fillers. The exponent ν in 〈RG(2)〉 ∼ N(2ν) is a typical value of self-avoiding walking chain at small εpf but it increases sharply to a bigger value at εpf > εpf*. The mean square displacement decreases with the increase in εpf. Moreover, the normal diffusion of the polymer at weak interactions changes to subnormal diffusion at moderate and strong attractions. We find that polymers diffuse in dilute filler regions at weak attraction and diffuse in dense filler regions at strong attraction. PMID:26568204

  14. Molecular cloning and sequence analysis of complementary DNA encoding rat mammary gland medium-chain S-acyl fatty acid synthetase thio ester hydrolase

    SciTech Connect

    Safford, R.; de Silva, J.; Lucas, C.; Windust, J.H.C.; Shedden, J.; James, C.M.; Sidebottom, C.M.; Slabas, A.R.; Tombs, M.P.; Hughes, S.G.

    1987-03-10

    Poly(A) + RNA from pregnant rat mammary glands was size-fractionated by sucrose gradient centrifugation, and fractions enriched in medium-chain S-acyl fatty acid synthetase thio ester hydrolase (MCH) were identified by in vitro translation and immunoprecipitation. A cDNA library was constructed, in pBR322, from enriched poly(A) + RNA and screened with two oligonucleotide probes deduced from rat MCH amino acid sequence data. Cross-hybridizing clones were isolated and found to contain cDNA inserts ranging from approx. 1100 to 1550 base pairs (bp). A 1550-bp cDNA insert, from clone 43H09, was confirmed to encode MCH by hybrid-select translation/immunoprecipitation studies and by comparison of the amino acid sequence deduced from the DNA sequence of the clone to the amino acid sequence of the MCH peptides. Northern blot analysis revealed the size of the MCH mRNA to be 1500 nucleotides, and it is therefore concluded that the 1550-bp insert (including G x C tails) of clone 43H09 represents a full- or near-full-length copy of the MCH gene. The rat MCH sequence is the first reported sequence of a thioesterase from a mammalian source, but comparison of the deduced amino acid sequences of MCH and the recently published mallard duck medium-chain S-acyl fatty acid synthetase thioesterase reveals significant homology. In particular, a seven amino acid sequence containing the proposed active serine of the duck thioesterase is found to be perfectly conserved in rat MCH.

  15. Characterization of the Medium- and Long-Chain n-Alkanes Degrading Pseudomonas aeruginosa Strain SJTD-1 and Its Alkane Hydroxylase Genes

    PubMed Central

    Liu, Huan; Xu, Jing; Liang, Rubing; Liu, Jianhua

    2014-01-01

    A gram-negative aliphatic hydrocarbon-degrading bacterium SJTD-1 isolated from oil-contaminated soil was identified as Pseudomonas aeruginosa by comparative analyses of the 16S rRNA sequence, phenotype, and physiological features. SJTD-1 could efficiently mineralize medium- and long-chain n-alkanes (C12-C30) as its sole carbon source within seven days, showing the most optimal growth on n-hexadecane, followed by n-octadecane, and n-eicosane. In 36 h, 500 mg/L of tetradecane, hexadecane, and octadecane were transformed completely; and 2 g/L n-hexadecane was degraded to undetectable levels within 72 h. Two putative alkane-degrading genes (gene 3623 and gene 4712) were characterized and our results indicated that their gene products were rate-limiting enzymes involved in the synergetic catabolism of C12–C16 alkanes. On the basis of bioinformatics and transcriptional analysis, two P450 monooxygenases, along with a putative AlmA-like oxygenase, were examined. Genetically defective mutants lacking the characteristic alkane hydroxylase failed to degrade n-octadecane, thereby suggesting a different catalytic mechanism for the microbial transformation of alkanes with chain lengths over C18. PMID:25165808

  16. Modulation of medium-chain fatty acid synthesis in Synechococcus sp. PCC 7002 by replacing FabH with a Chaetoceros Ketoacyl-ACP synthase

    DOE PAGES

    Gu, Huiya; Jinkerson, Robert E.; Davies, Fiona K.; Sisson, Lyle A.; Schneider, Philip E.; Posewitz, Matthew C.

    2016-05-26

    The isolation or engineering of algal cells synthesizing high levels of medium-chain fatty acids (MCFAs) is attractive to mitigate the high clouding point of longer chain fatty acids in algal based biodiesel. To develop a more informed understanding of MCFA synthesis in photosynthetic microorganisms, we isolated several algae from Great Salt Lake and screened this collection for MCFA accumulation to identify strains naturally accumulating high levels of MCFA. A diatom, Chaetoceros sp. GSL56, accumulated particularly high levels of C14 (up to 40%), with the majority of C14 fatty acids allocated in triacylglycerols. Using whole cell transcriptome sequencing and de novomore » assembly, putative genes encoding fatty acid synthesis enzymes were identified. Enzymes from this Chaetoceros sp. were expressed in the cyanobacterium Synechococcus sp. PCC 7002 to validate gene function and to determine whether eukaryotic enzymes putatively lacking bacterial evolutionary control mechanisms could be used to improve MCFA production in this promising production strain. Replacement of the Synechococcus 7002 native FabH with a Chaetoceros ketoacyl-ACP synthase Ill increased MCFA synthesis up to fivefold. In conclusion, the level of increase is dependent on promoter strength and culturing conditions.« less

  17. Characterization of the medium- and long-chain n-alkanes degrading Pseudomonas aeruginosa strain SJTD-1 and its alkane hydroxylase genes.

    PubMed

    Liu, Huan; Xu, Jing; Liang, Rubing; Liu, Jianhua

    2014-01-01

    A gram-negative aliphatic hydrocarbon-degrading bacterium SJTD-1 isolated from oil-contaminated soil was identified as Pseudomonas aeruginosa by comparative analyses of the 16S rRNA sequence, phenotype, and physiological features. SJTD-1 could efficiently mineralize medium- and long-chain n-alkanes (C12-C30) as its sole carbon source within seven days, showing the most optimal growth on n-hexadecane, followed by n-octadecane, and n-eicosane. In 36 h, 500 mg/L of tetradecane, hexadecane, and octadecane were transformed completely; and 2 g/L n-hexadecane was degraded to undetectable levels within 72 h. Two putative alkane-degrading genes (gene 3623 and gene 4712) were characterized and our results indicated that their gene products were rate-limiting enzymes involved in the synergetic catabolism of C12-C16 alkanes. On the basis of bioinformatics and transcriptional analysis, two P450 monooxygenases, along with a putative AlmA-like oxygenase, were examined. Genetically defective mutants lacking the characteristic alkane hydroxylase failed to degrade n-octadecane, thereby suggesting a different catalytic mechanism for the microbial transformation of alkanes with chain lengths over C18. PMID:25165808

  18. Increasing the Thermal Conductivity of Graphene-Polyamide-6,6 Nanocomposites by Surface-Grafted Polymer Chains: Calculation with Molecular Dynamics and Effective-Medium Approximation.

    PubMed

    Gao, Yangyang; Müller-Plathe, Florian

    2016-02-25

    By employing reverse nonequilibrium molecular dynamics simulations in a full atomistic resolution, the effect of surface-grafted chains on the thermal conductivity of graphene-polyamide-6.6 (PA) nanocomposites has been investigated. The interfacial thermal conductivity perpendicular to the graphene plane is proportional to the grafting density, while it first increases and then saturates with the grafting length. Meanwhile, the intrinsic in-plane thermal conductivity of graphene drops sharply as the grafting density increases. The maximum overall thermal conductivity of nanocomposites appears at an intermediate grafting density because of these two competing effects. The thermal conductivity of the composite parallel to the graphene plane increases with the grafting density and grafting length which is attributed to better interfacial coupling between graphene and PA. There exists an optimal balance between grafting density and grafting length to obtain the highest interfacial and parallel thermal conductivity. Two empirical formulas are suggested, which quantitatively account for the effects of grafting length and density on the interfacial and parallel thermal conductivity. Combined with effective medium approximation, for ungrafted graphene in random orientation, the model overestimates the thermal conductivity at low graphene volume fraction (f < 10%) compared with experiments, while it underestimates it at high graphene volume fraction (f > 10%). For unoriented grafted graphene, the model matches the experimental results well. In short, this work provides some valuable guides to obtain the nanocomposites with high thermal conductivity by grafting chain on the surface of graphene.

  19. Increasing the Thermal Conductivity of Graphene-Polyamide-6,6 Nanocomposites by Surface-Grafted Polymer Chains: Calculation with Molecular Dynamics and Effective-Medium Approximation.

    PubMed

    Gao, Yangyang; Müller-Plathe, Florian

    2016-02-25

    By employing reverse nonequilibrium molecular dynamics simulations in a full atomistic resolution, the effect of surface-grafted chains on the thermal conductivity of graphene-polyamide-6.6 (PA) nanocomposites has been investigated. The interfacial thermal conductivity perpendicular to the graphene plane is proportional to the grafting density, while it first increases and then saturates with the grafting length. Meanwhile, the intrinsic in-plane thermal conductivity of graphene drops sharply as the grafting density increases. The maximum overall thermal conductivity of nanocomposites appears at an intermediate grafting density because of these two competing effects. The thermal conductivity of the composite parallel to the graphene plane increases with the grafting density and grafting length which is attributed to better interfacial coupling between graphene and PA. There exists an optimal balance between grafting density and grafting length to obtain the highest interfacial and parallel thermal conductivity. Two empirical formulas are suggested, which quantitatively account for the effects of grafting length and density on the interfacial and parallel thermal conductivity. Combined with effective medium approximation, for ungrafted graphene in random orientation, the model overestimates the thermal conductivity at low graphene volume fraction (f < 10%) compared with experiments, while it underestimates it at high graphene volume fraction (f > 10%). For unoriented grafted graphene, the model matches the experimental results well. In short, this work provides some valuable guides to obtain the nanocomposites with high thermal conductivity by grafting chain on the surface of graphene. PMID:26800434

  20. Modulation of Medium-Chain Fatty Acid Synthesis in Synechococcus sp. PCC 7002 by Replacing FabH with a Chaetoceros Ketoacyl-ACP Synthase

    PubMed Central

    Gu, Huiya; Jinkerson, Robert E.; Davies, Fiona K.; Sisson, Lyle A.; Schneider, Philip E.; Posewitz, Matthew C.

    2016-01-01

    The isolation or engineering of algal cells synthesizing high levels of medium-chain fatty acids (MCFAs) is attractive to mitigate the high clouding point of longer chain fatty acids in algal based biodiesel. To develop a more informed understanding of MCFA synthesis in photosynthetic microorganisms, we isolated several algae from Great Salt Lake and screened this collection for MCFA accumulation to identify strains naturally accumulating high levels of MCFA. A diatom, Chaetoceros sp. GSL56, accumulated particularly high levels of C14 (up to 40%), with the majority of C14 fatty acids allocated in triacylglycerols. Using whole cell transcriptome sequencing and de novo assembly, putative genes encoding fatty acid synthesis enzymes were identified. Enzymes from this Chaetoceros sp. were expressed in the cyanobacterium Synechococcus sp. PCC 7002 to validate gene function and to determine whether eukaryotic enzymes putatively lacking bacterial evolutionary control mechanisms could be used to improve MCFA production in this promising production strain. Replacement of the Synechococcus 7002 native FabH with a Chaetoceros ketoacyl-ACP synthase III increased MCFA synthesis up to fivefold. The level of increase is dependent on promoter strength and culturing conditions. PMID:27303412

  1. NMR metabolomics profiling of blood plasma mimics shows that medium- and long-chain fatty acids differently release metabolites from human serum albumin

    NASA Astrophysics Data System (ADS)

    Jupin, M.; Michiels, P. J.; Girard, F. C.; Spraul, M.; Wijmenga, S. S.

    2014-02-01

    Metabolite profiling by NMR of body fluids is increasingly used to successfully differentiate patients from healthy individuals. Metabolites and their concentrations are direct reporters of body biochemistry. However, in blood plasma the NMR-detected free-metabolite concentrations are also strongly affected by interactions with the abundant plasma proteins, which have as of yet not been considered much in metabolic profiling. We previously reported that many of the common NMR-detected metabolites in blood plasma bind to human serum albumin (HSA) and many are released by fatty acids present in fatted HSA. HSA is the most abundant plasma protein and main transporter of endogenous and exogenous metabolites. Here, we show by NMR how the two most common fatty acids (FAs) in blood plasma - the long-chain FA, stearate (C18:0) and medium-chain FA, myristate (C14:0) - affect metabolite-HSA interaction. Of the set of 18 common NMR-detected metabolites, many are released by stearate and/or myristate, lactate appearing the most strongly affected. Myristate, but not stearate, reduces HSA-binding of phenylalanine and pyruvate. Citrate signals were NMR invisible in the presence of HSA. Only at high myristate-HSA mole ratios 11:1, is citrate sufficiently released to be detected. Finally, we find that limited dilution of blood-plasma mimics releases HSA-bound metabolites, a finding confirmed in real blood plasma samples. Based on these findings, we provide recommendations for NMR experiments for quantitative metabolite profiling.

  2. Modulation of Medium-Chain Fatty Acid Synthesis in Synechococcus sp. PCC 7002 by Replacing FabH with a Chaetoceros Ketoacyl-ACP Synthase.

    PubMed

    Gu, Huiya; Jinkerson, Robert E; Davies, Fiona K; Sisson, Lyle A; Schneider, Philip E; Posewitz, Matthew C

    2016-01-01

    The isolation or engineering of algal cells synthesizing high levels of medium-chain fatty acids (MCFAs) is attractive to mitigate the high clouding point of longer chain fatty acids in algal based biodiesel. To develop a more informed understanding of MCFA synthesis in photosynthetic microorganisms, we isolated several algae from Great Salt Lake and screened this collection for MCFA accumulation to identify strains naturally accumulating high levels of MCFA. A diatom, Chaetoceros sp. GSL56, accumulated particularly high levels of C14 (up to 40%), with the majority of C14 fatty acids allocated in triacylglycerols. Using whole cell transcriptome sequencing and de novo assembly, putative genes encoding fatty acid synthesis enzymes were identified. Enzymes from this Chaetoceros sp. were expressed in the cyanobacterium Synechococcus sp. PCC 7002 to validate gene function and to determine whether eukaryotic enzymes putatively lacking bacterial evolutionary control mechanisms could be used to improve MCFA production in this promising production strain. Replacement of the Synechococcus 7002 native FabH with a Chaetoceros ketoacyl-ACP synthase III increased MCFA synthesis up to fivefold. The level of increase is dependent on promoter strength and culturing conditions. PMID:27303412

  3. Inclusion of potential vorticity uncertainties into a hydrometeorological forecasting chain: application to a medium size basin of Mediterranean Spain

    NASA Astrophysics Data System (ADS)

    Amengual, A.; Romero, R.; Vich, M.; Alonso, S.

    2009-06-01

    The improvement of the short- and mid-range numerical runoff forecasts over the flood-prone Spanish Mediterranean area is a challenging issue. This work analyses four intense precipitation events which produced floods of different magnitude over the Llobregat river basin, a medium size catchment located in Catalonia, north-eastern Spain. One of them was a devasting flash flood - known as the "Montserrat" event - which produced 5 fatalities and material losses estimated at about 65 million euros. The characterization of the Llobregat basin's hydrological response to these floods is first assessed by using rain-gauge data and the Hydrologic Engineering Center's Hydrological Modeling System (HEC-HMS) runoff model. In second place, the non-hydrostatic fifth-generation Pennsylvania State University/NCAR mesoscale model (MM5) is nested within the ECMWF large-scale forecast fields in a set of 54 h period simulations to provide quantitative precipitation forecasts (QPFs) for each hydrometeorological episode. The hydrological model is forced with these QPFs to evaluate the reliability of the resulting discharge forecasts, while an ensemble prediction system (EPS) based on perturbed atmospheric initial and boundary conditions has been designed to test the value of a probabilistic strategy versus the previous deterministic approach. Specifically, a Potential Vorticity (PV) Inversion technique has been used to perturb the MM5 model initial and boundary states (i.e. ECMWF forecast fields). For that purpose, a PV error climatology has been previously derived in order to introduce realistic PV perturbations in the EPS. Results show the benefits of using a probabilistic approach in those cases where the deterministic QPF presents significant deficiencies over the Llobregat river basin in terms of the rainfall amounts, timing and localization. These deficiences in precipitation fields have a major impact on flood forecasts. Our ensemble strategy has been found useful to reduce the

  4. Inclusion of potential vorticity uncertainties into a hydrometeorological forecasting chain: application to a medium size basin of Mediterranean Spain

    NASA Astrophysics Data System (ADS)

    Amengual, A.; Romero, R.; Vich, M.; Alonso, S.

    2009-01-01

    The improvement of the short- and mid-range numerical runoff forecasts over the flood-prone Spanish Mediterranean area is a challenging issue. This work analyses four intense precipitation events which produced floods of different magnitude over the Llobregat river basin, a medium size catchment located in Catalonia, north-eastern Spain. One of them was a devasting flash flood - known as the "Montserrat" event - which produced 5 fatalities and material losses estimated at about 65 million euros. The characterization of the Llobregat basin's hydrological response to these floods is first assessed by using rain-gauge data and the Hydrologic Engineering Center's Hydrological Modeling System (HEC-HMS) runoff model. In second place, the non-hydrostatic fifth-generation Pennsylvania State University/NCAR mesoscale model (MM5) is nested within the ECMWF large-scale forecast fields in a set of 54 h period simulations to provide quantitative precipitation forecasts (QPFs) for each hydrometeorological episode. The hydrological model is forced with these QPFs to evaluate the reliability of the resulting discharge forecasts, while an ensemble prediction system (EPS) based on perturbed atmospheric initial and boundary conditions has been designed to test the value of a probabilistic strategy versus the previous deterministic approach. Specifically, a Potential Vorticity (PV) Inversion technique has been used to perturb the MM5 model initial and boundary states (i.e. ECMWF forecast fields). For that purpose, a PV error climatology has been previously derived in order to introduce realistic PV perturbations in the EPS. Results show the benefits of using a probabilistic approach in those cases where the deterministic QPF presents significant deficiencies over the Llobregat river basin in terms of the rainfall amounts, timing and localization. These deficiences in precipitation fields have a major impact on flood forecasts. Our ensemble strategy has been found useful to reduce the

  5. The Collaborative Study on the Enzymatic Analysis of Positional Distribution of Short- and Medium-chain Fatty Acids in Milk Fat Using Immobilized Candida antarctica Lipase B.

    PubMed

    Yoshinaga, Kazuaki; Sato, Shinichi; Sasaki, Ryo; Asada, Mihoko; Hori, Ryuji; Imagi, Jun; Miyazaki, Yosuke; Nagai, Toshiharu; Saito, Katsuyoshi; Sano, Takashi; Sasaki, Akiko; Sato, Chiemi; Tsukahara, Yuki; Yamashita, Atsushi; Watanabe, Shimpei; Watanabe, Yomi

    2016-01-01

    The positional distributions of fatty acids (FAs) in milk fat containing short- and medium-chain FAs were analyzed by sn-1(3)-selective transesterification of triacylglycerols (TAGs) with ethanol using immobilized Candida antarctica lipase B (CALB), in a collaborative study conducted by 10 laboratories. The mean C4:0, C6:0, and C8:0 FA contents, when analyzed as propyl esters (PEs) using gas chromatography (GC) with a DB-23 capillary column, were found to be 3.0, 2.0, and, 1.3 area%, respectively. Their reproducibility standard deviations were 0.33, 0.18, and 0.19, respectively. The mean C4:0, C6:0, and C8:0 contents at the sn-2 position were 0.3, 0.4, and 1.0 area%, respectively. Their reproducibility standard deviations were 0.17, 0.11, and 0.19, respectively. The reproducibility standard deviations of C4:0, C6:0, and C8:0 FAs at the sn-2 position were either the same as or smaller than those for milk fat, although the FA contents at the sn-2 position were smaller than those in the milk fat. Therefore, it was concluded that the CALB method for estimating the regiospecific distribution is applicable to TAGs containing short- and medium-chain FAs. When estimating the short-chain (SC) FA contents in fats and oils by GC, it is better to analyze SCFAs as PEs or butyl esters, and not as methyl esters, in order to prevent loss of SCFAs during the experimental procedure because of their volatility and water solubility. This study also revealed that the stationary phase of the GC capillary column affected the flame ionization detector (FID) response of SCFAs. The theoretical FID correction factor (MWFA / active carbon number / atomic weight of carbon) fitted well with the actual FID responses of C4:0-C12:0 FAs when they were analyzed as PEs using a DB-23 column; however, this was not the case when the GC analysis was performed using wax-type columns. PMID:26972465

  6. Activation and repression of Epstein-Barr Virus and Kaposi's sarcoma-associated herpesvirus lytic cycles by short- and medium-chain fatty acids.

    PubMed

    Gorres, Kelly L; Daigle, Derek; Mohanram, Sudharshan; Miller, George

    2014-07-01

    The lytic cycles of Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are induced in cell culture by sodium butyrate (NaB), a short-chain fatty acid (SCFA) histone deacetylase (HDAC) inhibitor. Valproic acid (VPA), another SCFA and an HDAC inhibitor, induces the lytic cycle of KSHV but blocks EBV lytic reactivation. To explore the hypothesis that structural differences between NaB and VPA account for their functional effects on the two related viruses, we investigated the capacity of 16 structurally related short- and medium-chain fatty acids to promote or prevent lytic cycle reactivation. SCFAs differentially affected EBV and KSHV reactivation. KSHV was reactivated by all SCFAs that are HDAC inhibitors, including phenylbutyrate. However, several fatty acid HDAC inhibitors, such as isobutyrate and phenylbutyrate, did not reactivate EBV. Reactivation of KSHV lytic transcripts could not be blocked completely by any fatty acid tested. In contrast, several medium-chain fatty acids inhibited lytic activation of EBV. Fatty acids that blocked EBV reactivation were more lipophilic than those that activated EBV. VPA blocked activation of the BZLF1 promoter by NaB but did not block the transcriptional function of ZEBRA. VPA also blocked activation of the DNA damage response that accompanies EBV lytic cycle activation. Properties of SCFAs in addition to their effects on chromatin are likely to explain activation or repression of EBV. We concluded that fatty acids stimulate the two related human gammaherpesviruses to enter the lytic cycle through different pathways. Importance: Lytic reactivation of EBV and KSHV is needed for persistence of these viruses and plays a role in carcinogenesis. Our direct comparison highlights the mechanistic differences in lytic reactivation between related human oncogenic gammaherpesviruses. Our findings have therapeutic implications, as fatty acids are found in the diet and produced by the human microbiota. Small

  7. Triglycerides and Triglyceride-Rich Lipoproteins in the Causal Pathway of Cardiovascular Disease.

    PubMed

    Budoff, Matthew

    2016-07-01

    Epidemiologic and clinical studies suggest that elevated triglyceride levels are a biomarker of cardiovascular (CV) risk. Consistent with these findings, recent genetic evidence from mutational analyses, genome-wide association studies, and Mendelian randomization studies provide robust evidence that triglycerides and triglyceride-rich lipoproteins are in the causal pathway for atherosclerotic CV disease, indicating that they may play a pathogenic role, much like low-density lipoprotein cholesterol (LDL-C). Although statins are the cornerstone of dyslipidemia management, high triglyceride levels may persist in some patients despite statin therapy. Several triglyceride-lowering agents are available, including fibrates, niacin, and omega-3 fatty acids, of which prescription omega-3 fatty acids have the best tolerability and safety profile. In clinical studies, omega-3 fatty acids have been shown to reduce triglyceride levels, but products containing both eicosapentaenoic acid and docosahexaenoic acid may increase LDL-C levels. Icosapent ethyl, a high-purity eicosapentaenoic acid-only product, does not raise LDL-C levels and also reduces triglyceride, non-high-density lipoprotein cholesterol, and triglyceride-rich lipoprotein levels. In conclusion, omega-3 fatty acids are currently being evaluated in large CV outcome studies in statin-treated patients; these studies should help to elucidate the causative role of triglycerides in atherosclerotic CV disease.

  8. Triglycerides and Triglyceride-Rich Lipoproteins in the Causal Pathway of Cardiovascular Disease.

    PubMed

    Budoff, Matthew

    2016-07-01

    Epidemiologic and clinical studies suggest that elevated triglyceride levels are a biomarker of cardiovascular (CV) risk. Consistent with these findings, recent genetic evidence from mutational analyses, genome-wide association studies, and Mendelian randomization studies provide robust evidence that triglycerides and triglyceride-rich lipoproteins are in the causal pathway for atherosclerotic CV disease, indicating that they may play a pathogenic role, much like low-density lipoprotein cholesterol (LDL-C). Although statins are the cornerstone of dyslipidemia management, high triglyceride levels may persist in some patients despite statin therapy. Several triglyceride-lowering agents are available, including fibrates, niacin, and omega-3 fatty acids, of which prescription omega-3 fatty acids have the best tolerability and safety profile. In clinical studies, omega-3 fatty acids have been shown to reduce triglyceride levels, but products containing both eicosapentaenoic acid and docosahexaenoic acid may increase LDL-C levels. Icosapent ethyl, a high-purity eicosapentaenoic acid-only product, does not raise LDL-C levels and also reduces triglyceride, non-high-density lipoprotein cholesterol, and triglyceride-rich lipoprotein levels. In conclusion, omega-3 fatty acids are currently being evaluated in large CV outcome studies in statin-treated patients; these studies should help to elucidate the causative role of triglycerides in atherosclerotic CV disease. PMID:27184174

  9. The synthesis of short- and medium-chain-length poly(hydroxyalkanoate) mixtures from glucose- or alkanoic acid-grown Pseudomonas oleovorans.

    PubMed

    Ashby, R D; Solaiman, D K Y; Foglia, T A

    2002-03-01

    Pseudomonas oleovorans NRRL B-778 accumulated mixtures of poly-3-hydroxybutyrate (PHB) and medium-chain-length poly(hydroxyalkanoates) (mcl-PHAs) when grown on glucose, octanoic acid or oleic acid, whereas growth on nonanoic acid or undecanoic acid resulted in copolymers of poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHB-co-HV). Acetone fractionation verified the presence of PHB/mcl-PHA mixtures. The acetone-insoluble (AIS) fractions of the polymers derived from glucose (PHA-glucose), octanoic acid (PHA-octanoic) and oleic acid (PHA-oleic) were exclusively PHB while the acetone-soluble (AS) fractions contained mcl-PHA composed of differing ratios of 3-hydroxy-acid monomer units, which ranged in chain length from 6 to 14 carbon atoms. In contrast, both the AIS and AS fractions from the polymers derived from nonanoic acid (PHA-nonanoic) and undecanoic acid (PHA-undecanoic) were composed of comparable ratios of 3-hydroxybutyrate (3HB) and 3-hydroxyvalerate (3HV). The unfractionated PHA-glucose, PHA-octanoic and PHA-oleic polymers had melting temperatures (Tm) between 177 and 179 degrees C, enthalpies of fusion (AHf) of 20 cal/g and glasstransition temperatures (Tg) of 3-4 degrees C. This was due to the large PHB content in the polymer mixtures. On the other hand, the PHA-nonanoic and PHA-undecanoic polymers had thermal properties that supported their copolymer nature. In both cases, the Tm values were 161 degrees C, deltaHf values were 7 cal/g and Tg values were - 3 degrees C. PMID:12074088

  10. Effects of Dietary Coconut Oil as a Medium-chain Fatty Acid Source on Performance, Carcass Composition and Serum Lipids in Male Broilers.

    PubMed

    Wang, Jianhong; Wang, Xiaoxiao; Li, Juntao; Chen, Yiqiang; Yang, Wenjun; Zhang, Liying

    2015-02-01

    This study was conducted to investigate the effects of dietary coconut oil as a medium-chain fatty acid (MCFA) source on performance, carcass composition and serum lipids in male broilers. A total of 540, one-day-old, male Arbor Acres broilers were randomly allotted to 1 of 5 treatments with each treatment being applied to 6 replicates of 18 chicks. The basal diet (i.e., R0) was based on corn and soybean meal and was supplemented with 1.5% soybean oil during the starter phase (d 0 to 21) and 3.0% soybean oil during the grower phase (d 22 to 42). Four experimental diets were formulated by replacing 25%, 50%, 75%, or 100% of the soybean oil with coconut oil (i.e., R25, R50, R75, and R100). Soybean oil and coconut oil were used as sources of long-chain fatty acid and MCFA, respectively. The feeding trial showed that dietary coconut oil had no effect on weight gain, feed intake or feed conversion. On d 42, serum levels of total cholesterol, low-density lipoprotein cholesterol, and low-density lipoprotein/high-density lipoprotein cholesterol were linearly decreased as the coconut oil level increased (p<0.01). Lipoprotein lipase, hepatic lipase, and total lipase activities were linearly increased as the coconut oil level increased (p<0.01). Abdominal fat weight/eviscerated weight (p = 0.05), intermuscular fat width (p<0.01) and subcutaneous fat thickness (p<0.01) showed a significant quadratic relationship, with the lowest value at R75. These results indicated that replacement of 75% of the soybean oil in diets with coconut oil is the optimum level to reduce fat deposition and favorably affect lipid profiles without impairing performance in broilers.

  11. Effects of Dietary Coconut Oil as a Medium-chain Fatty Acid Source on Performance, Carcass Composition and Serum Lipids in Male Broilers

    PubMed Central

    Wang, Jianhong; Wang, Xiaoxiao; Li, Juntao; Chen, Yiqiang; Yang, Wenjun; Zhang, Liying

    2015-01-01

    This study was conducted to investigate the effects of dietary coconut oil as a medium-chain fatty acid (MCFA) source on performance, carcass composition and serum lipids in male broilers. A total of 540, one-day-old, male Arbor Acres broilers were randomly allotted to 1 of 5 treatments with each treatment being applied to 6 replicates of 18 chicks. The basal diet (i.e., R0) was based on corn and soybean meal and was supplemented with 1.5% soybean oil during the starter phase (d 0 to 21) and 3.0% soybean oil during the grower phase (d 22 to 42). Four experimental diets were formulated by replacing 25%, 50%, 75%, or 100% of the soybean oil with coconut oil (i.e., R25, R50, R75, and R100). Soybean oil and coconut oil were used as sources of long-chain fatty acid and MCFA, respectively. The feeding trial showed that dietary coconut oil had no effect on weight gain, feed intake or feed conversion. On d 42, serum levels of total cholesterol, low-density lipoprotein cholesterol, and low-density lipoprotein/high-density lipoprotein cholesterol were linearly decreased as the coconut oil level increased (p<0.01). Lipoprotein lipase, hepatic lipase, and total lipase activities were linearly increased as the coconut oil level increased (p<0.01). Abdominal fat weight/eviscerated weight (p = 0.05), intermuscular fat width (p<0.01) and subcutaneous fat thickness (p<0.01) showed a significant quadratic relationship, with the lowest value at R75. These results indicated that replacement of 75% of the soybean oil in diets with coconut oil is the optimum level to reduce fat deposition and favorably affect lipid profiles without impairing performance in broilers. PMID:25557818

  12. Screening of atmospheric short- and medium-chain chlorinated paraffins in India and Pakistan using polyurethane foam based passive air sampler.

    PubMed

    Chaemfa, Chakra; Xu, Yue; Li, Jun; Chakraborty, Paromita; Hussain Syed, Jabir; Naseem Malik, Riffat; Wang, Yan; Tian, Chongguo; Zhang, Gan; Jones, Kevin C

    2014-05-01

    Production and use of chlorinated paraffins (CPs) have been increasing in India. Distribution of CPs in the area and vicinity have become a great concern due to their persistency and toxicity. Polyurethane foam based passive air samplers (PUF-PAS) was deployed in order to screen the presence of short- and medium- chain chlorinated paraffins (SCCPs and MCCPs) in the outdoor atmosphere at many sites in India (in winter 2006) and Pakistan (in winter 2011). Concentrations of SCCPs and MCCPs ranged from not detected (ND) to 47.4 and 0 to 38.2 ng m(-3) with means of 8.11 and 4.83 ng m(-3), respectively. Indian concentrations showed higher average levels of both SCCPs and MCCPs India (10.2 ng m(-3) and 3.62 ng m(-3)than the samples from Pakistan (5.13 ng m(-3) and 4.21 ng m(-3)). Relative abundance patterns of carbon number are C10 > C11 > C12 ∼ C13 for SCCPs and C14 > C15 > C16 C17 for MCCP with similarity to the profiles of samples from China, the biggest CPs producer in the world. Principal Component Analysis suggested that detected SCCPs and MCCPs in this study originated from the same emission source.

  13. Rapid detection of medium chain acyl-CoA dehydrogenase gene mutations by non-radioactive, single strand conformation polymorphism minigels.

    PubMed Central

    Iolascon, A; Parrella, T; Perrotta, S; Guardamagna, O; Coates, P M; Sartore, M; Surrey, S; Fortina, P

    1994-01-01

    Medium chain acyl-CoA dehydrogenase (MCAD) deficiency is a common inherited metabolic disorder affecting fatty acid beta oxidation. Identification of carriers is important since the disease can be fatal and is readily treatable once diagnosed. Twelve molecular defects have been identified in the MCAD gene; however, a single highly prevalent mutation, A985G, accounts for > 90% of mutant alleles in the white population. In order to facilitate the molecular diagnosis of MCAD deficiency, oligonucleotide primers were designed to amplify the exon regions encompassing the 12 mutations enzymatically, and PCR products were then screened with a single strand conformation polymorphism (SSCP) based method. Minigels were used allowing much faster run times, and silver staining was used after gel electrophoresis to eliminate the need for radioisotopic labelling strategies. Our non-radioactive, minigel SSCP approach showed that normals can be readily distinguished from heterozygotes and homozygotes for all three of the 12 known MCAD mutations which were detected in our sampling of 48 persons. In addition, each band pattern is characteristic for a specific mutation, including those mapping in the same PCR product like A985G and T1124C. When necessary, the molecular defect was confirmed using either restriction enzyme digestion of PCR products or by direct DNA sequence analysis or both. This rapid, non-radioactive approach can become routine for molecular diagnosis of MCAD deficiency and other genetic disorders. Images PMID:7966191

  14. Effect of medium-chain glycerides on the membrane transport of D-glucose and sulfanilic acid in the intestinal brush-border membrane vesicles.

    PubMed

    Sagara, K; Higaki, K; Yamazaki, A; Hashida, M; Sezaki, H

    1990-01-01

    To clarify the influence of medium-chain glycerides (MCG) on a biological membrane, we investigated the membrane transport of D-glucose and sulfanilic acid in the brush-border membrane (BBM) vesicles pretreated with MCG. The size distribution of the BBM vesicles determined by electron microscopic observation was not significantly different between the vesicles incorporated with MCG and those of the control. However, the amount of D-glucose taken up by the vesicles at an equilibrated stage (30 min) was significantly decreased in the MCG-treated ones based on unit content of protein. Based on these results we estimated the membrane transport of D-glucose and sulfanilic acid in consideration of vesiculation or filter-capturing efficiency in MCG-treated vesicles. The rates of Na+ gradient-independent D-glucose transport and sulfanilic acid transport were significantly greater in MCG-treated vesicles than in the control. On the other hand, the magnitude of overshooting effect in Na+ gradient-dependent uptake of D-glucose in MCG-treated vesicles was maintained similar to the control. Comparison of kinetic parameters for active D-glucose transport at different concentrations indicated that Km and Vmax were not significantly different between MCG-treated and the control vesicles. These results indicated that passive diffusion of D-glucose and sulfanilic acid was significantly increased but Na(+)-glucose cotransporter was not significantly changed by the incorporation of MCG in the intestinal BBM vesicles.

  15. 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

  16. Rheology of Hyperbranched Poly(triglyceride)-Based Thermoplastic Elastomers via RAFT polymerization

    NASA Astrophysics Data System (ADS)

    Yan, Mengguo; Cochran, Eric

    2014-03-01

    In this contribution we discuss how melt- and solid-state properties are influenced by the degree of branching and molecular weight in a family of hyperbranched thermoplastics derived from soybean oil. Acrylated epoxidized triglycerides from soybean oils have been polymerized to hyperbranched thermoplastic elastomers using reversible addition-fragmentation chain transfer (RAFT) polymerization. With the proper choice of chain transfer agent, both homopolymer and block copolymer can be synthesized. By changing the number of acrylic groups per triglycerides, the chain architectures can range from nearly linear to highly branched. We show how the fundamental viscoelastic properties (e.g. entanglement molecular weight, plateau modulus, etc.) are influenced by chain architecture and molecular weight.

  17. Do triglycerides modulate the effectiveness of clozapine?

    PubMed

    Pande, S; Procyshyn, R M; Nazerali, M; Attwood, D; Chow, K

    2002-07-01

    We describe a case in which a patient's clinical response to clozapine appears to correlate positively with his serum triglyceride concentrations. We propose that the observed clinical response may partly be the result of the physical interaction of clozapine with the very low-density lipoproteins. We base this supposition on our previous in-vitro study showing that the plasma distribution of clozapine is significantly altered by increases in plasma triglyceride concentrations. Although this case only represents one patient, it highlights the possibility that serum lipids may be potential contributors to the clinical effectiveness of clozapine. PMID:12131604

  18. Evaluation of the use of esterified fatty acid oils enriched in medium-chain fatty acids in weight loss diets for dogs.

    PubMed

    Fragua, V; Barroeta, A C; Manzanilla, E G; Codony, R; Villaverde, C

    2015-04-01

    Esterified fatty acid oils (EAOs) are obtained from esterification of vegetable acid oils with glycerol. These fat sources have the same fatty acid (FA) composition as their respective native oils but new chemical properties. Several studies have confirmed the potential of medium-chain fatty acids (MCFA) to reduce fat mass (FM) in humans and rodents. This study investigates the use of EAOs with different MCFA proportions on food preferences, digestibility and weight loss management in dogs. A basal diet was supplemented with 8% of three different fat sources: C0: soya bean-canola EAO, C20: soya bean-canola (80%) coconut (20%) EAO and C40: soya bean-canola (60%) coconut (40%) EAO. Food preference of these EAOs was tested using a two-pan preference test. Dogs presented a higher daily food intake of C20 and C40 compared to C0 (C20: 155 ± 18.6 g vs. C0: 17 ± 7.0 g, p < 0.001; C40: 117 ± 13.9 g vs. C0: 28 ± 10.5 g, p < 0.05 respectively). Also, the digestibility of the three experimental diets was tested. C20 and C40 showed higher ether extract, total FA and saturated FA digestibilities (p < 0.05) than C0 diet. Lastly, the three diets were investigated in a 14-week weight loss study, following 16 weeks of ad libitum feeding to induce overweight condition. Body weight (BW) reduction was lower (C0: 20.1 ± 2.32%, C20: 14.6 ± 1.43% and C40: 15.7 ± 1.23%, p < 0.05) and FM was higher (FM, 18.7 ± 3.42%, 27.9 ± 3.90% and 28.2 ± 2.88% for C0, C20 and C40, respectively, p < 0.05) for diets C20 and C40 than for C0. Feeding diets with MCFA at these inclusion levels to experimentally overweight dogs during 14 weeks do not result in faster weight loss compared to unsaturated long-chain FA.

  19. Evaluation of the use of esterified fatty acid oils enriched in medium-chain fatty acids in weight loss diets for dogs.

    PubMed

    Fragua, V; Barroeta, A C; Manzanilla, E G; Codony, R; Villaverde, C

    2015-04-01

    Esterified fatty acid oils (EAOs) are obtained from esterification of vegetable acid oils with glycerol. These fat sources have the same fatty acid (FA) composition as their respective native oils but new chemical properties. Several studies have confirmed the potential of medium-chain fatty acids (MCFA) to reduce fat mass (FM) in humans and rodents. This study investigates the use of EAOs with different MCFA proportions on food preferences, digestibility and weight loss management in dogs. A basal diet was supplemented with 8% of three different fat sources: C0: soya bean-canola EAO, C20: soya bean-canola (80%) coconut (20%) EAO and C40: soya bean-canola (60%) coconut (40%) EAO. Food preference of these EAOs was tested using a two-pan preference test. Dogs presented a higher daily food intake of C20 and C40 compared to C0 (C20: 155 ± 18.6 g vs. C0: 17 ± 7.0 g, p < 0.001; C40: 117 ± 13.9 g vs. C0: 28 ± 10.5 g, p < 0.05 respectively). Also, the digestibility of the three experimental diets was tested. C20 and C40 showed higher ether extract, total FA and saturated FA digestibilities (p < 0.05) than C0 diet. Lastly, the three diets were investigated in a 14-week weight loss study, following 16 weeks of ad libitum feeding to induce overweight condition. Body weight (BW) reduction was lower (C0: 20.1 ± 2.32%, C20: 14.6 ± 1.43% and C40: 15.7 ± 1.23%, p < 0.05) and FM was higher (FM, 18.7 ± 3.42%, 27.9 ± 3.90% and 28.2 ± 2.88% for C0, C20 and C40, respectively, p < 0.05) for diets C20 and C40 than for C0. Feeding diets with MCFA at these inclusion levels to experimentally overweight dogs during 14 weeks do not result in faster weight loss compared to unsaturated long-chain FA. PMID:25865422

  20. Effect of supplementing coconut or krabok oil, rich in medium-chain fatty acids on ruminal fermentation, protozoa and archaeal population of bulls.

    PubMed

    Panyakaew, P; Boon, N; Goel, G; Yuangklang, C; Schonewille, J Th; Hendriks, W H; Fievez, V

    2013-12-01

    Medium-chain fatty acids (MCFA), for example, capric acid (C10:0), myristic (C14:0) and lauric (C12:0) acid, have been suggested to decrease rumen archaeal abundance and protozoal numbers. This study aimed to compare the effect of MCFA, either supplied through krabok (KO) or coconut (CO) oil, on rumen fermentation, protozoal counts and archaeal abundance, as well as their diversity and functional organization. KO contains similar amounts of C12:0 as CO (420 and 458 g/kg FA, respectively), but has a higher proportion of C14:0 (464 v. 205 g/kg FA, respectively). Treatments contained 35 g supplemental fat per kg DM: a control diet with tallow (T); a diet with supplemental CO; and a diet with supplemental KO. A 4th treatment consisted of a diet with similar amounts of MCFA (i.e. C10:0+C12:0+C14:0) from CO and KO. To ensure isolipidic diets, extra tallow was supplied in the latter treatment (KO+T). Eight fistulated bulls (two bulls per treatment), fed a total mixed ration predominantly based on cassava chips, rice straw, tomato pomace, rice bran and soybean meal (1.5% of BW), were used. Both KO and CO increased the rumen volatile fatty acids, in particular propionate and decreased acetate proportions. Protozoal numbers were reduced through the supplementation of an MCFA source (CO, KO and KO+T), with the strongest reduction by KO. Quantitative real-time polymerase chain reaction assays based on archaeal primers showed a decrease in abundance of Archaea when supplementing with KO and KO+T compared with T and CO. The denaturing gradient gel electrophoresis profiles of the rumen archaeal population did not result in a grouping of treatments. Richness indices were calculated from the number of DGGE bands, whereas community organization was assessed from the Pareto-Lorenz evenness curves on the basis of DGGE band intensities. KO supplementation (KO and KO+T treatments) increased richness and evenness within the archaeal community. Further research including methane

  1. 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 ...

  2. 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...

  3. Temporal Trends and Pattern Changes of Short- and Medium-Chain Chlorinated Paraffins in Marine Mammals from the South China Sea over the Past Decade.

    PubMed

    Zeng, Lixi; Lam, James C W; Wang, Yawei; Jiang, Guibin; Lam, Paul K S

    2015-10-01

    Temporal trends of short- (SCCPs) and medium-chain chlorinated paraffins (MCCPs) were examined in blubber samples of 50 finless porpoises (Neophocaena phocaenoides) and 25 Indo-Pacific humpback dolphins (Sousa chinensis) collected from the South China Sea between 2004 and 2014. Elevated levels of SCCPs and MCCPs were detected in all blubber samples of both cetacean species. Concentrations of SCCPs ranged from 280 to 3900 ng·g(-1) dry weight (dw) in porpoises and from 430 to 9100 ng·g(-1) dw in dolphins, while concentrations of MCCPs ranged from 320 to 8600 ng·g(-1) dw in porpoises and from 530 to 23 000 ng·g(-1) dw in dolphins. Significantly higher concentrations were present in dolphins than porpoises due to their exposure levels in their living habitats. Strongly linear correlations existed between SCCPs and MCCPs, but there were no significant concentration differences between the genders of the two cetacean species in the same sampling year. Significantly temporal increasing trends of ∑SCCPs and ∑MCCPs have been observed in both porpoise and dolphin samples over the past decade, which reflect the influence of histories of production and usage on the bioaccumulation of CPs in marine mammals in China. An apparent temporal shift trend from SCCPs to MCCPs was also observed in CP accumulation profiles. Complex environmental fractionation from localized sources in the study region via atmospheric transport, oceanic/offshore water transport, and trophic transfer have resulted in different CP accumulation levels and homologue patterns in the two cetacean species. This is the first report of systematic temporal trends of SCCPs and MCCPs in marine mammals. PMID:26335162

  4. A salting out system for improving the efficiency of the headspace solid-phase microextraction of short and medium chain free fatty acids.

    PubMed

    Fiorini, Dennis; Pacetti, Deborah; Gabbianelli, Rosita; Gabrielli, Serena; Ballini, Roberto

    2015-08-28

    Given the importance of short and medium chain free fatty acids (FFAs) in several fields, this study sought to improve the extraction efficiency of the solid-phase microextraction (SPME) of FFAs by evaluating salting out agents that appear promising for this application. The salts ammonium sulfate ((NH4)2SO4) and sodium dihydrogen phosphate (NaH2PO4) were tried on their own and in combination (3.7/1), in four different total amounts, as salting out agents in the headspace-SPME-gas chromatographic (HS-SPME-GC) analysis of the FFAs from acetic acid (C2) to decanoic acid (C10). Their performance in a model system of an aqueous standard mixture of FFAs at a pH of 3.5 was compared to that of the more commonly used sodium chloride (NaCl) and sodium sulfate (Na2SO4). All of the salts and salt systems evaluated, in proper amount, gave improved results compared to NaCl (saturated), which instead gave interesting results only for the least volatile FFAs C8 and C10. For C2-C6, the salt system that gave the best results compared to NaCl was (NH4)2SO4/NaH2PO4, in the highest of the four amounts evaluated, with factor increases between 1.2 and 4.1-fold, and NaH2PO4, between 1.0 and 4.3-fold. The SPME extraction efficiency given by the mixture (NH4)2SO4/NaH2PO4 was also assessed on biological and food samples, confirming that overall it performed better than NaCl.

  5. Marked synergistic bactericidal effects and mode of action of medium-chain fatty acids in combination with organic acids against Escherichia coli O157:H7.

    PubMed

    Kim, S A; Rhee, M S

    2013-11-01

    The aim of this study was to examine the synergistic bactericidal effects of medium-chain fatty acids (MCFAs; caprylic, capric, and lauric acid) and organic acids (OAs; acetic, lactic, malic, and citric acid) against Escherichia coli O157:H7 and to identify their underlying mechanism(s) of action. E. coli O157:H7 was treated with MCFAs, OAs, or different combinations of MCFAs and OAs. Membrane damage and cell morphology were examined by flow cytometry and transmission electron microscopy, respectively. Combined treatment resulted in an additional log-unit reduction compared with the sum of the reductions obtained after individual treatment. For example, caprylic acid (1.0 mM, or 0.016%) and citric acid (1.0 mM, or 0.012%) alone showed negligible bactericidal effects (0.30- and 0.06-log-unit reductions, respectively); however, a marked synergistic effect (>7.15-log-unit reduction) was observed when the two were combined. Although flow cytometry and microscopic analyses of bacteria treated with individual MCFAs and OAs showed evidence of membrane disruption, the bacteria were still able to form colonies; thus, the cell damage was recoverable. In contrast, cells exposed to combined treatments showed clear membrane disintegration and/or cell death (irreversible damage). The mechanism underlying the antimicrobial effects of combined treatment with MCFAs or OAs may involve disruption of the bacterial membrane, which then facilitates the entry of other antimicrobial compounds into the cytoplasm. The main advantage of combined treatment with very low concentrations of natural antimicrobial compounds is that it is very cost-effective. Thus, this approach may be an alternative to more conventional antimicrobial treatments, such as those currently used in public health, medical centers, and the food industry.

  6. Short- and medium-chain chlorinated paraffins in urban soils of Shanghai: spatial distribution, homologue group patterns and ecological risk assessment.

    PubMed

    Wang, Xue-Tong; Wang, Xi-Kui; Zhang, Yuan; Chen, Lei; Sun, Yan-Feng; Li, Mei; Wu, Ming-Hong

    2014-08-15

    Chlorinated paraffins (CPs) are toxic, bioaccumulative, persistent, and ubiquitously present in the environment. Data on the presence of short- and medium-chain chlorinated paraffins (SCCPs and MCCPs) in urban areas with dense population are still scarce to date. SCCPs and MCCPs were measured in urban soils from Shanghai to comprehensively investigate their levels, spatial distribution, homologue group patterns and ecological risk. The concentrations of CPs in soils varied from ND to 615 ng g(-1) with a median value of 15.7 ng g(-1) for SCCPs and from 1.95 to 188 ng g(-1) with a median value of 7.98 ng g(-1) for MCCPs, respectively. The concentrations of SCCPs in most soils were higher than those of MCCPs. The total CP concentrations in soil samples were between 4.10 and 625 ng g(-1) with a median value of 26.4 ng g(-1). For different functional zones, the median concentrations of soil CPs were found higher in green land including park, greenbelt and campus than those in roadside. The highest concentrations of CPs in soils could be derived from sewage sludge application and wastewater irrigation for green land. Three types of soils were classified by hierarchical cluster analysis (HCA) for SCCPs and MCCPs, the most abundant homologue groups in the bulk of the soil samples were C11Cl5-7 and C13Cl5-7 for SCCPs, and C14Cl7-8 and C15Cl7-8 for MCCPs. Correlation analysis and PCA suggested that SCCPs and MCCPs in soils in the studied area derived from different sources. The preliminary ecological risk assessment indicates that soil CPs at present levels poses no significant ecological risk for soil-dwelling organisms.

  7. Improved production of medium-chain-length polyhydroxyalkanoates in glucose-based fed-batch cultivations of metabolically engineered Pseudomonas putida strains.

    PubMed

    Poblete-Castro, Ignacio; Rodriguez, Andre Luis; Lam, Carolyn Ming Chi; Kessler, Wolfgang

    2014-01-01

    One of the major challenges in metabolic engineering for enhanced synthesis of value-added chemicals is to design and develop new strains that can be translated into well-controlled fermentation processes using bioreactors. The aim of this study was to assess the influence of various fed-batch strategies in the performance of metabolically engineered Pseudomonas putida strains, Δgcd and Δgcd-pgl, for improving production of medium-chain-length polyhydroxyalkanoates (mcl-PHAs) using glucose as the only carbon source. First we developed a fed-batch process that comprised an initial phase of biomass accumulation based on an exponential feeding carbon-limited strategy. For the mcl-PHA accumulation stage, three induction techniques were tested under nitrogen limitation. The substrate-pulse feeding was more efficient than the constant-feeding approach to promote the accumulation of the desirable product. Nonetheless, the most efficient approach for maximum PHA synthesis was the application of a dissolved-oxygen-stat feeding strategy (DO-stat), where P. putida Δgcd mutant strain showed a final PHA content and specific PHA productivity of 67% and 0.83 g·l(-1)·h(-1), respectively. To our knowledge, this mcl-PHA titer is the highest value that has been ever reported using glucose as the sole carbon and energy source. Our results also highlighted the effect of different fed-batch strategies upon the extent of realization of the intended metabolic modification of the mutant strains.

  8. Temporal Trends and Pattern Changes of Short- and Medium-Chain Chlorinated Paraffins in Marine Mammals from the South China Sea over the Past Decade.

    PubMed

    Zeng, Lixi; Lam, James C W; Wang, Yawei; Jiang, Guibin; Lam, Paul K S

    2015-10-01

    Temporal trends of short- (SCCPs) and medium-chain chlorinated paraffins (MCCPs) were examined in blubber samples of 50 finless porpoises (Neophocaena phocaenoides) and 25 Indo-Pacific humpback dolphins (Sousa chinensis) collected from the South China Sea between 2004 and 2014. Elevated levels of SCCPs and MCCPs were detected in all blubber samples of both cetacean species. Concentrations of SCCPs ranged from 280 to 3900 ng·g(-1) dry weight (dw) in porpoises and from 430 to 9100 ng·g(-1) dw in dolphins, while concentrations of MCCPs ranged from 320 to 8600 ng·g(-1) dw in porpoises and from 530 to 23 000 ng·g(-1) dw in dolphins. Significantly higher concentrations were present in dolphins than porpoises due to their exposure levels in their living habitats. Strongly linear correlations existed between SCCPs and MCCPs, but there were no significant concentration differences between the genders of the two cetacean species in the same sampling year. Significantly temporal increasing trends of ∑SCCPs and ∑MCCPs have been observed in both porpoise and dolphin samples over the past decade, which reflect the influence of histories of production and usage on the bioaccumulation of CPs in marine mammals in China. An apparent temporal shift trend from SCCPs to MCCPs was also observed in CP accumulation profiles. Complex environmental fractionation from localized sources in the study region via atmospheric transport, oceanic/offshore water transport, and trophic transfer have resulted in different CP accumulation levels and homologue patterns in the two cetacean species. This is the first report of systematic temporal trends of SCCPs and MCCPs in marine mammals.

  9. Three RFLPs defining a haplotype associated with the common mutation in a human medium-chain acyl-CoA dehydrogenase (MCAD) deficiency occur in Alu repeats

    SciTech Connect

    Zhifang Zhang; Yeqing Zhou; Kelly, D.P.; Strauss, A.W. St. Louis Children's Hospital, MO ); Kolvraa, S.; Gregersen, N. )

    1993-06-01

    Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a common inborn error of fatty-acid oxidation and may cause sudden infant death. Previous studies revealed that (i) homozygosity for an A-to-G mutation at nucleotide 985 of the mRNA coding region (A985G) is an extremely common cause of MCAD deficiency and (ii) MCAD deficiency is strongly associated with a particular haplotype for RFLPs for BanII, PstI, and TaqI. TaqI allele 2 is always associated with the A985G mutation in human MCAD deficiency. In this study, the authors have delineated the molecular basis of the RFLPs for PstI, BamHI, and TaqI in the human MCAD gene. Their results prove that the three RFLPs are caused by point mutations in the 8 kb of DNA encompassing exons 8--10 of the human MCAD gene. The TaqI polymorphism is caused by a C-to-A substitution 392 bp upstream of the exon 8, and the PstI and BamHI polymorphisms are due to T-to-C and G-to-A substitutions, respectively, which are 727 and 931 bp downstream of exon 10, respectively. All three RFLPs lie within Alu repetitive sequences. Comparison of intronic sequences immediately following exon 10 from two normal individuals with different haplotypes showed that this region contains densely packed Alu repeats and is highly polymorphic. The results are consistent both with a founder effect as the cause of the high prevalence of a single (A985G) mutation in MCAD deficiency and with its association with a particular haplotype for these intragenic RFLPs. 27 refs., 6 figs., 1 tab.

  10. Medium-chain TAG improve energy metabolism and mitochondrial biogenesis in the liver of intra-uterine growth-retarded and normal-birth-weight weanling piglets.

    PubMed

    Zhang, Hao; Li, Yue; Hou, Xiang; Zhang, Lili; Wang, Tian

    2016-05-01

    We previously reported that medium-chain TAG (MCT) could alleviate hepatic oxidative damage in weanling piglets with intra-uterine growth retardation (IUGR). There is a relationship between oxidative status and energy metabolism, a process involved in substrate availability and glucose flux. Therefore, the aim of this study was to investigate the effects of IUGR and MCT on hepatic energy metabolism and mitochondrial function in weanling piglets. Twenty-four IUGR piglets and twenty-four normal-birth-weight (NBW) piglets were fed a diet of either soyabean oil (SO) or MCT from 21 d of postnatal age to 49 d of postnatal age. Then, the piglets' biochemical parameters and gene expressions related to energy metabolism and mitochondrial function were determined (n 4). Compared with NBW, IUGR decreased the ATP contents and succinate oxidation rates in the liver of piglets, and reduced hepatic mitochondrial citrate synthase (CS) activity (P<0·05). IUGR piglets exhibited reductions in hepatic mitochondrial DNA (mtDNA) contents and gene expressions related to mitochondrial biogenesis compared with NBW piglets (P<0·05). The MCT diet increased plasma ghrelin concentration and hepatic CS and succinate dehydrogenase activities, but decreased hepatic pyruvate kinase activity compared with the SO diet (P<0·05). The MCT-fed piglets showed improved mtDNA contents and PPARγ coactivator-1α expression in the liver (P<0·05). The MCT diet alleviated decreased mRNA abundance of the hepatic PPARα induced by IUGR (P<0·05). It can therefore be postulated that MCT may have beneficial effects in improving energy metabolism and mitochondrial function in weanling piglets.

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

    PubMed

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

    1979-11-01

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

  12. 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

  13. Quantitative 'Omics Analyses of Medium Chain Length Polyhydroxyalkanaote Metabolism in Pseudomonas putida LS46 Cultured with Waste Glycerol and Waste Fatty Acids.

    PubMed

    Fu, Jilagamazhi; Sharma, Parveen; Spicer, Vic; Krokhin, Oleg V; Zhang, Xiangli; Fristensky, Brian; Cicek, Nazim; Sparling, Richard; Levin, David B

    2015-01-01

    Transcriptomes and proteomes of Pseudomonas putida LS46 cultured with biodiesel-derived waste glycerol or waste free fatty acids, as sole carbon sources, were compared under conditions that were either permissive or non-permissive for synthesis of medium chain length polyhydroxyalkanoates (mcl-PHA). The objectives of this study were to elucidate mechanisms that influence activation of biopolymer synthesis, intra-cellular accumulation, and monomer composition, and determine if these were physiologically specific to the carbon sources used for growth of P. putida LS46. Active mcl-PHA synthesis by P. putida LS46 was associated with high expression levels of key mcl-PHA biosynthesis genes and/or gene products including monomer-supplying proteins, PHA synthases, and granule-associated proteins. 'Omics data suggested that expression of these genes were regulated by different genetic mechanisms in P. putida LS46 cells in different physiological states, when cultured on the two waste carbon sources. Optimal polymer production by P. putida LS46 was primarily limited by less efficient glycerol metabolism during mcl-PHA synthesis on waste glycerol. Mapping the 'Omics data to the mcl-PHA biosynthetic pathway revealed significant variations in gene expression, primarily involved in: 1) glycerol transportation; 2) enzymatic reactions that recycle reducing equivalents and produce key mcl-PHA biosynthesis pathway intermediates (e.g. NADH/NADPH, acetyl-CoA). Active synthesis of mcl-PHAs was observed during exponential phase in cultures with waste free fatty acids, and was associated with the fatty acid beta-oxidation pathway. A putative Thioesterase in the beta-oxidation pathway that may regulate the level of fatty acid beta-oxidation intermediates, and thus carbon flux to mcl-PHA biosynthesis, was highly up-regulated. Finally, the data suggested that differences in expression of selected fatty acid metabolism and mcl-PHA monomer-supplying enzymes may play a role in determining the

  14. Atmospheric occurrence, homologue patterns and source apportionment of short- and medium-chain chlorinated paraffins in Shanghai, China: Biomonitoring with Masson pine (Pinus massoniana L.) needles.

    PubMed

    Wang, Xue-Tong; Zhou, Jun; Lei, Bing-Li; Zhou, Jing-Ming; Xu, Si-Yue; Hu, Bao-Ping; Wang, De-Qing; Zhang, Dong-Ping; Wu, Ming-Hong

    2016-08-01

    A comprehensive survey was conducted to Masson pine (Pinus massoniana L.) needles widely distributed in Shanghai in order to investigate the levels and homologue group patterns of short- and medium-chain chlorinated paraffins (SCCPs and MCCPs), to identify and quantitatively assess source contributions to the total CPs in pine needle samples. The concentration ranged from not detected (ND) to 13,600ngg(-1) with a geometric mean (GM) value of 63.7ngg(-1) for ΣSCCPs, from 12.4 to 33,500ngg(-1) with a GM value of 677ngg(-1) for ΣMCCPs, and from 14.0 to 45,700ngg(-1) with a GM value of 768ngg(-1) for total CPs. For different sampling units, the pollution levels both for SCCPs and MCCPs in pine needles were in the same orders: Pudong>suburbs>Puxi>Chongming. These significant differences in SCCPs and MCCPs among four sampling units could be associated with difference in industrial activities and to some extent also in population density. All pine needle samples (n=131) were divided into 2 groups by hierarchical cluster analysis (HCA) for SCCPs and MCCPs, the most abundant homologue groups in the bulk of pine needle samples were C11Cl5-7 and C13Cl5-7 for SCCPs, and C14Cl7-8 and C15Cl7-8 for MCCPs. Correlation analysis suggested that SCCPs and MCCPs in pine needles in the studied area may be derived from different sources. Four sources for pine needles were identified by the FA-MLR model; their relative contributions to the total CP burden in pine needles were 18.0% for F1 (attributed to commercial SCCP mixture), 42.2% for F2 (attributed to commercial MCCP mixture), 29.3% for F3 (attributed to LRAT), and 10.5% for F4 (unknown source). CP contamination of atmospheric air by point sources and long-range atmospheric transport in Shanghai should receive more attention by local government. PMID:27096489

  15. Quantitative ‘Omics Analyses of Medium Chain Length Polyhydroxyalkanaote Metabolism in Pseudomonas putida LS46 Cultured with Waste Glycerol and Waste Fatty Acids

    PubMed Central

    Fu, Jilagamazhi; Sharma, Parveen; Spicer, Vic; Krokhin, Oleg V.; Zhang, Xiangli; Fristensky, Brian; Cicek, Nazim; Sparling, Richard; Levin, David. B.

    2015-01-01

    Transcriptomes and proteomes of Pseudomonas putida LS46 cultured with biodiesel-derived waste glycerol or waste free fatty acids, as sole carbon sources, were compared under conditions that were either permissive or non-permissive for synthesis of medium chain length polyhydroxyalkanoates (mcl-PHA). The objectives of this study were to elucidate mechanisms that influence activation of biopolymer synthesis, intra-cellular accumulation, and monomer composition, and determine if these were physiologically specific to the carbon sources used for growth of P. putida LS46. Active mcl-PHA synthesis by P. putida LS46 was associated with high expression levels of key mcl-PHA biosynthesis genes and/or gene products including monomer-supplying proteins, PHA synthases, and granule-associated proteins. ‘Omics data suggested that expression of these genes were regulated by different genetic mechanisms in P. putida LS46 cells in different physiological states, when cultured on the two waste carbon sources. Optimal polymer production by P. putida LS46 was primarily limited by less efficient glycerol metabolism during mcl-PHA synthesis on waste glycerol. Mapping the ‘Omics data to the mcl-PHA biosynthetic pathway revealed significant variations in gene expression, primarily involved in: 1) glycerol transportation; 2) enzymatic reactions that recycle reducing equivalents and produce key mcl-PHA biosynthesis pathway intermediates (e.g. NADH/NADPH, acetyl-CoA). Active synthesis of mcl-PHAs was observed during exponential phase in cultures with waste free fatty acids, and was associated with the fatty acid beta-oxidation pathway. A putative Thioesterase in the beta-oxidation pathway that may regulate the level of fatty acid beta-oxidation intermediates, and thus carbon flux to mcl-PHA biosynthesis, was highly up-regulated. Finally, the data suggested that differences in expression of selected fatty acid metabolism and mcl-PHA monomer-supplying enzymes may play a role in determining

  16. Palm-based medium-and-long-chain triacylglycerol (P-MLCT): production via enzymatic interesterification and optimization using response surface methodology (RSM).

    PubMed

    Lee, Yee-Ying; Tang, Teck-Kim; Phuah, Eng-Tong; Karim, Nur Azwani Ab; Alwi, Siti Maslina Mohd; Lai, Oi-Ming

    2015-02-01

    Structured lipid such as medium-and long-chain triacylglycerol (MLCT) is claimed to be able to suppress body fat accumulation and be used to manage obesity. Response surface methodology (RSM) with four factors and three levels (+1,0,-1) faced centered composite design (FCCD) was employed for optimization of the enzymatic interesterification conditions of palm-based MLCT (P-MLCT) production. The effect of the four variables namely: substrate ratio palm kernel oil: palm oil, PKO:PO (40:60-100:0 w/w), temperature (50-70 °C), reaction time (0.5-7.5 h) and enzyme load (5-15 % w/w) on the P-MLCT yield (%) and by products (%) produced were investigated. The responses were determined via acylglycerol composition obtained from high performance liquid chromatography. Well-fitted models were successfully established for both responses: P-MLCT yield (R (2) = 0.9979) and by-products (R (2) = 0.9892). The P-MLCT yield was significantly (P < 0.05) affected by substrate ratio, reaction time and reaction temperature but not enzyme load (P > 0.05). Substrate ratio PKO: PO (100:0 w/w) gave the highest yield of P-MLCT (61 %). Nonetheless, substrate ratio of PKO: PO (90:10w/w) was chosen to improve the fatty acid composition of the P-MLCT. The optimized conditions for substrate ratio PKO: PO (90:10 w/w) was 7.26 h, 50 °C and 5 % (w/w) Lipozyme TLIM lipase, which managed to give 60 % yields of P-MLCT. Up scaled results in stirred tank batch reactor gave similar yields as lab scale. A 20 % increase in P-MLCT yield was obtained via RSM. The effect of enzymatic interesterification on the physicochemical properties of PKO:PO (90:10 w/w) were also studied. Thermoprofile showed that the P-MLCT oil melted below body temperature of 37 °C. PMID:25694677

  17. Atherogenicity of triglyceride-rich lipoproteins.

    PubMed

    Krauss, R M

    1998-02-26

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

  18. Biopolymer from microbial assisted in situ hydrolysis of triglycerides and dimerization of fatty acids.

    PubMed

    Kavitha, V; Radhakrishnan, N; Madhavacharyulu, E; Sailakshmi, G; Sekaran, G; Reddy, B S R; Rajkumar, G Suseela; Gnanamani, Arumugam

    2010-01-01

    The present study demonstrates biopolymer production by in situ bio-based dimerization of fatty acids by microorganism isolated from marine sediments. Microbial isolate grown in Zobell medium in the presence of triglycerides for the period of 24-240 h at 37 degrees C, hydrolyze the applied triglycerides and sequentially dimerized the hydrolyzed products and subsequently polymerized and transformed to a biopolymer having appreciable adhesive properties. Physical (nature, odour, stickyness and tensile strength), chemical (instrumentation) and biochemical (cell free broth) methods of analyses carried out provided the hypotheses involved in the formation of the product as well as the nature of the product formed. Results revealed, lipolytic enzymes released during initial period of growth and the biosurfactant production during later period, respectively, hydrolyze the applied triglycerides and initiate the dimerization and further accelerated when the incubation period extended. The existence and the non-existence of in situ hydrolysis of various triglycerides followed by dimerization and polymerization and the mechanism of transformation of triglycerides to biopolymer are discussed in detail.

  19. 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

  20. 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)

  1. 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...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended...

  2. 21 CFR 862.1705 - Triglyceride test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Triglyceride test system. 862.1705 Section 862...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended...

  3. 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...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended...

  4. 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...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended...

  5. 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...) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1705 Triglyceride test system. (a) Identification. A triglyceride test system is a device intended...

  6. 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...

  7. Triglycerides: how much credit do they deserve?

    PubMed

    Kohli, Payal; Cannon, Christopher P

    2012-01-01

    In the modern era of statin therapy, major advances have been made in treating coronary heart disease. However, despite intensive treatment with statin therapy, residual cardiovascular risk persists and has been attributed to the persistence of atherogenic dyslipidemia and, in part, elevated triglycerides (TGs). In this review, the authors focus on the mechanism of elevated TGs and provide a discussion of the challenges of measuring TGs as a biomarker, its role in the pathogenesis of atherosclerotic heart disease, and results of several recent studies that have elucidated the relationship between TGs and cardiovascular morbidity and mortality.

  8. 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

  9. The Role of Triglycerides in Atherosclerosis

    PubMed Central

    Talayero, Beatriz G.; Sacks, Frank M.

    2011-01-01

    Hypertriglyceridemia is a prevalent risk factor for cardiovascular disease (CVD) and increasingly important in the setting of current obesity and insulin resistance epidemics. High triglyceride (TG) levels are markers for several types of atherogenic lipoproteins. Patients who have hypertriglyceridemia may be at significant risk for CVD even if low-density lipoprotein cholesterol levels are at goal, and therefore warrant treatment that optimizes diet, reduces overweight, and promotes regular exercise. High-risk patients with hypertriglyceridemia, such as those with diabetes, CVD, or metabolic syndrome, may benefit from additional drug treatment aside from a statin to address other lipid abnormalities. In this discussion, we review the role of hypertriglyceridemia and its associated atherogenic lipoproteins in the pathogenesis of atherosclerosis, the relevance of a high TG level as a predictor of CVD, the cardiovascular outcomes from TG-lowering intervention trials, and the current guidelines for treating hypertriglyceridemia. PMID:21968696

  10. 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

  11. 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.

  12. Saturated fatty acid chain length and positional distribution in infant formula: effects on growth and plasma lipids and ketones in piglets.

    PubMed

    Innis, S M; Quinlan, P; Diersen-Schade, D

    1993-03-01

    Human milk contains a large proportion of palmitic acid (16:0) with > 70% esterified to the center sn-2 position of the milk triglyceride. Infant formulas often use 8:0 + 10:0 [medium-chain triglyceride (MCT)] or 12:0 + 14:0 (coconut oil) as the saturated fat. The effect of formula saturated fatty acid composition; 8:0 + 10:0, 12:0 + 14:0, or 16:0 from palm oil or synthesized triglyceride containing predominantly sn-2 16:0 on plasma lipids and fatty acids was studied in piglets. Although the formulas contained similar 18:1 and 18:2n-6, plasma lipid percentages of 18:1 and 18:2n-6 were higher in piglets fed the formula with MCT or coconut oil rather than the formulas with 16:0, or sow milk. The sn-2 16:0 of the synthesized triglyceride had unique properties. Specifically, piglets fed synthesized triglyceride had significantly higher cholesteryl ester 16:0 identical to that in piglets fed sow milk and higher plasma total and high-density-lipoprotein cholesterol than piglets fed the other formulas. PMID:8438772

  13. Surface-enhanced Raman spectroscopic monitor of triglyceride hydrolysis in a skin pore phantom

    NASA Astrophysics Data System (ADS)

    Weldon, Millicent K.; Morris, Michael D.

    1999-04-01

    Bacterial hydrolysis of triglycerides is followed in a sebum probe phantom by microprobe surface-enhanced Raman scattering (SERS) spectroscopy. The phantom consists of a purpose-built syringe pump operating at physiological flow rates connected to a 300 micron i.d. capillary. We employ silicon substrate SERS microprobes to monitor the hydrolysis products. The silicon support allows some tip flexibility that makes these probes ideal for insertion into small structures. Propionibacterium acnes are immobilized on the inner surface of the capillary. These bacteria hydrolyze the triglycerides in a model sebum emulsion flowing through the capillary. The transformation is followed in vitro as changes in the SERS caused by hydrolysis of triglyceride to fatty acid. The breakdown products consists of a mixture of mono- and diglycerides and their parent long chain fatty acids. The fatty acids adsorb as their carboxylates and can be readily identified by their characteristic spectra. The technique can also confirm the presence of bacteria by detection of short chain carboxylic acids released as products of glucose fermentation during the growth cycle of these cells. Co-adsorption of propionate is observed. Spatial localization of the bacteria is obtained by ex-situ line imaging of the probe.

  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. Stereoselective hydrolysis of triglycerides by animal and microbial lipases.

    PubMed

    Rogalska, E; Cudrey, C; Ferrato, F; Verger, R

    1993-01-01

    In the present paper, a study on the stereoselectivity of 25 lipases of animal and microbial origin towards homogeneous prochiral triglycerides is presented. All the lipases tested catalyse the hydrolysis of the chemically alike but sterically nonequivalent ester groups in trioctanoin and triolein with different degrees of stereobias, depending on the fatty acyl chain length of the substrate (Rogalska et al., J. Biol. Chem. 256:20271-20276, 1990). Hydrolysis of the sn-2 ester group is catalysed by very few lipases and only Candida antarctica A shows a clear preference for this position. Most of the lipases investigated (12 with trioctanoin and 16 with triolein) showed a preference for the sn-1 position. Using trioctanoin as substrate we observed a total stereoselectivity for position sn-1 with Pseudomonas sp. and Pseudomonas aeruginosa and for position sn-3 with Candida antarctica B. This was not the case with triolein as substrate. Among the 23 lipases studied here and the other two lipases described previously (Rogalska et al., J. Biol. Chem. 256:20271-20276, 1990), 17 show a higher stereoselectivity with trioctanoin than with triolein. With guinea pig pancreatic lipase and with three mold lipases (Geotrichum candidum M, Geotrichum candidum A, and Candida antarctica B), the preference switches from sn-3 to sn-1 when the acyl chain length increases from eight to 18 carbon atoms. The main conclusion to emerge from the present study is that the specific stereopreference of each lipase for a given substrate under given lipolytic conditions can be said to be its fingerprint.

  16. Process for enzymatic hydrolysis of fatty acid triglycerides with oat caryopses

    SciTech Connect

    Hammond, E.G.; Lee, I.

    1992-02-18

    This patent describes the process for enzymatic hydrolysis of fatty acid triglycerides to obtain free fatty acids and glycerol. It comprises: increasing the water content of dehulled whole oat caryopses to a total water content of 17 to 44% the thus moistened caryopses having active oat lipase associated with the outer surfaces thereof; contacting the moistened whole caryopses with a liquid medium, continuing the contacting until at least 20% by volume of the triglyceride reactant has been hydrolyzed to free fatty acids and glycerol, most of the free fatty acids dissolving in the oil phase external to the caryopses and most of the glycerol being absorbed into the water within the caryopses; and separating the glycerol-containing caryopses from the fatty acid-containing oil phase.

  17. Unique plasma metabolomic signatures of individuals with inherited disorders of long-chain fatty acid oxidation.

    PubMed

    McCoin, Colin S; Piccolo, Brian D; Knotts, Trina A; Matern, Dietrich; Vockley, Jerry; Gillingham, Melanie B; Adams, Sean H

    2016-05-01

    Blood and urine acylcarnitine profiles are commonly used to diagnose long-chain fatty acid oxidation disorders (FAOD: i.e., long-chain hydroxy-acyl-CoA dehydrogenase [LCHAD] and carnitine palmitoyltransferase 2 [CPT2] deficiency), but the global metabolic impact of long-chain FAOD has not been reported. We utilized untargeted metabolomics to characterize plasma metabolites in 12 overnight-fasted individuals with FAOD (10 LCHAD, two CPT2) and 11 healthy age-, sex-, and body mass index (BMI)-matched controls, with the caveat that individuals with FAOD consume a low-fat diet supplemented with medium-chain triglycerides (MCT) while matched controls consume a typical American diet. In plasma 832 metabolites were identified, and partial least squared-discriminant analysis (PLS-DA) identified 114 non-acylcarnitine variables that discriminated FAOD subjects and controls. FAOD individuals had significantly higher triglycerides and lower specific phosphatidylethanolamines, ceramides, and sphingomyelins. Differences in phosphatidylcholines were also found but the directionality differed by metabolite species. Further, there were few differences in non-lipid metabolites, indicating the metabolic impact of FAOD specifically on lipid pathways. This analysis provides evidence that LCHAD/CPT2 deficiency significantly alters complex lipid pathway flux. This metabolic signature may provide new clinical tools capable of confirming or diagnosing FAOD, even in subjects with a mild phenotype, and may provide clues regarding the biochemical and metabolic impact of FAOD that is relevant to the etiology of FAOD symptoms. PMID:26907176

  18. ReaxFF molecular dynamics simulations of the initial pyrolysis mechanism of unsaturated triglyceride.

    PubMed

    Zhang, Zhiqiang; Yan, Kefeng; Zhang, Jilong

    2014-03-01

    To understand the impact of C = C double bonds in acyl chains of unsaturated triglycerides on the reaction mechanism and product composition in their initial pyrolysis process, ReaxFF molecular dynamics simulations were carried out using a molecular model, trilinolenin, at temperatures of 2000, 2250, and 2500 K. Analyses indicated that the observed pyrolysis mechanisms of unsaturated triglyceride are nearly identical to the saturated triglyceride, and the pyrolysis products also include alkanes, alkenes, alkadienes, aromatics, oxygenated species, CO₂, and H₂. The formation of intermediates and products is a sequential process. Three C--O bonds in trilinolenin molecule are usually successive dissociated first, leading to the formation of unsaturated C₃H₅· radical and straight-chain C₁₈H₂₉O₂· (RCOO·) radicals. Following that, the deoxygenated alkenyl chain is produced through decarboxylation of RCOO · radicals with consequent release of CO₂. The resulting hydrocarbon radicals undergo a variety of disproportionation, isomerization, and hydrogen-transfer reactions, yielding straight and branched-chain hydrocarbons. It was found that the scission of C--O bond and decarboxylation should preferentially occur before the cleavage of the C--C bond β to the C = C bond in the initial decomposition process of unsaturated trilinolenin. In addition, the formation of cyclic hydrocarbons could proceed through intramolecular cyclization mechanisms, including non-radical electrocyclic, biradical cyclization and cyclization of alkenyl radical, which are inconsistent with previously proposed bimolecular Diels-Alder addition mechanisms. More rapid pyrolysis of trilinolenin would occur at higher temperatures without significantly affecting the apparent reaction mechanisms of trilinolenin pyrolysis in the considered temperature range. Aromatic ring structures are observed to be stable after formation and do not decay within the 500 ps simulation period

  19. What Are High Blood Cholesterol and Triglycerides?

    MedlinePlus

    ... and for cooking in many restaurants and fast-food chains. It’s also found naturally in milk and beef. Reduce the amount of trans fat in your diet by limiting foods with “hydrogenated oils” in the ingredients list. • Polyunsaturated ...

  20. Production of medium-chain volatile fatty acids by mixed ruminal microorganisms is enhanced by ethanol in co-culture with Clostridium kluyveri.

    PubMed

    Weimer, Paul J; Nerdahl, Michael; Brandl, Dane J

    2015-01-01

    Mixed bacterial communities from the rumen ferment cellulosic biomass primarily to C2-C4 volatile fatty acids, and perform only limited chain extension to produce C5 (valeric) and C6 (caproic) acids. The aim of this study was to increase production of caproate and valerate in short-term in vitro incubations. Co-culture of mixed ruminal microbes with a rumen-derived strain of the bacterium Clostridium kluyveri converted cellulosic biomass (alfalfa stems or switchgrass herbage) plus ethanol to VFA mixtures that include valeric and caproic acids as the major fermentation products over a 48-72h run time. Concentrations of caproate reached 6.1gL(-1), similar to or greater than those reported in most conventional carboxylate fermentations that employ substantially longer run times.

  1. Determination of the triglyceride composition of avocado oil by high-performance liquid chromatography using a light-scattering detector.

    PubMed

    Hierro, M T; Tomás, M C; Fernández-Martín, F; Santa-María, G

    1992-08-28

    The triglyceride composition of avocado oil was determined by high-performance liquid chromatography using a light-scattering detector. Two avocado varieties, Fuerte and Hass, were analysed, and the qualitative composition of each was found to be similar, though quantitative differences were detected. The triglyceride composition was predicted using a system of equations based on the relationship between log k' and the molecular variables equivalent carbon number, chain length and number of double bonds for each of the fatty acids in the glycerides. A total of 24 molecular species of triglycerides were identified. The chromatographic system used successfully separated the critical pairs OOO-LOS, PaPaO-LnPP and PaOO-LOP (O = olein; L = linolein; S = stearin; Pa = palmitolein; Ln = linolenin; P = palmitin). Detector response was found to have a linear relationship with the amount of sample injected over the injection range 10-70 micrograms.

  2. Improvement of hepatocyte viability after cryopreservation by supplementation of long-chain oligosaccharide in the freezing medium in rats and humans.

    PubMed

    Miyamoto, Yoshitaka; Suzuki, Satoshi; Nomura, Kou; Enosawa, Shin

    2006-01-01

    Factors affecting cell viability, plating efficiency, and survival of hepatocytes after cryopreservation have been investigated. We focused especially on the effect of including trehalose and related oligosaccharides in the cryopreservation fluid. This was supplemented with either glucose, trehalose, maltotriose, or other sugars, in addition to dimethyl sulfoxide (10%) and first tested with primary rat hepatocytes cooled in a controlled rate freezer. After thawing, viability by trypan blue exclusion of cells frozen in oligosaccharide-supplemented medium was significantly higher than for those cryopreserved without oligosaccharides. Use of oligosaccharides with higher molecular weights resulted in greatest improvement in viability. Moreover, attachment and survival rates in plastic dishes were approximately 1.2-1.8-fold greater after freezing in the presence of di-, tri-, and tetrasaccharides. Human hepatocytes isolated from untransplantable liver showed the same tendency regarding viability, but cell adherence was not similarly improved by the addition of oligosaccharides. Possible reasons for these differences may be prior cell damage during extended cold ischemia of the human liver, donor age, or cell degradation caused by progression of fatty liver in humans, and/or species differences.

  3. Binding of a double-chain surfactant-cobalt(III) complex to CT DNA: effect of β-cyclodextrin in the medium.

    PubMed

    Nagaraj, Karuppiah; Arunachalam, Sankaralingam

    2013-11-01

    The interaction of cis-[Co(phen)2(HA)2](ClO4)3, a cationic surfactant complex (phen=1,10-phenanthroline, HA=hexadecylamine), with calf thymus DNA has been studied by UV-vis absorption, fluorescence spectroscopy, cyclic voltammetry, circular dichroism, and viscosity measurements. The spectroscopic studies together with cyclic voltammetry and viscosity experiments support that the surfactant-cobalt(III) complex binds to calf thymus DNA (CT DNA) by intercalation through the aliphatic chain present in the complex into the base pairs of DNA. The presence of phenanthroline ligand with larger π-frame work may also enhance intercalation. Besides the effect of binding of surfactant cobalt(III) complex to DNA in presence of β-cyclodextrin has also studied. In presence of β-cyclodextrin the binding occurs through surface and (or) groove binding. The complex was investigated as one of the potential selective anticancer prodrugs. The complex was tested also in vitro on human monolayer tumor cell lines: HepG2 (human hepatocellular liver carcinoma). PMID:24041997

  4. An improved holographic recording medium

    NASA Technical Reports Server (NTRS)

    Gange, R. A.

    1973-01-01

    Solid, linear chain hydrocarbons with molecular weight ranging from about 300 to 2000 can serve as long-lived recording medium in optical memory system. Suitable recording hydrocarbons include microcrystalline waxes and low molecular weight polymers or ethylene.

  5. Hydrolysis of milk triglycerides by human gastric lipase.

    PubMed

    Jaśkiewicz, J; Szafran, Z; Popiela, T; Szafran, H

    1980-01-01

    The concentrations of myristic, palmitic, palmitoleic, stearic and oleic acids were determined in the products of hydrolysis of lipids of cow milk incubated with human gastric juice using thin-layer chromatography for the separation of lipid fractions, and gas liquid chromatography for the determination of fatty acids. It was found that the percentage ratio of the above fatty acids in hydrolysis products was similar to that in milk triglycerides. It was concluded that triglycerides containing higher fatty acids present in milk are hydrolysed by the lipase appearing in human gastric juice, the rate of hydrolysis of the individual acids being roughly proportional to the concentration of these acids in triglyceride substrate.

  6. The occurrence of triglycerides in Namibian Shelf diatomaceous ooze

    NASA Astrophysics Data System (ADS)

    Boon, Jaap J.; Irene, W.; Rijpstra, C.; de Leeuw, J. W.; Burlingame, A. L.

    1980-01-01

    The triglyceride fraction, isolated from extractable lipids of a diatomaceous ooze off shore Walvis Bay (S.W. Africa) by TLC methods, was analyzed by direct probe low and high resolution mass spectrometry. The mass spectral data reveal the fatty acid moieties and their relative distribution in the triglycerides identified. The C 12, C 14, C 15 and C 16 are the major composing fatty acid moieties. The triglycerides are thought to be present in protective structures such as diatom spores, which were found to be present by scanning electron microscopy.

  7. Unreliability of triglyceride measurement to predict turbidity induced interference.

    PubMed

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

    2003-11-01

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

  8. Occurrence and gas/particle partitioning of short- and medium-chain chlorinated paraffins in the atmosphere of Fildes Peninsula of Antarctica

    NASA Astrophysics Data System (ADS)

    Ma, Xindong; Zhang, Haijun; Zhou, Hongqiang; Na, Guangshui; Wang, Zhen; Chen, Chen; Chen, Jingwen; Chen, Jiping

    2014-06-01

    Chlorinated paraffins (CPs) were measured in air samples at a remote air monitoring site established in Georgia King Island, Fildes Peninsula of Antarctica (Great Wall Station, China) to study the long-range atmospheric transport of these anthropogenic pollutants to the Antarctic. Gas- and particle-phase CPs were collected using polyurethane foam plugs (PUF) and glass fiber filters (GFF) respectively during summertime of 2012. The total atmospheric levels of SCCPs and MCCPs ranged from 9.6 to 20.8 pg m-3 (average: 14.9 pg m-3) and 3.7-5.2 pg m-3 (average: 4.5 pg m-3), respectively. C10 and C11 carbon chain homologues with Cl5 and Cl6 chlorine atoms predominated in SCCP formula groups both in gas- and particle-phase. Significant linear correlation was found between gas/particle partition coefficients (KP) and sub-cooled liquid vapor pressures (pL°) (R2 = 0.437, p < 0.01), as well as KP and octanol-air partition coefficients (KOA) (R2 = 0.442, p < 0.01). Absolute slope values of two regression models (0.31 and 0.39) were less than 0.6 indicating that the way of absorption into organic matter of aerosol played a more important role on atmospheric partitioning and transferring of CPs in remote Antarctic area. Both the Junge-Pankow model and the KOA-based model tended to underestimate the sorption of lower chlorinated CPs and overestimate the sorption of highly chlorinated CPs.

  9. Expression of poly-3-(R)-hydroxyalkanoate (PHA) polymerase and acyl-CoA-transacylase in plastids of transgenic potato leads to the synthesis of a hydrophobic polymer, presumably medium-chain-length PHAs.

    PubMed

    Romano, Andrea; van der Plas, Linus H W; Witholt, Bernard; Eggink, Gerrit; Mooibroek, Hans

    2005-01-01

    Medium-chain-length poly-3-(R)-hydroxyalkanoates (mcl-PHAs) belong to the group of microbial polyesters. The minimum gene-set for the accumulation of mcl-PHAs from de novo fatty acid biosynthesis has been identified in prokaryotes as consisting of the Pha-C1 polymerase and the ACP-CoA-transacylase. In this paper, the synthesis of mcl-PHAs has been attempted in transgenic potato (Solanum tuberosum L.) using the same set of genes that were introduced into potato by particle bombardment. Polymer contents of transgenic lines were analysed by gas chromatography and by a new simple method employing a size-exclusion filter column. The expression of the Pha-C1 polymerase and the ACP-CoA-transacylase in the plastids of transgenic potato led to the synthesis of a hydrophobic polymer composed of mcl-hydroxy-fatty acids with carbon chain lengths ranging from C-6 to C-12 in leaves of the selected transgenic lines. We strongly suggest that the polymer observed consists of mcl-PHAs and that this report establishes for the first time a possible route for the production of mcl-PHAs from de novo fatty acid biosynthesis in plants. PMID:15351883

  10. Novel quaternary ammonium salts derived from triglycerides and their application in skin and hair products.

    PubMed

    Baydar, A; Johnston, R

    1991-08-01

    Synopsis An investigation has been carried out into the synthesis of quaternary ammonium salts of triglycerides. The aim of this work was to produce such compounds without breaking the triglyceride skeleton. The reaction of chloracetyl chloride with the triglyceride of ricinoleic acid which is the major constituent (88-90%) of castor oil gave an intermediate derivative with pendant chloro groups. Quaternization with stearyl dimethylamine gave a 98% yield of a quaternary ammonium salt containing three quaternary groups per molecule. This reaction sequence overcame the steric hindrance problems encountered in unsuccessful attempts to quaternize halogen groups attached directly to the main chain. Using the same procedure, a quaternary salt was prepared from castor oil. In skin care studies this quaternary was used at a low level in a moisturizing lotion. Subjective assessment of the ease of application of the test lotion versus control was significantly in favour of the test. Viscoelastic measurements of the skin were made using two techniques before and after application of the lotion. Both showed an advantage to the test lotion. No difference between the test and control lotions was found when sebum levels and transepidermal water loss measurements were measured. A C-12 quaternary synthesized from dimethyl-dodecylamine exhibited antimicrobial activity. An aqueous dispersion of the C-18 quaternary when applied to bleached hair in order to improve combing, gave excellent results showing superiority to four other commercially available quaternary ammonium salts.

  11. Short- and medium-chain chlorinated paraffins in air and soil of subtropical terrestrial environment in the pearl river delta, South China: distribution, composition, atmospheric deposition fluxes, and environmental fate.

    PubMed

    Wang, Yan; Li, Jun; Cheng, Zhineng; Li, Qilu; Pan, Xiaohui; Zhang, Ruijie; Liu, Di; Luo, Chunling; Liu, Xiang; Katsoyiannis, Athanasios; Zhang, Gan

    2013-03-19

    Research on the environmental fate of short- and medium-chain chlorinated paraffins (SCCPs and MCCPs) in highly industrialized subtropical areas is still scarce. Air, soil, and atmospheric deposition process in the Pearl River Delta of South China were investigated, and the average SCCP and MCCP concentrations were 5.2 μg/sampler (17.69 ng/m(3)) and 4.1 μg/sampler for passive air samples, 18.3 and 59.3 ng/g for soil samples, and 5.0 and 5.3 μg/(m(2)d) for deposition samples, respectively. Influenced by primary sources and the properties of chlorinated paraffins (CPs), a gradient trend of concentrations and a fractionation of composition from more to less industrialized areas were discovered. Intense seasonal variations with high levels in summer air and winter deposition samples indicated that the air and deposition CP levels were controlled mainly by the vapor and particle phase, respectively. Complex environmental processes like volatilization and fractionation resulted in different CP profiles in different environment matrixes and sampling locations, with C(10-11) C(l6-7) and C(14) C(l6-7), C(10-12) C(l6-7) and C(14) C(l6-8), and C(11-12) C(l6-8) and C(14) C(l7-8) dominating in air, soil, and atmospheric deposition, respectively. Shorter-chain and less chlorinated congeners were enriched in air in the less industrialized areas, while longer-chain and higher chlorinated congeners were concentrated in soil in the more industrialized areas. This is suggesting that the gaseous transport of CPs is the dominant mechanism responsible for the higher concentrations of lighter and likely more mobile CPs in the rural areas.

  12. Associations between Dietary Patterns, ADRβ2 Gln27Glu and ADRβ3 Trp64Arg with Regard to Serum Triglyceride Levels: J-MICC Study.

    PubMed

    Nanri, Hinako; Nishida, Yuichiro; Nakamura, Kazuyo; Tanaka, Keitaro; Naito, Mariko; Yin, Guang; Hamajima, Nobuyuki; Takashima, Naoyuki; Suzuki, Sadao; Nindita, Yora; Kohno, Michiko; Uemura, Hirokazu; Koyama, Teruhide; Hosono, Satoyo; Mikami, Haruo; Kubo, Michiaki; Tanaka, Hideo

    2016-01-01

    Interactions between dietary patterns and 2 β-adrenergic receptor (ADRβ) gene polymorphisms (ADRβ2 Gln27Glu and ADRβ3 Trp64Arg) were examined with regard to the effects on serum triglyceride levels. The cross-sectional study comprised 1720 men and women (aged 35-69 years) enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. Genotyping was conducted using a multiplex polymerase chain reaction-based invader assay. We used 46 items from a validated short food frequency questionnaire and examined major dietary patterns by factor analysis. We identified four dietary patterns: healthy, Western, seafood and bread patterns. There was no significant association between any dietary pattern and serum triglyceride levels. After a separate genotype-based analysis, significant interactions between ADRβ3 Trp64Arg genotype and the bread pattern (p for interaction = 0.01) were associated with serum triglyceride levels; specifically, after adjusting for confounding factors, Arg allele carriers with the bread pattern had lower serum triglycerides (p for trend = 0.01). However, the Trp/Trp homozygous subjects with the bread pattern showed no association with serum triglycerides (p for trend = 0.55). Interactions between other dietary patterns and ADRβ polymorphisms were not significant for serum triglyceride levels. Our findings suggest that ADRβ3 polymorphism modifies the effects of the bread pattern on triglyceride levels. PMID:27608039

  13. Associations between Dietary Patterns, ADRβ2 Gln27Glu and ADRβ3 Trp64Arg with Regard to Serum Triglyceride Levels: J-MICC Study

    PubMed Central

    Nanri, Hinako; Nishida, Yuichiro; Nakamura, Kazuyo; Tanaka, Keitaro; Naito, Mariko; Yin, Guang; Hamajima, Nobuyuki; Takashima, Naoyuki; Suzuki, Sadao; Nindita, Yora; Kohno, Michiko; Uemura, Hirokazu; Koyama, Teruhide; Hosono, Satoyo; Mikami, Haruo; Kubo, Michiaki; Tanaka, Hideo

    2016-01-01

    Interactions between dietary patterns and 2 β-adrenergic receptor (ADRβ) gene polymorphisms (ADRβ2 Gln27Glu and ADRβ3 Trp64Arg) were examined with regard to the effects on serum triglyceride levels. The cross-sectional study comprised 1720 men and women (aged 35–69 years) enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. Genotyping was conducted using a multiplex polymerase chain reaction-based invader assay. We used 46 items from a validated short food frequency questionnaire and examined major dietary patterns by factor analysis. We identified four dietary patterns: healthy, Western, seafood and bread patterns. There was no significant association between any dietary pattern and serum triglyceride levels. After a separate genotype-based analysis, significant interactions between ADRβ3 Trp64Arg genotype and the bread pattern (p for interaction = 0.01) were associated with serum triglyceride levels; specifically, after adjusting for confounding factors, Arg allele carriers with the bread pattern had lower serum triglycerides (p for trend = 0.01). However, the Trp/Trp homozygous subjects with the bread pattern showed no association with serum triglycerides (p for trend = 0.55). Interactions between other dietary patterns and ADRβ polymorphisms were not significant for serum triglyceride levels. Our findings suggest that ADRβ3 polymorphism modifies the effects of the bread pattern on triglyceride levels. PMID:27608039

  14. 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 ...

  15. 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

  16. 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

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

    PubMed

    Krauss, R M

    1998-07-01

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

  18. Novel extracellular medium-chain-length polyhydroxyalkanoate depolymerase from Streptomyces exfoliatus K10 DSMZ 41693: a promising biocatalyst for the efficient degradation of natural and functionalized mcl-PHAs.

    PubMed

    Martínez, Virginia; de Santos, Patricia Gómez; García-Hidalgo, Javier; Hormigo, Daniel; Prieto, M Auxiliadora; Arroyo, Miguel; de la Mata, Isabel

    2015-11-01

    Cloning and biochemical characterization of a novel extracellular medium-chain-length polyhydroxyalkanoate (mcl-PHA) depolymerase from Streptomyces exfoliatus K10 DSMZ 41693 are described. The primary structure of the depolymerase (PhaZSex2) includes the lipase consensus sequence (serine-histidine-aspartic acid) which is known for serine hydrolases. Secondary structure analysis shows 7.9 % α-helix, 43.9 % β-sheet, 19.4 % β-turns, and 31.2 % random coil, suggesting that this enzyme belongs to the α/β hydrolase fold family, in agreement with other PHA depolymerases and lipases. The enzyme was efficiently produced as an extracellular active form in Rhodococcus and purified by two consecutive hydrophobic chromatographic steps. Matrix-assisted laser desorption-time-of-flight (MALDI-TOF) analysis of the purified enzyme revealed a monomer of 27.6 kDa with a midpoint transition temperature of 44.2 °C. Remarkably, the activity is significantly enhanced by low concentrations of nonionic and anionic detergents and thermal stability is improved by the presence of 10 % glycerol. PhaZSex2 is an endo-exohydrolase that cleaves both large and small PHA molecules, producing (R)-3-hydroxyoctanoic acid monomers as the main reaction product. Markedly, PhaZSex2 is able to degrade functionalized polymers containing thioester groups in the side chain (PHACOS), releasing functional thioester-based monomers and oligomers demonstrating the potentiality of this novel biocatalyst for the industrial production of enantiopure (R)-3-hydroxyalkanoic acids. PMID:26156240

  19. A medium-chain fatty acid, capric acid, inhibits RANKL-induced osteoclast differentiation via the suppression of NF-κB signaling and blocks cytoskeletal organization and survival in mature osteoclasts.

    PubMed

    Kim, Hyun-Ju; Yoon, Hye-Jin; Kim, Shin-Yoon; Yoon, Young-Ran

    2014-08-01

    Fatty acids, important components of a normal diet, have been reported to play a role in bone metabolism. Osteoclasts are bone-resorbing cells that are responsible for many bone-destructive diseases such as osteoporosis. In this study, we investigated the impact of a medium-chain fatty acid, capric acid, on the osteoclast differentiation, function, and survival induced by receptor activator of NF-κB ligand (RANKL) and macrophage colony-stimulating factor (MCSF). Capric acid inhibited RANKL-mediated osteoclastogenesis in bone marrow-derived macrophages and suppressed RANKL-induced IκBα phosphorylation, p65 nuclear translocation, and NF-κB transcriptional activity. Capric acid further blocked the RANKL-stimulated activation of ERK without affecting JNK or p38. The induction of NFATc1 in response to RANKL was also attenuated by capric acid. In addition, capric acid abrogated M-CSF and RANKL-mediated cytoskeleton reorganization, which is crucial for the efficient bone resorption of osteoclasts. Capric acid also increased apoptosis in mature osteoclasts through the induction of Bim expression and the suppression of ERK activation by M-CSF. Together, our results reveal that capric acid has inhibitory effects on osteoclast development. We therefore suggest that capric acid may have potential therapeutic implications for the treatment of bone resorption-associated disorders.

  20. Comparison of a potentiometric and a micromechanical triglyceride biosensor.

    PubMed

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

    2009-01-01

    Sensitive biosensors for detection of triglyceride concentration are important. In this paper we report on two types of silicon based triglyceride sensors: an electrolyte-insulator-semiconductor capacitor (EISCAP) which is a potentiometric device and a polysilicon microcantilever. The detection principle for both sensors is based on the enzymatic hydrolysis of triglyceride though the sensing mechanisms are different: electronic for the EISCAP and mechanical for the microcantilever. The characteristics and performances of the two sensors are critically compared. The EISCAP sensor necessitates the presence of a buffer for stable measurements which limits the sensitivity of the sensor at low concentrations of the bioanalyte to 1mM. The cantilever sensor works without a buffer which improves the lower level of sensitivity to 10 microm. Both sensors are found to give reproducible and reliable results.

  1. Triglyceride accumulation and altered composition of triglyceride-associated fatty acids in the skin of tenascin-X-deficient mice.

    PubMed

    Matsumoto, Ken-ichi; Sato, Takashige; Oka, Seiko; Orba, Yasuko; Sawa, Hirofumi; Kabayama, Kazuya; Inokuchi, Jin-ichi; Ariga, Hiroyoshi

    2004-08-01

    Tenascin-X (TNX) is a member of the tenascin family of glycoproteins of the extracellular matrix. Here, we observed abnormalities in the skin of TNX-deficient mice in comparison with that of wild-type mice. Histological analysis with Oil Red O staining demonstrated that there was considerable accumulation of lipid in the skin of TNX-deficient (TNX-/-) mice. By thin-layer chromatography of total lipids, it was found that the level of triglyceride was significantly increased in TNX-/- mice. The mRNA levels of most of the lipogenic enzyme genes examined were remarkably increased in TNX-/- mice. By gas chromatography-mass spectrometry analysis of triglyceride-associated fatty acids in the skin, saturated fatty acid palmitoic acid was decreased, whereas unsaturated fatty acids palmitoleic acid and oleic acid were increased in TNX-/- mice compared with those in wild-type mice. Conversely, fibroblast cell lines transfected with TNX showed a significant decrease in the amount of triglyceride. An increase in the saturated fatty acid stearic acid and decreases in the unsaturated fatty acids palmitoleic acid, oleic acid and linoleic acid, compared to those in mock-transfected cells were also caused by over-expression of TNX. These results indicate that TNX is involved in the regulation of triglyceride synthesis and the regulation of composition of triglyceride-associated fatty acids.

  2. Hormone-sensitive lipase, the rate-limiting enzyme in triglyceride hydrolysis, is expressed and active in beta-cells.

    PubMed

    Mulder, H; Holst, L S; Svensson, H; Degerman, E; Sundler, F; Ahrén, B; Rorsman, P; Holm, C

    1999-01-01

    Triglycerides in the beta-cell may be important for stimulus-secretion coupling, through provision of a lipid-derived signal, and for pathogenetic events in NIDDM, where lipids may adversely affect beta-cell function. In adipose tissues, hormone-sensitive lipase (HSL) is rate-limiting in triglyceride hydrolysis. Here, we investigated whether this enzyme is also expressed and active in beta-cells. Northern blot analysis and reverse transcription-polymerase chain reaction demonstrated that HSL is expressed in rat islets and in the clonal beta-cell lines INS-1, RINm5F, and HIT-T15. Western blot analysis identified HSL in mouse and rat islets and the clonal beta-cells. In mouse and rat, immunocytochemistry showed a predominant occurrence of HSL in beta-cells, with a presumed cytoplasmic localization. Lipase activity in homogenates of the rodent islets and clonal beta-cells constituted 2.1 +/- 0.6% of that in adipocytes; this activity was immunoinhibited by use of antibodies to HSL. The established HSL expression and activity in beta-cells offer a mechanism whereby lipids are mobilized from intracellular stores. Because HSL in adipocytes is activated by cAMP-dependent protein kinase (PKA), PKA-regulated triglyceride hydrolysis in beta-cells may participate in the regulation of insulin secretion, possibly by providing a lipid-derived signal, e.g., long-chain acyl-CoA and diacylglycerol.

  3. 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

  4. 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

  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. 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

  7. Highly efficient extraction and lipase-catalyzed transesterification of triglycerides from Chlorella sp. KR-1 for production of biodiesel.

    PubMed

    Lee, Ok Kyung; Kim, Young Hyun; Na, Jeong-Geol; Oh, You-Kwan; Lee, Eun Yeol

    2013-11-01

    We developed a method for the highly efficient lipid extraction and lipase-catalyzed transesterification of triglyceride from Chlorella sp. KR-1 using dimethyl carbonate (DMC). Almost all of the total lipids, approximately 38.9% (w/w) of microalgae dry weight, were extracted from the dried microalgae biomass using a DMC and methanol mixture (7:3 (v/v)). The extracted triglycerides were transesterified into fatty acid methyl esters (FAMEs) using Novozyme 435 as the biocatalyst in DMC. Herein, DMC was used as the reaction medium and acyl acceptor. The reaction conditions were optimized and the FAMEs yield was 293.82 mg FAMEs/g biomass in 6 h of reaction time at 60 °C in the presence of 0.2% (v/v) water. Novozyme 435 was reused more than ten times while maintaining relative FAMEs conversion that was greater than 90% of the initial FAMEs conversion. PMID:23999257

  8. A Dietary Medium-Chain Fatty Acid, Decanoic Acid, Inhibits Recruitment of Nur77 to the HSD3B2 Promoter In Vitro and Reverses Endocrine and Metabolic Abnormalities in a Rat Model of Polycystic Ovary Syndrome.

    PubMed

    Lee, Bao Hui; Indran, Inthrani Raja; Tan, Huey Min; Li, Yu; Zhang, Zhiwei; Li, Jun; Yong, Eu-Leong

    2016-01-01

    Hyperandrogenism is the central feature of polycystic ovary syndrome (PCOS). Due to the intricate relationship between hyperandrogenism and insulin resistance in PCOS, 50%-70% of these patients also present with hyperinsulinemia. Metformin, an insulin sensitizer, has been used to reduce insulin resistance and improve fertility in women with PCOS. In previous work, we have noted that a dietary medium-chain fatty acid, decanoic acid (DA), improves glucose tolerance and lipid profile in a mouse model of diabetes. Here, we report for the first time that DA, like metformin, inhibits androgen biosynthesis in NCI-H295R steroidogenic cells by regulating the enzyme 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase type 2 (HSD3B2). The inhibitory effect on HSD3B2 and androgen production required cAMP stimulation, suggesting a mechanistic action via the cAMP-stimulated pathway. Specifically, both DA and metformin reduced cAMP-enhanced recruitment of the orphan nuclear receptor Nur77 to the HSD3B2 promoter, coupled with decreased transcription and protein expression of HSD3B2. In a letrozole-induced PCOS rat model, treatment with DA or metformin reduced serum-free testosterone, lowered fasting insulin, and restored estrous cyclicity. In addition, DA treatment lowered serum total testosterone and decreased HSD3B2 protein expression in the adrenals and ovaries. We conclude that DA inhibits androgen biosynthesis via mechanisms resulting in the suppression of HSD3B2 expression, an effect consistently observed both in vitro and in vivo. The efficacy of DA in reversing the endocrine and metabolic abnormalities of the letrozole-induced PCOS rat model are promising, raising the possibility that diets including DA could be beneficial for the management of both hyperandrogenism and insulin resistance in PCOS.

  9. Investigation of some characteristics of polyhydroxy milkweed triglycerides and their acylated derivatives in relation to lubricity.

    PubMed

    Harry-O'kuru, Rogers E; Biresaw, Girma; Cermak, Steven C; Gordon, Sherald H; Vermillion, Karl

    2011-05-11

    Most industrial lubricants are derived from nonrenewable petroleum-based sources. As useful as these lubricants are, their unintended consequences are the pollution of the Earth's environment as a result of the slow degradation of the spent materials. Native seed oils, on the other hand, are renewable and are also biodegradable in the environment, but these oils often suffer a drawback in having lower thermal stability and a shorter shelf life because of the intrinsic -C═C- unsaturation in their structures. This drawback can be overcome, yet the inherent biodegradative property retained, by appropriate derivatization of the oil. Pursuant to this, this study investigated derivatized polyhydroxy milkweed oil to assess its suitability as lubricant. The milkweed plant is a member of the Asclepiadaceae, a family with many genera including the common milkweeds, Asclepias syriaca L., Asclepias speciosa L., Asclepias tuberosa L., etc. The seeds of these species contain mainly C-18 triglycerides that are highly unsaturated, 92%. The olefinic character of this oil has been chemically modified by generating polyhydroxy triglycerides (HMWO) that show high viscosity and excellent moisturizing characteristics. In this work, HMWO have been chemically modified by esterifying their hydroxyl groups with acyl groups of various chain lengths (C2-C5). The results of investigation into the effect of the acyl derivatives' chemical structure on kinematic and dynamic viscosity, oxidation stability, cold-flow (pour point, cloud point) properties, coefficient of friction, wear, and elastohydrodynamic film thickness are discussed.

  10. Investigation of some characteristics of polyhydroxy milkweed triglycerides and their acylated derivatives in relation to lubricity.

    PubMed

    Harry-O'kuru, Rogers E; Biresaw, Girma; Cermak, Steven C; Gordon, Sherald H; Vermillion, Karl

    2011-05-11

    Most industrial lubricants are derived from nonrenewable petroleum-based sources. As useful as these lubricants are, their unintended consequences are the pollution of the Earth's environment as a result of the slow degradation of the spent materials. Native seed oils, on the other hand, are renewable and are also biodegradable in the environment, but these oils often suffer a drawback in having lower thermal stability and a shorter shelf life because of the intrinsic -C═C- unsaturation in their structures. This drawback can be overcome, yet the inherent biodegradative property retained, by appropriate derivatization of the oil. Pursuant to this, this study investigated derivatized polyhydroxy milkweed oil to assess its suitability as lubricant. The milkweed plant is a member of the Asclepiadaceae, a family with many genera including the common milkweeds, Asclepias syriaca L., Asclepias speciosa L., Asclepias tuberosa L., etc. The seeds of these species contain mainly C-18 triglycerides that are highly unsaturated, 92%. The olefinic character of this oil has been chemically modified by generating polyhydroxy triglycerides (HMWO) that show high viscosity and excellent moisturizing characteristics. In this work, HMWO have been chemically modified by esterifying their hydroxyl groups with acyl groups of various chain lengths (C2-C5). The results of investigation into the effect of the acyl derivatives' chemical structure on kinematic and dynamic viscosity, oxidation stability, cold-flow (pour point, cloud point) properties, coefficient of friction, wear, and elastohydrodynamic film thickness are discussed. PMID:21428293

  11. Metabolic abnormalities: triglyceride and low-density lipoprotein.

    PubMed

    Krauss, Ronald M; Siri, Patty W

    2004-06-01

    Increased plasma triglyceride and reduced high-density lipoprotein cholesterol are key features of the metabolic syndrome. Although elevated low-density lipoprotein cholesterol is not an integral characteristic of this syndrome, there is commonly an increase in the proportion of small, dense low-density lipoprotein particles. Together, these abnormalities constitute the atherogenic dyslipidemia of the metabolic syndrome. This article reviews the pathophysiology of altered triglyceride and low-density lipoprotein metabolism in the metabolic syndrome, outlines the relationship of these lipoprotein abnormalities to increased risk of coronary heart disease,and highlights the application of this information to clinical practice. The role of reduced high-density lipoprotein in the metabolic syndrome is discussed elsewhere in this issue.

  12. The effect of lean fish consumption on triglyceride levels.

    PubMed

    Leaf, David A; Hatcher, Lauren

    2009-04-01

    Marine omega-3 fatty acids have an important role in reducing the risk of coronary artery disease (CAD). The American Heart Association recommends 1 g/day of omega-3 fatty acids for patients with CAD, and for those without CAD, the consumption of a variety of fish (preferably fatty fish) at least twice a week is recommended. Greater amounts of omega-3 fatty acids (4 g per day) are recommended to treat hypertriglyceridemia. Fish oil capsules are often needed to provide the greater quantities of omega-3 fatty acids necessary to treat hypertriglyceridemia, which should not obscure the important triglyceride-lowering effects of seafood consumption. The effects of fish consumption on plasma lipids and lipoproteins are well described in studies that have generally been conducted with fatty fish and fish oil capsules. This study of a group of men and women in a strictly controlled dietary setting showed that compared with a cholesterol-free diet, both lean fish and beef diets raised plasma low-density lipoprotein cholesterol levels, but the fish diet resulted in lower levels of plasma total cholesterol, very-low-density lipoprotein (VLDL) triglycerides, and VLDL cholesterol, while the beef diet resulted in higher plasma high-density lipoprotein cholesterol levels. These findings can help practitioners to extend their dietary recommendations to incorporate significant quantities of low-fat fish to reduce triglyceride levels. PMID:20048486

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

    PubMed

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

    2016-02-01

    We compared the effects of prolonged sitting with the effects of sitting interrupted by regular walking and the effects of prolonged sitting after continuous walking on postprandial triglyceride in postmenopausal women. 15 participants completed 3 trials in random order: 1) prolonged sitting, 2) regular walking, and 3) prolonged sitting preceded by continuous walking. During the sitting trial, participants rested for 8 h. For the walking trials, participants walked briskly in either twenty 90-sec bouts over 8 h or one 30-min bout in the morning (09:00-09:30). Except for walking, both exercise trials mimicked the sitting trial. In each trial, participants consumed a breakfast (08:00) and lunch (11:00). Blood samples were collected in the fasted state and at 2, 4, 6 and 8 h after breakfast. The serum triglyceride incremental area under the curve was 15 and 14% lower after regular walking compared with prolonged sitting and prolonged sitting after continuous walking (4.73±2.50 vs. 5.52±2.95 vs. 5.50±2.59 mmol/L∙8 h respectively, main effect of trial: P=0.023). Regularly interrupting sitting time with brief bouts of physical activity can reduce postprandial triglyceride in postmenopausal women. PMID:26509374

  14. Effects of feed access after hatch and inclusion of fish oil and medium chain fatty acids in a pre-starter diet on broiler chicken growth performance and humoral immunity.

    PubMed

    Lamot, D M; van der Klein, S A S; van de Linde, I B; Wijtten, P J A; Kemp, B; van den Brand, H; Lammers, A

    2016-09-01

    Delayed feed and water access is known to impair growth performance of day old broiler chickens. Although effects of feed access on growth performance and immune function of broilers have been examined before, effects of dietary composition and its potential interaction with feed access are hardly investigated. This experiment aimed to determine whether moment of first feed and water access after hatch and pre-starter composition (0 to 7 days) affect growth rate and humoral immune function in broiler chickens. Direct fed chickens received feed and water directly after placement in the grow-out facility, whilst delayed fed chickens only after 48 h. Direct and delayed fed chickens received a control pre-starter diet, or a diet containing medium chain fatty acids (MCFA) or fish oil. At 21 days, chickens were immunized by injection of sheep red blood cells. The mortality rate depended on an interaction between feed access and pre-starter composition (P=0.014). Chickens with direct feed access fed the control pre-starter diet had a higher risk for mortality than chickens with delayed feed access fed the control pre-starter diet (16.4% v. 4.2%) whereas the other treatment groups were in-between. BW gain and feed intake till 25 days in direct fed chickens were higher compared with delayed fed chickens, whilst gain to feed ratio was lower. Within the direct fed chickens, the control pre-starter diet resulted in the highest BW at 28 days and the MCFA pre-starter diet the lowest (Δ=2.4%), whereas this was opposite for delayed fed chickens (Δ=3.0%; P=0.033). Provision of MCFA resulted in a 4.6% higher BW gain and a higher gain to feed ratio compared with other pre-starter diets, but only during the period it was provided (2 to 7 days). Minor treatment effects were found for humoral immune response by measuring immunoglobulins, agglutination titers, interferon gamma (IFN- γ ), and complement activity. Concluding, current inclusion levels of fish oil (5 g/kg) and MCFA (30 g

  15. Hydrothermal deoxygenation of triglycerides over Pd/C aided by in situ hydrogen production from glycerol reforming.

    PubMed

    Hollak, Stefan A W; Ariëns, Maxim A; de Jong, Krijn P; van Es, Daan S

    2014-04-01

    A one-pot catalytic hydrolysis-deoxygenation reaction for the conversion of unsaturated triglycerides and free fatty acids to linear paraffins and olefins is reported. The hydrothermal deoxygenation reactions are performed in hot compressed water at 250 °C over a Pd/C catalyst in the absence of external H2 . We show that aqueous-phase reforming (APR) of glycerol and subsequent water-gas-shift reaction result in the in situ formation of H2 . While this has a significant positive effect on the deoxygenation activity, the product selectivity towards high-value, long-chain olefins remains high. PMID:24596129

  16. 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...

  17. Thermal properties of systems containing cholesteryl esters and triglycerides.

    PubMed

    Lundberg, B

    1976-01-01

    Binary and ternary systems of the three cholesteryl esters, linoleate, oleate, and stearate and the two triglycerides, triolein and tristearin were studied in order to determine the phase transitions and the conditions for the cholesteric and smectic mesophases. Phase transitions were determined using differential thermal analysis, melting point determination, and polarizing microscopy. Of the cholesterol esters the linoleate-oleate system showed complete miscibility in both the liquid and solid phases. The linoleate-stearate and oleate-stearate systems are of the eutectic type with limited solid solubility. The mesophases are monotropic as to the crystalline state and exist over the entire composition interval in all cholesteryl ester systems studied.

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

    PubMed

    Hodúlová, Miloslava; Šedová, Lucie; Křenová, Drahomíra; Liška, František; Krupková, Michaela; Kazdová, Ludmila; Tremblay, Johanne; Hamet, Pavel; Křen, Vladimír; Šeda, Ondřej

    2014-01-01

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

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

    PubMed Central

    Hodúlová, Miloslava; Šedová, Lucie; Křenová, Drahomíra; Liška, František; Krupková, Michaela; Kazdová, Ludmila; Tremblay, Johanne; Hamet, Pavel; Křen, Vladimír; Šeda, Ondřej

    2014-01-01

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

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

    PubMed

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

    2001-03-01

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

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

    PubMed

    Yücel, Alp; Özcan, Hakkı Mevlüt; Sağıroğlu, Ayten

    2016-01-01

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

  2. 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

  3. 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

  4. 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

  5. Role of lipase from community-associated methicillin-resistant Staphylococcus aureus strain USA300 in hydrolyzing triglycerides into growth-inhibitory free fatty acids.

    PubMed

    Cadieux, Brigitte; Vijayakumaran, Vithooshan; Bernards, Mark A; McGavin, Martin J; Heinrichs, David E

    2014-12-01

    Part of the human host innate immune response involves the secretion of bactericidal lipids on the skin and delivery of triglycerides into abscesses to control invading pathogens. Two Staphylococcus aureus lipases, named SAL1 and SAL2, were identified in the community-associated methicillin-resistant S. aureus strain USA300, which, presumably, are produced and function to degrade triglycerides to release free fatty acids. We show that the SAL2 lipase is one of the most abundant proteins secreted by USA300 and is proteolytically processed from the 72-kDa proSAL2 to the 44-kDa mature SAL2 by the metalloprotease aureolysin. We show that spent culture supernatants had lipase activity on both short- and long-chain fatty acid substrates and that deletion of gehB, encoding SAL2, resulted in the complete loss of these activities. With the use of gas chromatography-mass spectrometry, we show that SAL2 hydrolyzed trilinolein to linoleic acid, a fatty acid with known antistaphylococcal properties. When added to cultures of USA300, trilinolein and, to a lesser extent, triolein inhibited growth in a SAL2-dependent manner. This effect was shown to be due to the enzymatic activity of SAL2 on these triglycerides, since the catalytically inactive SAL2 Ser412Ala mutant was incapable of hydrolyzing the triglycerides or yielding delayed growth in their presence. Overall, these results reveal that SAL2 hydrolyzes triglycerides of both short- and long-chain fatty acids and that the released free fatty acids have the potential to cause significant delays in growth, depending on the chemical nature of the free fatty acid. PMID:25225262

  6. Role of lipase from community-associated methicillin-resistant Staphylococcus aureus strain USA300 in hydrolyzing triglycerides into growth-inhibitory free fatty acids.

    PubMed

    Cadieux, Brigitte; Vijayakumaran, Vithooshan; Bernards, Mark A; McGavin, Martin J; Heinrichs, David E

    2014-12-01

    Part of the human host innate immune response involves the secretion of bactericidal lipids on the skin and delivery of triglycerides into abscesses to control invading pathogens. Two Staphylococcus aureus lipases, named SAL1 and SAL2, were identified in the community-associated methicillin-resistant S. aureus strain USA300, which, presumably, are produced and function to degrade triglycerides to release free fatty acids. We show that the SAL2 lipase is one of the most abundant proteins secreted by USA300 and is proteolytically processed from the 72-kDa proSAL2 to the 44-kDa mature SAL2 by the metalloprotease aureolysin. We show that spent culture supernatants had lipase activity on both short- and long-chain fatty acid substrates and that deletion of gehB, encoding SAL2, resulted in the complete loss of these activities. With the use of gas chromatography-mass spectrometry, we show that SAL2 hydrolyzed trilinolein to linoleic acid, a fatty acid with known antistaphylococcal properties. When added to cultures of USA300, trilinolein and, to a lesser extent, triolein inhibited growth in a SAL2-dependent manner. This effect was shown to be due to the enzymatic activity of SAL2 on these triglycerides, since the catalytically inactive SAL2 Ser412Ala mutant was incapable of hydrolyzing the triglycerides or yielding delayed growth in their presence. Overall, these results reveal that SAL2 hydrolyzes triglycerides of both short- and long-chain fatty acids and that the released free fatty acids have the potential to cause significant delays in growth, depending on the chemical nature of the free fatty acid.

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

    PubMed Central

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

    2015-01-01

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

  8. Falling chains

    NASA Astrophysics Data System (ADS)

    Wong, Chun Wa; Yasui, Kosuke

    2006-06-01

    The one-dimensional fall of a folded chain with one end suspended from a rigid support and a chain falling from a resting heap on a table is studied. Because their Lagrangians contain no explicit time dependence, the falling chains are conservative systems. Their equations of motion are shown to contain a term that enforces energy conservation when masses are transferred between subchains. We show that Cayley's 1857 energy nonconserving solution for a chain falling from a resting heap is incorrect because it neglects the energy gained when a link leaves a subchain. The maximum chain tension measured by Calkin and March for the falling folded chain is given a simple if rough interpretation. Other aspects of the falling folded chain are briefly discussed.

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

    PubMed

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

    2014-03-10

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

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

    PubMed

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

    2014-03-10

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

  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. 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

  13. 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

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

    PubMed

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

    2014-12-16

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

  15. Understanding solid-state properties of triglycerides used in pharmaceutical and food microencapsulation.

    PubMed

    Elviri, Lisa; Mangia, Mattia; Menabeni, Roberta; Della Bella, Andrea; Camellini, Claudia; Beltrami, Diego; Arduini, Lauro; Bettini, Ruggero

    2015-01-01

    Hydrophobic materials, in particular hydrogenated vegetable oils, HVO, are extensively used as coating materials in food and pharmaceutical systems. Correct application of these coatings requires an evaluation of their behaviour as a function of various parameters such as melting temperature, solubility, concentration and/or pH. The purpose of this study was to assess the physico-chemical properties of an HVO in terms of composition, crystallisation, phase transition and polymorphism using a variety of analytical techniques, such as electrospray mass spectrometry (ESI-MS), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). High-resolution ESI-MS allowed establishment of the HVO main composition of long-chain triglycerides (average molecular weight 1183 Da). DSC results showed that thermal history determines the formation of at least two polymorphs of HVO, namely two different crystal forms, assigned as form α, melting point (m.p.) 48 °C, and form β', m.p. 60 °C. A third polymorph, the more thermodynamically stable β-form, having a melting point at 62 °C, is obtained by solution-mediated re-crystallisation. Phase transformation paths were investigated by isothermal DSC experiments, which evidenced that the α-form is kinetically stable at temperatures lower than 25 °C. These data are of particular interest in practical applications such as spray freezing or pan coating where significant heat transfer phenomena are involved.

  16. The lipid droplet enzyme Tgl1p hydrolyzes both steryl esters and triglycerides in the yeast, Saccharomyces cerevisiae.

    PubMed

    Jandrositz, Anita; Petschnigg, Julia; Zimmermann, Robert; Natter, Klaus; Scholze, Hubert; Hermetter, Albin; Kohlwein, Sepp D; Leber, Regina

    2005-06-15

    Based on sequence homology to mammalian acid lipases, yeast reading frame YKL140w was predicted to encode a triacylglycerol (TAG) lipase in yeast and was hence named as TGL1, triglyceride lipase 1. A deletion of TGL1, however, resulted in an increase of the cellular steryl ester content. Fluorescently labeled lipid analogs that become covalently linked to the enzyme active site upon catalysis were used to discriminate between the lipase and esterase activities of Tgl1p. Tgl1p preferred single-chain esterase inhibitors over lipase inhibitors in vitro. Under assay conditions optimal for acid lipases, Tgl1p exhibited steryl esterase activity only and lacked any triglyceride lipase activity. In contrast, at pH 7.4, Tgl1p also exhibited TAG lipase activity; however, steryl ester hydrolase activity was still predominant. Tgl1p localized exclusively to lipid droplets which are the intracellular storage compartment of steryl esters and triacylglycerols in the yeast S. cerevisiae. In a tgl1 deletion mutant, the mobilization of steryl esters in vivo was delayed, but not abolished, suggesting the existence of additional enzymes involved in steryl ester mobilization.

  17. Triglycerides potentiate the inflammatory response in rat Kupffer cells.

    PubMed

    Budick-Harmelin, Noga; Dudas, Jozsef; Demuth, Julia; Madar, Zecharia; Ramadori, Giuliano; Tirosh, Oren

    2008-12-01

    Accumulation of fat in the liver, also known as steatosis, may lead to inflammation and tissue damage. Kupffer cells (KCs) are the resident macrophages of the liver and have an important role in inflammatory reactions. The inflammatory response of isolated rat KCs to endotoxin in the presence of lipids was investigated in this study. KCs were treated with lipopolysaccharide (LPS) and triglycerides (TGs) alone or in combination. TGs had no effect on the expression of pro-inflammatory mediators, but adding TGs to LPS enhanced the induction of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and granulocyte colony-stimulating factor (G-CSF), compared with LPS treatment alone. Increased DNA binding of NF-kappaB transcription factor was seen on simultaneous exposure of the cells to TGs and LPS, which was accompanied by decreased intracellular ROS production and increased GSH levels. The inflammation-potentiating effect of TGs on iNOS expression was abolished on NF-kappaB inhibition. This enhanced inflammatory response might indicate a contribution of lipids to the inflammatory conditions in the fatty liver by increased activation of KCs. PMID:18710323

  18. Triglycerides potentiate the inflammatory response in rat Kupffer cells.

    PubMed

    Budick-Harmelin, Noga; Dudas, Jozsef; Demuth, Julia; Madar, Zecharia; Ramadori, Giuliano; Tirosh, Oren

    2008-12-01

    Accumulation of fat in the liver, also known as steatosis, may lead to inflammation and tissue damage. Kupffer cells (KCs) are the resident macrophages of the liver and have an important role in inflammatory reactions. The inflammatory response of isolated rat KCs to endotoxin in the presence of lipids was investigated in this study. KCs were treated with lipopolysaccharide (LPS) and triglycerides (TGs) alone or in combination. TGs had no effect on the expression of pro-inflammatory mediators, but adding TGs to LPS enhanced the induction of inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and granulocyte colony-stimulating factor (G-CSF), compared with LPS treatment alone. Increased DNA binding of NF-kappaB transcription factor was seen on simultaneous exposure of the cells to TGs and LPS, which was accompanied by decreased intracellular ROS production and increased GSH levels. The inflammation-potentiating effect of TGs on iNOS expression was abolished on NF-kappaB inhibition. This enhanced inflammatory response might indicate a contribution of lipids to the inflammatory conditions in the fatty liver by increased activation of KCs.

  19. 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.

  20. Efficient phagocytosis requires triacylglycerol hydrolysis by adipose triglyceride lipase.

    PubMed

    Chandak, Prakash G; Radovic, Branislav; Aflaki, Elma; Kolb, Dagmar; Buchebner, Marlene; Fröhlich, Eleonore; Magnes, Christoph; Sinner, Frank; Haemmerle, Guenter; Zechner, Rudolf; Tabas, Ira; Levak-Frank, Sanja; Kratky, Dagmar

    2010-06-25

    Macrophage phagocytosis is an essential biological process in host defense and requires large amounts of energy. To date, glucose is believed to represent the prime substrate for ATP production in macrophages. To investigate the relative contribution of free fatty acids (FFAs) in this process, we determined the phagocytosis rates in normal mouse macrophages and macrophages of adipose triglyceride lipase (ATGL)-deficient mice. ATGL was shown to be the rate-limiting enzyme for the hydrolysis of lipid droplet-associated triacylglycerol (TG) in many tissues. Here, we demonstrate that Atgl(-/-) macrophages fail to efficiently hydrolyze cellular TG stores leading to decreased cellular FFA concentrations and concomitant accumulation of lipid droplets, even in the absence of exogenous lipid loading. The reduced availability of FFAs results in decreased cellular ATP concentrations and impaired phagocytosis suggesting that fatty acids must first go through a cycle of esterification and re-hydrolysis before they are available as energy substrate. Exogenously added glucose cannot fully compensate for the phagocytotic defect in Atgl(-/-) macrophages. Hence, phagocytosis was also decreased in vivo when Atgl(-/-) mice were challenged with bacterial particles. These findings imply that phagocytosis in macrophages depends on the availability of FFAs and that ATGL is required for their hydrolytic release from cellular TG stores. This novel mechanism links ATGL-mediated lipolysis to macrophage function in host defense and opens the way to explore possible roles of ATGL in immune response, inflammation, and atherosclerosis.

  1. Structure of the human hepatic triglyceride lipase gene

    SciTech Connect

    Cai, Shengjian; Wong, D.M.; Chen, Sanhwan; Chan, L. )

    1989-11-14

    The structure of the human hepatic triglyceride lipase gene was determined from multiple cosmid clones. All the exons, exon-intron junctions, and 845 bp of the 5{prime} and 254 bp of the 3{prime} flanking DNA were sequenced. Comparison of the exon sequences to three previously published cDNA sequences revealed differences in the sequence of the codons for residue 133, 193, 202, and 234 that may represent sequence polymorphisms. By primer extension, hepatic lipase mRNA initiates at an adenine 77 bases upstream of the translation initiation site. The hepatic lipase gene spans over 60 kb containing 9 exons and 8 introns, the latter being all located within the region encoding the mature protein. The exons are all of average size (118-234 bp). Exon 1 encodes the signal peptide, exon 4, a region that binds to the lipoprotein substrate, and exon 5, an evolutionarily highly conserved region of potential catalytic function, and exons 6 and 9 encode sequences rich in basic amino acids thought to be important in anchoring the enzyme to the endothelial surface by interacting with acidic domains of the surface glycosaminoglycans. The human lipoprotein lipase gene has been recently reported to have an identical exon-intron organization containing the analogous structural domains. The observations strongly support the common evolutionary origin of these two lipolytic enzymes.

  2. [Prevention of atherosclerosis. The positional specificity of blood triglycerides and lipases, the particular milk lipids, and the modification of the fatty acids of vegetable oils and animal fats].

    PubMed

    Titov, V N; Krylin, V V; Shiriaeva, Iu K

    2011-03-01

    Milk is a biological medium that bears no resemblance to any of the biological fluids and tissues in primates and mammals in the positional composition of fatty acids (FA) in triglycerides. This is determined by the fact that at the very early phylogenesis of mammals, milk is to ensure a high postnatal bioavailability (absorption) of saturated palmitic FA, a substrate for neonatal energy supply despite all obstacles that are formed in the baby's intestine in vivo. Milk is destined for infant nutrition in the biology-destined period (not more than a year); assimilation of triglycerides that are so structurally unusual requires a) high isomerization activity in the enterocytes and b) the ability of blood lipases to hydrolyze palmitate-oleate-palmitate triglycerides as a component of oleic very-low-density lipoproteins. After the period permitted by nature, there is virtually no possibility to physiologically consume milk that contains structurally unusual triglycerides. The use of whole milk and its products by adults impairs the active, receptor cell absorption of FAs as ligand lipoproteins via apoE/B-100-endocytosis and enhances the generation of small, dense low-density lipoproteins as biological debris. The impaired biological function of endoecology and the debris accumulation of the intercellular medium lead to the activation of atheromatosis, atherothrombosis, and coronary sclerosis. Nature has given no sanction for turning the mammals that are not on milk to those on milk for whole life. Up to one year of age, the baby has in vivo conditions for the absorption and hydrolysis of triglycerides with palmitic FA at the sn-2 position. After one year of age, the expression of these lipases and coenzymes is over; re-expression occurs only with the activation of the biological function of locomotion - long-term strenuous physical activity. High physical activity expresses other genes, enzymes, coenzymes, and carrier proteins, which activate the hydrolysis of

  3. 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

  4. 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.

  5. 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.

  6. 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.

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

    PubMed Central

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

    2009-01-01

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

  8. Relationship between Plasma Triglyceride Level and Severity of Hypertriglyceridemic Pancreatitis

    PubMed Central

    Wang, Sheng-Huei; Chou, Yu-Ching; Shangkuan, Wei-Chuan; Wei, Kuang-Yu; Pan, Yu-Han; Lin, Hung-Che

    2016-01-01

    Background Hypertriglyceridemia is the third most common cause of acute pancreatitis, but whether the level of triglyceride (TG) is related to severity of pancreatitis is unclear. Aim To evaluate the effect of TG level on the severity of hypertriglyceridemic pancreatitis (HTGP). Design Retrospective cohort study. Methods We reviewed the records of 144 patients with HTGP from 1999 to 2013 at Tri-Service General Hospital. Patients with possible etiology of pancreatitis, such as gallstones, those consuming alcohol or drugs, or those with infections were excluded. The classification of severity of pancreatitis was based on the revised Atlanta classification. We allocated the patients into high-TG and low-TG groups based on the optimal cut-off value (2648 mg/dL), which was derived from the receiver operating characteristic (ROC) curve between TG level and severity of HTGP. We then compared the clinical characteristics, pancreatitis severity, and mortality rates of the groups. Results There were 66 patients in the low-TG group and 78 patients in the high-TG group. There was no significant difference in the age, sex ratio, body mass index, and comorbidity between the 2 groups. The high-TG group had significantly higher levels of glucose (P = 0.022), total cholesterol (P = 0.002), and blood urea nitrogen (P = 0.037), and lower levels of sodium (P = 0.003) and bicarbonate (P = 0.002) than the low-TG group. The incidences of local complication (P = 0.002) and severe and moderate form of pancreatitis (P = 0.004) were significantly higher in the high-TG group than in the low-TG group. The mortality rate was higher in the high-TG group than in the low-TG group (P = 0.07). Conclusions Higher TG level in patients with HTGP may be associated with adverse prognosis, but randomized and prospective studies are needed in the future verify this relationship. PMID:27727299

  9. 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

  10. Development and pathomechanisms of cardiomyopathy in very long-chain acyl-CoA dehydrogenase deficient (VLCAD(-/-)) mice.

    PubMed

    Tucci, Sara; Flögel, Ulrich; Hermann, Sven; Sturm, Marga; Schäfers, Michael; Spiekerkoetter, Ute

    2014-05-01

    Hypertrophic cardiomyopathy is a typical manifestation of very long-chain acyl-CoA dehydrogenase deficiency (VLCADD), the most common long-chain β-oxidation defects in humans; however in some patients cardiac function is fully compensated. Cardiomyopathy may also be reversed by supplementation of medium-chain triglycerides (MCT). We here characterize cardiac function of VLCAD-deficient (VLCAD(-/-)) mice over one year. Furthermore, we investigate the long-term effect of a continuous MCT diet on the cardiac phenotype. We assessed cardiac morphology and function in VLCAD(-/-) mice by in vivo MRI. Cardiac energetics were measured by (31)P-MRS and myocardial glucose uptake was quantified by positron-emission-tomography (PET). Metabolic adaptations were identified by the expression of genes regulating glucose and lipid metabolism using real-time-PCR. VLCAD(-/-) mice showed a progressive decrease in heart function over 12 months accompanied by a reduced phosphocreatine-to-ATP-ratio indicative of chronic energy deficiency. Long-term MCT supplementation aggravated the cardiac phenotype into dilated cardiomyopathy with features similar to diabetic heart disease. Cardiac energy production and function in mice with a β-oxidation defect cannot be maintained with age. Compensatory mechanisms are insufficient to preserve the cardiac energy state over time. However, energy deficiency by impaired β-oxidation and long-term MCT induce cardiomyopathy by different mechanisms. Cardiac MRI and MRS may be excellent tools to assess minor changes in cardiac function and energetics in patients with β-oxidation defects for preventive therapy.

  11. 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

  12. 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

  13. 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

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

    PubMed Central

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

    2015-01-01

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

  15. An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing.

    PubMed

    Pennacchio, L A; Olivier, M; Hubacek, J A; Cohen, J C; Cox, D R; Fruchart, J C; Krauss, R M; Rubin, E M

    2001-10-01

    Comparison of genomic DNA sequences from human and mouse revealed a new apolipoprotein (APO) gene (APOAV) located proximal to the well-characterized APOAI/CIII/AIV gene cluster on human 11q23. Mice expressing a human APOAV transgene showed a decrease in plasma triglyceride concentrations to one-third of those in control mice; conversely, knockout mice lacking Apoav had four times as much plasma triglycerides as controls. In humans, single nucleotide polymorphisms (SNPs) across the APOAV locus were found to be significantly associated with plasma triglyceride levels in two independent studies. These findings indicate that APOAV is an important determinant of plasma triglyceride levels, a major risk factor for coronary artery disease.

  16. 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.

  17. Effects of specimen turbidity and glycerol concentration on nine enzymatic methods for triglyceride determination.

    PubMed

    Sampson, M; Ruddel, M; Elin, R J

    1994-02-01

    We compared the effects of specimen turbidity and glycerol concentration on nine enzymatic methods for triglyceride measurement. We assayed 51 specimens with triglyceride concentrations of 0.85-8.21 mmol/L (75-727 mg/dL) and turbidity at 420 nm equivalent to > or = 0.1 mmol/L (8.8 mg/dL) triglyceride (measured as part of our comparison method). The data were analyzed by multiple regression, which gave coefficients for the effects of glycerol concentration and the change in turbidity during the reaction. The effects of specimen turbidity and glycerol concentration were method-dependent and ranged from 6.20% to -15.67% of the measured result. The magnitude of the turbidity effect (in assays with a significant turbidity interference) was similar to that for glycerol (in assays with a significant glycerol interference). A triglyceride assay with a bichromatic measurement was less subject to interference from turbidity.

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

    PubMed

    Nordestgaard, Børge G

    2016-02-19

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

  19. Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels.

    PubMed

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

    2002-11-15

    The recently identified apolipoprotein A5 gene (APOA5) has been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. We previously identified an APOA5 haplotype (designated APOA5*2) that is present in approximately 16% of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA5*3) containing the rare allele of the single nucleotide polymorphism c.56C>G that changes serine to tryptophan at codon 19 and is independently associated with high plasma triglyceride levels in three different populations. In a sample of 264 Caucasian men and women with plasma triglyceride concentrations above the 90th percentile or below the 10th percentile, the APOA5*3 haplotype was more than three-fold more common in the group with high plasma triglyceride levels. In a second independently ascertained sample of Caucasian men and women (n=419) who were studied while consuming their self-selected diets as well as after high-carbohydrate diets and high-fat diets, the APOA5*3 haplotype was associated with increased plasma triglyceride levels on all three dietary regimens. In a third population comprising 2660 randomly selected individuals, the APOA5*3 haplotype was found in 12% of Caucasians, 14% of African-Americans and 28% of Hispanics and was associated with increased plasma triglyceride levels in both men and women in each ethnic group. These findings establish that the APOA5 locus contributes significantly to inter-individual variation in plasma triglyceride levels in humans. Together, the APOA5*2 and APOA5*3 haplotypes are found in 25-50% of African-Americans, Hispanics and Caucasians and support the contribution of common human variation to quantitative phenotypes in the general population.

  20. Two independent apolipoprotein a5 Haplotypes influence human plasma triglyceride levels

    SciTech Connect

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

    2002-09-16

    The recently identified apolipoprotein A5 gene (APOA5) has been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. We previously identified an APOA5 haplotype (designated APOA5*2) that is present in {approx}16 percent of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA5*3) containing the rare allele of the single nucleotide polymorphism c.56C>G that changes serine to tryptophan at codon 19 and is independently associated with high plasma triglyceride levels in three different populations. In a sample of 264 Caucasian men and women with plasma triglyceride concentrations above the 90th percentile or below the 10th percentile, the APOA5*3 haplotype was more than three-fold more common in the group with high plasma triglyceride levels. In a second independently ascertained sample of Caucasian men and women (n 1/4 419) who were studied while consuming their self-selected diets as well as after high-carbohydrate diets and high-fat diets, the APOA5*3 haplotype was associated with increased plasma triglyceride levels on all three dietary regimens. In a third population comprising 2660 randomly selected individuals, the APOA5*3 haplotype was found in 12 percent of Caucasians, 14 percent of African-Americans and 28 percent of Hispanics and was associated with increased plasma triglyceride levels in both men and women in each ethnic group. These findings establish that the APOA5 locus contributes significantly to inter-individual variation in plasma triglyceride levels in humans. Together, the APOA5*2 and APOA5*3 haplotypes are found in 25 50 percent of African-Americans, Hispanics and Caucasians and support the contribution of common human variation to quantitative phenotypes in the general population.

  1. 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.

  2. Decreased triglyceride-rich lipoproteins in transgenic skinny mice overexpressing leptin.

    PubMed

    Matsuoka, N; Ogawa, Y; Masuzaki, H; Ebihara, K; Aizawa-Abe, M; Satoh, N; Ishikawa, E; Fujisawa, Y; Kosaki, A; Yamada, K; Kuzuya, H; Nakao, K

    2001-02-01

    Leptin is an adipocyte-derived circulating satiety factor with a variety of biological effects. Evidence has accumulated suggesting that leptin may modulate glucose and lipid metabolism. In the present study, we examined lipid metabolism in transgenic skinny mice with elevated plasma leptin concentrations. The plasma concentrations of triglycerides and free fatty acids in transgenic skinny mice were 71.5 (P < 0.01) and 89.1% (P < 0.05) of those in their nontransgenic littermates, respectively. Separation of plasma into lipoprotein classes by ultracentrifugation revealed that very low density lipoprotein-triglyceride concentrations were markedly reduced in transgenic skinny mice relative to the controls. The clearance of triglycerides estimated by a fat-loading test was enhanced in transgenic skinny mice; the triglyceride concentration in transgenic skinny mice 3 h after fat loading was 39.7% (P < 0.05) of that of their nontransgenic littermates. Postheparin plasma lipoprotein lipase activity increased 1.4-fold (P < 0.05) in transgenic skinny mice. Our data demonstrated a significant reduction in plasma triglyceride concentrations, accompanied by increased lipoprotein lipase activity in transgenic skinny mice overexpressing leptin, suggesting that leptin plays a role in long-term triglyceride metabolism.

  3. Hydrolysis characteristics of bovine milk fat and monoacid triglycerides mediated by pregastric lipase from goats and kids.

    PubMed

    Lai, D T; MacKenzie, A D; O'Connor, C J; Turner, K W

    1997-10-01

    Commercial extracts from oro-pharyngeal tissues of goats and kids have been used as the source of pregastric lipase and have been processed to yield partially purified samples of the primary pregastric lipase. The activity of these lipases against tributyrylglycerol has been determined over a range of pH and temperatures. Optimum pH conditions for pregastric lipase ranged from pH 5.6 to 6.5 for goats and from pH 5.5 to 6.2 for kids, respectively; the optimum temperature ranged from 43 to 60 degrees C. Optima for kid lipase extended slightly below pH 5.5 and higher than 60 degrees C; which were the limits of the test conditions. The enzymes were also used as catalysts for the hydrolysis of monoacid triglycerides (C4:0 to C12:0) at 40 degrees C and pH 6.5; activity was maximum against tributyrylglycerol (C4:0). Values for the Michaelis-Menten constant, increased as carbon chain length of the carboxylic moiety on the triglycerides increased, but values were identical for pregastric lipases of both goats and kids. Anhydrous milk fat was hydrolyzed by the commercial extracts of pregastric lipases of goats and kids, and the resulting profiles for free fatty acids were very similar to one another and to the corresponding profile for a commercial sample of Parmesan cheese. There appear to be no significant differences in activity between the enzyme preparations from goats and kids.

  4. Chain Gang

    NASA Technical Reports Server (NTRS)

    2006-01-01

    6 August 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a chain of clustered and battered craters. These were formed by secondary impact. That is, somewhere to the south (beyond the bottom of this image), a large impact crater formed. When this occurred, material ejected from the crater was thrown tens to hundreds of kilometers away. This material then impacted the martian surface, forming clusters and chains of smaller craters.

    Location near: 15.8oN, 35.6oW Image width: 3 km (1.9 mi) Illumination from: upper left Season: Northern Spring

  5. Low erucic acid canola oil does not induce heart triglyceride accumulation in neonatal pigs fed formula.

    PubMed

    Green, T J; Innis, S M

    2000-06-01

    Canola oil is not approved for use in infant formula largely because of concerns over possible accumulation of triglyceride in heart as a result of the small amounts of erucic acid (22:1n-9) in the oil. Therefore, the concentration and composition of heart triglyceride were determined in piglets fed from birth for 10 (n = 4-6) or 18 (n = 6) d with formula containing about 50% energy fat as 100% canola oil (0.5% 22:1n-9) or 100% soybean oil, or 26% canola oil or soy oil (blend) with palm, high-oleic sunflower and coconut oil, providing amounts of 16:0 and 18:1 closer to milk, or a mix of soy, high-oleic sunflower and flaxseed oils with C16 and C18 fatty acids similar to canola oil but without 22:1. Biochemical analysis found no differences in heart triglyceride concentrations among the groups at 10 or 18 d. Assessment of heart triglycerides using Oil Red O staining in select treatments confirmed no differences between 10-d-old piglets fed formula with 100% canola oil (n = 4), 100% soy oil (n = 4), or the soy oil blend (n = 2). Levels of 22:1n-9 in heart triglyceride and phospholipid, however, were higher (P<0.01) in piglets fed 100% canola oil or the canola oil blend, with higher levels found in triglycerides compared with phospholipids. The modest accumulation of 22:1n-9 associated with feeding canola oil was not associated with biochemical evidence of heart triglyceride accumulation at 10 and 18 d. PMID:10901421

  6. Amphiphilic phase-transforming catalysts for transesterification of triglycerides

    NASA Astrophysics Data System (ADS)

    Nawaratna, Gayan Ivantha

    Heterogeneous catalytic reactions that involve immiscible liquid-phase reactants are challenging to conduct due to limitations associated with mass transport. Nevertheless, there are numerous reactions such as esterification, transesterification, etherification, and hydrolysis where two immiscible liquid reactants (such as polar and non-polar liquids) need to be brought into contact with a catalyst. With the intention of alleviating mass transport issues associated with such systems but affording the ability to separate the catalyst once the reaction is complete, the overall goal of this study is geared toward developing a catalyst that has emulsification properties as well as the ability to phase-transfer (from liquid-phase to solid-phase) while the reaction is ongoing and evaluating the effectiveness of such a catalytic process in a practical reaction. To elucidate this concept, the transesterification reaction was selected. Metal-alkoxides that possess acidic and basic properties (to catalyze the reaction), amphiphilic properties (to stabilize the alcohol/oil emulsion) and that can undergo condensation polymerization when heated (to separate as a solid subsequent to the completion of the reaction) were used to test the concept. Studies included elucidating the effect of metal sites and alkoxide sites and their concentration effects on transesterification reaction, effect of various metal alkoxide groups on the phase stability of the reactant system, and kinetic effects of the reaction system. The studies revealed that several transition-metal alkoxides, especially, titanium and yttrium based, responded positively to this reaction system. These alkoxides were able to be added to the reaction medium in liquid phase and were able to stabilize the alcohol/oil system. The alkoxides were selective to the transesterification reaction giving a range of ester yields (depending on the catalyst used). It was also observed that transition-metal alkoxides were able to be

  7. Genomic interval engineering of mice identifies a novel modulator of triglyceride production.

    PubMed

    Zhu, Y; Jong, M C; Frazer, K A; Gong, E; Krauss, R M; Cheng, J F; Boffelli, D; Rubin, E M

    2000-02-01

    To accelerate the biological annotation of novel genes discovered in sequenced regions of mammalian genomes, we are creating large deletions in the mouse genome targeted to include clusters of such genes. Here we describe the targeted deletion of a 450-kb region on mouse chromosome 11, which, based on computational analysis of the deleted murine sequences and human 5q orthologous sequences, codes for nine putative genes. Mice homozygous for the deletion had a variety of abnormalities, including severe hypertriglyceridemia, hepatic and cardiac enlargement, growth retardation, and premature mortality. Analysis of triglyceride metabolism in these animals demonstrated a several-fold increase in hepatic very-low density lipoprotein triglyceride secretion, the most prevalent mechanism responsible for hypertriglyceridemia in humans. A series of mouse BAC and human YAC transgenes covering different intervals of the 450-kb deleted region were assessed for their ability to complement the deletion induced abnormalities. These studies revealed that OCTN2, a gene recently shown to play a role in carnitine transport, was able to correct the triglyceride abnormalities. The discovery of this previously unappreciated relationship between OCTN2, carnitine, and hepatic triglyceride production is of particular importance because of the clinical consequence of hypertriglyceridemia and the paucity of genes known to modulate triglyceride secretion.

  8. 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.

  9. Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease.

    PubMed

    Kawano, Yuki; Cohen, David E

    2013-04-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation in the absence of excess alcohol intake. NAFLD is the most common chronic liver disease, and ongoing research efforts are focused on understanding the underlying pathobiology of hepatic steatosis with the anticipation that these efforts will identify novel therapeutic targets. Under physiological conditions, the low steady-state triglyceride concentrations in the liver are attributable to a precise balance between acquisition by uptake of non-esterified fatty acids from the plasma and by de novo lipogenesis, versus triglyceride disposal by fatty acid oxidation and by the secretion of triglyceride-rich lipoproteins. In NAFLD patients, insulin resistance leads to hepatic steatosis by multiple mechanisms. Greater uptake rates of plasma non-esterified fatty acids are attributable to increased release from an expanded mass of adipose tissue as a consequence of diminished insulin responsiveness. Hyperinsulinemia promotes the transcriptional upregulation of genes that promote de novo lipogenesis in the liver. Increased hepatic lipid accumulation is not offset by fatty acid oxidation or by increased secretion rates of triglyceride-rich lipoproteins. This review discusses the molecular mechanisms by which hepatic triglyceride homeostasis is achieved under normal conditions, as well as the metabolic alterations that occur in the setting of insulin resistance and contribute to the pathogenesis of NAFLD. PMID:23397118

  10. Hypoxia-induced mobilization of stored triglycerides in the euryoxic goby Gillichthys mirabilis.

    PubMed

    Gracey, Andrew Y; Lee, Tsung-Han; Higashi, Richard M; Fan, Teresa

    2011-09-15

    Environmental hypoxia is a common challenge that many aquatic organisms experience in their habitat. Responding to hypoxia requires metabolic reprogramming so that energy-demanding processes are regulated to match available energy reserves. In this study we explored the transcriptional control of metabolic reorganization in the liver of a hypoxia-tolerant burrow-dwelling goby, Gillichthys mirabilis. Gene expression data revealed that pathways associated with triglyceride hydrolysis were upregulated by hypoxia whereas pathways associated with triglyceride synthesis were downregulated. This finding was supported by tissue histology, which showed that the size of hepatic lipid droplets declined visibly during exposure to hypoxia. Proton nuclear magnetic resonance analysis confirmed the mobilization of hepatic triglycerides, which declined 2.7-fold after 5 days of hypoxia. The enzyme, adipose triglyceride lipase, was implicated in the mobilization of triglycerides because its expression increased at the level of both transcript and protein. This observation raises questions regarding the regulation of fat metabolism during hypoxia and the role played by the hypoxia-responsive gene leptin.

  11. Distinct metabolic and vascular effects of dietary triglycerides and cholesterol in atherosclerotic and diabetic mouse models.

    PubMed

    Laplante, Marc-André; Charbonneau, Alexandre; Avramoglu, Rita Kohen; Pelletier, Patricia; Fang, Xiangping; Bachelard, Hélène; Ylä-Herttuala, Seppo; Laakso, Markku; Després, Jean-Pierre; Deshaies, Yves; Sweeney, Gary; Mathieu, Patrick; Marette, André

    2013-09-01

    Cholesterol and triglyceride-rich Western diets are typically associated with an increased occurrence of type 2 diabetes and vascular diseases. This study aimed to assess the relative impact of dietary cholesterol and triglycerides on glucose tolerance, insulin sensitivity, atherosclerotic plaque formation, and endothelial function. C57BL6 wild-type (C57) mice were compared with atherosclerotic LDLr(-/-) ApoB(100/100) (LRKOB100) and atherosclerotic/diabetic IGF-II × LDLr(-/-) ApoB(100/100) (LRKOB100/IGF) mice. Each group was fed either a standard chow diet, a 0.2% cholesterol diet, a high-fat diet (HFD), or a high-fat 0.2% cholesterol diet for 6 mo. The triglyceride-rich HFD increased body weight, glucose intolerance, and insulin resistance but did not alter endothelial function or atherosclerotic plaque formation. Dietary cholesterol, however, increased plaque formation in LRKOB100 and LRKOB100/IGF animals and decreased endothelial function regardless of genotype. However, cholesterol was not associated with an increase of insulin resistance in LRKOB100 and LRKOB100/IGF mice and, unexpectedly, was even found to reduce the insulin-resistant effect of dietary triglycerides in these animals. Our data indicate that dietary triglycerides and cholesterol have distinct metabolic and vascular effects in obese atherogenic mouse models resulting in dissociation between the impairment of glucose homeostasis and the development of atherosclerosis.

  12. The regulation of triglyceride synthesis and fatty acid synthesis in rat epididymal adipose tissue. Effects of insulin, adrenaline and some metabolites in vitro

    PubMed Central

    Saggerson, E. D.; Greenbaum, A. L.

    1970-01-01

    1. Adipose tissues from rats fed a balanced diet were incubated in the presence of glucose (20mm) with the following additions: insulin, anti-insulin serum, insulin+acetate, insulin+pyruvate, insulin+lactate, insulin+phenazine methosulphate, insulin+oleate+albumin, insulin+adrenaline+albumin, insulin+6-N-2′-O-dibutyryl 3′:5′-cyclic AMP+albumin. 2. Measurements were made of the whole tissue concentrations of adenine nucleotides, hexose phosphates, triose phosphates, glycerol 1-phosphate, 3 phosphoglycerate, 6-phosphogluconate, long-chain fatty acyl-CoA, acid-soluble CoA, citrate, isocitrate, malate and 2-oxoglutarate, and of the release into the incubation medium of lactate, pyruvate and glycerol after 1h of incubation. 3. Fluxes of [14C]glucose carbon through the major pathways of glucose metabolism were calculated from the yields of 14C in various products after 2h of incubation. Fluxes of [14C]acetate, [14C]pyruvate or [14C]lactate carbon in the presence of glucose were also determined. 4. Measurements were also made of the whole-tissue concentrations of metabolites in tissues taken directly from Nembutal-anaesthetized rats. 5. Whole tissue mass-action ratios for phosphofructokinase, phosphoglucose isomerase and the combined (aldolase×triose phosphate isomerase) reaction were similar in vivo and in vitro. The reactants of phosphofructokinase appeared to be far from mass-action equilibrium. In vitro, the reactants of hexokinase also appeared to be far from mass-action equilibrium. 6. Correlation of observed changes in glycolytic flux with changes in fructose 6-phosphate concentration suggested that phosphofructokinase may show regulatory behaviour. The enzyme appeared to be activated in the presence of oleate or adrenaline and to be inhibited in the presence of lactate or pyruvate. 7. Evidence is presented that the reactants of lactate dehydrogenase and glycerol 1-phosphate dehydrogenase may be near to mass-action equilibrium in the cytoplasm. 8. No

  13. Perilipin-5 is regulated by statins and controls triglyceride contents in the hepatocyte

    PubMed Central

    Langhi, Cédric; Marquart, Tyler J.; Allen, Ryan M.; Baldán, Ángel

    2014-01-01

    Background & Aims Perilipin-5 (PLIN5) is a member of the perilipin family of lipid droplet (LD)-associated proteins. PLIN5 is expressed in oxidative tissues including the liver, and is critical during LD biogenesis. Studies showed that statins reduce hepatic triglyceride contents in some patients with non-alcoholic fatty liver disease and in rodent models of diet-induced hepatosteatosis. Whether statins alter triglyceride synthesis, storage, and/or utilization within the hepatocyte is unknown, though. Here we tested the hypothesis that statins alter the metabolism of LD in the hepatocyte during physiological conditions, such as fasting-induced steatosis. Methods Mice were gavaged with saline or atorvastatin, and the expression of LD-associated genes was determined in fed and fasted animals. The accumulation of triglycerides and LD was studied in mouse or human primary hepatocytes in response to statins, and following knock-down of SREBP2 or PLIN5. Results We show that statins decrease the levels of PLIN5, but not other LD-associated genes, in both mouse liver and mouse/human primary hepatocytes, which is paralleled by a significant reduction in both intracellular triglycerides and the number of LD. We identify an atypical negative sterol regulatory sequence in the proximal promoter of mouse/human PLIN5 that recruits the transcription factor SREBP2 and confers response to statins. Finally, we show that the statin-dependent reduction of hepatocyte triglyceride contents is mimicked by partial knock-down of PLIN5; conversely, ectopic overexpression of PLIN5 reverts the statin effect. Conclusions PLIN5 is a physiological regulator of triglyceride metabolism in the liver, and likely contributes to the pleiotropic effects of statins. PMID:24768901

  14. Safety assessment of EPA-rich triglyceride oil produced from yeast: genotoxicity and 28-day oral toxicity in rats.

    PubMed

    Belcher, Leigh A; MacKenzie, Susan A; Donner, Maria; Sykes, Greg P; Frame, Steven R; Gillies, Peter J

    2011-02-01

    The 28-day repeat-dose oral and genetic toxicity of eicosapentaenoic acid triglyceride oil (EPA oil) produced from genetically modified Yarrowia lipolytica yeast were assessed. Groups of rats received 0 (olive oil), 940, 1880, or 2820 mg EPA oil/kg/day, or fish oil (sardine/anchovy source) by oral gavage. Lower total serum cholesterol was seen in all EPA and fish oil groups. Liver weights were increased in the medium and high-dose EPA (male only), and fish oil groups but were considered non-adverse physiologically adaptive responses. Increased thyroid follicular cell hypertrophy was observed in male high-dose EPA and fish oil groups, and was considered to be an adaptive response to high levels of polyunsaturated fatty acids. No adverse test substance-related effects were observed on body weight, nutritional, or other clinical or anatomic pathology parameters. The oil was not mutagenic in the in vitro Ames or mouse lymphoma assay, and was not clastogenic in the in vivo mouse micronucleus test. In conclusion, exposure for 28 days to EPA oil derived from yeast did not produce adverse effects at doses up to 2820 mg/kg/day and was not genotoxic. The safety profile of the EPA oil in these tests was comparable to a commercial fish oil.

  15. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) deficiencies affect expression of lipolytic activities in mouse adipose tissues.

    PubMed

    Morak, Maria; Schmidinger, Hannes; Riesenhuber, Gernot; Rechberger, Gerald N; Kollroser, Manfred; Haemmerle, Guenter; Zechner, Rudolf; Kronenberg, Florian; Hermetter, Albin

    2012-12-01

    Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are key enzymes involved in intracellular degradation of triacylglycerols. It was the aim of this study to elucidate how the deficiency in one of these proteins affects the residual lipolytic proteome in adipose tissue. For this purpose, we compared the lipase patterns of brown and white adipose tissue from ATGL (-/-) and HSL (-/-) mice using differential activity-based gel electrophoresis. This method is based on activity-recognition probes possessing the same substrate analogous structure but carrying different fluorophores for specific detection of the enzyme patterns of two different tissues in one electrophoresis gel. We found that ATGL-deficiency in brown adipose tissue had a profound effect on the expression levels of other lipolytic and esterolytic enzymes in this tissue, whereas HSL-deficiency hardly showed any effect in brown adipose tissue. Neither ATGL- nor HSL-deficiency greatly influenced the lipase patterns in white adipose tissue. Enzyme activities of mouse tissues on acylglycerol substrates were analyzed as well, showing that ATGL-and HSL-deficiencies can be compensated for at least in part by other enzymes. The proteins that responded to ATGL-deficiency in brown adipose tissue were overexpressed and their activities on acylglycerols were analyzed. Among these enzymes, Es1, Es10, and Es31-like represent lipase candidates as they catalyze the hydrolysis of long-chain acylglycerols.

  16. Synthetic laser medium

    DOEpatents

    Stokowski, Stanley E.

    1989-01-01

    A laser medium is particularly useful in high average power solid state lasers. The laser medium includes a chormium dopant and preferably neodymium ions as codopant, and is primarily a gadolinium scandium gallium garnet, or an analog thereof. Divalent cations inhibit spiral morphology as large boules from which the laser medium is derived are grown, and a source of ions convertible between a trivalent state and a tetravalent state at a low ionization energy are in the laser medium to reduce an absorption coefficient at about one micron wavelength otherwise caused by the divalent cations. These divalent cations and convertible ions are dispersed in the laser medium. Preferred convertible ions are provided from titanium or cerium sources.

  17. Synthetic laser medium

    DOEpatents

    Stokowski, S.E.

    1987-10-20

    A laser medium is particularly useful in high average power solid state lasers. The laser medium includes a chromium dopant and preferably neodymium ions as codopant, and is primarily a gadolinium scandium gallium garnet, or an analog thereof. Divalent cations inhibit spiral morphology as large boules from which the laser medium is derived are grown, and a source of ions convertible between a trivalent state and a tetravalent state at a low ionization energy are in the laser medium to reduce an absorption coefficient at about one micron wavelength otherwise caused by the divalent cations. These divalent cations and convertible ions are dispersed in the laser medium. Preferred convertible ions are provided from titanium or cerium sources.

  18. Processing of coriander fruits for the production of essential oil, triglyceride, and high protein seed meal

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Coriander (Coriandrum sativum L.) is a summer annual traditionally grown for use as a fresh green herb or as a spice. The essential oil extracted from coriander fruit is also widely used as flavoring in a variety of food products. The fatty oil (triglyceride) fraction in the seed is rich in petrosel...

  19. Genetic variation in Tanis was associated with elevating plasma triglyceride level in Chinese nondiabetic subjects

    PubMed Central

    2013-01-01

    Background The association of genetic polymorphisms of Tanis with triglyceride concentration in human has not been thoroughly examined. We aimed to investigate the relationship between triglyceride concentrations and Tanis genetic polymorphisms. Methods All participants (n=1497) selected from subjects participating in the Cardiovascular Risk Survey (CRS) study were divided into two groups according to ethnicity (Han: n=1059; Uygur: n= 438). Four tagging SNPs (rs12910524, rs1384565, rs2101171, rs4965814) of Tanis gene were genotyped using TaqMan® assays from Applied Biosystems following the manufacturer’s suggestions and analyzed in an ABI 7900HT Fast Real-Time PCR System. Results We found that the SNP rs12910524 was associated with triglyceride levels by analyses of a dominant model (P<0.001), recessive model (P <0.001) and additive model (P < 0.001) not only in Han ethnic but also in Uygur ethnic group, and the difference remained significant after the adjustment of sex, age, alcohol intake, smoking, BMI and plasma glucose (GLU) level (All P < 0.001). However, this relationship was not observed in rs1384565, rs2101171, and rs4965814 before and after multivariate adjustment (All P > 0.05). Furthermore, there were significant interactions between rs12910524 and GLU on TG both in Han (P=0.001) and Uygur population (P=2.60×10-4). Conclusion Our results indicated that the rs12910524 in the Tanis gene was associated with triglyceride concentrations in subjects without diabetes in China. PMID:23829426

  20. Comprehensive Experiment--Clinical Biochemistry: Determination of Blood Glucose and Triglycerides in Normal and Diabetic Rats

    ERIC Educational Resources Information Center

    Jiao, Li; Xiujuan, Shi; Juan, Wang; Song, Jia; Lei, Xu; Guotong, Xu; Lixia, Lu

    2015-01-01

    For second year medical students, we redesigned an original laboratory experiment and developed a combined research-teaching clinical biochemistry experiment. Using an established diabetic rat model to detect blood glucose and triglycerides, the students participate in the entire experimental process, which is not normally experienced during a…

  1. Detection of triglycerides using immobilized enzymes in food and biological samples

    NASA Astrophysics Data System (ADS)

    Raichur, Ashish; Lesi, Abiodun; Pedersen, Henrik

    1996-04-01

    A scheme for the determination of total triglyceride (fat) content in biomedical and food samples is being developed. The primary emphasis is to minimize the reagents used, simplify sample preparation and develop a robust system that would facilitate on-line monitoring. The new detection scheme developed thus far involves extracting triglycerides into an organic solvent (cyclohexane) and performing partial least squares (PLS) analysis on the NIR (1100 - 2500 nm) absorbance spectra of the solution. A training set using 132 spectra of known triglyceride mixtures was complied. Eight PLS calibrations were generated and were used to predict the total fat extracted from commercial samples such as mayonnaise, butter, corn oil and coconut oil. The results typically gave a correlation coefficient (r) of 0.99 or better. Predictions were typically within 90% and better at higher concentrations. Experiments were also performed using an immobilized lipase reactor to hydrolyze the fat extracted into the organic solvent. Performing PLS analysis on the difference spectra of the substrate and product could enhance specificity. This is being verified experimentally. Further work with biomedical samples is to be performed. This scheme may be developed into a feasible detection method for triglycerides in the biomedical and food industries.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2015-05-01

    The aim of the present study was to determine whether single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) can non-invasively assess triglyceride content in both supraclavicular fat depots and subcutaneous white adipose tissue (WAT) to determine whether these measurements correlate to metabolic variables. A total of 25 healthy volunteers were studied using (18)F-fluorodeoxyglucose positron emission tomography (PET) and (15)O-H2O PET perfusion during cold exposure, and (1)H-MRS at ambient temperature. Image-guided biopsies were collected from nine volunteers. The supraclavicular triglyceride content determined by (1)H-MRS varied between 60 and 91% [mean ± standard deviation (s.d.) 77 ± 10%]. It correlated positively with body mass index, waist circumference, subcutaneous and visceral fat masses and 8-year diabetes risk based on the Framingham risk score and inversely with HDL cholesterol and insulin sensitivity (M-value; euglycaemic-hyperinsulinaemic clamp). Subcutaneous WAT had a significantly higher triglyceride content, 76-95% (mean ± s.d. 87 ± 5%; p = 0.0002). In conclusion, the triglyceride content in supraclavicular fat deposits measured by (1)H-MRS may be an independent marker of whole-body insulin sensitivity, independent of brown adipose tissue metabolic activation. PMID:25586670

  4. Intercorrelations among plasma high density lipoprotein, obesity and triglycerides in a normal population

    SciTech Connect

    Albrink, M.J.; Krauss, R.M.; Lindgren, F.T.; von der Groeben, J.; Pan, S.; Wood, P.D.

    1980-01-01

    The interrelationships among fatness measures, plasma triglycerides and high density lipoproteins (HDL) were examined in 131 normal adult subjects: 38 men aged 27 to 46, 50 men aged 47 to 66, 29 women aged 27 to 46 and 24 women aged 47 to 66. None of the women were taking estrogens or oral contraceptive medication. The HDL concentration was subdivided into HDL/sub 2b/, HDL/sub 2a/ and HDL by a computerized fitting of the total schileren pattern to reference schlieren patterns. Anthropometric measures employed included skinfolds at 3 sites, 2 weight/height indices and 2 girth measurements. A high correlation was found among the various fatness measures. These measures were negatively correlated with total HDL, reflecting the negative correlation between fatness measures and HDL/sub 2/ (as the sum of HDL/sub 2a/ and /sub 2b/). Fatness measures showed no relationship to HDL/sub 3/. There was also an inverse correlation between triglyceride concentration and HDL/sub 2/. No particular fatness measure was better than any other for demonstrating the inverse correlation with HDL but multiple correlations using all of the measures of obesity improved the correlations. Partial correlations controlling for fatness did not reduce any of the significnt correlations between triglycerides and HDL/sub 2/ to insignificance. The weak correlation between fatness and triglycerides was reduced to insigifnicance when controlled for HDL/sub 2/.

  5. Heterogeneous catalysts for the transformation of fatty acid triglycerides and their derivatives to fuel hydrocarbons

    NASA Astrophysics Data System (ADS)

    Yakovlev, Vadim A.; Khromova, Sofia A.; Bukhtiyarov, Valerii I.

    2011-10-01

    The results of studies devoted to the catalysts for transformation of fatty acid triglycerides and their derivatives to fuel hydrocarbons are presented and described systematically. Various approaches to the use of heterogeneous catalysts for the production of biofuel from these raw materials are considered. The bibliography includes 134 references.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  8. Osage Orange (Maclura pomifera L.) Seed Oil Poly(α-hydroxydibutylamine) Triglycerides: Synthesis and Characterization.

    PubMed

    Harry-O'kuru, Rogers E; Tisserat, Brent; Gordon, Sherald H; Gravett, Alan

    2015-07-29

    Milled Osage orange seeds (Maclura pomifera (Raf.) Schneid) were Soxhlet extracted with hexane, and portions of the extract were treated with activated carbon before solvent removal. The crude oil was winterized and degummed by centrifugation at low temperature. Decantation of the centrifugate gave an admixture of the triglycerides and free fatty acids. The free fatty acid content of the oil was removed when portions of the admixture were diluted with hexane and shaken with cold aqueous ammonium hydroxide (0.1 M) solution. The desiccant-dried organic phase was concentrated under reduced pressure to give the cleaned Osage orange triglyceride after solvent removal by rotary evaporation at 67 °C. Epoxidation of the resulting cleaned triglyceride was effected by reaction with in situ generated peroxy performic acid in H2O2. The oxirane rings of the derivatized oil were then opened using N,N-dibutylamine catalyzed by anhydrous ZnCl2 to afford the poly(α-hydroxydibutylamine) triglyceride. The purpose of this work was to derivatize and thereby stabilize this highly unsaturated tree oil for its eventual use in lubrication applications. PMID:26189408

  9. Genetic APOC3 mutation, serum triglyceride concentrations, and coronary heart disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent decades have witnessed an increased awareness of the importance of lowering triglyceride concentrations in conjunction with lowering LDL cholesterol (LDL-C) to achieve optimal reduction of the risk for coronary heart disease (CHD). Historically, LDL-C was the only target of pharmacologic ther...

  10. Preoperative Body Mass Index, Blood Albumin and Triglycerides Predict Survival for Patients with Gastric Cancer

    PubMed Central

    Liu, Bin Zheng; Tao, Lin; Chen, Yun Zhao; Li, Xu Zhe; Dong, Yu Ling; Ma, Ya Jing; Li, Shu Gang; Li, Feng; Zhang, Wen Jie

    2016-01-01

    Background Gastric cancer (GC) is common and its prognosis is often poor due to difficulties in early diagnosis and optimal treatment strategies. TNM staging system is useful in predicting prognosis but only possible after surgery. Therefore, it is desirable to investigate prognostic factors/markers that may predict prognosis before surgery by which helps appropriate management decisions preoperatively. Methods A total of 320 GC patients were consecutively recruited from 2004 to 2013 and followed up for 127 months (10.6 years) after surgery. These patients’ were examined for body mass index (BMI) and blood levels of albumin, triglyceride, total cholesterol, low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C). Kaplan-Meier method and log rank test were used to analyze long-term survival using the above potential risk markers. We first employed medians of these variables to reveal maximal potentials of the above prognostic predictors. Results Three major findings were obtained: (1) Preoperative BMI was positively correlated with albumin (r = 0.144, P<0.05) and triglyceride (r = 0.365, P<0.01), but negatively correlated with TNM staging (r = -0.265, P<0.05). Preoperative albumin levels were positively correlated with triglyceride (r = 0.173, P<0.05) but again, negatively correlated with TNM staging (r = -0.137, P<0.05); (2) Poor survival was observed in GC patients with lower levels of BMI (P = 0.028), albumin (P = 0.004), and triglyceride (P = 0.043), respectively. Receiver operating characteristic (ROC) curve analyses suggested BMI, albumin and triglyceride to have survival-predictor powers similar to TNM system; and (3) Cox multi-factorial analyses demonstrated that age (P = 0.049), BMI (P = 0.016), cell differentiation (P = 0.001), and TNM staging (P = 0.011) were independent overall survival-predictors for GC patients. Conclusions Preoperative BMI, albumin, and triglyceride levels are capable of predicting survival for

  11. Spatiotemporal irregularity in an excitable medium with shear flow.

    PubMed

    Biktashev, V N; Biktasheva, I V; Holden, A V; Tsyganov, M A; Brindley, J; Hill, N A

    1999-08-01

    We consider an excitable medium moving with relative shear, subjected to a localized disturbance that in a stationary medium would produce a pair of spiral waves. The spiral waves so created are distorted and then broken by the motion of the medium. Such breaks generate new spiral waves, and so a "chain reaction" of spiral wave births and deaths is observed. This leads to a complicated spatiotemporal pattern, the "frazzle gas" [term suggested by Markus et al., Nature (London) 371, 402 (1994)], which eventually fills the whole medium. In this paper, we display and interpret the main features of the pattern. PMID:11969978

  12. Apolipoprotein A-V: a potential modulator of plasma triglyceride levels in Turks.

    PubMed

    Hodoglugil, Ugur; Tanyolaç, Sinan; Williamson, David W; Huang, Yadong; Mahley, Robert W

    2006-01-01

    The apolipoprotein A-V gene (APOA5) plays an important role in determining plasma triglyceride levels. We studied the effects of APOA5 polymorphisms on plasma triglyceride levels in Turks, a population with low levels of HDL cholesterol and a high prevalence of coronary artery disease. We found 15 polymorphisms, three of which were novel. Seven haplotype-tagging single nucleotide polymorphisms (SNPs) were chosen and genotyped in approximately 3,000 subjects. The rare alleles of the -1464T>C, -1131T>C, S19W, and 1259T>C SNPs were significantly associated with increased triglyceride levels (19-86 mg/dl; P < 0.05) and had clear gene-dose effects. Haplotype analysis of the nine common APOA5 haplotypes revealed significant effects on triglyceride levels (P < 0.001). Detailed analysis of haplotypes clearly showed that the -1464T>C polymorphism had no effect by itself but was a marker for the -1131T>C, S19W, and 1259T>C polymorphisms. The -1131T>C and 1259T>C polymorphisms were in a strong but incomplete linkage disequilibrium and appeared to have independent effects. Thus, the APOA5 -1131T>C, S19W, and 1259T>C rare alleles were associated with significant increases in plasma triglyceride levels. At least one of these alleles was present in approximately 40% of the Turks. Similar associations were observed for -1131T>C and S19W in white Americans living in San Francisco, California.

  13. Microbial biosurfactants and hydrolytic enzymes mediates in situ development of stable supra-molecular assemblies in fatty acids released from triglycerides.

    PubMed

    Gnanamani, Arumugam; Kavitha, V; Radhakrishnan, N; Sekaran, G; Rajakumar, G Suseela; Mandal, A B

    2010-07-01

    The present study demonstrates in situ formation of multilamellar stable vesicles (MLSVs) of fatty acids released during the growth of microorganisms in the presence of triglycerides. Release of lipase during initial phase of growth hydrolyzes the triglycerides and release free fatty acids (mono or diglycerides) and glycerol. By extending the growth and the prevailing composition of media (unspent nutrients, salts, pH of the medium, biosurfactants, fatty acids, glycerol) and agitation transforms free fatty acids to MLSV of both cylindrical and spherical macroscopic structures via micelle formation with in 240h of incubation. Cross-sectional view and SEM analysis of macroscopic structures reveal the existence of continuous multilayering. Thermo-gravimetric analysis illustrates the stability of the vesicles. FT-IR analysis emphasizes the presence of amide linkages, responsible for self-assembly processes. Schematic representation of formation of MLSV demonstrated for further understanding. Additional exploration on MLSV formation in arteries and the relationship between MLSV and in situ plaque formation by the components of blood in the arteries are schematically explained and submitted as supporting information (SI-2).

  14. An esterase on the outer membrane of Pseudomonas aeruginosa for the hydrolysis of long chain acyl esters.

    PubMed

    Ohkawa, I; Shiga, S; Kageyama, M

    1979-09-01

    A new esterase activity which hydrolyzes palmitoyl-CoA was found in the membrane fraction of Pseudomonas aeruginosa. All the 11 strains of P. aeruginosa tested possessed this esterase activity. The esterase was constitutive and was fully active on the intact cell bodies toward substrates in the medium. It was located on the outer membrane of the cell envelope, and was not released into the culture medium. This activity was designated as OM (outer membrane) esterase. OM esterase was solubilized from the cell envelope with EDTA-Triton X-100 and purified 690-fold. It was a minor component of the outer membrane. Its molecular weight was approximately 55,000. The activity was rather stable to heat, a wide range of pH, and treatment with detergents and organic solvents. No cofactors were required. The pH optimum of the reaction was 8.5. Among various acyl-CoAs, only long chain (C12--C18) thioesters were hydrolyzed. OM esterase also hydrolyzed some kinds of oxy-esters such as p-nitrophenyl acyl esters, monoacyl esters of sucrose and Tween 80 (polyoxyethylene sorbitan monooleate). On the other hand, triglycerides, phospholipids, or hydrophobic monoesters were not hydrolyzed at all. Thus, this enzyme seems to have specificity for long chain acyl esters with hydrophilic groups, whether thio- or oxy-ester. Mutants deficient in this esterase activity were isolated. These mutants were unable to grow on Tween 80 as a sole carbon source. This suggests a possible role of OM esterase in the utilization of acyl esters as carbon sources.

  15. Brief Communication: Discordant ability of the triglyceride to apolipoprotein B ratio to predict triglyceride-rich lipoprotein particle size in normal-weight and obese men.

    PubMed

    Amigo-Benavent, Miryam; Sinausia, Laura; Montero, Emilio; Perona, Javier S

    2016-10-01

    The atherogenicity of triglyceride-rich lipoproteins (TRLs) is dependent of their particle size as it determines their metabolic fate. Since TRL possess a single apolipoprotein B (Apo B) molecule per particle, the triglyceride (TG)/Apo B ratio has been used as a convenient method to estimate TRL size. The aim of this study was to validate this approach by correlating the serum TG/Apo B ratio, and the TRL particle size measured by dynamic light scattering (DLS). Twenty-four male volunteers (12 normal-weight and 12 obese individuals) received a high-fat meal. Preprandial (0 h) and postprandial (2 and 4 h) serum samples were collected after meal ingestion, and TRLs were isolated. Serum TG and Apo B levels were quantified, and the TG/Apo B ratio was plotted against TRL particle size measured by DLS for correlation. A strong association between TRL particle size and serum TG/Apo B ratio for normal-weight subjects (P ≤ 0.001) was observed but not for obese subjects (P = 0.6116). TG/Apo B ratio correlates with particle size in healthy normal-weight males but not in obese individuals. Whether this ratio is useful to estimate TRL size in females and in other dyslipidemic patients should be subject of future investigations.

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

    PubMed Central

    2014-01-01

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

  17. Development and pathomechanisms of cardiomyopathy in very long-chain acyl-CoA dehydrogenase deficient (VLCAD(-/-)) mice.

    PubMed

    Tucci, Sara; Flögel, Ulrich; Hermann, Sven; Sturm, Marga; Schäfers, Michael; Spiekerkoetter, Ute

    2014-05-01

    Hypertrophic cardiomyopathy is a typical manifestation of very long-chain acyl-CoA dehydrogenase deficiency (VLCADD), the most common long-chain β-oxidation defects in humans; however in some patients cardiac function is fully compensated. Cardiomyopathy may also be reversed by supplementation of medium-chain triglycerides (MCT). We here characterize cardiac function of VLCAD-deficient (VLCAD(-/-)) mice over one year. Furthermore, we investigate the long-term effect of a continuous MCT diet on the cardiac phenotype. We assessed cardiac morphology and function in VLCAD(-/-) mice by in vivo MRI. Cardiac energetics were measured by (31)P-MRS and myocardial glucose uptake was quantified by positron-emission-tomography (PET). Metabolic adaptations were identified by the expression of genes regulating glucose and lipid metabolism using real-time-PCR. VLCAD(-/-) mice showed a progressive decrease in heart function over 12 months accompanied by a reduced phosphocreatine-to-ATP-ratio indicative of chronic energy deficiency. Long-term MCT supplementation aggravated the cardiac phenotype into dilated cardiomyopathy with features similar to diabetic heart disease. Cardiac energy production and function in mice with a β-oxidation defect cannot be maintained with age. Compensatory mechanisms are insufficient to preserve the cardiac energy state over time. However, energy deficiency by impaired β-oxidation and long-term MCT induce cardiomyopathy by different mechanisms. Cardiac MRI and MRS may be excellent tools to assess minor changes in cardiac function and energetics in patients with β-oxidation defects for preventive therapy. PMID:24530811

  18. [DELAYED RESULTS OF ENZYME REPLACEMENT THERAPY, PRESCRIBED BY RESULTS OF 13C-TRIGLYCERIDE BREATH TEST].

    PubMed

    Chernyavskiy, V V; Gvozdetska, L S

    2015-01-01

    Maldigestion persists in most patients with chronic pancreatitis (CP). The objective lipase and amylase insufficiency diagnosis is needed to achieve an adequate clinical response to oral pancreatic enzyme substitution therapy. The novel data is presented in the article about the role of 13C-mixed triglyceride breath test as a tool for exocrine pancreatic insufficiency diagnosis, for evaluating fat malabsorbtion in CP patients. 135 patients were included in the investigation. Delayed results of enzyme replacement therapy were estimated after 1 and 2 year of surveillance. It has been shown, that partial recovery of exocrine pancreatic function is possible, and replacement therapy leads to patients nutritional status improving. Thus 13C-triglyceride breath test could be useful tool in clinical practice for CP diagnosis. The test make it possible to choose the initial pancreatic enzyme dosage and are beneficial during the treatment for pancreatic enzyme dose correction. PMID:26827447

  19. Optimization of conjugated linoleic acid triglycerides via enzymatic esterification in no-solvent system

    NASA Astrophysics Data System (ADS)

    Yi, Dan; Sun, Xiuqin; Li, Guangyou; Liu, Fayi; Lin, Xuezheng; Shen, Jihong

    2009-09-01

    We compared four esterifiable enzymes. The lipase Novozym 435 possessed the highest activity for the conjugated linoleic acid esterification during the synthesis of triglycerides. The triglycerides were synthesized by esterification of glycerol and conjugated linoleic acid (CLA) in a no-solvent system using lipase catalysis. We investigated the effects of temperature, enzyme concentration, water content, and time on esterification. Enzyme and water concentrations of up to 1% of the total reaction volume and a system temperature of 60°C proved optimal for esterification. Similarly, when the esterification was carried out for 24 h, the reaction ratio improved to 94.11%. The esterification rate of the rotating screen basket remained high (87.28%) when the enzyme was re-used for the 5th time. We evaluated the substrate selectivity of lipase (NOVO 435) and determined that this lipase prefers the 10,12-octadacadienoic acid to the 9,11-octadecadienoic acid.

  20. [DELAYED RESULTS OF ENZYME REPLACEMENT THERAPY, PRESCRIBED BY RESULTS OF 13C-TRIGLYCERIDE BREATH TEST].

    PubMed

    Chernyavskiy, V V; Gvozdetska, L S

    2015-01-01

    Maldigestion persists in most patients with chronic pancreatitis (CP). The objective lipase and amylase insufficiency diagnosis is needed to achieve an adequate clinical response to oral pancreatic enzyme substitution therapy. The novel data is presented in the article about the role of 13C-mixed triglyceride breath test as a tool for exocrine pancreatic insufficiency diagnosis, for evaluating fat malabsorbtion in CP patients. 135 patients were included in the investigation. Delayed results of enzyme replacement therapy were estimated after 1 and 2 year of surveillance. It has been shown, that partial recovery of exocrine pancreatic function is possible, and replacement therapy leads to patients nutritional status improving. Thus 13C-triglyceride breath test could be useful tool in clinical practice for CP diagnosis. The test make it possible to choose the initial pancreatic enzyme dosage and are beneficial during the treatment for pancreatic enzyme dose correction.

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

    PubMed

    Maher, K D; Bressler, D C

    2007-09-01

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

  2. Gas chromatographic analysis of synthetic glycidol esters, mono-, di- and triglycerides.

    PubMed

    Engbersen, J A; van Stijn, F

    1976-03-01

    The gas chromatographic analysis of glycidol esters and mono-, di-,and triglycerides of palmitic-, stearic-, and oleic acid mixtures is described. The composition of the products was determined by gas chromatography on OV-17 after trimethylsilylation. Base-line separations between 1- and 2-monoglycerides and between 1,2- and 1,3-diglycerides were obtained. Isomerisation of the trimethylsilyl ethers of monoglycerides was not observed, contrary to published work.

  3. Calorie Restricted High Protein Diets Downregulate Lipogenesis and Lower Intrahepatic Triglyceride Concentrations in Male Rats

    PubMed Central

    Margolis, Lee M.; Rivas, Donato A.; Ezzyat, Yassine; Gaffney-Stomberg, Erin; Young, Andrew J.; McClung, James P.; Fielding, Roger A.; Pasiakos, Stefan M.

    2016-01-01

    The purpose of this investigation was to assess the influence of calorie restriction (CR) alone, higher-protein/lower-carbohydrate intake alone, and combined CR higher-protein/lower-carbohydrate intake on glucose homeostasis, hepatic de novo lipogenesis (DNL), and intrahepatic triglycerides. Twelve-week old male Sprague Dawley rats consumed ad libitum (AL) or CR (40% restriction), adequate (10%), or high (32%) protein (PRO) milk-based diets for 16 weeks. Metabolic profiles were assessed in serum, and intrahepatic triglyceride concentrations and molecular markers of de novo lipogenesis were determined in liver. Independent of calorie intake, 32% PRO tended to result in lower homeostatic model assessment of insulin resistance (HOMA-IR) values compared to 10% PRO, while insulin and homeostatic model assessment of β-cell function (HOMA-β) values were lower in CR than AL, regardless of protein intake. Intrahepatic triglyceride concentrations were 27.4 ± 4.5 and 11.7 ± 4.5 µmol·g−1 lower (p < 0.05) in CR and 32% PRO compared to AL and 10% PRO, respectively. Gene expression of fatty acid synthase (FASN), stearoyl-CoA destaurase-1 (SCD1) and pyruvate dehydrogenase kinase, isozyme 4 (PDK4) were 45% ± 1%, 23% ± 1%, and 57% ± 1% lower (p < 0.05), respectively, in CR than AL, regardless of protein intake. Total protein of FASN and SCD were 50% ± 1% and 26% ± 1% lower (p < 0.05) in 32% PRO compared to 10% PRO, independent of calorie intake. Results from this investigation provide evidence that the metabolic health benefits associated with CR—specifically reduction in intrahepatic triglyceride content—may be enhanced by consuming a higher-protein/lower-carbohydrate diet. PMID:27649241

  4. Calorie Restricted High Protein Diets Downregulate Lipogenesis and Lower Intrahepatic Triglyceride Concentrations in Male Rats.

    PubMed

    Margolis, Lee M; Rivas, Donato A; Ezzyat, Yassine; Gaffney-Stomberg, Erin; Young, Andrew J; McClung, James P; Fielding, Roger A; Pasiakos, Stefan M

    2016-01-01

    The purpose of this investigation was to assess the influence of calorie restriction (CR) alone, higher-protein/lower-carbohydrate intake alone, and combined CR higher-protein/lower-carbohydrate intake on glucose homeostasis, hepatic de novo lipogenesis (DNL), and intrahepatic triglycerides. Twelve-week old male Sprague Dawley rats consumed ad libitum (AL) or CR (40% restriction), adequate (10%), or high (32%) protein (PRO) milk-based diets for 16 weeks. Metabolic profiles were assessed in serum, and intrahepatic triglyceride concentrations and molecular markers of de novo lipogenesis were determined in liver. Independent of calorie intake, 32% PRO tended to result in lower homeostatic model assessment of insulin resistance (HOMA-IR) values compared to 10% PRO, while insulin and homeostatic model assessment of β-cell function (HOMA-β) values were lower in CR than AL, regardless of protein intake. Intrahepatic triglyceride concentrations were 27.4 ± 4.5 and 11.7 ± 4.5 µmol·g(-1) lower (p < 0.05) in CR and 32% PRO compared to AL and 10% PRO, respectively. Gene expression of fatty acid synthase (FASN), stearoyl-CoA destaurase-1 (SCD1) and pyruvate dehydrogenase kinase, isozyme 4 (PDK4) were 45% ± 1%, 23% ± 1%, and 57% ± 1% lower (p < 0.05), respectively, in CR than AL, regardless of protein intake. Total protein of FASN and SCD were 50% ± 1% and 26% ± 1% lower (p < 0.05) in 32% PRO compared to 10% PRO, independent of calorie intake. Results from this investigation provide evidence that the metabolic health benefits associated with CR-specifically reduction in intrahepatic triglyceride content-may be enhanced by consuming a higher-protein/lower-carbohydrate diet. PMID:27649241

  5. Apolipoprotein E polymorphism influences postprandial retinyl palmitate but not triglyceride concentrations

    SciTech Connect

    Boerwinkle, E. ); Brown, S.; Patsch, W. ); Sharrett, A.R. ); Heiss, G. )

    1994-02-01

    To quantify the effect of the apolipoprotein (apo) E polymorphism on the magnitude of postprandial lipemia, the authors have defined its role in determining the response to a single high-fat meal in a large sample of (N = 474) individuals taking part in the biethnic Atherosclerosis Risk in Communities Study. The profile of postprandial response in plasma was monitored over 8 h by triglyceride, triglyceride-rich lipoprotein (TGRL)-triglyceride, apo B-48/apo B-100 ratio, and retinyl palmitate concentrations, and the apo E polymorphism was determined by DNA amplification and digestion. The frequency of the apo E alleles and their effects on fasting lipid levels in this sample with vitamin A was significantly different among apo E genotypes, with delayed clearance in individuals with an [var epsilon]2 allele, compared with [var epsilon]3/3 and [var epsilon]3/4 individuals. In the sample of 397 Caucasians, average retinyl palmitate response was 1,489 [mu]g/dl in [var epsilon]2/3 individuals, compared with 1,037 [mu]g/dl in [var epsilon]3/3 individuals and 1,108 [mu]g/dl in [var epsilon]3/4 individuals. The apo E polymorphism accounted for 7.1% of the interindividual variation in postprandial retinyl palmitate response, a contribution proportionally greater than its well-known effect on fasting LDL-cholesterol. However, despite this effect on postprandial retinyl palmitate, the profile of postprandial triglyceride response was not significantly different among apo E genotypes. The profile of postprandial response was consistent between the sample of Caucasians and a smaller sample of black subjects. While these data indicate that the removal of remnant particles from circulation is delayed in subjects with the [var epsilon]2/3 genotype, there is no reported evidence that the [var epsilon]2 allele predisposes to coronary artery disease (CAD). 82 refs., 6 figs., 4 tabs.

  6. Calorie Restricted High Protein Diets Downregulate Lipogenesis and Lower Intrahepatic Triglyceride Concentrations in Male Rats.

    PubMed

    Margolis, Lee M; Rivas, Donato A; Ezzyat, Yassine; Gaffney-Stomberg, Erin; Young, Andrew J; McClung, James P; Fielding, Roger A; Pasiakos, Stefan M

    2016-09-15

    The purpose of this investigation was to assess the influence of calorie restriction (CR) alone, higher-protein/lower-carbohydrate intake alone, and combined CR higher-protein/lower-carbohydrate intake on glucose homeostasis, hepatic de novo lipogenesis (DNL), and intrahepatic triglycerides. Twelve-week old male Sprague Dawley rats consumed ad libitum (AL) or CR (40% restriction), adequate (10%), or high (32%) protein (PRO) milk-based diets for 16 weeks. Metabolic profiles were assessed in serum, and intrahepatic triglyceride concentrations and molecular markers of de novo lipogenesis were determined in liver. Independent of calorie intake, 32% PRO tended to result in lower homeostatic model assessment of insulin resistance (HOMA-IR) values compared to 10% PRO, while insulin and homeostatic model assessment of β-cell function (HOMA-β) values were lower in CR than AL, regardless of protein intake. Intrahepatic triglyceride concentrations were 27.4 ± 4.5 and 11.7 ± 4.5 µmol·g(-1) lower (p < 0.05) in CR and 32% PRO compared to AL and 10% PRO, respectively. Gene expression of fatty acid synthase (FASN), stearoyl-CoA destaurase-1 (SCD1) and pyruvate dehydrogenase kinase, isozyme 4 (PDK4) were 45% ± 1%, 23% ± 1%, and 57% ± 1% lower (p < 0.05), respectively, in CR than AL, regardless of protein intake. Total protein of FASN and SCD were 50% ± 1% and 26% ± 1% lower (p < 0.05) in 32% PRO compared to 10% PRO, independent of calorie intake. Results from this investigation provide evidence that the metabolic health benefits associated with CR-specifically reduction in intrahepatic triglyceride content-may be enhanced by consuming a higher-protein/lower-carbohydrate diet.

  7. ELMOD2 is anchored to lipid droplets by palmitoylation and regulates adipocyte triglyceride lipase recruitment.

    PubMed

    Suzuki, Michitaka; Murakami, Tatsuro; Cheng, Jinglei; Kano, Hiroyuki; Fukata, Masaki; Fujimoto, Toyoshi

    2015-06-15

    Adipocyte triglyceride lipase (ATGL) is the major enzyme involved in the hydrolysis of triglycerides. The Arf1-coat protein complex I (COPI) machinery is known to be engaged in the recruitment of ATGL to lipid droplets (LDs), but the regulatory mechanism has not been clarified. In the present study, we found that ELMOD2, a putative noncanonical Arf-GTPase activating protein (GAP) localizing in LDs, plays an important role in controlling ATGL transport to LDs. We showed that knockdown of ELMOD2 by RNA interference induced an increase in the amount of ATGL existing in LDs and decreased the total cellular triglycerides. These effects of ELMOD2 knockdown were canceled by transfection of small interfering RNA-resistant cDNA of wild-type ELMOD2 but not by that of mutated ELMOD2 lacking the Arf-GAP activity. ELMOD2 was distributed in the endoplasmic reticulum and mitochondria as well as in LDs, but palmitoylation was required only for distribution to LDs. An ELMOD2 mutant deficient in palmitoylation failed to reconstitute the ATGL transport after the ELMOD2 knockdown, indicating that distribution in LDs is indispensable to the functionality of ELMOD2. These results indicate that ELMOD2 regulates ATGL transport and cellular lipid metabolism by modulating the Arf1-COPI activity in LDs.

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

    PubMed Central

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

    2014-01-01

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

  9. ELMOD2 is anchored to lipid droplets by palmitoylation and regulates adipocyte triglyceride lipase recruitment.

    PubMed

    Suzuki, Michitaka; Murakami, Tatsuro; Cheng, Jinglei; Kano, Hiroyuki; Fukata, Masaki; Fujimoto, Toyoshi

    2015-06-15

    Adipocyte triglyceride lipase (ATGL) is the major enzyme involved in the hydrolysis of triglycerides. The Arf1-coat protein complex I (COPI) machinery is known to be engaged in the recruitment of ATGL to lipid droplets (LDs), but the regulatory mechanism has not been clarified. In the present study, we found that ELMOD2, a putative noncanonical Arf-GTPase activating protein (GAP) localizing in LDs, plays an important role in controlling ATGL transport to LDs. We showed that knockdown of ELMOD2 by RNA interference induced an increase in the amount of ATGL existing in LDs and decreased the total cellular triglycerides. These effects of ELMOD2 knockdown were canceled by transfection of small interfering RNA-resistant cDNA of wild-type ELMOD2 but not by that of mutated ELMOD2 lacking the Arf-GAP activity. ELMOD2 was distributed in the endoplasmic reticulum and mitochondria as well as in LDs, but palmitoylation was required only for distribution to LDs. An ELMOD2 mutant deficient in palmitoylation failed to reconstitute the ATGL transport after the ELMOD2 knockdown, indicating that distribution in LDs is indispensable to the functionality of ELMOD2. These results indicate that ELMOD2 regulates ATGL transport and cellular lipid metabolism by modulating the Arf1-COPI activity in LDs. PMID:25904333

  10. Effect of cholesterol and triglycerides levels on the rheological behavior of human blood

    NASA Astrophysics Data System (ADS)

    Moreno, Leonardo; Calderas, Fausto; Sanchez-Olivares, Guadalupe; Medina-Torres, Luis; Sanchez-Solis, Antonio; Manero, Octavio

    2015-02-01

    Important public health problems worldwide such as obesity, diabetes, hyperlipidemia and coronary diseases are quite common. These problems arise from numerous factors, such as hyper-caloric diets, sedentary habits and other epigenetic factors. With respect to Mexico, the population reference values of total cholesterol in plasma are around 200 mg/dL. However, a large proportion has higher levels than this reference value. In this work, we analyze the rheological properties of human blood obtained from 20 donors, as a function of cholesterol and triglyceride levels, upon a protocol previously approved by the health authorities. Samples with high and low cholesterol and triglyceride levels were selected and analyzed by simple-continuous and linear-oscillatory shear flow. Rheometric properties were measured and related to the structure and composition of human blood. In addition, rheometric data were modeled by using several constitutive equations: Bautista-Manero-Puig (BMP) and the multimodal Maxwell equations to predict the flow behavior of human blood. Finally, a comparison was made among various models, namely, the BMP, Carreau and Quemada equations for simple shear rate flow. An important relationship was found between cholesterol, triglycerides and the structure of human blood. Results show that blood with high cholesterol levels (400 mg/dL) has flow properties fully different (higher viscosity and a more pseudo-plastic behavior) than blood with lower levels of cholesterol (tendency to Newtonian behavior or viscosity plateau at low shear rates).

  11. Cilostazol Inhibits Accumulation of Triglyceride in Aorta and Platelet Aggregation in Cholesterol-Fed Rabbits

    PubMed Central

    Ito, Hideki; Uehara, Kenji; Matsumoto, Yutaka; Hashimoto, Ayako; Nagano, Chifumi; Niimi, Manabu; Miyakoda, Goro; Nagano, Keisuke

    2012-01-01

    Cilostazol is clinically used for the treatment of ischemic symptoms in patients with chronic peripheral arterial obstruction and for the secondary prevention of brain infarction. Recently, it has been reported that cilostazol has preventive effects on atherogenesis and decreased serum triglyceride in rodent models. There are, however, few reports on the evaluation of cilostazol using atherosclerotic rabbits, which have similar lipid metabolism to humans, and are used for investigating the lipid content in aorta and platelet aggregation under conditions of hyperlipidemia. Therefore, we evaluated the effect of cilostazol on the atherosclerosis and platelet aggregation in rabbits fed a normal diet or a cholesterol-containing diet supplemented with or without cilostazol. We evaluated the effects of cilostazol on the atherogenesis by measuring serum and aortic lipid content, and the lesion area after a 10-week treatment and the effect on platelet aggregation after 1- and 10-week treatment. From the lipid analyses, cilostazol significantly reduced the total cholesterol, triglyceride and phospholipids in serum, and moreover, the triglyceride content in the atherosclerotic aorta. Cilostazol significantly reduced the intimal atherosclerotic area. Platelet aggregation was enhanced in cholesterol-fed rabbits. Cilostazol significantly inhibited the platelet aggregation in rabbits fed both a normal diet and a high cholesterol diet. Cilostazol showed anti-atherosclerotic and anti-platelet effects in cholesterol-fed rabbits possibly due to the improvement of lipid metabolism and the attenuation of platelet activation. The results suggest that cilostazol is useful for prevention and treatment of atherothrombotic diseases with the lipid abnormalities. PMID:22761774

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

    SciTech Connect

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

    1989-03-01

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

  13. Metabolic and lifestyle determinants of postprandial lipemia differ from those of fasting triglycerides: The Atherosclerosis Risk In Communities (ARIC) study.

    PubMed

    Sharrett, A R; Heiss, G; Chambless, L E; Boerwinkle, E; Coady, S A; Folsom, A R; Patsch, W

    2001-02-01

    Despite the reported association of lipoprotein responses to a fatty meal with atherosclerosis, little is known about the determinants of these responses. Plasma triglyceride, retinyl palmitate, and apolipoprotein B-48 responses to a standardized fatty meal containing a vitamin A marker were measured in 602 Atherosclerosis Risk in Communities (ARIC) study participants. To focus on postprandial responses specifically, which have been reported to be related to atherosclerosis independently of fasting triglycerides, analyses for determinants of postprandial responses were adjusted for fasting triglycerides. Major determinants of fasting triglycerides, namely, diabetes, obesity, other factors related to insulin resistance, and male sex, were not independently associated with postprandial responses. Fasting triglycerides were the strongest predictor of postprandial lipids, but independent of triglycerides, the predictors of postprandial responses were smoking, diet, creatinine, and alcohol. Smokers had substantially increased retinyl palmitate and apolipoprotein B-48 responses, indicators of chylomicrons and their remnants. Persons who consume more calories or omega3 fatty acids had reduced chylomicron responses. Triglyceride responses were associated positively with serum creatinine levels and negatively with moderate alcohol consumption. Thus, determinants of fasting and postprandial lipids differ. The independent atherogenic influence of postprandial lipids may relate more to smoking and diet than to obesity and insulin resistance. PMID:11156865

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

    PubMed

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

    2014-12-01

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

  15. Long-chain omega-3 fatty acids, fibrates and niacin as therapeutic options in the treatment of hypertriglyceridemia: a review of the literature.

    PubMed

    Ito, Matthew K

    2015-10-01

    Hypertriglyceridemia affects approximately 33% of the US population. Elevated triglyceride levels are independently associated with cardiovascular disease (CVD) risk, and severe hypertriglyceridemia is a risk factor for acute pancreatitis. Guidelines for the management of severe hypertriglyceridemia (≥5.6 mmol/L [≥500 mg/dL]) recommend immediate use of triglyceride-lowering agents; however, statins remain the first line of therapy for the management of mild to moderate hypertriglyceridemia (1.7-5.6 mmol/L [150-499 mg/dL]). Statins primarily target elevated low-density lipoprotein cholesterol levels, but have also been shown to reduce mean triglyceride levels by up to 18% (or 43% in patients with triglyceride levels≥3.1 mmol/L [≥273 mg/dL]). However, individuals with hypertriglyceridemia may need additional reduction in triglyceride-rich lipoproteins and remnant particles to further reduce residual CVD risk. A number of guidelines recommend the addition of fibrates, niacin, or long-chain omega-3 fatty acids if elevated triglyceride or non-high-density lipoprotein cholesterol levels persist despite the use of high-intensity statin therapy. This review evaluates the impact of fibrates, niacin, and long-chain omega-3 fatty acids on lipid profiles and cardiovascular outcomes in patients with hypertriglyceridemia. It also assesses the adverse effects and drug-drug interactions associated with these triglyceride-lowering agents, because although they have all been shown to effectively reduce triglyceride levels in patients with hypertriglyceridemia, they differ with regard to their associated benefit-risk profiles. Long-chain omega-3 fatty acids may be a well-tolerated and effective alternative to fibrates and niacin, yet further large-scale clinical studies are required to evaluate their effects on cardiovascular outcomes and CVD risk reduction in patients with hypertriglyceridemia. PMID:26296750

  16. Long-chain omega-3 fatty acids, fibrates and niacin as therapeutic options in the treatment of hypertriglyceridemia: a review of the literature.

    PubMed

    Ito, Matthew K

    2015-10-01

    Hypertriglyceridemia affects approximately 33% of the US population. Elevated triglyceride levels are independently associated with cardiovascular disease (CVD) risk, and severe hypertriglyceridemia is a risk factor for acute pancreatitis. Guidelines for the management of severe hypertriglyceridemia (≥5.6 mmol/L [≥500 mg/dL]) recommend immediate use of triglyceride-lowering agents; however, statins remain the first line of therapy for the management of mild to moderate hypertriglyceridemia (1.7-5.6 mmol/L [150-499 mg/dL]). Statins primarily target elevated low-density lipoprotein cholesterol levels, but have also been shown to reduce mean triglyceride levels by up to 18% (or 43% in patients with triglyceride levels≥3.1 mmol/L [≥273 mg/dL]). However, individuals with hypertriglyceridemia may need additional reduction in triglyceride-rich lipoproteins and remnant particles to further reduce residual CVD risk. A number of guidelines recommend the addition of fibrates, niacin, or long-chain omega-3 fatty acids if elevated triglyceride or non-high-density lipoprotein cholesterol levels persist despite the use of high-intensity statin therapy. This review evaluates the impact of fibrates, niacin, and long-chain omega-3 fatty acids on lipid profiles and cardiovascular outcomes in patients with hypertriglyceridemia. It also assesses the adverse effects and drug-drug interactions associated with these triglyceride-lowering agents, because although they have all been shown to effectively reduce triglyceride levels in patients with hypertriglyceridemia, they differ with regard to their associated benefit-risk profiles. Long-chain omega-3 fatty acids may be a well-tolerated and effective alternative to fibrates and niacin, yet further large-scale clinical studies are required to evaluate their effects on cardiovascular outcomes and CVD risk reduction in patients with hypertriglyceridemia.

  17. Milk production, peripartal liver triglyceride concentration and plasma metabolites of dairy cows fed diets supplemented with calcium soaps or hydrogenated triglycerides of palm oil.

    PubMed

    Karcagi, Roland G; Gaál, Tibor; Ribiczey, Piroska; Huszenicza, Gyula; Husvéth, Ferenc

    2010-05-01

    The aim of the study was to test the effect of rumen-inert fat supplements of different chemical forms or containing different unsaturated/saturated (U/S) fatty acid contents on milk production, milk composition and liver and blood metabolic variables of high-yielding dairy cows in the peripartal period. Thirty Holstein-Friesian dairy cows were divided into three equal groups and fed a corn silage-based diet, without fat supplementation (control) or supplemented with 11.75 MJ NEl per day of calcium soaps of palm oil fatty acids (CAS; U/S=61/39) or with 11.75 MJ NEl per day of hydrogenated palm oil triglyceride (HTG; U/S=6/94). Each diet was fed from 25+/-2 d prior to the expected calving to 100+/-5 d post partum. Compared with the control, both CAS and HTG supplementation resulted in an increase of the average milk yield. Milk fat content and fat-corrected milk yield were higher in the HTG group but lower in the CAS group than in the control group. In all groups liver triglyceride concentrations (TGL) increased from 15 d prepartum to 5 d post partum, and then decreased thereafter. At 5 d TGL was lower in the HTG group than control or CAS cows. No significant differences were detected in TGL among dietary treatments at 15 d prepartum and 25 d post partum. Higher plasma glucose and insulin and lower non-esterified fatty acids and beta-hydroxybutyrate concentrations and aspartate aminotransferase activity were measured in the HTG group than in the control or CAS groups at 5 d or 25 d post partum. Our results show that HTG may provide a better energy supply for high-yielding dairy cows in negative energy balance than CAS around calving.

  18. Partial deletion of beta9 loop in pancreatic lipase-related protein 2 reduces enzyme activity with a larger effect on long acyl chain substrates.

    PubMed

    Dridi, Kaouthar; Amara, Sawsan; Bezzine, Sofiane; Rodriguez, Jorge A; Carrière, Frédéric; Gaussier, Hélène

    2013-07-01

    Structural studies on pancreatic lipase have revealed a complex architecture of surface loops surrounding the enzyme active site and potentially involved in interactions with lipids. Two of them, the lid and beta loop, expose a large hydrophobic surface and are considered as acyl chain binding sites based on their interaction with an alkyl phosphonate inhibitor. While the role of the lid in substrate recognition and selectivity has been extensively studied, the implication of beta9 loop in acyl chain stabilization remained hypothetical. The characterization of an enzyme with a natural deletion of the lid, guinea pig pancreatic lipase-related protein 2 (GPLRP2), suggests however an essential contribution of the beta9 loop in the stabilization of the acyl enzyme intermediate formed during the lipolysis reaction. A GPLRP2 mutant with a seven-residue deletion of beta9 loop (GPLRP2-deltabeta9) was produced and its enzyme activity was measured using various substrates (triglycerides, monoglycerides, galactolipids, phospholipids, vinyl esters) with short, medium and long acyl chains. Whatever the substrate tested, GPLRP2-deltabeta9 activity is drastically reduced compared to that of wild-type GPLRP2 and this effect is more pronounced as the length of substrate acyl chain increases. Changes in relative substrate selectivity and stereoselectivity remained however weak. The deletion within beta9 loop has also a negative effect on the rate of enzyme inhibition by alkyl phosphonates. All these findings indicate that the reduced enzyme turnover observed with GPLRP2-deltabeta9 results from a weaker stabilization of the acyl enzyme intermediate due to a loss of hydrophobic interactions. PMID:24046870

  19. [About effect of habitat and motor activity of molluscs on fatty acid composition of triglycerides and phospholipids].

    PubMed

    Arakelova, E S; Chebotareva, M A; Zabelinskiĭ, S A; Ivanova, V P

    2009-01-01

    A comparative analysis of fatty acids (FA) in neutral and phospholipids of digestive gland and pedal muscle has been performed in molluscs from various ecological groups differing by belonging to sea or fresh water, trophic types or the associated motor activity. In freshwater pulmonary gastropods Lymnaea stagnalis and Limnaea ovalis and marine prosobranchial molluscs Buccinum undatum and Littorina littorea the total content of omega3-acids in phospholipids of the studied tissues differed more than twice, predominantly due to the combined effect of temperature and salinity of the habitat. The lower viscosity of cell membranes in marine species (omega3/omega6 < 1) is determined to the greatest degree by the presence of eicosapentaenoic acid that accounts for 22-25 % of the FA sum in marine species. Comparison of the molluscs by their trophic belonging has revealed the presence of linoleic acid in triglycerides in digestive glands of phytophages (8-12 %), but the practically complete absence of this acid in the predator B. undulatum (<0.8 %. By mobility, L. littorea inhabiting the high-low tide littoral was inferior to freshwater pulmonary gastropods and to marine predator, as it stops moving twice a day during the low tide. In phospholipids of pedal muscle of this mollusc the amount of long-chain polyunsaturated C:22 FA was 3-6 times lower than that in other studied species, which might possibly indicate the role of these acids in functioning of the pedal muscle contractile tissue. On the whole, use of the FA characteristics as parameters determining belonging to certain ecological group requires a certain caution due to a complex action of biotic and abiotic factors on the animal metabolism. The exception is the omega3/omega6 ratio in total phospholipids of freshwater and marine gastropods. PMID:19370988

  20. [About effect of habitat and motor activity of molluscs on fatty acid composition of triglycerides and phospholipids].

    PubMed

    Arakelova, E S; Chebotareva, M A; Zabelinskiĭ, S A; Ivanova, V P

    2009-01-01

    A comparative analysis of fatty acids (FA) in neutral and phospholipids of digestive gland and pedal muscle has been performed in molluscs from various ecological groups differing by belonging to sea or fresh water, trophic types or the associated motor activity. In freshwater pulmonary gastropods Lymnaea stagnalis and Limnaea ovalis and marine prosobranchial molluscs Buccinum undatum and Littorina littorea the total content of omega3-acids in phospholipids of the studied tissues differed more than twice, predominantly due to the combined effect of temperature and salinity of the habitat. The lower viscosity of cell membranes in marine species (omega3/omega6 < 1) is determined to the greatest degree by the presence of eicosapentaenoic acid that accounts for 22-25 % of the FA sum in marine species. Comparison of the molluscs by their trophic belonging has revealed the presence of linoleic acid in triglycerides in digestive glands of phytophages (8-12 %), but the practically complete absence of this acid in the predator B. undulatum (<0.8 %. By mobility, L. littorea inhabiting the high-low tide littoral was inferior to freshwater pulmonary gastropods and to marine predator, as it stops moving twice a day during the low tide. In phospholipids of pedal muscle of this mollusc the amount of long-chain polyunsaturated C:22 FA was 3-6 times lower than that in other studied species, which might possibly indicate the role of these acids in functioning of the pedal muscle contractile tissue. On the whole, use of the FA characteristics as parameters determining belonging to certain ecological group requires a certain caution due to a complex action of biotic and abiotic factors on the animal metabolism. The exception is the omega3/omega6 ratio in total phospholipids of freshwater and marine gastropods.

  1. Hypermedia as medium

    NASA Technical Reports Server (NTRS)

    Dede, Christopher J.

    1990-01-01

    Claims and rebuttals that hypermedia (the associative, nonlinear interconnection of multimedia materials) is a fundamentally innovative means of thinking and communicating are described. This representational architecture has many advantages that make it a major advance over other media; however, it also has several intrinsic problems that severly limits its effectiveness as a medium. These advantages and limits in applications are discussed.

  2. Holographic recording medium

    NASA Technical Reports Server (NTRS)

    Gange, Robert Allen (Inventor)

    1977-01-01

    A holographic recording medium comprising a conductive substrate, a photoconductive layer and an electrically alterable layer of a linear, low molecular weight hydrocarbon polymer has improved fatigue resistance. An acrylic barrier layer can be interposed between the photoconductive and electrically alterable layers.

  3. Requirements of glycerol and fatty acid for triglyceride synthesis and ketogenesis by hepatocytes from normal and triiodothyronine-treated rats

    SciTech Connect

    Olubadewo, J.O.; Heimberg, M.

    1985-11-15

    Hepatocytes from T3-treated rats synthesized less triglyceride and more ketone bodies from (1-/sup 14/C)oleate at all concentrations from 0-2 mM, than did hepatocytes from euthyroid animals; addition of 1.0 mM glycerol increased triglyceride synthesis and reduced ketogenesis in hepatocytes from T3-treated rats to the rates observed in euthyroid hepatocytes in the absence of added glycerol. Glycerol did not alter triglyceride synthesis, but reduced ketogenesis genesis by euthyroid hepatocytes. It is probable from these and other data that, in the hyperthyroid rat, glycero-3-P, and not fatty acid, is rate limiting for synthesis of triglyceride, and, secondarily for reducing rates of ketogenesis in the hepatocyte.

  4. Apolipoprotein AV accelerates plasma hydrolysis of triglyceride-rich lipoproteins by interaction with proteoglycan-bound lipoprotein lipase.

    PubMed

    Merkel, Martin; Loeffler, Britta; Kluger, Malte; Fabig, Nathalie; Geppert, Gesa; Pennacchio, Len A; Laatsch, Alexander; Heeren, Joerg

    2005-06-01

    Apolipoprotein A5 (APOA5) is associated with differences in triglyceride levels and familial combined hyperlipidemia. In genetically engineered mice, apoAV plasma levels are inversely correlated with plasma triglycerides. To elucidate the mechanism by which apoAV influences plasma triglycerides, metabolic studies and in vitro assays resembling physiological conditions were performed. In human APOA5 transgenic mice (hAPOA5tr), catabolism of chylomicrons and very low density lipoprotein (VLDL) was accelerated due to a faster plasma hydrolysis of triglycerides by lipoprotein lipase (LPL). Hepatic VLDL and intestinal chylomicron production were not affected. The functional interplay between apoAV and LPL was further investigated by cross-breeding a human LPL transgene with the apoa5 knock-out and the hAPOA5tr to an lpl-deficient background. Increased LPL activity completely normalized hypertriglyceridemia of apoa5-deficient mice; however, overexpression of human apoAV modulated triglyceride levels only slightly when LPL was reduced. To reflect the physiological situation in which LPL is bound to cell surface proteoglycans, we examined hydrolysis in the presence or absence of proteoglycans. Without proteoglycans, apoAV derived either from triglyceride-rich lipoproteins, hAPOA5tr high density lipoprotein, or a recombinant source did not alter the LPL hydrolysis rate. In the presence of proteoglycans, however, apoAV led to a significant and dose-dependent increase in LPL-mediated hydrolysis of VLDL triglycerides. These results were confirmed in cell culture using a proteoglycan-deficient cell line. A direct interaction between LPL and apoAV was found by ligand blotting. It is proposed, that apoAV reduces triglyceride levels by guiding VLDL and chylomicrons to proteoglycan-bound LPL for lipolysis.

  5. Effects of Serum Triglycerides on Prostate Cancer and Breast Cancer Risk: A Meta-Analysis of Prospective Studies.

    PubMed

    Ma, Hong-Qun; Cui, Lian-Hua; Li, Cheng-Cheng; Yu, Zhuang; Piao, Jin-Mei

    2016-10-01

    Epidemiological studies show conflicting results regarding the link between serum triglyceride and the risk of prostate cancer and breast cancer. Therefore, we performed a meta-analysis of prospective studies to clarify this association. We searched PubMed, EMBASE, the Chinese Biomedical Database (CBM), and the China National Knowledge Infrastructure (CNKI) database to identify relevant prospective studies of the relationship between serum triglyceride and prostate cancer and breast cancer risk. Study-specific estimates adjusting for potential confounders were combined to evaluate a summary relative risks (RRs) and 95% confidence intervals (95% CIs) using a fixed- or random-effects model. A total of 11 prospective studies (619,410 subjects and 15,691 incident prostate cancer patients) and 8 prospective studies (590,878 subjects and 12,177 incident breast cancer patients) were respectively included in our meta-analysis to assess the associations of serum triglyceride with prostate cancer and breast cancer risk. The pooled adjusted RR estimates for prostate cancer and breast cancer for the highest versus the lowest exposure levels of serum triglycerides were 0.95 (95% CI: 0.87-1.04) and 0.94 (95% CI: 0.87-1.00), respectively. Additionally, a dose-response analysis revealed that serum levels of triglycerides were not associated with the risk of prostate cancer and breast cancer. We found that serum triglyceride was not related to the risk of prostate cancer and breast cancer. PMID:27618148

  6. 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

  7. 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.

  8. Piromelatine decreases triglyceride accumulation in insulin resistant 3T3-L1 adipocytes: role of ATGL and HSL.

    PubMed

    Wang, Ping-Ping; She, Mei-Hua; He, Ping-Ping; Chen, Wu-Jun; Laudon, Moshe; Xu, Xuan-Xuan; Yin, Wei-Dong

    2013-08-01

    Piromelatine, a novel investigational multimodal sleep medicine, is developed for the treatment of patients with primary and co-morbid insomnia. Piromelatine has been shown to inhibit weight gain and improve insulin sensitivity in high-fat/high-sucrose-fed (HFHS) rats. Considering that piromelatine has also been implicated in lowering of triglyceride levels in HFHS rats, this work elucidated whether this effect involves in the regulation of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) in triglyceride (TG) metabolism. In this study, we investigated the effects of piromelatine and MT2 receptors inhibition on TG content, insulin-stimulated glucose uptake, and the expressions of ATGL and HSL in 3T3-L1 adipocytes preincubated in high glucose and high insulin (HGI) conditions. Our results showed that culturing 3T3-L1 adipocytes under HGI conditions increased triglyceride accumulation with concomitant decrease of ATGL and HSL expression, inducing insulin resistance in 3T3-L1 adipocytes. We also found that triglyceride accumulation was significantly inhibited and the levels of ATGL/HSL increased after melatonin or piromelatine treatment. The effects of melatonin/piromelatine (10 nM) were counteracted by pretreatment with the relatively selective MT2 receptor antagonist luzindole (100 nM). In this study, our data demonstrate that piromelatine reverses high glucose and high insulin-induced triglyceride accumulation in 3T3-L1 adipocytes, possibly through up-regulating of ATGL and HSL expression via a melatonin-dependent manner.

  9. Effect on days of lactation and methionine hydroxy analog on incorporation of plasma fatty acids into plasma triglycerides

    SciTech Connect

    Pullen, D.L.; Emergy, R.S. ); Palmquist, D.L. )

    1989-01-01

    Methionine hydroxy analog has been proposed to stimulate hepatic lipoprotein synthesis and incorporation of plasma fatty acids into plasma triglyceride. Seven cows were fed diets containing 0 to 30 g analog/d starting 14 d prepartum. At approximately 30 and 60 d postpartum, cows were continuously infused intravenously with 1-({sup 14}C)palmitic acid for 160 min to achieve steady-state labeling of plasma fatty acid and triglyceride. Turnover of fatty acid and transfer quotients for triglyceride and CO{sub 2} were 3.3 an 2.7 mmol min{sup {minus}1}; 13.0 and 10.0%; and 8.0 and 5.0%, for control and analog, respectively. Proportion of fatty acid turnover incorporated into triglyceride and CO{sub 2} were 14.0 and 15.0%; and 21.0 and 18.0, respectively, for control and analog. Analog increased {sup 14}C recovered in milk fat (52 vs. 36%). Plasma concentration of fatty acids, percent oxidized to CO{sub 2}, and percent of CO{sub 2} from fatty acids decreased with increasing lactation days. Milk fat percent and yield fatty acid turnover, and oxidation were positively correlated with concentration of plasma fatty acids, whereas fatty acid incorporated into plasma triglyceride was negatively correlated with fatty acid concentration. The data suggest that hepatic triglyceride secretion is not increased in early lactation; further, no effects of analog on lipid metabolism were detected.

  10. Liquid chromatographic extraction medium

    DOEpatents

    Horwitz, E. Philip; Dietz, Mark L.

    1994-01-01

    A method and apparatus for extracting strontium and technetium values from biological, industrial and environmental sample solutions using a chromatographic column is described. An extractant medium for the column is prepared by generating a solution of a diluent containing a Crown ether and dispersing the solution on a resin substrate material. The sample solution is highly acidic and is introduced directed to the chromatographic column and strontium or technetium is eluted using deionized water.

  11. Liquid chromatographic extraction medium

    DOEpatents

    Horwitz, E.P.; Dietz, M.L.

    1994-09-13

    A method and apparatus are disclosed for extracting strontium and technetium values from biological, industrial and environmental sample solutions using a chromatographic column. An extractant medium for the column is prepared by generating a solution of a diluent containing a Crown ether and dispersing the solution on a resin substrate material. The sample solution is highly acidic and is introduced directed to the chromatographic column and strontium or technetium is eluted using deionized water. 1 fig.

  12. Relationships between plasma insulin triglyceride, body mass index, and plasminogen activator inhibitor 1.

    PubMed

    Juhan-Vague, I; Vague, P; Alessi, M C; Badier, C; Valadier, J; Aillaud, M F; Atlan, C

    1987-07-01

    Low fibrinolytic activity, as measured by euglobulin (EFA), has been observed in obese subjects, and hypofibrinolysis may play a role in the pathogenesis of atherosclerosis and its complications. Blood fibrinolytic activity is regulated through a complex system of activators and inhibitors, especially plasminogen activator inhibitors (PA Inhibitors). In a group of 35 non-diabetic subjects with a wide range of body mass index (BMI), EFA was negatively correlated, and PA Inhibitor activity positively correlated, with BMI and plasma insulin levels. In a population of 49 non-diabetic obese women (differing from a control group of normal weight by lower EFA and higher level, of PA Inhibitor activity, plasma insulin and triglyceride), the PA Inhibitor activity was positively correlated with BMI, insulin and triglyceride. The increase in PA Inhibitor activity was associated with a high value of PA Inhibitor 1 antigen measured by an immuno-radiometric assay, indicating that the increased activity was due to a high level of circulating PA Inhibitor 1. Plasma insulin was lowered in obese non-diabetic subjects, without modification of the body weight, by a 24 hour fast or by treatment with Metformin. After 24 hours' fast, ten obese subjects had lower levels of insulin and PA Inhibitor activity and an increase in EFA. Treatment for 15 days by 1.75 g Metformin (or placebo), on a weight maintaining diet, induced, in the Metformin group, a decrease in plasma insulin, triglyceride and PA Inhibitor activity and an increase in EFA, while no change was observed in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Polyamine Triglycerides: Synthesis and Study of Their Potential in Lubrication, Neutralization, and Sequestration.

    PubMed

    Harry-O'kuru, Rogers E; Biresaw, Girma; Murray, Rex E

    2015-07-22

    Renewable resources have evoked a new awakening in both scientific and industrial circles in the past decade. Vegetable oil is one category of renewables that is amenable as a source of new industrial products. Because the source feedstock, seeds, are environmentally friendly, the derivatized products from these at the end of their lifetime could also be benign when designed appropriately. Bioethanol and biodiesel are examples of biobased industrial products currently in the market place and have become resources for uplifting the rural economy. Biolubricants also are playing a more prominent role because they have become closely competitive with petroleum-based lubricants. These products are renewable because the crops from which the feedstuff for the biofuels and biolubricants are produced are grown annually in contrast to nonrenewable mineral sources. Added to their renewability is the inherent biodegradability of their end-use products after their useful lifetime. In a recent study of the lubricity characteristics of peracylated polyhydroxy milkweed oil, the derivatives were found to exhibit good oxidative stability as well as excellent antiwear properties. To further explore an expansion in the properties of such materials in lubrication and other applications, in this study the polyhydroxy (OH) moieties of derivatized milkweed triglycerides were replaced with -NHR groupings in the oil. In this process novel polyketo triglyceride intermediates leading to polyamine derivatives of the vegetable oil have been synthesized. The polyamine triglyceride markedly improved the stability of the parent oil to oxidative stress. It has also attenuated the extreme viscosity of the starting polyhydroxy oil to a more useful product that could be amenable for use as a lubricating agent, for example, hydraulic fluid. Both the polyketone and polyimine intermediates of the polyamine have chelating properties. The intermediates and the polyamine were characterized spectroscopically

  14. 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.

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

    PubMed

    Khairallah, Ramzi J; Khairallah, Maya; Gélinas, Roselle; Bouchard, Bertrand; Young, Martin E; Allen, Bruce G; Lopaschuk, Gary D; Deschepper, Christian F; Des Rosiers, Christine

    2008-08-01

    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 impact of its chronic activation on cardiac energy metabolism using mice overexpressing a constitutively active cytoplasmic guanylate cyclase (GC(+/0)) in cardiomyocytes. Ex vivo working GC(+/0) heart perfusions with (13)C-labeled substrates revealed an altered pattern of exogenous substrate fuel selection compared to controls, namely a 38+/-9% lower contribution of exogenous fatty acids to acetyl-CoA formation, while that of carbohydrates remains unchanged despite a two-fold increase in glycolysis. The lower contribution of exogenous fatty acids to energy production is not associated with changes in energy demand or supply (contractile function, oxygen consumption, tissue acetyl-CoA or CoA levels, citric acid cycle flux rate) or in the regulation of beta-oxidation (acetyl-CoA carboxylase activity, tissue malonyl-CoA levels). However, GC(+/0) hearts show a two-fold increase in the incorporation of exogenous oleate into triglycerides. Furthermore, the following molecular data are consistent with a concomitant increase in triglyceride hydrolysis: (i) increased abundance of hormone sensitive lipase (HSL) protein (24+/-11%) and mRNA (22+/-4%) as well as (ii) several phosphorylation events related to HSL inhibitory (AMPK) and activation (ERK 1/2) sites, which should contribute to enhance its activity. These changes in exogenous fatty acid trafficking in GC(+/0) hearts appear to be functionally relevant, as demonstrated by their resistance to fasting-induced triglyceride accumulation. While the documented metabolic profile of GC(+/0) mouse hearts is partly reminiscent of hypertrophied hearts, the observed changes in lipid trafficking have not been previously documented, and may

  16. Polyamine Triglycerides: Synthesis and Study of Their Potential in Lubrication, Neutralization, and Sequestration.

    PubMed

    Harry-O'kuru, Rogers E; Biresaw, Girma; Murray, Rex E

    2015-07-22

    Renewable resources have evoked a new awakening in both scientific and industrial circles in the past decade. Vegetable oil is one category of renewables that is amenable as a source of new industrial products. Because the source feedstock, seeds, are environmentally friendly, the derivatized products from these at the end of their lifetime could also be benign when designed appropriately. Bioethanol and biodiesel are examples of biobased industrial products currently in the market place and have become resources for uplifting the rural economy. Biolubricants also are playing a more prominent role because they have become closely competitive with petroleum-based lubricants. These products are renewable because the crops from which the feedstuff for the biofuels and biolubricants are produced are grown annually in contrast to nonrenewable mineral sources. Added to their renewability is the inherent biodegradability of their end-use products after their useful lifetime. In a recent study of the lubricity characteristics of peracylated polyhydroxy milkweed oil, the derivatives were found to exhibit good oxidative stability as well as excellent antiwear properties. To further explore an expansion in the properties of such materials in lubrication and other applications, in this study the polyhydroxy (OH) moieties of derivatized milkweed triglycerides were replaced with -NHR groupings in the oil. In this process novel polyketo triglyceride intermediates leading to polyamine derivatives of the vegetable oil have been synthesized. The polyamine triglyceride markedly improved the stability of the parent oil to oxidative stress. It has also attenuated the extreme viscosity of the starting polyhydroxy oil to a more useful product that could be amenable for use as a lubricating agent, for example, hydraulic fluid. Both the polyketone and polyimine intermediates of the polyamine have chelating properties. The intermediates and the polyamine were characterized spectroscopically

  17. Laser amplifier chain

    DOEpatents

    Hackel, R.P.

    1992-10-20

    A laser amplifier chain has a plurality of laser amplifiers arranged in a chain to sequentially amplify a low-power signal beam to produce a significantly higher-power output beam. Overall efficiency of such a chain is improved if high-gain, low efficiency amplifiers are placed on the upstream side of the chain where only a very small fraction of the total pumped power is received by the chain and low-gain, high-efficiency amplifiers are placed on the downstream side where a majority of pumping energy is received by the chain. 6 figs.

  18. Laser amplifier chain

    DOEpatents

    Hackel, Richard P.

    1992-01-01

    A laser amplifier chain has a plurality of laser amplifiers arranged in a chain to sequentially amplify a low-power signal beam to produce a significantly higher-power output beam. Overall efficiency of such a chain is improved if high-gain, low efficiency amplifiers are placed on the upstream side of the chain where only a very small fraction of the total pumped power is received by the chain and low-gain, high-efficiency amplifiers are placed on the downstream side where a majority of pumping energy is received by the chain.

  19. Elevated triglyceride and decreased high density lipoprotein level in carbon disulfide workers in Taiwan.

    PubMed

    Luo, Jiin-Chyuan John; Chang, Ho-Yuan; Chang, Shu-Ju; Chou, Tzu-Chieh; Chen, Chiou-Jong; Shih, Tung-Sheng; Huang, Chin-Chang

    2003-01-01

    Carbon disulfide (CS2) is a man-made product utilized primarily in the manufacture of viscose rayon. Overexposure to CS2 has been associated with an increase in coronary heart disease. The aims of this study were to examine the dose-response relationship of CS2 exposure and elevated lipid profile tests among CS2-exposed workers in Taiwan. A total of 132 workers were recruited from two viscose rayon plants. Air sampling was performed to determine the CS2 exposure of workers. Demographic data and work history were gathered by a standard self-administered questionnaire. Lipid profile tests were also performed by routine methods. The average CS2 exposure concentration was 50.6 +/- 25.6 ppm (range: 24-127 ppm) in the high-exposure group, 12.9 +/- 5 ppm (range: 5.2-22.3 ppm) in the mid-exposure group, and 3.5 +/- 1.2 ppm (range 0.97-5.2 ppm) in the low-exposure group. There were 21 out of 33 (63.7%) elevated triglyceride levels among high-CS2-exposure workers, 27 out of 64 (42.2%) among the middle-CS2-exposure, and 14 out of 35 (40%) among low-CS2-exposure workers, respectively. Compared to the low-CS2-exposure workers, the age- and weight-adjusted odds ratios (and 95% confidence intervals) of the prevalence of elevated triglyceride value were 1.12 (0.5, 2.7) for middle-CS2-exposure workers, and 2.81 (1.02, 7.8) for high-CS2-exposure workers. There was a significant linear trend between CS2 exposure and the prevalence of elevated triglyceride value (P = 0.046) after adjusting for other factors. There was also a lower prevalence of elevated HDL level in high-CS2-exposure workers than low-CS2-exposure workers (15.2% versus 31.4%). Compared to the low-CS2-exposure workers, the age- and weight-adjusted odds ratio (and 95% confidence intervals) of elevated HDL level were 0.34 (0.1, 1.18) for high-CS2-exposure workers, which was borderline significant. In conclusion, this study suggests that elevated triglyceride level and decreased HDL level are associated with CS2 exposure

  20. New secoiridoids from the fruits of Ligustrum lucidum Ait with triglyceride accumulation inhibitory effects.

    PubMed

    Zhang, Yi; Liu, Lili; Gao, Jing; Wu, Chunhua; Han, Lifeng; Liu, Erwei; Shi, Pingping; Gao, Xiumei; Wang, Tao

    2013-12-01

    Five new secoiridoids, nuzhenal C (1), 6'-O-trans-cinnamoyl iso-8-epikingisidic acid (2), ligulucidumosides A (3), B (4), and C (5), were obtained from the fruits of Ligustrum lucidum Ait. Their structures were elucidated by chemical and spectroscopic methods (UV, IR, HRESI-TOF-MS, 1D and 2D NMR). Among them, compound 3 is the first 1-OCH3 substituent secoiridoid obtained from plant kingdom. Furthermore, activity screening results showed that all of the isolates had triglyceride accumulation inhibitory effects in HepG2 cells. PMID:24001714

  1. Fatty acid profiles in relation to triglyceride level in the liver of dairy cows.

    PubMed

    Sato, Hiroshi; Mohamed, Tharwat; Goto, Akiko; Oikawa, Shin; Kurosawa, Takashi

    2004-01-01

    To elucidate possible relationships between triglyceride (TG) levels and fatty acid composition in bovine liver, hepatic TG and seven individual fatty acids were measured in 23 Holstein dairy cows, of them 6 are healthy. Liver TG level was greater than 3 % in 12 cows which were ruled fatty liver. Palmitic and oleic acid proportions were significantly higher in fatty liver cows than in the healthy cows, while stearic acid was lower in fatty liver cows. With increased liver TG, stearic acid proportions decreased dramatically. Results indicate that hepatic lipidosis markedly alters the proportions of the various fatty acids in the liver of dairy cows.

  2. A Two-Dimensional Model for the Analysis of Contaminant Transport in a Fractured Porous Medium.

    1991-03-05

    CHAINT-MC is a two-dimensional finite element model applicable to the transport of a dissolved radionuclide in a fractured porous medium along with radioactive chain decay and subsequent transport of the dissolved daughters.

  3. Porcine pancreatic lipase related protein 2 has high triglyceride lipase activity in the absence of colipase.

    PubMed

    Xiao, Xunjun; Ross, Leah E; Sevilla, Wednesday A; Wang, Yan; Lowe, Mark E

    2013-09-01

    Efficient dietary fat digestion is essential for newborns who consume more dietary fat per body weight than at any other time of life. In many mammalian newborns, pancreatic lipase related protein 2 (PLRP2) is the predominant duodenal lipase. Pigs may be an exception since PLRP2 expression has been documented in the intestine but not in the pancreas. Because of the differences in tissue-specific expression, we hypothesized that the kinetic properties of porcine PLRP2 would differ from those of other mammals. To characterize its properties, recombinant porcine PLRP2 was expressed in HEK293T cells and purified to homogeneity. Porcine PLRP2 had activity against tributyrin, trioctanoin and triolein. The activity was not inhibited by bile salts and colipase, which is required for the activity of pancreatic triglyceride lipase (PTL), minimally stimulated PLRP2 activity. Similar to PLRP2 from other species, PLRP2 from pigs had activity against galactolipids and phospholipids. Importantly, porcine PLRP2 hydrolyzed a variety of dietary substrates including pasteurized human mother's milk and infant formula and its activity was comparable to that of PTL. In conclusion, porcine PLRP2 has broad substrate specificity and has high triglyceride lipase activity even in the absence of colipase. The data suggest that porcine PLRP2 would be a suitable lipase for inclusion in recombinant preparations for pancreatic enzyme replacement therapy.

  4. Azuki Bean Juice Lowers Serum Triglyceride Concentrations in Healthy Young Women

    PubMed Central

    Maruyama, Chizuko; Araki, Risa; Kawamura, Mito; Kondo, Naoko; Kigawa, Mieko; Kawai, Yukari; Takanami, Yoshikazu; Miyashita, Koichi; Shimomitsu, Teruichi

    2008-01-01

    Effects of azuki bean juice supplementation, prescribed according to a Kanpo medicine regimen, on serum lipid concentrations were studied. Healthy young Japanese women were recruited and were randomly assigned to one of the three groups using a parallel-group design. Control (n = 10), azuki (n = 11) and Concentrated azuki (CA) (n = 12) juice groups consumed 150 g daily of the isocaloric assigned juice for one menstrual cycle with their usual diet. Triglyceride concentrations were decreased in the azuki juice group (p<0.05) and tended to be decreased in the CA juice group (p = 0.055). Triglyceride concentrations in the azuki and CA juice groups decreased by 0.170 mmol/liter (15.4%) and 0.159 mmol/liter (17.9%), respectively (p<0.05). The azuki and CA juice used in this study inhibited pancreatic lipase activity 29.2% and 56.9%, respectively, in vitro. Lipid peroxide changes, based on ANCOVA with the initial level and α-tocopherol changes as covariates, did not differ among the three groups. Serum low density lipoprotein-cholesterol and high density lipoprotein-cholesterol (HDL) cholesterol concentrations did not change. Thus, azuki bean juice intake, as a traditional Kampo prescription, might be beneficial for preventing hypertriglyceridemia. PMID:18648655

  5. Human lactation: maternal transfer of dietary triglycerides labeled with stable isotopes

    SciTech Connect

    Hachey, D.L.; Thomas, M.R.; Emken, E.A.; Garza, C.; Brown-Booth, L.; Adlof, R.O.; Klein, P.D.

    1987-10-01

    A stable isotope tracer method was utilized to measure quantitatively the secretion of diet-derived fatty acids (FA) into human milk. A mixture of (/sup 2/H6)tripalmitin, (/sup 2/H18)-triolein, and (/sup 2/H12)trilinolein was administered to three healthy, lactating women 22 to 30 years of age. Milk and blood samples were collected sequentially for 72 hr. The FA composition and concentration of total plasma, lipoprotein, and milk triglycerides were determined by gas-liquid chromatography (GLC) and the isotopic enrichment was determined by gas-liquid chromatography-mass spectrometry (GLC-MS). There were no statistically significant differences in mammary secretion of the individual fats, either by a single individual or between subjects. The mean secretion of fat by one breast was 5.11 +/- 1.26% of the dose (CV = 25%). There was a significant 6.0-hr delay between peak occurrence of the tracer in plasma and its occurrence in milk. The lipids are transported to the mammary gland primarily by the chylomicron and very low density lipoprotein triglycerides.

  6. Interrelated effects of dietary fiber and fat on lymphatic cholesterol and triglyceride absorption in rats.

    PubMed

    Ikeda, I; Tomari, Y; Sugano, M

    1989-10-01

    Lymph cannulated rats were administered intragastrically a test emulsion containing 25 mg of [14C]cholesterol, 50 mg of either guar gum, cellulose or chitosan, and 200 mg of either safflower, high-oleic safflower or palm oil, and the absorption of labeled cholesterol and fatty acids was measured. The type of both dietary fiber (P less than 0.001) and fat (P less than 0.05) significantly influenced cholesterol absorption. A significant interaction of fiber and fat on cholesterol absorption (P less than 0.05) was also observed. Chitosan effectively lowered cholesterol absorption more than did guar gum or cellulose, and this effect was more significant when given with safflower or high-oleic safflower oil than with palm oil. When guar gum was the source of dietary fiber, dietary fats did not modify cholesterol absorption. Dietary fiber also significantly affected triglyceride absorption (P less than 0.05). Absorption tended to be low in the chitosan, high in the cellulose and intermediate in the guar gum group. Absorption of safflower and high-oleic safflower oils tended to be higher than that of palm oil when cellulose or guar gum was fed. Guar gum, as compared with the other fibers, altered the absorption pattern of both cholesterol and triglyceride. The results showed that the type of dietary fat significantly influenced the effect that dietary fiber exerted on lipid absorption. PMID:2555465

  7. 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.

  8. Rhythms in cholesterol, cholesteryl esters, free fatty acids, and triglycerides in blood of lactating dairy cows.

    PubMed

    Bitman, J; Wood, D L; Lefcourt, A M

    1990-04-01

    Blood samples from six lactating dairy cows were analyzed to determine whether circulating neutral lipids exhibit rhythmic variations. Plasma neutral lipids were measured by quantitative TLC on every fourth integrated 15-min blood sample taken over 48-h periods. Cows were housed in an environmental chamber at 20 degrees C with 16 h light:8 h dark (lights on at 0700 h), fed daily at 0900 h, and milked at 0830 and 2000 h. Other variables monitored included: body temperature, ammonia nitrogen, urea nitrogen, glucose, triiodothyronine, thyroxine, somatotropin, insulin, cortisol, and prolactin. Mean concentrations of cholesterol, cholesteryl esters, free fatty acids, and triglycerides were 21.4, 175.4, 3.1, and 6.3 mg/dl, respectively. Visual and power spectral analysis of the pulsatile fluctuations in lipids indicated rhythms with periods of 2 to 3 h. Amplitudes of rhythms for free fatty acids and triglycerides were 60% of mean concentrations and for cholesterol and cholesteryl esters were 20% of mean concentrations. The presence of these rhythms was conserved when data were averaged across time by cow. However, because of nonstationary conditions, rhythms identified by spectral analysis were not statistically significant. There was no evidence of circadian patterns in circulating neutral lipid components. All other metabolic and hormonal variables except cortisol exhibited distinct circadian rhythms. PMID:2345205

  9. Heterozygous Deficiency of Endoglin Decreases Insulin and Hepatic Triglyceride Levels during High Fat Diet

    PubMed Central

    Beiroa, Daniel; Romero-Picó, Amparo; Langa, Carmen; Bernabeu, Carmelo; López, Miguel; López-Novoa, José M.; Nogueiras, Ruben; Diéguez, Carlos

    2013-01-01

    Endoglin is a transmembrane auxiliary receptor for transforming growth factor-beta (TGF-beta) that is predominantly expressed on proliferating endothelial cells. It plays a wide range of physiological roles but its importance on energy balance or insulin sensitivity has been unexplored. Endoglin deficient mice die during midgestation due to cardiovascular defects. Here we report for first time that heterozygous endoglin deficiency in mice decreases high fat diet-induced hepatic triglyceride content and insulin levels. Importantly, these effects are independent of changes in body weight or adiposity. At molecular level, we failed to detect relevant changes in the insulin signalling pathway at basal levels in liver, muscle or adipose tissues that could explain the insulin-dependent effect. However, we found decreased triglyceride content in the liver of endoglin heterozygous mice fed a high fat diet in comparison to their wild type littermates. Overall, our findings indicate that endoglin is a potentially important physiological mediator of insulin levels and hepatic lipid metabolism. PMID:23336009

  10. Loss of adipose triglyceride lipase is associated with human cancer and induces mouse pulmonary neoplasia.

    PubMed

    Al-Zoughbi, Wael; Pichler, Martin; Gorkiewicz, Gregor; Guertl-Lackner, Barbara; Haybaeck, Johannes; Jahn, Stephan W; Lackner, Carolin; Liegl-Atzwanger, Bernadette; Popper, Helmut; Schauer, Silvia; Nusshold, Elisa; Kindt, Alida S D; Trajanoski, Zlatko; Speicher, Michael R; Haemmerle, Guenther; Zimmermann, Robert; Zechner, Rudolf; Vesely, Paul W; Hoefler, Gerald

    2016-06-01

    Metabolic reprogramming is a hallmark of cancer. Understanding cancer metabolism is instrumental to devise innovative therapeutic approaches. Anabolic metabolism, including the induction of lipogenic enzymes, is a key feature of proliferating cells. Here, we report a novel tumor suppressive function for adipose triglyceride lipase (ATGL), the rate limiting enzyme in the triglyceride hydrolysis cascade.In immunohistochemical analysis, non-small cell lung cancers, pancreatic adenocarcinoma as well as leiomyosarcoma showed significantly reduced levels of ATGL protein compared to corresponding normal tissues. The ATGL gene was frequently deleted in various forms of cancers. Low levels of ATGL mRNA correlated with significantly reduced survival in patients with ovarian, breast, gastric and non-small cell lung cancers. Remarkably, pulmonary neoplasia including invasive adenocarcinoma developed spontaneously in mice lacking ATGL pointing to an important role for this lipase in controlling tumor development.Loss of ATGL, as detected in several forms of human cancer, induces spontaneous development of pulmonary neoplasia in a mouse model. Our results, therefore, suggest a novel tumor suppressor function for ATGL and contribute to the understanding of cancer metabolism. We propose to evaluate loss of ATGL protein expression for the diagnosis of malignant tumors. Finally, modulation of the lipolytic pathway may represent a novel therapeutic approach in the treatment of human cancer.

  11. Isotopomer spectral analysis of triglyceride fatty acid synthesis in 3T3-L1 cells.

    PubMed

    Kharroubi, A T; Masterson, T M; Aldaghlas, T A; Kennedy, K A; Kelleher, J K

    1992-10-01

    A new analysis of stable isotope data for biosynthesis reaction, isotopomer spectral analysis (ISA), is demonstrated. ISA is theoretically applicable for polymerization biosynthesis where data are collected using selected ion-monitoring gas chromatography-mass spectrometry. ISA utilizes the discrete spectrum of isotopomer abundances and the multinomial distribution to estimate two key parameters related to the biosynthesis. These parameters are 1) the dilution of the precursor immediately before biosynthesis and 2) the dilution of the newly synthesized product in the sampled compartment. Differentiated 3T3-L1 cells incorporated 2 mM [1,2-13C]acetate into triglyceride palmitate, yielding a spectrum of mass isotopomers of palmitate. The set of equations for the first nine isotopomers were solved for the two parameters using nonlinear regression. We found that precursor dilutions for acetate and glucose were constant over time, whereas the product dilution parameter increased with time, as expected for cells accumulating triglyceride palmitate. Mathematical procedures are presented for calculating 1) the predicted isotopomer fractional abundance values and 2) the correction for atoms other than the tracer atom in the mass ion. PMID:1415685

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

    PubMed

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

    1995-12-01

    Elevated plasma levels of apolipoprotein B (apoB)-containing lipoproteins constitute a major risk factor for the development of coronary heart disease. In the rare recessively inherited disorder abetalipoproteinemia (ABL) the production of apoB-containing lipoproteins is abolished, despite no abnormality of the apoB gene. In the current study we have characterized the gene encoding a microsomal triglyceride-transfer protein (MTP), localized to chromosome 4q22-24, and have identified a mutation of the MTP gene in both alleles of all individuals in a cohort of eight patients with classical ABL. Each mutant allele is predicted to encode a truncated form of MTP with a variable number of aberrant amino acids at its C-terminal end. Expression of genetically engineered forms of MTP in Cos-1 cells indicates that the C-terminal portion of MTP is necessary for triglyceride-transfer activity. Deletion of 20 amino acids from the carboxyl terminus of the 894-amino-acid protein and a missense mutation of cysteine 878 to serine both abolished activity. These results establish that defects of the MTP gene are the predominant, if not sole, cause of hereditary ABL and that an intact carboxyl terminus is necessary for activity. PMID:8533758

  13. Loss of adipose triglyceride lipase is associated with human cancer and induces mouse pulmonary neoplasia

    PubMed Central

    Al-Zoughbi, Wael; Pichler, Martin; Gorkiewicz, Gregor; Guertl-Lackner, Barbara; Haybaeck, Johannes; Jahn, Stephan W.; Lackner, Carolin; Liegl-Atzwanger, Bernadette; Popper, Helmut; Schauer, Silvia; Nusshold, Elisa; Kindt, Alida S. D.; Trajanoski, Zlatko; Speicher, Michael R.; Haemmerle, Guenther; Zimmermann, Robert; Zechner, Rudolf; Vesely, Paul W.; Hoefler, Gerald

    2016-01-01

    Metabolic reprogramming is a hallmark of cancer. Understanding cancer metabolism is instrumental to devise innovative therapeutic approaches. Anabolic metabolism, including the induction of lipogenic enzymes, is a key feature of proliferating cells. Here, we report a novel tumor suppressive function for adipose triglyceride lipase (ATGL), the rate limiting enzyme in the triglyceride hydrolysis cascade. In immunohistochemical analysis, non-small cell lung cancers, pancreatic adenocarcinoma as well as leiomyosarcoma showed significantly reduced levels of ATGL protein compared to corresponding normal tissues. The ATGL gene was frequently deleted in various forms of cancers. Low levels of ATGL mRNA correlated with significantly reduced survival in patients with ovarian, breast, gastric and non-small cell lung cancers. Remarkably, pulmonary neoplasia including invasive adenocarcinoma developed spontaneously in mice lacking ATGL pointing to an important role for this lipase in controlling tumor development. Loss of ATGL, as detected in several forms of human cancer, induces spontaneous development of pulmonary neoplasia in a mouse model. Our results, therefore, suggest a novel tumor suppressor function for ATGL and contribute to the understanding of cancer metabolism. We propose to evaluate loss of ATGL protein expression for the diagnosis of malignant tumors. Finally, modulation of the lipolytic pathway may represent a novel therapeutic approach in the treatment of human cancer. PMID:27213586

  14. Inheritance of rare functional GCKR variants and their contribution to triglyceride levels in families

    PubMed Central

    Rees, Matthew G.; Raimondo, Anne; Wang, Jian; Ban, Matthew R.; Davis, Mindy I.; Barrett, Amy; Ranft, Jessica; Jagdhuhn, David; Waterstradt, Rica; Baltrusch, Simone; Simeonov, Anton; Collins, Francis S.; Hegele, Robert A.; Gloyn, Anna L.

    2014-01-01

    Significant resources have been invested in sequencing studies to investigate the role of rare variants in complex disease etiology. However, the diagnostic interpretation of individual rare variants remains a major challenge, and may require accurate variant functional classification and the collection of large numbers of variant carriers. Utilizing sequence data from 458 individuals with hypertriglyceridemia and 333 controls with normal plasma triglyceride levels, we investigated these issues using GCKR, encoding glucokinase regulatory protein. Eighteen rare non-synonymous GCKR variants identified in these 791 individuals were comprehensively characterized by a range of biochemical and cell biological assays, including a novel high-throughput-screening-based approach capable of measuring all variant proteins simultaneously. Functionally deleterious variants were collectively associated with hypertriglyceridemia, but a range of in silico prediction algorithms showed little consistency between algorithms and poor agreement with functional data. We extended our study by obtaining sequence data on family members; however, functional variants did not co-segregate with triglyceride levels. Therefore, despite evidence for their collective functional and clinical relevance, our results emphasize the low predictive value of rare GCKR variants in individuals and the complex heritability of lipid traits. PMID:24879641

  15. Discovery of Novel Splice Variants and Regulatory Mechanisms for Microsomal Triglyceride Transfer Protein in Human Tissues

    PubMed Central

    Suzuki, Takashi; Swift, Larry L.

    2016-01-01

    Microsomal triglyceride transfer protein (MTP) is a unique lipid transfer protein essential for the assembly of triglyceride-rich lipoproteins by the liver and intestine. Previous studies in mice identified a splice variant of MTP with an alternate first exon. Splice variants of human MTP have not been reported. Using PCR approaches we have identified two splice variants in human tissues, which we have named MTP-B and MTP-C. MTP-B has a unique first exon (Ex1B) located 10.5 kb upstream of the first exon (Ex1A) for canonical MTP (MTP-A); MTP-C contains both first exons for MTP-A and MTP-B. MTP-B was found in a number of tissues, whereas MTP-C was prominent in brain and testis. MTP-B does not encode a protein; MTP-C encodes the same protein encoded by MTP-A, although MTP-C translation is strongly inhibited by regulatory elements within its 5′-UTR. Using luciferase assays, we demonstrate that the promoter region upstream of exon 1B is quite adequate to drive expression of MTP. We conclude that alternate splicing plays a key role in regulating cellular MTP levels by introducing distinct promoter regions and unique 5′-UTRs, which contain elements that alter translation efficiency, enabling the cell to optimize MTP activity. PMID:27256115

  16. Adipose triglyceride lipase is a TG hydrolase of the small intestine and regulates intestinal PPARα signaling.

    PubMed

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

    2013-02-01

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

  17. Cholesterol and triglyceride management: "if I take my medication, can I eat what I want?".

    PubMed

    Braun, Lynne T

    2010-01-01

    The medications we use for cholesterol and triglyceride lowering are powerful and have substantial outcome data. However, even with aggressive statin therapy, there is residual risk for recurrent cardiovascular events. Strict dietary modification has been shown to reduce low-density lipoprotein (LDL) cholesterol by 20% to 30%. Low-fat and Mediterranean-type diets have also been associated with atherosclerosis regression and fewer coronary heart disease events. On the other hand, a high-fat diet can produce postprandial lipemia and an increase in cardiovascular disease risk. Patients with atherogenic dyslipidemia (low high-density lipoprotein cholesterol, increased triglycerides and non-high-density lipoprotein cholesterol, small dense low-density lipoprotein particles) and visceral adiposity are particularly prone to postprandial lipemia. These individuals typically have insulin resistance, which is associated with endothelial dysfunction and an increased risk for thrombosis. Lifestyle intervention is the key to reducing postprandial lipemia, specifically weight reduction and increased physical activity. Although medications can improve postprandial lipemia, poor dietary choices can overwhelm the effects of medication and negatively impact the health of arteries, thus promoting atherosclerosis. Therefore, patients who are treated with medications for dyslipidemia must be counseled on consuming a heart-healthy diet.

  18. Discovery of Novel Splice Variants and Regulatory Mechanisms for Microsomal Triglyceride Transfer Protein in Human Tissues.

    PubMed

    Suzuki, Takashi; Swift, Larry L

    2016-01-01

    Microsomal triglyceride transfer protein (MTP) is a unique lipid transfer protein essential for the assembly of triglyceride-rich lipoproteins by the liver and intestine. Previous studies in mice identified a splice variant of MTP with an alternate first exon. Splice variants of human MTP have not been reported. Using PCR approaches we have identified two splice variants in human tissues, which we have named MTP-B and MTP-C. MTP-B has a unique first exon (Ex1B) located 10.5 kb upstream of the first exon (Ex1A) for canonical MTP (MTP-A); MTP-C contains both first exons for MTP-A and MTP-B. MTP-B was found in a number of tissues, whereas MTP-C was prominent in brain and testis. MTP-B does not encode a protein; MTP-C encodes the same protein encoded by MTP-A, although MTP-C translation is strongly inhibited by regulatory elements within its 5'-UTR. Using luciferase assays, we demonstrate that the promoter region upstream of exon 1B is quite adequate to drive expression of MTP. We conclude that alternate splicing plays a key role in regulating cellular MTP levels by introducing distinct promoter regions and unique 5'-UTRs, which contain elements that alter translation efficiency, enabling the cell to optimize MTP activity. PMID:27256115

  19. Studying the Relation of Postprandial Triglyceride with Coronary Artery Disease (CAD)

    PubMed Central

    Manochehri, Mohammad; Moghadam, Adel Johari

    2016-01-01

    Background: Coronary artery disease (CAD) is the most common cause of mortality worldwide and determination of contributing factors is essential. Aim: This study was conducted to study the relation of postprandial triglyceride as a risk of coronary artery disease in patients with proven CAD by angiography, referred to 502 Hospital of Army in 2015. Material and Methods: This observational study conducted as a case-control and contained 80 male participants referred to 502 Hospital of Army. Half of these participants had proven CAD by angiography test and the other ones were healthy as a control group. Fasting serum triglyceride was evaluated in all participants and postprandial TG was checked 4 hours after a standard meal. Obtained data were analyzed by SPSS ver. 13. Results: The results indicated that fasting TG and postprandial TG level were significantly higher in CAD patients (P-value=0.001). It was also shown evaluation of postprandial TG is more sensitive test than fasting TG in case of CAD patients. Conclusion: Our obtained results shown, evaluation of high level of postprandial TG is more reliable than fasting TG for patients whom suffer from CAD. PMID:27703285

  20. Mfge8 regulates enterocyte lipid storage by promoting enterocyte triglyceride hydrolase activity

    PubMed Central

    Khalifeh-Soltani, Amin; Gupta, Deepti; Ha, Arnold; Iqbal, Jahangir; Hussain, Mahmood; Podolsky, Michael J.

    2016-01-01

    The small intestine has an underappreciated role as a lipid storage organ. Under conditions of high dietary fat intake, enterocytes can minimize the extent of postprandial lipemia by storing newly absorbed dietary fat in cytoplasmic lipid droplets. Lipid droplets can be subsequently mobilized for the production of chylomicrons. The mechanisms that regulate this process are poorly understood. We report here that the milk protein Mfge8 regulates hydrolysis of cytoplasmic lipid droplets in enterocytes after interacting with the αvβ3 and αvβ5 integrins. Mice deficient in Mfge8 or the αvβ3 and αvβ5 integrins accumulate excess cytoplasmic lipid droplets after a fat challenge. Mechanistically, interruption of the Mfge8-integrin axis leads to impaired enterocyte intracellular triglyceride hydrolase activity in vitro and in vivo. Furthermore, Mfge8 increases triglyceride hydrolase activity through a PI3 kinase/mTORC2–dependent signaling pathway. These data identify a key role for Mfge8 and the αvβ3 and αvβ5 integrins in regulating enterocyte lipid processing. PMID:27812539

  1. The Local Interstellar Medium

    NASA Astrophysics Data System (ADS)

    Ferlet, Roger

    Substantial progress in the field of the Local Interstellar Medium has been largely due to recent launches of space missions, mostly in the UV and X-ray domains, but also to ground-based observations, mainly in high resolution spectroscopy. However, a clear gap seems to remain between the wealth of new data and the theoretical understanding. This paper gives an overview of some observational aspects, with no attempt of completeness or doing justice to all the people involved in the field. As progress rarely evolves in straight paths, we can expect that our present picture of the solar system surroundings is not definitive.

  2. DENSE MEDIUM CYCLONE OPTIMIZATON

    SciTech Connect

    Gerald H. Luttrell; Chris J. Barbee; Peter J. Bethell; Chris J. Wood

    2005-06-30

    Dense medium cyclones (DMCs) are known to be efficient, high-tonnage devices suitable for upgrading particles in the 50 to 0.5 mm size range. This versatile separator, which uses centrifugal forces to enhance the separation of fine particles that cannot be upgraded in static dense medium separators, can be found in most modern coal plants and in a variety of mineral plants treating iron ore, dolomite, diamonds, potash and lead-zinc ores. Due to the high tonnage, a small increase in DMC efficiency can have a large impact on plant profitability. Unfortunately, the knowledge base required to properly design and operate DMCs has been seriously eroded during the past several decades. In an attempt to correct this problem, a set of engineering tools have been developed to allow producers to improve the efficiency of their DMC circuits. These tools include (1) low-cost density tracers that can be used by plant operators to rapidly assess DMC performance, (2) mathematical process models that can be used to predict the influence of changes in operating and design variables on DMC performance, and (3) an expert advisor system that provides plant operators with a user-friendly interface for evaluating, optimizing and trouble-shooting DMC circuits. The field data required to develop these tools was collected by conducting detailed sampling and evaluation programs at several industrial plant sites. These data were used to demonstrate the technical, economic and environmental benefits that can be realized through the application of these engineering tools.

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

    PubMed

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

    2014-02-01

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

  4. ApoAV reduces plasma triglycerides by inhibiting very low density lipoprotein-triglyceride (VLDL-TG) production and stimulating lipoprotein lipase-mediated VLDL-TG hydrolysis.

    PubMed

    Schaap, Frank G; Rensen, Patrick C N; Voshol, Peter J; Vrins, Carlos; van der Vliet, Hendrik N; Chamuleau, Robert A F M; Havekes, Louis M; Groen, Albert K; van Dijk, Ko Willems

    2004-07-01

    ApoAV has been discovered recently as a novel modifier of triglyceride (TG) metabolism, but the pathways involved are currently unknown. To gain insight into the function of apoAV, adenovirus-mediated gene transfer of murine apoa5 to C57Bl/6 mice was employed. The injection of low doses of Ad-apoa5 (1-5 x 10(8) plaqueforming units/mouse) dose-dependently reduced plasma very low density lipoprotein (VLDL)-TG levels. First, we evaluated whether a reduced hepatic VLDL production contributed to the TG-lowering effect. Ad-apoa5 treatment dose-dependently diminished (29-37%) the VLDL-TG production rate without affecting VLDL particle production, suggesting that apoAV impairs the lipidation of apoB. Second, Ad-apoa5 treatment dose-dependently reduced (68-88%) the postprandial hypertriglyceridemia following an intragastric fat load, suggesting that apoAV also stimulates the lipoprotein lipase (LPL)-dependent clearance of TG-rich lipoproteins. Indeed, recombinant apoAV was found to dose-dependently stimulate LPL activity up to 2.3-fold in vitro. Accordingly, intravenously injected VLDL-like TG-rich emulsions were cleared at an accelerated rate concomitant with the increased uptake of emulsion TG-derived fatty acids by skeletal muscle and white adipose tissue in Ad-apoa5-treated mice. From these data, we conclude that apoAV is a potent stimulator of LPL activity. Thus, apoAV lowers plasma TG by both reducing the hepatic VLDL-TG production rate and by enhancing the lipolytic conversion of TG-rich lipoproteins.

  5. Contribution of Adipose Triglyceride Lipase and Hormone-sensitive Lipase to Lipolysis in hMADS Adipocytes*

    PubMed Central

    Bezaire, Véronic; Mairal, Aline; Ribet, Carole; Lefort, Corinne; Girousse, Amandine; Jocken, Johan; Laurencikiene, Jurga; Anesia, Rodica; Rodriguez, Anne-Marie; Ryden, Mikael; Stenson, Britta M.; Dani, Christian; Ailhaud, Gérard; Arner, Peter; Langin, Dominique

    2009-01-01

    Lipolysis is the catabolic pathway by which triglycerides are hydrolyzed into fatty acids. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) have the capacity to hydrolyze in vitro the first ester bond of triglycerides, but their respective contributions to whole cell lipolysis in human adipocytes is unclear. Here, we have investigated the roles of HSL, ATGL, and its coactivator CGI-58 in basal and forskolin-stimulated lipolysis in a human white adipocyte model, the hMADS cells. The hMADS adipocytes express the various components of fatty acid metabolism and show lipolytic capacity similar to primary cultured adipocytes. We show that lipolysis and fatty acid esterification are tightly coupled except in conditions of stimulated lipolysis. Immunocytochemistry experiments revealed that acute forskolin treatment promotes HSL translocation from the cytosol to small lipid droplets and redistribution of ATGL from the cytosol and large lipid droplets to small lipid droplets, resulting in enriched colocalization of the two lipases. HSL or ATGL overexpression resulted in increased triglyceride-specific hydrolase capacity, but only ATGL overexpression increased whole cell lipolysis. HSL silencing had no effect on basal lipolysis and only partially reduced forskolin-stimulated lipolysis. Conversely, silencing of ATGL or CGI-58 significantly reduced basal lipolysis and essentially abolished forskolin-stimulated lipolysis. Altogether, these results suggest that ATGL/CGI-58 acts independently of HSL and precedes its action in the sequential hydrolysis of triglycerides in human hMADS adipocytes. PMID:19433586

  6. Contribution of adipose triglyceride lipase and hormone-sensitive lipase to lipolysis in hMADS adipocytes.

    PubMed

    Bezaire, Véronic; Mairal, Aline; Ribet, Carole; Lefort, Corinne; Girousse, Amandine; Jocken, Johan; Laurencikiene, Jurga; Anesia, Rodica; Rodriguez, Anne-Marie; Ryden, Mikael; Stenson, Britta M; Dani, Christian; Ailhaud, Gérard; Arner, Peter; Langin, Dominique

    2009-07-01

    Lipolysis is the catabolic pathway by which triglycerides are hydrolyzed into fatty acids. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) have the capacity to hydrolyze in vitro the first ester bond of triglycerides, but their respective contributions to whole cell lipolysis in human adipocytes is unclear. Here, we have investigated the roles of HSL, ATGL, and its coactivator CGI-58 in basal and forskolin-stimulated lipolysis in a human white adipocyte model, the hMADS cells. The hMADS adipocytes express the various components of fatty acid metabolism and show lipolytic capacity similar to primary cultured adipocytes. We show that lipolysis and fatty acid esterification are tightly coupled except in conditions of stimulated lipolysis. Immunocytochemistry experiments revealed that acute forskolin treatment promotes HSL translocation from the cytosol to small lipid droplets and redistribution of ATGL from the cytosol and large lipid droplets to small lipid droplets, resulting in enriched colocalization of the two lipases. HSL or ATGL overexpression resulted in increased triglyceride-specific hydrolase capacity, but only ATGL overexpression increased whole cell lipolysis. HSL silencing had no effect on basal lipolysis and only partially reduced forskolin-stimulated lipolysis. Conversely, silencing of ATGL or CGI-58 significantly reduced basal lipolysis and essentially abolished forskolin-stimulated lipolysis. Altogether, these results suggest that ATGL/CGI-58 acts independently of HSL and precedes its action in the sequential hydrolysis of triglycerides in human hMADS adipocytes. PMID:19433586

  7. Two meals with different carbohydrate, fat and protein contents render equivalent postprandial plasma levels of calprotectin, cortisol, triglycerides and zonulin.

    PubMed

    Ohlsson, Bodil; Darwiche, Gassan; Roth, Bodil; Höglund, Peter

    2016-11-01

    The aim was to compare postprandial plasma levels of calprotectin, cortisol, triglycerides and zonulin between a control breakfast and a moderately low-carbohydrate test breakfast, given randomly after 10-h fast. Blood samples were collected before and repeatedly after the meal. Plasma calprotectin, cortisol, triglycerides and zonulin were analyzed. The total area under the curve (tAUC) and change in AUC from baseline (dAUC) were calculated. Ratios between the test and control values were calculated to investigate equivalence. Healthy volunteers (8 men and 12 women; 46.0 ± 14.5 years) were included. tAUCs of cortisol and triglycerides did not differ between the breakfasts (p = 0.158 versus p = 0.579). Cortisol dAUCs were decreased and triglyceride dAUCs were increased after both breakfasts, with no differences between the breakfasts (p = 0.933 versus p = 0.277). Calprotectin and zonulin levels were unaffected. The meals were bioequivalent for cortisol, triglycerides and zonulin, but not for calprotectin.

  8. 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.

  9. Lipoprotein lipase release from BFC-1 beta adipocytes. Effects of triglyceride-rich lipoproteins and lipolysis products.

    PubMed

    Sasaki, A; Goldberg, I J

    1992-07-25

    Lipoprotein lipase (LPL), synthesized by adipocytes and myocytes, must be transported to the luminal endothelial cell surface where it then interacts with circulating lipoproteins. The first step in this extracellular LPL transport pathway is LPL release from the surface of LPL-synthesizing cells. Because hydrolysis of triglyceride (TG)-rich lipoproteins releases LPL from the apical surface of endothelial cells, we hypothesized that the same substances dissociate LPL from adipocytes. 125I-LPL was bound to the surface of brown adipocytes (BFC-1 beta). LPL binding to the adipocyte surface was greater than to endothelial cell surfaces. Using low concentrations of heparin, more LPL was released from endothelial cells than BFC-1 beta, suggesting that the affinity of LPL binding to the adipocytes was greater than LPL affinity for endothelial cells. Greater than 3-fold more LPL was released from the cell surface when very low density lipoproteins (VLDL) were added to culture medium containing 3% bovine serum albumin. LPL remaining on the cell surface decreased with VLDL addition. Endogenously produced LPL activity was also released from the cells by VLDL. Low and high density lipoproteins did not release 125I-LPL or LPL activity from the adipocytes. To assess whether lipolysis was necessary for LPL release, BFC-1 beta were incubated with TG-rich lipoproteins from a patient with apoCII deficiency. The apoCII-deficient lipoproteins did not release LPL unless an exogenous source of apoCII was added. Apolipoproteins E and Cs and high molar ratios of oleic acid:bovine serum albumin did not release surface-associated LPL. Lysolecithin (25 and 100 microM), but not lecithin, monoglycerides, or diglycerides, released adipocyte surface LPL. Because lysolecithin also released LPL during a 4 degrees C incubation, cellular metabolic functions are not required for LPL dissociation from the cells. Lysolecithin also inhibited LPL binding to endothelial cells; however, this effect was

  10. Crater chains on Mercury

    NASA Astrophysics Data System (ADS)

    Shevchenko, V.; Skobeleva, T.

    After discovery of disruption comet Shoemaker-Levy 9 into fragment train before it's collision with Jupiter there was proposed that linear crater chains on the large satellites of Jupiter and on the Moon are impact scars of past tidally disrupted comets.It's known that radar images have revealed the possible presence of water ice deposits in polar regions of Mercury. Impacts by a few large comets seem to provide the best explanation for both the amount and cleanliness of the ice deposits on Mercury because they have a larger volatile content that others external sources, for example, asteroid. A number of crater chains on the surface of Mercury are most likely the impact tracks of "fragment trains" of comets tidally disrupted by Sun or by Mercury and are not secondary craters. Mariner 10 image set (the three Mariner 10 flybys in 1974-1975) was used to recognize the crater chains these did not associate with secondary crater ejecta from observed impact structures. As example, it can be shown such crater chain located near crater Imhotep and crater Ibsen (The Kuiper Quadrangle of Mercury). Resolution of the Mariner 10 image is about 0.54 km/pixel. The crater chain is about 50 km long. It was found a similar crater chain inside large crater Sophocles (The Tolstoj Quadrangle of Mercury). The image resolution is about 1.46 km/pixel. The chain about 50 km long is located in northen part of the crater. Image resolution limits possibility to examine the form of craters strongly. It seems the craters in chains have roughly flat floor and smooth form. Most chain craters are approximately circular. It was examined many images from the Mariner 10 set and there were identified a total 15 crater chains and were unable to link any of these directly to any specific large crater associated with ejecta deposits. Chain craters are remarkably aligned. All distinguished crater chains are superposed on preexisting formations. A total of 127 craters were identified in the 15 recognized

  11. Angptl4 links α-cell proliferation following glucagon receptor inhibition with adipose tissue triglyceride metabolism

    PubMed Central

    Ben-Zvi, Danny; Barrandon, Ornella; Hadley, Stephanie; Blum, Barak; Peterson, Quinn P.; Melton, Douglas A.

    2015-01-01

    Type 2 diabetes is characterized by a reduction in insulin function and an increase in glucagon activity that together result in hyperglycemia. Glucagon receptor antagonists have been developed as drugs for diabetes; however, they often increase glucagon plasma levels and induce the proliferation of glucagon-secreting α-cells. We find that the secreted protein Angiopoietin-like 4 (Angptl4) is up-regulated via Pparγ activation in white adipose tissue and plasma following an acute treatment with a glucagon receptor antagonist. Induction of adipose angptl4 and Angptl4 supplementation promote α-cell proliferation specifically. Finally, glucagon receptor antagonist improves glycemia in diet-induced obese angptl4 knockout mice without increasing glucagon levels or α-cell proliferation, underscoring the importance of this protein. Overall, we demonstrate that triglyceride metabolism in adipose tissue regulates α-cells in the endocrine pancreas. PMID:26621734

  12. Isolation and Identification of Triglycerides and Ester Oligomers from Partial Degradation of Potato Suberin

    PubMed Central

    Wang, Weimin; Tian, Shiying; Stark, Ruth E.

    2010-01-01

    Suberized cell walls from wound-healing potato tubers (Solanum tuberosum) were depolymerized under mild conditions using methanolic potassium hydroxide in order to investigate the chemical linkages present in this protective plant biopolymer. Analysis of the resulting soluble oligomeric fragments with HPLC, 1D and 2D NMR, LC/MS and MSn methods allowed identification of several novel compounds: a family of homologous triglycerides, a family of homologous aliphatic ester trimers, and an ether linked phenylacetic acid dimer. These findings illustrate the diversity of rigid and flexible molecular linkages present in both poly(aliphatic) and poly(aromatic) domains of potato suberin, and they point toward architectures that may account for its function as a potent hydrophobic barrier to water, thermal equilibration, and microbial pathogens. PMID:20028122

  13. Continuous Flow Metathesis for Direct Valorization of Food Waste: An Example of Cocoa Butter Triglyceride

    PubMed Central

    2015-01-01

    The direct chemical conversion of cocoa butter triglycerides, a material available as a postmanufacture waste stream from the food industry, to 1-decene by way of ethenolysis is reported. The conversion of the raw waste material was made possible by use of 1 mol % of the [RuCl2(iBu-phoban)2(3-phenylindenyl)] catalyst. The process has been investigated in both batch and flow conditions, where the latter approach employs a Teflon AF-2400 tube-in-tube gas–liquid membrane contactor to deliver ethylene to the reaction system. These preliminary studies culminate in a continuous processing system, which maintained a constant output over a 150 min period tested. PMID:26322250

  14. Kinetic analysis of free-radical reactions in the low-temperature autoxidation of triglycerides

    SciTech Connect

    Zhu, Jingmin; Sevilla, M.D. )

    1990-02-22

    The kinetics of the low-temperature autoxidation of triglycerides has been investigated by electron spin resonance spectroscopy. After initial radical production, four reaction stages are found in the overall autoxidation of unsaturated lipids: (1) formation of peroxyl radicals by addition of molecular oxygen to the initial carbon radicals, (2) consumption of oxygen in the autoxidation cycle, (3) decay of the lipid peroxyl radical into allylic and pentadienyl radicals, and (4) recombination of the carbon-centered radicals. Peroxyl radical decay in saturated lipids follows second-order kinetics with an apparent activation energy of ca. 50 kJ/mol. The authors find that, for polyunsaturated lipids, even at quite low temperatures (120 K), the autoxidation process occurs readily and must be considered in the storage of biological samples.

  15. An application of Love SH waves for the viscosity measurement of triglycerides at high pressures

    NASA Astrophysics Data System (ADS)

    Rostocki, A. J.; Siegoczyński, R. M.; Kiełczyński, P.; Szalewski, M.

    2010-03-01

    A new ultrasonic method of viscosity measurements at a high-pressure conditions has been presented. The method is based on the Love wave amplitude measurement. The same electronic setup as in the Bleustein-Gulyaev (B-G) wave method applied by the authors recently for a high-pressure measurement was adopted. The new sensors were made of metallic materials, which make them more reliable at high-pressure conditions. The method has been successfully applied for the viscosity measurement of some triglycerides at high-pressure conditions up to 1 GPa. The results have been compared with the earlier results obtained using B-G waves. This comparison has shown that Love wave method sensors are more reliable than B-G wave sensors and are also cheaper in fabrication, although the sensitivity of Love wave sensors is lower. During the measurement, the phase transitions in the investigated liquids were observed.

  16. Comprehensive experiment-clinical biochemistry: determination of blood glucose and triglycerides in normal and diabetic rats.

    PubMed

    Jiao, Li; Xiujuan, Shi; Juan, Wang; Song, Jia; Lei, Xu; Guotong, Xu; Lixia, Lu

    2015-01-01

    For second year medical students, we redesigned an original laboratory experiment and developed a combined research-teaching clinical biochemistry experiment. Using an established diabetic rat model to detect blood glucose and triglycerides, the students participate in the entire experimental process, which is not normally experienced during a standard clinical biochemistry exercise. The students are not only exposed to techniques and equipment but are also inspired to think more about the biochemical mechanisms of diseases. When linked with lecture topics about the metabolism of carbohydrates and lipids, the students obtain a better understanding of the relevance of abnormal metabolism in relation to diseases. Such understanding provides a solid foundation for the medical students' future research and for other clinical applications.