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Sample records for medium-chain triglycerides mct

  1. Medium chain triglycerides (MCT) formulas in paediatric and allergological practice

    PubMed Central

    Łoś-Rycharska, Ewa; Kieraszewicz, Zuzanna

    2016-01-01

    Fats constitute the most significant nutritional source of energy. Their proper use by the body conditions a number of complex mechanisms of digestion, absorption, distribution, and metabolism. These mechanisms are facilitated by fats made of medium chain fatty acids; therefore, they are an easy and quick source of energy. Thus, an increased supply of medium chain triglycerides (MCT) is particularly important in patients with disturbances of digestion and absorption such as disturbed bile secretion, classic coeliac disease, short bowel syndrome, inflammatory diseases of the intestines, disturbed outflow of lymph, some metabolic disease, and severe food allergies, as well as in prematurely born neonates. Use of preparations containing an additive of MCT is limited, especially if they are to be used for a longer period of time. With a large quantity of MCT in a diet, there is a risk of deficiency of necessary unsaturated fatty acids and some fat-soluble vitamins. The caloricity of MTC compared to long-chain triglycerides is lower, and formulas with MCT are characterised by higher osmolality. Medium chain triglycerides is not recommended as an additive to standard formulas for healthy children. The use of MCT should be limited to strictly specified medical indications. PMID:28053676

  2. Medium chain triglycerides (MCT) formulas in paediatric and allergological practice.

    PubMed

    Łoś-Rycharska, Ewa; Kieraszewicz, Zuzanna; Czerwionka-Szaflarska, Mieczysława

    2016-01-01

    Fats constitute the most significant nutritional source of energy. Their proper use by the body conditions a number of complex mechanisms of digestion, absorption, distribution, and metabolism. These mechanisms are facilitated by fats made of medium chain fatty acids; therefore, they are an easy and quick source of energy. Thus, an increased supply of medium chain triglycerides (MCT) is particularly important in patients with disturbances of digestion and absorption such as disturbed bile secretion, classic coeliac disease, short bowel syndrome, inflammatory diseases of the intestines, disturbed outflow of lymph, some metabolic disease, and severe food allergies, as well as in prematurely born neonates. Use of preparations containing an additive of MCT is limited, especially if they are to be used for a longer period of time. With a large quantity of MCT in a diet, there is a risk of deficiency of necessary unsaturated fatty acids and some fat-soluble vitamins. The caloricity of MTC compared to long-chain triglycerides is lower, and formulas with MCT are characterised by higher osmolality. Medium chain triglycerides is not recommended as an additive to standard formulas for healthy children. The use of MCT should be limited to strictly specified medical indications.

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

    PubMed

    Kaunitz, H

    1986-01-01

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

  4. Lack of toxicity by medium chain triglycerides (MCT) in canines during a 90-day feeding study.

    PubMed

    Matulka, Ray A; Thompson, D V M Larry; Burdock, George A

    2009-01-01

    Dietary fats in food are natural energy sources to animals and are included in the American Association of Feed Control Officials (AAFCO) manual as a requirement for dog food. Medium chain triglycerides are comprised of a glycerol backbone esterified to medium chain length (8-12 carbon) fatty acids (FA) and, in the context of this report, are all saturated FA. Unlike esterified long chain (>12 carbons) FA (long chain triglycerides or LCT), MCT are lower in caloric value, and are eliminated from the body more quickly than LCT. The objective of this study was to determine the safety of MCT when fed to beagles for 90 days at levels of 0%, 5%, 10%, and 15% MCT added to conventional feed. The beagles were monitored for signs of toxicity by clinical observations, body weight measurements, food consumption level, physical examinations, hematology and serum chemistry, ophthalmic examinations, and urinalysis. There were no signs of toxic effects observed in any of the animals that were related to feed, and the animal viability was 100% at the end of the study. Some animals exhibited significant increased blood urea nitrogen, potassium and cholesterol levels in the 10% and 15% MCT-fed groups. Also, in the same groups with elevated nitrogen, there were concomitant reductions in total blood protein and urine volumes. These changes in serum chemistry may be the result of protein sparing effects due to the high levels of MCT intake, and are not deemed to be pathological in nature. Animals receiving 15% MCT in feed had lower levels of food intake due to palatability issues. From the other examination parameters, there were no significant changes noted between groups receiving MCT and vehicle feed. No safety concerns were noted at any dose level, although an issue with palatability precluded identifying 15% as the highest dose level tested.

  5. Effect of medium chain triglycerides (MCT) on jejunal mucosa mass and protein synthesis.

    PubMed Central

    Schwartz, S; Farriol, M; Garcia-Arumi, E; Andreu, A L; López Hellín, J; Arbós, M A

    1994-01-01

    The effects of medium chain triglycerides (MCT) on jejunal mucosa mass and protein synthesis were compared with results from previous experiments with rats fed by parenteral nutrition or enteral nutrition. Other published studies have also been analysed. Three experimental models were studied. In the traumatic model, production of a femoral fracture was followed by Kirschner pin insertion into the medullary canal of both fragments at reduction. (Forty ras were fed enteral nutrition and 93 were given parenteral nutrition.) A second model entailed resection under ether anaesthesia using the technique described by Higgins. (Fifty five rats were fed enteral nutrition and 28 with parenteral nutrition.) A third model entailed a terminolateral portocaval shunt under anaesthesia with pentobarbital. (Sixty nine rats were treated this way and then given enteral nutrition.) Proportions of medium chain/long chain triglycerides (LCT) were as follows: 0/100, 20/80, 40/60, 50/50, and 92/8 for enteral nutrition and 0/100, 30/70, 50/50, and 70/30 for parenteral nutrition. Faecal losses of alpha amino nitrogen, protein, total fats, and free fatty acids were analysed together with the quantitative intake, weight gain of the rats, jejunal mucosal mass, and protein synthesis in relation to the MCT proportion ingested or given by enteral nutrition or parenteral nutrition. From analysis of our results and those of others, several conclusions could be drawn. Firstly, the route of administration of MCT is extremely important and enterocytes might be considered one of the main target sites. Secondly, a high proportion of MCT (more than 80%) offers no advantage for jejunal mucosa and produces undesirable side effects. Thirdly, the effect of MCT on jejunal mucosal protein synthesis depends on the metabolic state. Finally, an increase in jejunal mucosal mass directly correlated with MCT concentrations, but no correlation was found between mass and protein synthesis. A positive correlation

  6. 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

  7. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. 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

  9. Medium chain triglycerides and hepatic encephalopathy

    PubMed Central

    Morgan, M. Hilary; Bolton, C. H.; Morris, J. S.; Read, A. E.

    1974-01-01

    The oral administration of short (C6) and medium (C8 and (C10) chain triglycerides produced no clinical or electroencephalographic changes in patients with cirrhosis of the liver. Arterial ammonia levels were also monitored in these patients and showed no significant change after medium chain triglycerides. It was concluded that medium chain triglycerides, known to be of potential value in the treatment of malabsorption in patients with cirrhosis, are not clinically contraindicated, even in patients with evidence of hepatic encephalopathy. PMID:4841275

  10. Metabolic control during exercise with and without medium-chain triglycerides (MCT) in children with long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency

    PubMed Central

    Gillingham, Melanie B.; Scott, Bradley; Elliott, Diane; Harding, Cary O.

    2009-01-01

    Exercise induced rhabdomyolysis is a complication of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (TFP) deficiency that frequently leads to exercise avoidance. Dietary therapy for most subjects includes medium-chain triglyceride (MCT) supplementation but analysis of diet records indicates that the majority of patients consume oral MCT only with breakfast and at bedtime. We hypothesized that MCT immediately prior to exercise would provide an alternative fuel source during that bout of exercise and improve exercise tolerance in children with LCHAD deficiency. Nine subjects completed two 45 min moderate intensity (60–70% predicted maximum heart rate (HR)) treadmill exercise tests. Subjects were given 4 oz of orange juice alone or orange juice and 0.5 g MCT per kg lean body mass, 20 min prior to exercise in a randomized cross-over design. ECG and respiratory gas exchange including respiratory quotient (RQ) were monitored. Blood levels of acylcarnitines, creatine kinase, lactate, and β-hydroxybutyrate were measured prior to and immediately after exercise, and again following 20min rest. Creatine kinase and lactate levels did not change with exercise. There was no significant difference in RQ between the two exercise tests but there was a decrease in steady-state HR following MCT supplementation. Cumulative long-chain 3-hydroxyacylcarnitines were 30% lower and β-hydroxybutyrate was three-fold higher after the MCT-pretreated exercise test compared to the test with orange juice alone. Coordinating MCT supplementation with periods of increased activity may improve the metabolic control of children with LCHAD and TFP deficiency following exercise. PMID:16876451

  11. The metabolic consequences of infusing emulsions containing medium chain triglycerides for parenteral nutrition: a comparative study with conventional lipid.

    PubMed Central

    Dennison, A. R.; Ball, M.; Crowe, P. J.; White, K.; Hands, L.; Watkins, R. M.; Kettlewell, M.

    1986-01-01

    In order to test the hypothesis that medium chain triglycerides (MCT's) are a safe and potentially superior energy source during parenteral nutrition 13 patients were entered into a randomised cross over trial. They received either a long chain triglyceride emulsion (LCT) or a 50% medium chain (MCT)/50% LCT mixture as part of their energy supply. Nitrogen balance was significantly better when MCT/LCT was infused and the greater levels of plasma ketones and lower plasma triglyceride levels suggested that MCT was more readily metabolised in these patients. Routine haematology, biochemistry and liver function tests gave no indication of harmful side effects from MCT. PMID:3089123

  12. Dietary medium-chain triglycerides attenuate hepatic lipid deposition in growing rats with protein malnutrition.

    PubMed

    Kuwahata, Masashi; Kubota, Hiroyo; Amano, Saki; Yokoyama, Meiko; Shimamura, Yasuhiro; Ito, Shunsuke; Ogawa, Aki; Kobayashi, Yukiko; Miyamoto, Ken-ichi; Kido, Yasuhiro

    2011-01-01

    The objective of this study was to investigate the effects of dietary medium-chain triglycerides (MCT) on hepatic lipid accumulation in growing rats with protein malnutrition. Weaning rats were fed either a low-protein diet (3%, LP) or control protein diet (20%, CP), in combination with or without MCT. The four groups were as follows: CP-MCT, CP+MCT, LP-MCT, and LP+MCT. Rats in the CP-MCT, CP+MCT and LP+MCT groups were pair-fed their respective diets based on the amount of diet consumed by the LP-MCT group. Rats were fed each experimental diet for 30 d. Four weeks later, the respiratory quotient was higher in the LP-MCT group than those in the other groups during the fasting period. Hepatic triglyceride content increased in the LP groups compared with the CP groups. Hepatic triglyceride content in the LP+MCT group, however, was significantly decreased compared with that in the LP-MCT group. Levels of carnitine palmitoyltransferase (CPT) 1a mRNA and CPT2 mRNA were significantly decreased in the livers of the LP-MCT group, as compared with corresponding mRNA levels of the other groups. These results suggest that ingestion of a low-protein diet caused fatty liver in growing rats. However, when rats were fed the low-protein diet with MCT, hepatic triglyceride deposition was attenuated, and mRNA levels encoding CPT1a and CPT2 were preserved at the levels of rats fed control protein diets.

  13. Medium-chain triglyceride feeding in premature infants: effects on fat and nitrogen absorption.

    PubMed

    Tantibhedhyangkul, P; Hashim, S A

    1975-03-01

    The effect of medium-chain triglycerides (MCT) on the "physiological" steatorrhea of prematurity was studied in 34 infants with birthweights below 2,000 gm. The infants were divided into three groups and fed three formulas identical in nutrient content except for the type of fat, as follows: group 1 (control): corn oil, oleo, and coconut oil (39:41:20); group 2: MCT, corn oil, and coconut oil (40:40:20); group 3: MCT and corn oil (80:20). The infants fed MCT-containing formulas had striking diminution in stool volume and frequency. Their total fat absorption was significantly improved when compared with controls; nitrogen absorption was slightly but significantly improved in the 80% MCT group. The results also suggest that nitrogen sparing may be enhanced in premature infants fed MCT-containing formulas.

  14. Medium Chain Triglycerides enhances exercise endurance through the increased mitochondrial biogenesis and metabolism

    PubMed Central

    Han, Yi; Xu, Jiping; Li, Zhaoshen

    2018-01-01

    Medium Chain Triglycerides (MCT) is a dietary supplement and usually used along with medications for treating food absorption disorders including diarrhea, steatorrhea and liver disease. It has been shown that MCT plays a role in lowering weight, and decreasing metabolic syndrome, abdominal obesity and inflammation. However, it is still unknown whether MCT enhances exercise endurance. Here, we demonstrated that MCT containing diet improves high temperature induced exercise performance impairment. We found that MCT up-regulates the expression and protein levels of genes involved in mitochondrial biogenesis and metabolism. Further investigation demonstrated that the increased mitochondrial biogenesis and metabolism is mediated through the activation of Akt and AMPK signaling pathways and inhibition of TGF-β signaling pathway. Collectively, our findings indicate a beneficial effect of dietary MCT in exercise performance through the increase of mitochondrial biogenesis and metabolism. PMID:29420554

  15. Medium Chain Triglycerides enhances exercise endurance through the increased mitochondrial biogenesis and metabolism.

    PubMed

    Wang, Ying; Liu, Zhenzhen; Han, Yi; Xu, Jiping; Huang, Wen; Li, Zhaoshen

    2018-01-01

    Medium Chain Triglycerides (MCT) is a dietary supplement and usually used along with medications for treating food absorption disorders including diarrhea, steatorrhea and liver disease. It has been shown that MCT plays a role in lowering weight, and decreasing metabolic syndrome, abdominal obesity and inflammation. However, it is still unknown whether MCT enhances exercise endurance. Here, we demonstrated that MCT containing diet improves high temperature induced exercise performance impairment. We found that MCT up-regulates the expression and protein levels of genes involved in mitochondrial biogenesis and metabolism. Further investigation demonstrated that the increased mitochondrial biogenesis and metabolism is mediated through the activation of Akt and AMPK signaling pathways and inhibition of TGF-β signaling pathway. Collectively, our findings indicate a beneficial effect of dietary MCT in exercise performance through the increase of mitochondrial biogenesis and metabolism.

  16. Medium-chain triglycerides are advantageous in promoting weight loss although not beneficial to exercise performance.

    PubMed

    Clegg, Miriam E

    2010-11-01

    Medium-chain triglycerides (MCT) are triglycerides with a fatty acid chain length varying between 6 and 10 carbon atoms. MCT differ from long-chain triglycerides as they are relatively soluble in water and, hence, rapidly hydrolysed and absorbed. MCT are transported in the blood through the portal system, consequently they bypass adipose tissue that makes them less susceptible to hormone-sensitive lipase and deposition into adipose tissue stores. Due to these properties, MCT have been researched for both benefits to exercise performance and health. The present review aims to assess whether MCT are beneficial in either of these situations. MCT have been proposed as a means to maximizing an athlete's ability to maintain their glycogen stores so they can be more competitive. However, only two studies to date have shown an improvement in exercise performance. From a health perspective, MCT increase fat oxidation and energy expenditure as well as reduce food intake and beneficially alter body composition. Results indicate that MCT feeding is ineffective in improving exercise performance and future work should focus on the health benefits and applications of MCT.

  17. Medium-chain triglyceride feeding in premature infants: effects on calcium and magnesium absorption.

    PubMed

    Tantibhedhyangkul, P; Hashim, S A

    1978-04-01

    The effect of medium-chain triglycerides (MCT) on the absorption of calcium and magnesium in premature infants was studied in 34 infants with birth weights lower than 2,000 gm. The infants were divided into three groups and fed three formulas similar in nutrient content except for the type of fat, as follows: group 1 (control): corn oil, oleo, and coconut oil (39:41:20); group 2: MCT, corn oil, and coconut oil (40:40:20); group 3: MCT and corn oil (80:20). The infants fed MCT-containing formulas absorbed significantly more calcium than the control group. Magnesium absorption was significantly increased in the 80% MCT group.

  18. Glycogen storage disease type 1: impact of medium-chain triglycerides on metabolic control and growth.

    PubMed

    Das, Anibh M; Lücke, Thomas; Meyer, Uta; Hartmann, Hans; Illsinger, Sabine

    2010-01-01

    Hypoketotic hypoglycaemia and hypertriglyceridaemia are biochemical hallmarks of glycogen storage disease (GSD) 1. Increased malonyl coenzyme A production which compromises oxidation of long-chain fatty acids via carnitine palmitoyltransferase (CPT) 1 inhibition plays a crucial role in the pathogenesis of these complications. Therapy consists primarily of nutritional support including frequent carbohydrate-rich meals. We studied the effect of a diet enriched in medium-chain triglycerides (MCT) on metabolic control/growth in GSD 1 as medium-chain fatty acids can be oxidised independently of CPT 1. An adult female, a 1.6-year-old boy with GSD 1a and a 6.5-year-old girl with GSD 1b treated with a classical GSD diet were enrolled; their 'classical GSD diet' was supplemented with MCT fats. Concentrations of glucose, lactate, ketone bodies triglycerides, uric acid, acylcarnitines in blood and organic acids in urine were determined. No clinical or biochemical side-effects were observed. The MCT diet led to a decrease in uric acid concentrations in all patients. Triglyceride levels were reduced only in the youngest patient, while lactate concentrations did not significantly decrease. The MCT diet allowed for a reduction in carbohydrate and caloric intake required to maintain euglycaemia and led to improvement in growth in the two prepubertal patients. MCT supplementation had a positive effect on metabolic control and growth in our patients suffering from GSD 1. (c) 2010 S. Karger AG, Basel.

  19. 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

  20. 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.

  1. Cellular and physiological effects of medium-chain triglycerides.

    PubMed

    Wanten, Geert J; Naber, Anton H

    2004-10-01

    From a nutritional standpoint, saturated triglycerides with a medium (6 to 12) carbon chain length (MCT) have traditionally been regarded as biologically inert substances, merely serving as a source of fuel calories that is relatively easily accessible for metabolic breakdown compared with long chain triglycerides (LCT). This quality of MCT has been shown to offer both benefits and risks depending on the clinical situation, with potential positive effects on protein metabolism in some studies on one side, and an increased risk for ketogenesis and metabolic acidosis on the other. At another level, studies regarding lipid effects of MCT on the immune system, as with LCT, so far have yielded equivocal results, although there is a recent experimental evidence to suggest that MCT possess immune modulating properties and should in fact be regarded as bioactive mediators. Most of this information comes from studies where effects of MCT have been compared with those of LCT in lipid emulsions, as part of parenteral (intravenous) nutrition formulations. Unfortunately, the relevance of these observations for clinical practice remains largely unclear because adequately powered trials that clearly point out the position of MCT in relation to structurally different lipids have not been performed. In the present paper we review the experimental and clinical evidence for cellular and physiological effects of nutritional MCT. In addition, studies describing possible mechanisms behind the observed effects of MCT will be discussed.

  2. 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.

  3. Protective Effects of Medium-Chain Triglycerides on the Liver and Gut in Rats Administered Endotoxin

    PubMed Central

    Kono, Hiroshi; Fujii, Hideki; Asakawa, Masami; Yamamoto, Masayuki; Matsuda, Masanori; Maki, Akira; Matsumoto, Yoshiro

    2003-01-01

    Objective To determine if medium-chain triglycerides (MCTs) prevent organ injuries and mortality in rats administered endotoxin and to investigate effects of MCT on the gut. Summary Background Data Since dietary MCTs prevent alcohol-induced liver injury by inhibiting activation of Kupffer cells in the enteral feeding model, the authors hypothesized that MCT could prevent deleterious conditions in endotoxemia. Methods After a preliminary experiment determined the optimal dose of MCT, rats were given MCT (5 g/kg per day) or the same dose of corn oil by gavage daily for 1 week. Then, lipopolysaccharide (LPS) was administered intravenously and survival was assessed for the next 24 hours. For analysis of mechanisms, rats were killed 9 hours after LPS injection and serum and liver sections were collected. To investigate effects of MCT on the gut, pathologic change, permeability, and microflora were assessed. Kupffer cells isolated by collagenase digestion and differential centrifugation were used for endotoxin receptor CD14 immunoblotting, phagocytic index, and TNF-α production assay. Results All rats given corn oil died after LPS administration; however, this mortality was prevented by MCT in a dose-dependent manner. Rats given corn oil showed liver injury after LPS administration. In contrast, MCT prevented this pathologic change nearly completely. MCT blunted CD14 expression on the Kupffer cells and TNF-α production by isolated Kupffer cells; however, there were no differences in phagocytic index between the two groups. The length of the intestinal epithelium was increased in the MCT group compared to the corn oil group. Further, after LPS administration, increases in gut permeability and injury were prevented by MCT. Importantly, MCT also prevented hepatic energy charge and gut injuries in this condition. Conclusions Enteral feeding using MCT could be a practical way of protecting the liver and intestine during endotoxemia. PMID:12560783

  4. Evidence for medium chain triglycerides in the treatment of primary intestinal lymphangiectasia.

    PubMed

    Desai, A P; Guvenc, B H; Carachi, R

    2009-08-01

    Primary intestinal lymphangiectasia is an uncommon congenital anomaly. It is an intrinsic abnormality of the intestinal lymphatics system. Over the years, various treatment options such as diuretics, albumin transfusions and a medium chain triglycerides (MCT) diet as well as surgical options such as resection of isolated segments and peritoneal-venous shunts have been used. An MCT diet, which is a low fat, high protein diet, is increasingly used in the management of this anomaly. The aim was to review the evidence for medium chain triglycerides as a therapeutic option in patients with primary intestinal lymphangiectasia. A literature search was performed and individual case details were extracted. We found 55 cases, of which 3 were from our own institute. The cases were divided in 2 groups: Group A (n=27) consisted of patients treated with MCT, and Group B (n=28) consisted patients not treated with MCT. Cases were analysed for symptomatic response to MCT as well as mortality. 17 of 27 cases (63%) treated with MCT had complete resolution of symptoms while only 10 of 28 (35.7%) patients in group B showed complete resolution. Mortality for Group A was 1 out of 27 (3.7%), while mortality in group B was 5 of 28 (17.85%) patients. We conclude that, although an MCT diet is not completely curative in all cases, it does improve the symptoms of primary intestinal lymphangiectasia and reduces mortality. Hence it is a valid option in the paediatric age group. Copyright Georg Thieme Verlag KG Stuttgart . New York.

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

    PubMed Central

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

    1993-01-01

    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

  6. 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

  7. The addition of medium-chain triglycerides to a purified fish oil-based diet alters inflammatory profiles in mice.

    PubMed

    Carlson, Sarah J; Nandivada, Prathima; Chang, Melissa I; Mitchell, Paul D; O'Loughlin, Alison; Cowan, Eileen; Gura, Kathleen M; Nose, Vania; Bistrian, Bruce R; Puder, Mark

    2015-02-01

    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. 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. 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. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Ketogenic Medium Chain Triglycerides Increase Brain Energy Metabolism in Alzheimer's Disease.

    PubMed

    Croteau, Etienne; Castellano, Christian-Alexandre; Richard, Marie Anne; Fortier, Mélanie; Nugent, Scott; Lepage, Martin; Duchesne, Simon; Whittingstall, Kevin; Turcotte, Éric E; Bocti, Christian; Fülöp, Tamàs; Cunnane, Stephen C

    2018-06-09

    In Alzheimer's disease (AD), it is unknown whether the brain can utilize additional ketones as fuel when they are derived from a medium chain triglyceride (MCT) supplement. To assess whether brain ketone uptake in AD increases in response to MCT as it would in young healthy adults. Mild-moderate AD patients sequentially consumed 30 g/d of two different MCT supplements, both for one month: a mixture of caprylic (55%) and capric acids (35%) (n = 11), followed by a wash-out and then tricaprylin (95%; n = 6). Brain ketone (11C-acetoacetate) and glucose (FDG) uptake were quantified by PET before and after each MCT intervention. Brain ketone consumption doubled on both types of MCT supplement. The slope of the relationship between plasma ketones and brain ketone uptake was the same as in healthy young adults. Both types of MCT increased total brain energy metabolism by increasing ketone supply without affecting brain glucose utilization. Ketones from MCT compensate for the brain glucose deficit in AD in direct proportion to the level of plasma ketones achieved.

  9. Emulsification Increases the Acute Ketogenic Effect and Bioavailability of Medium-Chain Triglycerides in Humans

    PubMed Central

    Courchesne-Loyer, Alexandre; Lowry, Carolyn-Mary; St-Pierre, Valérie; Vandenberghe, Camille; Fortier, Mélanie; Castellano, Christian-Alexandre; Wagner, J Richard; Cunnane, Stephen C

    2017-01-01

    Abstract Background: Lower-brain glucose uptake is commonly present before the onset of cognitive deterioration associated with aging and may increase the risk of Alzheimer disease. Ketones are the brain's main alternative energy substrate to glucose. Medium-chain triglycerides (MCTs) are rapidly β-oxidized and are ketogenic but also have gastrointestinal side effects. We assessed whether MCT emulsification into a lactose-free skim-milk matrix [emulsified MCTs (MCT-Es)] would improve ketogenesis, reduce side effects, or both compared with the same oral dose of MCTs consumed without emulsification [nonemulsified MCTs (MCT-NEs)]. Objectives: Our aims were to show that, in healthy adults, MCT-Es will induce higher ketonemia and have fewer side effects than MCT-NEs and the effects of MCT-NEs and MCT-Es on ketogenesis and plasma medium-chain fatty acids (MCFAs) will be dose-dependent. Methods: Using a metabolic study day protocol, 10 healthy adults were each given 3 separate doses (10, 20, or 30 g) of MCT-NEs or MCT-Es with a standard breakfast or no treatment [control (CTL)]. Blood samples were taken every 30 min for 4 h to measure plasma ketones (β-hydroxybutyrate and acetoacetate), octanoate, decanoate, and other metabolites. Participants completed a side-effects questionnaire at the end of each study day. Results: Compared with CTL, MCT-NEs increased ketogenesis by 2-fold with no significant differences between doses. MCT-Es increased total plasma ketones by 2- to 4-fold in a dose-dependent manner. Compared with MCT-NEs, MCT-Es increased plasma MCFA bioavailability (F) by 2- to 3-fold and decreased the number of side effects by ∼50%. Conclusions: Emulsification increased the ketogenic effect and decreased side effects in a dose-dependent manner for single doses of MCTs ≤30 g under matching conditions. Further investigation is needed to establish whether emulsification could sustain ketogenesis and minimize side effects and therefore be used as a treatment to

  10. Effect of medium-chain triglycerides on the release behavior of Endostar encapsulated PLGA microspheres.

    PubMed

    Meng, Boyu; Li, Ling; Hua, Su; Wang, Qingsong; Liu, Chunhui; Xu, Xiangyang; Yin, Xiaojin

    2010-09-15

    The incomplete release of Endostar from PLGA microspheres was observed in our previous study. In the present study, we focused on the effect of medium-chain triglycerides (MCT) on the in vitro/in vivo release behavior of Endostar encapsulated PLGA microspheres, which were prepared by a water-in-oil-in-water (W/O/W) double-emulsion method with or without MCT. The in vitro accumulated release of Endostar from microspheres co-encapsulated with 30% MCT was found to be 79.04% after a 30-day incubation period in PBS (pH 7.4) at 37 degrees C. However, the accumulated release of Endostar from MCT-free microspheres was found to be only 32.22%. Pouches containing Endostar encapsulated PLGA microspheres were implanted subcutaneously in rats. The effect of MCT on the in vivo release showed a similar trend to the in vitro release. After 30 days, only 9.87% of the total encapsulated Endostar was retained in microspheres co-encapsulated with 30% MCT, while 42.25% of Endostar was retained in MCT-free microspheres. The co-encapsulation of MCT provided the microspheres with a porous surface, which significantly improved the in vitro/in vivo release of Endostar from PLGA microspheres. In addition, in vitro experiments showed that MCT co-encapsulated PLGA microspheres had more inter-connected pores, faster degradation of PLGA, and faster swelling of microspheres, which helped to explain the mechanism of the effect of MCT on improving the release of Endostar from PLGA microspheres. Copyright 2010 Elsevier B.V. All rights reserved.

  11. Coconut oil has less satiating properties than medium chain triglyceride oil.

    PubMed

    Kinsella, R; Maher, T; Clegg, M E

    2017-10-01

    It is well established that the consumption of medium-chain triglycerides (MCT) can increase satiety and reduce food intake. Many media articles promote the use of coconut oil for weight loss advocating similar health benefits to that of MCT. The aim of this study was to examine the effect of MCT oil compared to coconut oil and control oil on food intake and satiety. Following an overnight fast, participants consumed a test breakfast smoothie containing 205kcal of either (i) MCT oil (ii) coconut oil or (iii) vegetable oil (control) on three separate test days. Participants recorded appetite ratings on visual analogue scales and were presented with an ad libitum lunch meal of preselected sandwiches 180min after consumption of the breakfast. The results showed a significant difference in energy and macronutrient intakes at the ad libitum meal between the three oils with the MCT oil reducing food intake compared to the coconut and control oil. Differences in food intake throughout the day were found for energy and fat, with the control having increased food intake compared to the MCT and coconut. The MCT also increased fullness over the three hours after breakfast compared to the control and coconut oils. The coconut oil was also reported as being less palatable than the MCT oil. The results of this study confirm the differences that exist between MCT and coconut oil such that coconut oil cannot be promoted as having similar effects to MCT oil on food intake and satiety. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  12. Aversion of the cat to dietary medium-chain triglycerides and caprylic acid.

    PubMed

    MacDonald, M L; Rogers, Q R; Morris, J G

    1985-09-01

    Young, specific-pathogen-free cats were fed purified diets containing different sources of fat. Food intake was depressed and cats lost weight when the diet contained either hydrogenated coconut oil (HCO) or medium-chain triglycerides (MCT). With an MCT preparation enriched in 8:0 (MCT8), cats would not eat after first tasting the diet. When cats were offered a choice of two high-fat diets, they chose the basal diet over a diet containing 30% HCO, by a ratio of 4.5:1. Low levels of MCT8 (5% or 10% by weight) were also rejected, whereas cats did not reject 5% or 15% MCT12. Caprylic acid, at 0.1-1.0% of the diet, was rejected. In other studies, food intake and body weight decreased when HCO was added to a fat-free diet. Cats fed 25% or 35% HCO lost weight. When 5% safflower seed oil was added to the HCO diets, body weights and food intake improved, but were still less than optimal. These studies indicate that the food intake depression in cats fed dietary HCO and MCT is primarily a result of impalatability, and that the fatty acid moiety may be responsible for the aversion.

  13. Energy metabolism of medium-chain triglycerides versus carbohydrates during exercise.

    PubMed

    Décombaz, J; Arnaud, M J; Milon, H; Moesch, H; Philippossian, G; Thélin, A L; Howald, H

    1983-01-01

    Medium-chain triglycerides (MCT) are known to be rapidly digested and oxidized. Their potential value as a source of dietary energy during exercise was compared with that of maltodextrins (MD). Twelve subjects exercised for 1 h on a bicycle ergometer (60% VO2 max), 1 h after the test meal (1MJ). The metabolism of MCT was followed using 1-13C-octanoate (Oc) as tracer and U-13C-glucose (G) was added to the 13C-naturally enriched MD. After MCT ingestion no insulin peak was observed with some accumulation of ketone bodies (KB), blood levels not exceeding 1 mM. Total losses of KB during exercise in urine, sweat and as breath acetone were small (less than 0.2 mmol X h-1). Hence, the influence of KB loss and storage on gas exchange data was negligible. The partition of fat and carbohydrate utilization during exercise as obtained by indirect calorimetry was practically the same after the MCT and the CHO meals. Oxidation over the 2-h period was 30% of dose for Oc and 45% for G. Glycogen decrements in the Vastus lateralis muscle were equal. It appears that with normal carbohydrate stores, a single meal of MCT or CHO did not alter the contribution of carbohydrates during 1 h of high submaximal exercise. The moderate ketonemia after MCT, despite substantial oxidation of this fat, led to no difference in muscle glycogen sparing between the diets.

  14. Influence of medium-chain triglycerides on lipid metabolism in the chick.

    PubMed

    Leveille, G A; Pardini, R S; Tillotson, J A

    1967-11-01

    The effect of corn oil, coconut oil, and medium-chain triglyceride (MCT, a glyceride mixture consisting almost exclusively of fatty acids of 8 and 10 carbons in length) ingestion on lipid metabolism was studied in chicks. In chicks fed cholesterol-free diets, MCT ingestion elevated plasma total lipids and cholesterol and depressed liver total lipids and cholesterol when compared to chicks receiving the corn oil diet. As a consequence of the opposite effects of MCT ingestion on plasma and liver cholesterol and total lipids, the plasma-liver cholesterol pool was not altered. When cholesterol was included in the diets, dietary MCT depressed liver and plasma total lipids and cholesterol as compared with corn oil, consequently also lowered the plasmaliver cholesterol pool.The in vitro cholesterol and fatty acid synthesis from acetate-1-(14)C was higher in liver slices from chicks fed MCT than in those from chicks fed corn oil. The percentage of radioactivity from acetate-1-(14)C incorporated into the carboxyl carbon of fatty acids by liver slices was not altered by MCT feeding, indicating that the increased acetate incorporation represented de novo fatty acid synthesis. The conversion of palmitate-1-(14)C to C(18) acids was increased in liver of chicks fed MCT, implying that fatty acid chain elongating activity was also increased. Studies on the conversion of stearate-2-(14)C to mono- and di-unsaturated C(18) acids showed that hepatic fatty acid desaturation activity was enhanced by MCT feeding. Data are presented on the plasma and liver fatty acid composition of chicks fed MCT-, corn oil-, or coconut oil-supplemented diets.

  15. Influence of medium-chain triglycerides on lipid metabolism in the rat.

    PubMed

    Leveille, G A; Pardini, R S; Tillotson, J A

    1967-07-01

    Lipid metabolism was studied in rats fed diets containing corn oil, coconut oil, or medium-chain triglyceride (MCT), a glyceride mixture containing fatty acids of 8 and 10 carbons in length. The ingestion of MCT-supplemented, cholesterolfree diets depressed plasma and liver total lipids and cholesterol as compared with corn oil-supplemented diets. In rats fed cholesterol-containing diets, plasma cholesterol levels were not influenced by dietary MCT, but liver cholesterol levels were significantly lower than in animals fed corn oil. In vitro cholesterol synthesis from acetate-1-(14)C was lower in liver slices of rats that consumed MCT than in similar preparations from corn oil-fed rats. Studies of fatty acid carboxyl labeling from acetate-1-(14)C and the conversion of palmitate-1-(14)C to C(18) acids by liver slices showed that chain-lengthening activity is greater in the liver tissue of rats fed MCT than in the liver of animals fed corn oil. The hepatic fatty acid desaturation mechanisms, evaluated by measuring the conversion of stearate-2-(14)C to oleate, was also enhanced by feeding MCT.Adipose tissue of rats fed MCT converts acetate-1-(14)C to fatty acids at a much faster rate than does tissue from animals fed corn oil. Evidence is presented to show that the enhanced incorporation of acetate into fatty acids by the adipose tissue of rats fed MCT represents de novo synthesis of fatty acids and not chain-lengthening activity. Data are also presented on the fatty acid composition of plasma, liver, and adipose tissue lipids of rats fed the different fats under study.

  16. Dietary Supplementation with Medium-Chain Triglycerides Reduces Candida Gastrointestinal Colonization in Preterm Infants.

    PubMed

    Arsenault, Amanda B; Gunsalus, Kearney T W; Laforce-Nesbitt, Sonia S; Przystac, Lynn; DeAngelis, Erik J; Hurley, Michaela E; Vorel, Ethan S; Tucker, Richard; Matthan, Nirupa R; Lichtenstein, Alice H; Kumamoto, Carol A; Bliss, Joseph M

    2018-03-24

    Candida is an important cause of infections in premature infants. Gastrointestinal colonization with Candida is a common site of entry for disseminated disease. The objective of this study was to determine whether a dietary supplement of medium-chain triglycerides (MCTs) reduces Candida colonization in preterm infants. Preterm infants with Candida colonization (n=12) receiving enteral feedings of either infant formula (n=5) or breastmilk (n=7) were randomized to MCT supplementation (n=8) or no supplementation (n=4). Daily stool samples were collected to determine fungal burden during a 3 week study period. Infants in the MCT group received supplementation during 1 week of the study period. The primary outcome was fungal burden during the supplementation period as compared to the periods before and after supplementation. Supplementation of MCT led to a marked increase in MCT intake relative to unsupplemented breast milk or formula as measured by capric acid content. In the treatment group, there was a significant reduction in fungal burden during the supplementation period as compared to the period before supplementation (RR = 0.15, p = 0.02), with a significant increase after supplementation was stopped (RR = 61, p < 0.001). Fungal burden in the control group did not show similar changes. Dietary supplementation with MCT may be an effective method to reduce Candida colonization in preterm infants.

  17. Medium-chain, triglyceride-containing lipid emulsions increase human neutrophil beta2 integrin expression, adhesion, and degranulation.

    PubMed

    Wanten, G J; Geijtenbeek, T B; Raymakers, R A; van Kooyk, Y; Roos, D; Jansen, J B; Naber, A H

    2000-01-01

    To test the hypothesis that lipid emulsions with different triglyceride structures have distinct immunomodulatory properties, we analyzed human neutrophil adhesion and degranulation after lipid incubation. Neutrophils, isolated from the blood of 10 healthy volunteers, were incubated in medium or physiologic (2.5 mmol/L) emulsions containing long-chain (LCT), medium-chain (MCT), mixed LCT/MCT, or structured (SL) triglycerides. Expression of adhesion molecules and degranulation markers was evaluated by flow cytometry. Also, functional adhesion was investigated by means of a flow cytometric assay using fluorescent beads coated with the integrin ligand intercellular adhesion molecule (ICAM)-1. Although LCT and SL had no effect, LCT/MCT significantly increased expression of the beta2 integrins lymphocyte-function-associated antigen 1 (+18%), macrophage antigen 1 (+387%), p150,95 (+82%), and (alphaDbeta2 (+230%). Degranulation marker expression for azurophilic (CD63, +210%) and specific granules (CD66b, +370%) also significantly increased, whereas L-selectin (CD62L, -70%) decreased. The effects of LCT/MCT were mimicked by the MCT emulsion. ICAM-1 adhesion (% beads bound) was increased by LCT/MCT (34% +/- 4%), whereas LCT (19% +/-3%) and SL (20% +/- 2%) had no effect compared with medium (17% +/- 3%). LCT/MCT and MCT, contrary to LCT and SL emulsions, increased neutrophil beta2 integrin expression, adhesion, and degranulation. Apart from other emulsion constituents, triglyceride chain length might therefore be a key feature in the interaction of lipid emulsions and the phagocyte immune system.

  18. Effects of medium-chain triglycerides, long-chain triglycerides, or 2-monododecanoin on fatty acid composition in the portal vein, intestinal lymph, and systemic circulation in rats.

    PubMed

    You, Yi-Qian Nancy; Ling, Pei-Ra; Qu, Jason Zhensheng; Bistrian, Bruce R

    2008-01-01

    Fatty acid absorption patterns can have a major impact on the fatty acid composition in the portal, intestinal lymph, and systemic circulation. This study sought to determine the effects of long-chain triglycerides (LCT), medium-chain triglycerides (MCT), and 2-monododecanoin (2mono) on intestinal fatty acid composition during continuous feeding over a brief period. The lipid sources were 100% LCT, 100% MCT, a 50:50 mixture of LCT and MCT (LCT/MCT), and a 50:50 mixture of LCT and 2mono (LCT/2mono). A total of 27 rats were randomly given 1 of the 4 diets at 200 kcal/kg/d, with 30% of total calories from lipids over 3 hours. MCT significantly increased each of the medium-chain fatty acids (C6:0, C8:0, and C10:0) as free fatty acids in the portal vein and about 10%/mol of C10:0 as triglycerides in the lymph compared with the other groups. There was significantly less C10:0 in lymphatic triglycerides with LCT/MCT than with MCT, but more than in the LCT and LCT/2mono diets. MCT also significantly increased the contents of C16:0, C18:0, C18:1, and C20:4 in the lymphatic triglycerides compared with all other groups including LCT/MCT. The amount of linoleic acid (C18:2) in lymphatic triglycerides followed the relative amounts of this fatty acid in the diet, with the greatest in LCT followed by LCT/MCT and LCT/2mono and least in MCT. A so-called structured lipid composed of the medium-chain fatty acid dodecanoic acid on the 2 position and long-chain fatty acids on the 1 and 3 positions appeared to be endogenously synthesized in response to the LCT/2mono diet. The original differences in MCT and LCT content in the diets were preserved in the fatty acid composition in the intestinal free fatty acids and triglycerides during feeding. In addition, the duration of lipid administration can play a role in altering fatty acid composition in the intestine.

  19. Effects of Medium-Chain Triglycerides, Long-Chain Triglycerides, or 2-Monododecanoin on Fatty Acid Composition in the Portal Vein, Intestinal Lymph, and Systemic Circulation in Rats

    PubMed Central

    Nancy You, Yi-Qian; Ling, Pei-Ra; Qu, Jason Zhensheng; Bistrian, Bruce R.

    2011-01-01

    Background Fatty acid absorption patterns can have a major impact on the fatty acid composition in the portal, intestinal lymph, and systemic circulation. This study sought to determine the effects of long-chain triglycerides (LCT), medium-chain triglycerides (MCT), and 2-monododecanoin (2mono) on intestinal fatty acid composition during continuous feeding over a brief period. Methods The lipid sources were 100% LCT, 100% MCT, a 50:50 mixture of LCT and MCT (LCT/MCT), and a 50:50 mixture of LCT and 2mono (LCT/2mono). A total of 27 rats were randomly given 1 of the 4 diets at 200 kcal/kg/d, with 30% of total calories from lipids over 3 hours. Results MCT significantly increased each of the medium-chain fatty acids (C6:0, C8:0, and C10:0) as free fatty acids in the portal vein and about 10%/mol of C10:0 as triglycerides in the lymph compared with the other groups. There was significantly less C10:0 in lymphatic triglycerides with LCT/MCT than with MCT, but more than in the LCT and LCT/2mono diets. MCT also significantly increased the contents of C16:0, C18:0, C18:1, and C20:4 in the lymphatic triglycerides compared with all other groups including LCT/MCT. The amount of linoleic acid (C18:2) in lymphatic triglycerides followed the relative amounts of this fatty acid in the diet, with the greatest in LCT followed by LCT/MCT and LCT/2mono and least in MCT. A so-called structured lipid composed of the medium-chain fatty acid dodecanoic acid on the 2 position and long-chain fatty acids on the 1 and 3 positions appeared to be endogenously synthesized in response to the LCT/2mono diet. Conclusions The original differences in MCT and LCT content in the diets were preserved in the fatty acid composition in the intestinal free fatty acids and triglycerides during feeding. In addition, the duration of lipid administration can play a role in altering fatty acid composition in the intestine. PMID:18407910

  20. Dietary medium-chain triglycerides promote oral allergic sensitization and orally induced anaphylaxis to peanut protein in mice

    PubMed Central

    Li, Jianing; Wang, Yu; Tang, Lihua; de Villiers, Willem JS; Cohen, Donald; Woodward, Jerold; Finkelman, Fred D; Eckhardt, Erik RM

    2012-01-01

    BACKGROUND The prevalence of peanut allergies is rising. Peanuts and many other allergen sources contain significant amounts of triglycerides, which affect absorption of antigens but have unknown effects on sensitization and anaphylaxis. We recently reported that dietary medium-chain triglycerides (MCT), which bypass mesenteric lymph and directly enter portal blood, reduce intestinal antigen absorption into blood compared to long-chain triglycerides (LCT), which stimulate mesenteric lymph flow and are absorbed in chylomicrons via mesenteric lymph. OBJECTIVE Test how dietary MCT affect food allergy. METHODS C3H/HeJ mice were fed peanut butter protein in MCT, LCT (peanut oil), or LCT plus an inhibitor of chylomicron formation (Pluronic L81; “PL81”). Peanut-specific antibodies in plasma, responses of the mice to antigen challenges, and intestinal epithelial cytokine expression were subsequently measured. RESULTS MCT suppressed antigen absorption into blood, but stimulated absorption into Peyer's patches. A single gavage of peanut protein with MCT as well as prolonged feeding in MCT-based diets caused spontaneous allergic sensitization. MCT-sensitized mice experienced IgG-dependent anaphylaxis upon systemic challenge and IgE-dependent anaphylaxis upon oral challenge. MCT feeding stimulated jejunal-epithelial TSLP, IL-25 and IL-33 expression compared to LCT, and promoted Th2 cytokine responses in splenocytes. Moreover, oral challenges of sensitized mice with antigen in MCT significantly aggravated anaphylaxis compared to challenges with LCT. Importantly, effects of MCT could be mimicked by adding PL81 to LCT, and in vitro assays indicated that chylomicrons prevent basophil activation. CONCLUSION Dietary MCT promote allergic sensitization and anaphylaxis by affecting antigen absorption and availability and by stimulating Th2 responses. PMID:23182172

  1. Parenteral medium-chain triglyceride-induced neutrophil activation is not mediated by a Pertussis Toxin sensitive receptor.

    PubMed

    Versleijen, Michelle W J; van Esterik, Joantine C J; Roelofs, Hennie M J; van Emst-de Vries, Sjenet E; Willems, Peter H G M; Wanten, Geert J A

    2009-02-01

    Lipid-induced immune modulation might contribute to the increased infection rate that is observed in patients using parenteral nutrition. We previously showed that emulsions containing medium-chain triglycerides (LCT/MCTs or pure MCTs), but not pure long-chain triglycerides (LCTs), impair neutrophil functions, modulate cell-signaling and induce neutrophil activation in vitro. It has recently been shown that medium-chain fatty acids are ligands for GPR84, a pertussis toxin (PT)-sensitive G-protein-coupled receptor (GPCR). This finding urged us to investigate whether MCT-induced neutrophil activation is mediated by PT-sensitive GPCRs. Neutrophils isolated from blood of healthy volunteers were pre-incubated with PT (0.5-1 microg/mL, 1.5 h) and analyzed for the effect of this pre-incubation on LCT/MCT (2.5 mmol/L)-dependent modulation of serum-treated zymosan (STZ)-induced intracellular Ca(2+) mobilization and on LCT/MCT (5 mmol/L)-induced expression of cell surface adhesion (CD11b) and degranulation (CD66b) markers and oxygen radical (ROS) production. PT did not inhibit the effects of LCT/MCT on the STZ-induced increase in cytosolic free Ca(2+) concentration. LCT/MCT increased ROS production to 146% of unstimulated cells. However, pre-incubation with PT did not inhibit the LCT/MCT-induced ROS production. Furthermore, the LCT/MCT-induced increase in CD11b and CD66b expression (196% and 235% of unstimulated cells, respectively) was not inhibited by pre-incubation with PT. LCT/MCT-induced neutrophil activation does not involve the action of a PT-sensitive G-protein-coupled receptor.

  2. Endogenous fat oxidation during medium chain versus long chain triglyceride feeding in healthy women.

    PubMed

    Papamandjaris, A A; White, M D; Raeini-Sarjaz, M; Jones, P J

    2000-09-01

    To compare the effect of medium chain triglycerides (MCT) vs long chain triglycerides (LCT) feeding on exogenous and endogenous oxidation of long chain saturated fatty acids (LCSFA) in women. Twelve healthy female subjects (age 19-26 y, body mass index (BMI) 17.5-28.6 kg/m2) In a randomized cross-over design, subjects were fed weight maintenance diets providing 15%, 45% and 40% of energy as protein, carbohydrate and fat, respectively, with 80% of this fat comprising either a combination of butter and coconut oil (MCT) or beef tallow (LCT). Following 6 days of feeding, subjects were given daily oral doses of 1-(13)C labelled-myristic, -palmitic and -stearic acids for 8 days. Expired 13CO2 was used as an index of LCSFA oxidation with CO2 production assessed by respiratory gas exchange. No difference in exogenous LCSFA oxidation was observed as a function of diet on day 7. On day 14, greater combined cumulative fractional LCSFA oxidation (16.9 +/- 2.5%/5.5 h vs 9.1 +/- 1.2%/5.5 h, P < 0.007), net LCSFA oxidation (2956 +/- 413 mg/5.5 h vs 1669 +/- 224 mg/5.5 h, P < 0.01), and percentage dietary LCSFA contribution to total fat oxidation (16.3 +/- 2.3%/5.5 h vs 9.5 +/- 1.5%/5.5 h; P < 0.01) were observed in women fed the MCT vs LCT diet. With the MCT diet, but not the LCT diet, combined cumulative fractional LCSFA oxidation (P < 0.03), net LCSFA oxidation (P < 0.03), and percentage dietary LCSFA contribution to total fat oxidation (P < 0.02) were increased at day 14 as compared to day 7. Day 14 results indicated increased endogenous LCSFA oxidation during MCT feeding. The capacity of MCT to increase endogenous oxidation of LCSFA suggests a role for MCT in body weight control over the long term.

  3. Role of medium-chain triglycerides in the alcohol-mediated cytochrome P450 2E1 induction of mitochondria.

    PubMed

    Lieber, Charles S; Cao, Qi; DeCarli, Leonore M; Leo, Maria A; Mak, Ki M; Ponomarenko, Anatoly; Ren, Chaoling; Wang, Xiaolei

    2007-10-01

    Chronic alcohol consumption is known to induce cytochrome P450 2E1 (CYP2E1) leading to lipid peroxidation, mitochondrial dysfunction and hepatotoxicity. We showed that replacement of dietary long-chain triglycerides (LCT) by medium-chain triglycerides (MCT) could be protective. We now wondered whether the induction of mitochondrial CYP2E1 plays a role and whether liver injury could be avoided through mitochondrial intervention. Rats were fed 4 different isocaloric liquid diets. The control group received our standard dextrin-maltose diet with intake limited to the average consumption of the 3 alcohol groups fed ad libitum the alcohol containing Lieber-DeCarli liquid diet. The fat was either 32% of calories as LCT (alcohol), or 16% as LCT + 16% as MCT (alcohol-MCT 16%), or 32% as MCT only (alcohol-MCT 32%). After 21 days, compared to the controls, the alcohol and both alcohol-MCT groups had a significant increase in mitochondrial CYP2E1 (p < 0.05 for both). As shown before, the same was found for the microsomal CYP2E1. When MCT replaced all the fat, like in the alcohol-MCT 32% group, CYP2E1 was significantly reduced by 40% in mitochondria (p < 0.05) and 30% in microsomes (p < 0.01). In mitochondria, 4-hydroxynonenal (4-HNE), a parameter of oxidative stress, paralleled CYP2E1. Compared to controls, alcohol and alcohol-MCT 16% significantly raised mitochondrial 4-HNE (p < 0.001), whereas the alcohol-MCT 32% diet brought it down to control levels (p < 0.001). Mitochondrial reduced glutathione (GSH) was also significantly lowered by alcohol consumption (p < 0.05), and it increased to almost normal levels with alcohol-MCT 32% (p = 0.006). These changes in the mitochondria reflected the reduction observed in total liver in which alcohol-MCT 32% decreased the alcohol-induced steatosis with a diminution of triglycerides (p < 0.001) and of the pro-inflammatory cytokine tumor necrosis factor-alpha (p < 0.001). Mitochondria participate in the induction of CYP2E1 by alcohol and

  4. Effects of dietary medium-chain triglycerides on plasma lipids and lipoprotein distribution and food aversion in cats.

    PubMed

    Trevizan, Luciano; de Mello Kessler, Alexandre; Bigley, Karen E; Anderson, Wendy H; Waldron, Mark K; Bauer, John E

    2010-04-01

    To determine possible diet aversion and lipid and lipoprotein alterations in cats fed diets containing medium-chain triglycerides (MCTs). 19 clinically normal adult female cats. Cats were assigned to 2 groups (low MCT diet [n = 10] and high MCT diet [9]) and fed the diets for 9 weeks according to metabolic body weight (100 kcal of metabolizable energy [ME] x kg(-0.67)/d). Daily consumption records and weekly body weight and body condition score (BCS) were used to adjust amounts fed and calculate daily ME factors for each cat to maintain ideal BCS. Blood samples were obtained after withholding food on days 0, 14, 28, and 56 for measurement of plasma triglyceride and total cholesterol concentrations and lipoprotein-cholesterol distributions. Repeated-measures ANOVA and Tukey multiple comparison tests were performed. No diet differences were found for food consumption, body weight, BCS, and ME factors. A significant increase in plasma triglyceride concentration was detected for the high MCT diet; however, values were within the reference ranges. No diet effects were observed for total cholesterol concentrations or lipoprotein-cholesterol distributions, although increases over time were observed. Inclusion of MCT in diets of cats did not result in feed refusal and had minimal effects on lipid metabolism. Such diets may be useful for both clinically normal cats and cats with metabolic disorders. The MCT oils are an example of a bioactive dietary lipid that may benefit feline metabolism and can serve as a useful functional food ingredient for cats.

  5. 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)

  6. Randomized clinical trial of new intravenous lipid (SMOFlipid 20%) versus medium-chain triglycerides/long-chain triglycerides in adult patients undergoing gastrointestinal surgery.

    PubMed

    Wu, Ming-Hsun; Wang, Ming-Yang; Yang, Chin-Yao; Kuo, Min-Liang; Lin, Ming-Tsan

    2014-09-01

    SMOFlipid 20% is intravenous lipid emulsion (ILE) containing long-chain triglycerides (LCT), medium-chain triglycerides (MCT), olive oil, and fish oil as a mixed emulsion containing α-tocopherol. The aim was to assess the efficacy of this new ILE in gastrointestinal surgery compared with MCT/LCT. In this prospective study, 40 patients were randomized to SMOFlipid 20% or MCT/LCT (Lipovenoes 20%) group. Clinical and biochemistry data were collected. Inflammatory markers (CRP, IL-6, IL-10, TNF-α, TGF-β1) and oxidative stress (ROS and superoxide) were measured. Thirty-five patients (17 males and 18 females) with a mean age of 57 years completed the study. The patients' demographic characteristics (age, gender, height, body weight, and BMI) were similar without significant differences between groups. The increment of triglyceride on day 6 from baseline was significantly lower in SMOFlipid group than in Lipovenoes MCT/LCT group. Inflammatory markers, as well as superoxide radical and total oxygen radical were not different between groups. Despite the comparable effect on inflammatory response, because of its well-balanced fatty acid pattern, relatively low n-6:n-3 ratio, and high vitamin E content, SMOFlipid had a better triglyceride-lowering effect as compared with MCT/LCT in adult patients undergoing gastrointestinal surgery. © 2013 American Society for Parenteral and Enteral Nutrition.

  7. Dietary medium-chain triglycerides promote oral allergic sensitization and orally induced anaphylaxis to peanut protein in mice.

    PubMed

    Li, Jianing; Wang, Yu; Tang, Lihua; de Villiers, Willem J S; Cohen, Donald; Woodward, Jerold; Finkelman, Fred D; Eckhardt, Erik R M

    2013-02-01

    The prevalence of peanut allergies is increasing. Peanuts and many other allergen sources contain significant amounts of triglycerides, which affect absorption of antigens but have unknown effects on sensitization and anaphylaxis. We recently reported that dietary medium-chain triglycerides (MCTs), which bypass mesenteric lymph and directly enter portal blood, reduce intestinal antigen absorption into blood compared with long-chain triglycerides (LCTs), which stimulate mesenteric lymph flow and are absorbed in chylomicrons through mesenteric lymph. We sought to test how dietary MCTs affect food allergy. C3H/HeJ mice were fed peanut butter protein in MCT, LCT (peanut oil), or LCT plus an inhibitor of chylomicron formation (Pluronic L81). Peanut-specific antibodies in plasma, responses of the mice to antigen challenges, and intestinal epithelial cytokine expression were subsequently measured. MCT suppressed antigen absorption into blood but stimulated absorption into Peyer patches. A single gavage of peanut protein with MCT, as well as prolonged feeding in MCT-based diets, caused spontaneous allergic sensitization. MCT-sensitized mice experienced IgG-dependent anaphylaxis on systemic challenge and IgE-dependent anaphylaxis on oral challenge. MCT feeding stimulated jejunal-epithelial thymic stromal lymphopoietin, Il25, and Il33 expression compared with that seen after LCT feeding and promoted T(H)2 cytokine responses in splenocytes. Moreover, oral challenges of sensitized mice with antigen in MCT significantly aggravated anaphylaxis compared with challenges with the LCT. Importantly, the effects of MCTs could be mimicked by adding Pluronic L81 to LCTs, and in vitro assays indicated that chylomicrons prevent basophil activation. Dietary MCTs promote allergic sensitization and anaphylaxis by affecting antigen absorption and availability and by stimulating T(H)2 responses. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All

  8. Dietary medium-chain triglycerides prevent chemically induced experimental colitis in rats.

    PubMed

    Kono, Hiroshi; Fujii, Hideki; Ishii, Kenichi; Hosomura, Naohiro; Ogiku, Masahito

    2010-03-01

    The effects of dietary medium-chain triglycerides (MCTs) on experimental colitis induced by 2,4,6-trinitrobenzene sulphonic acid (TNBS) were investigated in rats. Male Wistar rats were given an intracolonic injection of TNBS and were then fed liquid diets containing MCTs or corn oil (AIN93) as controls. Serum and tissue samples were collected 1 week after TNBS enema. The severity of colitis was evaluated pathologically, and tissue myeloperoxidase (MPO) activity was measured. Furthermore, messenger RNA (mRNA) and protein levels for inflammatory cytokines and a chemokine were assessed by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. In another set of experiments, the protein expression of Toll-like receptor (TLR)-4 in the colon was measured 1 week after feeding of liquid diets. To investigate the effects of MCTs on macrophages, RAW246.7 macrophages were incubated with media containing albumin conjugated with MCT or linoleic acid, which is the major component of corn oil. Then, the production of tumor necrosis factor-alpha (TNF-alpha) was measured. Dietary MCTs blunted significantly the protein levels of TLR-4 in the colon. Furthermore, the expression of TLR-4 was significantly blunted in RAW264.7 cells incubated with MCTs compared with cells incubated with linoleic acid. Induction of interleukin 1beta (IL-1beta), TNF-alpha, and macrophage inflammatory protein-2 (MIP-2) in the colon was attenuated by dietary MCT. Furthermore, MPO activities in the colonic tissue were significantly blunted in animals fed the MCT diets compared with those fed the control diets. As a result, dietary MCTs improved chemically induced colitis significantly. MCTs most likely are useful for the therapy of inflammatory bowel disease as an anti-inflammatory immunomodulating nutrient. Copyright 2010 Mosby, Inc. All rights reserved.

  9. 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.

  10. Disrupted fat distribution and composition due to medium-chain triglycerides in mice with a β-oxidation defect.

    PubMed

    Tucci, Sara; Flögel, Ulrich; Sturm, Marga; Borsch, Elena; Spiekerkoetter, Ute

    2011-08-01

    Because of the enhanced recognition of inherited long-chain fatty acid oxidation disorders by worldwide newborn screening programs, an increasing number of asymptomatic patients receive medium-chain triglyceride (MCT) supplements to prevent the development of cardiomyopathy and myopathy. MCT supplementation has been recognized as a safe dietary intervention, but long-term observations into later adulthood are still not available. We investigated the consequences of a prolonged MCT diet on abdominal fat distribution and composition and on liver fat. Mice with very-long-chain acyl-coenzyme A dehydrogenase deficiency (VLCAD(-/-)) were supplemented for 1 y with a diet in which MCTs replaced long-chain triglycerides without increasing the total fat content. The dietary effects on abdominal fat accumulation and composition were analyzed by in vivo (1)H- and (13)C-magnetic resonance spectroscopy (9.4 Tesla). After 1 y of MCT supplementation, VLCAD(-/-) mice accumulated massive visceral fat and had a dramatic increase in the concentration of serum free fatty acids. Furthermore, we observed a profound shift in body triglyceride composition, ie, concentrations of physiologically important polyunsaturated fatty acids dramatically decreased. (1)H-Magnetic resonance spectroscopy analysis and histologic evaluation of the liver also showed pronounced fat accumulation and marked oxidative stress. Although the MCT-supplemented diet has been reported to prevent the development of cardiomyopathy and skeletal myopathy in fatty acid oxidation disorders, our data show that long-term MCT supplementation results in a severe clinical phenotype similar to that of nonalcoholic steatohepatitis and the metabolic syndrome.

  11. Medium-chain triglycerides impair lipid metabolism and induce hepatic steatosis in very long-chain acyl-CoA dehydrogenase (VLCAD)-deficient mice.

    PubMed

    Tucci, Sara; Primassin, Sonja; Ter Veld, Frank; Spiekerkoetter, Ute

    2010-09-01

    A medium-chain-triglyceride (MCT)-based diet is mainstay of treatment in very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD), a long-chain fatty acid beta-oxidation defect. Beneficial effects have been reported with an MCT-bolus prior to exercise. Little is known about the impact of a long-term MCT diet on hepatic lipid metabolism. Here we investigate the effects of MCT-supplementation on liver and blood lipids in the murine model of VLCADD. Wild-type (WT) and VLCAD-knock-out (KO) mice were fed (1) a long-chain triglyceride (LCT)-diet over 5weeks, (2) an MCT diet over 5 weeks and (3) an LCT diet plus MCT-bolus. Blood and liver lipid content were determined. Expression of genes regulating lipogenesis was analyzed by RT-PCR. Under the LCT diet, VLCAD-KO mice accumulated significantly higher blood cholesterol concentrations compared to WT mice. The MCT-diet induced severe hepatic steatosis, significantly higher serum free fatty acids and impaired hepatic lipid mobilization in VLCAD-KO mice. Expression at mRNA level of hepatic lipogenic genes was up-regulated. The long-term MCT diet stimulates lipogenesis and impairs hepatic lipid metabolism in VLCAD-KO mice. These results suggest a critical reconsideration of a long-term MCT-modified diet in human VLCADD. In contrast, MCT in situations of increased energy demand appears to be a safer treatment alternative.

  12. Enteral diets enriched with medium-chain triglycerides and N-3 fatty acids prevent chemically induced experimental colitis in rats.

    PubMed

    Kono, Hiroshi; Fujii, Hideki; Ogiku, Masahito; Tsuchiya, Masato; Ishii, Kenichi; Hara, Michio

    2010-11-01

    The specific purpose of this study was to evaluate the significant effects of medium-chain triglycerides (MCTs) and N-3 fatty acids on chemically induced experimental colitis induced by 2,4,6-trinitrobenzene sulphonic acid (TNBS) in rats. Male Wistar rats were fed liquid diets enriched with N-6 fatty acid (control diets), N-3 fatty acid (MCT- diets), and N-3 fatty acid and MCT (MCT+ diets) for 2 weeks and then were given an intracolonic injection of TNBS. Serum and tissue samples were collected 5 days after ethanol or TNBS enema. The severity of colitis was evaluated pathologically, and tissue myeloperoxidase activity was measured in colonic tissues. Furthermore, protein levels for inflammatory cytokines and a chemokine were assessed by an enzyme-linked immunosorbent assay in colonic tissues. Induction of proinflammatory cytokines tumor necrosis factor-α and interleukin-1β in the colon by TNBS enema was markedly attenuated by the MCT+ diet among the 3 diets studied. Furthermore, the induction of chemokines macrophage inflammatory protein-2 and monocyte chemotactic protein-1 also was blunted significantly in animals fed the MCT+ diets. As a result, MPO activities in the colonic tissue also were blunted significantly in animals fed the MCT+ diets compared with those fed the control diets or the MCT- diets. Furthermore, the MCT+ diet improved chemically induced colitis significantly among the 3 diets studied. Diets enriched with both MCTs and N-3 fatty acids may be effective for the therapy of inflammatory bowel disease as antiinflammatory immunomodulating nutrients. Copyright © 2010 Mosby, Inc. All rights reserved.

  13. Influence of the dietary intake of medium chain triglycerides on body composition, energy expenditure and satiety: a systematic review.

    PubMed

    Rego Costa, A C; Rosado, E L; Soares-Mota, M

    2012-01-01

    Increased prevalence of obesity is associated with the growth of chronic degenerative diseases. One of the main factors associated with this increase is the change in nutritional status of individuals. Medium chain triglycerides (MCT) are rapidly metabolized and less stored in the adipose tissue, being a possible tool for weight control. In order to analyze the influence of consumption of this lipid on satiety, body composition and energy expenditure (EE), a literature review was performed of controlled clinical studies reported in PUBMED and ELSEVIER between the years 2000 and 2010. Fourteen articles were selected presenting short and long-term intervention. Among these, six showed a decrease in body mass of individuals, with consequent loss of weight. Only one showed a positive effect on satiation and four showed an increase in EE. Thus the results are inconclusive and there is a need for further controlled studies with standardized amounts of MCT, so that its use can become an alternative for obesity nutritional treatment.

  14. A comparison of long-chain triglycerides and medium-chain triglycerides on weight loss and tumour size in a cachexia model.

    PubMed Central

    Tisdale, M. J.; Brennan, R. A.

    1988-01-01

    A comparison has been made between the ability of long-chain triglycerides (LCT) and medium-chain triglycerides (MCT) to prevent weight loss induced by the cachexia-inducing colon adenocarcinoma (MAC16) and to reduce tumour size. There was no difference in calorie consumption or nitrogen intake between the various groups. When compared with a normal control high carbohydrate, low fat diet, animals fed MCT showed a reduced weight loss and a marked reduction in tumour size. In contrast neither weight loss nor tumour size differed significantly from the controls in animals fed the LCT diet. An elevated plasma level of 3-hydroxybuturate was found only in the animals fed the MCT diets. Administration of LCT caused an increase in the plasma level of FFA, which was not observed in the MCT group. These results suggest that diets containing MCT would provide the best ketogenic regime to reverse the weight loss in cancer cachexia with a concomitant reduction in tumour size. PMID:3219268

  15. Structural aspects of digestion of medium chain triglycerides studied in real time using sSAXS and Cryo-TEM.

    PubMed

    Phan, Stephanie; Hawley, Adrian; Mulet, Xavier; Waddington, Lynne; Prestidge, Clive A; Boyd, Ben J

    2013-12-01

    The purpose of this study was to investigate the colloidal structures formed on digestion of medium chain triglyceride (MCT) with a specific objective of identifying and characterizing a previously reported vesicular phase, which has been linked to supersaturation and anomalous digestion kinetics, and to evaluate the influence of lipid mass and enzyme inhibition on self assembled structure. MCT was digested in vitro and nanostructure was monitored in real time using synchrotron small angle X-ray scattering (sSAXS), and morphology was studied using cryogenic transmission electron microscopy (cryo-TEM). Formation of the putative vesicular phase formed on digestion of MCT was confirmed and its structural attributes were determined. Vesicle formation was dependent on lipid mass and bile salt concentration. The use of enzyme inhibitor for offline analysis of lipolysis samples did influence structural aspects of the digestion medium when compared to real time evaluation. The formation of a vesicular phase was directly linked to the kinetics of lipid digestion. Vesicle formation is linked to lipid mass, or more specifically the ratio of lipid to bile salts present in the digestion mixture. Inhibition of lipase to halt digestion during sampling for offline analysis must be done with caution as structural aspects were shown to differ for the MCT digests with and without inhibitor present.

  16. Immune activation by medium-chain triglyceride-containing lipid emulsions is not modulated by n-3 lipids or toll-like receptor 4.

    PubMed

    Olthof, Evelyn D; Gülich, Alexandra F; Renne, Mike F; Landman, Sija; Joosten, Leo A B; Roelofs, Hennie M J; Wanten, Geert J A

    2015-10-01

    Saturated medium-chain triglycerides (MCT) as part of the parenteral lipid regimen (50% MCT and 50% long chain triglycerides (LCT)) activate the immune system in vitro. Fish oil (FO)-derived n-3 fatty acids (FA) inhibit saturated FA-induced immune activation via a toll-like receptor (TLR)-4 mediated mechanism. We hypothesized that effects of parenteral MCTs on immune cells involve TLR-4 signaling and that these effects are modulated by n-3 FA that are present in FO. To test this hypothesis we assessed effects of addition of various commercially available mixed parenteral lipid emulsions, n-3 FA and of TLR-4 inhibition on MCT-induced human immune cell activation by evaluation of the expression of leukocyte membrane activation markers and reactive oxygen species (ROS) production. All MCT-containing lipid emulsions activated leukocytes by inducing changes in expression of membrane markers and stimulus induced ROS production, whereas MCT-free lipid emulsions lacked this effect. Moreover, addition of n-3 FA to LCT/MCT did not prevent MCT-induced immune activation. TLR-4 inhibitors did not distinctly modulate MCT-induced changes in immune function. Taken together, these findings suggest that leukocyte activation by parenteral MCTs does not involve TLR-4 signaling and is not modulated by n-3 FA in FO-, but is exerted via different signaling pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Medium-chain triglyceride ameliorates insulin resistance and inflammation in high fat diet-induced obese mice.

    PubMed

    Geng, Shanshan; Zhu, Weiwei; Xie, Chunfeng; Li, Xiaoting; Wu, Jieshu; Liang, Zhaofeng; Xie, Wei; Zhu, Jianyun; Huang, Cong; Zhu, Mingming; Wu, Rui; Zhong, Caiyun

    2016-04-01

    The aim of the present study was to investigate the in vivo effects of dietary medium-chain triglyceride (MCT) on inflammation and insulin resistance as well as the underlying potential molecular mechanisms in high fat diet-induced obese mice. Male C57BL/6J mice (n = 24) were fed one of the following three diets for a period of 12 weeks: (1) a modified AIN-76 diet with 5 % corn oil (normal diet); (2) a high-fat control diet (17 % w/w lard and 3 % w/w corn oil, HFC); (3) an isocaloric high-fat diet supplemented with MCT (17 % w/w MCT and 3 % w/w corn oil, HF-MCT). Glucose metabolism was evaluated by fasting blood glucose levels and intraperitoneal glucose tolerance test. Insulin sensitivity was evaluated by fasting serum insulin levels and the index of homeostasis model assessment-insulin resistance. The levels of serum interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α were measured by ELISA, and hepatic activation of nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways was determined using western blot analysis. Compared to HFC diet, consumption of HF-MCT did not induce body weight gain and white adipose tissue accumulation in mice. HFC-induced increases in serum fasting glucose and insulin levels as well as glucose intolerance were prevented by HF-MCT diet. Meanwhile, HF-MCT resulted in significantly lower serum IL-6 level and higher IL-10 level, and lower expression levels of inducible nitric oxide synthase and cyclooxygenase-2 protein in liver tissues when compared to HFC. In addition, HF-MCT attenuated HFC-triggered hepatic activation of NF-κB and p38 MAPK. Our study demonstrated that MCT was efficacious in suppressing body fat accumulation, insulin resistance, inflammatory response, and NF-κB and p38 MAPK activation in high fat diet-fed mice. These data suggest that MCT may exert beneficial effects against high fat diet-induced insulin resistance and inflammation.

  18. Nutritional and physiological role of medium-chain triglycerides and medium-chain fatty acids in piglets.

    PubMed

    Zentek, J; Buchheit-Renko, S; Ferrara, F; Vahjen, W; Van Kessel, A G; Pieper, R

    2011-06-01

    Medium-chain fatty acids (MCFAs) are found at higher levels in milk lipids of many animal species and in the oil fraction of several plants, including coconuts, palm kernels and certain Cuphea species. Medium-chain triglycerides (MCTs) and fatty acids are efficiently absorbed and metabolized and are therefore used for piglet nutrition. They may provide instant energy and also have physiological benefits beyond their energetic value contributing to several findings of improved performance in piglet-feeding trials. MCTs are effectively hydrolyzed by gastric and pancreatic lipases in the newborn and suckling young, allowing rapid provision of energy for both enterocytes and intermediary hepatic metabolism. MCFAs affect the composition of the intestinal microbiota and have inhibitory effects on bacterial concentrations in the digesta, mainly on Salmonella and coliforms. However, most studies have been performed in vitro up to now and in vivo data in pigs are still scarce. Effects on the gut-associated and general immune function have been described in several animal species, but they have been less studied in pigs. The addition of up to 8% of a non-esterified MCFA mixture in feed has been described, but due to the sensory properties this can have a negative impact on feed intake. This may be overcome by using MCTs, allowing dietary inclusion rates up to 15%. Feeding sows with diets containing 15% MCTs resulted in a lower mortality of newborns and better development, particularly of underweight piglets. In conclusion, MCFAs and MCTs offer advantages for the improvement of energy supply and performance of piglets and may stabilize the intestinal microbiota, expanding the spectrum of feed additives supporting piglet health in the post-weaning period.

  19. Effects of medium-chain triglycerides on intestinal morphology and energy metabolism of intrauterine growth retarded weanling piglets.

    PubMed

    Zhang, Li-Li; Zhang, Hao; Li, Yue; Wang, Tian

    2017-06-01

    It has been shown that there is a relationship between intrauterine growth retardation (IUGR) and postnatal intestinal damage involved in energy deficits. Therefore, the present study was conducted to investigate the effect of medium-chain triglycerides (MCT) on the intestinal morphology, intestinal function and energy metabolism of piglets with IUGR. At weaning (21 ± 1.1 d of age), 24 IUGR piglets and 24 normal birth weight (NBW) piglets were selected according to their birth weights (BW) (IUGR: 0.95 ± 0.04 kg BW; NBW: 1.58 ± 0.04 kg BW) and their weights at the time of weaning (IUGR: 5.26 ± 0.15 kg BW; NBW: 6.98 ± 0.19 kg BW). The piglets were fed a diet of either long-chain triglycerides (LCT) (containing 5% LCT) or MCT (containing 1% LCT and 4% MCT) for 28 d. Then, the piglets' intestinal morphology, biochemical parameters and mRNA abundance related to intestinal damage and energy metabolism were determined. IUGR was found to impair intestinal morphology, with evidence of decreased villus height and increased crypt depth; however, these negative effects of IUGR were ameliorated by MCT treatment. IUGR piglets showed compromised intestinal digestion and absorption functions when compared with NBW piglets. However, feeding MCT increased the maltase activity in the jejunum and alleviated IUGR-induced reductions in plasma d-xylose concentrations and jejunal sucrase activity. IUGR decreased the efficiency of the piglets' intestinal energy metabolism; however, piglets fed an MCT diet exhibited increased adenosine triphosphate (ATP) concentrations and ATP synthase F1 complex beta polypeptide expression, as well as decreased adenosine monophosphate-activated kinase alpha 1 expression in the jejunum of piglets. In addition, up-regulation of the piglets' citrate synthase and succinate dehydrogenase levels was found to occur following MCT treatment at both the activity and the transcriptional levels of the jejunum. Therefore, it can be postulated that

  20. Sustained enrichment of liver phospholipids and triglycerides in eicosapentaenoate after a bolus intravenous injection of a medium-chain triglycerides:fish oil emulsion to streptozotocin (Type 1) and Goto-Kakizaki (Type 2) diabetic rats.

    PubMed

    Carpentier, Yvon A; Fontaine, David; Otto, Anne; Portois, Laurence; Fontaine, Jeanine; Malaisse, Willy J

    2006-04-01

    This study deals with the sustained enrichment of liver phospholipids and triglycerides in long-chain polyunsaturated omega3 fatty acids (omega3) found after the bolus intravenous injection of a novel medium-chain triglyceride:fish oil emulsion (MCT:FO) to streptozotocin (Type 1) and Goto-Kakizaki (Type 2) diabetic rats. Twenty hours after injection of the MCT:FO emulsion, the relative concentration of omega3 was indeed higher in liver phospholipids and triglycerides than that found in rats injected with either saline or a control medium-chain triglyceride:long-chain triglyceride emulsion. This coincided with a decrease in the ponderal percentage of C18:3omega3, C20:4omega6 and/or C22:4omega6 in liver triglycerides. The present study further documents differences between streptozotocin-induced and Goto-Kakizaki diabetic rats in terms of body weight, glycemia, liver triglyceride content and the fatty acid pattern of both liver phospholipids and triglycerides, as well as a close correlation in the latter animals between liver and plasma phospholipids or triglycerides as far as the ratio in the relative concentration of selected fatty acids representative of desaturase and elongase activities is concerned. In light of these and previous findings, it is proposed that the beneficial metabolic and functional events of the MCT:FO emulsion may display not solely a rapid but also sustained time course.

  1. Stimulation of insulin secretion by medium-chain triglycerides in patients with cirrhosis 1

    PubMed Central

    McCullough, Frank S.; Tzagournis, Manuel; Greenberger, Norton J.; Linscheer, Willem G.

    1971-01-01

    Oral medium-chain triglycerides were given to 10 normal volunteers, 12 cirrhotics (group I) without and 28 cirrhotics (group II) with abnormal portal systemic communications (ascites, splenomegaly, oesophageal varices, or surgically-created portacaval shunts). After 30 ml of medium-chain triglyceride oil there was no appreciable change in serum glucose levels in any of the three groups nor in serum insulin levels in the normals and in cirrhotics in group I. However, there was a significant increase in serum insulin levels in the cirrhotic patients in group II. It is suggested that the rise in serum insulin levels after medium-chain triglycerides noted in the cirrhotics with shunts is due to shunting of insulin-containing portal blood around the liver (anatomical shunts) and to a diminished hepatic cell mass capable of extracting insulin (functional shunt). This differential response of serum insulin levels to medium-chain triglycerides may prove to be of value in detecting the presence of abnormal portal systemic communications in cirrhotic patients. PMID:5548559

  2. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. The Effect of Lipid Emulsion on Pharmacokinetics of Bupivacaine in Rats: Long-Chain Triglyceride Versus Long- and Medium-Chain Triglyceride.

    PubMed

    Tang, Wan; Wang, Quanguang; Shi, Kejian; Dong, Jiaojiao; Lin, Shengxian; Zhao, Shishi; Wu, Cong; Xia, Yun; Papadimos, Thomas J; Xu, Xuzhong

    2016-11-01

    Lipid infusions have been proposed to treat local anesthetic-induced cardiac toxicity. This study compared the effects of long-chain triglyceride (LCT) emulsions with those of long- and medium-chain triglyceride (LCT/MCT) emulsions on the pharmacokinetics of bupivacaine in a rat model. After administration of intravenous infusion of bupivacaine at 2 mg·kg·min for 5 minutes in Sprague-Dawley (SD) rats, either Intralipid 20%, an LCT emulsion (LCT group, n = 6), or Lipovenoes 20%, an LCT/MCT emulsion (LCT/MCT group, n = 6), was infused at 2mg·kg·min for 5 minutes. The concentrations of total plasma bupivacaine and bupivacaine that were not bound by lipid (lipid unbound) were measured by a liquid chromatography-tandem mass spectrometric method. A 2-compartmental analysis was performed to calculate the lipid-bound percentage of bupivacaine and its pharmacokinetics. In the LCT group, the clearance (15 ± 2 vs 10 ± 1 mL·min·kg, P = .003) was higher; the volume of distribution (0.57 ± 0.10 vs 0.36 ± 0.11 L·kg, P = .007) and K21 (0.0100 ± 0.0018 vs 0.0070 ± 0.0020 min, P = .021, P' = .032) were larger; and the area under the blood concentration-time curve 0 - t; (605 ± 82 vs 867 ± 110 mgL·min, P =.001) and the area under the blood concentration-time curve (0 - ∞) (697 ± 111 vs 991 ± 121 mgL·min, P =.001) were less, when compared with the LCT/MCT group. LCT emulsions are more effective than LCT/MCT emulsions in the metabolism of bupivacaine through demonstration of a superior pharmacokinetic profile.

  4. 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

  5. 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

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

    2016-01-01

    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. 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. 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. 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. 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 nutrition.

  6. Effect of two medium chain triglycerides-supplemented diets on synaptic morphology in the cerebellar cortex of late-adult rats.

    PubMed

    Balietti, Marta; Fattoretti, Patrizia; Giorgetti, Belinda; Casoli, Tiziana; Di Stefano, Giuseppina; Platano, Daniela; Aicardi, Giorgio; Lattanzio, Fabrizia; Bertoni-Freddari, Carlo

    2009-12-01

    Ketogenic diets (KDs) have shown beneficial effects in experimental models of neurodegeneration, designating aged individuals as possible recipients. However, few studies have investigated their consequences on aging brain. Here, late-adult rats (19 months of age) were fed for 8 weeks with two medium chain triglycerides-supplemented diets (MCT-SDs) and the average area (S), numeric density (Nv(s)), and surface density (S(v)) of synapses, as well as the average volume (V), numeric density (Nv(m)), and volume density (V(v)) of synaptic mitochondria were evaluated in granule cell layer of the cerebellar cortex (GCL-CCx) by computer-assisted morphometric methods. MCT content was 10 or 20%. About 10%MCT-SD induced the early appearance of senescent patterns (decreased Nv(s) and Nv(m); increased V), whereas 20%MCT-SD caused no changes. Recently, we have shown that both MCT-SDs accelerate aging in the stratum moleculare of CA1 (SM CA1), but are "antiaging" in the outer molecular layer of dentate gyrus (OML DG). Since GCL-CCx is more vulnerable to age than OML DG but less than SM CA1, present and previous results suggest that the effects of MCT-SDs in the aging brain critically depend on neuronal vulnerability to age, besides MCT percentage.

  7. 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.

  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. 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

    2016-05-12

    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.

  10. [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.

  11. Mechanisms of action for the medium-chain triglyceride ketogenic diet in neurological and metabolic disorders.

    PubMed

    Augustin, Katrin; Khabbush, Aziza; Williams, Sophie; Eaton, Simon; Orford, Michael; Cross, J Helen; Heales, Simon J R; Walker, Matthew C; Williams, Robin S B

    2018-01-01

    High-fat, low-carbohydrate diets, known as ketogenic diets, have been used as a non-pharmacological treatment for refractory epilepsy. A key mechanism of this treatment is thought to be the generation of ketones, which provide brain cells (neurons and astrocytes) with an energy source that is more efficient than glucose, resulting in beneficial downstream metabolic changes, such as increasing adenosine levels, which might have effects on seizure control. However, some studies have challenged the central role of ketones because medium-chain fatty acids, which are part of a commonly used variation of the diet (the medium-chain triglyceride ketogenic diet), have been shown to directly inhibit AMPA receptors (glutamate receptors), and to change cell energetics through mitochondrial biogenesis. Through these mechanisms, medium-chain fatty acids rather than ketones are likely to block seizure onset and raise seizure threshold. The mechanisms underlying the ketogenic diet might also have roles in other disorders, such as preventing neurodegeneration in Alzheimer's disease, the proliferation and spread of cancer, and insulin resistance in type 2 diabetes. Analysing medium-chain fatty acids in future ketogenic diet studies will provide further insights into their importance in modified forms of the diet. Moreover, the results of these studies could facilitate the development of new pharmacological and dietary therapies for epilepsy and other disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Humid Heat Autoclaving of Hybrid Nanoparticles Achieved by Decreased Nanoparticle Concentration and Improved Nanoparticle Stability Using Medium Chain Triglycerides as a Modifier.

    PubMed

    Gou, Jingxin; Chao, Yanhui; Liang, Yuheng; Zhang, Ning; He, Haibing; Yin, Tian; Zhang, Yu; Xu, Hui; Tang, Xing

    2016-09-01

    Humid heat autoclaving is a facile technique widely used in the sterilization of injections, but the high temperature employed would destroy nanoparticles composed of biodegradable polymers. The aim of this study was to investigate whether incorporation of medium chain triglycerides (MCT) could stabilize nanoparticles composed of poly (ethylene glycol)-b-polycaprolactone (PEG-b-PCL) during autoclaving (121°C, 10 min). Polymeric nanoparticles with different MCT contents were prepared by dialysis. Block copolymer degradation was studied by GPC. The critical aggregation concentrations of nanoparticles at different temperatures were determined using pyrene fluorescence. The size, morphology and weight averaged molecular weight of pristine/autoclaved nanoparticles were studied using DLS, TEM and SLS, respectively. Drug loading content and release profile were determined using RP-HPLC. The protecting effect of MCT on nanoparticles was dependent on the amount of MCT incorporated. Nanoparticles with high MCT contents, which assumed an emulsion-like morphology, showed reduced block copolymer degradation and particle disassociation after incubation at 100°C for 24 h. Nanoparticles with high MCT content showed the lowest critical aggregation concentration (CAC) under either room temperature or 60°C and the lowest particle concentration among all samples. And the particle size, drug loading content, physical stability and release profile of nanoparticles with high MCT contents remained nearly unchanged after autoclaving. Incorporation of high amount of MCT changed the morphology of PEG-b-PCL based nanoparticles to an emulsion-like structure and the nanoparticles prepared could withstand autoclaving due to improved particle stability and decreased particle concentration caused by MCT incorporation.

  13. Optimized self nano-emulsifying systems of ezetimibe with enhanced bioavailability potential using long chain and medium chain triglycerides.

    PubMed

    Bandyopadhyay, Shantanu; Katare, O P; Singh, Bhupinder

    2012-12-01

    The objective of the current work is to develop systematically optimized self-nanoemulsifying drug delivery systems (SNEDDS) using long chain triglycerides (LCT's) and medium chain triglycerides (MCT's) of ezetimibe employing Formulation by Design (FbD), and evaluate their in vitro and in vivo performance. Equilibrium solubility studies indicated the choice of Maisine 35-1 and Capryol 90 as lipids, and of Labrasol and Tween 80 as emulgents for formulating the LCT and MCT systems, respectively. Ternary phase diagrams were constructed to select the areas of nanoemulsion, and the amounts of lipid (X(1)) and emulgent (X(2)) as the critical factor variables. The SNEDDS were systematically optimized using 3(2) central composite design and the optimized formulations located using overlay plot. TEM studies on reconstituted SNEDDS demonstrated uniform shape and size of globules. The nanometer size range and high negative values of zeta potential depicted non-coalescent nature of the optimized SNEDDS. Thermodynamic studies, cloud point determination and accelerated stability studies ascertained the stability of optimized formulations. In situ perfusion (SPIP) studies in Sprague Dawley (SD) rats construed remarkable enhancement in the absorptivity and permeability parameters of SNEDDS vis-à-vis the conventional marketed product. In vivo pharmacodynamic studies in SD rats indicated significantly superior modification in plasma lipid levels of optimized SNEDDS vis-à-vis marketed product, inclusion complex and pure drug. The studies, therefore, indicate the successful formulation development of self-nanoemulsifying systems with distinctly improved bioavailability potential of ezetimibe. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  15. Dietary enrichment with medium chain triglycerides (AC-1203) elevates polyunsaturated fatty acids in the parietal cortex of aged dogs: implications for treating age-related cognitive decline.

    PubMed

    Taha, Ameer Y; Henderson, Samuel T; Burnham, W M

    2009-09-01

    Dogs demonstrate an age-related cognitive decline, which may be related to a decrease in the concentration of omega-3 polyunsaturated fatty acids (n-3 PUFA) in the brain. Medium chain triglycerides (MCT) increase fatty acid oxidation, and it has been suggested that this may raise brain n-3 PUFA levels by increasing mobilization of n-3 PUFA from adipose tissue to the brain. The goal of the present study was to determine whether dietary MCT would raise n-3 PUFA concentrations in the brains of aged dogs. Eight Beagle dogs were randomized to a control diet (n = 4) or an MCT (AC-1203) enriched diet (n = 4) for 2 months. The animals were then euthanized and the parietal cortex was removed for phospholipid, cholesterol and fatty acid determinations by gas-chromatography. Dietary enrichment with MCT (AC-1203) resulted in a significant increase in brain phospholipid and total lipid concentrations (P < 0.05). In particular, n-3 PUFA within the phospholipid, unesterified fatty acid, and total lipid fractions were elevated in AC-1203 treated subjects as compared to controls (P < 0.05). Brain cholesterol concentrations did not differ significantly between the groups (P > 0.05). These results indicate that dietary enrichment with MCT, raises n-3 PUFA concentrations in the parietal cortex of aged dogs.

  16. 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. © 2014 Japanese Society of Animal Science.

  17. Partial replacement of ω-6 fatty acids with medium-chain triglycerides, but not olive oil, improves colon cytokine response and damage in experimental colitis.

    PubMed

    Bertevello, Pedro L; De Nardi, Leticia; Torrinhas, Raquel S; Logullo, Angela F; Waitzberg, Dan L

    2012-07-01

    Soybean oil is rich in ω-6 fatty acids, which are associated with higher incidence and more severe cases of inflammatory bowel diseases. The authors evaluated whether partial replacement of soybean oil by medium-chain triglycerides (MCTs) or olive oil influenced the incidence and severity of experimental ulcerative colitis by using different parenteral lipid emulsions (LEs). Wistar rats (n = 40) were randomized to receive parenteral infusion of the following LE: 100% soybean oil (SO), 50% MCT mixed with 50% soybean oil (MCT/SO), 80% olive oil mixed with 20% soybean oil (OO/SO), or saline (CC). After 72 hours of infusion, acetic acid experimental colitis was induced. After 24 hours, colon histology and cytokine expression were analyzed. SO was not significantly associated with overall tissue damage. MCT/SO was not associated with necrosis (P < .005), whereas OO/SO had higher frequencies of ulcer and necrosis (P < .005). SO was associated with increased expression of interferon-γ (P = .005) and OO/SO with increased interleukin (IL)-6 and decreased tumor necrosis factor-α expression (P < .05). MCT/SO appeared to decrease IL-1 (P < .05) and increase IL-4 (P < .001) expression. Parenteral SO with high concentration of ω-6 fatty acids was not associated with greater tissue damage in experimental colitis. SO partial replacement with MCT/SO decreased the frequency of histological necrosis and favorably modulated cytokine expression in the colon; however, replacement with OO/SO had unfavorable effects.

  18. Medium-chain triglycerides in infant formulas and their relation to plasma ketone body concentrations.

    PubMed

    Wu, P Y; Edmond, J; Auestad, N; Rambathla, S; Benson, J; Picone, T

    1986-04-01

    A mild ketosis is known to prevail in the mother, fetus, and newborn infant during the 3rd trimester and in the early neonatal period. It has been shown that during an equivalent period in the rat ketone bodies are readily oxidized and serve as key substrates for lipogenesis in brain. Since medium-chain triglycerides are known to be ketogenic, preterm infants may benefit from dietary medium-chain triglycerides beyond the point of enhanced fat absorption. Our objective was to determine the ketogenic response in preterm infants (gestational age: 33 +/- 0.8 wk) fed three different isocaloric formulas by measuring the concentrations of 3-hydroxybutyrate and acetoacetate in the plasma of these infants. At the time of entrance to the study the infants were receiving 110 kcal/kg/24 h. Study I (11 infants): the infants were fed sequentially in the order; PM 60/40 (PM), Special Care Formula (SCF), and Similac 20 (SIM). In SCF greater than 50% of the fat consists of medium-chain length fatty acids while PM and SIM contain about 25%. The concentration of 3-hydroxybutyrate in plasma was significantly higher when infants were fed SCF than PM and SIM [0.14 +/- 0.03, 0.06 +/- 0.01, and 0.05 +/- 0.01 mM, respectively (p less than 0.01)]. Study II (12 infants); the infants were fed SCF, then SIM, or the reverse. The concentration of acetoacetate in plasma was 0.05 +/- 0.01 and 0.03 +/- 0.01 mM when infants were fed SCF and SIM, respectively (0.1 greater than p greater than 0.05). The concentrations of 3-hydroxybutyrate in plasma were similar to those measured in study I for the respective formulas.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Familial chylomicronemia syndrome and response to medium-chain triglyceride therapy in an infant with novel mutations in GPIHBP1.

    PubMed

    Ahmad, Zahid; Wilson, Don P

    2014-01-01

    Severe hypertriglyceridemia predisposes to attacks of acute pancreatitis, a serious condition complicated by multiorgan failure, pancreatic necrosis, and mortality rates up to 20% in adults and 6.5% in children. We describe an infant who suffered from an episode of acute pancreatitis from severe hypertriglyceridemia. Two major challenges complicate the case: identifying the etiology of severe hypertriglyceridemia and finding an efficacious treatment. A thorough history, physical examination, and laboratory workup failed to identify a clear etiology, prompting a genetic workup that identified compound heterozygous mutations in the glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) gene. This patient's hypertriglyceridemia responded to an infant formula rich in medium chain triglycerides (MCTs), and she remained free of pancreatitis 6 months later. This case highlights the need to pursue a genetic evaluation in the absence of secondary causes of severe hypertriglyceridemia in infants. Patients with mutations in GPIHBP1 fail to respond to currently available lipid-lowering agents so dietary management-specifically, an extremely low-fat diet and supplementation with MCT-remains the cornerstone of therapy. Treatment in infants should focus on dietary measures rather than pharmacologic agents. Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  20. 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.

  1. The safety of Lipistart, a medium-chain triglyceride based formula, in the dietary treatment of long-chain fatty acid disorders: a phase I study.

    PubMed

    MacDonald, Anita; Webster, Rachel; Whitlock, Matthew; Gerrard, Adam; Daly, Anne; Preece, Mary Anne; Evans, Sharon; Ashmore, Catherine; Chakrapani, Anupam; Vijay, Suresh; Santra, Saikat

    2018-03-28

    Children with long-chain fatty acid β-oxidation disorders (LCFAOD) presenting with clinical symptoms are treated with a specialist infant formula, with medium chain triglyceride (MCT) mainly replacing long chain triglyceride (LCT). It is essential that the safety and efficacy of any new specialist formula designed for LCFAOD be tested in infants and children. In an open-label, 21-day, phase I trial, we studied the safety of a new MCT-based formula (feed 1) in six well-controlled children (three male), aged 7-13 years (median 9 years) with LCFAOD (very long chain acyl CoA dehydrogenase deficiency [VLCADD], n=2; long chain 3-hydroxyacyl CoA dehydrogenase deficiency [LCHADD], n=2; carnitine acyl carnitine translocase deficiency [CACTD], n=2). Feed 1 (Lipistart; Vitaflo) contained 30% energy from MCT, 7.5% LCT and 3% linoleic acid and it was compared with a conventional MCT feed (Monogen; Nutricia) (feed 2) containing 17% energy from MCT, 3% LCT and 1.1% linoleic acid. Subjects consumed feed 2 for 7 days then feed 1 for 7 days and finally resumed feed 2 for 7 days. Vital signs, blood biochemistry, ECG, weight, height, food/feed intake and symptoms were monitored. Five subjects completed the study. Their median daily volume of both feeds was 720 mL (range 500-1900 mL/day). Feed 1 was associated with minimal changes in tolerance, free fatty acids (FFA), acylcarnitines, 3-hydroxybutyrate (3-HB), creatine kinase (CK), blood glucose, liver enzymes and no change in an electrocardiogram (ECG). No child complained of muscle pain or symptoms associated with LCFAOD on either feed. This is the first safety trial reported of an MCT formula specifically designed for infants and children with LCFAOD. In this short-term study, it appeared safe and well tolerated in this challenging group.

  2. Partial replacement of dietary (n-6) fatty acids with medium-chain triglycerides decreases the incidence of spontaneous colitis in interleukin-10-deficient mice.

    PubMed

    Mañé, Josep; Pedrosa, Elisabet; Lorén, Violeta; Ojanguren, Isabel; Fluvià, Lourdes; Cabré, Eduard; Rogler, Gerhard; Gassull, Miquel A

    2009-03-01

    Enteral nutrition has a primary therapeutic effect in active Crohn's disease. It is unknown which nutrient(s) account for this action, but a role for both the amount and type of dietary fat has been postulated. Some clinical and experimental data suggest that medium-chain triglycerides (MCT) may reduce intestinal inflammation. We aimed to assess the effect of replacing part of the dietary fat with MCT on the incidence and severity of colitis in interleukin (IL)-10(-/-) mice under specific pathogen-free conditions. Twenty-four IL-10(-/-) 4-wk-old mice were randomized to receive a control diet based on sunflower oil [(n-6) fatty acids (FA)] and an experimental isocaloric, isonitrogenous diet with 50% sunflower and 50% coconut oil (MCT diet). When the mice were 12 wk old, they were killed and the colon was examined for the presence of colitis, lymphocyte subpopulations and apoptosis, ex vivo cytokine production in supernatant of colon explants, toll-like receptor (TLR)-2 and TLR-9 mRNA, and FA profile in colonic tissue homogenates. Colitis incidence was lower in the IL-10(-/-) mice fed the MCT diet (1/12) than in the mice fed the control diet (8/12; P = 0.03). The histological damage score was also lower in the former (P < 0.0005). Feeding the MCT diet resulted in fewer total and apoptotic intraepithelial CD3+ and lamina propria CD3+CD4+ lymphocytes, as well as downregulated production of IL-6 and interferon-gamma, and reduced TLR-9 mRNA. We conclude that partial replacement of dietary (n-6) FA with MCT decreases the incidence of colitis in a model of spontaneous intestinal inflammation and provide experimental arguments for a possible primary therapeutic effect of MCT in human Crohn's disease.

  3. Preliminary study of the safety and efficacy of medium-chain triglycerides for use as an intraocular tamponading agent in minipigs.

    PubMed

    Soler, Vincent J; Laurent, Camille; Sakr, Frédéric; Regnier, Alain; Tricoire, Cyrielle; Cases, Olivier; Kozyraki, Renata; Douet, Jean-Yves; Pagot-Mathis, Véronique

    2017-08-01

    To date, only silicone oils and gases have the appropriate characteristics for use in vitreo-retinal surgery as vitreous substitutes with intraocular tamponading properties. This preliminary study evaluated the safety and efficacy of medium-chain triglycerides (MCTs) for use as a tamponading agent in minipigs. In 15 minipigs, 15 right eyes underwent vitrectomies followed by injection of MCT tamponade (day 1). Two groups were defined. In Group A (ten eyes), the surgical procedure before MCT injection included induced rhegmatogenous retinal detachment (RRD), retina flattening, and retinopexy. In Group B (five eyes), MCT was injected without inducing RRD; in these eyes, MCT was removed on day 90. Pigs were sacrificed on day 45 (Group A) or 120 (Group B). Eyes were examined on days 1, 5, 15, and 45 in both groups and on days 90 and 120 in Group B. In Group B only, we performed bilateral electroretinography examinations on days 1 and 120, and histological examinations of MCTs and controlateral eyes were performed after sacrifice. In Group A eyes (n = 9; one eye was non-assessable), on day 45, the retina was flat in seven eyes and two RRD detachments were observed in insufficiently MCT-filled eyes. In Group B, electroretinography showed no significant differences between MCT eyes and controls on days 1 or 120. Histological analyses revealed no signs of retinal toxicity. This study showed that MCT tamponade seems to be effective and safe; however, additional studies are needed before it becomes commonly used as a tamponading agent in humans.

  4. Safety of medium-chain triglycerides used as an intraocular tamponading agent in an experimental vitrectomy model rabbit.

    PubMed

    Auriol, Sylvain; Mahieu, Laurence; Brousset, Pierre; Malecaze, François; Mathis, Véronique

    2013-01-01

    To evaluate safety of medium-chain triglycerides used as a possible intraocular tamponading agent. A 20-gauge pars plana vitrectomy was performed in the right eye of 28 rabbits. An ophthalmologic examination was performed every week until rabbits were killed. At days 7, 30, 60, and 90, rabbits were killed and the treated eyes were examined macroscopically and prepared for histologic examination. Principal outcome was retinal toxicity evaluated by light and electron microscopy, and secondary outcomes were the presence of medium-chain triglyceride emulsification, inflammatory reactions, and the development of cataract. Histologic examination did not reveal any retinal toxicity. Two cases of moderate emulsification were observed, but in these cases, emulsification was caused by the perioperative injection of the agent and did not increase during the postoperative period. We noted 13 cases of inflammatory reaction in vitreous cavity and no case of inflammatory reaction in anterior chamber. Two eyes developed cataract as a result of perioperative trauma to the lens with the vitreous cutter and not secondary to the presence of medium-chain triglycerides in the vitreous cavity. Medium-chain triglycerides did not induce morphologic evidence of retinal toxicity. The results suggest that medium-chain triglycerides could be a promising alternative intraocular tamponading agent for the treatment of retinal detachments.

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

    PubMed

    Silverman, Julian R; John, George

    2015-12-09

    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.

  6. 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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Caprylic acid and medium-chain triglycerides inhibit IL-8 gene transcription in Caco-2 cells: comparison with the potent histone deacetylase inhibitor trichostatin A

    PubMed Central

    Hoshimoto, Aihiro; Suzuki, Yasuo; Katsuno, Tatsuro; Nakajima, Hiroshi; Saito, Yasushi

    2002-01-01

    Medium-chain triglyceride (MCT) is often administered to patients with Crohn's disease (CD) or short-bowel syndrome. However, little is known about the effects of medium-chain fatty acids (MCFAs) and MCT on intestinal inflammation. In this study we examined whether caprylic acid, one of the MCFAs, and MCT suppress IL-8 secretion by differentiated Caco-2 cells.We found for the first time that caprylic acid and MCT suppress IL-8 secretion by Caco-2 cells at the transcriptional level when precultured together for 24 h. We also tried to clarify the mechanism of IL-8 gene inhibition by examining the activation of NF-κB and other transcription factors by electrophoretic mobility shift assay (EMSA), and found that caprylic acid did not modulate their activation.The result of dual-luciferase assay using Caco-2 cells transfected with IL-8 promoter/luciferase reporter plasmid revealed that caprylic acid inhibited the activation of IL-8 promoter.Similar results were observed when cells were precultured with the well-known potent histone deacetylase inhibitor trichostatin A (TSA).We examined the state of H4 acetylation in IL-8 promoter using the technique known as chromatin immunoprecipitation (Chr-IP). TSA rapidly induced H4 acetylation in IL-8 promoter chromatin, whereas caprylic acid did not. These results suggest that the inhibition of IL-8 gene transcription induced by caprylic acid and TSA does not necessarily require the marked suppression of transcription factors, and the mechanism of inhibition of IL-8 gene transcription may be different between caprylic acid and TSA. PMID:12010777

  8. High-oil-load encapsulation of medium-chain triglycerides and D-limonene mixture in modified starch by spray drying.

    PubMed

    Paramita, Vita; Furuta, Takeshi; Yoshii, Hidefumi

    2012-02-01

    Oil mixtures of medium-chain triglycerides (MCT) and D-limonene in mixing ratios from 10 to 100 wt% were encapsulated in modified starch (wall material) by spray drying to produce oil-rich powders. The oil load (mass ratio of oil mixture to wall material) of the infeed emulsion markedly influenced the properties of the infeed liquid and the characteristics of the resulting powder. The viscosity of the infeed liquid and the particle size of the powder exponentially decreased with increasing oil load, while the emulsion droplet size in the infeed liquid increased. In addition, retention of D-limonene during spray drying also decreased markedly with increasing oil load. Irrespective of the different oil loads and concentrations of the wall material, D-limonene retention was well correlated with the emulsion droplet diameter of the infeed liquid. The encapsulation efficiency of the oil mixture exhibited a maximum value (almost 100%) at an oil load between 0.5 and 1.0, before decreasing at higher oil loads. At an oil load of 2.0, the encapsulation efficiency of D-limonene was reduced to almost zero, while around 40% of the initial MCT was encapsulated in the powder. The increase in oil load also led to increased amounts of surface oil of MCT and D-limonene in the resulting powder due to the increasing emulsion droplet diameter of the infeed liquids. This study proposes the microencapsulation of medium-chain triglycerides under high-oil-load conditions by spray drying. The powders prepared by this process provide significant benefits in terms of rapid energy conversion after consumption without accumulation in the body. Important quality factors of the powder products such as the encapsulation efficiency and the amount of surface oil were examined to understand the optimum process conditions for spray drying. © 2012 Institute of Food Technologists®

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

    PubMed

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

    2014-11-01

    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.

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

    PubMed

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

    2014-01-01

    Medium chain triglycerides (MCTs) are used to treat neurologic disorders with metabolic impairments, including childhood epilepsy and early Alzheimer's disease. However, the metabolic effects of MCTs in the brain are still unclear. Here, we studied the effects of feeding even and uneven MCTs on brain glucose metabolism in the mouse. Adult mice were fed 35% (calories) of trioctanoin or triheptanoin (the triglycerides of octanoate or heptanoate, respectively) or a matching control diet for 3 weeks. Enzymatic assays and targeted metabolomics by liquid chromatography tandem mass spectrometry were used to quantify metabolites in extracts from the hippocampal formations (HFs). Both oils increased the levels of 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.

  11. 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

  12. Nonclinical safety and pharmacokinetics of Miglyol 812: A medium chain triglyceride in exenatide once weekly suspension.

    PubMed

    Buss, Nicholas; Ryan, Patricia; Baughman, Todd; Roy, Denis; Patterson, Claire; Gordon, Carolyn; Dixit, Rakesh

    2018-05-28

    Exenatide, a glucagon-like peptide-1 receptor agonist was originally developed as either a twice daily or once weekly injectable therapeutic for patients with type 2 diabetes. Exenatide QW suspension was developed for use with an autoinjector device, in which the microspheres are suspended in Miglyol 812, a mixture of medium chain triglycerides (MCTs). MCTs are a class of lipids whose fatty acid chains contain from six to 12 carbon atoms (medium chain fatty acids or MCFAs). While MCTs are edible oils present in many foods, including foodstuffs containing coconut and palm kernel oils, limited information is available regarding the oral and subcutaneous bioavailability of MCTs as well as safety following subcutaneous injection. These studies were designed to investigate the non-clinical pharmacokinetics and safety of MCTs. In a single dose pharmacokinetic study, MCFAs were rapidly detected in the plasma of rats following oral administration of either Miglyol 812 or tricaprylin at doses of 10 or 9.48 g kg -1 , respectively. Following subcutaneous dosing with Miglyol 812, MCFAs were rapidly absorbed with a similar profile to that following oral dosing. Furthermore, the toxicity of Miglyol 812 alone was evaluated in a 3 month repeat dose toxicology studies in cynomolgus monkeys. In this study, weekly subcutaneous doses of 0.15 g kg -1 did not elicit any treatment-related effects in cynomolgus monkeys. In conclusion, these studies alongside the available literature data show that Miglyol 812 is a safe excipient for use in subcutaneously administered therapeutics. Copyright © 2018 John Wiley & Sons, Ltd.

  13. 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.

  14. 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

  15. Evaluation of various extracted vegetable oils, roasted soybeans, medium-chain triglyceride and an animal-vegetable fat blend for postweaning swine.

    PubMed

    Cera, K R; Mahan, D C; Reinhart, G A

    1990-09-01

    A total of 280 crossbred pigs weaned at 21 d of age and weighing approximately 6 kg were utilized in five replicates to evaluate pig growth responses when fed a basal diet or one of several dietary lipid sources during a 4-wk postweaning period. A basal corn-soybean meal-corn starch-dried whey diet was compared with diets supplemented at a 7.75% level with one of the following lipid sources: corn oil, coconut oil, soybean oil, medium-chain triglyceride (MCT) or an animal-vegetable blend. A sixth treatment evaluated a roasted soybean diet formulated to an energy:lysine level equivalent to that of the fat-supplemented diets. In Exp. II, 36 crossbred weanling barrows were used to determine apparent fat and N digestibilities when soybean oil, roasted soybean, coconut oil or the MCT-supplemented diets were fed. Although pigs fed coconut oil grew somewhat faster, fat inclusion generally did not increase pig growth rate or result in lowered feed intake during the initial weeks postweaning; during the latter portion of the starter phase the addition of dietary fat resulted in a higher growth rate but feed intake was unaffected, resulting in an overall improvement in feed-to-gain ratio (P less than .05) for all but the roasted soybean diet. Pigs fed coconut oil had higher serum triglyceride and lower serum urea concentrations than did pigs fed diets containing most other lipid sources. Pigs fed MCT and coconut oil diets had a higher (P less than .01) apparent fat digestibility during the initial 2 wk postweaning than pigs fed soybean oil or roasted soybean diets. Pigs fed MCT and roasted soybeans had poorest growth rates; apparent fat and N digestibilities were lowest (P less than .05) for the roasted soybean diet.

  16. Medium-Chain Triglycerides in Combination with Leucine and Vitamin D Benefit Cognition in Frail Elderly Adults: A Randomized Controlled Trial.

    PubMed

    Abe, Sakiko; Ezaki, Osamu; Suzuki, Motohisa

    2017-01-01

    The combined supplementation of medium-chain triglycerides (MCTs), L-leucine-rich amino acids, and cholecalciferol (vitamin D 3 ) increase muscle strength and function in frail elderly individuals. However, their effects on cognition are unknown. We enrolled 38 elderly nursing home residents (mean age±SD, 86.6±4.8 y) in a 3-mo randomized, controlled, parallel group trial. The participants were randomly allocated to 3 groups: the first group received a L-leucine (1.2 g)- and cholecalciferol (20 μg)-enriched supplement with 6 g of MCT (LD+MCT); the second group received the same supplement with 6 g of long-chain triglycerides (LD+LCT); and the third group did not receive any supplements (control). Cognition was assessed at baseline and after the 3-mo intervention. The difference in changes among the groups was assessed with ANCOVA, adjusting for age and the baseline value as covariates. After 3 mo, the Mini-Mental State Examination (MMSE) score in the LD+MCT group increased by 10.6% (from 16.6 to 18.4 points, p<0.05). After 3 mo, the Nishimura geriatric rating scale for mental status (NM scale) score in the LD+MCT group increased by 30.6% (from 24.6 to 32.2 points, p<0.001), whereas that in the LD+LCT and control groups decreased by 11.2% (from 31.2 to 27.7 points, p<0.05) and 26.1% (from 27.2 to 20.1 points, p<0.001), respectively. The combined supplementation of MCTs (6 g), L-leucine-rich amino acids, and cholecalciferol may improve cognitive function in frail elderly individuals.

  17. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. The diverse nature of saturated fats and the case of medium-chain triglycerides: how one recommendation may not fit all.

    PubMed

    Bhavsar, Nilam; St-Onge, Marie-Pierre

    2016-03-01

    The adverse cardiovascular health effects of saturated fats have been debated recently since the publication of studies reporting no increase in cardiovascular risk with saturated fat intakes. We purport that this may be because of the varied nature of saturated fats, which range in length from 2 to over 20 carbon atoms, and review evidence surrounding the cardiovascular health effects of medium-chain triglycerides (MCT). MCTs are saturated fats of shorter chain length than other, more readily consumed saturated fats. Studies have reported that consumption of MCT may lead to improvements in body composition without adversely affecting cardio-metabolic risk factors. There may also be synergistic actions between MCT and n-3 polyunsaturated fats that may lead to improvements in cardiovascular health. It is clinically relevant to distinguish between sources of saturated fats for cardiovascular health. Medium, and possibly shorter chain, saturated fats behave differently than long-chain saturated fats and should not be judged similarly when it comes to their cardio-metabolic health effects. Given their neutral, and potentially beneficial cardiovascular health effects, they should not be categorized together.

  19. Medium Chain Triglyceride Oil Consumption as Part of a Weight Loss Diet Does Not Lead to an Adverse Metabolic Profile When Compared to Olive Oil

    PubMed Central

    St-Onge, Marie-Pierre; Bosarge, Aubrey; Goree, Laura Lee T.; Darnell, Betty

    2010-01-01

    Objective Medium chain triglyceride (MCT) consumption may have a beneficial impact on weight management, however, some studies point to a negative impact of MCT oil consumption on cardiovascular disease risk. This study examined the effects of MCT oil consumption, as part of a weight loss diet, on metabolic risk profile compared to olive oil. Design Thirty-one men and women, age 19–50 y and body mass index 27–33 kg/m2, completed this randomized, controlled, 16-week weight loss program. Oils were consumed at a level of ~12% of the subjects’ prescribed energy intakes in the form of muffins and liquid oil. Results After controlling for body weight, there was a significant effect of time on fasting serum glucose (P = 0.0177) and total cholesterol (P = 0.0386) concentrations, and on diastolic blood pressure (P = 0.0413), with reductions in these variables occurring over time; there was no time-by-diet interaction for any of the parameters studied. Two of the 3 subjects in the MCT oil group with evidence of the metabolic syndrome at baseline did not have metabolic syndrome at endpoint. In the olive oil group, 6 subjects had the metabolic syndrome at baseline; 2 subjects no longer had metabolic syndrome at endpoint, 1 person developed metabolic syndrome, and 4 subjects did not have any change in their metabolic syndrome status. Conclusions Our results suggest that MCT oil can be incorporated into a weight loss program without fear of adversely affecting metabolic risk factors. Distinction should be made regarding chain length when it comes to discussing the effects of saturated fats on metabolic risk factors. PMID:18845704

  20. Antimicrobial efficacy of an innovative emulsion of medium chain triglycerides against canine and feline periodontopathogens.

    PubMed

    Laverty, G; Gilmore, B F; Jones, D S; Coyle, L; Folan, M; Breathnach, R

    2015-04-01

    To test the in vitro antimicrobial efficacy of a non-toxic emulsion of free fatty acids against clinically relevant canine and feline periodontopathogens Antimicrobial kill kinetics were established utilising an alamarBlue(®) viability assay against 10 species of canine and feline periodontopathogens in the biofilm mode of growth at a concentration of 0·125% v/v medium chain triglyceride (ML:8) emulsion. The results were compared with 0·12% v/v chlorhexidine digluconate and a xylitol-containing dental formulation. Mammalian cellular cytotoxicity was also investigated for both the ML:8 emulsion and chlorhexidine digluconate (0·25 to 0·0625% v/v) using in vitro tissue culture techniques. No statistically significant difference was observed in the antimicrobial activity of the ML:8 emulsion and chlorhexidine digluconate; a high percentage kill rate (>70%) was achieved within 5 minutes of exposure and was maintained at subsequent time points. A statistically significant improvement in antibiofilm activity was observed with the ML:8 emulsion compared with the xylitol-containing formulation. The ML:8 emulsion possessed a significantly lower (P < 0·001) toxicity profile compared with the chlorhexidine digluconate in mammalian cellular cytotoxicity assays. The ML:8 emulsion exhibited significant potential as a putative effective antimicrobial alternative to chlorhexidine- and xylitol- based products for the reduction of canine and feline periodontopathogens. © 2015 British Small Animal Veterinary Association.

  1. Influence of medium-chain triglycerides on expansion and rheological properties of extruded corn starch.

    PubMed

    Horvat, Mario; Emin, M Azad; Hochstein, Bernhard; Willenbacher, Norbert; Schuchmann, Heike Petra

    2013-04-02

    Enhancement of product properties of extruded starch based products can be achieved by incorporating health promoting oil into the matrix. In order to achieve a preferably high expansion with a homogeneous pore structure, the expansion mechanisms have to be understood. In our study, we applied a customized twin-screw extruder set up to feed medium-chain triglycerides after complete gelatinization of corn starch, minimizing its effect on the starch gelatinization. Despite the fact, that the addition of up to 3.5% oil showed no influence on the extrusion parameters, we observed a three-fold increase in sectional expansion. Longitudinal expansion was less affected by the oil content. Rheological properties of the gelatinized starch were measured using an inline slit die rheometer. In addition to shear viscosity, we presented a method to determine the Bagley pressure, which reflects the elongational properties of a fluid. We were able to observe an increase in the Bagley pressure from about 25 bar up to 35-37 bar due to the addition of oil. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Effects of parenteral infusion with medium-chain triglycerides and safflower oil emulsions on hepatic lipids, plasma amino acids and inflammatory mediators in septic rats.

    PubMed

    Yeh, S; Chao, C; Lin, M; Chen, W

    2000-04-01

    This study was designed to investigate the effects of preinfusion with total parenteral nutrition (TPN) using medium-chain triglycerides (MCT) versus safflower oil (SO) emulsion as fat sources on hepatic lipids, plasma amino acid profiles, and inflammatory-related mediators in septic rats. Normal rats, with internal jugular catheters, were divided into two groups and received TPN. TPN provided 300kcal/kg/day with 40% of the non-protein energy provided as fat. All TPN solutions were isonitrogenous and identical in nutrient composition except for the fat emulsion, which was made of SO or a mixture of MCT and soybean oil (9:1) (MO). After receiving TPN for 6 days, each group of rats was further divided into control and sepsis subgroups. Sepsis was induced by cecal ligation and puncture, whereas control rats received sham operation. All rats were classified into four groups as follows: MCT control group (MOC, n= 8), MCT sepsis group (MOS, n= 8), safflower oil control group (SOC, n= 8), and safflower oil sepsis group (SOS, n= 11). The results of the study demonstrated that the MOS group had lower hepatic lipids than did the SOS group. Plasma leucine and isoleucine levels were significantly lower in the SOS than in the SOC group, but no differences in these two amino acids were observed between the MOC and MOS groups. Plasma arginine levels were significantly lower in septic groups than in those without sepsis despite whether MCT or safflower oil was infused. Plasma glutamine and alanine levels, however, did not differ between septic and non-septic groups either in the SO or MO groups. No differences in interleukin-1b, interleukin-6, tumor necrosis factor-alpha, and leukotriene B(4)concentrations in peritoneal lavage fluid were observed between the two septic groups. These results suggest that catabolic reaction is septic rats preinfused MCT is not as obvious as those preinfused safflower oil. Compared with safflower oil, TPN with MCT administration has better effects on

  3. Medium-chain triglyceride-rich enteral nutrition is more effective than low-fat enteral nutrition in rat colitis, but is equal in enteritis.

    PubMed

    Tsujikawa, T; Ohta, N; Nakamura, T; Yasuoka, T; Satoh, J; Fukunaga, T; Itohi, A; Uda, K; Ihara, T; Andoh, A; Sasaki, M; Fujiyama, Y; Bamba, T

    2001-10-01

    Although enteral nutrition (EN) therapy for Crohn's disease has been confirmed to be as effective as steroid therapy, the precise mechanism responsible for the effects of EN remains unclear, although some of the therapeutic effects of EN are believed to be due to a low dietary fat content. In order to elucidate the influence of fat in EN, it is important to investigate not only the quantity of fat, but also the source of the fat. We compared two enteral nutritional formulae: Elental (Ajinomoto) (elemental diet; ED), which contains only 1.5% fat, provided as long-chain triglycerides (LCT), versus Twinline (Snow Brand Milk Products) (TL), which contains a high percentage of fat (20.4%), provided mainly as medium-chain triglycerides (MCT). These formulae were tested on rat enteritis and rat colitis induced by trinitrobenzene sulfonic acid (TNBS). Both ED and TL reduced the manifestations of enteritis. TL had a stronger anti-inflammatory effect than ED for colitis. TL also had nutritional advantages as compared with ED, as shown by the total serum protein in the TL group being significantly higher than that in the ED group. The results indicate that intraluminal MCT is suitable as a fat energy source during intestinal inflammation in rats. We suggest that Twinline may be more useful to improve nutritional status and to reduce the mucosal inflammation in rat colitis, but that Twinline is equal in effect to Elental for rat enteritis.

  4. Effects of medium-chain triglycerides on weight loss and body composition: a meta-analysis of randomized controlled trials.

    PubMed

    Mumme, Karen; Stonehouse, Welma

    2015-02-01

    Medium-chain triglycerides (MCTs) may result in negative energy balance and weight loss through increased energy expenditure and lipid oxidation. However, results from human intervention studies investigating the weight reducing potential of MCTs, have been mixed. To conduct a systematic review and meta-analysis of randomized controlled trials comparing the effects of MCTs, specifically C8:0 and C10:0, to long-chain triglycerides (LCTs) on weight loss and body composition in adults. Changes in blood lipid levels were secondary outcomes. Randomized controlled trials >3 weeks' duration conducted in healthy adults were identified searching Web of Knowledge, Discover, PubMed, Scopus, New Zealand Science, and Cochrane CENTRAL until March 2014 with no language restriction. Identified trials were assessed for bias. Mean differences were pooled and analyzed using inverse variance models with fixed effects. Heterogeneity between studies was calculated using I(2) statistic. An I(2)>50% or P<0.10 indicated heterogeneity. Thirteen trials (n=749) were identified. Compared with LCTs, MCTs decreased body weight (-0.51 kg [95% CI-0.80 to -0.23 kg]; P<0.001; I(2)=35%); waist circumference (-1.46 cm [95% CI -2.04 to -0.87 cm]; P<0.001; I(2)=0%), hip circumference (-0.79 cm [95% CI -1.27 to -0.30 cm]; P=0.002; I(2)=0%), total body fat (standard mean difference -0.39 [95% CI -0.57 to -0.22]; P<0.001; I(2)=0%), total subcutaneous fat (standard mean difference -0.46 [95% CI -0.64 to -0.27]; P<0.001; I(2)=20%), and visceral fat (standard mean difference -0.55 [95% CI -0.75 to -0.34]; P<0.001; I(2)=0%). No differences were seen in blood lipid levels. Many trials lacked sufficient information for a complete quality assessment, and commercial bias was detected. Although heterogeneity was absent, study designs varied with regard to duration, dose, and control of energy intake. Replacement of LCTs with MCTs in the diet could potentially induce modest reductions in body weight and composition

  5. Intensified synthesis of medium chain triglycerides using ultrasonic reactors at a capacity of 4L.

    PubMed

    Mohod, Ashish V; Gogate, Parag R

    2018-04-01

    Lipids are considered as one of the most crucial nutrients for humans and among the various classes, medium chain triglycerides (MCTs) are considered as the most important functional foods and nutraceuticals. The present work deals with the intensification of synthesis of MCTs at a large capacity of 4L based on the use of ultrasonic bath and ultrasonic longitudinal horn. The effect of operating parameters like molar ratio of the reactants, type of catalyst and catalyst loading as well as the temperature on the extent of conversion has been investigated. The effect of molar ratio of lauric acid and glycerol was investigated over the range of 1:2 to 1:8 whereas the effect of loading of sulfuric acid was studied over the range of 4 ml/L-10 ml/L and zinc chloride loading over the range of 1 g/L-4 g/L. The effect of temperature was also studied using the conventional approach where it has been observed that 90 °C is an optimum temperature giving the extent of conversion as 72%. Also, the use of homogeneous catalyst as sulphuric acid was found to be more effective as compared to the solid catalyst as zinc chloride. It was observed that the maximum extent of conversion as 77.5% was obtained at 8 ml/L of sulfuric acid and molar ratio of 1:6 using ultrasonic longitudinal horn with US bath giving lower conversion as compared to US longitudinal horn but higher than the conventional approach under same operating conditions. The present work clearly established the intensification benefits in terms of reduction in time and higher conversion using cavitational reactors. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. 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.

  7. The odd-carbon medium-chain fatty triglyceride triheptanoin does not reduce hepatic steatosis.

    PubMed

    Comhair, Tine M; Garcia Caraballo, Sonia C; Dejong, Cornelis H C; Lamers, Wouter H; Koehler, S Eleonore

    2017-02-01

    Non-alcoholic fatty-liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Previously, we showed that a high-protein diet minimized diet-induced development of fatty liver and even reversed pre-existing steatosis. A high-protein diet leads to amino-acid catabolism, which in turn causes anaplerosis of the tricarboxylic-acid (TCA) cycle. Therefore, we hypothesized that anaplerosis of the TCA cycle could be responsible for the high-protein diet-induced improvement of NAFLD by channeling amino acids into the TCA cycle. Next we considered that an efficient anaplerotic agent, the odd-carbon medium-chain triglyceride triheptanoin (TH), might have similar beneficial effects. C57BL/6J mice were fed low-fat (8en%) or high-fat (42en%) oleate-containing diets with or without 15en% TH for 3 weeks. TH treatment enhanced the hepatic capacity for fatty-acid oxidation by a selective increase in hepatic Ppara, Acox, and Cd36 expression, and a decline in plasma acetyl-carnitines. It also induced pyruvate cycling through an increased hepatic PCK1 protein concentration and it increased thermogenesis reflected by an increased Ucp2 mRNA content. TH, however, did not reduce hepatic lipid content. The comparison of the present effects of dietary triheptanoin with a previous study by our group on protein supplementation shows that the beneficial effects of the high-protein diet are not mimicked by TH. This argues against anaplerosis as the sole explanatory mechanism for the anti-steatotic effect of a high-protein diet. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

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

    PubMed

    Ronis, Martin J J; Baumgardner, January N; Sharma, Neha; Vantrease, Jamie; Ferguson, Matthew; Tong, Yudong; Wu, Xianli; Cleves, Mario A; Badger, Thomas M

    2013-02-01

    Metabolic syndrome is often accompanied by development of hepatic steatosis and less frequently by non-alcoholic fatty liver disease (NAFLD) leading to non-alcoholic steatohepatitis (NASH). Replacement of corn oil with medium chain triacylglycerols (MCT) in the diets of alcohol-fed rats has been shown to protect against steatosis and alcoholic liver injury. The current study was designed to determine if a similar beneficial effect of MCT occurs in a rat model of NAFLD. Groups of male rats were isocalorically overfed diets containing 10%, 35% or 70% total energy as corn oil or a 70% fat diet in which corn oil was replaced with increasing concentrations of saturated fat (18:82, beef tallow:MCT oil) from 20% to 65% for 21 days using total enteral nutrition (TEN). As dietary content of corn oil increased, hepatic steatosis and serum alanine amino transferases were elevated (P < 0.05). This was accompanied by greater expression of cytochrome P450 enzyme CYP2E1 (P < 0.05) and higher concentrations of polyunsaturated 18:2 and 20:4 fatty acids (FA) in the hepatic lipid fractions (P < 0.05). Keeping the total dietary fat at 70%, but increasing the proportion of MCT-enriched saturated fat resulted in a dose-dependent reduction in steatosis and necrosis without affecting CYP2E1 induction. There was no incorporation of C8-C10 FAs into liver lipids, but increasing the ratio of MCT to corn oil: reduced liver lipid 18:2 and 20:4 concentrations; reduced membrane susceptibility to radical attack; stimulated FA β- and ω-oxidation as a result of activation of peroxisomal proliferator activated receptor (PPAR)α, and appeared to increase mitochondrial respiration through complex III. These data suggest that replacing unsaturated fats like corn oil with MCT oil in the diet could be utilized as a potential treatment for NAFLD.

  9. Insulin-loaded W/O/W multiple emulsions: comparison of the performances of systems prepared with medium-chain-triglycerides and fish oil.

    PubMed

    Cournarie, Fabienne; Savelli, Marie-Pierre; Rosilio, Véronique; Bretez, Françoise; Vauthier, Christine; Grossiord, Jean-Louis; Seiller, Monique

    2004-11-01

    Insulin-loaded W/O/W multiple emulsions (ME) composed of medium-chain triglycerides have been shown to decrease the blood glucose level after oral administration to diabetic rats. Fish oil (very long-chain triglycerides) could be an alternative to medium-chain triglycerides because its chronic consumption has beneficial therapeutic effects. The aim of this work was twofold: to obtain stable fish oil containing ME, based on a formulation optimized in a previous work with low medium-chain triglycerides content, and to compare their characteristics to those of ME composed of medium-chain triglycerides. Due to the higher viscosity and surface tension of fish oil compared to medium-chain triglycerides, preparation of ME appeared difficult to achieve. However, a stable unloaded-ME with low fish oil content was formed, by adapting the emulsification process. The characteristics of unloaded fish oil ME were almost similar to those of medium-chain triglycerides ME. In contrast to medium-chain triglycerides ME, the introduction of insulin did not improve the elasticity and consequently the characteristics and stability of fish oil ME. Nevertheless, the insulin-loaded fish oil containing ME was shown to be stable for 6 weeks at 4 degrees C.

  10. Primary intestinal lymphangiectasia diagnosed by double-balloon enteroscopy and treated by medium-chain triglycerides: a case report

    PubMed Central

    2013-01-01

    Introduction Primary intestinal lymphangiectasia is a disorder characterized by exudative enteropathy resulting from morphologic abnormalities of the intestinal lymphatics. Intestinal lymphangiectasia can be primary or secondary, so the diagnosis of primary intestinal lymphangiectasia must first exclude the possibility of secondary intestinal lymphangiectasia. A double-balloon enteroscopy and biopsy, as well as the pathology can be used to confirm the diagnosis of intestinal lymphangiectasia. A polymeric diet containing medium-chain triglycerides and total parenteral nutrition may be a useful therapy. Case presentation A 17-year-old girl of Mongoloid ethnicity was admitted to our hospital with a history of diarrhea and edema. She was diagnosed with protein-losing enteropathy caused by intestinal lymphangiectasia. This was confirmed by a double-balloon enteroscopy and multi-dot biopsy. After treatment with total parenteral nutrition in hospital, which was followed by a low-fat and medium-chain triglyceride diet at home, she was totally relieved of her symptoms. Conclusion Intestinal lymphangiectasia can be diagnosed with a double-balloon enteroscopy and multi-dot biopsy, as well as the pathology of small intestinal tissue showing edema of the submucosa and lymphangiectasia. Because intestinal lymphangiectasia can be primary or secondary, the diagnosis of primary intestinal lymphangiectasia must first exclude the possibility of secondary intestinal lymphangiectasia. A positive clinical response to the special diet therapy, namely a low-fat and medium-chain triglyceride diet, can further confirm the diagnosis of primary intestinal lymphangiectasia. PMID:23316917

  11. Primary intestinal lymphangiectasia diagnosed by double-balloon enteroscopy and treated by medium-chain triglycerides: a case report.

    PubMed

    Lai, Yu; Yu, Tao; Qiao, Xiao-Yu; Zhao, Li-Na; Chen, Qi-Kui

    2013-01-14

    Primary intestinal lymphangiectasia is a disorder characterized by exudative enteropathy resulting from morphologic abnormalities of the intestinal lymphatics. Intestinal lymphangiectasia can be primary or secondary, so the diagnosis of primary intestinal lymphangiectasia must first exclude the possibility of secondary intestinal lymphangiectasia. A double-balloon enteroscopy and biopsy, as well as the pathology can be used to confirm the diagnosis of intestinal lymphangiectasia. A polymeric diet containing medium-chain triglycerides and total parenteral nutrition may be a useful therapy. A 17-year-old girl of Mongoloid ethnicity was admitted to our hospital with a history of diarrhea and edema. She was diagnosed with protein-losing enteropathy caused by intestinal lymphangiectasia. This was confirmed by a double-balloon enteroscopy and multi-dot biopsy. After treatment with total parenteral nutrition in hospital, which was followed by a low-fat and medium-chain triglyceride diet at home, she was totally relieved of her symptoms. Intestinal lymphangiectasia can be diagnosed with a double-balloon enteroscopy and multi-dot biopsy, as well as the pathology of small intestinal tissue showing edema of the submucosa and lymphangiectasia. Because intestinal lymphangiectasia can be primary or secondary, the diagnosis of primary intestinal lymphangiectasia must first exclude the possibility of secondary intestinal lymphangiectasia. A positive clinical response to the special diet therapy, namely a low-fat and medium-chain triglyceride diet, can further confirm the diagnosis of primary intestinal lymphangiectasia.

  12. Hepatic beta-oxidation and carnitine palmitoyltransferase I in neonatal pigs after dietary treatments of clofibric acid, isoproterenol, and medium-chain triglycerides.

    PubMed

    Peffer, Pasha Lyvers; Lin, Xi; Odle, Jack

    2005-06-01

    A suckling piglet model was used to study nutritional and pharmacologic means of stimulating hepatic fatty acid beta-oxidation. Newborn pigs were fed milk diets containing either long- or medium-chain triglycerides (LCT or MCT). The long-chain control diet was supplemented further with clofibric acid (0.5%) or isoproterenol (40 ppm), and growth was monitored for 10-12 days. Clofibrate increased rates of hepatic peroxisomal and mitochondrial beta-oxidation of [1-(14)C]-palmitate by 60 and 186%, respectively. Furthermore, malonyl-CoA sensitive carnitine palmitoyltransferase (CPT I) activity increased 64% (P < 0.05) in pigs receiving clofibrate. Increased CPT I activity was not congruent with changes in message, as elevated abundance of CPT I mRNA was not detected (P = 0.16) when assessed by qRT-PCR. Neither rates of beta-oxidation nor CPT activities were affected by dietary MCT or by isoproterenol treatment (P > 0.1). Collectively, these findings indicate that clofibrate effectively induced hepatic CPT activity concomitant with increased fatty acid beta-oxidation.

  13. Metabolic Modulation by Medium-Chain Triglycerides Reduces Oxidative Stress and Ameliorates CD36-Mediated Cardiac Remodeling in Spontaneously Hypertensive Rat in the Initial and Established Stages of Hypertrophy.

    PubMed

    Saifudeen, Ismael; Subhadra, Lakshmi; Konnottil, Remani; Nair, R Renuka

    2017-03-01

    Left ventricular hypertrophy (LVH) is characterized by a decrease in oxidation of long-chain fatty acids, possibly mediated by reduced expression of the cell-surface protein cluster of differentiation 36 (CD36). Spontaneously hypertensive rats (SHRs) were therefore supplemented with medium-chain triglycerides (MCT), a substrate that bypasses CD36, based on the assumption that the metabolic modulation will ameliorate ventricular remodeling. The diet of 2-month-old and 6-month-old SHRs was supplemented with 5% MCT (Tricaprylin), for 4 months. Metabolic modulation was assessed by mRNA expression of peroxisome proliferator-activated receptor α and medium-chain acyl-CoA dehydrogenase. Blood pressure was measured noninvasively. LVH was assessed with the use of hypertrophy index, cardiomyocyte cross-sectional area, mRNA expression of B-type natriuretic peptide, cardiac fibrosis, and calcineurin-A levels. Oxidative stress indicators (cardiac malondialdehyde, protein carbonyl, and 3-nitrotyrosine levels), myocardial energy level (ATP, phosphocreatine), and lipid profile were determined. Supplementation of MCT stimulated fatty acid oxidation in animals of both age groups, reduced hypertrophy and oxidative stress along with the maintenance of energy level. Blood pressure, body weight, and lipid profile were unaffected by the treatment. The results indicate that modulation of myocardial fatty acid metabolism by MCT prevents progressive cardiac remodeling in SHRs, possibly by maintenance of energy level and decrease in oxidative stress. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Effectiveness of Medium-Chain Triglyceride Oil Therapy in Two Japanese Citrin-Deficient Siblings: Evaluation Using Oral Glucose Tolerance Tests.

    PubMed

    Otsuka, Hiroki; Sasai, Hideo; Abdelkreem, Elsayed; Kawamoto, Norio; Kawamoto, Minako; Kamiya, Toshiya; Tanimoto, Yasuo; Kikuchi, Atsuo; Kure, Shigeo; Numakura, Chikahiko; Hayasaka, Kiyoshi; Fukao, Toshiyuki

    2016-12-01

    Citrin deficiency, an inherited defect of the liver-type mitochondrial aspartate/glutamate carrier isoform (citrin), may cause impairment of glycolysis because of an increase in the cytosolic NADH/NAD + ratio. We report a Japanese boy whose main complaint was recurrent hypoglycemic episodes. He was suspected as having citrin deficiency because of his peculiar preference for protein- and fat-rich food. His young sister also had a similar food preference. Both siblings were diagnosed with citrin deficiency by genetic analysis. The brother and sister underwent an oral glucose tolerance test (OGTT) at 10 and 7 yr of age, respectively. Blood glucose, ammonia, lactic acid, pyruvic acid, and insulin levels were monitored before starting the test, and then every 30 min. During this test, they maintained blood glucose levels until 180 min. At 210 min, they experienced vomiting, feeling ill, and decreased blood glucose levels (2.9 and 2.8 mmol/l in the brother and sister, respectively). The sister and brother recovered uneventfully by intravenous glucose injection. In a second OGTT, 4 months after medium-chain triglyceride (MCT) oil supplementation, they had no major symptoms and normal glucose levels were maintained, even after 240 min. Additionally, after MCT oil therapy, their food preference slightly changed as they started eating more carbohydrates. Our OGTT data suggest excess carbohydrate intake has adverse consequences in patients with citrin deficiency, including hypoglycemia after a few hours. MCT oil therapy may be effective in preventing such hypoglycemia and improving metabolic derangement, even during the so-called apparently healthy period.

  15. Successful treatment of severe hypertriglyceridemia with a formula diet rich in omega-3 fatty acids and medium-chain triglycerides.

    PubMed

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

    2010-01-01

    Patients with highly increased plasma triglyceride levels are at risk of developing serious complications such as pancreatitis, coronary heart disease and stroke. Therefore it is important to rapidly decrease plasma triglyceride levels. A sufficient control of triglyceride levels with drugs like fibrates, statins or nicotinic acid can usually only be attained after a couple of weeks. Plasma exchange appears to be a fast but expensive method to reduce triglyceride levels. In this study we describe the use of a new omega-3 fatty acid and medium-chain triglyceride-rich formula diet as a therapeutic concept to reduce plasma triglyceride levels fast and effectively. Thirty-two patients with severe hypertriglyceridemia were treated with the especially composed formula diet for a period of 7 days. Within this period of time, plasma triglycerides decreased from 1,601 (402-4,555) to 554 (142-2,382) mg/dl (p < 0.05). Total cholesterol levels were reduced from 417 (211-841) to 287 (165-457) mg/dl (p < 0.001). Fasting glucose and uric acid levels also slightly decreased (-8%; -12%). The formula diet as a 1-week treatment was well tolerated and accepted by the patients. This diet was successfully used as an acute treatment in severe hypertriglyceridemia and showed effectiveness in rapidly and safely lowering plasma triglyceride levels. (c) 2010 S. Karger AG, Basel.

  16. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. With medium-chain triglycerides, higher and faster oxygen radical production by stimulated polymorphonuclear leukocytes occurs.

    PubMed

    Kruimel, J W; Naber, A H; Curfs, J H; Wenker, M A; Jansen, J B

    2000-01-01

    Parenteral lipid emulsions are suspected of suppressing the immune function. However, study results are contradictory and mainly concern the conventional long-chain triglyceride emulsions. Polymorphonuclear leukocytes were preincubated with parenteral lipid emulsions. The influence of the lipid emulsions on the production of oxygen radicals by these stimulated leukocytes was studied by measuring chemiluminescence. Three different parenteral lipid emulsions were tested: long-chain triglycerides, a physical mixture of medium- and long-chain triglycerides, and structured triglycerides. Structured triglycerides consist of triglycerides where the medium- and long-chain fatty acids are attached to the same glycerol molecule. Stimulated polymorphonuclear leukocytes preincubated with the physical mixture of medium- and long-chain triglycerides showed higher levels of oxygen radicals (p < .005) and faster production of oxygen radicals (p < .005) compared with polymorphonuclear leukocytes preincubated with long-chain triglycerides or structured triglycerides. Additional studies indicated that differences in results of various lipid emulsions were not caused by differences in emulsifier. The overall production of oxygen radicals was significantly lower after preincubation with the three lipid emulsions compared with controls without lipid emulsion. A physical mixture of medium- and long-chain triglycerides induced faster production of oxygen radicals, resulting in higher levels of oxygen radicals, compared with long-chain triglycerides or structured triglycerides. This can be detrimental in cases where oxygen radicals play either a pathogenic role or a beneficial one, such as when rapid phagocytosis and killing of bacteria is needed. The observed lower production of oxygen radicals by polymorphonuclear leukocytes in the presence of parenteral lipid emulsions may result in immunosuppression by these lipids.

  18. Neuronal decanoic acid oxidation is markedly lower than that of octanoic acid: A mechanistic insight into the medium-chain triglyceride ketogenic diet.

    PubMed

    Khabbush, Aziza; Orford, Michael; Tsai, Yi-Chen; Rutherford, Tricia; O'Donnell, Maura; Eaton, Simon; Heales, Simon J R

    2017-08-01

    The medium-chain triglyceride (MCT) ketogenic diet contains both octanoic (C8) and decanoic (C10) acids. The diet is an effective treatment for pharmacoresistant epilepsy. Although the exact mechanism for its efficacy is not known, it is emerging that C10, but not C8, interacts with targets that can explain antiseizure effects, for example, peroxisome proliferator-activated receptor-γ (eliciting mitochondrial biogenesis and increased antioxidant status) and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. For such effects to occur, significant concentrations of C10 are likely to be required in the brain. To investigate how this might occur, we measured the β-oxidation rate of 13 C-labeled C8 and C10 in neuronal SH-SY5Y cells using isotope-ratio mass spectrometry. The effects of carnitine palmitoyltransferase I (CPT1) inhibition, with the CPT1 inhibitor etomoxir, on C8 and C10 β-oxidation were also investigated. Both fatty acids were catabolized, as judged by 13 CO 2 release. However, C10 was β-oxidized at a significantly lower rate, 20% that of C8. This difference was explained by a clear dependence of C10 on CPT1 activity, which is low in neurons, whereas 66% of C8 β-oxidation was independent of CPT1. In addition, C10 β-oxidation was decreased further in the presence of C8. It is concluded that, because CPT1 is poorly expressed in the brain, C10 is relatively spared from β-oxidation and can accumulate. This is further facilitated by the presence of C8 in the MCT ketogenic diet, which has a sparing effect upon C10 β-oxidation. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  19. A stable and practical etoposide-containing intravenous long-/medium-chain triglycerides-based lipid emulsion formulation: pharmacokinetics, biodistribution, toxicity, and antitumor efficacy.

    PubMed

    Dong, Wenna; Zhang, Luna; Niu, Yantao; Fan, Dongjiao; Wu, Xiaorong; Tang, Xing; Cai, Cuifang

    2013-05-01

    This work aimed to evaluate pharmacokinetics, biodistribution, toxicity, and antitumor activities of a highly stable long-/medium-chain triglycerides (LCT/MCT)-based etoposide parenteral emulsion (EPE) in comparison to etoposide parenteral solution (EPS). Using high-pressure homogenization method, EPE was prepared and sterilized at 121°C for 10 min by autoclaving. The biological samples were analyzed using the UPLC-ESI-MS/MS method. Superior stability of EPE was verified with no significant changes in physicochemical properties in the accelerating and long-term stability tests. Similar pharmacokinetic behavior in beagle dogs was obtained and the AUC 0 - 12h values were 1196.73 ± 320.85 and 1505.56 ± 617.93 µg.h/L for EPE and EPS (p > 0.5), respectively. Likewise, no remarkable difference in biodistribution profiles in mice was found for both formulations. Safety assessment studies including hemolysis test, rabbit ear vein test and injection anaphylaxis were undertaken and the EPE was proven to be safe for intravenous administration. Specifically, after consecutive 12 weeks administration in rats, systematic and local toxicity induced by EPE were alleviated relative to that of EPS. Furthermore, significant and comparable antitumor activities to EPS were also demonstrated by EPE with tumor suppression rate (TSR) of 66.63, 55.94, and 60.16% against H460, Hep G2, and BCAP-37 human cancer cell lines in nude mice at the dose of 15 mg/kg, respectively. These results suggest that this LCT/MCT-based lipid emulsion is a promising alternative intravenous carrier for etoposide with high stability, improved convenience, alleviated toxicity, and noncompromised antitumor efficacy.

  20. Feeding Healthy Beagles Medium-Chain Triglycerides, Fish Oil, and Carnitine Offsets Age-Related Changes in Serum Fatty Acids and Carnitine Metabolites

    PubMed Central

    Hall, Jean A.; Jewell, Dennis E.

    2012-01-01

    The purpose of this study was to determine if feeding dogs medium-chain triglycerides (MCT), fish oil, and L-carnitine enriched foods offsets age-associated changes in serum fatty acids (FA) and carnitine metabolites. Forty-one healthy Beagles, mean age 9.9 years (range 3.1 to 14.8), were fed control or one of two treatment foods for 6 months. All foods were complete and balanced and met the nutrient requirements for adult dogs, and had similar concentrations of moisture, protein, and fat (approx. 7.4%, 14.0%, and 18.1%, respectively). The treatment diets both contained added L-carnitine (300 mg/kg) and 0.6% (treatment food 1) or 1.5% (treatment food 2) added fish oil. Treatment food 2 also had increased MCT from coconut oil, added corn oil, and reduced animal fat. Composition of serum FA was determined by gas chromatography of FA methyl esters. Metabolomic profiles of serum samples were determined from extracted supernatants that were split and run on GC/MS and LC/MS/MS platforms, for identification and relative quantification of small metabolites. Body composition was determined by dual energy x-ray absorptiometry. Among dog groups, there was no change in total-lean-body weight, or in serum total protein and serum albumin concentrations, based on time or dietary treatment. Serum concentrations of carnitine metabolites were decreased in geriatric (>7 years) vs. mature adult (≤7 years) dogs, and supplementation with L-carnitine attenuated the effects of aging. The ratio of PUFA to SFA was significantly greater in mature dogs at baseline (P≤0.05). Serum concentrations of eicosapentaenoic and docosahexaenoic FA increased in a dose-dependent manner. Dogs consuming treatment food 2 also had increased serum concentrations of lauric and myristic FA, and decreased concentrations of SFA, MUFA, and arachidonate (all P≤0.05) and their PUFA to SFA ratio increased. In summary, dietary MCT, fish oil, and L-carnitine counterbalanced the effects of aging on circulating

  1. Feeding healthy beagles medium-chain triglycerides, fish oil, and carnitine offsets age-related changes in serum fatty acids and carnitine metabolites.

    PubMed

    Hall, Jean A; Jewell, Dennis E

    2012-01-01

    The purpose of this study was to determine if feeding dogs medium-chain triglycerides (MCT), fish oil, and L-carnitine enriched foods offsets age-associated changes in serum fatty acids (FA) and carnitine metabolites. Forty-one healthy Beagles, mean age 9.9 years (range 3.1 to 14.8), were fed control or one of two treatment foods for 6 months. All foods were complete and balanced and met the nutrient requirements for adult dogs, and had similar concentrations of moisture, protein, and fat (approx. 7.4%, 14.0%, and 18.1%, respectively). The treatment diets both contained added L-carnitine (300 mg/kg) and 0.6% (treatment food 1) or 1.5% (treatment food 2) added fish oil. Treatment food 2 also had increased MCT from coconut oil, added corn oil, and reduced animal fat. Composition of serum FA was determined by gas chromatography of FA methyl esters. Metabolomic profiles of serum samples were determined from extracted supernatants that were split and run on GC/MS and LC/MS/MS platforms, for identification and relative quantification of small metabolites. Body composition was determined by dual energy x-ray absorptiometry. Among dog groups, there was no change in total-lean-body weight, or in serum total protein and serum albumin concentrations, based on time or dietary treatment. Serum concentrations of carnitine metabolites were decreased in geriatric (>7 years) vs. mature adult (≤ 7 years) dogs, and supplementation with L-carnitine attenuated the effects of aging. The ratio of PUFA to SFA was significantly greater in mature dogs at baseline (P ≤ 0.05). Serum concentrations of eicosapentaenoic and docosahexaenoic FA increased in a dose-dependent manner. Dogs consuming treatment food 2 also had increased serum concentrations of lauric and myristic FA, and decreased concentrations of SFA, MUFA, and arachidonate (all P ≤ 0.05) and their PUFA to SFA ratio increased. In summary, dietary MCT, fish oil, and L-carnitine counterbalanced the effects of aging on circulating

  2. Tricaprylin Alone Increases Plasma Ketone Response More Than Coconut Oil or Other Medium-Chain Triglycerides: An Acute Crossover Study in Healthy Adults

    PubMed Central

    Vandenberghe, Camille; St-Pierre, Valérie; Pierotti, Tyler; Fortier, Mélanie; Castellano, Christian-Alexandre; Cunnane, Stephen C

    2017-01-01

    Abstract Background: Ketones are the brain's main alternative fuel to glucose. Dietary medium-chain triglyceride (MCT) supplements increase plasma ketones, but their ketogenic efficacy relative to coconut oil (CO) is not clear. Objective: The aim was to compare the acute ketogenic effects of the following test oils in healthy adults: coconut oil [CO; 3% tricaprylin (C8), 5% tricaprin (C10)], classical MCT oil (C8-C10; 55% C8, 35% C10), C8 (>95% C8), C10 (>95% C10), or CO mixed 50:50 with C8-C10 or C8. Methods: In a crossover design, 9 participants with mean ± SD ages 34 ± 12 y received two 20-mL doses of the test oils prepared as an emulsion in 250 mL lactose-free skim milk. During the control (CTL) test, participants received only the milk vehicle. The first test dose was taken with breakfast and the second was taken at noon but without lunch. Blood was sampled every 30 min over 8 h for plasma acetoacetate and β-hydroxybutyrate (β-HB) analysis. Results: C8 was the most ketogenic test oil with a day-long mean ± SEM of +295 ± 155 µmol/L above the CTL. C8 alone induced the highest plasma ketones expressed as the areas under the curve (AUCs) for 0–4 and 4–8 h (780 ± 426 µmol ⋅ h/L and 1876 ± 772 µmol ⋅ h/L, respectively); these values were 813% and 870% higher than CTL values (P < 0.01). CO plasma ketones peaked at +200 µmol/L, or 25% of the C8 ketone peak. The acetoacetate-to-β-HB ratio increased 56% more after CO than after C8 after both doses. Conclusions: In healthy adults, C8 alone had the highest net ketogenic effect over 8 h, but induced only half the increase in the acetoacetate-to-β-HB ratio compared with CO. Optimizing the type of MCT may help in developing ketogenic supplements designed to counteract deteriorating brain glucose uptake associated with aging. This trial was registered at clinicaltrials.gov as NCT 02679222.

  3. Medium-Chain Triglycerides in Combination with Leucine and Vitamin D Increase Muscle Strength and Function in Frail Elderly Adults in a Randomized Controlled Trial.

    PubMed

    Abe, Sakiko; Ezaki, Osamu; Suzuki, Motohisa

    2016-05-01

    Sarcopenia, the loss of skeletal muscle mass, strength, and function, is common in elderly individuals but difficult to treat. A combination of nutrients was investigated to treat sarcopenia in very frail elderly adults. We enrolled 38 elderly nursing home residents (11 men and 27 women with a mean ± SD age of 86.6 ± 4.8 y) in a 3-mo randomized, controlled, single-blind, parallel group trial. The participants were randomly allocated to 3 groups. The first group received a daily l-leucine (1.2 g) and cholecalciferol (20 μg)-enriched supplement with 6 g medium-chain triglycerides (TGs) (MCTs) (LD + MCT); the second group received the same leucine and cholecalciferol-enriched supplement with 6 g long-chain TGs (LD + LCT); and the third group did not receive any supplements (control). The supplement and oils were taken at dinner, and changes in muscle mass, strength, and function were monitored. The increase in body weight in the LD + MCT (1.1 ± 1.0 kg) and LD + LCT (0.8 ± 1.1 kg) groups was greater than that in the control group (-0.5 ± 0.9 kg) (P < 0.05). After 3 mo, participants in the LD + MCT group had a 13.1% increase in right-hand grip strength (1.2 ± 1.0 kg, P < 0.01), a 12.5% increase in walking speed (0.078 ± 0.080 m/s, P < 0.05), a 68.2% increase in a 10-s leg open-and-close test performance (2.31 ± 1.68 n/10 s, P < 0.001), and a 28.2% increase in peak expiratory flow (53 ± 59 L/min, P < 0.01). No significant improvements in muscle mass, strength, or function were observed in the LD + LCT or control groups. The combined supplementation of MCTs (6 g), leucine-rich amino acids, and cholecalciferol at dinner may improve muscle strength and function in frail elderly individuals. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry as UMIN000017567. © 2016 American Society for Nutrition.

  4. 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

  5. Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides

    PubMed Central

    Otto, Christoph; Kaemmerer, Ulrike; Illert, Bertram; Muehling, Bettina; Pfetzer, Nadja; Wittig, Rainer; Voelker, Hans Ullrich; Thiede, Arnulf; Coy, Johannes F

    2008-01-01

    Background Among the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT). Methods Twenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132/87. The animals were then randomly split into two feeding groups and fed either a ketogenic diet (KD group; n = 12) or a standard diet (SD group; n = 12) ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on tumour growth and survival time (interval between tumour cell injection and attainment of target tumour volume). Results The ketogenic diet was well accepted by the KD mice. The tumour growth in the KD group was significantly delayed compared to that in the SD group. Tumours in the KD group reached the target tumour volume at 34.2 ± 8.5 days versus only 23.3 ± 3.9 days in the SD group. After day 20, tumours in the KD group grew faster although the differences in mean tumour growth continued significantly. Importantly, they revealed significantly larger necrotic areas than tumours of the SD group and the areas with vital tumour cells appear to have had fewer vessels than tumours of the SD group. Viable tumour cells in the border zone surrounding the necrotic areas of tumours of both groups exhibited a glycolytic phenotype with expression of glucose transporter-1 and transketolase-like 1 enzyme. Conclusion Application of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT delayed tumour growth in

  6. Role of Medium Chain Triglycerides (Axona®) in the Treatment of Mild to Moderate Alzheimer's Disease.

    PubMed

    Sharma, Alok; Bemis, Marc; Desilets, Alicia R

    2014-08-01

    Treatment of Alzheimer's disease (AD) with acetylcholinesterase inhibitors or N-methyl-D-aspartate (NMDA) receptor antagonists provides symptomatic relief but do not prevent its progression. Thus, additional approaches aimed at slowing the progression of the disease have been investigated. Reports detailing reduced brain glucose metabolism in the early stages of AD led to the hypothesis that alternate energy sources aimed at increasing neuronal metabolism may protect neurons and thus benefit patients with AD. Medium-chain triglycerides (MCTs) are metabolized to ketone bodies that serve as an alternative source of energy for neurons. Data from clinical trials suggest that MCTs improve cognition in patients with mild to moderate AD in apolipoprotein E4-negative patients. Adverse events observed were mild and included minor gastrointestinal problems such as diarrhea, dyspepsia, and flatulence. However, since genomic profiles are not routinely conducted in patients with AD in a clinical setting, the role of MCTs in clinical practice seems to be minimal. © The Author(s) 2014.

  7. The effects of starter microbiota and the early life feeding of medium chain triglycerides on the gastric transcriptome profile of 2- or 3-week-old cesarean delivered piglets.

    PubMed

    Trevisi, Paolo; Priori, Davide; Motta, Vincenzo; Luise, Diana; Jansman, Alfons J M; Koopmans, Sietse-Jan; Bosi, Paolo

    2017-01-01

    The stomach is an underestimated key interface between the ingesta and the digestive system, affecting the digestion and playing an important role in several endocrine functions. The quality of starter microbiota and the early life feeding of medium chain triglycerides may affect porcine gastric maturation. Two trials (T1, T2) were carried out on 12 and 24 cesarean-delivered piglets (birth, d0), divided over two microbiota treatments, but slaughtered and sampled at two or three weeks of age, respectively. All piglets were fed orally: sow serum (T1) or pasteurized sow colostrum (T2) on d0; simple starter microbiota ( Lactobacillus amylovorus , Clostridium glycolicum and Parabacteroides spp.) (d1-d3); complex microbiota inoculum (sow diluted feces, CA) or a placebo (simple association, SA) (d3-d4) and milk replacer ad libitum (d0-d4). The The T1 piglets and half of the T2 piglets were then fed a moist diet (CTRL); the remaining half of the T2 piglets were fed the CTRL diet fortified with medium chain triglycerides and 7% coconut oil (MCT). Total mRNA from the oxyntic mucosa was analyzed using Affymetrix©Porcine Gene array strips. Exploratory functional analysis of the resulting values was carried out using Gene Set Enrichment Analysis. Complex microbiota upregulated 11 gene sets in piglets of each age group vs. SA. Of these sets, 6 were upregulated at both ages, including the set of gene markers of oxyntic mucosa. In comparison with the piglets receiving SA, the CA enriched the genes in the sets related to interferon response when the CTRL diet was given while the same sets were impoverished by CA with the MCT diet. Early colonization with a complex starter microbiota promoted the functional maturation of the oxyntic mucosa in an age-dependent manner. The dietary fatty acid source may have affected the recruitment and the maturation of the immune cells, particularly when the piglets were early associated with a simplified starter microbiota.

  8. Protein sparing during general anesthesia with a propofol solution containing medium-chain triglycerides for gastrectomy: comparison with sevoflurane anesthesia.

    PubMed

    Nagao, Yoshiaki; Tatara, Tsuneo; Fujita, Kimihiko; Sugi, Takashi; Kotani, Joji; Hirose, Munetaka

    2013-06-01

    Despite the importance of the inhibition of catabolic response to surgery, the effects of different anesthetic techniques on the catabolic response in surgical patients are controversial. This study compared the endocrine-metabolic responses and protein catabolism during gastrectomy in patients who received either sevoflurane or propofol anesthesia with remifentanil. Thirty-seven patients (American Society of Anesthesiologists status I-III) aged 20-79 years undergoing elective gastrectomy were randomly assigned to receive sevoflurane anesthesia with remifentanil (n = 19) or intravenous propofol anesthesia (Propofol-Lipuro(®) 1 %; B. Braun, Melshungen AG, Germany) with remifentanil (n = 18). Urine samples were collected every 1 h after skin incision (0 h) and the urinary 3-methylhistidine:creatinine ratio (3-MH/Cr ratio) was used as a marker of protein catabolism. Respiratory quotient was measured during a 1 h period following skin incision. The 3-MH/Cr ratio significantly increased at 1-2 and 2-3 h compared to 0 and 0-1 h in both groups, but the propofol group exhibited a lower 3-MH/Cr ratio (nmol/μmol) than the sevoflurane group at 1-2 h (15.7 vs. 18.2, P = 0.012) and 2-3 h (15.9 vs. 18.1, P = 0.025). A difference was observed in the respiratory quotient between the sevoflurane and propofol groups (0.726 vs. 0.707, P = 0.003). A lower 3-MH/Cr ratio and a lower respiratory quotient during propofol anesthesia, compared to those exhibited during sevoflurane anesthesia, suggest that protein sparing probably occurs through the utilization of medium-chain triglycerides contained in the fat emulsion of propofol solution as a fuel source.

  9. [Eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids improves body composition and lipid profile in a patient with human immunodeficiency virus lipodystrophy].

    PubMed

    Vázquez, C; Reyes, R; Alcaraz, F; Balsa, J A; Botella-Carretero, J I

    2006-01-01

    Lipodystrophy is a frequent disorder among patients with human immunodeficiency virus (HIV) infection, characterized by a loss of adipose tissue from the extremities, gluteal region and face, with excess fat in the neck and abdominal region. Metabolic abnormalities such as hyperlipidaemia and diabetes mellitus frequently coexist, posing these patients to an increased cardiovascular risk. Drug therapy may improve some of these metabolic disturbances, but to date there are no treatments for lipodystrophy with proven benefit. A 42-year-old man with HIV lipodystrophy was started on a standard low caloric diet with <30% of total fat and <10% of saturated fat, together with rosiglitazone 8 mg daily. After five months of treatment, given that lipodystrophic features and dyslipidaemia were still present in our patient, we tried to further improve therapeutic results by eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids. Three months later, a dramatic change in body composition was shown with an increase in lean mass and a decrease in fat mass, together with an improvement in lipid profile. Eucaloric substitution of medium chain triglycerides for dietary long chain fatty acids may produce therapeutic benefits in HIV lipodystrophy.

  10. Comparison of serum concentrations of symmetric dimethylarginine and creatinine as kidney function biomarkers in healthy geriatric cats fed reduced protein foods enriched with fish oil, L-carnitine, and medium-chain triglycerides.

    PubMed

    Hall, J A; Yerramilli, M; Obare, E; Yerramilli, M; Yu, S; Jewell, D E

    2014-12-01

    The purpose of this study was to determine whether feeding cats reduced protein and phosphorus foods with added fish oil, L-carnitine, and medium-chain triglycerides (MCT) altered serum biomarkers of renal function. Thirty-two healthy cats, mean age 14.0 (8.3-19.6) years, were fed control food or one of two experimental foods for 6 months. All foods had similar concentrations of moisture, protein, and fat (approximately 8.0%, 26.5%, and 20.0%, respectively). Both experimental foods contained added fish oil (1.5%) and L-carnitine (500 mg/kg). Experimental-food 2 also contained increased MCT (10.5% from coconut oil), 1.5% added corn oil, and reduced animal fat. Glomerular filtration rate (GFR), serum biochemistries, renal function biomarkers including serum creatinine (sCr) and symmetrical dimethylarginine (SDMA), and plasma metabolomic profiles were measured at baseline, and at 1.5, 3, and 6 months. Body composition was determined by dual-energy X-ray absorptiometry. Although both experimental foods altered plasma fatty acids, carnitine and related metabolites, and lysophospholipid concentrations, there were no changes in renal function biomarkers. There was, however, a benefit in using SDMA versus sCr to assess renal function in older cats with less total lean mass. Compared with cats <12 years, those >15 years had lower total lean mass (P < 0.01), lower GFR (P = 0.04), and lower sCr concentrations (P < 0.01). However, SDMA concentrations (P < 0.01) were higher in older cats. This study shows that in cats, serum SDMA concentration is more highly correlated with GFR than sCr concentration, and, unlike sCr, which declines with age because of muscle wasting, SDMA increases as GFR declines with age. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Medium-chain triglycerides supplement therapy with a low-carbohydrate formula can supply energy and enhance ammonia detoxification in the hepatocytes of patients with adult-onset type II citrullinemia.

    PubMed

    Hayasaka, Kiyoshi; Numakura, Chikahiko; Yamakawa, Mitsunori; Mitsui, Tetsuo; Watanabe, Hisayoshi; Haga, Hiroaki; Yazaki, Masahide; Ohira, Hiromasa; Ochiai, Yasuo; Tahara, Toshiyuki; Nakahara, Tamio; Yamashiki, Noriyo; Nakayama, Takahiro; Kon, Takashi; Mitsubuchi, Hiroshi; Yoshida, Hiroshi

    2018-04-12

    Citrin, encoded by SLC25A13, constitutes the malate-aspartate shuttle, the main NADH-shuttle in the liver. Citrin deficiency causes neonatal intrahepatic cholestasis (NICCD) and adult-onset type II citrullinemia (CTLN2). Citrin deficiency is predicted to impair hepatic glycolysis and de novo lipogenesis, resulting in hepatic energy deficit. Secondary decrease in hepatic argininosuccinate synthetase (ASS1) expression has been considered a cause of hyperammonemia in CTLN2. We previously reported that medium-chain triglyceride (MCT) supplement therapy with a low-carbohydrate formula was effective in CTLN2 to prevent a relapse of hyperammonemic encephalopathy. We present the therapy for six CTLN2 patients. All the patients' general condition steadily improved and five patients with hyperammonemic encephalopathy recovered from unconsciousness in a few days. Before the treatment, plasma glutamine levels did not increase over the normal range and rather decreased to lower than the normal range in some patients. The treatment promptly decreased the blood ammonia level, which was accompanied by a decrease in plasma citrulline levels and an increase in plasma glutamine levels. These findings indicated that hyperammonemia was not only caused by the impairment of ureagenesis at ASS1 step, but was also associated with an impairment of glutamine synthetase (GS) ammonia-detoxification system in the hepatocytes. There was no decrease in the GS expressing hepatocytes. MCT supplement with a low-carbohydrate formula can supply the energy and/or substrates for ASS1 and GS, and enhance ammonia detoxification in hepatocytes. Histological improvement in the hepatic steatosis and ASS1-expression was also observed in a patient after long-term treatment.

  12. 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.

  13. Evaluation of Resveratrol, Green Tea Extract, Curcumin, Oxaloacetic Acid, and Medium-Chain Triglyceride Oil on Life Span of Genetically Heterogeneous Mice

    PubMed Central

    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. PMID:22451473

  14. 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

  15. Absorption of calcium and magnesium in patients with intestinal resections treated with medium chain fatty acids

    PubMed Central

    Haderslev, K; Jeppesen, P; Mortensen, P; Staun, M

    2000-01-01

    BACKGROUND—Steatorrhoea is associated with increased faecal loss of calcium and magnesium. Medium chain C8-C10 triglycerides (MCTs) improve fat absorption in patients with small bowel resections but the effects on intestinal absorption of divalent cations are not clear.
AIM—To assess the effect of dietary replacement of long chain triglycerides (LCTs) with MCTs on calcium and magnesium absorption in patients with small bowel resections.
PATIENTS—Nineteen adult patients with a remaining small intestine averaging 171 cm (range 50-300).
METHODS—In a crossover design, patients were randomised to two high fat diets (10 MJ/day, 50% as fat) for four days each separated by one day of washout. Diets were prepared in duplicate and were based on either LCT (LCT period) or equal quantities of LCT and MCT (L/MCT period). Metabolic balances were calculated during the last three days of each period.
RESULTS—Mean stool volume increased significantly with the L/MCT diet and was 336 ml more than that with the LCT diet (95% confidence interval of mean difference, 26-649 ml). There was no significant change in the net absorption of calcium and magnesium between the two diets. On average, percentage calcium absorption was 8.6% with the LCT diet and 12.5% with the L/MCT diet. Mean percentage magnesium absorption was 5.4% with the LCT diet and 2.9% with the L/MCT diet.
CONCLUSIONS—Dietary replacement of 50% long chain triglycerides with medium chain triglycerides in small bowel resected patients increased faecal volume significantly. No changes in the intestinal net absorption of calcium and magnesium were demonstrated.


Keywords: medium chain triglycerides; calcium absorption; magnesium absorption; intestinal resections; fat absorption PMID:10807894

  16. Hypoglycemia, hepatic dysfunction, muscle weakness, cardiomyopathy, free carnitine deficiency and long-chain acylcarnitine excess responsive to medium chain triglyceride diet.

    PubMed

    Glasgow, A M; Engel, A G; Bier, D M; Perry, L W; Dickie, M; Todaro, J; Brown, B I; Utter, M F

    1983-05-01

    Fraternal twins who had fasting hypoglycemia, hypoketonemia, muscle weakness, and hepatic dysfunction are reported. The hepatic dysfunction occurred only during periods of caloric deprivation. The surviving patient developed a cardiomyopathy. In this sibling, muscle weakness and cardiomyopathy were markedly improved by a diet high in medium chain triglycerides. There was a marked deficiency of muscle total carnitine and a mild deficiency of hepatic total carnitine. Unlike patients with systemic carnitine deficiency, serum and muscle long-chain acylcarnitine were elevated and renal reabsorption of carnitine was normal. It was postulated that the defect in long-chain fatty acid oxidation in this disorder is caused by an abnormality in the mitochondrial acylcarnitine transport. Detailed studies of the cause of the hypoglycemia revealed that insulin, growth hormone, cortisol, and glucagon secretion were appropriate and that it is unlikely that there was a major deficiency of a glycolytic or gluconeogenic enzyme. Glucose production and alanine conversion to glucose were in the low normal range when compared to normal children in the postabsorptive state. The hypoglycemia in our patients was probably due to a modest increase in glucose consumption, secondary to the decreased oxidation of fatty acids and ketones, alternate fuels which spare glucose utilization, plus a modest decrease in hepatic glucose production secondary to decreased available hepatic energy substrates.

  17. Short-Term Use of Parenteral Nutrition With a Lipid Emulsion Containing a Mixture of Soybean Oil, Olive Oil, Medium-Chain Triglycerides, and Fish Oil

    PubMed Central

    Devlieger, Hugo; Jochum, Frank; Allegaert, Karel

    2012-01-01

    Background: For premature neonates needing parenteral nutrition (PN), a balanced lipid supply is crucial. The authors hypothesized that a lipid emulsion containing medium-chain triglycerides (MCTs) and soybean, olive, and fish oils would be as safe and well tolerated as a soybean emulsion while beneficially influencing the fatty acid profile. Methods: Double-blind, controlled study in 53 neonates (<34 weeks’ gestation) randomized to receive at least 7 days of PN containing either an emulsion of MCTs and soybean, olive, and fish oils or a soybean oil emulsion. Target lipid dosage was 1.0 g fat/kg body weight [BW]/d on days 1–3, 2 g/kg BW/d on day 4, 3 g/kg BW/d on day 5, and 3.5 g/kg BW/d on days 6–14. Results: Test emulsion vs control, mean ± SD: baseline triglyceride concentrations were 0.52 ± 0.16 vs 0.54 ± 0.19 mmol/L and increased similarly in both groups to 0.69 ± 0.38 vs 0.67 ± 0.36 on day 8 of treatment (P = .781 for change). A significantly higher decrease in total and direct bilirubin vs baseline was seen in the test group compared with the control group P < .05 between groups). In plasma and red blood cell phospholipids, eicosapentaenoic acid and docosahexaenoic acid were higher, and the n-6/n-3 fatty acid ratio was lower in the test group (P < .05 vs control). Conclusions: The lipid emulsion, based on a mixture of MCTs and soybean, olive, and fish oils, was safe and well tolerated by preterm infants while beneficially modulating the fatty acid profile. PMID:22237883

  18. Benefits of use, and tolerance of, medium-chain triglyceride medical food in the management of Japanese patients with Alzheimer's disease: a prospective, open-label pilot study.

    PubMed

    Ohnuma, Tohru; Toda, Aiko; Kimoto, Ayako; Takebayashi, Yuto; Higashiyama, Ryoko; Tagata, Yuko; Ito, Masanobu; Ota, Tsuneyoshi; Shibata, Nobuto; Arai, Heii

    2016-01-01

    This is the first clinical trial of this type in Japan, designed to analyze two important aspects of Alzheimer's disease (AD) management using medium-chain triglycerides. Axona was administered for 3 months (40 g of powder containing 20 g of caprylic triglycerides). We used an indurating, four-step dose-titration method (from 10 to 40 g per day) for 7 days before the trial, and examined the tolerance and adverse effects of this intervention. We also investigated its effect on cognitive function in mild-to-moderate AD patients. This was a clinical intervention in 22 Japanese patients with sporadic AD at a mild-to-moderate stage (ten females, 12 males), mean age (± standard deviation) 63.9 (±8.5) years, Mini-Mental State Examination (MMSE) score, 10-25, seven patients were ApoE4-positive. During Axona administration, we examined changes in cognitive function by obtaining MMSE and AD assessment-scale scores. Intolerance and serum ketone concentrations were also examined. The tolerance of Axona was good, without severe gastrointestinal adverse effects. Axona did not improve cognitive function in our sample of AD patients, even in those patients without the ApoE4 allele. However, some ApoE4-negative patients with baseline MMSE score ≥14 showed improvement in their cognitive functions. The modified dose-titration method, starting with a low dose of Axona, decreased gastrointestinal adverse effects in Japanese patients. Axona might be effective for some relatively mildly affected patients with AD (with cognitive function MMSE score of ≥14 and lacking the ApoE4 allele).

  19. Study of drug concentration effects on in vitro lipolysis kinetics in medium-chain triglycerides by considering oil viscosity and surface tension.

    PubMed

    Arnold, Yvonne Elisabeth; Imanidis, Georgios; Kuentz, Martin

    2011-10-09

    Simple oil formulations are widely used in oral drug delivery and the fate of these systems is governed mainly by the dispersion and digestion process. The current work aimed to study concentration effects of six poorly water-soluble drugs on the in vitro lipolysis rate of medium-chain triglycerides. The results were compared with drug effects on oil viscosity and surface tension. First the different drugs were characterized by molecular modeling and their influence on physical oil properties was assessed. Herein capillary viscosimetry was employed as well as dynamic surface tensiometry. Subsequently, an apparent in vitro lipolysis rate was determined in biorelevant medium using an automated pH stat titrator linked to a thermo-controlled vessel. The different drugs exhibited varying effects on oil viscosity and surface tension. However, all drugs significantly lowered the apparent lipolysis rate of the oil. This effect was very similar among the different compounds with exception of orlistat, which practically blocked lipolysis because of a potent direct inhibition. The other drugs affected lipolysis kinetics most likely by different mechanism(s). In light of the obtained results, a drug effect on oil viscosity or surface tension appeared to play a minor role in reducing the lipolysis rate. The lipolysis kinetics was further not affected by the drug load, which was deemed advantageous from a pharmaceutical viewpoint. Different dose strengths are therefore not assumed to alter lipolysis kinetics, which is beneficial for limiting the variability of in vivo drug release. Further studies of drug solubility kinetics in the evolving digestion phases are, however, needed to finally assess potential effects of dosage strength in simple oil formulations. Copyright © 2011. Published by Elsevier B.V.

  20. 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.

  1. Growth of human colon cancer cells in nude mice is delayed by ketogenic diet with or without omega-3 fatty acids and medium-chain triglycerides.

    PubMed

    Hao, Guang-Wei; Chen, Yu-Sheng; He, De-Ming; Wang, Hai-Yu; Wu, Guo-Hao; Zhang, Bo

    2015-01-01

    Tumors are largely unable to metabolize ketone bodies for energy due to various deficiencies in one or both of the key mitochondrial enzymes, which may provide a rationale for therapeutic strategies that inhibit tumor growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat. Thirty-six male BALB/C nude mice were injected subcutaneously with tumor cells of the colon cancer cell line HCT116. The animals were then randomly split into three feeding groups and fed either a ketogenic diet rich in omega-3 fatty acids and MCT (MKD group; n=12) or lard only (LKD group; n=12) or a standard diet (SD group; n=12) ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The three diets were compared for tumor growth and survival time (interval between tumor cell injection and attainment of target tumor volume). The tumor growth in the MKD and LKD groups was significantly delayed compared to that in the SD group. Application of an unrestricted ketogenic diet delayed tumor growth in a mouse xenograft model. Further studies are needed to address the mechanism of this diet intervention and the impact on other tumor-relevant parameters such as invasion and metastasis.

  2. Comparing Growth Rates after Hospital Discharge of Preterm Infants Fed with Either Post-Discharge Formula or High-Protein, Medium-Chain Triglyceride Containing Formula.

    PubMed

    Ekcharoen, Chanikarn; Tantibhaedhyangkul, Ruangvith

    2015-12-01

    To evaluate whether a high energy, high-protein, MCT-containing formula (HPMCT) is as appropriate as a post-discharge formula (PDF) for feeding preterm infants after hospital discharge by comparing growth, adverse effects, and cost per gram of bodyweight gain. The present study was a randomized controlled trial. The calculated sample size was 20 infants for each intervention group. After the consent procedure, preterm infants who had postconceptional age (PCA) 35⁺¹ to 36⁺⁰ weeks and weight between 1,800 and 3,000 g at hospital discharge were randomly enrolled to receive either PDF or HPMCT starting from the discharge day. Intervention period lasted at least 28 days and until the infant's weight was at least 3,000 g or PCA was at least 40⁺⁰ weeks. Body weight, length, and head circumference were measured on days 0, 14, 28, 56, and 84 after hospital discharge. Formula intakes and adverse symptoms (abdominal distension, diarrhea, and constipation) were recorded by parents before each visit in diaries provided by the study group. Cost was calculated from estimated actual formula intakes. There were six and five infants enrolled into PDF and HPMCT group, respectively. Demographic data were not different between the two groups. There were no significant differences of growth rates in both groups at days 28, 56, and 84 after hospital discharge. Adverse effects and costs were not different either. PDF and HPMCT might be comparably appropriate for feeding catching-up preterm infants after hospital discharge, as noted from growth rates, adverse effects, and costs. However, further studies involving biochemical and neurodevelopmental evaluation, with long-term follow-up in larger populations are needed to clearly compare both formulas.

  3. A ketogenic diet supplemented with medium-chain triglycerides enhances the anti-tumor and anti-angiogenic efficacy of chemotherapy on neuroblastoma xenografts in a CD1-nu mouse model.

    PubMed

    Aminzadeh-Gohari, Sepideh; Feichtinger, René Günther; Vidali, Silvia; Locker, Felix; Rutherford, Tricia; O'Donnel, Maura; Stöger-Kleiber, Andrea; Mayr, Johannes Adalbert; Sperl, Wolfgang; Kofler, Barbara

    2017-09-12

    Neuroblastoma (NB) is a pediatric malignancy characterized by a marked reduction in aerobic energy metabolism. Recent preclinical data indicate that targeting this metabolic phenotype by a ketogenic diet (KD), especially in combination with calorie restriction, slows tumor growth and enhances metronomic cyclophosphamide (CP) therapy of NB xenografts. Because calorie restriction would be contraindicated in most cancer patients, the aim of the present study was to optimize the KD such that the tumors are sensitized to CP without the need of calorie restriction. In a NB xenograft model, metronomic CP was combined with KDs of different triglyceride compositions and fed to CD1-nu mice ad libitum . Metronomic CP in combination with a KD containing 8-carbon medium-chain triglycerides exerted a robust anti-tumor effect, suppressing growth and causing a significant reduction of tumor blood-vessel density and intratumoral hemorrhage, accompanied by activation of AMP-activated protein kinase in NB cells. Furthermore, the KDs caused a significant reduction in the serum levels of essential amino acids, but increased those of serine, glutamine and glycine. Our data suggest that targeting energy metabolism by a modified KD may be considered as part of a multimodal treatment regimen to improve the efficacy of classic anti-NB therapy.

  4. Effects of a meal rich in medium-chain saturated fat on postprandial lipemia in relatives of type 2 diabetics.

    PubMed

    Pietraszek, Anna; Hermansen, Kjeld; Pedersen, Steen B; Langdahl, Bente L; Holst, Jens J; Gregersen, Søren

    2013-01-01

    Patients with type 2 diabetes and their relatives (REL) have increased risk for cardiovascular disease (CVD). Postprandial triglyceridemia (PPL), which is influenced by diet, is an independent risk factor for CVD. Little is known about the effects of medium-chain saturated fatty acids (medium-chain SFA) on PPL and gene expression in REL. The objective of this study was to test the hypothesis that medium-chain SFA cause larger PPL response in REL compared with controls (CON) and have a differential effect on circulating incretins and ghrelin and gene expression in muscle and adipose tissue in REL and CON. Seventeen REL and 17 CON received a fat-rich meal (79 energy percent from fat) based on medium-chain SFA (coconut oil). Plasma concentrations of triglycerides (TG), free-fatty acids, insulin, glucose, glucagon-like peptide-1, glucose-dependent insulintropic peptide, and ghrelin were measured before and during 240 min postprandially. Muscle and adipose tissue biopsies were taken at baseline and after the test meal. After the test meal, REL had a higher plasma TG response (P = 0.002) and a tendency toward higher insulin response (P = 0.100). A number of genes were upregulated in response to the meal rich in medium-chain SFA in CON, but not in REL. A meal high in medium-chain SFA resulted in larger PPL response in REL than in CON. It remains to be clarified whether this can be reproduced by a pure medium-chain fat (MCT) load. The meal exerted a differential effect on gene expression in muscle, but not adipose tissue, of REL compared with CON. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Comparison of effects of ingested medium- and long-chain triglyceride on gallbladder volume and release of cholecystokinin and other gut peptides.

    PubMed

    Isaacs, P E; Ladas, S; Forgacs, I C; Dowling, R H; Ellam, S V; Adrian, T E; Bloom, S R

    1987-05-01

    In a double-blind, crossover study of the effect of ingested medium-chain triglyceride (MCT) and long-chain triglyceride (LCT) in six normal subjects, the gallbladder did not contract after ingestion of MCT but instead had significantly increased in volume at 2 hr after the meal. Plasma cholecystokinin (CCK) increased after the MCT meal, but gastrin, motilin, pancreatic polypeptide (PP), and GIP were unaffected. The long-chain triglyceride meal evoked a brisk and sustained gallbladder contraction, higher levels of CCK, and a significant increase in plasma PP and GIP levels.

  6. Short-term use of parenteral nutrition with a lipid emulsion containing a mixture of soybean oil, olive oil, medium-chain triglycerides, and fish oil: a randomized double-blind study in preterm infants.

    PubMed

    Rayyan, Maissa; Devlieger, Hugo; Jochum, Frank; Allegaert, Karel

    2012-01-01

    For premature neonates needing parenteral nutrition (PN), a balanced lipid supply is crucial. The authors hypothesized that a lipid emulsion containing medium-chain triglycerides (MCTs) and soybean, olive, and fish oils would be as safe and well tolerated as a soybean emulsion while beneficially influencing the fatty acid profile. Double-blind, controlled study in 53 neonates (<34 weeks' gestation) randomized to receive at least 7 days of PN containing either an emulsion of MCTs and soybean, olive, and fish oils or a soybean oil emulsion. Target lipid dosage was 1.0 g fat/kg body weight [BW]/d on days 1-3, 2 g/kg BW/d on day 4, 3 g/kg BW/d on day 5, and 3.5 g/kg BW/d on days 6-14. Test emulsion vs control, mean ± SD: baseline triglyceride concentrations were 0.52 ± 0.16 vs 0.54 ± 0.19 mmol/L and increased similarly in both groups to 0.69 ± 0.38 vs 0.67 ± 0.36 on day 8 of treatment (P = .781 for change). A significantly higher decrease in total and direct bilirubin vs baseline was seen in the test group compared with the control group P < .05 between groups). In plasma and red blood cell phospholipids, eicosapentaenoic acid and docosahexaenoic acid were higher, and the n-6/n-3 fatty acid ratio was lower in the test group (P < .05 vs control). The lipid emulsion, based on a mixture of MCTs and soybean, olive, and fish oils, was safe and well tolerated by preterm infants while beneficially modulating the fatty acid profile.

  7. Liver Disease, Systemic Inflammation, and Growth Using a Mixed Parenteral Lipid Emulsion, Containing Soybean Oil, Fish Oil, and Medium Chain Triglycerides, Compared With Soybean Oil in Parenteral Nutrition-Fed Neonatal Piglets.

    PubMed

    Turner, Justine M; Josephson, Jessica; Field, Catherine J; Wizzard, Pamela R; Ball, Ronald O; Pencharz, Paul B; Wales, Paul W

    2016-09-01

    The optimal parenteral lipid emulsion for neonates should reduce the risk of intestinal failure-associated liver disease and inflammation, while supporting growth and development. This could be best achieved by balanced content of ω-6 and ω-3 polyunsaturated fatty acids (PUFAs). Using a neonatal piglet model of parenteral nutrition (PN), we compared a 100% soy oil-based emulsion (ω-6:ω-3 PUFA: 7:1) with a mixed lipid emulsion comprising 30% soy oil, 30% medium-chain triglycerides, 25% olive oil, and 15% fish oil (ω-6:ω-3 PUFA: approximately 2.5:1) with regard to liver disease, inflammation, and fatty acid content in plasma and brain. Neonatal piglets, 3-6 days old, underwent jugular catheter insertion for isonitrogenous, isocaloric PN delivery over 14 days. The IL group (n = 8) was treated with Intralipid; the ML group (n = 10) was treated with the mixed lipid (SMOFlipid). Bile flow, liver chemistry, C-reactive protein (CRP), and PUFA content in plasma phospholipids and brain were compared. Compared with the IL group, ML-treated piglets had increased bile flow (P = .008) and lower total bilirubin (P = .001) and CRP (P = .023) concentrations. The ω-6 long-chain PUFA content was lower in plasma and brain for the ML group. The key ω-3 long-chain PUFA for neonatal development, docosahexaenoic acid (DHA), was not different between groups. The mixed lipid, having less ω-6 PUFA and more ω-3 PUFA, was able to prevent liver disease and reduce systemic inflammation in PN-fed neonatal piglets. However, this lipid did not increase plasma or brain DHA status, which would be desirable for neonatal developmental outcomes. © 2015 American Society for Parenteral and Enteral Nutrition.

  8. Safety and efficacy of a lipid emulsion containing a mixture of soybean oil, medium-chain triglycerides, olive oil, and fish oil: a randomised, double-blind clinical trial in premature infants requiring parenteral nutrition.

    PubMed

    Tomsits, Erika; Pataki, Margit; Tölgyesi, Andrea; Fekete, György; Rischak, Katalin; Szollár, Lajos

    2010-10-01

    Safety, tolerability, and efficacy of a novel lipid emulsion containing a mixture of soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOFlipid 20%) with reduced n-6 fatty acids (FA), increased monounsaturated and n-3 FA, and enriched in vitamin E were evaluated in premature infants compared with a soybean oil-based emulsion. Sixty (30/30) premature neonates (age 3-7 days, gestational age ≤ 34 weeks, birth weights 1000-2500 g) received parenteral nutrition (PN) with either SMOFlipid 20% (study group) or a conventional lipid emulsion (Intralipid 20%, control group) for a minimum of 7 up to 14 days. Lipid supply started at 0.5 g · kg body weight(-1) · day(-1) on day 1 and increased stepwise (by 0.5 g) up to 2 g · kg body weight(-1) · day(-1) on days 4 to 14. Safety and efficacy parameters were assessed on days 0, 8, and 15 if PN was continued. Adverse events, serum triglycerides, vital signs, local tolerance, and clinical laboratory did not show noticeable group differences, confirming the safety of study treatment. At study end, γ-glutamyl transferase was lower in the study versus the control group (107.8 ± 81.7 vs 188.8 ± 176.7 IU/L, P < 0.05). The relative increase in body weight (day 8 vs baseline) was 5.0% ± 6.5% versus 5.1% ± 6.6% (study vs control, not significant). In the study group, an increase in n-3 FA in red blood cell phospholipids and n-3:n-6 FA ratio was observed. Plasma α-tocopherol (study vs control) was increased versus baseline on day 8 (26.35 ± 10.03 vs 3.67 ± 8.06 μmol/L, P < 0.05) and at study termination (26.97 ± 18.32 vs 8.73 ± 11.41 μmol/L, P < 0.05). Parenteral infusion of SMOFlipid was safe and well tolerated and showed a potential beneficial influence on cholestasis, n-3 FA, and vitamin E status in premature infants requiring PN.

  9. A new intravenous fat emulsion containing soybean oil, medium-chain triglycerides, olive oil, and fish oil: a single-center, double-blind randomized study on efficacy and safety in pediatric patients receiving home parenteral nutrition.

    PubMed

    Goulet, Olivier; Antébi, Helena; Wolf, Claude; Talbotec, Cécile; Alcindor, Louis-Gérald; Corriol, Odile; Lamor, Michèle; Colomb-Jung, Virginie

    2010-01-01

    SMOFlipid 20% is an intravenous lipid emulsion (ILE) containing soybean oil, medium-chain triglycerides, olive oil, and fish oil developed to provide energy, essential fatty acids (FAs), and long-chain ω-3 FAs as a mixed emulsion containing α-tocopherol. The aim was to assess the efficacy and safety of this new ILE in pediatric patients receiving home parenteral nutrition (HPN) compared with soybean oil emulsion (SOE). This single-center, randomized, double-blind study included 28 children on HPN allocated to receive either SMOFlipid 20% (n = 15) or a standard SOE (Intralipid 20%, n = 13). ILE was administered 4 to 5 times per week (goal dose, 2.0 g/kg/d) within a parenteral nutrition regimen. Assessments, including safety and efficacy parameters, were performed on day 0 and after the last study infusion (day 29). Lipid peroxidation was determined by measurement of thiobarbituric acid reactive substances (TBARS). There were no significant differences in laboratory safety parameters, including liver enzymes, between the groups on day 29. The mean ± standard deviation changes in the total bilirubin concentration between the initial and final values (day 29 to day 0) were significantly different between groups: SMOFlipid group -1.5 ± 2.4 µmol/L vs SOE group 2.3 ± 3.5 µmol/L, P < .01; 95% confidence interval [CI], -6.2 to -1.4). In plasma and red blood cell (RBC) phospholipids, the ω-3 FAs C20:5ω-3 (eicosapentaenoic acid) and + C22:6ω-3 (docosahexaenoic acid) increased significantly in the SMOFlipid group on day 29. The ω-3:ω-6 FA ratio was significantly elevated with SMOFlipid 20% compared with SOE group (plasma, day 29: 0.15 ± 0.06 vs 0.07 ± 0.02, P < .01, 95% CI, 0.04-0.11; and RBC, day 29: 0.23 ± 0.07 vs 0.14 ± 0.04, P < .01, 95% CI, 0.04-0.13). Plasma α-tocopherol concentration increased significantly more with SMOFlipid 20% (15.7 ± 15.9 vs 5.4 ± 15.2 µmol/L, P < .05; 95% CI, -2.1 to 22.6). The low-density lipoprotein-TBARS concentrations were

  10. An Increased Dietary Supply of Medium-Chain Fatty Acids during Early Weaning in Rodents Prevents Excessive Fat Accumulation in Adulthood

    PubMed Central

    van de Heijning, Bert J. M.; Oosting, Annemarie; Kegler, Diane; van der Beek, Eline M.

    2017-01-01

    Medium-chain fatty acids (MCFA) are a directly and readily absorbed source of energy. Exposure early-in-life to increased MCFA levels might affect development and impact (lipid) metabolism later in life. We tested whether an increased MCFA intake early-in-life positively affects adult body composition and metabolic status when challenged by a western-style diet (WSD). Male offspring of C57Bl/6j mice and Wistar rats were fed a control diet (CTRL; 10 w% fat, 14% MCFA) or a medium-chain triglycerides (MCT) diet with 20% MCFA until postnatal (PN) day 42, whereupon animals were fed a WSD (10 w% fat) until PN day 98. Body composition was monitored by Dual Energy X-ray Absorptiometry (DEXA). In rats, glucose homeostasis was assessed by glucose tolerance test (GTT) and insulin tolerance test (ITT); in mice, the HOmeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated. At autopsy on PN day 98, plasma lipid profiles, glucose, insulin, and adipokines were measured; organs and fat pads were collected and the adipocyte size distribution was analysed. Milk analysis in mice showed that the maternal MCT diet was not translated into milk, and pups were thus only exposed to high MCT levels from early weaning onward: PN day 16 until 42. Mice exposed to MCT showed 28% less fat accumulation vs. CTRL during WSD. The average adipocyte cell size, fasting plasma triglycerides (TG), and leptin levels were reduced in MCT mice. In rats, no effects were found on the adult body composition, but the adipocyte cell size distribution shifted towards smaller adipocytes. Particularly mice showed positive effects on glucose homeostasis and insulin sensitivity. Increased MCFA intake early-in-life protected against the detrimental effects of an obesogenic diet in adulthood. PMID:28632178

  11. Meta-Analysis of Structured Triglyceride versus Physical Mixture Medium- and Long-Chain Triglycerides for PN in Liver Resection Patients.

    PubMed

    Zhao, Yajie; Wang, Chengfeng

    2017-01-01

    The use of total parenteral nutrition can affect liver function, causing a series of problems such as cholestasis. The aim of this meta-analysis was to compare structured triglyceride- (STG-) based lipid emulsions with physical medium-chain triglyceride (MCT)/long-chain triglyceride (LCT) mixtures in patients who had undergone liver surgery to identify any differences between these two types of parenteral nutrition. We searched the databases of PubMed, the Cochrane Library, Web of Science, EMBASE, and Chinese Biomedicine Database from January 2007 to March 2017 and included studies that compared STG-based lipid emulsions with physical MCT/LCT mixtures for surgical patients with liver disease. The STG was more beneficial than physical MCT/LCT on recovery of liver function and immune function. Therefore, STGs may represent a promising alternative to other types of lipid emulsions for hepatic surgery patients.

  12. Structured triglyceride emulsions in parenteral nutrition.

    PubMed

    Chambrier, C; Lauverjat, M; Bouletreau, P

    2006-08-01

    Over the past 3 decades, various concepts for IV fat emulsions (IVFE) have been developed. A randomized, structured-lipid emulsion based on an old technology has recently become available. This structured-lipid emulsion is produced by mixing medium-chain triglycerides and long-chain triglycerides, then allowing hydrolysis to form free fatty acids, followed by random transesterification of the fatty acids into mixed triglyceride molecules. Studies in animals have shown an improvement in nitrogen balance with the use of these lipid emulsions. Only 8 human clinical studies with these products have been performed. The results of these human clinical studies have been less promising than the animal studies; however, an improvement in nitrogen balance and lipid metabolism exceeds results associated with infusion of long-chain triglycerides (LCT) or a physical mixture of long-chain triglycerides and medium-chain triglycerides (LCT-MCT). Structured-lipid emulsion seems to induce less elevation in serum liver function values compared with standard IVFEs. In addition, structured-lipid emulsions have no detrimental effect on the reticuloendothelial system. Further studies are necessary in order to recommend the use of structured-lipid emulsions. The clinical community hopes that chemically defined structured triglycerides will make it possible to determine the distribution of specific fatty acids on a specific position on the glycerol core and therefore obtain specific activity for a specific clinical situation.

  13. Comparison of serum triglyceride levels with propofol in long chain triglyceride and propofol in medium and long chain triglyceride after short term anesthesia in pediatric patients.

    PubMed

    Bhukal, Ishwar; Thimmarayan, Gokul; Bala, Indu; Solanki, Sohan Lal; Samra, Tanvir

    2014-11-01

    Significant increase in serum triglyceride (ST) concentration have been described in adult population after prolonged administration of propofol formulation containing long chain triglyceride (LCT). Though, medium chain triglyceride-LCT (MCT-LCT) propofol when compared with LCT propofol for long-term sedation in adults resulted in identical triglyceride levels, the elimination of triglyceride was faster in patients administered MCT-LCT propofol. A total of 40 children were randomized into two groups of 20 each; Group I were induced with 1% LCT propofol (3 mg/kg) and Group II with 1% medium and LCT propofol and maintained with descalating dose of 20.15 and 10 mg/kg/h at 10 min intervals. Blood samples for ST concentration were obtained before induction of anesthesia, at the end of propofol infusion and 4 h after terminating propofol infusion. ST levels were raised significantly above the basal values in both the groups but the rise was significantly higher in Group I (P < 0.05). Four hours after stopping propofol infusion the triglyceride levels were similar to the basal values in Group II, whereas in Group I the values were significantly greater than the baseline (P < 0.05) as well as those of Group II (P < 0.05). No clinically significant adverse effect of hypertriglyceridemia was observed. Even short term anesthesia with LCT and MCT-LCT propofol (1%) leads to elevated ST levels. The increase in ST levels is less with MCT-LCT propofol and elimination of triglyceride is also rapid after terminating MCT-LCT propofol infusion.

  14. Hepatocellular integrity in patients requiring parenteral nutrition: comparison of structured MCT/LCT vs. a standard MCT/LCT emulsion and a LCT emulsion.

    PubMed

    Piper, S N; Röhm, K D; Boldt, J; Odermatt, B; Maleck, W H; Suttner, S W

    2008-07-01

    The aetiology of parenteral nutrition-associated hepatic injury remains unresolved. The aim of the study was to evaluate the effects of structured triglycerides in parenteral nutrition compared either to a physical medium-chain triglycerides (MCT)/long-chain triglcerides (LCT) mixture or to a LCT emulsion on hepatic integrity. In a randomized, double-blinded trial, we studied 45 patients undergoing abdominal surgery, who were expected to receive parenteral nutrition for 5 days. Patients were allocated to one of three nutrition regimens: Group A (n = 15) received structured triglycerides, Group B (n = 15) a MCT/LCT and Group C (n = 15) a LCT lipid emulsion. Before the start of parenteral nutrition (T0), 24 h (T1), 48 h (T2), 72 h (T3) and 120 h (T4) after start of infusion the following parameters were measured: Alpha-glutathione S-transferase (alpha-GST), alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose and serum triglycerides. At T3 and T4, alpha-GST levels were significantly higher in Group B (T3: 9.4 +/- 9.9; T4: 14.6 +/- 19.5 microg L-1) and Group C (T3: 14.2 +/- 20.8; T4: 22.4 +/- 39.3 microg L-1) compared with the patients receiving structured triglycerides (T3: 1.9 +/- 1.8; T4: 3.2 +/- 2.7 microg L-1). Whereas the mean alpha-GST-levels in structured triglycerides group always remained in the normal range, this was not the case in both other groups at T3 and T4. There were no significant differences concerning ALT, AST and glucose levels. At T3 and T4, triglyceride levels were significantly lower in Group A than in Groups B and C. Hepatic integrity was well retained with the administration of structured triglycerides, whereas both MCT/LCT emulsion and LCT emulsion caused subclinical hepatic injury.

  15. 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. © 2015 FEBS.

  16. Triglycerides

    MedlinePlus

    ... physical activity Not smoking Limiting sugar and refined foods Limiting alcohol Switching from saturated fats to healthier fats Some people will also need to take cholesterol medicines to lower their triglycerides.

  17. Impact of medium and long chain triglycerides consumption on appetite and food intake in overweight men

    PubMed Central

    St-Onge, Marie-Pierre; Mayrsohn, Brian; O’Keeffe, Majella; Kissileff, Harry R.; Choudhury, Arindam Roy; Laferrère, Blandine

    2014-01-01

    Background Medium chain triglycerides (MCT) enhance thermogenesis and may reduce food intake relative to long chain triglycerides (LCT). The goal of this study was to establish the effects of MCT on appetite and food intake and determine whether differences were due to differences in hormone concentrations. Methods Two randomized, crossover studies were conducted in which overweight men consumed 20 g of MCT or corn oil (LCT) at breakfast. Blood samples were obtained over 3 h. In Study 1 (n=10), an ad lib lunch was served after 3 h. In Study 2 (n=7), a pre-load containing 10 g of test oil was given at 3 h and lunch was served 1 h later. Linear mixed model analyses were performed to determine the effects of MCT and LCT oil on change in hormones and metabolites from fasting, adjusting for body weight. Correlations were computed between differences in hormones just before the test meals and differences in intakes after the two oils for Study 1 only. Results Food intake at the lunch test meal after the MCT pre-load (Study 2) was (mean ± SEM) 532 ± 389 kcal vs. 804 ± 486 kcal after LCT (P < 0.05). MCT consumption resulted in a lower rise in triglycerides (P = 0.014) and glucose (P = 0.066) and a higher rise in peptide YY (P = 0.017) and leptin (P = 0.036) compared to LCT (combined data). Correlations between differences in hormone levels (GLP-1, PYY) and differences in food intake were in the opposite direction to expectations. Conclusions MCT consumption reduced food intake acutely but this does not seem to be mediated by changes in GLP-1, PYY, and insulin. PMID:25074387

  18. Impact of medium and long chain triglycerides consumption on appetite and food intake in overweight men.

    PubMed

    St-Onge, M-P; Mayrsohn, B; O'Keeffe, M; Kissileff, H R; Choudhury, A R; Laferrère, B

    2014-10-01

    Medium chain triglycerides (MCT) enhance thermogenesis and may reduce food intake relative to long chain triglycerides (LCT). The goal of this study was to establish the effects of MCT on appetite and food intake and determine whether differences were due to differences in hormone concentrations. Two randomized, crossover studies were conducted in which overweight men consumed 20 g of MCT or corn oil (LCT) at breakfast. Blood samples were obtained over 3 h. In Study 1 (n=10), an ad lib lunch was served after 3 h. In Study 2 (n=7), a preload containing 10 g of test oil was given at 3 h and lunch was served 1 h later. Linear mixed model analyses were performed to determine the effects of MCT and LCT oil on change in hormones and metabolites from fasting, adjusting for body weight. Correlations were computed between differences in hormones just before the test meals and differences in intakes after the two oils for Study 1 only. Food intake at the lunch test meal after the MCT preload (Study 2) was (mean±s.e.m.) 532±389 kcal vs 804±486 kcal after LCT (P<0.05). MCT consumption resulted in a lower rise in triglycerides (P=0.014) and glucose (P=0.066) and a higher rise in peptide YY (PYY, P=0.017) and leptin (P=0.036) compared with LCT (combined data). Correlations between differences in hormone levels (glucagon-like peptide (GLP-1), PYY) and differences in food intake were in the opposite direction to expectations. MCT consumption reduced food intake acutely but this does not seem to be mediated by changes in GLP-1, PYY and insulin.

  19. Pharmacoeconomics of parenteral nutrition in surgical and critically ill patients receiving structured triglycerides in China.

    PubMed

    Wu, Guo Hao; Ehm, Alexandra; Bellone, Marco; Pradelli, Lorenzo

    2017-01-01

    A prior meta-analysis showed favorable metabolic effects of structured triglyceride (STG) lipid emulsions in surgical and critically ill patients compared with mixed medium-chain/long-chain triglycerides (MCT/LCT) emulsions. Limited data on clinical outcomes precluded pharmacoeconomic analysis. We performed an updated meta-analysis and developed a cost model to compare overall costs for STGs vs MCT/LCTs in Chinese hospitals. We searched Medline, Embase, Wanfang Data, the China Hospital Knowledge Database, and Google Scholar for clinical trials comparing STGs to mixed MCT/LCTs in surgical or critically ill adults published between October 10, 2013 and September 19, 2015. Newly identified studies were pooled with the prior studies and an updated meta-analysis was performed. A deterministic simulation model was used to compare the effects of STGs and mixed MCT/LCT's on Chinese hospital costs. The literature search identified six new trials, resulting in a total of 27 studies in the updated meta-analysis. Statistically significant differences favoring STGs were observed for cumulative nitrogen balance, pre- albumin and albumin concentrations, plasma triglycerides, and liver enzymes. STGs were also associated with a significant reduction in the length of hospital stay (mean difference, -1.45 days; 95% confidence interval, -2.48 to -0.43; p=0.005) versus mixed MCT/LCTs. Cost analysis demonstrated a net cost benefit of ¥675 compared with mixed MCT/LCTs. STGs are associated with improvements in metabolic function and reduced length of hospitalization in surgical and critically ill patients compared with mixed MCT/LCT emulsions. Cost analysis using data from Chinese hospitals showed a corresponding cost benefit.

  20. Treatment with medium chain fatty acids milk of CD36-deficient preschool children.

    PubMed

    Nagasaka, Hironori; Hirano, Ken-Ichi; Yorifuji, Tohru; Komatsu, Haruki; Takatani, Tomonozumi; Morioka, Ichiro; Hirayama, Satoshi; Miida, Takashi

    2018-06-01

    CD36 deficiency is characterized by limited cellular long chain fatty acid uptake in the skeletal and cardiac muscles and often causes energy crisis in these muscles. However, suitable treatment for CD36 deficiency remains to be established. The aim of this study was to evaluate the clinical and metabolic effects of medium chain triacylglycerols (MCTs) in two CD36-deficient preschool children who often developed fasting hypoglycemia and exercise-induced myalgia. Fasting blood glucose, total ketone bodies, and free fatty acids were examined and compared for usual supper diets and for diets with replacement of one component with 2 g/kg of 9% MCT-containing milk (MCT milk). Changes in serum creatine kinase and alanine aminotransferase levels, resulting from replacement of glucose water intake with 1 g/kg of MCT milk and determined by using bicycle pedaling tasks, were examined and compared. Hypoglycemic and/or myalgia episodes in daily life were also investigated. Biochemically, participants' blood glucose and total ketone bodies levels after overnight fasting substantially increased after dietary suppers containing MCT milk. Increases in serum creatine kinase and alanine aminotransferase levels resulting from the bicycle pedaling task were suppressed by MCT milk. Hypoglycemia leading to unconsciousness and tachycardia before breakfast decreased after introduction of dietary suppers containing MCT milk. Occurrence of myalgia in the lower limbs also decreased after intakes of MCT milk before long and/or strenuous exercising. Our results suggest that MCTs can prevent fasting hypoglycemia and exercise-induced myalgia in CD36-deficient young children. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Administration of structured lipid composed of MCT and fish oil reduces net protein catabolism in enterally fed burned rats.

    PubMed Central

    Teo, T C; DeMichele, S J; Selleck, K M; Babayan, V K; Blackburn, G L; Bistrian, B R

    1989-01-01

    The effects of enteral feeding with safflower oil or a structured lipid (SL) derived from 60% medium-chain triglyceride (MCT) and 40% fish oil (MCT/fish oil) on protein and energy metabolism were compared in gastrostomy-fed burned rats (30% body surface area) by measuring oxygen consumption, carbon dioxide production, nitrogen balance, total liver protein, whole-body leucine kinetics, and rectus muscle and liver protein fractional synthetic rates (FSR, %/day). Male Sprague-Dawley rats (195 +/- 5g) received 50 ml/day of an enteral regimen containing 50 kcal, 2 g amino acids, and 40% nonprotein calories as lipid for three days. Protein kinetics were estimated by using a continuous L-[1-14C] leucine infusion technique on day 2. Thermally injured rats enterally fed MCT/fish oil yielded significantly higher daily and cumulative nitrogen balances (p less than or equal to 0.025) and rectus muscle (39%) FSR (p less than or equal to 0.05) when compared with safflower oil. MCT/fish oil showed a 22% decrease (p less than or equal to 0.005) in per cent flux oxidized and a 7% (p less than or equal to 0.05) decrease in total energy expenditure (TEE) versus safflower oil. A 15% increase in liver FSR was accompanied by a significant elevation (p less than or equal to 0.025) in total liver protein with MCT/fish oil. This novel SL shares the properties of other structured lipids in that it reduces the net protein catabolic effects of burn injury, in part, by influencing tissue protein synthetic rates. The reduction in TEE is unique to MCT/fish oil and may relate to the ability of fish oil to diminish the injury response. PMID:2500898

  2. Lymphatic absorption of structured triglycerides vs. physical mix in a rat model of fat malabsorption.

    PubMed

    Tso, P; Lee, T; Demichele, S J

    1999-08-01

    Comparison was made between the intestinal absorption and lymphatic transport of a randomly interesterified fish oil and medium-chain triglyceride (MCT) structured triglycerides (STG) vs. the physical mix in rat small intestine following ischemia and reperfusion (I/R) injury. Under halothane anesthesia, the superior mesenteric artery (SMA) was occluded for 20 min and then reperfused in I/R rats. The SMA was isolated but not occluded in control rats. In both treatment groups, the mesenteric lymph duct was cannulated and a gastric tube was inserted. Each treatment group received 1 ml of the fish oil-MCT STG or physical mix (7 rats/group) through the gastric tube followed by an infusion of PBS at 3 ml/h for 8 h. Lymph was collected hourly for 8 h. Lymph triglyceride, cholesterol, and decanoic and eicosapentaenoic acids increased rapidly and maintained a significantly higher output (P < 0.01) with STG compared with physical mix in control rats over 8 h. After I/R, lymphatic triglyceride output decreased 50% compared with control. Gastric infusion of STG significantly improved lipid transport by having a twofold higher triglyceride, cholesterol, and decanoic and eicosapentaenoic acids output to lymph compared with its physical mix (P < 0.01). We conclude that STG is absorbed into lymph significantly better than physical mix by both the normal intestine and the intestine injured by I/R.

  3. Structured Mono- and Diacylglycerols with a High Content of Medium Chain Fatty Acids.

    PubMed

    Esperón-Rojas, Alaina A; Baeza-Jiménez, R; Cano-Sarmiento, Cynthia; García, Hugo S

    2017-09-01

    In the present work, direct enzyme-catalysed esterification of medium chain fatty acids (MCFA) from three different sources (Medium chain triacylglycerols, MCT; saponified MCT and a mixture of free MCFA) was evaluated to obtain structured mono- and diacylglycerols. The esterifications were carried out mixing the different sources of MCFA with glycerol at two weight ratios (1:1 and 4:1, w/w), using three immobilized lipases: Novozym 435, Lipozyme RM IM and Lipozyme TL IM; different reaction times (t = 0, 15, 30, 60, 120 min); enzyme loadings (5, 10 or 15% with respect to the total weight of substrates). The extent of esterification was determined by gas chromatography (GC) analysis of the acylglycerols produced. The highest incorporation of free MCFA into glycerol was obtained for a 1:1 (w/w) glycerol to free MCFA ratio, 5% of Novozym 435, at 50°C, 300 rpm, 10% of molecular sieves and a commercial MCFA mixture as starting material. Under these conditions, incorporation of at least 90% of MCFA into glycerol was achieved after 30 min of reaction.

  4. A rich medium-chain triacylglycerol diet benefits adiposity but has adverse effects on the markers of hepatic lipogenesis and beta-oxidation.

    PubMed

    Chamma, Carolina Maria de Oliveira; Bargut, Thereza Cristina Lonzetti; Mandarim-de-Lacerda, Carlos Alberto; Aguila, Marcia Barbosa

    2017-02-22

    We investigated the increasing amounts of medium-chain triacylglycerol (MCT) in the diet on hepatic lipid metabolism. Mature C57BL/6 male mice were randomly divided into five groups (n = 10/group). The animals received their diet for 12 weeks, as a control (C group, 10% of energy from lipids); high-fat lard (HF group, isoenergetic diet, 50% of energy from lipids with lard); a mixture of lard and MCT oil (with a gradual replacement of lard by MCT: HF-MCT25%, HF-MCT75%, and HF-MCT100% groups). At euthanasia, we collected blood and dissected the liver for analyses (glucose, insulin, HOMA-IR, QUICK index, and triacylglycerol, light microscopy, western blotting, and RT-qPCR). The HF diet groups showed a greater body mass gain compared to the C group, but the HF-MCT100% group showed diminished adiposity and amelioration of insulin resistance. All the HF groups also showed a clear increase in hepatic lipid accumulation, increased lipogenesis and decreased PPAR-alpha expression, although HF-MCT groups showed improved local insulin signaling. Lastly, the HF-MCT100% group had raised markers of beta-oxidation (UCP3 and MCAD) and mitochondrial biogenesis (PGC1-alpha and NRF1). In conclusion, the findings demonstrated that a high amount of MCT (HF-MCT100% group) added to an HF diet reduces the body fat accumulation and insulin resistance. However, the lipid accumulation as well as the lipid metabolism is altered in the liver of animals fed with a very high MCT diet, indicating that higher doses of MCT may be harmful in a long-term.

  5. Medium-Chain Fatty Acids Improve Cognitive Function in Intensively Treated Type 1 Diabetic Patients and Support In Vitro Synaptic Transmission During Acute Hypoglycemia

    PubMed Central

    Page, Kathleen A.; Williamson, Anne; Yu, Namyi; McNay, Ewan C.; Dzuira, James; McCrimmon, Rory J.; Sherwin, Robert S.

    2009-01-01

    OBJECTIVE We examined whether ingestion of medium-chain triglycerides could improve cognition during hypoglycemia in subjects with intensively treated type 1 diabetes and assessed potential underlying mechanisms by testing the effect of β-hydroxybutyrate and octanoate on rat hippocampal synaptic transmission during exposure to low glucose. RESEARCH DESIGN AND METHODS A total of 11 intensively treated type 1 diabetic subjects participated in stepped hyperinsulinemic- (2 mU · kg−1 · min−1) euglycemic- (glucose ∼5.5 mmol/l) hypoglycemic (glucose ∼2.8 mmol/l) clamp studies. During two separate sessions, they randomly received either medium-chain triglycerides or placebo drinks and performed a battery of cognitive tests. In vitro rat hippocampal slice preparations were used to assess the ability of β-hydroxybutyrate and octanoate to support neuronal activity when glucose levels are reduced. RESULTS Hypoglycemia impaired cognitive performance in tests of verbal memory, digit symbol coding, digit span backwards, and map searching. Ingestion of medium-chain triglycerides reversed these effects. Medium-chain triglycerides also produced higher free fatty acids and β-hydroxybutyrate levels compared with placebo. However, the increase in catecholamines and symptoms during hypoglycemia was not altered. In hippocampal slices β-hydroxybutyrate supported synaptic transmission under low-glucose conditions, whereas octanoate could not. Nevertheless, octanoate improved the rate of recovery of synaptic function upon restoration of control glucose concentrations. CONCLUSIONS Medium-chain triglyceride ingestion improves cognition without adversely affecting adrenergic or symptomatic responses to hypoglycemia in intensively treated type 1 diabetic subjects. Medium-chain triglycerides offer the therapeutic advantage of preserving brain function under hypoglycemic conditions without causing deleterious hyperglycemia. PMID:19223595

  6. 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.

    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 formore » 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.« less

  7. Stability of citral in oil-in-water emulsions prepared with medium-chain triacylglycerols and triacetin.

    PubMed

    Choi, Seung Jun; Decker, Eric Andrew; Henson, Lulu; Popplewell, L Michael; McClements, David Julian

    2009-12-09

    Citral is widely used in the beverage, food, and fragrance industries for its characteristic flavor profile. However, it chemically degrades over time in aqueous solutions due to an acid-catalyzed reaction, which leads to loss of desirable flavor notes and formation of off-flavor notes. The objective of this research was to examine the impact of organic phase composition [triacetin and medium-chain triacylglycerols (MCT)] on the oil-water partitioning and chemical degradation of citral in oil-in-water emulsions. MCT was present as emulsion droplets (d approximately 900 nm), whereas triacetin was present as microemulsion droplets (d approximately 10 nm). In the absence of organic phase, the rate of citral degradation increased as the aqueous phase pH was reduced from 7 to 3. The percentage of citral within the aqueous phase increased with increasing triacetin concentration at both pH 3 and 7, which was attributed to a reduction in MCT droplet concentration. There was no significant change in the particle size distribution of the emulsions during storage, independent of triacetin concentration and pH, which indicated that they were physically stable. Both 5 wt % MCT as emulsion droplets and 5 wt % triacetin as microemulsion droplets were able to appreciably slow citral degradation at pH 3. These results may have important implications for understanding and improving the chemical stability of citral in beverage emulsions.

  8. Microbial synthesis of medium-chain chemicals from renewables.

    PubMed

    Sarria, Stephen; Kruyer, Nicholas S; Peralta-Yahya, Pamela

    2017-12-01

    Linear, medium-chain (C8-C12) hydrocarbons are important components of fuels as well as commodity and specialty chemicals. As industrial microbes do not contain pathways to produce medium-chain chemicals, approaches such as overexpression of endogenous enzymes or deletion of competing pathways are not available to the metabolic engineer; instead, fatty acid synthesis and reversed β-oxidation are manipulated to synthesize medium-chain chemical precursors. Even so, chain lengths remain difficult to control, which means that purification must be used to obtain the desired products, titers of which are typically low and rarely exceed milligrams per liter. By engineering the substrate specificity and activity of the pathway enzymes that generate the fatty acyl intermediates and chain-tailoring enzymes, researchers can boost the type and yield of medium-chain chemicals. Development of technologies to both manipulate chain-tailoring enzymes and to assay for products promises to enable the generation of g/L yields of medium-chain chemicals.

  9. Ease of oral administration and owner-perceived acceptability of triglyceride oil, dissolving thin film strip, and gelatin capsule formulations to healthy cats.

    PubMed

    Traas, Anne M; Fleck, Timothy; Ellings, Andrea; Mahabir, Sean; Stuebner, Kathy; Brown, Dorothy C; Durso, Dana; DiGregorio, Michael; Bode, Lora; Kievit, Kelly I; McCall, Robert

    2010-06-01

    To compare owner-assessed ease of administration and overall acceptability of 3 chemically inactive formulations administered PO to cats. 90 healthy client-owned cats. Cats were randomly assigned to receive 1 of 3 formulations PO once daily for 14 days: medium chain triglyceride (MCT) oil, dissolving thin film strips (proprietary ingredients), or gelatin capsules filled with microcrystalline cellulose. Owners administered the formulations and rated ease of administration daily on a 10-cm visual analogue scale (VAS). At the end of the study, owners rated overall acceptability of formulations from their own perspective and their overall perception of acceptability to their cat. Mean VAS scores for daily ease of administration of MCT oil and film strips were significantly higher than scores for gelatin capsules at all time points, except on days 2, 4, and 7. There was no difference between MCT oil and film strip formulation scores. Mean VAS scores were 8.8 (MCT oil), 8.9 (film strips), and 7.4 (gelatin capsules) for overall acceptability to owners and 8.0 (MCT oil), 8.3 (film strips), and 6.7 (gelatin capsules) for overall owner-perceived acceptability to cats. Daily ease of administration on 11 of 14 days and overall owner-perceived acceptability to cats were scored significantly higher for film strips and MCT oil, compared with scores for gelatin capsules. Overall acceptability to owners followed a similar pattern; however, the differences were not significant. Dissolving thin film strip or MCT oil vehicles may allow for easier PO administration of medication to cats than does administration of gelatin capsules.

  10. Sensations induced by medium and long chain triglycerides: role of gastric tone and hormones

    PubMed Central

    Barbera, R; Peracchi, M; Brighenti, F; Cesana, B; Bianchi, P; Basilisco, G

    2000-01-01

    BACKGROUND—The relative roles of gastric relaxation and the neuroendocrine signals released by the small intestine in the perception of nutrient induced sensations are controversial. The different effects of long chain (LCT) and medium chain (MCT) triglyceride ingestion on perception, gastric relaxation, and hormonal release may help to elucidate the mechanisms underlying nutrient induced sensations.
AIMS—To compare the effects of intraduodenal LCT and MCT infusions on perception, gastric tone, and plasma gut hormone levels in healthy subjects.
SUBJECTS—Nine fasting healthy volunteers.
METHODS—The subjects received duodenal infusions of saline followed by LCTs and MCTs in a randomised order on two different days. The sensations were rated on a visual analogue scale. Gastric tone was measured using a barostat, and plasma gut hormone levels by radioimmunoassay.
RESULTS—LCT infusion increased satiation scores, reduced gastric tone, and increased the levels of plasma cholecystokinin, gastric inhibitory polypeptide, neurotensin, and pancreatic polypeptide. MCT infusion reduced gastric tone but did not significantly affect perception or plasma gut hormone levels. LCTs produced greater gastric relaxation than MCTs.
CONCLUSIONS—The satiation induced by intraduodenal LCT infusion seems to involve changes in gastric tone and plasma gut hormone levels. The gastric relaxation induced by MCT infusion, together with the absence of any significant change in satiation scores and plasma hormone levels, suggests that, at least up to a certain level, gastric relaxation is not sufficient to induce satiation and that nutrient induced gastric relaxation may occur through cholecystokinin independent mechanisms.


Keywords: gastric tone; triglyceride; hormones; satiation; cholecystokinin; nutrients PMID:10601051

  11. Rapid cellular enrichment of eicosapentaenoate after a single intravenous injection of a novel medium-chain triacylglycerol:fish-oil emulsion in humans123

    PubMed Central

    Carpentier, Yvon A; Hacquebard, Mirjam; Portois, Laurence; Dupont, Isabelle E; Deckelbaum, Richard J

    2010-01-01

    Background: Dietary deficiency in n−3 (omega-3) polyunsaturated fatty acids (PUFAs) prevails in Western populations and potentially results in adverse health outcomes. To circumvent the slow n−3 PUFA incorporation in phospholipids of key cells after oral supplementation, a new preparation for intravenous bolus injection was developed with 20 g triacylglycerols/100 mL of a mixture of 80% medium-chain triacylglycerols (MCTs) and 20% fish oil (FO) (wt:wt), and 0.4 g α-tocopherol/100 mL of the same mixture. Objective: Our objective was to document the enrichment of n−3 PUFAs in leukocyte and platelet phospholipids after a bolus intravenous injection of MCT:FO in men. Design: Twelve healthy male subjects received injections over a 5-min period of 50 mL of either MCT:FO or a control MCT:long-chain triacylglycerol (MCT:LCT) emulsion containing 20 g triacylglycerols/100 mL with equal amounts (wt:wt) of MCT and soybean triacylglycerols (LCT) and containing 0.02 g α-tocopherol/100 mL; after an 8-wk interval, the subjects received injections of the other preparation. Results: Clinical and biological variables that assessed tolerance and safety remained unchanged. Plasma elimination was faster for MCT:FO than for MCT:LCT (half-life: 24.5 ± 3.5 min compared with 32.9 ± 3.0 min; P < 0.025). This was associated with a greater increase in the plasma nonesterified fatty acid concentration. The content of n−3 PUFAs, specifically eicosapentaenoic acid (20:5n−3), increased in leukocyte and platelet phospholipids within 60 min and ≥24 h after MCT:FO injection. Conclusion: Bolus intravenous injection of a novel MCT:FO emulsion allows rapid enrichment of cells with n−3 PUFAs. PMID:20147473

  12. The critical micelle concentration of lecithin in bulk oils and medium chain triacylglycerol is influenced by moisture content and total polar materials.

    PubMed

    Kim, JiSu; Kim, Mi-Ja; Lee, JaeHwan

    2018-09-30

    Effects of different moisture contents and oxidised compounds on the critical micelle concentration (CMC) of lecithin were determined in bulk oils and in medium-chain triacylglycerols (MCT). CMC of lecithin in MCT was significantly higher than that in other vegetable oils including olive, soybean, corn, and rapeseed oils (p < 0.05). Presence of moisture significantly affected the CMC of lecithin in MCT (p < 0.05). CMC of lecithin was high when the moisture content was below 900 ppm, whereas at a moisture content of 1000 ppm, CMC of lecithin decreased significantly (p < 0.05), and then started to increase. Addition of total polar materials (TPM), which are oxidation products, at 3 and 5% concentrations, decreased CMC of lecithin significantly (p < 0.05) in MCT, compared to when 0, 1, and 1.5% of TPM was added to MCT. As the degree of oxidation increased in corn oil, CMC of lecithin gradually decreased. Additionally, under different moisture contents, corn oils showed a similar pattern of CMC of lecithin in MCT, whereas oxidised corn oil had a little lower CMC of lecithin than unoxidised corn oil. The results clearly showed that the concentration of lecithin for the formation of micelles is greatly influenced by the presence of oxidation products and the moisture content in bulk oils. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Preventive Effects of the Dietary Intake of Medium-chain Triacylglycerols on Immobilization-induced Muscle Atrophy in Rats.

    PubMed

    Nishimura, Shuhei; Inai, Makoto; Takagi, Tetsuo; Nonaka, Yudai; Urashima, Shogo; Honda, Kazumitsu; Aoyama, Toshiaki; Terada, Shin

    2017-08-01

    Previous studies have shown that medium-chain triacylglycerols (MCTs) exert favorable effects on protein metabolism. This study evaluated the effects of the dietary intake of MCTs on rat skeletal muscle mass and total protein content during casting-induced hindlimb immobilization, which causes substantial protein degradation and muscle atrophy. Rats were fed a standard diet containing long-chain triacylglycerols (LCTs) or MCTs for 3 days and then a unilateral hindlimb was immobilized while they received the same diet. After immobilization for 3, 7, and 14 days, muscle mass and total protein content in immobilized soleus muscle in the LCT-fed rats had markedly decreased compared to the contralateral muscle; however, these losses were partially suppressed in MCT-fed rats. Autophagosomal membrane proteins (LC-I and -II), which are biomarkers of autophagy-lysosome activity, did not differ significantly between the LCT- and MCT-fed rats. In contrast, the immobilization-induced increase in muscle-specific E3 ubiquitin ligase MuRF-1 protein expression in immobilized soleus muscle relative to contralateral muscle was completely blocked in the MCT-fed rats and was significantly lower than that observed in the LCT-fed rats. Collectively, these results indicate that the dietary intake of MCTs at least partly alleviates immobilization-induced muscle atrophy by inhibiting the ubiquitin-proteasome pathway.

  14. 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.

  15. Structured triglycerides versus physical mixtures of medium- and long-chain triglycerides for parenteral nutrition in surgical or critically ill adult patients: Systematic review and meta-analysis.

    PubMed

    Wu, Guo Hao; Zaniolo, Orietta; Schuster, Heidi; Schlotzer, Ewald; Pradelli, Lorenzo

    2017-02-01

    New generations of parenteral lipid emulsions combine Long Chain Triglycerides (LCTs) with Medium Chain Triglycerides (MCTs) either by physically mixing MCT- and LCT-containing oils or by using synthetically structured triglycerides (STGs). In order to clarify some open issues relating to their comparative effect, in particular in terms of clinical outcomes, pertinent evidence was systematically identified, reviewed and meta-analyzed. PubMed, Scopus, Wanfang Data, China Hospital Knowledge Database and Google Scholar were searched for published clinical trials comparing STGs vs. MCTs/LCTs PN regimens administered over 5-7 days in surgical and/or critically ill patients. Two independent investigators performed screening and data extraction using a predefined list of parameters. Data were pooled using RevMan ® 5.2. Quality of evidence was assessed according to Cochrane's risk of bias tool. Pre-specified high quality (HQ), incremental analyses and a post hoc subgroup analysis were performed. 21 studies were included. The meta-analysis revealed a significantly better cumulative nitrogen balance (Std. mean difference [95% CI]) (1.34 [0.98-1.7], p < 0.00001), as well as higher values for pre-albumin (24.99 mg/L [6.71-43.27], p < 0.000001), and albumin (1.22 g/L [0.66-1.77] p < 0.0001), while plasma triglycerides were significantly lower (-0.28 mmol/L [-0.41 to -0.15], p < 0.0001) in the STG vs. MCT/LCT group. ALT, AST, and GGT were significantly lower with STGs than with MCTs/LCTs, while for total bilirubin and ALP only a trend was observed. STGs were also associated with a trend to a shorter hospital length of stay (LOS) (-1.74 days [-3.49 to 0.01] p = 0.05). Quality of evidence was affected by an unclear risk of selection bias, mostly due to the lack of detailed reporting (random sequence generation, allocation concealment). For the other domains, most of the weighted information was judged at low risk of bias. HQ estimated effects, incremental and

  16. Intestinal absorption of medium chain fatty acids: in vivo studies in pigs devoid of exocrine pancreatic secretion.

    PubMed

    Guillot, E; Lemarchal, P; Dhorne, T; Rerat, A

    1994-10-01

    In order to study the influence of pancreatic enzyme secretion on the intestinal absorption of medium-chain fatty acids (MCFA), three growing pigs (mean body-weight 61 kg) with ligated and severed pancreatic ducts were fitted with a permanent fistula in the duodenum and with two catheters in the portal vein and carotid artery respectively. An electromagnetic flow probe was also set up around the portal vein. A mixture of octanoic and decanoic acids, esterified as medium-chain triacylglycerols, together with maltose dextrine and nitrogenous fraction was continuously infused for 1 h into the duodenum. Samples of blood were withdrawn from the two vessels at regular intervals of time for 8 h and further analysed for their non-esterified octanoic and decanoic acid contents. The concentrations of non-esterified octanoic and decanoic acid in the portal blood increased slowly after the beginning of each infusion, reaching about 10 times higher values than the basal level. Only 26% of octanoic acid infused in the duodenum and 27% of decanoic acid were recovered in the portal flow throughout each experiment. The possible mechanisms underlying the appearance of MCFA in the portal blood in the absence of pancreatic enzyme secretions and the importance of duodenal absorption of MCT in such physiological conditions have been discussed.

  17. Long-chain fatty acid triglyceride (TG) metabolism disorder impairs male fertility: a study using adipose triglyceride lipase deficient mice.

    PubMed

    Masaki, Hidetake; Kim, Namhyo; Nakamura, Hitomi; Kumasawa, Keiichi; Kamata, Eriko; Hirano, Ken-Ichi; Kimura, Tadashi

    2017-07-01

    Does the deletion of adipose triglyceride lipase (Atgl) gene impair male fertility? The deletion of Atgl gene impaired male fertility but the effect was partially reversed by a low long-chain triglyceride (TG) diet. ATGL specifically hydrolyses long-chain fatty acid TG to diacylglycerol and a high level of expression of ATGL in testes has been reported. However, the role of ATGL in male fertility is unknown. To investigate the effect of deletion of Atgl gene on male fertility, cauda epididymides and testes were collected from wild-type, heterozygous and homozygous Atgl-deficient mice at 10 weeks of age and epididymal sperm analysis and histological analysis of the testes were performed. To investigate whether a medium-chain triglycerides (MCTs) replacement diet mitigated the impaired male fertility by deletion of Atgl gene, homozygous Atgl-deficient mice were fed a MCT replacement diet, or a standard diet including long-chain triglycerides (LCTs) in a control group, for 6 weeks from 5 weeks of age (n = 22). The systematic and local effects of the MCT replacement diet on spermatogenesis and sperm maturation in the epididymis were analyzed at 10 weeks of age. Hematoxylin and eosin staining in paraffin-embedded sections of testes and Oil Red O staining in frozen sections of testes were performed. The epididymal sperm concentrations were analyzed. Statistical analyses were performed using the Student's t-test or Mann-Whitney U test with Shapiro-Wilk Normality test. Although heterozygous mice were fertile and showed a similar number of epididymal total and motile sperm concentrations to wild-type mice, the deletion of Atgl gene in homozygous mice led to accumulation of TG deposits in testes and impaired spermatogenesis. The deletion of Atgl gene also impaired the sperm maturation process required for sperm to acquire the ability to move forward in the epididymis. The MCT replacement diet for 6 weeks increased the plasma level of non-esterified fatty acid (NEFA) (1

  18. Effects of short-term and long-term treatment with medium- and long-chain triglycerides ketogenic diet on cortical spreading depression in young rats.

    PubMed

    de Almeida Rabello Oliveira, Marcela; da Rocha Ataíde, Terezinha; de Oliveira, Suzana Lima; de Melo Lucena, Ana Luíza; de Lira, Carla Emmanuela Pereira Rodrigues; Soares, Anderson Acioli; de Almeida, Clarissa Beatriz Santos; Ximenes-da-Silva, Adriana

    2008-03-21

    The ketogenic diet (KD) is a high fat and low carbohydrate and protein diet. It is used in the clinical treatment of epilepsy, in order to decrease cerebral excitability. KD is usually composed by long-chain triglycerides (LCT) while medium-chain triglycerides (MCT) diet is beginning to be used in some clinical treatment of disorders of pyruvate carboxylase enzyme and long-chain fatty acid oxidation. Our study aimed to analyze the effects of medium- and long-chain KD on cerebral electrical activity, analyzing the propagation of the phenomenon of cortical spreading depression (CSD). Three groups of weaned rats (21 days old) received, for 7 weeks, either a control (AIN-93G diet), or a MCT-KD (rich in triheptanoin oil), or a LCT-KD (rich in soybean oil). They were compared to another three groups (21 days old) receiving the same diets for just 10 days. CSD propagation was evaluated just after ending the dietary treatments. Results showed that short-term KD treatment resulted in a significant reduction of the CSD velocity of propagation (control group: 4.02+/-1.04mm/min; MCT-KD: 0.81+/-1.46mm/min and LCT-KD: 2.26+/-0.41mm/min) compared to the control group. However, long-term treatment with both KDs had no effect on the CSD velocity (control group: 3.10+/-0.41mm/min, MCT-KD: 2.91+/-1.62mm/min, LCT-KD: 3.02+/-2.26mm/min) suggesting that both short-term KDs have a positive effect in decreasing brain cerebral excitability in young animals. These data show for the first time that triheptanoin has an effect on central nervous system.

  19. Lipid Emulsions Containing Medium Chain Triacylglycerols Blunt Bradykinin-Induced Endothelium-Dependent Relaxation in Porcine Coronary Artery Rings.

    PubMed

    Amissi, Said; Boisramé-Helms, Julie; Burban, Mélanie; Rashid, Sherzad K; León-González, Antonio J; Auger, Cyril; Toti, Florence; Meziani, Ferhat; Schini-Kerth, Valérie B

    2017-03-01

    Lipid emulsions for parenteral nutrition are used to provide calories and essential fatty acids for patients. They have been associated with hypertriglyceridemia, hypercholesterolemia, and metabolic stress, which may promote the development of endothelial dysfunction in patients. The aim of the present study was to determine whether five different industrial lipid emulsions may affect the endothelial function of coronary arteries. Porcine coronary artery rings were incubated with lipid emulsions 0.5, 1, or 2% (v/v) for 30 min before the determination of vascular reactivity in organ chambers and the level of oxidative stress using electron paramagnetic resonance. Incubation of coronary artery rings with either Lipidem ® , Medialipid ® containing long- and medium-chain triacylglycerols (LCT/MCT), or SMOFlipid ® containing LCT, MCT, omega-9, and -3, significantly reduced the bradykinin-induced endothelium-dependent relaxation, affecting both the nitric oxide (NO) and endothelium-dependent hyperpolarization (EDH) components, whereas, Intralipid ® containing LCT (soybean oil) and ClinOleic ® containing LCT (soybean and olive oil) did not have such an effect. The endothelial dysfunction induced by Lipidem ® was significantly improved by indomethacin, a cyclooxygenase (COX) inhibitor, inhibitors of oxidative stress (N-acetylcysteine, superoxide dismutase, catalase) and transition metal chelating agents (neocuproine, tetrathiomolybdate, deferoxamine and L-histidine). Lipidem ® significantly increased the arterial level of oxidative stress. The present findings indicate that lipid emulsions containing LCT/MCT induce endothelial dysfunction in coronary artery rings by blunting both NO- and EDH-mediated relaxations. The Lipidem ® -induced endothelial dysfunction is associated with increased vascular oxidative stress and the formation of COX-derived vasoconstrictor prostanoids.

  20. Importance of medium chain fatty acids in animal nutrition

    NASA Astrophysics Data System (ADS)

    Baltić, B.; Starčević, M.; Đorđević, J.; Mrdović, B.; Marković, R.

    2017-09-01

    Fats in animal and human nutrition are a common subject of research. These studies most often pay attention to particular fat groups (saturated, unsaturated, polyunsaturated fats or fats grouped by the length of their fatty acid chains into short, medium or long chain fatty acids). Medium chain fatty acids (MCFAs) have two main sources: milk and coconut oil. To date, research has shown these acids have positive effects on health, production, feed digestibility and lower body and muscle fats in broilers and swine. MCFAs possess antibacterial, anticoccidial and antiviral effects. Also, it has been proven that these acids act synergistically if they are used together with organic acids, essential oils, or probiotics. Nowadays, commercial MCFA products are available for use in animal nutrition as feed additives.

  1. Safety evaluation of a medium- and long-chain triacylglycerol oil produced from medium-chain triacylglycerols and edible vegetable oil.

    PubMed

    Matulka, R A; Noguchi, O; Nosaka, N

    2006-09-01

    To reduce the incorporation of dietary lipids into adipose tissue, modified fats and oils have been developed, such as medium-chain triacylglycerols (MCT). Typical dietary lipids from vegetable oils, termed long-chain triacylglycerols (LCT), are degraded by salivary, intestinal and pancreatic lipases into two fatty acids and a monoacyl glycerol; whereas, MCT are degraded by the same enzymes into three fatty acids and the simple glycerol backbone. Medium-chain fatty acids (MCFA) are readily absorbed from the small intestine directly into the bloodstream and transported to the liver for hepatic metabolism, while long-chain fatty acids (LCFA) are incorporated into chylomicrons and enter the lymphatic system. MCFA are readily broken down to carbon dioxide and two-carbon fragments, while LCFA are re-esterified to triacylglycerols and either metabolized for energy or stored in adipose tissue. Therefore, consumption of MCT decreases the incorporation of fatty acids into adipose tissue. However, MCT have technological disadvantages precluding their use in many food applications. A possible resolution is the manufacture and use of a triacylglycerol containing both LCT and MCT, termed medium- and long-chain triacylglycerol (MLCT). This manuscript describes studies performed for the safety evaluation of a MLCT oil enzymatically produced from MCT and edible vegetable oil (containing LCT), by a transesterification process. The approximate fatty acid composition of this MLCT consists of caprylic acid (9.7%), capric acid (3.3%), palmitic acid (3.8%), stearic acid (1.7%), oleic acid (51.2%), linoleic acid (18.4%), linolenic acid (9.0%), and other fatty acids (2.9%). The approximate percentages of long (L) and medium (M) fatty acids in the triacylglyerols are as follows: L, L, L (55.1%), L, L, M (35.2%), L, M, M (9.1%), and M, M, M (0.6%). The studies included: (1) acute study in rats (LD50>5000 mg/kg); (2) 6 week repeat-dose safety study via dietary administration to rats (NOAEL

  2. MCT/MOSFET Switch

    NASA Technical Reports Server (NTRS)

    Rippel, Wally E.

    1990-01-01

    Metal-oxide/semiconductor-controlled thyristor (MCT) and metal-oxide/semiconductor field-effect transistor (MOSFET) connected in switching circuit to obtain better performance. Offers high utilization of silicon, low forward voltage drop during "on" period of operating cycle, fast turnon and turnoff, and large turnoff safe operating area. Includes ability to operate at high temperatures, high static blocking voltage, and ease of drive.

  3. 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. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

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

    PubMed Central

    Schönfeld, Peter; Wojtczak, Lech

    2016-01-01

    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. Synergistic effect of PLGA nanoparticles and submicron triglyceride droplets in enhancing the intestinal solubilisation of a lipophilic weak base.

    PubMed

    Joyce, Paul; Prestidge, Clive A

    2018-06-15

    A novel hybrid microparticulate system composed of poly(lactic-co-glycolic) acid (PLGA) nanoparticles and submicron medium-chain triglyceride (MCT) droplets was fabricated to overcome the pH-dependent solubility and precipitation challenges associated with a model poorly water-soluble weak base, cinnarizine (CIN). Molecular CIN was confined within both the lipid and polymer phase of PLGA-lipid hybrid (PLH) and PLGA-lipid-mannitol hybrid (PLMH) particles, which offered significant biopharmaceutical advantages in comparison to the unformulated drug, submicron MCT droplets and PLGA nanoparticles. This was highlighted by a substantial reduction in the pH-induced precipitation during in vitro gastrointestinal two-step dissolution studies. A >2.5-fold solubilisation enhancement was observed for the composite particles during simulated intestinal conditions, compared to pure CIN. Furthermore, the drug solubilisation capacity during in vitro intestinal digesting conditions was ~2-2.5 times greater for PLMH particles compared to the precursor emulsion droplets and PLGA nanoparticles. The observations from this study indicate that a synergy exists between the degradation products of PLGA nanoparticles and lipid droplets, whereby the dual-phase release and dissolution mechanism of the hybrid particles aids in prolonging pH-provoked precipitation. Subsequently, the ability for PLGA polymers and oligomers to act as polymeric precipitation inhibitors has been highlighted for the first time. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. 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. © FASEB.

  7. [Applied studies of structured triglycerides for parenteral nutrition in severe hemorrhagic shock patients after resuscitation].

    PubMed

    Su, Mao-sheng; He, Lei; Liu, Zhi-wei; Ma, Huan-xian; Zhao, Qing-hua; Zhang, Wen-zhi

    2012-03-27

    To evaluate the effects of structured triglycerides in parenteral nutrition versus a physical medium-chain triglycerides (MCT)/long-chain triglycerides (LCT) mixture on severe hemorrhagic shock patients after resuscitation. In a randomized trial, we studied 20 critical patients with a total blood loss of over 3000 ml perioperatively and/or intraoperatively. The use of triglycerides started from Day 3 postoperation and parenteral nutrition lasted for no less than 5 days. They were allocated to receive one of two nutrition regiments: structured triglycerides in Group A (n = 10) and MCT/LCT in Group B (n = 10). There were no significant differences of general conditions in two groups. Before the start of parenteral nutrition (d0), d1 d3 and d5 after start of infusion, the following parameters were measured: hemoglobin (Hb), platelet count (Plt), alanine aminotransferase (ALT), total bilirubin (TB), direct bilirubin (DB), serum triglycerides (TG), prealbumin (PA) and transferrin (TF). And mean artery pressure (MAP), heart rate (HR) and central vein pressure (CVP) were also recorded at the same time-points. Then the post-TG changes of the above data were compared in both groups. After the use of triglycerides, there were no significant differences of MAP, HR, CVP, Hb and Plt in both groups (P > 0.05). At D3 and D5, the serum levels of TG ((2.1 ± 0.4) vs (1.6 ± 0.6) mg/L, (2.3 ± 0.7) vs (1.5 ± 0.3) mg/L) and alanine aminotransferase ((133 ± 58) vs (97 ± 26) U/L; (116 ± 48) vs (77 ± 31) U/L) were significantly higher in Group B versus those receiving structured triglycerides in Group A (P < 0.05). TB ((18 ± 15) vs (18 ± 11) µmol/L) and DB ((8.9 ± 3.2) vs (8.8 ± 2.5) µmol/L) had no significant differences in two groups (P > 0.05). The serum levels of such nutrition markers as PA ((195 ± 55) vs (166 ± 55) mg/L,(245 ± 53) vs (195 ± 58) mg/L) and TF ((2.6 ± 0.5) vs (2.5 ± 0.6) g/L, (3.3 ± 0.8) vs (2.9 ± 0.6) g/L)were significantly higher in Group A than

  8. Micellar emulsions composed of mPEG-PCL/MCT as novel nanocarriers for systemic delivery of genistein: a comparative study with micelles

    PubMed Central

    Zhang, Tianpeng; Wang, Huan; Ye, Yanghuan; Zhang, Xingwang; Wu, Baojian

    2015-01-01

    Polymeric micelles receive considerable attention as drug delivery vehicles, depending on the versatility in drug solubilization and targeting therapy. However, their use invariably suffers with poor stability both in in vitro and in vivo conditions. Here, we aimed to develop a novel nanocarrier (micellar emulsions, MEs) for a systemic delivery of genistein (Gen), a poorly soluble anticancer agent. Gen-loaded MEs (Gen-MEs) were prepared from methoxy poly(ethylene glycol)-block-(ε-caprolactone) and medium-chain triglycerides (MCT) by solvent-diffusion technique. Nanocarriers were characterized by dynamic light scattering, transmission electron microscopy, and in vitro release. The resulting Gen-MEs were approximately 46 nm in particle size with a narrow distribution. Gen-MEs produced a different in vitro release profile from the counterpart of Gen-ME. The incorporation of MCT significantly enhanced the stability of nanoparticles against dilution with simulated body fluid. Pharmacokinetic study revealed that MEs could notably extend the mean retention time of Gen, 1.57- and 7.38-fold as long as that of micelles and solution formulation, respectively, following intravenous injection. Furthermore, MEs markedly increased the elimination half-life (t1/2β) of Gen, which was 2.63-fold larger than that of Gen solution. Interestingly, Gen distribution in the liver and kidney for MEs group was significantly low relative to the micelle group in the first 2 hours, indicating less perfusion in such two tissues, which well accorded with the elongated mean retention time. Our findings suggested that MEs may be promising carriers as an alternative of micelles to systemically deliver poorly soluble drugs. PMID:26491290

  9. Optimization of the Synthesis of Structured Phosphatidylcholine with Medium Chain Fatty Acid.

    PubMed

    Ochoa-Flores, Angélica A; Hernández-Becerra, Josafat A; Cavazos-Garduño, Adriana; Vernon-Carter, Eduardo J; García, Hugo S

    2017-11-01

    Structured phosphatidylcholine was successfully produced by acidolysis between phosphatidylcholine and free medium chain fatty acid, using phospholipase A 1 immobilized on Duolite A568. Response surface methodology was applied to optimize the reaction system using three process parameters: molar ratio of substrates (phosphatidylcholine to free medium chain fatty acid), enzyme loading, and reaction temperature. All parameters evaluated showed linear and quadratic significant effects on the production of modified phosphatidylcholine; molar ratio of substrates contributed positively, but temperature influenced negatively. Increased enzyme loading also led to increased production of modified phosphatidylcholine but only during the first 9 hours of the acidolysis reaction. Optimal conditions obtained from the model were a ratio of phosphatidylcholine to free medium chain fatty acid of 1:15, an enzyme loading of 12%, and a temperature of 45°C. Under these conditions a production of modified phosphatidylcholine of 52.98 % were obtained after 24 h of reaction. The prediction was confirmed from the verification experiments; the production of modified phosphatidylcholine was 53.02%, the total yield of phosphatidylcholine 64.28% and the molar incorporation of medium chain fatty acid was 42.31%. The acidolysis reaction was scaled-up in a batch reactor with a similar production of modified phosphatidylcholine, total yield of phosphatidylcholine and molar incorporation of medium chain fatty acid. Purification by column chromatography of the structured phosphatidylcholine yielded 62.53% of phosphatidylcholine enriched with 42.52% of medium chain fatty acid.

  10. Structured triglycerides were well tolerated and induced increased whole body fat oxidation compared with long-chain triglycerides in postoperative patients.

    PubMed

    Sandström, R; Hyltander, A; Körner, U; Lundholm, K

    1995-01-01

    It has been proposed, on the basis of animal experiments, that medium-chain triglycerides (MCT) may exert more favorable effects on whole body metabolism of injured animals than long-chain triglycerides (LCT). Therefore, the present study was designed to evaluate whether structured triglycerides are associated with increased whole body fat oxidation without promotion of ketogenesis in postoperative patients. A structured lipid emulsion (73403 Pharmacia, Sweden) containing medium- and long-chain fatty acids, esterified randomly to glycerol in a triglyceride structure, was used. Whole body fat oxidation was determined by indirect calorimetry in the postoperative period. Patients were randomized to receive structured lipids 1 day followed by LCT (Intralipid, Pharmacia) the next day or vice versa during 6 postoperative days. In part 1 of the study patients received fat at 1.0 g/kg per day in the presence of 80% of the basal requirement of nonprotein calories. In part 2 patients received fat at 1.5 g/kg per day in the presence of 120% of the nonprotein caloric requirement. Amino acids were always provided at 0.15 g N/kg per day. Structured lipids were not associated with any side effects, were rapidly cleared from the plasma compartment, and were rapidly oxidized without any significant hyperlipidemia or ketosis. Provision of structured lipids in the presence of excess of nonprotein calories (part 2) caused a significantly higher whole body fat oxidation (2.4 +/- 0.05 g/kg per day) compared with LCT provision (1.9 +/- 0.06 g/kg per day) (p < .0001) examined in the same patients. The results demonstrated for the first time in man that provision of structured triglycerides were associated with increased whole body fat oxidation in stressed postoperative patients, which is in line with the original metabolic and biochemical concept for structured triglycerides. The study provided evidence to support that structured lipids may represent a next generation of IV fat emulsions

  11. Monocarboxylate Transporters MCT1 and MCT4 Regulate Migration and Invasion of Pancreatic Ductal Adenocarcinoma Cells.

    PubMed

    Kong, Su Chii; Nøhr-Nielsen, Asbjørn; Zeeberg, Katrine; Reshkin, Stephan Joel; Hoffmann, Else Kay; Novak, Ivana; Pedersen, Stine Falsig

    2016-08-01

    Novel treatments for pancreatic ductal adenocarcinoma (PDAC) are severely needed. The aim of this work was to explore the roles of H-lactate monocarboxylate transporters 1 and 4 (MCT1 and MCT4) in PDAC cell migration and invasiveness. Monocarboxylate transporter expression, localization, activity, and function were explored in human PDAC cells (MIAPaCa-2, Panc-1, BxPC-3, AsPC-1) and normal human pancreatic ductal epithelial (HPDE) cells, by quantitative polymerase chain reaction, immunoblotting, immunocytochemistry, lactate flux, migration, and invasion assays. MCT1 and MCT4 (messenger RNA, protein) were robustly expressed in all PDAC lines, localizing to the plasma membrane. Lactate influx capacity was highest in AsPC-1 cells and lowest in HPDE cells and was inhibited by the MCT inhibitor α-cyano-4-hydroxycinnamate (4-CIN), MCT1/MCT2 inhibitor AR-C155858, or knockdown of MCT1 or MCT4. PDAC cell migration was largely unaffected by MCT1/MCT2 inhibition or MCT1 knockdown but was reduced by 4-CIN and by MCT4 knockdown (BxPC-3). Invasion measured in Boyden chamber (BxPC-3, Panc-1) and spheroid outgrowth (BxPC-3) assays was attenuated by 4-CIN and AR-C155858 and by MCT1 or MCT4 knockdown. Human PDAC cells exhibit robust MCT1 and MCT4 expression and partially MCT1- and MCT4-dependent lactate flux. PDAC cell migration is partially dependent on MCT4; and invasion, on MCT1 and MCT4. Inhibition of MCT1 and MCT4 may have clinical relevance in PDAC.

  12. Metabolism of defined structured triglyceride particles compared to mixtures of medium and long chain triglycerides intravenously infused in dogs.

    PubMed

    Simoens, Ch; Deckelbaum, R J; Carpentier, Y A

    2004-08-01

    The present study aimed to determine whether including medium-chain fatty acids (MCFA) in specifically designed structured triglycerides (STG) with a MCFA in sn-1 and sn-3 positions and a long-chain (LC) FA in sn-2 position (MLM) would lead to different effects on plasma lipids and FA distribution into plasma and tissue lipids by comparison to a mixture of separate MCT and LCT molecules (MMM/LLL). The fatty acid (FA) composition was comparable in both lipid emulsions. Lipids were infused over 9h daily, in 2 groups of dogs (n = 6 each), for 28 days as a major component (55% of the non-protein energy intake) of total parenteral nutrition (TPN). Blood samples were obtained on specific days, before starting and just before stopping TPN. The concentration of plasma lipids was measured before starting and before stopping TPN on days 1, 2, 3, 4, 5, 8, 10, 12, 16 and 28. Biopsies were obtained from liver, muscle and adipose tissue 15 days before starting, and again on the day following cessation of TPN. In addition, the spleen was removed after the TPN period. FA composition in plasma and tissue lipids was analysed by gas liquid chromatography in different lipid components of plasma and tissues. No differences in either safety or tolerance parameters were detected between both lipid preparations. A lower rise of plasma TG (P < 0.05) was observed during MLM infusion, indicating a faster elimination rate of MLM vs MMM/LLL emulsion. In spite of the differences of TG molecules which would be assumed to affect the site of FA delivery and metabolic fate, FA distribution in phospholipids (PL) of hepatic and extrahepatic tissues did not substantially differ between both emulsions. Copyright 2003 Elsevier Ltd.

  13. Triglycerides Test

    MedlinePlus

    ... Other names for a triglycerides test: TG, TRIG, lipid panel, fasting lipoprotein panel What is it used ... A triglycerides test is usually part of a lipid profile. Lipid is another word for fat. A ...

  14. Triglyceride level

    MedlinePlus

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

  15. Medium-chain fatty acid synthesis in lactating-rabbit mammary gland. Intracellular concentration and specificity of medium-chain acyl thioester hydrolase.

    PubMed Central

    Knudsen, J

    1979-01-01

    The concentration of medium-chain acyl thioester hydrolase and of fatty acid synthetase was determined by rocket immunoelectrophoresis in nine different particle-free supernatant fractions from lactating-rabbit mammary gland. The molar ratio of the hydrolase to fatty acid synthetase was 1.99 +/- 0.66 (mean +/- S.D.). A rate-limiting concentration of malonyl-CoA was required to ensure the predominant synthesis of medium-chain fatty acids when 2 mol of the hydrolase was added per mol of fatty acid synthetase. The interaction of the hydrolase with fatty acid synthetase was concentration-dependent, though an optimum concentration of hydrolase to synthetase could not be obtained. The lactating-rabbit mammary gland hydrolase altered the pattern of fatty acids synthesized by fatty acid synthetases prepared from cow, goat, sheep and rabbit lactating mammary glands, rabbit liver and cow adipose tissue. PMID:574008

  16. Effect of GPR84 deletion on obesity and diabetes development in mice fed long chain or medium chain fatty acid rich diets.

    PubMed

    Du Toit, Eugene; Browne, Liam; Irving-Rodgers, Helen; Massa, Helen M; Fozzard, Nicolette; Jennings, Michael P; Peak, Ian R

    2017-04-20

    Although there is good evidence showing that diets rich in medium chain fatty acids (MCFAs) have less marked obesogenic and diabetogenic effects than diets rich in long chain fatty acids (LCFAs), the role of the pro-inflammatory, medium chain fatty acid receptor (GPR84) in the aetiology of obesity and glucose intolerance is not well characterised. We set out to determine whether GPR84 expression influences obesity and glucose intolerance susceptibility in MCFA and LCFA rich diet fed mice. Wild type (WT) and GPR84 knockout (KO) mice were fed a control, MCFA or LCFA diet, and body mass, heart, liver and epididymal fat mass was assessed, as well as glucose tolerance and adipocyte size. LCFA diets increased body mass and decreased glucose tolerance in both WT and GPR84 KO animals while MCFA diets had no effect on these parameters. There were no differences in body weight when comparing WT and GPR84 KO mice on the respective diets. Glucose tolerance was also similar in WT and GPR84 KO mice irrespective of diet. Liver mass was increased following LCFA feeding in WT but not GPR84 KO mice. Hepatic triglyceride content was increased in GPR84 KO animals fed MCFA, and myocardial triglyceride content was increased in GPR84 KO animals fed LCFA. GPR84 deletion had no effects on body weight or glucose tolerance in mice fed either a high MCFA or LCFA diet. GPR84 may influence lipid metabolism, as GPR84 KO mice had smaller livers and increased myocardial triglyceride accumulation when fed LCFA diets, and increased liver triglyceride accumulation in responses to increased dietary MCFAs.

  17. MCT1 modulates cancer cell pyruvate export and growth of tumors that co-express MCT1 and MCT4

    PubMed Central

    Hong, Candice Sun; Graham, Nicholas A.; Gu, Wen; Camacho, Carolina Espindola; Mah, Vei; Maresh, Erin L.; Alavi, Mohammed; Bagryanova, Lora; Krotee, Pascal A. L.; Gardner, Brian K.; Behbahan, Iman Saramipoor; Horvath, Steve; Chia, David; Mellinghoff, Ingo K.; Hurvitz, Sara A.; Dubinett, Steven M.; Critchlow, Susan E.; Kurdistani, Siavash K.; Goodglick, Lee; Braas, Daniel; Graeber, Thomas G.; Christofk, Heather R.

    2016-01-01

    SUMMARY Monocarboxylate Transporter 1 (MCT1) inhibition is thought to block tumor growth through disruption of lactate transport and glycolysis. Here we show MCT1 inhibition impairs proliferation of glycolytic breast cancer cells co-expressing MCT1 and MCT4 via disruption of pyruvate rather than lactate export. MCT1 expression is elevated in glycolytic breast tumors, and high MCT1 expression predicts poor prognosis in breast and lung cancer patients. Acute MCT1 inhibition reduces pyruvate export but does not consistently alter lactate transport or glycolytic flux in breast cancer cells that co-express MCT1 and MCT4. Despite the lack of glycolysis impairment, MCT1 loss-of-function decreases breast cancer cell proliferation and blocks growth of mammary fat pad xenograft tumors. Our data suggest MCT1 expression is elevated in glycolytic cancers to promote pyruvate export, which when inhibited enhances oxidative metabolism and reduces proliferation. This study presents an alternative molecular consequence of MCT1 inhibitors further supporting their use as anti-cancer therapeutics. PMID:26876179

  18. MCT1 Modulates Cancer Cell Pyruvate Export and Growth of Tumors that Co-express MCT1 and MCT4.

    PubMed

    Hong, Candice Sun; Graham, Nicholas A; Gu, Wen; Espindola Camacho, Carolina; Mah, Vei; Maresh, Erin L; Alavi, Mohammed; Bagryanova, Lora; Krotee, Pascal A L; Gardner, Brian K; Behbahan, Iman Saramipoor; Horvath, Steve; Chia, David; Mellinghoff, Ingo K; Hurvitz, Sara A; Dubinett, Steven M; Critchlow, Susan E; Kurdistani, Siavash K; Goodglick, Lee; Braas, Daniel; Graeber, Thomas G; Christofk, Heather R

    2016-02-23

    Monocarboxylate transporter 1 (MCT1) inhibition is thought to block tumor growth through disruption of lactate transport and glycolysis. Here, we show MCT1 inhibition impairs proliferation of glycolytic breast cancer cells co-expressing MCT1 and MCT4 via disruption of pyruvate rather than lactate export. MCT1 expression is elevated in glycolytic breast tumors, and high MCT1 expression predicts poor prognosis in breast and lung cancer patients. Acute MCT1 inhibition reduces pyruvate export but does not consistently alter lactate transport or glycolytic flux in breast cancer cells that co-express MCT1 and MCT4. Despite the lack of glycolysis impairment, MCT1 loss-of-function decreases breast cancer cell proliferation and blocks growth of mammary fat pad xenograft tumors. Our data suggest MCT1 expression is elevated in glycolytic cancers to promote pyruvate export that when inhibited, enhances oxidative metabolism and reduces proliferation. This study presents an alternative molecular consequence of MCT1 inhibitors, further supporting their use as anti-cancer therapeutics. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Medium-chain fatty acids as ligands for orphan G protein-coupled receptor GPR84.

    PubMed

    Wang, Jinghong; Wu, Xiaosu; Simonavicius, Nicole; Tian, Hui; Ling, Lei

    2006-11-10

    Free fatty acids (FFAs) play important physiological roles in many tissues as an energy source and as signaling molecules in various cellular processes. Elevated levels of circulating FFAs are associated with obesity, dyslipidemia, and diabetes. Here we show that GPR84, a previously orphan G protein-coupled receptor, functions as a receptor for medium-chain FFAs with carbon chain lengths of 9-14. Medium-chain FFAs elicit calcium mobilization, inhibit 3',5'-cyclic AMP production, and stimulate [35S]guanosine 5'-O-(3-thiotriphosphate) binding in a GPR84-dependent manner. The activation of GPR84 by medium-chain FFAs couples primarily to a pertussis toxin-sensitive G(i/o) pathway. In addition, we show that GPR84 is selectively expressed in leukocytes and markedly induced in monocytes/macrophages upon activation by lipopolysaccharide. Furthermore, we demonstrate that medium-chain FFAs amplify lipopolysaccharide-stimulated production of the proinflammatory cytokine interleukin-12 p40 through GPR84. Our results indicate a role for GPR84 in directly linking fatty acid metabolism to immunological regulation.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  1. Structured medium and long chain triglycerides show short-term increases in fat oxidation, but no changes in adiposity in men.

    PubMed

    Roynette, Catherine E; Rudkowska, Iwona; Nakhasi, Dilip K; Jones, Peter J H

    2008-05-01

    Medium chain triglycerides (MCT) have been suggested as modulators of human energy expenditure (EE) and thus may influence total and regional body fat distribution. To investigate in overweight men the effects of structured medium and long chain triglycerides on EE, substrate oxidation and body adiposity, compared to extra virgin olive oil (OO). In a 6 week single-blind crossover study, 23 overweight men were randomly assigned to consume a standard high-fat diet of which 75% total fat was provided as either structured medium and long chain triglycerides referred to as structured oil (StO), or OO. EE and body composition were measured using indirect calorimetry and magnetic resonance imaging, respectively, at weeks 1 and 6 of each phase. Body weight decreased (p<0.01) from baseline to end-point during consumption of both the StO (-1.46+/-0.4k g) and OO (-1.17+/-0.4 kg); however, no significant treatment differences were observed. There were no changes in body composition among treatment groups. No differences between diets for EE measurements were reported. Fat oxidation rates did not differ between oils, but were reduced (p<0.05) in the StO group between baseline (0.0020+/-0.0003 g/kg fat free mass per min) in comparison to after week 6 (0.0013+/-0.0001 g/kg fat free mass per min). No differences in carbohydrate oxidation rate were noted across diets or time. The present structured medium and long chain triglyceride oil increases short-term fat oxidation but fails to modulate body weight or adiposity through a change in EE.

  2. Dietary medium-chain triacylglycerols versus long-chain triacylglycerols for body composition in adults: systematic review and meta-analysis of randomized controlled trials.

    PubMed

    Bueno, Nassib B; de Melo, Ingrid V; Florêncio, Telma T; Sawaya, Ana L

    2015-01-01

    To assess the effect of replacing dietary long-chain triacylglycerols (LCTs) with medium-chain triacylglycerols (MCTs) on body composition in adults. We conducted a meta-analysis of randomized controlled trials (RCTs), to determine whether individuals assigned to replace at least 5 g of dietary LCTs with MCTs for a minimum of 4 weeks show positive modifications on body composition. We systematically searched, through July 2013, the CENTRAL, EMBASE, LILACS, and MEDLINE databases for RCTs that investigated the effects of MCT intake on body composition in adults. Two authors independently extracted data and assessed risk of bias. Weighted mean differences (WMDs) were calculated for net changes in the outcomes. We assessed heterogeneity by the Cochran Q test and I(2) statistic and publication bias with the Egger's test. Prespecified sensitivity analyses were performed. In total, 11 trials were included, from which 5 presented low risk of bias. In the overall analysis, including all studies, individuals who replaced dietary LCT with MCT showed significantly reduced body weight (WMD, -0.69 kg; 95% confidence interval [CI], -1.1 to -0.28; p = 0.001); body fat (-0.89 kg; 95% CI, -1.27 to -0.51; p < 0.001), and WC (-1.78 cm; 95% CI, -2.4 to -1.1; p < 0.001). The overall quality of the evidence was low to moderate. Trials with a crossover design were responsible for the heterogeneity. Despite statistically significant results, the recommendation to replace dietary LCTs with MCTs must be cautiously taken, because the available evidence is not of the highest quality.

  3. Condensing enzymes from Cuphea wrightii associated with medium chain fatty acid biosynthesis.

    PubMed

    Slabaugh, M B; Leonard, J M; Knapp, S J

    1998-03-01

    Seed oils of most Cuphea species contain > 90% medium chain (C8-C14) fatty acids. Thioesterases with specificity for these substrates are important determinants of the medium chain phenotype. The role of condensing enzymes, however, has not been investigated. cDNA clones encoding beta-ketoacyl-acyl carrier protein (ACP) synthase (KAS) were isolated from C. wrightii, a C10/C12-producing species. Deduced amino acid sequences of four unique clones were approximately 60% identical to plant KAS I sequences and approximately 75% identical to a distinct class of KAS sequences recently identified in castor and barley. A 46 kDa protein that was observed only in developing and mature seed was detected using antiserum directed against recombinant Cuphea KAS protein. The 46 kDa protein was abundant in developing seeds of six medium chain-producing Cuphea species but barely detected in one long chain-producing species. A 48 kDa protein identified immunologically as KAS I was expressed in both medium and long chain-producing Cuphea species and was detected in all tissues tested. In in vitro assays, extracts from C. wrightii and C. viscosissima developing embryos were unable to extend fatty acid chains beyond C10 following treatment with 10 microns cerulenin, a potent inhibitor of KAS I. However, a C. viscosissima mutant, cpr-1, whose seed oils are deficient in caprate relative to wild type, was impaired in extension of C8 to C10 in this assay and Western analysis revealed a specific deficiency in 46 kDa KAS in cpr-1 embryos. These results implicate cerulenin-resistant condensing activity in production of medium chain fatty acids in Cuphea.

  4. Application of MCT Failure Criterion using EFM

    DTIC Science & Technology

    2010-03-26

    because HELIUS:MCT™ does not facilitate this. Attempts have been made to use ABAQUS native thermal expansion model combined in addition to Helius-MCT... ABAQUS using a user defined element subroutine EFM. Comparisons have been made between the analysis results using EFM-MCT code and HELIUS:MCT™ code...using the Element-Failure Method (EFM) in ABAQUS . The EFM-MCT has been implemented in ABAQUS using a user defined element subroutine EFM. Comparisons

  5. Impact of MCT1 Haploinsufficiency on the Mouse Retina.

    PubMed

    Peachey, Neal S; Yu, Minzhong; Han, John Y S; Lengacher, Sylvain; Magistretti, Pierre J; Pellerin, Luc; Philp, Nancy J

    2018-01-01

    The monocarboxylate transporter 1 (MCT1) is highly expressed in the outer retina, suggesting that it plays a critical role in photoreceptors. We examined MCT1 +/- heterozygotes, which express half of the normal complement of MCT1. The MCT1 +/- retina developed normally and retained normal function, indicating that MCT1 is expressed at sufficient levels to support outer retinal metabolism.

  6. Effect of different polysorbates on development of self-microemulsifying drug delivery systems using medium chain lipids.

    PubMed

    Shah, Ankita; Thool, Prajwal; Sorathiya, Komal; Prajapati, Hetal; Dalrymple, Damon; Serajuddin, Abu T M

    2018-02-01

    The primary objective of this study was to develop lipid-based self-microemulsifying drug delivery systems (SMEDDS) without using any organic cosolvents that would spontaneously form microemulsions upon dilution with water. Cosolvents were avoided to prevent possible precipitation of drug upon dilution and other stability issues. Different polysorbates, namely, Tween 20, Tween 40, Tween 60, and Tween 80, were used as surfactants, and Captex 355 EP/NF (glycerol tricaprylate/caprate) or its 1:1 mixture with Capmul MCM NF (glycerol monocaprylocaprate) were used as lipids. Captex 355-Tween-water ternary phase diagrams showed that oil-in-water microemulsions were formed only when the surfactant content was high (80-90%) and the lipid content low (10-20%). Thus, mixtures of Tweens with Captex 355 alone were not suitable to prepare SMEDDS with substantial lipid contents. However, when Captex 355 was replaced with the 1:1 mixture of Captex 355 and Capmul MCM, clear isotropic microemulsion regions in phase diagrams with sizes in the increasing order of Tween 20 < Tween 40 < Tween 60 < Tween 80 were obtained. Tween 80 had the most profound effect among all surfactants as microemulsions were formed with lipid to surfactant ratios as high as 7:3, which may be attributed to the presence of double bond in its side chain that increased the curvature of surfactant layer. Thus, lipid-surfactant mixtures containing 1:1 mixture of medium chain triglyceride (Captex 355) and monoglyceride (Capmul MCM) and as low as 30% Tween 80 were identified as organic cosolvent-free systems for the preparation of SMEDDS. Formulations with a model drug, probucol, dispersed spontaneously and rapidly upon dilution with water to form microemulsions without any drug precipitation.

  7. Stability of MCT/LCT-based total nutrient admixtures for neonatal use over 30 hours at room temperature: applying pharmacopeial standards.

    PubMed

    Driscoll, David F; Silvestri, Anthony P; Bistrian, Bruce R

    2010-01-01

    United States Pharmacopeial Chapter <729> places a limit on the percentage of large fat globules >5 microm, expressed as a PFAT5 of <0.05% for all native lipid emulsions. Some adult total nutrient admixtures (TNAs) have also remained below this limit for up to 48 hours. In 2003, medium-chain/long-chain triglyceride (MCT/LCT)-based neonatal TNAs with between 2% and 3% amino acid (AA) concentrations were shown to be similarly stable by the PFAT5 parameter. Stability assessment of neonatal TNAs with AA <2% or > or =3% were tested. Eight neonatal TNAs with various combinations of AA (1%, 1.5%, 3%, and 4%), glucose (G; 5% and 10%), and MCT/LCT (ML; 2% and 4%) and standard concentrations of additives were tested in triplicate (n = 24) over 30 hours (immediately after mixing, then at 6, 24, and 30 hours) at 25 degrees C +/- 2 degrees C. PFAT5 determinations for all 24 formulations were made in duplicate, immediately after mixing, and then at 6, 24, and 30 hours later. Mean droplet size (MDS) and pH were assessed at the outset and end of the study. The differences in the PFAT5 levels were significant (P < .001) by a 2-way analysis of variance based on formula and time as the independent variables. The TNAs with 1% and 1.5% AA with all Gs and MLs (group 1, n = 12) had PFAT5 levels >0.05% (up to 0.50%) in most samples (68 of 96 samples, or 71% of cases) in the study, whereas in the same TNAs, but made with 3% and 4% AA (group 2, n = 12), 100% of samples (all 96 cases) had PFAT5 levels <0.05% (up to 0.04%), and this difference was significant (P < .001). Pairwise comparisons between groups based on overall values of PFAT5, MDS, and pH showed significant differences between groups for all variables. For neonatal TNAs, AA level is the most sensitive determinant of stability, and the PFAT5 parameter is the most sensitive indicator of stability.

  8. Optimisation of immunofluorescence methods to determine MCT1 and MCT4 expression in circulating tumour cells.

    PubMed

    Kershaw, Stephen; Cummings, Jeffrey; Morris, Karen; Tugwood, Jonathan; Dive, Caroline

    2015-05-10

    The monocarboxylate transporter-1 (MCT1) represents a novel target in rational anticancer drug design while AZD3965 was developed as an inhibitor of this transporter and is undergoing Phase I clinical trials ( http://www.clinicaltrials.gov/show/NCT01791595 ). We describe the optimisation of an immunofluorescence (IF) method for determination of MCT1 and MCT4 in circulating tumour cells (CTC) as potential prognostic and predictive biomarkers of AZD3965 in cancer patients. Antibody selectivity was investigated by western blotting (WB) in K562 and MDAMB231 cell lines acting as positive controls for MCT1 and MCT4 respectively and by flow cytometry also employing the control cell lines. Ability to detect MCT1 and MCT4 in CTC as a 4(th) channel marker utilising the Veridex™ CellSearch system was conducted in both human volunteer blood spiked with control cells and in samples collected from small cell lung cancer (SCLC) patients. Experimental conditions were established which yielded a 10-fold dynamic range (DR) for detection of MCT1 over MCT4 (antibody concentration 6.25 μg/mL; integration time 0.4 seconds) and a 5-fold DR of MCT4 over MCT 1 (8 μg/100 μL and 0.8 seconds). The IF method was sufficiently sensitive to detect both MCT1 and MCT4 in CTCs harvested from cancer patients. The first IF method has been developed and optimised for detection of MCT 1 and MCT4 in cancer patient CTC.

  9. Minimum Competency Testing (MCT). Some Remarks.

    ERIC Educational Resources Information Center

    Howell, John F.

    The effort to institute minimum competency testing (MCT) is nearly universal despite the need to debate its basic definitions, implications, and consequences beforehand. There are seven distinct reasons for the MCT movement: (1) legislative zeal; (2) unfavorable allegations by local and national press; (3) economic accountability; (4) the…

  10. MCT1, MCT4 and CD147 gene polymorphisms in healthy horses and horses with myopathy.

    PubMed

    Mykkänen, A K; Koho, N M; Reeben, M; McGowan, C M; Pösö, A R

    2011-12-01

    Polymorphisms in human lactate transporter proteins (monocarboxylate transporters; MCTs), especially the MCT1 isoform, can affect lactate transport activity and cause signs of exercise-induced myopathy. Muscles express MCT1, MCT4 and CD147, an ancillary protein, indispensable for the activity of MCT1 and MCT4. We sequenced the coding sequence (cDNA) of horse MCT4 for the first time and examined polymorphisms in the cDNA of MCT1, MCT4 and CD147 of 16 healthy horses. To study whether signs of myopathy are linked to the polymorphisms, biopsy samples were taken from 26 horses with exercise-induced recurrent myopathy. Two polymorphisms that cause a change in amino acid sequence were found in MCT1 (Val(432)Ile and Lys(457)Gln) and one in CD147 (Met(125)Val). All polymorphisms in MCT4 were silent. Mutations in MCT1 or CD147 in equine muscle were not associated with myopathy. In the future, a functional study design is needed to evaluate the physiological role of the polymorphisms found. Copyright © 2010 Elsevier Ltd. All rights reserved.

  11. Standard Review Risk Assessment on Medium-chain and Long-chain Chlorinated paraffin PMN submissions by Dover Chemical

    EPA Pesticide Factsheets

    This assessment was conducted under EPA’s TSCA Section 5 New Chemicals Program. EPA is assessing Medium-chain Chlorinated Paraffin (MCCP) and Long-Chain Chlorinated Paraffin (LCCP) chemicals as part of its New Chemicals Review program.

  12. Standard Review Risk Assessment on Medium-chain and Long-chain Chlorinated paraffin PMN submissions by INEOS Chlor Americas

    EPA Pesticide Factsheets

    This assessment was conducted under EPA’s TSCA Section 5 New Chemicals Program. EPA is assessing Medium-chain Chlorinated Paraffin (MCCP) and Long-Chain Chlorinated Paraffin (LCCP) chemicals as part of its New Chemicals Review program.

  13. Standard Review Risk Assessment on Medium-chain and Long-chain Chlorinated paraffin PMN submissions by Qualice, LLC

    EPA Pesticide Factsheets

    This assessment was conducted under EPA’s TSCA Section 5 New Chemicals Program. EPA is assessing Medium-chain Chlorinated Paraffin (MCCP) and Long-Chain Chlorinated Paraffin (LCCP) chemicals as part of its New Chemicals Review program.

  14. A search for microorganisms producing medium-chain alkanes from aldehydes.

    PubMed

    Ito, Masakazu; Kambe, Hiromi; Kishino, Shigenobu; Muramatsu, Masayoshi; Ogawa, Jun

    2018-01-01

    Microorganisms with medium-chain alkane-producing activity are promising for the bio-production of drop-in fuel. In this study, we screened for microorganisms producing tridecane from tetradecanal. The activity of aldehyde decarbonylation was found in a wide range of microbes. In particular, the genus Klebsiella in the Enterobacteriaceae family was found to have a high ability to produce alkanes from aldehydes via enzyme catalyzed reaction. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  15. Cuphea: a new plant source of medium-chain fatty acids.

    PubMed

    Graham, S A

    1989-01-01

    The plant genus Cuphea (family Lythraceae) promises to provide a new source of industrially and nutritionally important medium-chain fatty acids, especially of lauric acid now supplied exclusively by coconut and palm kernel oils from foreign sources. The seed lipids of Cuphea were first discovered in the 1960s to contain high percentages of several medium-chain fatty acids, including caprylic, capric, lauric, and myristic acid. Research is still in the early stages, but it is intensifying toward the goal of developing the genus into a new temperate climate crop for production of specialty oils. Given the diversity of Cuphea seed lipid composition and the wide ecological and distributional range of the genus, it may be possible to tailor crops to produce selected fatty acids on demand under a variety of growing conditions. Cuphea comprises about 260 species, most native to the New World tropics. Its morphology, classification, chromosome numbers, distribution, ecology, and folk uses are presented. Seed structure is described and seed lipid composition for 73 species is summarized. Problems in domestication and agronomic progress are reviewed. Knowledge of the biosynthetic mechanism controlling the lipids produced by Cuphea remains very limited. Future research in this area, and particularly successful employment of gene transfer techniques, may allow genes controlling the mechanism to be transferred to an already established seed oil producer such as rapeseed. Presently, both traditional plant breeding techniques and newer biotechnological methods are directed toward Cuphea oilseed development.

  16. A novel regulatory system in plants involving medium-chain fatty acids.

    PubMed

    Hunzicker, Gretel Mara

    2009-12-01

    Polyethylene glycol sorbitan monoacylates (Tween) are detergents of widespread use in plant sciences. However, little is known about the plant response to these compounds. Interestingly, the structure of Tweens' detergents (especially from Tween 20) resembles the lipid A structure from gram-negative bacteria polysaccharides (a backbone with short saturated fatty acids). Thus, different assays (microarray, GC-MS, RT-PCR, Northern blots, alkalinization and mutant analyses) were conducted in order to elucidate physiological changes in the plant response to Tween 20 detergent. Tween 20 causes a rapid and complex change in transcript abundance which bears all characteristics of a pathogenesis-associated molecular pattern (PAMP)/elicitor-induced defense response, and they do so at concentrations which cause no detectable deleterious effects on plant cellular integrity. In the present work, it is shown that the PAMP/elicitor-induced defense responses are caused by medium-chain fatty acids which are efficiently released from the Tween backbone by the plant, notably lauric acid (12:0) and methyl lauric acid. These compounds induce the production of ethylene, medium alkalinization and gene activation in a jasmonate-independent manner. Medium-chain fatty acids are thus novel elicitors/regulators of plant pathogen defense as they have being proved in animals.

  17. Metabolic Engineering for Enhanced Medium Chain Omega Hydroxy Fatty Acid Production in Escherichia coli

    PubMed Central

    Xiao, Kang; Yue, Xiu-Hong; Chen, Wen-Chao; Zhou, Xue-Rong; Wang, Lian; Xu, Lin; Huang, Feng-Hong; Wan, Xia

    2018-01-01

    Medium chain hydroxy fatty acids (HFAs) at ω-1, 2, or 3 positions (ω-1/2/3) are rare in nature but are attractive due to their potential applications in industry. They can be metabolically engineered in Escherichia coli, however, the current yield is low. In this study, metabolic engineering with P450BM3 monooxygenase was applied to regulate both the chain length and sub-terminal position of HFA products in E. coli, leading to increased yield. Five acyl-acyl carrier protein thioesterases from plants and bacteria were first evaluated for regulating the chain length of fatty acids. Co-expression of the selected thioesterase gene CcFatB1 with a fatty acid metabolism regulator fadR and monooxygenase P450BM3 boosted the production of HFAs especially ω-3-OH-C14:1, in both the wild type and fadD deficient strain. Supplementing renewable glycerol to reduce the usage of glucose as a carbon source further increased the HFAs production to 144 mg/L, representing the highest titer of such HFAs obtained in E. coli under the comparable conditions. This study illustrated an improved metabolic strategy for medium chain ω-1/2/3 HFAs production in E. coli. In addition, the produced HFAs were mostly secreted into culture media, which eased its recovery. PMID:29467747

  18. Characterization of medium-chain-length polyhydroxyalkanoate biosynthesis by Pseudomonas mosselii TO7 using crude glycerol.

    PubMed

    Liu, Ming-Hsu; Chen, Yi-Jr; Lee, Chia-Yin

    2018-03-01

    Polyhydroxyalkanoates (PHAs) are biopolyesters produced by microorganisms that are environmentally friendly. PHAs can be used to replace traditional plastic to reduce environmental pollution in various fields. PHA production costs are high because PHA must be produced from a carbon substrate. The purpose of this study was to find the strain that can used the BDF by-product as the sole carbon source to produce high amounts of medium-chain-length PHA. Three isolates were evaluated for potential PHA production by using biodiesel-derived crude glycerol as the sole carbon source. Among them, Pseudomonas mosselii TO7 yielded high PHA content. The PHA produced from P. mosselii TO7 were medium-chain-length-PHAs. The PHA content of 48% cell dry weight in 48 h with a maximum PHA productivity of 13.16 mg PHAs L -1  h -1 . The narrow polydispersity index value of 1.3 reflected the homogeneity of the polymer chain, which was conducive to industrial applications.

  19. Enhanced Bioavailability of Curcumin Nanoemulsions Stabilized with Phosphatidylcholine Modified with Medium Chain Fatty Acids.

    PubMed

    Ochoa-Flores, Angélica A; Hernández-Becerra, Josafat A; Cavazos-Garduño, Adriana; Soto-Rodríguez, Ida; Sanchez-Otero, Maria Guadalupe; Vernon-Carter, Eduardo J; García, Hugo S

    2017-01-01

    Curcumin is a natural, oil-soluble polyphenolic compound with potent anticancer, anti-inflammatory, and antioxidant activities. In its free form, it is very poorly absorbed in the gut due to its very low solubility. The use of nanoemulsions as carrier is a feasible way for improving curcumin bioavailability. To this end, the choice of emulsifying agent for stabilizing the nanoemulsions is of the upmost importance for achieving a desired functionality. Phosphatidylcholine (PC) and phosphatidycholine enriched (PCE) with medium chain fatty acids (42.5 mol %) in combination with glycerol as co-surfactant, were used for preparing oil-in water nanoemulsions coded as NEPC and NEPCE, respectively. NEPCE displayed significantly smaller mean droplet size (30 nm), equal entrapment efficiency (100%), better droplet stability and suffered lower encapsulation efficiency loss (3%) during storage time (120 days, 4ºC) than NEPC. Bioavailability, measured in terms of area under the curve of curcumin concentration versus time, and maximum curcumin plasma concentration, was in general terms significantly higher for NEPCE than for NEPC, and for curcumin coarse aqueous suspension (CCS). Also, NEPCE produced significantly higher curcumin concentrations in liver and lung than NEPC and CCS. These data support the role of phosphatidylcholine enriched with medium chain fatty acids to increase the bioavailability of nanoemulsions for therapeutic applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Recurrent Ventricular Tachycardia in Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency.

    PubMed

    Bala, P; Ferdinandusse, S; Olpin, S E; Chetcuti, P; Morris, A A M

    2016-01-01

    We report a baby with medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency who presented on day 2 with poor feeding and lethargy. She was floppy with hypoglycaemia (1.8 mmol/l) and hyperammonaemia (182 μmol/l). Despite correction of these and a continuous intravenous infusion of glucose at 4.5-6.2 mg/kg/min, she developed generalised tonic clonic seizures on day 3. She also suffered two episodes of pulseless ventricular tachycardia, from which she was resuscitated successfully. Unfortunately, she died on day 5, following a third episode of pulseless ventricular tachycardia. Arrhythmias are generally thought to be rarer in MCAD deficiency than in disorders of long-chain fatty acid oxidation. This is, however, the sixth report of ventricular tachyarrhythmias in MCAD deficiency. Five of these involved neonates and it may be that patients with MCAD deficiency are particularly prone to ventricular arrhythmias in the newborn period. Three of the patients (including ours) had normal blood glucose concentrations at the time of the arrhythmias and had been receiving intravenous glucose for many hours. These cases suggest that arrhythmias can be induced by medium-chain acylcarnitines or other metabolites accumulating in MCAD deficiency. Ventricular tachyarrhythmias can occur in MCAD deficiency, especially in neonates.

  1. Synthesis Gas (Syngas)-Derived Medium-Chain-Length Polyhydroxyalkanoate Synthesis in Engineered Rhodospirillum rubrum

    PubMed Central

    Heinrich, Daniel; Raberg, Matthias; Fricke, Philipp; Kenny, Shane T.; Morales-Gamez, Laura; Babu, Ramesh P.; O'Connor, Kevin E.

    2016-01-01

    ABSTRACT The purple nonsulfur alphaproteobacterium Rhodospirillum rubrum S1 was genetically engineered to synthesize a heteropolymer of mainly 3-hydroxydecanoic acid and 3-hydroxyoctanoic acid [P(3HD-co-3HO)] from CO- and CO2-containing artificial synthesis gas (syngas). For this, genes from Pseudomonas putida KT2440 coding for a 3-hydroxyacyl acyl carrier protein (ACP) thioesterase (phaG), a medium-chain-length (MCL) fatty acid coenzyme A (CoA) ligase (PP_0763), and an MCL polyhydroxyalkanoate (PHA) synthase (phaC1) were cloned and expressed under the control of the CO-inducible promoter PcooF from R. rubrum S1 in a PHA-negative mutant of R. rubrum. P(3HD-co-3HO) was accumulated to up to 7.1% (wt/wt) of the cell dry weight by a recombinant mutant strain utilizing exclusively the provided gaseous feedstock syngas. In addition to an increased synthesis of these medium-chain-length PHAs (PHAMCL), enhanced gene expression through the PcooF promoter also led to an increased molar fraction of 3HO in the synthesized copolymer compared with the Plac promoter, which regulated expression on the original vector. The recombinant strains were able to partially degrade the polymer, and the deletion of phaZ2, which codes for a PHA depolymerase most likely involved in intracellular PHA degradation, did not reduce mobilization of the accumulated polymer significantly. However, an amino acid exchange in the active site of PhaZ2 led to a slight increase in PHAMCL accumulation. The accumulated polymer was isolated; it exhibited a molecular mass of 124.3 kDa and a melting point of 49.6°C. With the metabolically engineered strains presented in this proof-of-principle study, we demonstrated the synthesis of elastomeric second-generation biopolymers from renewable feedstocks not competing with human nutrition. IMPORTANCE Polyhydroxyalkanoates (PHAs) are natural biodegradable polymers (biopolymers) showing properties similar to those of commonly produced petroleum-based nondegradable

  2. Synthesis Gas (Syngas)-Derived Medium-Chain-Length Polyhydroxyalkanoate Synthesis in Engineered Rhodospirillum rubrum.

    PubMed

    Heinrich, Daniel; Raberg, Matthias; Fricke, Philipp; Kenny, Shane T; Morales-Gamez, Laura; Babu, Ramesh P; O'Connor, Kevin E; Steinbüchel, Alexander

    2016-10-15

    The purple nonsulfur alphaproteobacterium Rhodospirillum rubrum S1 was genetically engineered to synthesize a heteropolymer of mainly 3-hydroxydecanoic acid and 3-hydroxyoctanoic acid [P(3HD-co-3HO)] from CO- and CO 2 -containing artificial synthesis gas (syngas). For this, genes from Pseudomonas putida KT2440 coding for a 3-hydroxyacyl acyl carrier protein (ACP) thioesterase (phaG), a medium-chain-length (MCL) fatty acid coenzyme A (CoA) ligase (PP_0763), and an MCL polyhydroxyalkanoate (PHA) synthase (phaC1) were cloned and expressed under the control of the CO-inducible promoter P cooF from R. rubrum S1 in a PHA-negative mutant of R. rubrum P(3HD-co-3HO) was accumulated to up to 7.1% (wt/wt) of the cell dry weight by a recombinant mutant strain utilizing exclusively the provided gaseous feedstock syngas. In addition to an increased synthesis of these medium-chain-length PHAs (PHA MCL ), enhanced gene expression through the P cooF promoter also led to an increased molar fraction of 3HO in the synthesized copolymer compared with the P lac promoter, which regulated expression on the original vector. The recombinant strains were able to partially degrade the polymer, and the deletion of phaZ2, which codes for a PHA depolymerase most likely involved in intracellular PHA degradation, did not reduce mobilization of the accumulated polymer significantly. However, an amino acid exchange in the active site of PhaZ2 led to a slight increase in PHA MCL accumulation. The accumulated polymer was isolated; it exhibited a molecular mass of 124.3 kDa and a melting point of 49.6°C. With the metabolically engineered strains presented in this proof-of-principle study, we demonstrated the synthesis of elastomeric second-generation biopolymers from renewable feedstocks not competing with human nutrition. Polyhydroxyalkanoates (PHAs) are natural biodegradable polymers (biopolymers) showing properties similar to those of commonly produced petroleum-based nondegradable polymers. The

  3. Parental Experiences of Raising a Child With Medium Chain Acyl-CoA Dehydrogenase Deficiency.

    PubMed

    Piercy, Hilary; Machaczek, Katarzyna; Ali, Parveen; Yap, Sufin

    2017-01-01

    Newborn screening enabling early diagnosis of medium chain acyl-CoA dehydrogenase deficiency (MCADD) has dramatically improved health outcomes in children with MCADD. Achieving those outcomes depends on effective management by parents. Understanding parental management strategies and associated anxieties and concerns is needed to inform provision of appropriate care and support. Semistructured interviews were conducted with a purposive sample of parents of children aged 2 to 12 years. Thematic analysis identified two main themes. Managing dietary intake examined how parents managed day-to-day dietary intake to ensure adequate intake and protection of safe fasting intervals. Managing and preventing illness events explored parental experiences of managing illness events and their approach to preventing these events. Management strategies were characterized by caution and vigilance and influenced by a lack of confidence in others to manage the condition. The study identifies the need for increased awareness of the condition, particularly in relation to emergency treatment.

  4. 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.

  5. Intestinal absorption and liver uptake of medium-chain fatty acids in non-anaesthetized pigs.

    PubMed

    Guillot, E; Vaugelade, P; Lemarchal, P; Rérat, A

    1993-03-01

    In order to study the rate of intestinal absorption and hepatic uptake of medium-chain fatty acids (MCFA), six growing pigs, mean body weight 65 kg, were fitted with a permanent fistula in the duodenum and with three catheters in the portal vein, carotid artery and hepatic vein respectively. Two electromagnetic flow probes were also set up, one around the portal vein and one around the hepatic artery. A mixture of octanoic and decanoic acids, esterified as medium-chain triacylglycerols, together with maltose dextrine and a nitrogenous fraction was continuously infused for 1 h into the duodenum. Samples of blood were withdrawn from the three vessels at regular intervals for 12 h and further analysed for their non-esterified octanoic and decanoic acid contents. The concentration of non-esterified octanoic and decanoic acids in the portal blood rose sharply after the beginning of each infusion and showed a biphasic time-course with two maximum values, one after 15 min and a later one between 75 and 90 min. Only 65% of octanoic acid infused into the duodenum and 54% of decanoic acid were recovered in the portal flow throughout each experiment. The amounts of non-esterified MCFA taken up per h by the liver were close to those absorbed from the gut via the portal vein within the same periods of time, showing that the liver is the main site of utilization of MCFA in pigs. These results have been discussed with a special emphasis laid on the possible mechanisms of the biphasic time-course of MCFA absorption and the incomplete recovery in the portal blood of the infused fatty acids.

  6. Effects of acute and chronic exercise on sarcolemmal MCT1 and MCT4 contents in human skeletal muscles: current status.

    PubMed

    Thomas, Claire; Bishop, David J; Lambert, Karen; Mercier, Jacques; Brooks, George A

    2012-01-01

    Two lactate/proton cotransporter isoforms (monocarboxylate transporters, MCT1 and MCT4) are present in the plasma (sarcolemmal) membranes of skeletal muscle. Both isoforms are symports and are involved in both muscle pH and lactate regulation. Accordingly, sarcolemmal MCT isoform expression may play an important role in exercise performance. Acute exercise alters human MCT content, within the first 24 h from the onset of exercise. The regulation of MCT protein expression is complex after acute exercise, since there is not a simple concordance between changes in mRNA abundance and protein levels. In general, exercise produces greater increases in MCT1 than in MCT4 content. Chronic exercise also affects MCT1 and MCT4 content, regardless of the initial fitness of subjects. On the basis of cross-sectional studies, intensity would appear to be the most important factor regulating exercise-induced changes in MCT content. Regulation of skeletal muscle MCT1 and MCT4 content by a variety of stimuli inducing an elevation of lactate level (exercise, hypoxia, nutrition, metabolic perturbations) has been demonstrated. Dissociation between the regulation of MCT content and lactate transport activity has been reported in a number of studies, and changes in MCT content are more common in response to contractile activity, whereas changes in lactate transport capacity typically occur in response to changes in metabolic pathways. Muscle MCT expression is involved in, but is not the sole determinant of, muscle H(+) and lactate anion exchange during physical activity.

  7. PGC-1alpha increases skeletal muscle lactate uptake by increasing the expression of MCT1 but not MCT2 or MCT4.

    PubMed

    Benton, Carley R; Yoshida, Yuko; Lally, James; Han, Xiao-Xia; Hatta, Hideo; Bonen, Arend

    2008-09-17

    We examined the relationship between PGC-1alpha protein; the monocarboxylate transporters MCT1, 2, and 4; and CD147 1) among six metabolically heterogeneous rat muscles, 2) in chronically stimulated red (RTA) and white tibialis (WTA) muscles (7 days), and 3) in RTA and WTA muscles transfected with PGC-1alpha-pcDNA plasmid in vivo. Among rat hindlimb muscles, there was a strong positive association between PGC-1alpha and MCT1 and CD147, and between MCT1 and CD147. A negative association was found between PGC-1alpha and MCT4, and CD147 and MCT4, while there was no relationship between PGC-1alpha or CD147 and MCT2. Transfecting PGC-1alpha-pcDNA plasmid into muscle increased PGC-1alpha protein (RTA +23%; WTA +25%) and induced the expression of MCT1 (RTA +16%; WTA +28%), but not MCT2 and MCT4. As a result of the PGC-1alpha-induced upregulation of MCT1 and its chaperone CD147 (+29%), there was a concomitant increase in the rate of lactate uptake (+20%). In chronically stimulated muscles, the following proteins were upregulated, PGC-1alpha in RTA (+26%) and WTA (+86%), MCT1 in RTA (+61%) and WTA (+180%), and CD147 in WTA (+106%). In contrast, MCT4 protein expression was not altered in either RTA or WTA muscles, while MCT2 protein expression was reduced in both RTA (-14%) and WTA (-10%). In these studies, whether comparing oxidative capacities among muscles or increasing their oxidative capacities by PGC-1alpha transfection and chronic muscle stimulation, there was a strong relationship between the expression of PGC-1alpha and MCT1, and PGC-1alpha and CD147 proteins. Thus, MCT1 and CD147 belong to the family of metabolic genes whose expression is regulated by PGC-1alpha in skeletal muscle.

  8. KAS IV: a 3-ketoacyl-ACP synthase from Cuphea sp. is a medium chain specific condensing enzyme.

    PubMed

    Dehesh, K; Edwards, P; Fillatti, J; Slabaugh, M; Byrne, J

    1998-08-01

    cDNA clones encoding a novel 3-ketoacyl-ACP synthase (KAS) have been isolated from Cuphea. The amino acid sequence of this enzyme is different from the previously characterized classes of KASs, designated KAS I and III, and similar to those designated as KAS II. To define the acyl chain specificity of this enzyme, we generated transgenic Brassica plants over-expressing the cDNA encoded protein in a seed specific manner. Expression of this enzyme in transgenic Brassica seeds which normally do not produce medium chain fatty acids does not result in any detectable modification of the fatty acid profile. However, co-expression of the Cuphea KAS with medium chain specific thioesterases, capable of production of either 12:0 or 8:0/10:0 fatty acids in seed oil, strongly enhances the levels of these medium chain fatty acids as compared with seed oil of plants expressing the thioesterases alone. By contrast, co-expression of the Cuphea KAS along with an 18:0/18.1-ACP thioesterase does not result in any detectable modification of the fatty acids. These data indicate that the Cuphea KAS reported here has a different acyl-chain specificity to the previously characterized KAS I, II and III. Therefore, we designate this enzyme KAS IV, a medium chain specific condensing enzyme.

  9. Draft Genome Sequence of Pseudomonas sp. Strain LFM046, a Producer of Medium-Chain-Length Polyhydroxyalkanoate

    PubMed Central

    Cardinali-Rezende, Juliana; Alexandrino, Paulo Moises Raduan; Nahat, Rafael Augusto Theodoro Pereira de Souza; Sant’Ana, Débora Parrine Vieira; Silva, Luiziana Ferreira; Gomez, José Gregório Cabrera

    2015-01-01

    Pseudomonas sp. LFM046 is a medium-chain-length polyhydroxyalkanoate (PHAMCL) producer capable of using various carbon sources (carbohydrates, organic acids, and vegetable oils) and was first isolated from sugarcane cultivation soil in Brazil. The genome sequence was found to be 5.97 Mb long with a G+C content of 66%. PMID:26294616

  10. 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.

  11. 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.

  12. 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

  13. Medium-chain fatty acid-sensing receptor, GPR84, is a proinflammatory receptor.

    PubMed

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

    2013-04-12

    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 [(35)S]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.

  14. 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

  15. Biosynthesis of medium chain length alkanes for bio-aviation fuel by metabolic engineered Escherichia coli.

    PubMed

    Wang, Meng; Nie, Kaili; Cao, Hao; Xu, Haijun; Fang, Yunming; Tan, Tianwei; Baeyens, Jan; Liu, Luo

    2017-09-01

    The aim of this work was to study the synthesis of medium-chain length alkanes (MCLA), as bio-aviation product. To control the chain length of alkanes and increase the production of MCLA, Escherichia coli cells were engineered by incorporating (i) a chain length specific thioesterase from Umbellularia californica (UC), (ii) a plant origin acyl carrier protein (ACP) gene and (iii) the whole fatty acid synthesis system (FASs) from Jatropha curcas (JC). The genetic combination was designed to control the product spectrum towards optimum MCLA. Decanoic, lauric and myristic acid were produced at concentrations of 0.011, 0.093 and 1.657mg/g, respectively. The concentration of final products nonane, undecane and tridecane were 0.00062mg/g, 0.0052mg/g, and 0.249mg/g respectively. Thioesterase from UC controlled the fatty acid chain length in a range of 10-14 carbons and the ACP gene with whole FASs from JC significantly increased the production of MCLA. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Medium Chain-Length Polyhydroxyalkanoate Copolymer Modified by Bacterial Cellulose for Medical Devices.

    PubMed

    Panaitescu, Denis Mihaela; Lupescu, Irina; Frone, Adriana Nicoleta; Chiulan, Ioana; Nicolae, Cristian Andi; Tofan, Vlad; Stefaniu, Amalia; Somoghi, Raluca; Trusca, Roxana

    2017-10-09

    Medium chain-length polyhydroxyalkanoates (mPHAs) are flexible elastomeric biopolymers with valuable properties for biomedical applications like artificial arteries and other medical implants. However, an environmentally friendly and high productivity process together with the tuning of the mechanical and biological properties of mPHAs are mandatory for this purpose. Here, for the first time, a melt processing technique was applied for the preparation of bionanocomposites starting from poly(3-hydroxyoctanoate) (PHO) and bacterial cellulose nanofibers (BC). The incorporation of only 3 wt % BC in PHO improved its thermal stability with 25 °C and reinforced it, increasing the Young's modulus with 76% and the tensile strength with 44%. The percolation threshold calculated with the aspect ratio of the fibers after melt processing was very low and close to 3 wt %. We showed that this bionanocomposite is able to preserve the ductile behavior during storage, no important aging being noted between 3 h and one month after compression-molding. Moreover, this study is the first to investigate the melt processability of PHO nanocomposite for tube extrusion. In addition, biocompatibility study showed no proinflammatory immune response and better cell adhesion for PHO/BC nanocomposite with 3 wt % BC and demonstrated the high feasibility of this bionanocomposite for in vivo application of tissue-engineered blood vessels.

  17. Effects of medium-chain triacylglycerols on Maillard reaction in bread baking.

    PubMed

    Toyosaki, Toshiyuki

    2018-06-01

    To investigate the relationship between the fatty acid composition of medium-chain triacylglycerols (MCTs) and the Maillard reaction induced during bread baking, a comparison with various fatty acids was conducted. Saturated fatty acids had a remarkable inhibitory effect on the amount of advanced glycation end products (AGEs) generated from the Maillard reaction in bread baking compared to unsaturated fatty acids. The amount of AGEs produced by each fatty acid (mg kg -1 ) was as follows: C18:0, 18.7; C12:0, 35.2; C16:0, 21.4; C18:0, 38.2; C18:1, 68.7; C18:2, 80.1; C20:4, 80.8; C22:4, 89.8. Saturated fatty acids were possibly involved in the Maillard reaction and, as a result, acted to inhibit it. In the case of unsaturated fatty acids, amounts of AGEs during the Maillard reaction in baking tended to increase as the degree of unsaturation increased. In other words, there was a positive correlation between the degree of unsaturation and the amount of AGEs. It was also confirmed that the air pore distribution in baked bread was closely related to AGEs. These results led us to conclude that the fatty acid composition of the added lipids also influences properties that determine the tastiness of bread. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  18. Production of medium chain fatty acid rich mustard oil using packed bed bioreactor.

    PubMed

    Sengupta, Avery; Roy, Susmita; Mukherjee, Sohini; Ghosh, Mahua

    2015-01-01

    A comparative study was done on the production of different medium chain fatty acid (MCFA) rich mustard oil using a stirred tank batchreactor (STBR) and packed bed bio reactor (PBBR) using three commercially available immobilised lipases viz. Thermomyces lanuginosus, Candida antarctica and Rhizomucor meihe. Three different MCFAs capric, caprylic and lauric acids were incorporated in the mustard oil. Reaction parameters, such as substrate molar ratio, reaction temperature and enzyme concentration were standardized in the STBR and maintained in the PBBR. To provide equal time of residence between the substrate and enzyme in both the reactors for the same amount of substrates, the substrate flow rate in the PBBR was maintainedat 0.27 ml/min. Gas liquid chromatography was used to monitor the incorporation of MCFA in mustard oil. The study showed that the PBBR was more efficient than the STBR in the synthesis of structured lipids with less migration of acyl groups. The physico-chemical parameters of the product along with fatty acid composition in all positions and sn-2 positions were also determined.

  19. The metabolic microenvironment of melanomas: Prognostic value of MCT1 and MCT4.

    PubMed

    Pinheiro, Céline; Miranda-Gonçalves, Vera; Longatto-Filho, Adhemar; Vicente, Anna L S A; Berardinelli, Gustavo N; Scapulatempo-Neto, Cristovam; Costa, Ricardo F A; Viana, Cristiano R; Reis, Rui M; Baltazar, Fátima; Vazquez, Vinicius L

    2016-06-02

    BRAF mutations are known drivers of melanoma development and, recently, were also described as players in the Warburg effect, while this reprogramming of energy metabolism has been identified as a possible strategy for treating melanoma patients. Therefore, the aim of this work was to evaluate the expression and prognostic value of a panel of glycolytic metabolism-related proteins in a series of melanomas. The immunohistochemical expression of MCT1, MCT4, GLUT1, and CAIX was evaluated in 356 patients presenting melanoma and 20 patients presenting benign nevi. Samples included 20 benign nevi, 282 primary melanomas, 117 lymph node and 54 distant metastases samples. BRAF mutation was observed in 29/92 (31.5%) melanoma patients and 17/20 (85%) benign nevi samples. NRAS mutation was observed in 4/36 (11.1%) melanoma patients and 1/19 (5.3%) benign nevi samples. MCT4 and GLUT1 expression was significantly increased in metastatic samples, and MCT1, MCT4 and GLUT1 were significantly associated with poor prognostic variables. Importantly, MCT1 and MCT4 were associated with shorter overall survival. In conclusion, the present study brings new insights on metabolic aspects of melanoma, paving the way for the development of new-targeted therapies.

  20. Glucose deprivation increases monocarboxylate transporter 1 (MCT1) expression and MCT1-dependent tumor cell migration.

    PubMed

    De Saedeleer, C J; Porporato, P E; Copetti, T; Pérez-Escuredo, J; Payen, V L; Brisson, L; Feron, O; Sonveaux, P

    2014-07-31

    The glycolytic end-product lactate is a pleiotropic tumor growth-promoting factor. Its activities primarily depend on its uptake, a process facilitated by the lactate-proton symporter monocarboxylate transporter 1 (MCT1). Therefore, targeting the transporter or its chaperon protein CD147/basigin, itself involved in the aggressive malignant phenotype, is an attractive therapeutic option for cancer, but basic information is still lacking regarding the regulation of the expression, interaction and activities of both proteins. In this study, we found that glucose deprivation dose-dependently upregulates MCT1 and CD147 protein expression and their interaction in oxidative tumor cells. While this posttranslational induction could be recapitulated using glycolysis inhibition, hypoxia, oxidative phosphorylation (OXPHOS) inhibitor rotenone or hydrogen peroxide, it was blocked with alternative oxidative substrates and specific antioxidants, pointing out at a mitochondrial control. Indeed, we found that the stabilization of MCT1 and CD147 proteins upon glucose removal depends on mitochondrial impairment and the associated generation of reactive oxygen species. When glucose was a limited resource (a situation occurring naturally or during the treatment of many tumors), MCT1-CD147 heterocomplexes accumulated, including in cell protrusions of the plasma membrane. It endowed oxidative tumor cells with increased migratory capacities towards glucose. Migration increased in cells overexpressing MCT1 and CD147, but it was inhibited in glucose-starved cells provided with an alternative oxidative fuel, treated with an antioxidant, lacking MCT1 expression, or submitted to pharmacological MCT1 inhibition. While our study identifies the mitochondrion as a glucose sensor promoting tumor cell migration, MCT1 is also revealed as a transducer of this response, providing a new rationale for the use of MCT1 inhibitors in cancer.

  1. 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

  2. Accumulation of medium-chain, saturated fatty acyl moieties in seed oils of transgenic Camelina sativa

    PubMed Central

    Dalal, Jyoti; Vasani, Naresh; Lopez, Harry O.; Sederoff, Heike W.

    2017-01-01

    With its high seed oil content, the mustard family plant Camelina sativa has gained attention as a potential biofuel source. As a bioenergy crop, camelina has many advantages. It grows on marginal land with low demand for water and fertilizer, has a relatively short life cycle, and is stress tolerant. As most other crop seed oils, camelina seed triacylglycerols (TAGs) consist of mostly long, unsaturated fatty acyl moieties, which is not desirable for biofuel processing. In our efforts to produce shorter, saturated chain fatty acyl moieties in camelina seed oil for conversion to jet fuel, a 12:0-acyl-carrier thioesterase gene, UcFATB1, from California bay (Umbellularia californica Nutt.) was expressed in camelina seeds. Up to 40% of short chain laurate (C12:0) and myristate (C14:0) were present in TAGs of the seed oil of the transgenics. The total oil content and germination rate of the transgenic seeds were not affected. Analysis of positions of these two fatty acyl moieties in TAGs indicated that they were present at the sn-1 and sn-3 positions, but not sn-2, on the TAGs. Suppression of the camelina KASII genes by RNAi constructs led to higher accumulation of palmitate (C16:0), from 7.5% up to 28.5%, and further reduction of longer, unsaturated fatty acids in seed TAGs. Co-transformation of camelina with both constructs resulted in enhanced accumulation of all three medium-chain, saturated fatty acids in camelina seed oils. Our results show that a California bay gene can be successfully used to modify the oil composition in camelina seed and present a new biological alternative for jet fuel production. PMID:28212406

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

    SciTech Connect

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

    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 polyclonalmore » 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.« less

  4. Accumulation of medium-chain, saturated fatty acyl moieties in seed oils of transgenic Camelina sativa.

    PubMed

    Hu, Zhaohui; Wu, Qian; Dalal, Jyoti; Vasani, Naresh; Lopez, Harry O; Sederoff, Heike W; Qu, Rongda

    2017-01-01

    With its high seed oil content, the mustard family plant Camelina sativa has gained attention as a potential biofuel source. As a bioenergy crop, camelina has many advantages. It grows on marginal land with low demand for water and fertilizer, has a relatively short life cycle, and is stress tolerant. As most other crop seed oils, camelina seed triacylglycerols (TAGs) consist of mostly long, unsaturated fatty acyl moieties, which is not desirable for biofuel processing. In our efforts to produce shorter, saturated chain fatty acyl moieties in camelina seed oil for conversion to jet fuel, a 12:0-acyl-carrier thioesterase gene, UcFATB1, from California bay (Umbellularia californica Nutt.) was expressed in camelina seeds. Up to 40% of short chain laurate (C12:0) and myristate (C14:0) were present in TAGs of the seed oil of the transgenics. The total oil content and germination rate of the transgenic seeds were not affected. Analysis of positions of these two fatty acyl moieties in TAGs indicated that they were present at the sn-1 and sn-3 positions, but not sn-2, on the TAGs. Suppression of the camelina KASII genes by RNAi constructs led to higher accumulation of palmitate (C16:0), from 7.5% up to 28.5%, and further reduction of longer, unsaturated fatty acids in seed TAGs. Co-transformation of camelina with both constructs resulted in enhanced accumulation of all three medium-chain, saturated fatty acids in camelina seed oils. Our results show that a California bay gene can be successfully used to modify the oil composition in camelina seed and present a new biological alternative for jet fuel production.

  5. 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

  6. Enhanced cerebral expression of MCT1 and MCT2 in a rat ischemia model occurs in activated microglial cells.

    PubMed

    Moreira, Tiago J T P; Pierre, Karin; Maekawa, Fumihiko; Repond, Cendrine; Cebere, Aleta; Liljequist, Sture; Pellerin, Luc

    2009-07-01

    Monocarboxylate transporters (MCTs) are essential for the use of lactate, an energy substrate known to be overproduced in brain during an ischemic episode. The expression of MCT1 and MCT2 was investigated at 48 h of reperfusion from focal ischemia induced by unilateral extradural compression in Wistar rats. Increased MCT1 mRNA expression was detected in the injured cortex and hippocampus of compressed animals compared to sham controls. In the contralateral, uncompressed hemisphere, increases in MCT1 mRNA level in the cortex and MCT2 mRNA level in the hippocampus were noted. Interestingly, strong MCT1 and MCT2 protein expression was found in peri-lesional macrophages/microglia and in an isolectin B4+/S100beta+ cell population in the corpus callosum. In vitro, MCT1 and MCT2 protein expression was observed in the N11 microglial cell line, whereas an enhancement of MCT1 expression by tumor necrosis factor-alpha (TNF-alpha) was shown in these cells. Modulation of MCT expression in microglia suggests that these transporters may help sustain microglial functions during recovery from focal brain ischemia. Overall, our study indicates that changes in MCT expression around and also away from the ischemic area, both at the mRNA and protein levels, are a part of the metabolic adaptations taking place in the brain after ischemia.

  7. Screening of short- and medium-chain chlorinated paraffins in selected riverine sediments and sludge from the Czech Republic.

    PubMed

    Pribylová, Petra; Klánová, Jana; Holoubek, Ivan

    2006-11-01

    Wide distribution of chlorinated paraffins in the environment has already been demonstrated in several studies; however, information about their levels in the Central Europe is still very limited. First study focused on the SCCP contamination of the Czech aquatic environment have been performed recently, and its results motivated the authors to analyze sediments from a wide set of the Czech rivers in order to obtain more detailed information. Thirty-six sediment samples from eleven rivers and five drainage vents neighboring the chemical factories were analyzed; special attention was paid to the industrial areas. For the first time in the Czech Republic, medium-chain in addition to short-chain chlorinated paraffins were analyzed using GC-ECNI-MS. Chlorinated paraffins were detected in sediment samples on the concentration levels up to 347 ngg(-1) for short-chain chlorinated paraffins, and 5575 ngg(-1) for medium-chain chlorinated paraffins. Average chlorination degree of SCCPs was 65%.

  8. Synthesis of medium-chain fatty acids and their incorporation into triacylglycerols by cell-free fractions from Cuphea embryos.

    PubMed

    Deerberg, S; von Twickel, J; Förster, H H; Cole, T; Fuhrmann, J; Heise, K P

    1990-02-01

    During their rapid maturation period, seeds of Cuphea wrightii A. Gray mainly accumulate medium-chain fatty acids (C8 to C14) in their storage lipids. The rate of lipid deposition (40-50 mg·d(-1)·(g fresh weight)(-1)) is fourfold higher than in seeds of Cuphea racemosa (L. f.) Spreng, which accumulate long-chain fatty acids (C16 to C18). Measurements of the key enzymes of fatty-acid synthesis in cell-free extracts of seeds of different maturities from Cuphea wrightii show that malonyl-CoA synthesis may be a triggering factor for the observed high capacity for fatty-acid synthesis. Experiments on the incorporation of [1-(14)C]acetate into fatty acids by purified plastid preparations from embryos of Cuphea wrightii have demonstrated that the biosynthesis of medium-chain fatty acids (C8 to C14) is localized in the plastid. Thus, in the presence of cofactors for lipid synthesis (ATP, NADPH, NADH, acyl carrier protein, and sn-glycerol-3-phosphate), purified plastid fractions predominantly synthesized free fatty acids, 30% of which were of medium chain length. Transesterification of the freshly synthesized fatty acids to coenzyme A and recombination with the microsomal fraction of the embryo homogenate induced triacylglycerol synthesis. It also stimulated fatty-acid synthesis by a factor 2-3 and increased the relative amount of medium-chain fatty acids bound to triacylglycerols, which corresponded to about 60-80% in this lipid fraction.

  9. Draft Genome Sequence of Pseudomonas sp. Strain LFM046, a Producer of Medium-Chain-Length Polyhydroxyalkanoate.

    PubMed

    Cardinali-Rezende, Juliana; Alexandrino, Paulo Moises Raduan; Nahat, Rafael Augusto Theodoro Pereira de Souza; Sant'Ana, Débora Parrine Vieira; Silva, Luiziana Ferreira; Gomez, José Gregório Cabrera; Taciro, Marilda Keico

    2015-08-20

    Pseudomonas sp. LFM046 is a medium-chain-length polyhydroxyalkanoate (PHAMCL) producer capable of using various carbon sources (carbohydrates, organic acids, and vegetable oils) and was first isolated from sugarcane cultivation soil in Brazil. The genome sequence was found to be 5.97 Mb long with a G+C content of 66%. Copyright © 2015 Cardinali-Rezende et al.

  10. Acute exercise increases brain region-specific expression of MCT1, MCT2, MCT4, GLUT1, and COX IV proteins.

    PubMed

    Takimoto, Masaki; Hamada, Taku

    2014-05-01

    The brain is capable of oxidizing lactate and ketone bodies through monocarboxylate transporters (MCTs). We examined the protein expression of MCT1, MCT2, MCT4, glucose transporter 1 (GLUT1), and cytochrome-c oxidase subunit IV (COX IV) in the rat brain within 24 h after a single exercise session. Brain samples were obtained from sedentary controls and treadmill-exercised rats (20 m/min, 8% grade). Acute exercise resulted in an increase in lactate in the cortex, hippocampus, and hypothalamus, but not the brainstem, and an increase in β-hydroxybutyrate in the cortex alone. After a 2-h exercise session MCT1 increased in the cortex and hippocampus 5 h postexercise, and the effect lasted in the cortex for 24 h postexercise. MCT2 increased in the cortex and hypothalamus 5-24 h postexercise, whereas MCT2 increased in the hippocampus immediately after exercise, and remained elevated for 10 h postexercise. Regional upregulation of MCT2 after exercise was associated with increases in brain-derived neurotrophic factor and tyrosine-related kinase B proteins, but not insulin-like growth factor 1. MCT4 increased 5-10 h postexercise only in the hypothalamus, and was associated with increased hypoxia-inducible factor-1α expression. However, none of the MCT isoforms in the brainstem was affected by exercise. Whereas GLUT 1 in the cortex increased only at 18 h postexercise, COX IV in the hippocampus increased 10 h after exercise and remained elevated for 24 h postexercise. These results suggest that acute prolonged exercise induces the brain region-specific upregulation of MCT1, MCT2, MCT4, GLUT1, and COX IV proteins.

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

    PubMed

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

    2012-12-01

    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 (K(D 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 K(m) for phenylbutyryl-CoA were 0.2 mM 34(-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. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. 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.

  13. Synthesis of medium-chain length capsinoids from coconut oil catalyzed by Candida rugosa lipases.

    PubMed

    Trbojević Ivić, Jovana; Milosavić, Nenad; Dimitrijević, Aleksandra; Gavrović Jankulović, Marija; Bezbradica, Dejan; Kolarski, Dušan; Veličković, Dušan

    2017-03-01

    A commercial preparation of Candida rugosa lipases (CRL) was tested for the production of capsinoids by esterification of vanillyl alcohol (VA) with free fatty acids (FA) and coconut oil (CO) as acyl donors. Screening of FA chain length indicated that C8-C12 FA (the most common FA found in CO triglycerides) are the best acyl-donors, yielding 80-85% of their specific capsinoids. Hence, when CO, which is rich in these FA, was used as the substrate, a mixture of capsinoids (vanillyl caprylate, vanillyl decanoate and vanillyl laurate) was obtained. The findings presented here suggest that our experimental method can be applied for the enrichment of CO with capsinoids, thus giving it additional health promoting properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Lipolysis of natural long chain and synthetic medium chain galactolipids by pancreatic lipase-related protein 2.

    PubMed

    Amara, Sawsan; Barouh, Nathalie; Lecomte, Jérôme; Lafont, Dominique; Robert, Sylvie; Villeneuve, Pierre; De Caro, Alain; Carrière, Frédéric

    2010-04-01

    Monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) are the most abundant lipids in nature, mainly as important components of plant leaves and chloroplast membranes. Pancreatic lipase-related protein 2 (PLRP2) was previously found to express galactolipase activity, and it is assumed to be the main enzyme involved in the digestion of these common vegetable lipids in the gastrointestinal tract. Most of the previous in vitro studies were however performed with medium chain synthetic galactolipids as substrates. It was shown here that recombinant guinea pig (Cavia porcellus) as well as human PLRP2 hydrolyzed at high rates natural DGDG and MGDG extracted from spinach leaves. Their specific activities were estimated by combining the pH-stat technique, thin layer chromatography coupled to scanning densitometry and gas chromatography. The optimum assay conditions for hydrolysis of these natural long chain galactolipids were investigated and the optimum bile salt to substrate ratio was found to be different from that established with synthetic medium chains MGDG and DGDG. Nevertheless the length of acyl chains and the nature of the galactosyl polar head of the galactolipid did not have major effects on the specific activities of PLRP2, which were found to be very high on both medium chain [1786+/-100 to 5420+/-85U/mg] and long chain [1756+/-208 to 4167+/-167U/mg] galactolipids. Fatty acid composition analysis of natural MGDG, DGDG and their lipolysis products revealed that PLRP2 only hydrolyzed one ester bond at the sn-1 position of galactolipids. PLRP2 might be used to produce lipid and free fatty acid fractions enriched in either 16:3 n-3 or 18:3 n-3 fatty acids, both found at high levels in galactolipids. 2010 Elsevier B.V. All rights reserved.

  15. A retrospective review of anesthesia and perioperative care in children with medium-chain acyl-CoA dehydrogenase deficiency.

    PubMed

    Allen, Claire; Perkins, Russell; Schwahn, Bernd

    2017-01-01

    Medium-chain acyl-CoA dehydrogenase deficiency is the most common genetically determined disorder of mitochondrial fatty acid oxidation. Decompensation can result in hypoglycemia, seizures, coma, and death but may be prevented by ensuring glycogen stores do not become depleted. Perioperative care is of interest as surgery, fasting, and infection may all trigger decompensation and the safety of anesthetic agents has been questioned. Current guidelines from the British Inherited Metabolic Disease Group advise on administering fluid containing 10% glucose during the perioperative period. To review the management of anesthesia and perioperative care for children with medium-chain acyl-CoA dehydrogenase deficiency and determine the frequency and nature of any complications. A retrospective review of case notes of children with medium-chain acyl-CoA dehydrogenase deficiency undergoing anesthesia between 1997 and 2014. Fourteen patients underwent 21 episodes of anesthesia. In 20 episodes, the patient received a glucose-containing fluid during their perioperative fast, of which eight received fluid containing 10% dextrose throughout the entire perioperative period. No episodes of hypoglycemia or decompensation occurred, but perioperative hyperglycemia occurred in five episodes. A propofol bolus was administered at induction in 16 episodes and volatile agents were administered for maintenance of anesthesia in all episodes without any observed complications. In one episode, delayed offset of atracurium was reported. Perioperative metabolic decompensation and hypoglycemia appear to be uncommon in children who are well and receive glucose supplementation. Hyperglycemia may occur as a consequence of surgery and glucose supplementation. Propofol boluses and volatile anesthetic agents were used without any apparent complications. Prolonged action of atracurium was reported in one case, suggesting that nondepolarizing muscle relaxants may have delayed offset in this patient group

  16. Development of environmentally friendly coatings and paints using medium-chain-length poly(3-hydroxyalkanoates) as the polymer binder.

    PubMed

    van der Walle, G A; Buisman, G J; Weusthuis, R A; Eggink, G

    1999-01-01

    Unsaturated medium-chain-length poly(3-hydroxyalkanoates) (mcl-PHAs) produced by Pseudomonas putida from linseed oil fatty acids (LOFA) and tall oil fatty acids (TOFA), were used as the polymer binder in the formulation of high solid alkyd-like paints. The relatively high concentration of unsaturated alkyl side chains incorporated into the PHA resins resulted in oxidative drying PHA paints having excellent coating properties. The homogeneously pigmented PHA coatings yielded high-gloss, smooth and strong films upon curing and showed an excellent flexibility, a good adhesion to different substrates, cohesive film properties and resistance to chipping.

  17. Fifty years of successful MCT research and production in France

    NASA Astrophysics Data System (ADS)

    Bensussan, Philippe; Tribolet, Philippe; Destéfanis, Gérard; Sirieix, Michel

    2009-05-01

    France has a long and fruitful history regarding Mercury Cadmium Telluride (MCT) research and production and is still one of the leading countries for the production of MCT IR detectors. To give a historical account of its development and progress, SAGEM Défense Sécurité will describe the early days of MCT developments in France. CEA-Leti (the French Atomic Energy Commission and a leading applied research center in electronics) will then present the research carried out on second- and third-generation MCT technologies, followed by Sofradir who will discuss the production of these new detector types.

  18. Intersubunit structure within heterodimers of medium-chain prenyl diphosphate synthases. Formation of a hybrid-type heptaprenyl diphosphate synthase.

    PubMed

    Koike-Takeshita, A; Koyama, T; Ogura, K

    1998-10-01

    Among prenyltransferases that catalyze the sequential condensation of isopentenyl diphosphate with allylic diphosphate to produce prenyl diphosphates with various chain lengths and stereochemistries, medium-chain prenyl diphosphate synthases are exceptional in that they comprise two dissociable heteromeric protein components. These components exist without binding with each other under physiological conditions, and neither of them has any prenyltransferase activity by itself. In order to elucidate the precise molecular mechanism underlying expression of the catalytic function by such a unique two-component system, we examined the possibility of forming a hybrid between two of the components of three different medium-chain prenyl diphosphate synthases, components I and II of heptaprenyl diphosphate synthase from Bacillus subtilis, components I' and II' of heptaprenyl diphosphate synthase from Bacillus stearothermophilus, and components A and B of hexaprenyl diphosphate synthase from Micrococcus luteus B-P 26. As a result, only the hybrid-type combination of component I and component II' gave distinct prenyltransferase activity. The hybrid-type enzyme catalyzed the synthesis of heptaprenyl diphosphate and showed moderate heat stability, which lay between those of the natural enzymes from B. subtilis and B. stearothermophilus. There is no possibility of forming a hybrid between the heptaprenyl and hexaprenyl diphosphate synthases.

  19. The effect of increasing levels of fish oil-containing structured triglycerides on protein metabolism in parenterally fed rats stressed by burn plus endotoxin.

    PubMed

    Gollaher, C J; Fechner, K; Karlstad, M; Babayan, V K; Bistrian, B R

    1993-01-01

    This report investigates the effect of various levels of medium-chain/fish oil structured triglycerides on protein and energy metabolism in hypermetabolic rats. Male Sprague-Dawley rats (192 to 226 g) were continuously infused with isovolemic diets that provided 200 kcal/kg per day and 2 g of amino acid nitrogen per kilogram per day. The percentage of nonnitrogen calories as structured triglyceride was varied: no fat, 5%, 15%, or 30%. A 30% long-chain triglyceride diet was also provided as a control to compare the protein-sparing abilities of these two types of fat. Nitrogen excretion, plasma albumin, plasma triglycerides, and whole-body and liver and muscle protein kinetics were determined after 3 days of feeding. Whole-body protein breakdown, flux, and oxidation were similar in all groups. The 15% structured triglyceride diet maximized whole-body protein synthesis (p < .05). Liver fractional synthetic rate was significantly greater in animals receiving 5% of nonprotein calories as structured triglyceride (p < .05). Muscle fractional synthetic rate was unchanged. Plasma triglycerides were markedly elevated in the 30% structured triglyceride-fed rats. The 30% structured triglyceride diet maintained plasma albumin levels better than those diets containing no fat, 5% medium-chain triglyceride/fish oil structured triglyceride, or 30% long-chain triglycerides. Nitrogen excretion was lower in animals receiving 30% of nonnitrogen calories as a structured triglyceride than in those receiving 30% as long-chain triglycerides, but this difference did not reach statistical significance (p = .1). These data suggest that protein metabolism is optimized when structured triglyceride is provided at relatively low dietary fat intakes.

  20. Computational Redesign of Acyl-ACP Thioesterase with Improved Selectivity toward Medium-Chain-Length Fatty Acids

    SciTech Connect

    Grisewood, Matthew J.; Hernández-Lozada, Néstor J.; Thoden, James B.

    Enzyme and metabolic engineering offer the potential to develop biocatalysts for converting natural resources to a wide range of chemicals. To broaden the scope of potential products beyond natural metabolites, methods of engineering enzymes to accept alternative substrates and/or perform novel chemistries must be developed. DNA synthesis can create large libraries of enzyme-coding sequences, but most biochemistries lack a simple assay to screen for promising enzyme variants. Our solution to this challenge is structure-guided mutagenesis, in which optimization algorithms select the best sequences from libraries based on specified criteria (i.e., binding selectivity). We demonstrate this approach by identifying medium-chain (C8–C12)more » acyl-ACP thioesterases through structure-guided mutagenesis. Medium-chain fatty acids, which are products of thioesterase-catalyzed hydrolysis, are limited in natural abundance, compared to long-chain fatty acids; the limited supply leads to high costs of C6–C10 oleochemicals such as fatty alcohols, amines, and esters. Here, we applied computational tools to tune substrate binding of the highly active ‘TesA thioesterase in Escherichia coli. We used the IPRO algorithm to design thioesterase variants with enhanced C12 or C8 specificity, while maintaining high activity. After four rounds of structure-guided mutagenesis, we identified 3 variants with enhanced production of dodecanoic acid (C12) and 27 variants with enhanced production of octanoic acid (C8). The top variants reached up to 49% C12 and 50% C8 while exceeding native levels of total free fatty acids. A comparably sized library created by random mutagenesis failed to identify promising mutants. The chain length-preference of ‘TesA and the best mutant were confirmed in vitro using acyl-CoA substrates. Molecular dynamics simulations, confirmed by resolved crystal structures, of ‘TesA variants suggest that hydrophobic forces govern ‘TesA substrate specificity

  1. Computational Redesign of Acyl-ACP Thioesterase with Improved Selectivity toward Medium-Chain-Length Fatty Acids

    DOE PAGES

    Grisewood, Matthew J.; Hernández-Lozada, Néstor J.; Thoden, James B.; ...

    2017-04-20

    Enzyme and metabolic engineering offer the potential to develop biocatalysts for converting natural resources to a wide range of chemicals. To broaden the scope of potential products beyond natural metabolites, methods of engineering enzymes to accept alternative substrates and/or perform novel chemistries must be developed. DNA synthesis can create large libraries of enzyme-coding sequences, but most biochemistries lack a simple assay to screen for promising enzyme variants. Our solution to this challenge is structure-guided mutagenesis, in which optimization algorithms select the best sequences from libraries based on specified criteria (i.e., binding selectivity). We demonstrate this approach by identifying medium-chain (C8–C12)more » acyl-ACP thioesterases through structure-guided mutagenesis. Medium-chain fatty acids, which are products of thioesterase-catalyzed hydrolysis, are limited in natural abundance, compared to long-chain fatty acids; the limited supply leads to high costs of C6–C10 oleochemicals such as fatty alcohols, amines, and esters. Here, we applied computational tools to tune substrate binding of the highly active ‘TesA thioesterase in Escherichia coli. We used the IPRO algorithm to design thioesterase variants with enhanced C12 or C8 specificity, while maintaining high activity. After four rounds of structure-guided mutagenesis, we identified 3 variants with enhanced production of dodecanoic acid (C12) and 27 variants with enhanced production of octanoic acid (C8). The top variants reached up to 49% C12 and 50% C8 while exceeding native levels of total free fatty acids. A comparably sized library created by random mutagenesis failed to identify promising mutants. The chain length-preference of ‘TesA and the best mutant were confirmed in vitro using acyl-CoA substrates. Molecular dynamics simulations, confirmed by resolved crystal structures, of ‘TesA variants suggest that hydrophobic forces govern ‘TesA substrate specificity

  2. MCT1 and MCT4 Expression and Lactate Flux Activity Increase During White and Brown Adipogenesis and Impact Adipocyte Metabolism.

    PubMed

    Petersen, Charlotte; Nielsen, Mette D; Andersen, Elise S; Basse, Astrid L; Isidor, Marie S; Markussen, Lasse K; Viuff, Birgitte M; Lambert, Ian H; Hansen, Jacob B; Pedersen, Stine F

    2017-10-12

    Adipose tissue takes up glucose and releases lactate, thereby contributing significantly to systemic glucose and lactate homeostasis. This implies the necessity of upregulation of net acid and lactate flux capacity during adipocyte differentiation and function. However, the regulation of lactate- and acid/base transporters in adipocytes is poorly understood. Here, we tested the hypothesis that adipocyte thermogenesis, browning and differentiation are associated with an upregulation of plasma membrane lactate and acid/base transport capacity that in turn is important for adipocyte metabolism. The mRNA and protein levels of the lactate-H + transporter MCT1 and the Na + ,HCO 3 - cotransporter NBCe1 were upregulated in mouse interscapular brown and inguinal white adipose tissue upon cold induction of thermogenesis and browning. MCT1, MCT4, and NBCe1 were furthermore strongly upregulated at the mRNA and protein level upon differentiation of cultured pre-adipocytes. Adipocyte differentiation was accompanied by increased plasma membrane lactate flux capacity, which was reduced by MCT inhibition and by MCT1 knockdown. Finally, in differentiated brown adipocytes, glycolysis (assessed as ECAR), and after noradrenergic stimulation also oxidative metabolism (OCR), was decreased by MCT inhibition. We suggest that upregulation of MCT1- and MCT4-mediated lactate flux capacity and NBCe1-mediated HCO 3 - /pH homeostasis are important for the physiological function of mature adipocytes.

  3. Disruption of plastid acyl:acyl carrier protein synthetases increases medium chain fatty acid accumulation in seeds of transgenic Arabidopsis.

    PubMed

    Tjellström, Henrik; Strawsine, Merissa; Silva, Jillian; Cahoon, Edgar B; Ohlrogge, John B

    2013-04-02

    Engineering transgenic plants that accumulate high levels of medium-chain fatty acids (MCFA) has been least successful for shorter chain lengths (e.g., C8). We demonstrate that one limitation is the activity of acyl-ACP synthetase (AAE) that re-activates fatty acids released by acyl-ACP thioesterases. Seed expression of Cuphea pulcherrima FATB acyl-ACP thioesterase in a double mutant lacking AAE15/16 increased 8:0 accumulation almost 2-fold compared to expression in wild type. These results also provide an in planta demonstration that AAE enzymes participate not only in activation of exogenously added MCFA but also in activation of MCFA synthesized in plastids. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  4. Analysis of Medium-Chain-Length Polyhydroxyalkanoate-Producing Bacteria in Activated Sludge Samples Enriched by Aerobic Periodic Feeding.

    PubMed

    Lee, Sun Hee; Kim, Jae Hee; Chung, Chung-Wook; Kim, Do Young; Rhee, Young Ha

    2018-04-01

    Analysis of mixed microbial populations responsible for the production of medium-chain-length polyhydroxyalkanoates (MCL-PHAs) under periodic substrate feeding in a sequencing batch reactor (SBR) was conducted. Regardless of activated sludge samples and the different MCL alkanoic acids used as the sole external carbon substrate, denaturing gradient gel electrophoresis analysis indicated that Pseudomonas aeruginosa was the dominant bacterium enriched during the SBR process. Several P. aeruginosa strains were isolated from the enriched activated sludge samples. The isolates were subdivided into two groups, one that produced only MCL-PHAs and another that produced both MCL- and short-chain-length PHAs. The SBR periodic feeding experiments with five representative MCL-PHA-producing Pseudomonas species revealed that P. aeruginosa has an advantage over other species that enables it to become dominant in the bacterial community.

  5. Medium-chain dehydrogenase/reductase and aldo-keto reductase scavenge reactive carbonyls in Synechocystis sp. PCC 6803.

    PubMed

    Shimakawa, Ginga; Kohara, Ayaka; Miyake, Chikahiro

    2018-03-01

    Reactive carbonyls (RCs), which are inevitably produced during respiratory and photosynthetic metabolism, have the potential to cause oxidative damage to photosynthetic organisms. Previously, we proposed a scavenging model for RCs in the cyanobacterium Synechocystis sp. PCC 6803 (S. 6803). In the current study, we constructed mutants deficient in the enzymes medium-chain dehydrogenase/reductase (ΔMDR) and aldo-keto reductase (ΔAKR) to investigate their contributions to RC scavenging in vivo. We found that treatment with the lipid-derived RC acrolein causes growth inhibition and promotes greater protein carbonylation in ΔMDR, compared with the wild-type and ΔAKR. In both ΔMDR and ΔAKR, photosynthesis is severely inhibited in the presence of acrolein. These results suggest that these enzymes function as part of the scavenging systems for RCs in S. 6803 in vivo. © 2018 Federation of European Biochemical Societies.

  6. A Specialized Diacylglycerol Acyltransferase Contributes to the Extreme Medium-Chain Fatty Acid Content of Cuphea Seed Oil1[OPEN

    PubMed Central

    Iskandarov, Umidjon; Silva, Jillian E.; Andersson, Mariette

    2017-01-01

    Seed oils of many Cuphea sp. contain >90% of medium-chain fatty acids, such as decanoic acid (10:0). These seed oils, which are among the most compositionally variant in the plant kingdom, arise from specialized fatty acid biosynthetic enzymes and specialized acyltransferases. These include lysophosphatidic acid acyltransferases (LPAT) and diacylglycerol acyltransferases (DGAT) that are required for successive acylation of medium-chain fatty acids in the sn-2 and sn-3 positions of seed triacylglycerols (TAGs). Here we report the identification of a cDNA for a DGAT1-type enzyme, designated CpuDGAT1, from the transcriptome of C. avigera var pulcherrima developing seeds. Microsomes of camelina (Camelina sativa) seeds engineered for CpuDGAT1 expression displayed DGAT activity with 10:0-CoA and the diacylglycerol didecanoyl, that was approximately 4-fold higher than that in camelina seed microsomes lacking CpuDGAT1. In addition, coexpression in camelina seeds of CpuDGAT1 with a C. viscosissima FatB thioesterase (CvFatB1) that generates 10:0 resulted in TAGs with nearly 15 mol % of 10:0. More strikingly, expression of CpuDGAT1 and CvFatB1 with the previously described CvLPAT2, a 10:0-CoA-specific Cuphea LPAT, increased 10:0 amounts to 25 mol % in camelina seed TAG. These TAGs contained up to 40 mol % 10:0 in the sn-2 position, nearly double the amounts obtained from coexpression of CvFatB1 and CvLPAT2 alone. Although enriched in diacylglycerol, 10:0 was not detected in phosphatidylcholine in these seeds. These findings are consistent with channeling of 10:0 into TAG through the combined activities of specialized LPAT and DGAT activities and demonstrate the biotechnological use of these enzymes to generate 10:0-rich seed oils. PMID:28325847

  7. Link between lipid metabolism and voluntary food intake in rainbow trout fed coconut oil rich in medium-chain TAG.

    PubMed

    Figueiredo-Silva, A Cláudia; Kaushik, Sadasivam; Terrier, Frédéric; Schrama, Johan W; Médale, Françoise; Geurden, Inge

    2012-06-01

    We examined the long-term effect of feeding coconut oil (CO; rich in lauric acid, C12) on voluntary food intake and nutrient utilisation in rainbow trout (Oncorhynchus mykiss), with particular attention to the metabolic use (storage or oxidation) of ingested medium-chain TAG. Trout were fed for 15 weeks one of the four isoproteic diets containing fish oil (FO) or CO as fat source (FS), incorporated at 5% (low fat, LF) or 15% (high fat, HF). Fat level or FS did not modify food intake (g/kg(0·8) per d), despite higher intestinal cholecystokinin-T mRNA in trout fed the HF-FO diet. The HF diets relative to the LF ones induced higher growth and adiposity, whereas the replacements of FO by CO resulted in similar growth and adiposity. This, together with the substantial retention of C12 (57% of intake), suggests the relatively low oxidation of ingested C12. The down-regulation of carnitine palmitoyl-transferase-1 (CPT-1) confirms the minor dependency of medium-chain fatty acids (MCFA) on CPT-1 to enter the mitochondria. However, MCFA did not up-regulate mitochondrial oxidation evaluated using hepatic hydroxyacyl-CoA dehydrogenase as a marker, in line with their high retention in body lipids. At a low lipid level, MCFA increased mRNA levels of fatty acid synthase, elongase and stearoyl-CoA desaturase in liver, showing the hepatic activation of fatty acid synthesis pathways by MCFA, reflected by increased 16 : 0, 18 : 0, 16 : 1, 18 : 1 body levels. The high capacity of trout to incorporate and transform C12, rather than to readily oxidise C12, contrasts with data in mammals and may explain the absence of a satiating effect of CO in rainbow trout.

  8. Medium-Chain Acyl-CoA Deficiency: Outlines from Newborn Screening, In Silico Predictions, and Molecular Studies

    PubMed Central

    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. 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.

  10. Triglycerides: A reappraisal.

    PubMed

    Wiesner, Philipp; Watson, Karol E

    2017-08-01

    Elevated cholesterol levels are clearly independently associated with adverse cardiovascular events. Another class of lipid particles, triglycerides, is also abundant in the human body and has been found in atherosclerotic plaques. Recent observational studies have demonstrated an association between elevated triglyceride levels and increased risk for future cardiovascular events. With this knowledge and the discovery of effective agents to lower triglyceride levels, the management of triglycerides is currently undergoing a renaissance. Unfortunately, no randomized, controlled clinical trials have been completed to date, proving that lowering triglycerides will reduce cardiovascular events. In this review we highlight some of the evidence that led to this stage and discuss the current data on pharmacologic intervention of triglyceride levels and the effect on clinical outcomes. Lastly, we want to give the reader insight on what the most recent lipid guidelines state about clinical triglyceride management, mention new pharmacological agents, and highlight the clinical evidence for safe and effective lowering of triglycerides levels with life style modification. Copyright © 2017. Published by Elsevier Inc.

  11. Small pixel pitch MCT IR-modules

    NASA Astrophysics Data System (ADS)

    Lutz, H.; Breiter, R.; Eich, D.; Figgemeier, H.; Fries, P.; Rutzinger, S.; Wendler, J.

    2016-05-01

    It is only some years ago, since VGA format detectors in 15μm pitch, manufactured with AIM's MCT n-on-p LPE standard technology, have been introduced to replace TV/4 format detector arrays as a system upgrade. In recent years a rapid increase in the demand for higher resolution, while preserving high thermal resolution, compactness and low power budget is observed. To satisfy these needs AIM has realized first prototypes of MWIR XGA format (1024x768) detector arrays in 10μm pitch. They fit in the same compact dewar as 640x512, 15μm pitch detector arrays. Therefore, they are best suited for system upgrade purposes to benefit from higher spatial resolution and keep cost on system level low. By combining pitch size reduction with recent development progress in the fields of miniature cryocoolers, short dewars and high operating temperatures the way ahead to ultra-compact high performance MWIR-modules is prepared. For cost reduction MBE grown MCT on commercially available GaAs substrates is introduced at AIM. Recently, 640x512, 15μm pitch FPAs, grown with MBE have successfully passed long-term high temperature storage tests as a crucial step towards serial production readiness level for use in future products. Pitch size reduction is not limited to arrays sensitive in the MWIR, but is of great interest for high performance LWIR or 3rd Gen solutions. Some applications such as rotorcraft pilotage require superior spatial resolution in a compact design to master severe weather conditions or degraded visual environment such as brown-out. For these applications AIM is developing both LWIR as well as dual band detector arrays in HD-format (1280x720) with 12μm pitch. This paper will present latest results in the development of detector arrays with small pitch sizes of 10μm and 12μm at AIM, together with their usage to realize compact cooled IR-modules.

  12. A Specialized Diacylglycerol Acyltransferase Contributes to the Extreme Medium-Chain Fatty Acid Content of Cuphea Seed Oil.

    PubMed

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

    2017-05-01

    Seed oils of many Cuphea sp. contain >90% of medium-chain fatty acids, such as decanoic acid (10:0). These seed oils, which are among the most compositionally variant in the plant kingdom, arise from specialized fatty acid biosynthetic enzymes and specialized acyltransferases. These include lysophosphatidic acid acyltransferases (LPAT) and diacylglycerol acyltransferases (DGAT) that are required for successive acylation of medium-chain fatty acids in the sn -2 and sn -3 positions of seed triacylglycerols (TAGs). Here we report the identification of a cDNA for a DGAT1-type enzyme, designated CpuDGAT1, from the transcriptome of C. avigera var pulcherrima developing seeds. Microsomes of camelina ( Camelina sativa ) seeds engineered for CpuDGAT1 expression displayed DGAT activity with 10:0-CoA and the diacylglycerol didecanoyl, that was approximately 4-fold higher than that in camelina seed microsomes lacking CpuDGAT1. In addition, coexpression in camelina seeds of CpuDGAT1 with a C. viscosissima FatB thioesterase (CvFatB1) that generates 10:0 resulted in TAGs with nearly 15 mol % of 10:0. More strikingly, expression of CpuDGAT1 and CvFatB1 with the previously described CvLPAT2, a 10:0-CoA-specific Cuphea LPAT, increased 10:0 amounts to 25 mol % in camelina seed TAG. These TAGs contained up to 40 mol % 10:0 in the sn -2 position, nearly double the amounts obtained from coexpression of CvFatB1 and CvLPAT2 alone. Although enriched in diacylglycerol, 10:0 was not detected in phosphatidylcholine in these seeds. These findings are consistent with channeling of 10:0 into TAG through the combined activities of specialized LPAT and DGAT activities and demonstrate the biotechnological use of these enzymes to generate 10:0-rich seed oils. © 2017 American Society of Plant Biologists. All Rights Reserved.

  13. Beta-ketoacyl-acyl carrier protein synthase IV: a key enzyme for regulation of medium-chain fatty acid synthesis in Cuphea lanceolata seeds.

    PubMed

    Schütt, Burkhardt Siegfried; Abbadi, Amine; Loddenkötter, Brigitte; Brummel, Monika; Spener, Friedrich

    2002-09-01

    With the aim of elucidating the mechanisms involved in the biosynthesis of medium-chain fatty acids in Cuphea lanceolata Ait., a crop accumulating up to 90% decanoic acid in seed triacylglycerols, cDNA clones of a beta-ketoacyl-acyl carrier protein (ACP) synthase IV (clKAS IV, EC 2.3.1.41) were isolated from C. lanceolata seed embryos. The amino acid sequence deduced from clKAS IV cDNA showed 80% identity to other plant KAS II-type enzymes, 55% identity towards plant KAS I and over 90% towards other Cuphea KAS IV-type sequences. Recombinant clKAS IV was functionally overexpressed in Escherichia coli, and substrate specificity of purified enzyme showed strong preference for elongation of short-chain and medium-chain acyl-ACPs (C4- to C10-ACP) with nearly equal activity. Further elongation steps were catalysed with distinctly less activity. Moreover, short- and medium-chain acyl-ACPs exerted a chain-length-specific and concentration-dependent substrate inhibition of clKAS IV. Based on these findings a regulatory mechanism for medium-chain fatty acid synthesis in C. lanceolata is presented.

  14. Designing and Creating a Synthetic Omega Oxidation Pathway in Saccharomyces cerevisiae Enables Production of Medium-Chain α, ω-Dicarboxylic Acids

    PubMed Central

    Han, Li; Peng, Yanfeng; Zhang, Yuangyuan; Chen, Wujiu; Lin, Yuping; Wang, Qinhong

    2017-01-01

    Medium-chain (C8–C14) α, ω-dicarboxylic acids (α, ω-DCAs), which have numerous applications as raw materials for producing various commodities and polymers in chemical industry, are mainly produced from chemical or microbial conversion of petroleum-derived alkanes or plant-derived fatty acids at present. Recently, significant attention has been gained to microbial production of medium-chain α, ω-DCAs from simple renewable sugars. Here, we designed and created a synthetic omega oxidation pathway in Saccharomyces cerevisiae to produce C10 and C12 α, ω-DCAs from renewable sugars and fatty acids by introducing a heterogeneous cytochrome P450 CYP94C1 and cytochrome reductase ATR1. Furthermore, the deletion of fatty acyl-CoA synthetase genes FAA1 and FAA4 increased the production of medium-chain α, ω-DCAs from 4.690 ± 0.088 mg/L to 12.177 ± 0.420 mg/L and enabled the production of C14 and C16 α, ω-DCAs at low percentage. But blocking β-oxidation pathway by deleting fatty-acyl coenzyme A oxidase gene POX1 and overexpressing different thioesterase genes had no significant impact on the production and the composition of α, ω-dicarboxylic acids. Overall, our study indicated the potential of microbial production of medium-chain α, ω-DCAs from renewable feedstocks using engineered yeast. PMID:29163455

  15. Megasphaera hexanoica sp. nov., a medium-chain carboxylic acid-producing bacterium isolated from a cow rumen.

    PubMed

    Jeon, Byoung Seung; Kim, Seil; Sang, Byoung-In

    2017-07-01

    Strain MHT, a strictly anaerobic, Gram-stain-negative, non-spore-forming, spherical coccus or coccoid-shaped microorganism, was isolated from a cow rumen during a screen for hexanoic acid-producing bacteria. The microorganism grew at 30-40 °C and pH 5.5-7.5 and exhibited production of various short- and medium-chain carboxylic acids (acetic acid, butyric acid, pentanoic acid, isobutyric acid, isovaleric acid, hexanoic acid, heptanoic acid and octanoic acid), as well as H2 and CO2 as biogas. Phylogenetic analysis based on 16S rRNA gene sequencing demonstrated that MHT represents a member of the genus Megasphaera, with the closest relatives being Megapsphaera indica NMBHI-10T (94.1 % 16S rRNA sequence similarity), Megasphaera elsdenii DSM 20460T (93.8 %) and Megasphaera paucivorans DSM 16981T (93.8 %). The major cellular fatty acids produced by MHT included C12 : 0, C16 : 0, C18 : 1cis 9, and C18 : 0, and the DNA G+C content of the MHT genome is 51.8 mol%. Together, the distinctive phenotypic and phylogenetic characteristics of MHT indicate that this microorganism represents a novel species of the genus Megasphaera, for which the name Megasphaera hexanoica sp. nov. is herein proposed. The type strain of this species is MHT (=KCCM 43214T=JCM 31403T).

  16. Tracking Dietary Sources of Short- and Medium-Chain Chlorinated Paraffins in Marine Mammals through a Subtropical Marine Food Web.

    PubMed

    Zeng, Lixi; Lam, James C W; Chen, Hui; Du, Bibai; Leung, Kenneth M Y; Lam, Paul K S

    2017-09-05

    Our previous study revealed an elevated accumulation of short-chain chlorinated paraffins (SCCPs) and medium-chain chlorinated paraffins (MCCPs) in marine mammals from Hong Kong waters in the South China Sea. To examine the bioaccumulation potential and biomagnification in these apex predators, we sampled the dietary items of marine mammals and tracked the sources of SCCPs and MCCPs through a marine food web in this region. Sixteen fish species, seven crustacean species, and four mollusk species were collected, and the main prey species were identified for two species of marine mammals. Concentrations of ∑SCCPs and ∑MCCPs in these collected species suggested a moderate pollution level in Hong Kong waters compared to the global range. Lipid content was found to mediate congener-specific bioaccumulation in these marine species. Significantly positive correlations were observed between trophic levels and concentrations of ∑SCCPs or ∑MCCPs (p < 0.05). Trophic magnification factors for ∑SCCPs and ∑MCCPs were 4.29 and 4.79, indicating that both of them have trophic magnification potentials. Elevated biomagnification of SCCPs and MCCPs from prey species to marine mammals was observed. This is the first report of dietary source tracking of SCCPs and MCCPs in marine mammals. The elevated biomagnification between prey and marine mammals raises environmental concerns about these contaminants.

  17. Medium-chain-length poly-3-hydroxyalkanoates-carbon nanotubes composite anode enhances the performance of microbial fuel cell.

    PubMed

    Hindatu, Y; Annuar, M S M; Subramaniam, R; Gumel, A M

    2017-06-01

    Insufficient power generation from a microbial fuel cell (MFC) hampers its progress towards utility-scale development. Electrode modification with biopolymeric materials could potentially address this issue. In this study, medium-chain-length poly-3-hydroxyalkanoates (PHA)/carbon nanotubes (C) composite (CPHA) was successfully applied to modify the surface of carbon cloth (CC) anode in MFC. Characterization of the functional groups on the anodic surface and its morphology was carried out. The CC-CPHA composite anode recorded maximum power density of 254 mW/m 2 , which was 15-53% higher than the MFC operated with CC-C (214 mW/m 2 ) and pristine CC (119 mW/m 2 ) as the anode in a double-chambered MFC operated with Escherichia coli as the biocatalyst. Electrochemical impedance spectroscopy and cyclic voltammetry showed that power enhancement was attributed to better electron transfer capability by the bacteria for the MFC setup with CC-CPHA anode.

  18. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Human Exposure to Short- and Medium-Chain Chlorinated Paraffins via Mothers' Milk in Chinese Urban Population.

    PubMed

    Xia, Dan; Gao, Lirong; Zheng, Minghui; Li, Jingguang; Zhang, Lei; Wu, Yongning; Tian, Qichang; Huang, Huiting; Qiao, Lin

    2017-01-03

    Chlorinated paraffins (CPs) are high production volume synthetic chemicals, found ubiquitously in various environmental matrices. However, little information is available on CP contamination in mothers' milk. In this study, 1370 urban mothers' milk samples were collected from 12 Chinese provinces in 2007 and 16 provinces in 2011. CP geographical distribution and congener group profiles were studied to assess the CP levels and figure out the source of exposure in humans. Twenty-eight pooled samples were analyzed for 48 short-chain CP (SCCP) and medium-chain CP (MCCP) congener groups using the GC × GC-ECNI-HRTOFMS method. The median concentrations of SCCPs were 681 and 733 ng/g lipid in 2007 and 2011, respectively; median concentrations of MCCPs were 60.4 and 64.3 ng/g lipid in 2007 and 2011, respectively. Variations of more than 2 orders of magnitude in CP exposure levels were found between different provinces. The levels of CPs increased from 2007 to 2011, which indicates that CP production and use may be an important exposure source. This is the first global comprehensive and large-scale investigation of CPs in mothers' milk, and it lays foundations for improving our understanding of the metabolism of CPs in humans. The high CP concentrations found in Chinese mothers' milk should raise concern about potential toxic effects in both mothers and breastfeeding infants.

  20. External Exposure to Short- and Medium-Chain Chlorinated Paraffins for the General Population in Beijing, China.

    PubMed

    Gao, Wei; Cao, Dandan; Wang, Yingjun; Wu, Jing; Wang, Ying; Wang, Yawei; Jiang, Guibin

    2018-01-02

    Chlorinated paraffins (CPs) are a class of compounds that are currently produced and used in large amounts in commercial products worldwide. In this study, food, indoor air, indoor dust, and drinking water samples were collected to evaluate the external exposure levels of CPs and possible pathway for the general population in Beijing, China. Short chain CPs (SCCPs) and medium chain CPs (MCCPs) in 199 samples were analyzed using a gas chromatography tandem time-of-flight high-resolution mass spectrometry (GC-TOF-HR-MS) method. High levels of CPs were observed in the indoor environment from residential houses, offices, and student dormitories. The geometric mean concentrations (GM) of ∑SCCPs and ∑MCCPs in indoor dust were 92 μg g -1 and 82 μg g -1 , respectively, while in indoor air, the concentrations were 80 ng m -3 and 3.4 ng m -3 , respectively. The GM of ∑SCCPs and ∑MCCPs in the diet were 83 ng g -1 dry weight (dw) and 56 ng g -1 dw, respectively. The most important external exposure routes to CPs to the general populations in Beijing were food intake and indoor dust ingestion. Indoor dust and indoor air posed higher risks for toddlers and infants than for adults.

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

    PubMed

    Hasan, Naser M Y

    2014-12-01

    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. 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. 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. 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.

  2. 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

  3. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Effects of weight loss using supplementation with Lactobacillus strains on body fat and medium-chain acylcarnitines in overweight individuals.

    PubMed

    Kim, Minkyung; Kim, Minjoo; Kang, Miso; Yoo, Hye Jin; Kim, Min Sun; Ahn, Young-Tae; Sim, Jae-Hun; Jee, Sun Ha; Lee, Jong Ho

    2017-01-25

    Our previous study showed that supplementation with a combination of Lactobacillus curvatus (L. curvatus) HY7601 and Lactobacillus plantarum (L. plantarum) KY1032 reduced the body weight, body fat percentage, body fat mass and L1 subcutaneous fat area in overweight subjects. We aimed to evaluate whether the changes in adiposity after supplementation with Lactobacillus strains were associated with metabolic intermediates. A randomized, double-blind, placebo-controlled study was conducted on 66 non-diabetic and overweight individuals. Over a 12-week period, the probiotic group consumed 2 g of probiotic powder, whereas the placebo group consumed the same product without the probiotics. To investigate metabolic alterations, we performed plasma metabolomics using ultra-performance liquid chromatography and mass spectrometry (UPLC-LTQ/Orbitrap MS). Probiotic supplementation significantly increased the levels of octenoylcarnitine (C8:1), tetradecenoylcarnitine (C14:1), decanoylcarnitine (C10) and dodecenoylcarnitine (C12:1) compared with the levels from placebo supplementation. In the probiotic group, the changes in the body weight, body fat percentage, body fat mass and L1 subcutaneous fat area were negatively associated with changes in the levels of C8:1, C14:1, C10 and C12:1 acylcarnitines. In overweight individuals, probiotic-induced weight loss and adiposity reduction from the probiotic supplementation were associated with an increase in medium-chain acylcarnitines.

  5. Medium Chain Fatty Acids Are Selective Peroxisome Proliferator Activated Receptor (PPAR) γ Activators and Pan-PPAR Partial Agonists

    PubMed Central

    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. PMID:22649490

  6. 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.

  7. 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.

  8. Metabolic engineering for microbial production and applications of copolyesters consisting of 3-hydroxybutyrate and medium-chain-length 3-hydroxyalkanoates.

    PubMed

    Zou, Xiang Hui; Chen, Guo-Qiang

    2007-02-12

    Poly(hydroxyalkanoate)s (PHAs) are a class of microbially synthesized polyesters that combine biological properties, such as biocompatibility and biodegradability, and non-bioproperties such as thermoprocessability, piezoelectricity, and nonlinear optical activity. PHA monomer structures and their contents strongly affect the PHA properties. Using metabolic engineering approaches, PHA structures and contents can be manipulated to achieve controllable monomer and PHA cellular contents. This paper focuses on metabolic engineering methods to produce PHA consisting of 3-hydroxybutyrate (3HB) and medium-chain-length 3-hydroxyalkanoates (3HA) in recombinant microbial systems. This type of copolyester has mechanical and thermal properties similar to conventional plastics such as poly(propylene) and poly(ethylene terephthalate) (PET). In addition, pathways containing engineered PHA synthases have proven to be useful for enhanced PHA production with adjustable PHA monomers and contents. The applications of PHA as implant biomaterials are briefly discussed here. In the very near term, metabolic engineering will help solve many problems in promoting PHA as a new type of plastic material for many applications.

  9. Molecular dynamics simulations of diffusion and clustering along critical isotherms of medium-chain n-alkanes.

    PubMed

    Mutoru, J W; Smith, W; O'Hern, C S; Firoozabadi, A

    2013-01-14

    Understanding the transport properties of molecular fluids in the critical region is important for a number of industrial and natural systems. In the literature, there are conflicting reports on the behavior of the self diffusion coefficient D(s) in the critical region of single-component molecular systems. For example, D(s) could decrease to zero, reach a maximum, or remain unchanged and finite at the critical point. Moreover, there is no molecular-scale understanding of the behavior of diffusion coefficients in molecular fluids in the critical regime. We perform extensive molecular dynamics simulations in the critical region of single-component fluids composed of medium-chain n-alkanes-n-pentane, n-decane, and n-dodecane-that interact via anisotropic united-atom potentials. For each system, we calculate D(s), and average molecular cluster sizes κ(cl) and numbers N(cl) at various cluster lifetimes τ, as a function of density ρ in the range 0.2ρ(c) ≤ ρ ≤ 2.0ρ(c) at the critical temperature T(c). We find that D(s) decreases with increasing ρ but remains finite at the critical point. Moreover, for any given τ < 1.2 × 10(-12) s, κ(cl) increases with increasing ρ but is also finite at the critical point.

  10. CD147 subunit of lactate/H+ symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors.

    PubMed

    Le Floch, Renaud; Chiche, Johanna; Marchiq, Ibtissam; Naiken, Tanesha; Naïken, Tanesha; Ilc, Karine; Ilk, Karine; Murray, Clare M; Critchlow, Susan E; Roux, Danièle; Simon, Marie-Pierre; Pouysségur, Jacques

    2011-10-04

    Malignant tumors exhibit increased dependence on glycolysis, resulting in abundant export of lactic acid, a hypothesized key step in tumorigenesis. Lactic acid is mainly transported by two H(+)/lactate symporters, MCT1/MCT4, that require the ancillary protein CD147/Basigin for their functionality. First, we showed that blocking MCT1/2 in Ras-transformed fibroblasts with AR-C155858 suppressed lactate export, glycolysis, and tumor growth, whereas ectopic expression of MCT4 in these cells conferred resistance to MCT1/2 inhibition and reestablished tumorigenicty. A mutant-derivative, deficient in respiration (res(-)) and exclusively relying on glycolysis for energy, displayed low tumorigenicity. These res(-) cells could develop resistance to MCT1/2 inhibition and became highly tumorigenic by reactivating their endogenous mct4 gene, highlighting that MCT4, the hypoxia-inducible and tumor-associated lactate/H(+) symporter, drives tumorigenicity. Second, in the human colon adenocarcinoma cell line (LS174T), we showed that combined silencing of MCT1/MCT4 via inducible shRNA, or silencing of CD147/Basigin alone, significantly reduced glycolytic flux and tumor growth. However, both silencing approaches, which reduced tumor growth, displayed a low level of CD147/Basigin, a multifunctional protumoral protein. To gain insight into CD147/Basigin function, we designed experiments, via zinc finger nuclease-mediated mct4 and basigin knockouts, to uncouple MCTs from Basigin expression. Inhibition of MCT1 in MCT4-null, Basigin(high) cells suppressed tumor growth. Conversely, in Basigin-null cells, in which MCT activity had been maintained, tumorigenicity was not affected. Collectively, these findings highlight that the major protumoral action of CD147/Basigin is to control the energetics of glycolytic tumors via MCT1/MCT4 activity and that blocking lactic acid export provides an efficient anticancer strategy.

  11. CD147 subunit of lactate/H+ symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors

    PubMed Central

    Le Floch, Renaud; Chiche, Johanna; Marchiq, Ibtissam; Naiken, Tanesha; Ilc, Karine; Murray, Clare M.; Critchlow, Susan E.; Roux, Danièle; Simon, Marie-Pierre; Pouysségur, Jacques

    2011-01-01

    Malignant tumors exhibit increased dependence on glycolysis, resulting in abundant export of lactic acid, a hypothesized key step in tumorigenesis. Lactic acid is mainly transported by two H+/lactate symporters, MCT1/MCT4, that require the ancillary protein CD147/Basigin for their functionality. First, we showed that blocking MCT1/2 in Ras-transformed fibroblasts with AR-C155858 suppressed lactate export, glycolysis, and tumor growth, whereas ectopic expression of MCT4 in these cells conferred resistance to MCT1/2 inhibition and reestablished tumorigenicty. A mutant-derivative, deficient in respiration (res−) and exclusively relying on glycolysis for energy, displayed low tumorigenicity. These res− cells could develop resistance to MCT1/2 inhibition and became highly tumorigenic by reactivating their endogenous mct4 gene, highlighting that MCT4, the hypoxia-inducible and tumor-associated lactate/H+ symporter, drives tumorigenicity. Second, in the human colon adenocarcinoma cell line (LS174T), we showed that combined silencing of MCT1/MCT4 via inducible shRNA, or silencing of CD147/Basigin alone, significantly reduced glycolytic flux and tumor growth. However, both silencing approaches, which reduced tumor growth, displayed a low level of CD147/Basigin, a multifunctional protumoral protein. To gain insight into CD147/Basigin function, we designed experiments, via zinc finger nuclease-mediated mct4 and basigin knockouts, to uncouple MCTs from Basigin expression. Inhibition of MCT1 in MCT4-null, Basiginhigh cells suppressed tumor growth. Conversely, in Basigin-null cells, in which MCT activity had been maintained, tumorigenicity was not affected. Collectively, these findings highlight that the major protumoral action of CD147/Basigin is to control the energetics of glycolytic tumors via MCT1/MCT4 activity and that blocking lactic acid export provides an efficient anticancer strategy. PMID:21930917

  12. 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.

  13. 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

  14. CD147 regulates the expression of MCT1 and lactate export in multiple myeloma cells

    PubMed Central

    Walters, Denise K; Arendt, Bonnie K; Jelinek, Diane F

    2013-01-01

    Increased use of the glycolytic pathway, even in the presence of oxygen, has recently been recognized as a key characteristic of malignant cells. However, the glycolytic phenotype results in increased lactic acid production and, in order to prevent cellular acidosis, tumor cells must increase proton efflux via upregulation of pH regulators such as proton-pumps, sodium-proton exchangers, and/or monocarboxylate transporters (MCT) (e.g., MCT1, MCT4). Interestingly, expression of MCT1 and MCT4 has been previously shown to be dependent upon expression of the transmembrane glycoprotein CD147. Recently, we demonstrated that primary patient multiple myeloma (MM) cells and human MM cell lines (HMCLs) overexpress CD147. Therefore, the goal of the current study was to specifically determine if MCT1 and MCT4 were also overexpressed in MM cells. RT-PCR analysis demonstrated both primary patient MM cells and HMCLs overexpress MCT1 and MCT4 mRNA. Notably, primary MM cells or HMCLs were found to express variable levels of MCT1 and/or MCT4 at the protein level despite CD147 expression. In those HMCLs positive for MCT1 and/or MCT4 protein expression, MCT1 and/or MCT4 were found to be associated with CD147. Specific siRNA-mediated downregulation of MCT1 but not MCT4 resulted in decreased HMCL proliferation, decreased lactate export, and increased cellular media pH. However, western blot analysis revealed that downregulation of MCT1 also downregulated CD147 and vice versa despite no effect on mRNA levels. Taken together, these data demonstrate the association between MCT1 and CD147 proteins in MM cells and importance of their association for lactate export and proliferation in MM cells. PMID:24013424

  15. CD147 regulates the expression of MCT1 and lactate export in multiple myeloma cells.

    PubMed

    Walters, Denise K; Arendt, Bonnie K; Jelinek, Diane F

    2013-10-01

    Increased use of the glycolytic pathway, even in the presence of oxygen, has recently been recognized as a key characteristic of malignant cells. However, the glycolytic phenotype results in increased lactic acid production and, in order to prevent cellular acidosis, tumor cells must increase proton efflux via upregulation of pH regulators such as proton-pumps, sodium-proton exchangers, and/or monocarboxylate transporters (MCT) (e.g., MCT1, MCT4). Interestingly, expression of MCT1 and MCT4 has been previously shown to be dependent upon expression of the transmembrane glycoprotein CD147. Recently, we demonstrated that primary patient multiple myeloma (MM) cells and human MM cell lines (HMCLs) overexpress CD147. Therefore, the goal of the current study was to specifically determine if MCT1 and MCT4 were also overexpressed in MM cells. RT-PCR analysis demonstrated both primary patient MM cells and HMCLs overexpress MCT1 and MCT4 mRNA. Notably, primary MM cells or HMCLs were found to express variable levels of MCT1 and/or MCT4 at the protein level despite CD147 expression. In those HMCLs positive for MCT1 and/or MCT4 protein expression, MCT1 and/or MCT4 were found to be associated with CD147. Specific siRNA-mediated downregulation of MCT1 but not MCT4 resulted in decreased HMCL proliferation, decreased lactate export, and increased cellular media pH. However, western blot analysis revealed that downregulation of MCT1 also downregulated CD147 and vice versa despite no effect on mRNA levels. Taken together, these data demonstrate the association between MCT1 and CD147 proteins in MM cells and importance of their association for lactate export and proliferation in MM cells.

  16. Improved high operating temperature MCT MWIR modules

    NASA Astrophysics Data System (ADS)

    Lutz, H.; Breiter, R.; Figgemeier, H.; Schallenberg, T.; Schirmacher, W.; Wollrab, R.

    2014-06-01

    High operating temperature (HOT) IR-detectors are a key factor to size, weight and power (SWaP) reduced IR-systems. Such systems are essential to provide infantrymen with low-weight handheld systems with increased battery lifetimes or most compact clip-on weapon sights in combination with high electro-optical performance offered by cooled IR-technology. AIM's MCT standard n-on-p technology with vacancy doping has been optimized over many years resulting in MWIR-detectors with excellent electro-optical performance up to operating temperatures of ~120K. In the last years the effort has been intensified to improve this standard technology by introducing extrinsic doping with Gold as an acceptor. As a consequence the dark current could considerably be suppressed and allows for operation at ~140K with good e/o performance. More detailed investigations showed that limitation for HOT > 140K is explained by consequences from rising dark current rather than from defective pixel level. Recently, several crucial parameters were identified showing great promise for further optimization of HOT-performance. Among those, p-type concentration could successfully be reduced from the mid 1016 / cm3 to the lower 1015/ cm3 range. Since AIM is one of the leading manufacturers of split linear cryocoolers, an increase in operating temperature will directly lead to IR-modules with improved SWaP characteristics by making use of the miniature members of its SX cooler family with single piston and balancer technology. The paper will present recent progress in the development of HOT MWIR-detector arrays at AIM and show electro-optical performance data in comparison to focal plane arrays produced in the standard technology.

  17. Expression of monocarboxylate transporter 1 (MCT1) in the dog intestine.

    PubMed

    Shimoyama, Yumiko; Kirat, Doaa; Akihara, Yuko; Kawasako, Kazufumi; Komine, Misa; Hirayama, Kazuko; Matsuda, Kazuya; Okamoto, Minoru; Iwano, Hidetomo; Kato, Seiyu; Taniyama, Hiroyuki

    2007-06-01

    In this study, the expression and distribution of monocarboxyolate transporter 1 (MCT1) along the intestines (duodenum, jejunum, ileum, cecum, colon and rectum) of dogs were investigated at both the mRNA and protein levels. The expression of MCT1 protein and its distribution were confirmed by Western blotting and immunohistochemical staining using the antibody for MCT1. We identified mRNA coding for MCT1 and a 43-kDa band of MCT1 protein in all regions from the duodenum to the rectum. Immunoreactive staining for MCT1 was also observed in epithelial cells throughout the intestines. MCT1 immunoreactivity was greater in the large intestine than in the small intestine. MCT1 protein was predominantly expressed on the basolateral membranes along intestinal epithelial cells, suggesting that MCT1 may play an important role in lactate efflux and transport of short-chain fatty acids (SCFAs) to the bloodstream across the basolateral membranes of the dog intestine.

  18. An Essential Physiological Role for MCT8 in Bone in Male Mice

    PubMed Central

    Leitch, Victoria D.; Di Cosmo, Caterina; Liao, Xiao-Hui; O’Boy, Sam; Galliford, Thomas M.; Evans, Holly; Croucher, Peter I.; Boyde, Alan; Dumitrescu, Alexandra; Weiss, Roy E.; Refetoff, Samuel; Williams, Graham R.

    2017-01-01

    T3 is an important regulator of skeletal development and adult bone maintenance. Thyroid hormone action requires efficient transport of T4 and T3 into target cells. We hypothesized that monocarboxylate transporter (MCT) 8, encoded by Mct8 on the X-chromosome, is an essential thyroid hormone transporter in bone. To test this hypothesis, we determined the juvenile and adult skeletal phenotypes of male Mct8 knockout mice (Mct8KO) and Mct8D1D2KO compound mutants, which additionally lack the ability to convert the prohormone T4 to the active hormone T3. Prenatal skeletal development was normal in both Mct8KO and Mct8D1D2KO mice, whereas postnatal endochondral ossification and linear growth were delayed in both Mct8KO and Mct8D1D2KO mice. Furthermore, bone mass and mineralization were decreased in adult Mct8KO and Mct8D1D2KO mice, and compound mutants also had reduced bone strength. Delayed bone development and maturation in Mct8KO and Mct8D1D2KO mice is consistent with decreased thyroid hormone action in growth plate chondrocytes despite elevated serum T3 concentrations, whereas low bone mass and osteoporosis reflects increased thyroid hormone action in adult bone due to elevated systemic T3 levels. These studies identify an essential physiological requirement for MCT8 in chondrocytes, and demonstrate a role for additional transporters in other skeletal cells during adult bone maintenance. PMID:28637283

  19. Concentrations of short- and medium-chain chlorinated paraffins in indoor dusts from malls in China: Implications for human exposure.

    PubMed

    Shi, Leimeng; Gao, Yuan; Zhang, Haijun; Geng, Ningbo; Xu, Jiazhi; Zhan, Faqiang; Ni, Yuwen; Hou, Xiaohong; Chen, Jiping

    2017-04-01

    Levels and distribution of short- and medium-chain chlorinated paraffins (SCCPs and MCCPs) were measured in indoor dusts from malls in China. The concentrations of SCCPs and MCCPs in dustfalls from a building material mall ranged from 6.0 to 361.4 μg g -1 and from 5.0 to 285.9 μg g -1 , respectively. Much heavier contamination was found in central air conditioner filter (CACF) dusts from a newly opened shopping mall, with SCCP concentrations of 114.7-707.0 μg g -1 and MCCP concentrations of 89.0-1082.9 μg g -1 . The C 13 - and C 14 -CPs were the dominant congeners, while the Cl 7 and Cl 8 groups were the major chlorine congeners in both kinds of dust samples. Significant correlation relationships (p ≤ 0.05) were found between ∑SCCPs and ∑MCCPs in CACF dusts and dustfalls. Varied exposure pathways including dust ingestion and dermal permeation have been evaluated. The average daily exposure doses of SCCPs and MCCPs for the adult in CACF dusts and dustfalls were estimated to be 0.394 and 0.150 μg kg -1  day -1 , respectively. The toddler had higher exposure risks with 5.918 and 2.658 μg kg -1  day -1 in the shopping and building material malls, respectively. Dermal permeation was the predominated exposure pathway for the adult, while dust ingestion was suggested to be more important for the toddler due to hand-to-mouth contact. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Production and characterization of medium-chain-length polyhydroxyalkanoate copolymer from Arctic psychrotrophic bacterium Pseudomonas sp. PAMC 28620.

    PubMed

    Sathiyanarayanan, Ganesan; Bhatia, Shashi Kant; Song, Hun-Suk; Jeon, Jong-Min; Kim, Junyoung; Lee, Yoo Kyung; Kim, Yun-Gon; Yang, Yung-Hun

    2017-04-01

    Arctic psychrotrophic bacterium Pseudomonas sp. PAMC 28620 was found to produce a distinctive medium-chain-length polyhydroxyalkanoate (MCL-PHA) copolymer when grown on structurally unrelated carbon sources including glycerol. The maximum MCL-PHA copolymer yield was obtained about 52.18±4.12% from 7.95±0.66g/L of biomass at 144h of fermentation when 3% glycerol was used as sole carbon and energy source during the laboratory-scale bioreactor process. Characterization of the copolymer was carried out using fourier transform infrared spectroscopy (FTIR), gas chromatography-mass spectrometry (GC-MS), proton ( 1 H) and carbon ( 13 C) nuclear magnetic resonance spectroscopy (NMR), gel permeation chromatography (GPC), differential scanning calorimeter (DSC) and thermo-gravimetric analysis (TGA). The copolymer produced by Pseudomonas sp. PAMC 28620 consisting of four PHA monomers and identified as 3-hydroxyoctanoate (3HO), 3-hydroxydecanoate (3HD), 3-hydroxydodecanoate (3HDD) and 3-hydroxytetradecanoate (3HTD). An average molecular weight of the copolymer was found approximately 30.244kDa with polydispersity index (PDI) value of 2.05. Thermal analysis showed the produced MCL-PHA copolymer to be low-crystalline (43.73%) polymer with great thermal stability, having the thermal decomposition temperature of 230°C-280°C, endothermic melting temperature (T m ) of 172.84°C, glass transition (T g ) temperature of 3.99°C, and apparent melting enthalpy fusion (ΔH m ) about 63.85Jg -1 . Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Impact of carbon monoxide partial pressures on methanogenesis and medium chain fatty acids production during ethanol fermentation.

    PubMed

    Esquivel-Elizondo, Sofia; Miceli, Joseph; Torres, Cesar I; Krajmalnik-Brown, Rosa

    2018-02-01

    Medium-chain fatty acids (MCFA) are important biofuel precursors. Carbon monoxide (CO) is a sustainable electron and carbon donor for fatty acid elongation, since it is metabolized to MCFA precursors, it is toxic to most methanogens, and it is a waste product generated in the gasification of waste biomass. The main objective of this work was to determine if the inhibition of methanogenesis through the continuous addition of CO would lead to increased acetate or MCFA production during fermentation of ethanol. The effects of CO partial pressures (P CO ; 0.08-0.3 atm) on methanogenesis, fatty acids production, and the associated microbial communities were studied in batch cultures fed with CO and ethanol. Methanogenesis was partially inhibited at P CO  ≥ 0.11 atm. This inhibition led to increased acetate production during the first phase of fermentation (0-19 days). However, a second addition of ethanol (day 19) triggered MCFA production only at P CO  ≥ 0.11 atm, which probably occurred through the elongation of acetate with CO-derived ethanol and H 2 :CO 2 . Accordingly, during the second phase of fermentation (days 20-36), the distribution of electrons to acetate decreased at higher P CO , while electrons channeled to MCFA increased. Most probably, Acetobacterium, Clostridium, Pleomorphomonas, Oscillospira, and Blautia metabolized CO to H 2 :CO 2 , ethanol and/or fatty acids, while Peptostreptococcaceae, Lachnospiraceae, and other Clostridiales utilized these metabolites, along with the provided ethanol, for MCFA production. These results are important for biotechnological systems where fatty acids production are preferred over methanogenesis, such as in chain elongation systems and microbial fuel cells. © 2017 Wiley Periodicals, Inc.

  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. Short- and medium-chain chlorinated paraffins in biota from the European Arctic -- differences in homologue group patterns.

    PubMed

    Reth, Margot; Ciric, Anita; Christensen, Guttorm N; Heimstad, Eldbjørg S; Oehme, Michael

    2006-08-15

    Congener and homologue group patterns of chlorinated paraffins (CPs) in biota can be influenced by different processes, but these are not well studied yet. Short- (SCCPs) and medium-chain chlorinated paraffins (MCCPs) were quantified in liver from Arctic char and seabirds (little auk and kittiwake) collected at Bear Island (European Arctic) as well as in cod from Iceland and Norway. CP concentrations were between 5 and 88 ng/g wet weight (ww) for SCCPs and between 5 and 55 ng/g ww for MCCPs with one exception of 370 ng/g measured in a liver sample from little auk. The SCCP homologue group patterns were compared with those of technical mixtures and of SCCPs present in cod liver from the Baltic Sea. The latter showed a more common SCCP homologue distribution (sum of C(11) and C(12)>60%) in contrast to cod liver from the Northwest of Europe, which had a high abundance of C(10) and C(12) congeners. Seabirds from Bear Island contained an equally distributed SCCP homologue group pattern. In Arctic char, the SCCP distribution was closer to technical products, but with a high proportion (average of 18.9%) of C(10) congeners. A comparison of C(10)/C(12) ratios confirmed the higher abundance of C(10) congeners in samples from higher latitudes. For the first time, MCCPs could be detected in Arctic samples. The average proportion of C(14) congeners was 65.8%. The C(14)/C(15) abundance ratio was similar to technical mixtures. High-chlorinated CPs (Cl(>7)) were also detectable. The average chlorine content of the SCCPs was 61.9% (59.0-63.3%), and that of the MCCPs 55.8% (54.5-57.4%).

  4. Identification and Biochemical Evidence of a Medium-Chain-Length Polyhydroxyalkanoate Depolymerase in the Bdellovibrio bacteriovorus Predatory Hydrolytic Arsenal

    PubMed Central

    Martínez, Virginia; de la Peña, Fernando; García-Hidalgo, Javier; de la Mata, Isabel; García, José Luis

    2012-01-01

    The obligate predator Bdellovibrio bacteriovorus HD100 shows a large set of proteases and other hydrolases as part of its hydrolytic arsenal needed for its predatory life cycle. We present genetic and biochemical evidence that open reading frame (ORF) Bd3709 of B. bacteriovorus HD100 encodes a novel medium-chain-length polyhydroxyalkanoate (mcl-PHA) depolymerase (PhaZBd). The primary structure of PhaZBd suggests that this enzyme belongs to the α/β-hydrolase fold family and has a typical serine hydrolase catalytic triad (serine-histidine-aspartic acid) in agreement with other PHA depolymerases and lipases. PhaZBd has been extracellularly produced using different hypersecretor Tol-pal mutants of Escherichia coli and Pseudomonas putida as recombinant hosts. The recombinant PhaZBd has been characterized, and its biochemical properties have been compared to those of other PHA depolymerases. The enzyme behaves as a serine hydrolase that is inhibited by phenylmethylsulfonyl fluoride. It is also affected by the reducing agent dithiothreitol and nonionic detergents like Tween 80. PhaZBd is an endoexohydrolase that cleaves both large and small PHA molecules, producing mainly dimers but also monomers and trimers. The enzyme specifically degrades mcl-PHA and is inactive toward short-chain-length polyhydroxyalkanoates (scl-PHA) like polyhydroxybutyrate (PHB). These studies shed light on the potentiality of these predators as sources of new biocatalysts, such as an mcl-PHA depolymerase, for the production of enantiopure hydroxyalkanoic acids and oligomers as building blocks for the synthesis of biobased polymers. PMID:22706067

  5. Synthesis of Medium-Chain-Length Polyhydroxyalkanoate Homopolymers, Random Copolymers, and Block Copolymers by an Engineered Strain of Pseudomonas entomophila.

    PubMed

    Wang, Ying; Chung, Ahleum; Chen, Guo-Qiang

    2017-04-01

    Medium-chain-length polyhydroxyalkanoates (mcl-PHAs), widely used in medical area, are commonly synthesized by Pseudomonas spp. This study tries to use β-oxidation pathways engineered P. entomophila to achieve single source of a series of mcl-monomers for microbial production of PHA homopolymers. The effort is proven successful for the first time to obtain a wide range of mcl-PHA homopolymers from engineered P. entomophila LAC23 grown on various fatty acids, respectively, ranging from poly(3-hydroxyheptanoate) to poly(3-hydroxytetradecanoate). Effects of a PHA monomer chain length on thermal and crystallization properties including the changes of T m , T g , and T d5% are investigated. Additionally, strain LAC23 is used to synthesize random copolymers of 3-hydroxyoctanoate (3HO) and 3-hydroxydodecanoate (3HDD) or 3-hydroxytetradecanoates, their compositions could be controlled by adjusting the ratios of two related fatty acids. Meanwhile, block copolymer P(3HO)-b-P(3HDD) is synthesized by the same strain. It is found for the first time that even- and odd number mcl-PHA homopolymers have different physical properties. When the gene of the PHA synthase in the engineered P. entomophila is replaced by phaC from Aeromonas hydrophila 4AK4, poly(3-hydroxybutyrate-co-30 mol%-3-hydroxyhexanoate) is synthesized. Therefore, P. entomophila can be used to synthesize the whole range of PHA (C7-C14) homopolymers, random- and block copolymers. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Immunohistochemical localization of GLUT3, MCT1, and MCT2 in the testes of mice and rats: the use of different energy sources in spermatogenesis.

    PubMed

    Kishimoto, Ayuko; Ishiguro-Oonuma, Toshina; Takahashi, Ritei; Maekawa, Mamiko; Toshimori, Kiyotaka; Watanabe, Masahiko; Iwanaga, Toshihiko

    2015-01-01

    Lactate represents a preferential energy substrate of germ cells rather than glucose. Testicular Sertoli cells are believed to produce lactate and pyruvate and to supply these to germ cells, particularly spermatocytes and spermatids. Monocarboxylate transporter (MCT), responsible for the transport of lactate and other monocarboxylates via the cell membrane, is abundant in the testes and sperm (MCT1, MCT2, and MCT4). For the uptake of glucose, germ cells within the seminiferous tubules and sperm have been known to intensely express GLUT3. The present study investigated expression profiles of MCTs and GLUTs and revealed their cellular and subcellular localization in the mouse and rat testis. An in situ hybridization analysis showed significant expressions of MCT1, MCT2, and GLUT3 mRNA in the testis. Immunohistochemically, spermatogonia, spermatocytes, and spermatids expressed MCT1 on their cell surfaces in a stage-dependent manner: in some seminiferous tubules, an intense expression of MCT1 was unique to the spermatogonia. MCT2 was restricted to the tails of elongated spermatids and sperm. An intense immunoreactivity for GLUT3 was shared by spermatocytes, spermatids, and sperm. Sertoli cells were devoid of any immunoreactivities for MCT1, MCT2, and GLUT3. The predominant energy source of germ cells may be lactate and other monocarboxylates--especially for spermatogonia, but glucose and other hexoses may be responsible for an energy supply to spermatocytes and spermatids.

  7. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Monocarboxylate transporters MCT1 and MCT4 are independent prognostic biomarkers for the survival of patients with clear cell renal cell carcinoma and those receiving therapy targeting angiogenesis.

    PubMed

    Cao, Yan-Wei; Liu, Yong; Dong, Zhen; Guo, Lei; Kang, En-Hao; Wang, Yong-Hua; Zhang, Wei; Niu, Hai-Tao

    2018-04-12

    Prognostic biomarkers for patients with clear cell renal cell carcinoma (ccRCC), particularly those receiving therapy targeting angiogenesis, are not well established. In this study, we examined the correlations of monocarboxylate transporter 1 (MCT1) and MCT4, 2 critical transporters for glycolytic metabolism, with various clinicopathological parameters as well as survival of patients with ccRCC and those treated with vascular endothelial growth factor receptor (VEGFR) inhibitors. A cohort of 150 ccRCC patients were recruited into this study. All patients underwent radical or partial nephrectomy as the first-line treatment, and 38 received targeted therapy (sorafenib or sunitinib) after the surgery. Expression levels of MCT1, MCT4, and CD34 were examined by immunohistochemistry. Correlations between MCT1 or MCT4 expression and different clinicopathological parameters or patient survival were analyzed among all as well as patients receiving targeted therapy. MCT1 or MCT4 expression did not significantly correlate with sex, age, tumor diameter, microvascular density, tumor staging, pathological Furmann grade, or MSKCC (P>0.05). High expression of either MCT1 or MCT4 significantly correlated with reduced overall survival (OS) and progression-free survival (PFS) among the total cohort of ccRCC patients. For patients receiving targeted therapy, high expression of either MCT1 or MCT4 significantly correlated with reduced PFS, but not OS. Both conditions were independent prognostic biomarkers for reduced PFS among all patients or those receiving targeted therapy. MCT1 and MCT4 are prognostic biomarkers for patients with ccRCC or those receiving targeted therapy. High expression of these 2 proteins predicts reduced PFS in these patients. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Prognostic significance of lactate/proton symporters MCT1, MCT4, and their chaperone CD147 expressions in urothelial carcinoma of the bladder.

    PubMed

    Choi, Jung-Woo; Kim, Younghye; Lee, Ju-Han; Kim, Young-Sik

    2014-07-01

    To investigate the prognostic significance of lactate/proton monocarboxylate transporters MCT1, MCT4, and their chaperone CD147 expressions in urothelial carcinoma of the bladder (UCB). We examined the expressions of MCT1, MCT4, and CD147 proteins in a total of 360 cases of UCB by immunohistochemistry. The immunohistochemical expressions were quantified using an ImageJ-based analysis program. MCT1, MCT4, and CD147 expressions were increased in 130 (36.1%), 168 (46.7%), and 228 (63.3%) UCB cases, respectively. Most tumor cells showed diffuse membranous staining, whereas normal urothelial cells showed negative or weak staining. High levels of MCT1 expression correlated with high World Health Organization grade (P<.001), advanced tumor node metastasis (TNM) stage (P<.001), nonpapillary growth type (P<.001), and lymphatic tumor invasion (P=.010), whereas high levels of MCT4 expression did not significantly correlate with any of these variables. High CD147 expression was associated with high World Health Organization grade (P<.001), advanced tumor node metastatis stage (P<.001), and nonpapillary growth type (P=.003). Univariate analyses revealed that high MCT1 (P<.001) and CD147 (P=.029) expressions were associated with poor overall survival and that high MCT4 expression was correlated with poor recurrence-free survival (P=.036). Multivariate analyses revealed that high MCT1 and MCT4 expressions were independent prognostic factors for poor overall survival and poor recurrence-free survival, respectively, in UCB patients. Our results indicate that increased MCT1, MCT4, and CD147 expressions have prognostic implications in UCB and suggest their roles in urothelial cancer metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Polymerized and functionalized triglycerides

    USDA-ARS?s Scientific Manuscript database

    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 ...

  11. Randomized structured triglycerides increase lymphatic absorption of tocopherol and retinol compared with the equivalent physical mixture in a rat model of fat malabsorption.

    PubMed

    Tso, P; Lee, T; DeMichele, S J

    2001-08-01

    Previously we demonstrated that the digestion, absorption and lymphatic transport of lipid and key essential fatty acids (EFA) from randomly interesterified fish oil/medium-chain structured triglycerides (STG) were significantly higher than an equivalent physical mixture (PM) in a normal lymph fistula rat model and in a rat model of lipid malabsorption caused by ischemia/reperfusion (I/R) injury. The goals of this study were to further explore the potential absorptive benefits of STG by comparing the intestinal absorption and lymphatic transport of tocopherol and retinol when delivered gastrically with either STG or PM under normal conditions and after I/R injury to the small bowel. Food-deprived male Sprague-Dawley rats were randomly assigned to two treatments (sham controls or I/R). Under halothane anesthesia, the superior mesenteric artery (SMA) was occluded for 20 min and then reperfused in I/R rats. The SMA was isolated but not occluded in control rats. In both groups, the mesenteric lymph duct was cannulated and a gastric tube was inserted. Each treatment group received 1 mL of the fish oil/MCT STG or PM (7 rats/group) along with (14)C-alpha-tocopherol and (3)H-retinol through the gastric tube followed by an infusion of PBS at 3 mL/h for 8 h. Lymph was collected hourly for 8 h. Under steady-state conditions, the amount of (14)C-alpha-tocopherol and (3)H-retinol transported into lymph was significantly higher in the STG-fed rats compared with those fed PM in both control and I/R groups. In addition, control and I/R rats given STG had earlier steady-state outputs of (14)C-alpha-tocopherol and (3)H-retinol and maintained approximately 30% higher outputs in lymph throughout the 8-h lymph collection period compared with rats given the PM. We conclude that STG provides the opportunity to potentiate improved absorption of fat-soluble vitamins under normal and malabsorptive states.

  12. Characterization of two acyl-acyl carrier protein thioesterases from developing Cuphea seeds specific for medium-chain- and oleoyl-acyl carrier protein.

    PubMed

    Dörmann, P; Spener, F; Ohlrogge, J B

    1993-03-01

    Two acyl-acyl carrier protein (ACP) thioesterases were partially purified from developing seeds of Cuphea lanceolata Ait., a plant with decanoic acid-rich triacylglycerols. The two enzymes differ markedly in their substrate specificity. One is specific for medium-chain acyl-ACPs, the other one for oleoyl-ACP. In addition, these enzymes are distinct with regard to molecular weight, pH optimum and sensitivity to salt. The thioesterases could be separated by Mono Q chromatography or gel filtration. The medium-chain acyl-ACP thioesterase and oleoyl-ACP thioesterase were purified from a crude extract 29- and 180-fold, respectively. In Cuphea wrightii A. Gray, which predominantly contains decanoic a nd lauric acid in the seeds, two different thioesterases were also found with a similar substrate specificity as in Cuphea lanceolata.

  13. Short- and medium-chain fatty acids enhance the cell surface expression and transport capacity of the bile salt export pump (BSEP/ABCB11).

    PubMed

    Kato, Takuya; Hayashi, Hisamitsu; Sugiyama, Yuichi

    2010-09-01

    The reduced expression of the bile salt export pump (BSEP/ABCB11) at the canalicular membrane is associated with cholestasis-induced hepatotoxicity due to the accumulation of bile acids in hepatocytes. We previously reported that 4-phenylbutyrate (4PBA), an approved drug for urea cycle disorders, is a promising agent for intrahepatic cholestasis because it increases both the cell surface expression and the transport capacity of BSEP. In the present study, we searched for effective compounds other than 4PBA by focusing on short- and medium-chain fatty acids, which have similar characteristics to 4PBA such as their low-molecular-weight and a carboxyl group. In transcellular transport studies using Madin-Darby canine kidney (MDCK) II cells, all short- and medium-chain fatty acids tested except for formate, acetate, and hexanoic acid showed more potent effects on wild type (WT) BSEP-mediated [3H]taurocholate transport than did 4PBA. The increase in WT BSEP transport with butyrate and octanoic acid treatment correlated with an increase in its expression at the cell surface. Two PFIC2-type variants, E297G and D482G BSEP, were similarly affected with both compounds treatment. The prolonged half-life of cell surface-resident WT BSEP was responsible for this increased octanoic acid-stimulated transport, but not for that of butyrate. In conclusion, short- and medium-chain fatty acids have potent effects on the increase in WT and PFIC2-type BSEP-mediated transport in MDCK II cells. Although both short- and medium-chain fatty acids enhance the transport capacity of WT and PFIC2-type BSEP by inducing those expressions at the cell surface, the underlying mechanism seems to differ between fatty acids. 2010 Elsevier B.V. All rights reserved.

  14. 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

  15. A Clostridium Group IV Species Dominates and Suppresses a Mixed Culture Fermentation by Tolerance to Medium Chain Fatty Acids Products

    PubMed Central

    Andersen, Stephen J.; De Groof, Vicky; Khor, Way Cern; Roume, Hugo; Props, Ruben; Coma, Marta; Rabaey, Korneel

    2017-01-01

    A microbial community is engaged in a complex economy of cooperation and competition for carbon and energy. In engineered systems such as anaerobic digestion and fermentation, these relationships are exploited for conversion of a broad range of substrates into products, such as biogas, ethanol, and carboxylic acids. Medium chain fatty acids (MCFAs), for example, hexanoic acid, are valuable, energy dense microbial fermentation products, however, MCFA tend to exhibit microbial toxicity to a broad range of microorganisms at low concentrations. Here, we operated continuous mixed population MCFA fermentations on biorefinery thin stillage to investigate the community response associated with the production and toxicity of MCFA. In this study, an uncultured species from the Clostridium group IV (related to Clostridium sp. BS-1) became enriched in two independent reactors that produced hexanoic acid (up to 8.1 g L−1), octanoic acid (up to 3.2 g L−1), and trace concentrations of decanoic acid. Decanoic acid is reported here for the first time as a possible product of a Clostridium group IV species. Other significant species in the community, Lactobacillus spp. and Acetobacterium sp., generate intermediates in MCFA production, and their collapse in relative abundance resulted in an overall production decrease. A strong correlation was present between the community composition and both the hexanoic acid concentration (p = 0.026) and total volatile fatty acid concentration (p = 0.003). MCFA suppressed species related to Clostridium sp. CPB-6 and Lactobacillus spp. to a greater extent than others. The proportion of the species related to Clostridium sp. BS-1 over Clostridium sp. CPB-6 had a strong correlation with the concentration of octanoic acid (p = 0.003). The dominance of this species and the increase in MCFA resulted in an overall toxic effect on the mixed community, most significantly on the Lactobacillus spp., which resulted in a decrease in total

  16. 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 (0·071 (sd 0·035) v. 0·053 (sd 0·028) 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.

  17. Cost-effectiveness analysis of universal newborn screening for medium chain acyl-CoA dehydrogenase deficiency in France

    PubMed Central

    2012-01-01

    Background Five diseases are currently screened on dried blood spots in France through the national newborn screening programme. Tandem mass spectrometry (MS/MS) is a technology that is increasingly used to screen newborns for an increasing number of hereditary metabolic diseases. Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is among these diseases. We sought to evaluate the cost-effectiveness of introducing MCADD screening in France. Methods We developed a decision model to evaluate, from a societal perspective and a lifetime horizon, the cost-effectiveness of expanding the French newborn screening programme to include MCADD. Published and, where available, routine data sources were used. Both costs and health consequences were discounted at an annual rate of 4%. The model was applied to a French birth cohort. One-way sensitivity analyses and worst-case scenario simulation were performed. Results We estimate that MCADD newborn screening in France would prevent each year five deaths and the occurrence of neurological sequelae in two children under 5 years, resulting in a gain of 128 life years or 138 quality-adjusted life years (QALY). The incremental cost per year is estimated at €2.5 million, down to €1 million if this expansion is combined with a replacement of the technology currently used for phenylketonuria screening by MS/MS. The resulting incremental cost-effectiveness ratio (ICER) is estimated at €7 580/QALY. Sensitivity analyses indicate that while the results are robust to variations in the parameters, the model is most sensitive to the cost of neurological sequelae, MCADD prevalence, screening effectiveness and screening test cost. The worst-case scenario suggests an ICER of €72 000/QALY gained. Conclusions Although France has not defined any threshold for judging whether the implementation of a health intervention is an efficient allocation of public resources, we conclude that the expansion of the French newborn screening programme

  18. Cost-effectiveness analysis of universal newborn screening for medium chain acyl-CoA dehydrogenase deficiency in France.

    PubMed

    Hamers, Françoise F; Rumeau-Pichon, Catherine

    2012-06-08

    Five diseases are currently screened on dried blood spots in France through the national newborn screening programme. Tandem mass spectrometry (MS/MS) is a technology that is increasingly used to screen newborns for an increasing number of hereditary metabolic diseases. Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is among these diseases. We sought to evaluate the cost-effectiveness of introducing MCADD screening in France. We developed a decision model to evaluate, from a societal perspective and a lifetime horizon, the cost-effectiveness of expanding the French newborn screening programme to include MCADD. Published and, where available, routine data sources were used. Both costs and health consequences were discounted at an annual rate of 4%. The model was applied to a French birth cohort. One-way sensitivity analyses and worst-case scenario simulation were performed. We estimate that MCADD newborn screening in France would prevent each year five deaths and the occurrence of neurological sequelae in two children under 5 years, resulting in a gain of 128 life years or 138 quality-adjusted life years (QALY). The incremental cost per year is estimated at €2.5 million, down to €1 million if this expansion is combined with a replacement of the technology currently used for phenylketonuria screening by MS/MS. The resulting incremental cost-effectiveness ratio (ICER) is estimated at €7 580/QALY. Sensitivity analyses indicate that while the results are robust to variations in the parameters, the model is most sensitive to the cost of neurological sequelae, MCADD prevalence, screening effectiveness and screening test cost. The worst-case scenario suggests an ICER of €72 000/QALY gained. Although France has not defined any threshold for judging whether the implementation of a health intervention is an efficient allocation of public resources, we conclude that the expansion of the French newborn screening programme to MCADD would appear to be cost

  19. Dietary exposure to short- and medium-chain chlorinated paraffins in meat and meat products from 20 provinces of China.

    PubMed

    Huang, Huiting; Gao, Lirong; Zheng, Minghui; Li, Jingguang; Zhang, Lei; Wu, Yongning; Wang, Runhua; Xia, Dan; Qiao, Lin; Cui, Lili; Su, Guijin; Liu, Wenbin; Liu, Guorui

    2018-02-01

    Food intake is one of the main pathways of human exposure to chlorinated paraffins (CPs). This study assessed the dietary exposure for the general Chinese population to short-chain chlorinated paraffin (SCCPs) and medium-chain chlorinated paraffins (MCCPs) through meat and meat products. Twenty samples of meat and meat products from 20 Chinese provinces were collected in 2011. As the sampling sites covered about two-thirds of the Chinese population, the meat samples were considered to be representative of the true characteristics of CPs contamination in Chinese meat products. The concentrations of SCCPs and MCCPs in the meat samples were measured using the comprehensive two-dimensional gas chromatography electron capture negative ionization high-resolution time-of-flight mass spectrometry method. Forty-eight SCCP and MCCP homolog groups were detected in the meat samples. The mean SCCP and MCCP concentrations in all meat samples were 129 ± 4.1 ng g -1 wet weight and 5.7 ± 0.59 ng g -1 wet weight, respectively. The concentrations of SCCPs and MCCPs varied in samples from different provinces. The geographical distribution of CP concentrations was similar to the distribution of CPs manufacturing plants in China. The most abundant groups of SCCPs in all samples were C 10-11 Cl 6-7 , and the most abundant groups of MCCPs in most samples were C 14 Cl 7-8 . The possible sources of SCCPs and MCCPs in meat and meat products might be CP-42 and CP-52. The 50th percentile estimated daily intakes of SCCPs and MCCPs through meat consumption for a "standard" Chinese adult male were 0.13 and 0.0047 μg kg -1 bw d -1 , respectively, both much lower than the tolerable daily intakes (TDIs) for SCCPs and MCCPs. This preliminary risk assessment has indicated that the indirect exposure of SCCPs and MCCPs through meat consumption does not pose significant risk to human health in China. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. 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. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  1. Parenteral structured triglyceride emulsion improves nitrogen balance and is cleared faster from the blood in moderately catabolic patients.

    PubMed

    Kruimel, J W; Naber, T H; van der Vliet, J A; Carneheim, C; Katan, M B; Jansen, J B

    2001-01-01

    Most postoperative patients lose net protein mass, which reflects loss of muscle tissue and organ function. Perioperative parenteral nutrition may reduce the loss of protein, but in general, with conventional lipid emulsions a waste of protein still remains. We compared the effects on nitrogen balance of an emulsion containing structured triglycerides, a new type of synthesized triglycerides, with an emulsion of a physical mixture of medium- and long-chain triglycerides as part of parenteral feeding in moderately catabolic patients. The first 5 days after placement of an aortic prosthesis patients received total parenteral nutrition (TPN) providing 0.2 g of nitrogen per kg body weight per day; energy requirement was calculated using Harris and Benedict's equation, adding 300 kcal per day for activity. Twelve patients were treated with the structured triglyceride emulsion and 13 patients with the emulsion of the physical mixture of medium- and long-chain triglycerides. The design was a randomized, double-blind parallel study. In the patients who completed the study, the mean cumulative nitrogen balance over the first 5 postoperative days was -8+/-2 g in 10 patients on the structured triglyceride emulsion and -21+/-4 g in 9 patients on the emulsion of the physical mixture of medium- and long-chain triglycerides; the mean difference was 13 g of nitrogen (95% confidence interval 4 to 22, p = .015) in favor of the structured triglyceride emulsion. On the first postoperative day serum triglyceride and plasma medium-chain free fatty acid levels increased less during infusion of the structured triglyceride emulsion than with the physical mixture emulsion. The parenteral structured triglyceride emulsion improves the nitrogen balance and is cleared faster from the blood, compared with the emulsion of the physical mixture of medium- and long-chain triglycerides, in moderately catabolic patients.

  2. Expression of lactate transporters MCT1, MCT2 and CD147 in the red blood cells of three horse breeds: Finnhorse, Standardbred and Thoroughbred.

    PubMed

    Mykkänen, A K; Pösö, A R; McGowan, C M; McKane, S A

    2010-11-01

    In exercising horses, up to 50% of blood lactate is taken up into red blood cells (RBCs). Lactate transporter proteins MCT1, MCT2 and CD147 (an ancillary protein for MCT1) are expressed in the equine RBC membrane. In Standardbreds (SB), lactate transport activity is bimodally distributed and correlates with the amount of MCT1 and CD147. About 75% of SB studied have high lactate transport activity in RBCs. In other breeds, the distribution of lactate transport activity is unknown. To study whether similar bimodal distribution of MCT1 and CD147 is present also in the racing Finnhorse (FH) and Thoroughbred (TB) as in the SB and to study the distribution of MCT2 in all 3 breeds and to determine if there is a connection between MCT expression and performance markers in TB racehorses. Venous blood samples were taken from 118 FHs, 98 TBs and 44 SBs. Red blood cell membranes were purified and MCT1, MCT2 and CD147 measured by western blot. The amount of transporters was compared with TB performance markers. In TBs, the distribution of MCT1 was bimodal and in all breeds distribution of MCT2 unimodal. The amount of CD147 was clearly bimodal in FH and SB, with 85 and 82% expressing high amounts of CD147. In TBs, 88% had high expression of CD147 and 11% low expression, but one horse showed intermediate expression not apparent in FH or SB. Performance markers did not correlate with the amount of MCT1, MCT2 or CD147. High lactate transport activity was present in all 3 racing breeds, with the greatest proportion in the TB, followed by the racing FH, then SB. There was no significant statistical correlation found between lactate transporters in RBC membrane and markers of racing performance in the TB. © 2010 EVJ Ltd.

  3. MCT1 and MCT4 kinetic of mRNA expression in different tissues after aerobic exercise at maximal lactate steady state workload.

    PubMed

    de Araujo, G G; Gobatto, C A; de Barros Manchado-Gobatto, F; Teixeira, L Fm; Dos Reis, I Gm; Caperuto, L C; Papoti, M; Bordin, S; Cavaglieri, C R; Verlengia, R

    2015-01-01

    We evaluate the mRNA expression of monocarboxylate transporters 1 and 4 (MCT1 and MCT4) in skeletal muscle (soleus, red and white gastrocnemius), heart and liver tissues in mice submitted to a single bout of swimming exercise at the maximal lactate steady state workload (MLSSw). After 72 h of MLSS test, the animals were submitted to a swimming exercise session for 25 min at individual MLSSw. Tissues and muscle samples were obtained at rest (control, n=5), immediately (n=5), 5 h (n=5) and 10 h (n=5) after exercise for determination of the MCT1 and MCT4 mRNA expression (RT-PCR). The MCT1 mRNA expression in liver increased after 10 h in relation to the control, immediate and 5 h groups, but the MCT4 remained unchanged. The MCT1 mRNA expression in heart increased by 31 % after 10 h when compared to immediate, but no differences were observed in relation to the control group. No significant differences were observed for red gastrocnemius in MCT1 and MCT4 mRNA expression. However, white gastrocnemius increased MCT1 mRNA expression immediately when compared to rest, 5 and 10 h test groups. In soleus muscle, the MCT1 mRNA expression increased immediately, 5 and 10 h after exercise when compared to the control. In relation to MCT4 mRNA expression, the soleus increased immediately and 10 h after acute exercise when compared to the control group. The soleus, liver and heart were the main tissues that showed improved the MCT1 mRNA expression, indicating its important role in controlling MLSS concentration in mice.

  4. AR-C155858 is a potent inhibitor of monocarboxylate transporters MCT1 and MCT2 that binds to an intracellular site involving transmembrane helices 7-10.

    PubMed

    Ovens, Matthew J; Davies, Andrew J; Wilson, Marieangela C; Murray, Clare M; Halestrap, Andrew P

    2010-01-15

    In the present study we characterize the properties of the potent MCT1 (monocarboxylate transporter 1) inhibitor AR-C155858. Inhibitor titrations of L-lactate transport by MCT1 in rat erythrocytes were used to determine the Ki value and number of AR-C155858-binding sites (Et) on MCT1 and the turnover number of the transporter (kcat). Derived values were 2.3+/-1.4 nM, 1.29+/-0.09 nmol per ml of packed cells and 12.2+/-1.1 s-1 respectively. When expressed in Xenopus laevis oocytes, MCT1 and MCT2 were potently inhibited by AR-C155858, whereas MCT4 was not. Inhibition of MCT1 was shown to be time-dependent, and the compound was also active when microinjected, suggesting that AR-C155858 probably enters the cell before binding to an intracellular site on MCT1. Measurement of the inhibitor sensitivity of several chimaeric transporters combining different domains of MCT1 and MCT4 revealed that the binding site for AR-C155858 is contained within the C-terminal half of MCT1, and involves TM (transmembrane) domains 7-10. This is consistent with previous data identifying Phe360 (in TM10) and Asp302 plus Arg306 (TM8) as key residues in substrate binding and translocation by MCT1. Measurement of the Km values of the chimaeras for L-lactate and pyruvate demonstrate that both the C- and N-terminal halves of the molecule influence transport kinetics consistent with our proposed molecular model of MCT1 and its translocation mechanism that requires Lys38 in TM1 in addition to Asp302 and Arg306 in TM8 [Wilson, Meredith, Bunnun, Sessions and Halestrap (2009) J. Biol. Chem. 284, 20011-20021].

  5. Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0524 TITLE:Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis PRINCIPAL INVESTIGATOR: Jeffrey D...29 Sep 2015 4. TITLE AND SUBTITLE Oligodendroglial MCT1 and Metabolic Support of Axons in Multiple Sclerosis 5a. CONTRACT NUMBER W81XWH-14-1-0524...MCT1 in injured oligodendroglia of multiple sclerosis patients contributes to axon neurodegeneration and that increasing MCT1 will be protective in the

  6. Monocarboxylate transporters 1-4 in NSCLC: MCT1 is an independent prognostic marker for survival.

    PubMed

    Eilertsen, Marte; Andersen, Sigve; Al-Saad, Samer; Kiselev, Yury; Donnem, Tom; Stenvold, Helge; Pettersen, Ingvild; Al-Shibli, Khalid; Richardsen, Elin; Busund, Lill-Tove; Bremnes, Roy M

    2014-01-01

    Monocarboxylate transporters (MCTs) 1-4 are lactate transporters crucial for cancers cells adaption to upregulated glycolysis. Herein, we aimed to explore their prognostic impact on disease-specific survival (DSS) in both cancer and tumor stromal cells in NSCLC. Tissue micro arrays (TMAs) were constructed, representing both cancer and stromal tumor tissue from 335 unselected patients diagnosed with stage I-IIIA NSCLC. Immunohistochemistry was used to evaluate the expression of MCT1-4. In univariate analyses; ↓ MCT1 (P = 0.021) and ↑ MCT4 (P = 0.027) expression in cancer cells, and ↑ MCT1 (P = 0.003), ↓ MCT2 (P = 0.006), ↓ MCT3 (P = 0.020) expression in stromal cells correlated significantly with a poor DSS. In multivariate analyses; ↓ MCT1 expression in cancer cells (HR: 1.9, CI 95%: 1.3-2.8, P = 0.001), ↓ MCT2 (HR: 2.4, CI 95%: 1.5-3.9, P<0.001), ↓ MCT3 (HR: 1.9, CI 95%: 1.1-3.5, P = 0.031) and ↑ MCT1 expression in stromal cells (HR: 1.7, CI 95%: 1.1-2.7, P = 0.016) were significant independent poor prognostic markers for DSS. We provide novel information of MCT1 as a candidate marker for prognostic stratification in NSCLC. Interestingly, MCT1 shows diverging, independent prognostic impact in the cancer cell and stromal cell compartments.

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

    PubMed Central

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

    2011-01-01

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

  8. 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

  9. Possible involvement of AMPK in acute exercise-induced expression of monocarboxylate transporters MCT1 and MCT4 mRNA in fast-twitch skeletal muscle.

    PubMed

    Takimoto, Masaki; Takeyama, Mirei; Hamada, Taku

    2013-11-01

    The regulatory mechanisms responsible for acute exercise-induced expression of monocarboxylate transporters MCT1 and MCT4 mRNA in skeletal muscle remain unclear. 5'-adenosine-activated protein kinase (AMPK) is a key signaling molecule that regulates gene expression at the mRNA level. We examined whether AMPK activation is involved in acute exercise-induced expression of MCT1 and MCT4 mRNA in fast-twitch muscle. Male Sprague-Dawley rats were subjected to an acute bout of either 5min high-intensity intermittent swimming (HIS) or 6-h low-intensity prolonged swimming (LIS). The effects of acute exercise on the phosphorylation of AMPK (p-AMPK), calcium/calmodulin pendent kinase II (p-CaMKII), p38 mitogen-activated protein kinase (p-p38MAPK), and MCTs mRNA were analyzed in vivo. To observe the direct effects of AMPK activation on MCTs mRNA, the effects of 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), caffeine, and dantrolene were analyzed in vitro using an isolated muscle incubation model. The p-AMPK increased in response to both HIS and LIS, although the p-CaMKII and p-p38MAPK were increased only following HIS. Irrespective of exercise intensity, MCT1 and MCT4 mRNA was also transiently upregulated by both HIS and LIS. Direct exposure of the epitrochlearis muscle to 0.5mmol/L AICAR or 1mmol/L caffeine, which activated p-AMPK increased both MCT1 and MCT4 mRNA levels. When pAMPK was inhibited by dantrolene, neither MCT1 nor MCT4 mRNA was increased. These results suggest that acute exercise-induced increases in MCT1 and MCT4 mRNA expression may be possibly mediated by AMPK activation, at least in part in fast-twitch muscle. © 2013.

  10. Organized metabolic crime in prostate cancer: The coexpression of MCT1 in tumor and MCT4 in stroma is an independent prognosticator for biochemical failure.

    PubMed

    Andersen, Sigve; Solstad, Ørjan; Moi, Line; Donnem, Tom; Eilertsen, Marte; Nordby, Yngve; Ness, Nora; Richardsen, Elin; Busund, Lill-Tove; Bremnes, Roy M

    2015-08-01

    Lactate import or export over cell membranes is facilitated by monocarboxylate transporters (MCTs) 1 and 4. Expression profiles can be markers of an oxidative or glycolytic phenotype. Descriptive studies and functional studies in neoplastic cells and fibroblasts in prostate cancer (PC) have suggested a distinct phenotype. We aimed to explore expression of MCT1 and MCT4 in PC cells and surrounding stroma in a large cohort. Additionally, we wanted to find out if distinct expression profiles were associated with biochemical failure-free survival (BFFS). Tissue microarrays were constructed from 535 patients with radical prostatectomies between January 1, 1995, and December 31, 2005. Immunohistochemistry was used to detect expression, and degrees of expression were evaluated semiquantitatively by 2 pathologists using light microscopy. For MCT1, there was only epithelial expression, whereas there was a low level of expression of MCT4 in tumor and stroma. A total of 172 patients had a low expression of MCT1 in tumor and MCT4 in stroma. There were 232 patients who had a high expression of MCT1 and a low expression of MCT4 in stroma. Only 11 patients had a low tumoral MCT1 expression and a high stromal MCT4 expression, and 26 patients (5%) had a high expression of both. Patients with a high-high combination had a significantly reduced BFFS (P = 0.011), and when adjusting for other factors, its effect was significant and independent (HR = 1.99, CI 95%: 1.09-3.62; P = 0.024). This study adds to the current understanding of the reversed Warburg effect to be a significant phenotype in PC. High coexpression of MCT1 in tumor and MCT4 in stroma is independently associated to a worse BFFS, and the strength of this association is as strong as having a Gleason score of ≥9. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Monocarboxylate Transporter 1 (MCT1) is an independent prognostic biomarker in endometrial cancer.

    PubMed

    Latif, Ayşe; Chadwick, Amy L; Kitson, Sarah J; Gregson, Hannah J; Sivalingam, Vanitha N; Bolton, James; McVey, Rhona J; Roberts, Stephen A; Marshall, Kay M; Williams, Kaye J; Stratford, Ian J; Crosbie, Emma J

    2017-01-01

    Endometrial cancer (EC) is a major health concern due to its rising incidence. Whilst early stage disease is generally cured by surgery, advanced EC has a poor prognosis with limited treatment options. Altered energy metabolism is a hallmark of malignancy. Cancer cells drive tumour growth through aerobic glycolysis and must export lactate to maintain intracellular pH. The aim of this study was to evaluate the expression of the lactate/proton monocarboxylate transporters MCT1 and MCT4 and their chaperone CD147 in EC, with the ultimate aim of directing future drug development. MCT1, MCT4 and CD147 expression was examined using immunohistochemical analysis in 90 endometrial tumours and correlated with clinico-pathological characteristics and survival outcomes. MCT1 and MCT4 expression was observed in the cytoplasm, the plasma membrane or both locations. CD147 was detected in the plasma membrane and associated with MCT1 ( p  = 0.003) but not with MCT4 ( p  = 0.207) expression. High MCT1 expression was associated with reduced overall survival ( p  = 0.029) and remained statistically significant after adjustment for survival covariates ( p  = 0.017). Our data suggest that MCT1 expression is an important marker of poor prognosis in EC. MCT1 inhibition may have potential as a treatment for advanced or recurrent EC.

  12. Integration of a 'proton antenna' facilitates transport activity of the monocarboxylate transporter MCT4.

    PubMed

    Noor, Sina Ibne; Pouyssegur, Jacques; Deitmer, Joachim W; Becker, Holger M

    2017-01-01

    Monocarboxylate transporters (MCTs) mediate the proton-coupled transport of high-energy metabolites like lactate and pyruvate and are expressed in nearly every mammalian tissue. We have shown previously that transport activity of MCT4 is enhanced by carbonic anhydrase II (CAII), which has been suggested to function as a 'proton antenna' for the transporter. In the present study, we tested whether creation of an endogenous proton antenna by introduction of a cluster of histidine residues into the C-terminal tail of MCT4 (MCT4-6xHis) could facilitate MCT4 transport activity when heterologously expressed in Xenopus oocytes. Our results show that integration of six histidines into the C-terminal tail does indeed increase transport activity of MCT4 to the same extent as did coexpression of MCT4-WT with CAII. Transport activity of MCT4-6xHis could be further enhanced by coexpression with extracellular CAIV, but not with intracellular CAII. Injection of an antibody against the histidine cluster into MCT4-expressing oocytes decreased transport activity of MCT4-6xHis, while leaving activity of MCT4-WT unaltered. Taken together, these findings suggest that transport activity of the proton-coupled monocarboxylate transporter MCT4 can be facilitated by integration of an endogenous proton antenna into the transporter's C-terminal tail. © 2016 Federation of European Biochemical Societies.

  13. Knockout of the regulatory site of 3-ketoacyl-ACP synthase III enhances short- and medium-chain acyl-ACP synthesis.

    PubMed

    Abbadi, A; Brummel, M; Spener, F

    2000-10-01

    3-ketoacyl-acyl carrier protein synthase (KAS) III catalyses the first condensing step of the fatty acid synthase (FAS) type II reaction in plants and bacteria, using acetyl CoA and malonyl-acyl carrier protein (ACP) as substrates. Enzymatic characterization of recombinant KAS III from Cuphea wrightii embryo shows that this enzyme is strongly inhibited by medium-chain acyl-ACP end products of the FAS reaction, i.e. inhibition by lauroyl-ACP was uncompetitive towards acetyl CoA and non-competitive with regard to malonyl-ACP. This indicated a distinct attachment site for regulatory acyl-ACPs. Based on alignment of primary structures of various KAS IIIs and 3-ketoacyl CoA synthases, we suspected the motif G290NTSAAS296 to be responsible for binding of regulatory acyl-ACPs. Deletion of the tetrapeptide G290NTS293 led to a change of secondary structure and complete loss of KAS III condensing activity. Exchange of asparagine291 to aspartate, alanine294 to serine and alanine295 to proline, however, produced mutant enzymes with slightly reduced condensing activity, yet with insensitivity towards acyl-ACPs. To assess the potential of unregulated KAS III as tool in oil production, we designed in vitro experiments employing FAS preparations from medium-chain fatty acid-producing Cuphea lanceolata seeds and long-chain fatty acid-producing rape seeds, each supplemented with a fivefold excess of the N291D KAS III mutant. High amounts of short-chain acyl-ACPs in the case of C. lanceolata, and of medium-chain acyl-ACPs in the case of rape seed preparations, were obtained. This approach targets regulation and offers new possibilities to derive transgenic or non-transgenic plants for production of seed oils with new qualities.

  14. The role of acyl carrier protein isoforms from Cuphea lanceolata seeds in the de-novo biosynthesis of medium-chain fatty acids.

    PubMed

    Schütt, B S; Brummel, M; Schuch, R; Spener, F

    1998-06-01

    To investigate the role of acyl carrier protein (ACP) in determining the fate of the acyl moieties linked to it in the course of de-novo fatty acid biosynthesis in higher plants, we carried out in vitro experiments to reconstitute the fatty acid synthase (FAS) reaction in extracts of spinach (Spinacia oleracea L.) leaves, rape (Brassica napus L.) seeds and Cuphea lanceolata Ait. seeds. The action of two major C. lanceolata ACP isoforms (ACP 1 and ACP 2) compared to ACP from Escherichia coli was monitored by saponification of the corresponding FAS products with subsequent analysis of the liberated fatty acids by high-performance liquid chromatography. In a second approach the preference of the medium-chain acyl-ACP-specific thioesterase (EC 3.1.2.14) of C. lanceolata seeds for the hydrolysis of acyl-ACPs prepared from the three ACP types was investigated. Both ACP isoforms from C. lanceolata seeds supported the synthesis of medium-chain fatty acids in a reconstituted FAS reaction of spinach leaf extracts. Compared to the isoform ACP 1, ACP 2 was more effective in supporting the synthesis of such fatty acids in the FAS reaction of rape seed extracts and caused a higher accumulation of FAS products in all experiments. No preference of the medium-chain thioesterase for one specific ACP isoform was observed. The results indicate that the presence of ACP 2 is essential for the synthesis of decanoic acid in C. lanceolata seeds, and its expression in the phase of accumulation of high levels of this fatty acid provides an additional and highly efficient cofactor for stimulating the FAS reaction.

  15. Association of exercise-induced hyperinsulinaemic hypoglycaemia with MCT1-expressing insulinoma.

    PubMed

    Marquard, J; Welters, A; Buschmann, T; Barthlen, W; Vogelgesang, S; Klee, D; Krausch, M; Raffel, A; Otter, S; Piemonti, L; Mayatepek, E; Otonkoski, T; Lammert, E; Meissner, T

    2013-01-01

    Exercise-induced hyperinsulinism (EIHI) is a hypoglycaemic disorder characterised by inappropriate insulin secretion following anaerobic exercise or pyruvate load. Activating promoter mutations in the MCT1 gene (also known as SCLA16A1), coding for monocarboxylate transporter 1 (MCT1), were shown to associate with EIHI. Recently, transgenic Mct1 expression in pancreatic beta cells was shown to introduce EIHI symptoms in mice. To date, MCT1 has not been demonstrated in insulin-producing cells from an EIHI patient. In vivo insulin secretion was studied during an exercise test before and after the resection of an insulinoma. The presence of MCT1 was analysed using immunohistochemistry followed by laser scanning microscopy, western blot analysis and real-time RT-PCR of MCT1. The presence of MCT1 protein was analysed in four additional insulinoma patients. Clinical testing revealed massive insulin secretion induced by anaerobic exercise preoperatively, but not postoperatively. MCT1 protein was not detected in the patient's normal islets. In contrast, immunoreactivity was clearly observed in the insulinoma tissue. Western blot analysis and real-time RT-PCR showed a four- to fivefold increase in MCT1 in the insulinoma tissue of the EIHI patient compared with human pancreatic islets. MCT1 protein was detected in three of four additional insulinomas. We show for the first time that an MCT1-expressing insulinoma was associated with EIHI and that MCT1 might be present in most insulinomas. Our data suggest that MCT1 expression in human insulin-producing cells can lead to EIHI and warrant further studies on the role of MCT1 in human insulinoma patients.

  16. The antagonism between MCT-1 and p53 affects the tumorigenic outcomes

    PubMed Central

    2010-01-01

    Background MCT-1 oncoprotein accelerates p53 protein degradation via a proteosome pathway. Synergistic promotion of the xenograft tumorigenicity has been demonstrated in circumstance of p53 loss alongside MCT-1 overexpression. However, the molecular regulation between MCT-1 and p53 in tumor development remains ambiguous. We speculate that MCT-1 may counteract p53 through the diverse mechanisms that determine the tumorigenic outcomes. Results MCT-1 has now identified as a novel target gene of p53 transcriptional regulation. MCT-1 promoter region contains the response elements reactive with wild-type p53 but not mutant p53. Functional p53 suppresses MCT-1 promoter activity and MCT-1 mRNA stability. In a negative feedback regulation, constitutively expressed MCT-1 decreases p53 promoter function and p53 mRNA stability. The apoptotic events are also significantly prevented by oncogenic MCT-1 in a p53-dependent or a p53-independent fashion, according to the genotoxic mechanism. Moreover, oncogenic MCT-1 promotes the tumorigenicity in mice xenografts of p53-null and p53-positive lung cancer cells. In support of the tumor growth are irrepressible by p53 reactivation in vivo, the inhibitors of p53 (MDM2, Pirh2, and Cop1) are constantly stimulated by MCT-1 oncoprotein. Conclusions The oppositions between MCT-1 and p53 are firstly confirmed at multistage processes that include transcription control, mRNA metabolism, and protein expression. MCT-1 oncogenicity can overcome p53 function that persistently advances the tumor development. PMID:21138557

  17. Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: in vivo insights from MCT1 haploinsufficient mice.

    PubMed

    Chatel, Benjamin; Bendahan, David; Hourdé, Christophe; Pellerin, Luc; Lengacher, Sylvain; Magistretti, Pierre; Le Fur, Yann; Vilmen, Christophe; Bernard, Monique; Messonnier, Laurent A

    2017-06-01

    The purpose of this study was to investigate the effects of a partial suppression of monocarboxylate transporter (MCT)-1 on skeletal muscle pH, energetics, and function (MCT1 +/- mice). Twenty-four MCT1 +/- and 13 wild-type (WT) mice were subjected to a rest-exercise-recovery protocol, allowing assessment of muscle energetics (by magnetic resonance spectroscopy) and function. The study included analysis of enzyme activities and content of protein involved in pH regulation. Skeletal muscle of MCT1 +/- mice had lower MCT1 (-61%; P < 0.05) and carbonic anhydrase (CA)-II (-54%; P < 0.05) contents. Although intramuscular pH was higher in MCT1 +/- mice at rest ( P < 0.001), the mice showed higher acidosis during the first minute of exercise ( P < 0.01). Then, the pH time course was similar among groups until exercise completion. MCT1 +/- mice had higher specific peak ( P < 0.05) and maximum tetanic ( P < 0.01) forces and lower fatigability ( P < 0.001) when compared to WT mice. We conclude that both MCT1 and CAII are involved in the homeostatic control of pH in skeletal muscle, both at rest and at the onset of exercise. The improved muscle function and resistance to fatigue in MCT1 +/- mice remain unexplained.-Chatel, B., Bendahan, D., Hourdé, C., Pellerin, L., Lengacher, S., Magistretti, P., Fur, Y. L., Vilmen, C., Bernard, M., Messonnier, L. A. Role of MCT1 and CAII in skeletal muscle pH homeostasis, energetics, and function: in vivo insights from MCT1 haploinsufficient mice. © FASEB.

  18. Comparative study on digestive lipase activities on the self emulsifying excipient Labrasol, medium chain glycerides and PEG esters.

    PubMed

    Fernandez, Sylvie; Jannin, Vincent; Rodier, Jean-David; Ritter, Nicolas; Mahler, Bruno; Carrière, Frédéric

    2007-05-01

    Labrasol is a lipid-based self-emulsifying excipient used in the preparation of lipophilic drugs intended for oral delivery. It is mainly composed of PEG esters and glycerides with medium acyl chains, which are potential substrates for digestive lipases. The hydrolysis of Labrasol by porcine pancreatic extracts, human pancreatic juice and several purified digestive lipases was investigated in the present study. Classical human pancreatic lipase (HPL) and porcine pancreatic lipase, which are the main lipases involved in the digestion of dietary triglycerides, showed very low levels of activity on the entire Labrasol excipient as well as on separated fractions of glycerides and PEG esters. On the other hand, gastric lipase, pancreatic lipase-related protein 2 (PLRP2) and carboxyl ester hydrolase (CEH) showed high specific activities on Labrasol. These lipases were found to hydrolyze the main components of Labrasol (PEG esters and monoglycerides) used as individual substrates, whereas these esters were found to be poor substrates for HPL. The lipolytic activity of pancreatic extracts and human pancreatic juice on Labrasol(R) is therefore mainly due to the combined action of CEH and PLRP2. These two pancreatic enzymes, together with gastric lipase, are probably the main enzymes involved in the in vivo lipolysis of Labrasol taken orally.

  19. Improvements of MCT MBE Growth on GaAs

    NASA Astrophysics Data System (ADS)

    Ziegler, J.; Wenisch, J.; Breiter, R.; Eich, D.; Figgemeier, H.; Fries, P.; Lutz, H.; Wollrab, R.

    2014-08-01

    In recent years, continuous progress has been published in the development of HgCdTe (MCT) infrared (IR) focal plane arrays (FPAs) fabricated by molecular beam epitaxy on GaAs substrates. In this publication, further characterization of the state-of-the art 1280 × 1024 pixel, 15- μm pitch detector fabricated from this material in both the mid-wavelength (MWIR) and long-wavelength (LWIR) IR region will be presented. For MWIR FPAs, the percentage of defective pixel remains below 0.5% up to an operating temperature ( T OP) of around 100 K. For the LWIR FPA, an operability of 99.25% was achieved for a T OP of 76 K. Additionally, the beneficial effect of the inclusion of MCT layers with a graded composition region was investigated and demonstrated on current-voltage ( IV) characteristics on test diodes in a MWIR FPA.

  20. Expression of the monocarboxylate transporter 1 (MCT1) in cells of the porcine intestine.

    PubMed

    Welter, Harald; Claus, Rolf

    2008-06-01

    Uptake of energy into cells and its allocation to individual cellular compartments by transporters are essential for tissue homeostasis. The present study gives an analysis of MCT1 expression and its cellular occurrence in the porcine intestine. Tissue portions from duodenum, jejunum, ileum, colon ascendens, colon transversum and colon descendens were collected and prepared for immunohistochemistry, Western blot and real time RT-PCR. A 169bp porcine MCT1 cDNA fragment was amplified and published. MCT1 mRNA expression in the large intestine was 20 fold higher compared to the small intestine. Western blot detected a single protein band of 41kDa at a much higher amount of MCT1 protein in the large intestine vs. the small intestine. MCT1 protein was detected in mitochondrial fractions of the large but not the small intestine. Immunohistochemistry in the small intestine showed that immune cells in the lamina propria and in the lymphoid follicles primarily expressed MCT1 while in the colon epithelial cells were the main source of MCT1. In summary, cellular expression of MCT1 differs between epithelial cells in the colon and small intestine. A possible role of MCT1 for uptake of butyrate into immune cells and the overall role of MCT1 for intestinal immune cell function remains elusive.

  1. 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

  2. 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.

  3. A simple quantitative approach for the determination of long and medium chain lipids in bio-relevant matrices by high performance liquid chromatography with refractive index detection.

    PubMed

    Lee, Kathy Wai Yu; Porter, Christopher J H; Boyd, Ben J

    2013-09-01

    There is increasing attention in the literature towards understanding the behaviour of lipid-based drug formulations under digestion conditions using in vitro and in vivo methods. This necessitates a convenient method for quantitation of lipids and lipid digestion products. In this study, a simple and accessible method for the separation and quantitative determination of typical formulation and digested lipids using high performance liquid chromatography coupled to refractive index detection (HPLC-RI) is described. Long and medium chain lipids were separated and quantified in a biological matrix (gastrointestinal content) without derivatisation using HPLC-RI on C18 and C8 columns, respectively. The intra- and inter-assay accuracy was between 92% and 106%, and the assays were precise to within a coefficient of variation of less than 10% over the range of 0.1-2 mg/mL for both long and medium chain lipids. This method is also shown to be suitable for quantifying the lipolysis products collected from the gastrointestinal tract in the course of in vivo lipid digestion studies.

  4. Hypoxia-mediated upregulation of MCT1 expression supports the glycolytic phenotype of glioblastomas.

    PubMed

    Miranda-Gonçalves, Vera; Granja, Sara; Martinho, Olga; Honavar, Mrinalini; Pojo, Marta; Costa, Bruno M; Pires, Manuel M; Pinheiro, Célia; Cordeiro, Michelle; Bebiano, Gil; Costa, Paulo; Reis, Rui M; Baltazar, Fátima

    2016-07-19

    Glioblastomas (GBM) present a high cellular heterogeneity with conspicuous necrotic regions associated with hypoxia, which is related to tumor aggressiveness. GBM tumors exhibit high glycolytic metabolism with increased lactate production that is extruded to the tumor microenvironment through monocarboxylate transporters (MCTs). While hypoxia-mediated regulation of MCT4 has been characterized, the role of MCT1 is still controversial. Thus, we aimed to understand the role of hypoxia in the regulation of MCT expression and function in GBM, MCT1 in particular. Expression of hypoxia- and glycolytic-related markers, as well as MCT1 and MCT4 isoforms was assessed in in vitro and in vivo orthotopic glioma models, and also in human GBM tissues by immunofluorescence/immunohistochemistry and Western blot. Following MCT1 inhibition, either pharmacologically with CHC (α-cyano-4-hydroxynnamic acid) or genetically with siRNAs, we assessed GBM cell viability, proliferation, metabolism, migration and invasion, under normoxia and hypoxia conditions. Hypoxia induced an increase in MCT1 plasma membrane expression in glioma cells, both in in vitro and in vivo models. Additionally, treatment with CHC and downregulation of MCT1 in glioma cells decreased lactate production, cell proliferation and invasion under hypoxia. Moreover, in the in vivo orthotopic model and in human GBM tissues, there was extensive co-expression of MCT1, but not MCT4, with the GBM hypoxia marker CAIX. Hypoxia-induced MCT1 supports GBM glycolytic phenotype, being responsible for lactate efflux and an important mediator of cell survival and aggressiveness. Therefore, MCT1 constitutes a promising therapeutic target in GBM.

  5. Hypoxia-mediated upregulation of MCT1 expression supports the glycolytic phenotype of glioblastomas

    PubMed Central

    Miranda-Gonçalves, Vera; Granja, Sara; Martinho, Olga; Honavar, Mrinalini; Pojo, Marta; Costa, Bruno M.; Pires, Manuel M.; Pinheiro, Célia; Cordeiro, Michelle; Bebiano, Gil; Costa, Paulo; Reis, Rui M.; Baltazar, Fátima

    2016-01-01

    Background Glioblastomas (GBM) present a high cellular heterogeneity with conspicuous necrotic regions associated with hypoxia, which is related to tumor aggressiveness. GBM tumors exhibit high glycolytic metabolism with increased lactate production that is extruded to the tumor microenvironment through monocarboxylate transporters (MCTs). While hypoxia-mediated regulation of MCT4 has been characterized, the role of MCT1 is still controversial. Thus, we aimed to understand the role of hypoxia in the regulation of MCT expression and function in GBM, MCT1 in particular. Methods Expression of hypoxia- and glycolytic-related markers, as well as MCT1 and MCT4 isoforms was assessed in in vitro and in vivo orthotopic glioma models, and also in human GBM tissues by immunofluorescence/immunohistochemistry and Western blot. Following MCT1 inhibition, either pharmacologically with CHC (α-cyano-4-hydroxynnamic acid) or genetically with siRNAs, we assessed GBM cell viability, proliferation, metabolism, migration and invasion, under normoxia and hypoxia conditions. Results Hypoxia induced an increase in MCT1 plasma membrane expression in glioma cells, both in in vitro and in vivo models. Additionally, treatment with CHC and downregulation of MCT1 in glioma cells decreased lactate production, cell proliferation and invasion under hypoxia. Moreover, in the in vivo orthotopic model and in human GBM tissues, there was extensive co-expression of MCT1, but not MCT4, with the GBM hypoxia marker CAIX. Conclusion Hypoxia-induced MCT1 supports GBM glycolytic phenotype, being responsible for lactate efflux and an important mediator of cell survival and aggressiveness. Therefore, MCT1 constitutes a promising therapeutic target in GBM. PMID:27331625

  6. Nitrogen sparing effect of structured triglycerides containing both medium-and long-chain fatty acids in critically ill patients; a double blind randomized controlled trial.

    PubMed

    Lindgren, B F; Ruokonen, E; Magnusson-Borg, K; Takala, J

    2001-02-01

    Patients with sepsis and trauma are characterised by hypermetabolism, insulin resistance and protein catabolism. Fat emulsions containing medium chain triglycerides have been suggested to be beneficial for these patients since medium chain fatty acids are a more readily available source of energy when compared to long chain fatty acids. The aim of this study was to compare a medium and long chain triglyceride emulsion consisting of structured triglycerides (ST) with a long chain triglyceride (LCT) emulsion in terms of effects on nitrogen balance, energy metabolism and safety. 30 ICU patients with sepsis or multiple injury received a fat emulsion with ST or 20% LCT (1.5 g triglycerides/kg body weight/day) as a component of total parenteral nutrition (TPN), for 5 days in a double blind randomised parallel group design. The main analysis was made on the 3 day per protocol population due to lack of patients at day 5. There were no differences in baseline characteristics of the two groups receiving either the LCT or the ST emulsion. The efficacy analysis was performed on the per protocol population (n=9 ST, n=11 LCT). There was a significant difference between the two treatments regarding daily nitrogen balances when the first 3 days were analysed P=0.0038). This resulted in an amelioration of the nitrogen balance on day 3 in the group on ST as compared to those on LCT (0.1+/-2.4 g vs -9.9+/-2.1 g P=0.01). The 3 day cumulative nitrogen balance was significantly better in the group receiving ST compared to those on LCT (-0.7+/-6.0 vs -16.7+/-3.9 P=0.03). This better cumulative nitrogen balance on day 3 was also preserved as a tendency (P=0.061) in the analysis of the intention to treat population, but on day 5 there was no significant difference (P=0.08). The ST emulsion was well tolerated and no difference was found compared to the LCT emulsion regarding respiratory quotient, energy expenditure, glucose or triglyceride levels during infusion. Administration of a

  7. CE: Triglycerides: Do They Matter?

    PubMed

    Scordo, Kristine; Pickett, Kim Anne

    2017-01-01

    : Since the introduction of HMG-CoA reductase inhibitors, also known as statins, as an adjunct to diet in the treatment of hyperlipidemia and the greater emphasis placed on reducing low-density lipoprotein (LDL) cholesterol levels in the prevention of atherosclerosis and cardiovascular disease (CVD), there has been less focus on the value of lowering serum triglyceride levels. Many patients are aware of their "good" and "bad" cholesterol levels, but they may not be aware of their triglyceride level or of the association between high triglycerides and the development of CVD. In recent years, however, in light of the increasing incidences of obesity, insulin resistance, and type 2 diabetes, lowering triglyceride levels has gained renewed interest. In addition to the focus on lowering LDL cholesterol levels in CVD prevention, clinicians need to be aware of the role of triglycerides-their contribution to CVD, and the causes and treatment of hypertriglyceridemia.

  8. Cancer metabolism, stemness and tumor recurrence: MCT1 and MCT4 are functional biomarkers of metabolic symbiosis in head and neck cancer.

    PubMed

    Curry, Joseph M; Tuluc, Madalina; Whitaker-Menezes, Diana; Ames, Julie A; Anantharaman, Archana; Butera, Aileen; Leiby, Benjamin; Cognetti, David M; Sotgia, Federica; Lisanti, Michael P; Martinez-Outschoorn, Ubaldo E

    2013-05-01

    Here, we interrogated head and neck cancer (HNSCC) specimens (n = 12) to examine if different metabolic compartments (oxidative vs. glycolytic) co-exist in human tumors. A large panel of well-established biomarkers was employed to determine the metabolic state of proliferative cancer cells. Interestingly, cell proliferation in cancer cells, as marked by Ki-67 immunostaining, was strictly correlated with oxidative mitochondrial metabolism (OXPHOS) and the uptake of mitochondrial fuels, as detected via MCT1 expression (p < 0.001). More specifically, three metabolic tumor compartments were delineated: (1) proliferative and mitochondrial-rich cancer cells (Ki-67+/TOMM20+/COX+/MCT1+); (2) non-proliferative and mitochondrial-poor cancer cells (Ki-67-/TOMM20-/COX-/MCT1-); and (3) non-proliferative and mitochondrial-poor stromal cells (Ki-67-/TOMM20-/COX-/MCT1-). In addition, high oxidative stress (MCT4+) was very specific for cancer tissues. Thus, we next evaluated the prognostic value of MCT4 in a second independent patient cohort (n = 40). Most importantly, oxidative stress (MCT4+) in non-proliferating epithelial cancer cells predicted poor clinical outcome (tumor recurrence; p < 0.0001; log-rank test), and was functionally associated with FDG-PET avidity (p < 0.04). Similarly, oxidative stress (MCT4+) in tumor stromal cells was specifically associated with higher tumor stage (p < 0.03), and was a highly specific marker for cancer-associated fibroblasts (p < 0.001). We propose that oxidative stress is a key hallmark of tumor tissues that drives high-energy metabolism in adjacent proliferating mitochondrial-rich cancer cells, via the paracrine transfer of mitochondrial fuels (such as L-lactate and ketone bodies). New antioxidants and MCT4 inhibitors should be developed to metabolically target "three-compartment tumor metabolism" in head and neck cancers. It is remarkable that two "non-proliferating" populations of cells (Ki-67-/MCT4+) within the tumor can actually

  9. The MCT4 Gene: A Novel, Potential Target for Therapy of Advanced Prostate Cancer.

    PubMed

    Choi, Stephen Yiu Chuen; Xue, Hui; Wu, Rebecca; Fazli, Ladan; Lin, Dong; Collins, Colin C; Gleave, Martin E; Gout, Peter W; Wang, Yuzhuo

    2016-06-01

    The management of castration-resistant prostate cancer (CRPC) is a major challenge in the clinic. Androgen receptor signaling-directed strategies are not curative in CRPC therapy, and new strategies targeting alternative, key cancer properties are needed. Using reprogrammed glucose metabolism (aerobic glycolysis), cancer cells typically secrete excessive amounts of lactic acid into their microenvironment, promoting cancer development, survival, and progression. Cellular lactic acid secretion is thought to be predominantly mediated by MCT4, a plasma membrane transporter protein. As such, the MCT4 gene provides a unique, potential therapeutic target for cancer. A tissue microarray of various Gleason grade human prostate cancers was stained for MCT4 protein. Specific, MCT4-targeting antisense oligonucleotides (MCT4 ASO) were designed and candidate MCT4 ASOs checked for effects on (i) MCT4 expression, lactic acid secretion/content, glucose consumption, glycolytic gene expression, and proliferation of human CRPC cells and (ii) growth of PC-3 tumors in nude mice. Elevated MCT4 expression was associated with human CRPC and an earlier time to relapse. The treatment of PC-3, DU145, and C4-2 CRPC cultures with candidate MCT4 ASOs led to marked inhibition of MCT4 expression, lactic acid secretion, to increased intracellular lactic acid levels, and markedly reduced aerobic glycolysis and cell proliferation. Treatment of PC-3 tumor-bearing nude mice with the MCT4 ASOs markedly inhibited tumor growth without inducing major host toxicity. MCT4-targeting ASOs that inhibit lactic acid secretion may be useful for therapy of CRPC and other cancers, as they can interfere with reprogrammed energy metabolism of cancers, an emerging hallmark of cancer. Clin Cancer Res; 22(11); 2721-33. ©2016 AACR. ©2016 American Association for Cancer Research.

  10. Regulation of monocarboxylate transporter MCT1 expression by p53 mediates inward and outward lactate fluxes in tumors.

    PubMed

    Boidot, Romain; Végran, Frédérique; Meulle, Aline; Le Breton, Aude; Dessy, Chantal; Sonveaux, Pierre; Lizard-Nacol, Sarab; Feron, Olivier

    2012-02-15

    The monocarboxylate transporter (MCT) family member MCT1 can transport lactate into and out of tumor cells. Whereas most oxidative cancer cells import lactate through MCT1 to fuel mitochondrial respiration, the role of MCT1 in glycolysis-derived lactate efflux remains less clear. In this study, we identified a direct link between p53 function and MCT1 expression. Under hypoxic conditions, p53 loss promoted MCT1 expression and lactate export produced by elevated glycolytic flux, both in vitro and in vivo. p53 interacted directly with the MCT1 gene promoter and altered MCT1 mRNA stabilization. In hypoxic p53(-/-) tumor cells, NF-κB further supported expression of MCT1 to elevate its levels. Following glucose deprivation, upregulated MCT1 in p53(-/-) cells promoted lactate import and favored cell proliferation by fuelling mitochondrial respiration. We also found that MCT1 expression was increased in human breast tumors harboring p53 mutations and coincident features of hypoxia, with higher MCT1 levels associated with poorer clinical outcomes. Together, our findings identify MCT1 as a target for p53 repression and they suggest that MCT1 elevation in p53-deficient tumors allows them to adapt to metabolic needs by facilitating lactate export or import depending on the glucose availability.

  11. Pharmacological treatment and BBB-targeted genetic therapy for MCT8-dependent hypomyelination in zebrafish

    PubMed Central

    2016-01-01

    ABSTRACT Hypomyelination is a key symptom of Allan-Herndon-Dudley syndrome (AHDS), a psychomotor retardation associated with mutations in the thyroid-hormone (TH) transporter MCT8 (monocarboxylate transporter 8). AHDS is characterized by severe intellectual deficiency, neuromuscular impairment and brain hypothyroidism. In order to understand the mechanism for TH-dependent hypomyelination, we developed an mct8 mutant (mct8−/−) zebrafish model. The quantification of genetic markers for oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes revealed reduced differentiation of OPCs into oligodendrocytes in mct8−/− larvae and adults. Live imaging of single glial cells showed that the number of oligodendrocytes and the length of their extensions are reduced, and the number of peripheral Schwann cells is increased, in mct8−/− larvae compared with wild type. Pharmacological analysis showed that TH analogs and clemastine partially rescued the hypomyelination in the CNS of mct8−/− larvae. Intriguingly, triiodothyronine (T3) treatment rescued hypomyelination in mct8−/− embryos before the maturation of the blood–brain barrier (BBB), but did not affect hypomyelination in older larvae. Thus, we expressed Mct8-tagRFP in the endothelial cells of the vascular system and showed that even relatively weak mosaic expression completely rescued hypomyelination in mct8−/− larvae. These results suggest potential pharmacological treatments and BBB-targeted gene therapy that can enhance myelination in AHDS and possibly in other TH-dependent brain disorders. PMID:27664134

  12. Pharmacological treatment and BBB-targeted genetic therapy for MCT8-dependent hypomyelination in zebrafish.

    PubMed

    Zada, David; Tovin, Adi; Lerer-Goldshtein, Tali; Appelbaum, Lior

    2016-11-01

    Hypomyelination is a key symptom of Allan-Herndon-Dudley syndrome (AHDS), a psychomotor retardation associated with mutations in the thyroid-hormone (TH) transporter MCT8 (monocarboxylate transporter 8). AHDS is characterized by severe intellectual deficiency, neuromuscular impairment and brain hypothyroidism. In order to understand the mechanism for TH-dependent hypomyelination, we developed an mct8 mutant (mct8 -/- ) zebrafish model. The quantification of genetic markers for oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes revealed reduced differentiation of OPCs into oligodendrocytes in mct8 -/- larvae and adults. Live imaging of single glial cells showed that the number of oligodendrocytes and the length of their extensions are reduced, and the number of peripheral Schwann cells is increased, in mct8 -/- larvae compared with wild type. Pharmacological analysis showed that TH analogs and clemastine partially rescued the hypomyelination in the CNS of mct8 -/- larvae. Intriguingly, triiodothyronine (T3) treatment rescued hypomyelination in mct8 -/- embryos before the maturation of the blood-brain barrier (BBB), but did not affect hypomyelination in older larvae. Thus, we expressed Mct8-tagRFP in the endothelial cells of the vascular system and showed that even relatively weak mosaic expression completely rescued hypomyelination in mct8 -/- larvae. These results suggest potential pharmacological treatments and BBB-targeted gene therapy that can enhance myelination in AHDS and possibly in other TH-dependent brain disorders. © 2016. Published by The Company of Biologists Ltd.

  13. Characterization and snubbing of a bidirectional MCT in a resonant ac link converter

    NASA Technical Reports Server (NTRS)

    Lee, Tony; Elbuluk, Malik E.; Zinger, Donald S.

    1993-01-01

    The MOS-Controlled Thyristor (MCT) is emerging as a powerful switch that combines the better characteristics of existing power devices. A study of switching stresses on an MCT switch under zero voltage resonant switching is presented. The MCT is used as a bidirectional switch in an ac/ac pulse density modulated inverter for induction motor drive. Current and voltage spikes are observed and analyzed with variations in the timing of the switching. Different snubber circuit configurations are under investigation to minimize the effect of these transients. The results will be extended to study and test the MCT switching in a medium power (5 hp) induction motor drive.

  14. MCT Expression and Lactate Influx/Efflux in Tanycytes Involved in Glia-Neuron Metabolic Interaction

    PubMed Central

    Cortés-Campos, Christian; Elizondo, Roberto; Llanos, Paula; Uranga, Romina María; Nualart, Francisco; García, María Angeles

    2011-01-01

    Metabolic interaction via lactate between glial cells and neurons has been proposed as one of the mechanisms involved in hypothalamic glucosensing. We have postulated that hypothalamic glial cells, also known as tanycytes, produce lactate by glycolytic metabolism of glucose. Transfer of lactate to neighboring neurons stimulates ATP synthesis and thus contributes to their activation. Because destruction of third ventricle (III-V) tanycytes is sufficient to alter blood glucose levels and food intake in rats, it is hypothesized that tanycytes are involved in the hypothalamic glucose sensing mechanism. Here, we demonstrate the presence and function of monocarboxylate transporters (MCTs) in tanycytes. Specifically, MCT1 and MCT4 expression as well as their distribution were analyzed in Sprague Dawley rat brain, and we demonstrate that both transporters are expressed in tanycytes. Using primary tanycyte cultures, kinetic analyses and sensitivity to inhibitors were undertaken to confirm that MCT1 and MCT4 were functional for lactate influx. Additionally, physiological concentrations of glucose induced lactate efflux in cultured tanycytes, which was inhibited by classical MCT inhibitors. Because the expression of both MCT1 and MCT4 has been linked to lactate efflux, we propose that tanycytes participate in glucose sensing based on a metabolic interaction with neurons of the arcuate nucleus, which are stimulated by lactate released from MCT1 and MCT4-expressing tanycytes. PMID:21297988

  15. Butyric acid increases transepithelial transport of ferulic acid through upregulation of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4).

    PubMed

    Ziegler, Kerstin; Kerimi, Asimina; Poquet, Laure; Williamson, Gary

    2016-06-01

    Ferulic acid is released by microbial hydrolysis in the colon, where butyric acid, a major by-product of fermentation, constitutes the main energy source for colonic enterocytes. We investigated how varying concentrations of this short chain fatty acid may influence the absorption of the phenolic acid. Chronic treatment of Caco-2 cells with butyric acid resulted in increased mRNA and protein abundance of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4), previously proposed to facilitate ferulic acid absorption in addition to passive diffusion. Short term incubation with butyric acid only led to upregulation of MCT4 while both conditions increased transepithelial transport of ferulic acid in the apical to basolateral, but not basolateral to apical, direction. Chronic treatment also elevated intracellular concentrations of ferulic acid, which in turn gave rise to increased concentrations of ferulic acid metabolites. Immunofluorescence staining of cells revealed uniform distribution of MCT1 protein in the cell membrane, whereas MCT4 was only detected in the lateral plasma membrane sections of Caco-2 cells. We therefore propose that MCT1 may be acting as an uptake transporter and MCT4 as an efflux system across the basolateral membrane for ferulic acid, and that this process is stimulated by butyric acid. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Optimization of Water/Oil/Surfactant System for Preparation of Medium-Chain-Length Poly-3-Hydroxyalkanoates (mcl-PHA)-Incorporated Nanoparticles via Nanoemulsion Templating Technique.

    PubMed

    Ishak, K A; Annuar, M Suffian M; Ahmad, N

    2017-12-01

    Polymeric nanoparticles gain a widespread interest in food and pharmaceutical industries as delivery systems that encapsulate, protect, and release lipophilic compounds such as omega-3 fatty acids, fat-soluble vitamins, carotenoids, carvedilol, cyclosporine, and ketoprofen. In this study, medium-chain-length poly-3-hydroxyalkanoate (mcl-PHA)-incorporated nanoparticle was developed via facile organic solvent-free nanoemulsion templating technique. The water content (W/surfactant-to-oil (S/O)), S/O, and Cremophor EL-to-Span 80 (Cremo/Sp80) ratios were first optimized using response surface methodology (RSM) to obtain nanoemulsion template prior to incorporation of mcl-PHA. Their effects on nanoemulsion formation were investigated. The mcl-PHA-incorporated nanoparticle system showed a good preservation capability of β-carotene and extended storage stability.

  17. Inflammatory changes in adipose tissue enhance expression of GPR84, a medium-chain fatty acid receptor: TNFα enhances GPR84 expression in adipocytes.

    PubMed

    Nagasaki, Hiroshi; Kondo, Takaaki; Fuchigami, Masahiro; Hashimoto, Hiroyuki; Sugimura, Yoshihisa; Ozaki, Nobuaki; Arima, Hiroshi; Ota, Akira; Oiso, Yutaka; Hamada, Yoji

    2012-02-17

    In this study we aimed to identify the physiological roles of G protein-coupled receptor 84 (GPR84) in adipose tissue, together with medium-chain fatty acids (MCFAs), the specific ligands for GPR84. In mice, high-fat diet up-regulated GPR84 expression in fat pads. In 3T3-L1 adipocytes, co-culture with a macrophage cell line, RAW264, or TNFα remarkably enhanced GPR84 expression. In the presence of TNFα, MCFAs down-regulated adiponectin mRNA expression in 3T3-L1 adipocytes. Taken together, our results suggest that GPR84 emerges in adipocytes in response to TNFα from infiltrating macrophages and exacerbates the vicious cycle between adiposity and diabesity. Copyright © 2012 Federation of European Biochemical Societies. All rights reserved.

  18. Does the newer preparation of propofol, an emulsion of medium/long chain triglycerides cause less injection pain in children when premixed with lignocaine?

    PubMed

    Varghese, Elsa; Krishna, Handattu Mahabaleswara; Nittala, Anuradha

    2010-04-01

    Injection pain during propofol administration can be particularly distressing in children. The newly available emulsion of propofol in medium and long chain triglycerides (LCT) is reported to cause less injection pain because of lower concentrations of free propofol. This study compared the incidence of injection pain during administration of propofol emulsion of LCT and propofol emulsion of medium and long chain triglycerides (MCT/LCT) both premixed with lignocaine in children. This prospective, randomized, double blind study was conducted after obtaining institutional ethics committee approval, parental consent and included 84 children aged 5-15 years. Preoperatively, an intravenous cannula was inserted in all children. four children were excluded. Those included, depending on the randomization, received 3 mg x kg(-1) of either propofol LCT or propofol MCT/LCT both premixed with lignocaine (0.1%). The incidence and intensity of injection pain was assessed. Pain on injection of propofol LCT with lignocaine was observed in 16/40 children (40%), five of these children complained of severe pain. In comparison, 14/40 (35%) children complained of pain following propofol MCT/LCT premixed with lignocaine (P = 0.644), the intensity being severe in two children (P = 0.698). Propofol MCT/LCT and propofol LCT premixed with lignocaine are both associated with pain on injection in children; the incidence and intensity of the injection pain are similar.

  19. 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.

  20. Tissue-specific regulation of medium-chain acyl-CoA dehydrogenase gene by thyroid hormones in the developing rat.

    PubMed

    Djouadi, F; Riveau, B; Merlet-Benichou, C; Bastin, J

    1997-05-15

    During development, gene expression of medium-chain acyl-CoA dehydrogenase (MCAD), a nuclear-encoded mitochondrial enzyme that catalyses the first step of medium-chain fatty acid beta-oxidation, is highly regulated in tissues in accordance with fatty acid utilization, but the factors involved in this regulation are largely unknown. To investigate a possible role of thyroid hormones, rat pups were made hypothyroid by the administration of propylthiouracyl to the mother from day 12 of gestation, and their kidneys, heart and liver were removed on postnatal day 16 to determine MCAD mRNA abundance, protein level and enzyme activity. Similar experiments were run in 3,3',5-tri-iodothyronine (T3)-replaced hypothyroid (1 microg of T3/100 g body weight from postnatal day 5 to 15) and euthyroid pups. Hypothyroidism led to an increase in MCAD mRNA abundance in kidney and a decrease in abundance in heart, but had no effect in liver. The protein levels and enzyme activity were lowered in hypothyroid heart and kidney, suggesting that hypothyroidism affects post-transcriptional steps of gene expression in the kidney. All the effects of hypothyroidism were completely reversed in both heart and kidney by T3 replacement. Injection of a single T3 dose into 16-day-old euthyroid rats also led to tissue-specific changes in mRNA abundance. Nuclear run-on assays performed from hypothyroid and hypothyroid plus T3 rats showed that T3 stimulates MCAD gene transcription in heart and represses it in the kidney. These results indicate that the postnatal rise in circulating T3 is essential to the developmental regulation of the MCAD gene in vivo.

  1. Cerebral cortex hyperthyroidism of newborn mct8-deficient mice transiently suppressed by lat2 inactivation.

    PubMed

    Núñez, Bárbara; Martínez de Mena, Raquel; Obregon, Maria Jesus; Font-Llitjós, Mariona; Nunes, Virginia; Palacín, Manuel; Dumitrescu, Alexandra M; Morte, Beatriz; Bernal, Juan

    2014-01-01

    Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2) cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8), in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated Lat2-/-, and Mct8-/yLat2-/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As described previously the single Mct8 KO neonates had a transient increase of 3,5,3'-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3'-triiodothyronine concentration and Hr expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development.

  2. Characterization of monocarboxylate transporters (MCTs) expression in soft tissue sarcomas: distinct prognostic impact of MCT1 sub-cellular localization

    PubMed Central

    2014-01-01

    Background Soft tissue sarcomas (STSs) are a group of neoplasms, which, despite current therapeutic advances, still confer a poor outcome to half of the patients. As other solid tumors, STSs exhibit high glucose consumption rates, associated with worse prognosis and therapeutic response. As highly glycolytic tumors, we hypothesized that sarcomas should present an increased expression of lactate transporters (MCTs). Methods Immunohistochemical expression of MCT1, MCT2, MCT4 and CD147 was assessed in a series of 86 STSs and the expression profiles were associated with patients’ clinical-pathological parameters. Results MCT1, MCT4 and CD147 were mainly observed in the plasma membrane of cancer cells (around 60% for MCTs and 40% for CD147), while MCT2 was conspicuously found in the cytoplasm (94.2%). Importantly, we observed MCT1 nuclear expression (32.6%). MCT1 and MCT4, alone or co-expressed with CD147 in the plasma membrane, were associated with poor prognostic variables including high tumor grade, disease progression and shorter overall survival. Conversely, we found MCT1 nuclear expression to be associated with low grade tumors and longer overall survival. Conclusions The present work represents the first report of MCTs characterization in STSs. We showed the original finding of MCT1 expression in the nucleus. Importantly, opposite biological roles should be behind the dual sub-cellular localization of MCT1, as plasma membrane expression of MCT1 is associated with worse patients’ prognosis, while nuclear expression is associated with better prognosis. PMID:24885736

  3. Characterization of monocarboxylate transporters (MCTs) expression in soft tissue sarcomas: distinct prognostic impact of MCT1 sub-cellular localization.

    PubMed

    Pinheiro, Céline; Penna, Valter; Morais-Santos, Filipa; Abrahão-Machado, Lucas F; Ribeiro, Guilherme; Curcelli, Emílio C; Olivieri, Marcus V; Morini, Sandra; Valença, Isabel; Ribeiro, Daniela; Schmitt, Fernando C; Reis, Rui M; Baltazar, Fátima

    2014-05-09

    Soft tissue sarcomas (STSs) are a group of neoplasms, which, despite current therapeutic advances, still confer a poor outcome to half of the patients. As other solid tumors, STSs exhibit high glucose consumption rates, associated with worse prognosis and therapeutic response. As highly glycolytic tumors, we hypothesized that sarcomas should present an increased expression of lactate transporters (MCTs). Immunohistochemical expression of MCT1, MCT2, MCT4 and CD147 was assessed in a series of 86 STSs and the expression profiles were associated with patients' clinical-pathological parameters. MCT1, MCT4 and CD147 were mainly observed in the plasma membrane of cancer cells (around 60% for MCTs and 40% for CD147), while MCT2 was conspicuously found in the cytoplasm (94.2%). Importantly, we observed MCT1 nuclear expression (32.6%). MCT1 and MCT4, alone or co-expressed with CD147 in the plasma membrane, were associated with poor prognostic variables including high tumor grade, disease progression and shorter overall survival. Conversely, we found MCT1 nuclear expression to be associated with low grade tumors and longer overall survival. The present work represents the first report of MCTs characterization in STSs. We showed the original finding of MCT1 expression in the nucleus. Importantly, opposite biological roles should be behind the dual sub-cellular localization of MCT1, as plasma membrane expression of MCT1 is associated with worse patients' prognosis, while nuclear expression is associated with better prognosis.

  4. High-performance MCT and QWIP IR detectors at Sofradir

    NASA Astrophysics Data System (ADS)

    Reibel, Yann; Rubaldo, Laurent; Manissadjian, Alain; Billon-Lanfrey, David; Rothman, Johan; de Borniol, Eric; Destéfanis, Gérard; Costard, E.

    2012-11-01

    Cooled IR technologies are challenged for answering new system needs like compactness and reduction of cryo-power which is key feature for the SWaP (Size, Weight and Power) requirements. This paper describes the status of MCT IR technology in France at Leti and Sofradir. A focus will be made on hot detector technology for SWAP applications. Sofradir has improved its HgCdTe technology to open the way for High Operating Temperature systems that release the Stirling cooler engine power consumption. Solutions for high performance detectors such as dual bands, much smaller pixel pitch or megapixels will also be discussed. In the meantime, the development of avalanche photodiodes or TV format with digital interface is key to bringing customers cutting-edge functionalities. Since 1997, Sofradir has been working with Thales and Research Technologies (TRT) to develop and produce Quantum Well Infrared Photodetectors (QWIP) as a complementary offer with MCT, to provide large LW staring arrays. A dualband MW-LW QWIP detector (25μm pitch 384×288 IDDCA) is currently under development. We will present in this paper its latest results.

  5. The effect of extracellular alkalinization on lactate metabolism of breast cancer stem cells: Overview of LDH-A, LDH-B, MCT1 and MCT4 gene expression

    NASA Astrophysics Data System (ADS)

    Neolaka, G. M. G.; Yustisia, I.; Sadikin, M.; Wanandi, S. I.

    2017-08-01

    Changes in the metabolic status of cancer cells are presumed to be correlated with the adjustment of these cells to extracellular changes. Cell glycolysis increases the production of intracellular lactate catalyzed by the lactate dehydrogenases, both LDH-A and LDH-B. An increase in intracellular lactate can affect extracellular pH balance through monocarboxylate transporters, particularly MCT1 and MCT4. This study aimed to analyze the effects of extracellular alkalinization on the lactate metabolism of human breast cancer stem cells (BCSCs). In this study, human primary BCSCs (CD24-/CD44+ cells) were treated with 100 mM sodium bicarbonate for 0.5, 24, and 48 h in DMEM F12/HEPES. After incubation, extracellular pH was measured and cells were harvested to extract the total RNA and protein. The expression of LDH-A, LDH-B, MCT1, and MCT4 mRNA genes were analyzed using qRT-PCR method. Our study shows that administration of sodium bicarbonate in the BCSC culture medium could increase extracellular pH. To balance the increase of extracellular pH, BCSCs regulated the expression of LDH-A, LDH-B, MCT1, and MCT4 genes. As the extracellular pH increases, the expression of LDH-A that converts pyruvate to lactate increased along with the increase of MCT 4 and MCT 1 expression, which act as lactate transporters. As the incubation time increases, the pH decreases, leading to the suppression of LDH-A and increase of LDH-B expression that converts lactate into pyruvate. Therefore, we suggest that the extracellular alkalinization by sodium bicarbonate in BCSCs affected the genes that regulate lactate metabolism.

  6. MCT1 promotes the cisplatin-resistance by antagonizing Fas in epithelial ovarian cancer.

    PubMed

    Yan, Chunxiao; Yang, Fan; Zhou, Chunxia; Chen, Xuejun; Han, Xuechuan; Liu, Xueqin; Ma, Hongyun; Zheng, Wei

    2015-01-01

    This study was designed to investigate the role of MCT1 in the development of cisplatin-resistant ovarian cancer and its possible relationship with Fas. We found the expression of MCT1 was obviously increased both in cisplatin-resistant ovarian cancer tissue and A2780/CP cells compared with sensitive ovarian cancer tissue and cell lines A2780. And in A2780 cells treated with Cisplatin, the expression of MCT1 increased in a concentration-dependent manner, MCT1 knockdown attenuates cisplatin-induced cell viability. In A2780 and A2780/CP cells transfected with MCT1 siRNA, the activation of several downstream targets of Fas, including FasL and FAP-1 were largely prevented, whereas the expression of Caspase-3 was increased, accompanying with increased abundance of Fas. Coimmunoprecipitation and immunofluorescence showed that there is interaction between endogenous MCT1 with Fas in vivo and in vitro. In vivo, depletion of MCT1 by shRNA reverses cisplatin-resistance and the expression of Fas. This study showed that down regulation of MCT1 promote the sensibility to Cisplatin in ovarian cancer cell line. And this effect appeared to be mediated via antagonizing the effect of Fas.

  7. Monocarboxylate transporter 1 (MCT1) in the liver of pre-ruminant and adult bovines.

    PubMed

    Kirat, D; Inoue, H; Iwano, H; Yokota, H; Taniyama, H; Kato, S

    2007-01-01

    This study investigated the distribution and expression of monocarboxylate transporter 1 (MCT1) in the livers of pre-ruminant calves and adult bovines (bulls and cows), using different molecular biological techniques. Reverse transcription-polymerase chain reaction (RT-PCR) verified the presence of mRNA encoding for MCT1 in both pre-ruminant and adult bovine livers. Immunohistochemically, MCT1 was clearly demonstrated on the sinusoidal surfaces of bovine hepatocytes but its expression varied widely between pre-ruminants and adult bovines. In pre-ruminants, a faint hepatocellular expression of MCT1 was observed in a few hepatocytes, whereas an intense immunoreactive staining for MCT1 was shown in the majority of adult bovine hepatocytes. Western blot analysis also confirmed the results of the immunohistochemistry. Quantitative immunoblotting, as estimated by densitometric analysis, showed that the level of MCT1 in the liver of adult bovines was 8-9-fold greater (P<0.01) than that in pre-ruminant calf livers although no significant differences were detected between bulls and cows. The results demonstrated that MCT1 may play a crucial role in the transport of propionate in bovine liver, suggesting that MCT1 expression may be influenced by developmental and metabolic regulations.

  8. Monocarboxylate Transporter MCT1 Promotes Tumor Metastasis Independently of Its Activity as a Lactate Transporter.

    PubMed

    Payen, Valéry L; Hsu, Myriam Y; Rädecke, Kristin S; Wyart, Elisabeth; Vazeille, Thibaut; Bouzin, Caroline; Porporato, Paolo E; Sonveaux, Pierre

    2017-10-15

    Extracellular acidosis resulting from intense metabolic activities in tumors promotes cancer cell migration, invasion, and metastasis. Although host cells die at low extracellular pH, cancer cells resist, as they are well equipped with transporters and enzymes to regulate intracellular pH homeostasis. A low extracellular pH further activates proteolytic enzymes that remodel the extracellular matrix to facilitate cell migration and invasion. Monocarboxylate transporter MCT1 is a passive transporter of lactic acid that has attracted interest as a target for small-molecule drugs to prevent metastasis. In this study, we present evidence of a function for MCT1 in metastasis beyond its role as a transporter of lactic acid. MCT1 activates transcription factor NF-κB to promote cancer cell migration independently of MCT1 transporter activity. Although pharmacologic MCT1 inhibition did not modulate MCT1-dependent cancer cell migration, silencing or genetic deletion of MCT1 in vivo inhibited migration, invasion, and spontaneous metastasis. Our findings raise the possibility that pharmacologic inhibitors of MCT1-mediated lactic acid transport may not effectively prevent metastatic dissemination of cancer cells. Cancer Res; 77(20); 5591-601. ©2017 AACR . ©2017 American Association for Cancer Research.

  9. MCT1 promotes the cisplatin-resistance by antagonizing Fas in epithelial ovarian cancer

    PubMed Central

    Yan, Chunxiao; Yang, Fan; Zhou, Chunxia; Chen, Xuejun; Han, Xuechuan; Liu, Xueqin; Ma, Hongyun; Zheng, Wei

    2015-01-01

    This study was designed to investigate the role of MCT1 in the development of cisplatin-resistant ovarian cancer and its possible relationship with Fas. We found the expression of MCT1 was obviously increased both in cisplatin-resistant ovarian cancer tissue and A2780/CP cells compared with sensitive ovarian cancer tissue and cell lines A2780. And in A2780 cells treated with Cisplatin, the expression of MCT1 increased in a concentration-dependent manner, MCT1 knockdown attenuates cisplatin-induced cell viability. In A2780 and A2780/CP cells transfected with MCT1 siRNA, the activation of several downstream targets of Fas, including FasL and FAP-1 were largely prevented, whereas the expression of Caspase-3 was increased, accompanying with increased abundance of Fas. Coimmunoprecipitation and immunofluorescence showed that there is interaction between endogenous MCT1 with Fas in vivo and in vitro. In vivo, depletion of MCT1 by shRNA reverses cisplatin-resistance and the expression of Fas. This study showed that down regulation of MCT1 promote the sensibility to Cisplatin in ovarian cancer cell line. And this effect appeared to be mediated via antagonizing the effect of Fas. PMID:26045776

  10. Differential protein abundance of a basolateral MCT1 transporter in the human gastrointestinal tract.

    PubMed

    Al-Mosauwi, Hashemeya; Ryan, Elizabeth; McGrane, Alison; Riveros-Beltran, Stefanie; Walpole, Caragh; Dempsey, Eugene; Courtney, Danielle; Fearon, Naomi; Winter, Desmond; Baird, Alan; Stewart, Gavin

    2016-12-01

    Bacterially derived short chain fatty acids (SCFAs), such as butyrate, are vital in maintaining the symbiotic relationship that exists between humans and their gastrointestinal microbial populations. A key step in this process is the transport of SCFAs across colonic epithelial cells via MCT1 transporters. This study investigated MCT1 protein abundance in various human intestinal tissues. Initial RT-PCR analysis confirmed the expected MCT1 RNA expression pattern of colon > small intestine > stomach. Using surgical resection samples, immunoblot analysis detected higher abundance of a 45 kDa MCT1 protein in colonic tissue compared to ileum tissue (P < 0.001, N = 4, unpaired t-test). Importantly, MCT1 abundance was found to be significantly lower in sigmoid colon compared to ascending colon (P < 0.01, N = 8-11, ANOVA). Finally, immunolocalization studies confirmed MCT1 to be abundant in the basolateral membranes of surface epithelial cells of the ascending, transverse, and descending colon, but significantly less prevalent in the sigmoid colon (P < 0.05, N = 5-21, ANOVA). In conclusion, these data confirm that basolateral MCT1 protein abundance is correlated to levels of bacterially derived SCFAs along the human gastrointestinal tract. These findings highlight the importance of precise tissue location in studies comparing colonic MCT1 abundance between normal and diseased states. © 2016 International Federation for Cell Biology.

  11. A Study of Middle School Athletes and Their Performance on the MCT2

    ERIC Educational Resources Information Center

    McEwen, Terrance Jacob

    2017-01-01

    The goal of this study was to determine whether there was a significant relationship between participation in athletic activities and academic achievement. Academic achievement was to be measured by the Mississippi Curriculum Test, Second Edition (MCT2). This study focused on MCT2 scores in mathematics and language arts for 8th grade male and…

  12. MCT2 Expression and Lactate Influx in Anorexigenic and Orexigenic Neurons of the Arcuate Nucleus

    PubMed Central

    Cortes-Campos, Christian; Elizondo, Roberto; Carril, Claudio; Martínez, Fernando; Boric, Katica; Nualart, Francisco; Garcia-Robles, Maria Angeles

    2013-01-01

    Hypothalamic neurons of the arcuate nucleus control food intake, releasing orexigenic and anorexigenic neuropeptides in response to changes in glucose concentration. Several studies have suggested that the glucosensing mechanism is governed by a metabolic interaction between neurons and glial cells via lactate flux through monocarboxylate transporters (MCTs). Hypothalamic glial cells (tanycytes) release lactate through MCT1 and MCT4; however, similar analyses in neuroendocrine neurons have yet to be undertaken. Using primary rat hypothalamic cell cultures and fluorimetric assays, lactate incorporation was detected. Furthermore, the expression and function of MCT2 was demonstrated in the hypothalamic neuronal cell line, GT1-7, using kinetic and inhibition assays. Moreover, MCT2 expression and localization in the Sprague Dawley rat hypothalamus was analyzed using RT-PCR, in situ hybridization and Western blot analyses. Confocal immunohistochemistry analyses revealed MCT2 localization in neuronal but not glial cells. Moreover, MCT2 was localized to ∼90% of orexigenic and ∼60% of anorexigenic neurons as determined by immunolocalization analysis of AgRP and POMC with MCT2-positives neurons. Thus, MCT2 distribution coupled with lactate uptake by hypothalamic neurons suggests that hypothalamic neurons control food intake using lactate to reflect changes in glucose levels. PMID:23638108

  13. Prognostic Indications of Elevated MCT4 and CD147 across Cancer Types: A Meta-Analysis

    PubMed Central

    Bovenzi, Cory D.; Hamilton, James; Tassone, Patrick; Johnson, Jennifer; Cognetti, David M.; Luginbuhl, Adam; Keane, William M.; Zhan, Tingting; Tuluc, Madalina; Bar-Ad, Voichita; Martinez-Outschoorn, Ubaldo; Curry, Joseph M.

    2015-01-01

    Background. Metabolism in the tumor microenvironment can play a critical role in tumorigenesis and tumor aggression. Metabolic coupling may occur between tumor compartments; this phenomenon can be prognostically significant and may be conserved across tumor types. Monocarboxylate transporters (MCTs) play an integral role in cellular metabolism via lactate transport and have been implicated in metabolic synergy in tumors. The transporters MCT1 and MCT4 are regulated via expression of their chaperone, CD147. Methods. We conducted a meta-analysis of existing publications on the relationship between MCT1, MCT4, and CD147 expression and overall survival and disease-free survival in cancer, using hazard ratios derived via multivariate Cox regression analyses. Results. Increased MCT4 expressions in the tumor microenvironment, cancer cells, or stromal cells were all associated with decreased overall survival and decreased disease-free survival (p < 0.001 for all analyses). Increased CD147 expression in cancer cells was associated with decreased overall survival and disease-free survival (p < 0.0001 for both analyses). Few studies were available on MCT1 expression; MCT1 expression was not clearly associated with overall or disease-free survival. Conclusion. MCT4 and CD147 expression correlate with worse prognosis across many cancer types. These results warrant further investigation of these associations. PMID:26779534

  14. Blocking Lactate Export by Inhibiting the Myc Target MCT1 Disables Glycolysis and Glutathione Synthesis

    PubMed Central

    Doherty, Joanne R.; Yang, Chunying; Scott, Kristen E. N.; Cameron, Michael D.; Fallahi, Mohammad; Li, Weimin; Hall, Mark A.; Amelio, Antonio L.; Mishra, Jitendra K.; Li, Fangzheng; Tortosa, Mariola; Genau, Heide Marika; Rounbehler, Robert J.; Lu, Yunqi; Dang, Chi. V.; Kumar, K. Ganesh; Butler, Andrew A.; Bannister, Thomas D.; Hooper, Andrea T.; Unsal-Kacmaz, Keziban; Roush, William R.; Cleveland, John L.

    2014-01-01

    Myc oncoproteins induce genes driving aerobic glycolysis, including lactate dehydrogenase-A that generates lactate. Here we report that Myc controls transcription of the lactate transporter SLC16A1/MCT1, and that elevated MCT1 levels are manifest in premalignant and neoplastic Eμ-Myc transgenic B cells and in human malignancies with MYC or MYCN involvement. Notably, disrupting MCT1 function leads to an accumulation of intracellular lactate that rapidly disables tumor cell growth and glycolysis, provoking marked alterations in glycolytic intermediates, and reductions in glucose transport, and in levels of ATP, NADPH and glutathione. Reductions in glutathione then lead to increases in hydrogen peroxide, mitochondrial damage and, ultimately, cell death. Finally, forcing glycolysis by metformin treatment augments this response and the efficacy of MCT1 inhibitors, suggesting an attractive combination therapy for MYC/MCT1-expressing malignancies. PMID:24285728

  15. Blocking lactate export by inhibiting the Myc target MCT1 Disables glycolysis and glutathione synthesis.

    PubMed

    Doherty, Joanne R; Yang, Chunying; Scott, Kristen E N; Cameron, Michael D; Fallahi, Mohammad; Li, Weimin; Hall, Mark A; Amelio, Antonio L; Mishra, Jitendra K; Li, Fangzheng; Tortosa, Mariola; Genau, Heide Marika; Rounbehler, Robert J; Lu, Yunqi; Dang, Chi V; Kumar, K Ganesh; Butler, Andrew A; Bannister, Thomas D; Hooper, Andrea T; Unsal-Kacmaz, Keziban; Roush, William R; Cleveland, John L

    2014-02-01

    Myc oncoproteins induce genes driving aerobic glycolysis, including lactate dehydrogenase-A that generates lactate. Here, we report that Myc controls transcription of the lactate transporter SLC16A1/MCT1 and that elevated MCT1 levels are manifest in premalignant and neoplastic Eμ-Myc transgenic B cells and in human malignancies with MYC or MYCN involvement. Notably, disrupting MCT1 function leads to an accumulation of intracellular lactate that rapidly disables tumor cell growth and glycolysis, provoking marked alterations in glycolytic intermediates, reductions in glucose transport, and in levels of ATP, NADPH, and ultimately, glutathione (GSH). Reductions in GSH then lead to increases in hydrogen peroxide, mitochondrial damage, and ultimately, cell death. Finally, forcing glycolysis by metformin treatment augments this response and the efficacy of MCT1 inhibitors, suggesting an attractive combination therapy for MYC/MCT1-expressing malignancies.

  16. PKC-dependent stimulation of the human MCT1 promoter involves transcription factor AP2.

    PubMed

    Saksena, Seema; Dwivedi, Alka; Gill, Ravinder K; Singla, Amika; Alrefai, Waddah A; Malakooti, Jaleh; Ramaswamy, Krishnamurthy; Dudeja, Pradeep K

    2009-02-01

    Monocarboxylate transporter (MCT1) plays an important role in the absorption of short-chain fatty acids (SCFA) such as butyrate in the human colon. Previous studies from our laboratory have demonstrated that phorbol ester, PMA (1 microM, 24 h), upregulates butyrate transport and MCT1 protein expression in human intestinal Caco-2 cells. However, the molecular mechanisms involved in the transcriptional regulation of MCT1 gene expression by PMA in the intestine are not known. In the present study, we showed that PMA (0.1 microM, 24 h) increased the MCT1 promoter activity (-871/+91) by approximately fourfold. A corresponding increase in MCT1 mRNA abundance in response to PMA was also observed. PMA-induced stimulation of MCT1 promoter activity was observed as early as 1 h and persisted until 24 h, suggesting that the effects of PMA are attributable to initial PKC activation. Kinase inhibitor and phosphorylation studies indicated that these effects may be mediated through activation of the atypical PKC-zeta isoform. 5'-deletion studies demonstrated that the MCT1 core promoter region (-229/+91) is the PMA-responsive region. Site-directed mutagenesis studies showed the predominant involvement of potential activator protein 2 (AP2) binding site in the activation of MCT1 promoter activity by PMA. In addition, overexpression of AP2 in Caco-2 cells significantly increased MCT1 promoter activity in a dose-dependent manner. These findings showing the regulation of MCT1 promoter by PKC and AP2 are of significant importance for an understanding of the molecular regulation of SCFA absorption in the human intestine.

  17. Activation and Repression of Epstein-Barr Virus and Kaposi's Sarcoma-Associated Herpesvirus Lytic Cycles by Short- and Medium-Chain Fatty Acids

    PubMed Central

    Gorres, Kelly L.; Daigle, Derek; Mohanram, Sudharshan

    2014-01-01

    ABSTRACT 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

  18. Lipozyme RM IM-catalyzed acidolysis of Cinnamomum camphora seed oil with oleic acid to produce human milk fat substitutes enriched in medium-chain fatty acids.

    PubMed

    Zou, Xian-Guo; Hu, Jiang-Ning; Zhao, Man-Li; Zhu, Xue-Mei; Li, Hong-Yan; Liu, Xiao-Ru; Liu, Rong; Deng, Ze-Yuan

    2014-10-29

    In the present study, a human milk fat substitute (HMFS) enriched in medium-chain fatty acids (MCFAs) was synthesized through acidolysis reaction from Cinnamomum camphora seed oil (CCSO) with oleic acid in a solvent-free system. A commercial immobilized lipase, Lipozyme RM IM, from Rhizomucor miehei, was facilitated as a biocatalyst. Effects of different reaction conditions, including substrate molar ratio, enzyme concentration, reaction temperature, and reaction time were investigated using response surface methodology (RSM) to obtain the optimal oleic acid incorporation. After optimization, results showed that the maximal incorporation of oleic acid into HMFS was 59.68%. Compared with CCSO, medium-chain fatty acids at the sn-2 position of HMFS accounted for >70%, whereas oleic acid was occupied predominantly at the sn-1,3 position (78.69%). Meanwhile, triacylglycerol (TAG) components of OCO (23.93%), CCO (14.94%), LaCO (13.58%), OLaO (12.66%), and OOO (11.13%) were determined as the major TAG species in HMFS. The final optimal reaction conditions were carried out as follows: substrate molar ratio (oleic acid/CCSO), 5:1; enzyme concentration, 12.5% (w/w total reactants); reaction temperature, 60 °C; and reaction time, 28 h. The reusability of Lipozyme RM IM in the acidolysis reaction was also evaluated, and it was found that it could be reused up to 9 times without significant loss of activities. Urea inclusion method was used to separate and purify the synthetic product. As the ratio of HMFS/urea increased to 1:2, the acid value lowered to the minimum. In a scale-up experiment, the contents of TAG and total tocopherols in HMFS (modified CCSO) were 77.28% and 12.27 mg/100 g, respectively. All of the physicochemical indices of purified product were within food standards. Therefore, such a MCFA-enriched HMFS produced by using the acidolysis method might have potential application in the infant formula industry.

  19. Advanced MCT technologies at LETI for space applications

    NASA Astrophysics Data System (ADS)

    Durand, A.; Destefanis, G.; Gravrand, O.; Rothmann, J.

    This document is a recap of an oral presentation made at Nice during the INSU Astrophysics Detector Workshop 2008. It aims at giving an overview of the achievements and ongoing developments presently carried out at CEA-LETI in the field of Infrared focal plane array. Although most of the research actually performed at LETI is not driven by space oriented application, the excellence and the cutting edge of the outcome is or can be applied to space-dedicated components. This paper focus on features and developments from which astrophysics observation would benefit in the near future on the European market. This encompassed “traditionnal” developments such as format enlargement, low dark current technology such as p/n structure but it also shade light on promising and thrilling development such as avalanche photodiode array. It eventually gives some hints of none MCT technologies processed at LETI.

  20. MCT1 in Invasive Ductal Carcinoma: Monocarboxylate Metabolism and Aggressive Breast Cancer.

    PubMed

    Johnson, Jennifer M; Cotzia, Paolo; Fratamico, Roberto; Mikkilineni, Lekha; Chen, Jason; Colombo, Daniele; Mollaee, Mehri; Whitaker-Menezes, Diana; Domingo-Vidal, Marina; Lin, Zhao; Zhan, Tingting; Tuluc, Madalina; Palazzo, Juan; Birbe, Ruth C; Martinez-Outschoorn, Ubaldo E

    2017-01-01

    Introduction: Monocarboxylate transporter 1 (MCT1) is an importer of monocarboxylates such as lactate and pyruvate and a marker of mitochondrial metabolism. MCT1 is highly expressed in a subgroup of cancer cells to allow for catabolite uptake from the tumor microenvironment to support mitochondrial metabolism. We studied the protein expression of MCT1 in a broad group of breast invasive ductal carcinoma specimens to determine its association with breast cancer subtypes and outcomes. Methods: MCT1 expression was evaluated by immunohistochemistry on tissue micro-arrays (TMA) obtained through our tumor bank. Two hundred and fifty-seven cases were analyzed: 180 cases were estrogen receptor and/or progesterone receptor positive (ER+ and/or PR+), 62 cases were human epidermal growth factor receptor 2 positive (HER2+), and 56 cases were triple negative breast cancers (TNBC). MCT1 expression was quantified by digital pathology with Aperio software. The intensity of the staining was measured on a continuous scale (0-black to 255-bright white) using a co-localization algorithm. Statistical analysis was performed using a linear mixed model. Results: High MCT1 expression was more commonly found in TNBC compared to ER+ and/or PR+ and compared to HER-2+ ( p < 0.001). Tumors with an in-situ component were less likely to stain strongly for MCT1 ( p < 0.05). High nuclear grade was associated with higher MCT1 staining ( p < 0.01). Higher T stage tumors were noted to have a higher expression of MCT1 ( p < 0.05). High MCT1 staining in cancer cells was associated with shorter progression free survival, increased risk of recurrence, and larger size independent of TNBC status ( p < 0.05). Conclusion: MCT1 expression, which is a marker of high catabolite uptake and mitochondrial metabolism, is associated with recurrence in breast invasive ductal carcinoma. MCT1 expression as quantified with digital image analysis may be useful as a prognostic biomarker and to design clinical trials using

  1. MCT1 in Invasive Ductal Carcinoma: Monocarboxylate Metabolism and Aggressive Breast Cancer

    PubMed Central

    Johnson, Jennifer M.; Cotzia, Paolo; Fratamico, Roberto; Mikkilineni, Lekha; Chen, Jason; Colombo, Daniele; Mollaee, Mehri; Whitaker-Menezes, Diana; Domingo-Vidal, Marina; Lin, Zhao; Zhan, Tingting; Tuluc, Madalina; Palazzo, Juan; Birbe, Ruth C.; Martinez-Outschoorn, Ubaldo E.

    2017-01-01

    Introduction: Monocarboxylate transporter 1 (MCT1) is an importer of monocarboxylates such as lactate and pyruvate and a marker of mitochondrial metabolism. MCT1 is highly expressed in a subgroup of cancer cells to allow for catabolite uptake from the tumor microenvironment to support mitochondrial metabolism. We studied the protein expression of MCT1 in a broad group of breast invasive ductal carcinoma specimens to determine its association with breast cancer subtypes and outcomes. Methods: MCT1 expression was evaluated by immunohistochemistry on tissue micro-arrays (TMA) obtained through our tumor bank. Two hundred and fifty-seven cases were analyzed: 180 cases were estrogen receptor and/or progesterone receptor positive (ER+ and/or PR+), 62 cases were human epidermal growth factor receptor 2 positive (HER2+), and 56 cases were triple negative breast cancers (TNBC). MCT1 expression was quantified by digital pathology with Aperio software. The intensity of the staining was measured on a continuous scale (0-black to 255-bright white) using a co-localization algorithm. Statistical analysis was performed using a linear mixed model. Results: High MCT1 expression was more commonly found in TNBC compared to ER+ and/or PR+ and compared to HER-2+ (p < 0.001). Tumors with an in-situ component were less likely to stain strongly for MCT1 (p < 0.05). High nuclear grade was associated with higher MCT1 staining (p < 0.01). Higher T stage tumors were noted to have a higher expression of MCT1 (p < 0.05). High MCT1 staining in cancer cells was associated with shorter progression free survival, increased risk of recurrence, and larger size independent of TNBC status (p < 0.05). Conclusion: MCT1 expression, which is a marker of high catabolite uptake and mitochondrial metabolism, is associated with recurrence in breast invasive ductal carcinoma. MCT1 expression as quantified with digital image analysis may be useful as a prognostic biomarker and to design clinical trials using MCT1

  2. Ultra-compact high-performance MCT MWIR engine

    NASA Astrophysics Data System (ADS)

    Lutz, H.; Breiter, R.; Eich, D.; Figgemeier, H.; Oelmaier, R.; Rutzinger, S.; Schenk, H.; Wendler, J.

    2017-02-01

    Size, weight and power (SWaP) reduction is highly desired by applications such as sights for the dismounted soldier or small gimbals for UAVs. But why have high performance and small size of IR systems inevitably exclude each other? Namely, recent development progress in the fields of miniature cryocoolers, short dewars and high operating temperature (HOT) FPAs combined with pitch size reduction opens the door for very compact MWIR-modules while keeping high electro-optical performance. Now, AIM has realized first prototypes of an ultra-compact high-performance MWIR engine in a total volume of only 18cl (60mm length x 60mm height x 50mm width). Impressive SWaP characteristics are completed by a total weight below 400g and a power consumption < 4W in basic imaging mode. The engine consists of a XGA-format (1024x768) MCT detector array with 10μm pitch and a low power consuming ROIC. It is cooled down to a typical operating temperature of 160K by the miniature linear cryocooler SX020. The dewar uses a short coldfinger and is designed to reduce the heat load as much as possible. The cooler drive electronics is implemented in the CCE layout in order to reduce the required space of the printed boards and to save power. Uncorrected 14bit video data is provided via Camera Link. Optionally, a small image processing board can be stacked on top of the CCE to gain access to basic functions such as BPR, 2- point NUC and dynamic reduction. This paper will present the design, functionalities and performance data of the ultra-compact MCT MWIR engine operated at HOT.

  3. Acquired intestinal lymphangiectasia successfully treated with a low-fat and medium-chain triacylglycerol-enriched diet in a patient with liver transplantation.

    PubMed

    Biselli, Maurizio; Andreone, Pietro; Gramenzi, Annagiulia; Cursaro, Carmela; Lorenzini, Stefania; Bonvicini, Fiorenza; Bernardi, Mauro

    2006-05-01

    Intestinal lymphangiectasia is defined as a dilatation of small bowel lymphatic capillaries and a loss of lymph into the bowel lumen. Clinically it is characterized by hypoproteinaemia and oedema. We present here a case of protein-losing enteropathy due to intestinal lymphangiectasia after liver transplantation in a 57-year-old man who was transplanted for hepatitis C virus. Four years after liver transplantation, the patient developed hypoalbuminaemia and ascites associated with recurrence of cirrhosis. The sudden fall in serum albumin led us to look for a cause of reduction other than or in addition to cirrhosis. Duodenal biopsies showed tall villi with dilated lymphatic vessels and widening of the villi caused by oedema, demonstrating intestinal lymphangiectasia. In this case a low-fat diet supplemented with medium-chain triacylglycerols achieved an early clinical improvement with increased serum albumin levels and ascites disappearance. Intestinal lymphangiectasia should be suspected in liver-transplanted patients developing hypoproteinaemia and hypoalbuminaemia after the recurrence of cirrhosis.

  4. Xenobiotic/medium chain fatty acid: CoA ligase - a critical review on its role in fatty acid metabolism and the detoxification of benzoic acid and aspirin.

    PubMed

    van der Sluis, Rencia; Erasmus, Elardus

    2016-10-01

    Activation of fatty acids by the acyl-CoA synthetases (ACSs) is the vital first step in fatty acid metabolism. The enzymatic and physiological characterization of the human xenobiotic/medium chain fatty acid: CoA ligases (ACSMs) has been severely neglected even though xenobiotics, such as benzoate and salicylate, are detoxified through this pathway. This review will focus on the nomenclature and substrate specificity of the human ACSM ligases; the biochemical and enzymatic characterization of ACSM1 and ACSM2B; the high sequence homology of the ACSM2 genes (ACSM2A and ACSM2B) as well as what is currently known regarding disease association studies. Several discrepancies exist in the current literature that should be taken note of. For example, the single nucleotide polymorphisms (SNPs) reported to be associated with aspirin metabolism and multiple risk factors of metabolic syndrome are incorrect. Kinetic data on the substrate specificity of the human ACSM ligases are non-existent and currently no data exist on the influence of SNPs on the enzyme activity of these ligases. One of the biggest obstacles currently in the field is that glycine conjugation is continuously studied as a one-step process, which means that key regulatory factors of the two individual steps remain unknown.

  5. Spectra-structure correlations of saturated and unsaturated medium-chain fatty acids. Near-infrared and anharmonic DFT study of hexanoic acid and sorbic acid

    NASA Astrophysics Data System (ADS)

    Grabska, Justyna; Beć, Krzysztof B.; Ishigaki, Mika; Wójcik, Marek J.; Ozaki, Yukihiro

    2017-10-01

    Quantum chemical reproduction of entire NIR spectra is a new trend, enabled by contemporary advances in the anharmonic approaches. At the same time, recent increase of the importance of NIR spectroscopy of biological samples raises high demand for gaining deeper understanding of NIR spectra of biomolecules, i.e. fatty acids. In this work we investigate saturated and unsaturated medium-chain fatty acids, hexanoic acid and sorbic acid, in the near-infrared region. By employing fully anharmonic density functional theory (DFT) calculations we reproduce the experimental NIR spectra of these systems, including the highly specific spectral features corresponding to the dimerization of fatty acids. Broad range of concentration levels from 5 · 10- 4 M in CCl4 to pure samples are investigated. The major role of cyclic dimers can be evidenced for the vast majority of these samples. A highly specific NIR feature of fatty acids, the elevation of spectral baseline around 6500-4000 cm- 1, is being explained by the contributions of combination bands resulting from the vibrations of hydrogen-bonded OH groups in the cyclic dimers. Based on the high agreement between the calculated and experimental NIR spectra, a detailed NIR band assignments are proposed for hexanoic acid and sorbic acid. Subsequently, the correlations between the structure and NIR spectra are elucidated, emphasizing the regions in which clear and universal traces of specific bands corresponding to saturated and unsaturated alkyl chains can be established, thus demonstrating the wavenumber regions highly valuable for structural identifications.

  6. Safety assessment of medium- and long-chain triacylglycerols containing 30% (w/w) medium-chain fatty acids in mice and rats.

    PubMed

    Zhou, Shengmin; Wang, Yueqiang; Jiang, Yuanrong; Yu, Liangli Lucy

    2017-06-01

    A novel medium- and long-chain triacylglycerols (MLCT), with 30% (w/w) medium-chain fatty acids (MCFA) was evaluated for its safety as a dietary fat in mice and rats. The subacute oral toxicity study showed that the maximum tolerated dose exceeded 54.33 g/kg body weight (kg bw)/day. In the 90-day feeding study, no dose-related adverse effects were observed in rats administered diets formulated with different levels of MLCT (2.0, 4.0, and 8.0 g/kg bw/day) as compared to the rapeseed oil control diet. Further safety assessment in pregnant rats did not reveal any significant difference relative to the control at a treatment level up to 8.0 g MLCT/kg bw/day. The results from this study indicated the safe use of MLCT with high contents of MCFA in food products for improving human health. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. 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. © 2016 Institute of Food Technologists®

  8. 2-Decenoic acid ethyl ester, a derivative of unsaturated medium-chain fatty acids, facilitates functional recovery of locomotor activity after spinal cord injury.

    PubMed

    Hirakawa, A; Shimizu, K; Fukumitsu, H; Soumiya, H; Iinuma, M; Furukawa, S

    2010-12-29

    There is increasing evidence that omega-3 polyunsaturated fatty acids (PUFAs) have therapeutic potential in various animal models of neuronal injury. However, very few studies have examined the effect of medium-chain fatty acids (MCFAs) on neuronal injury. So in the present study we synthesized various MCFAs and their derivatives, and found that exposure to trans-2-decenoic acid ethyl ester (DAEE) markedly activated extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in cultured cortical neurons. Therefore, we examined the effect of DAEE treatment on a rat model of spinal cord injury. DAEE (150 μg/kg body weight) administered after hemisection of the spinal cord resulted in improved functional recovery, decreased the lesion size, increased the activation of ERK1/2, and enhanced the expression of bcl-2 and brain-derived neurotrophic factor (BDNF) mRNA in the injury site of the spinal cord. Furthermore, it also increased neuronal survival after spinal cord injury. These results indicate that the possibility that DAEE will become a promising tool for reducing the secondary damage observed following primary physical injury to the spinal cord. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

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

    SciTech Connect

    Gu, Huiya; Jinkerson, Robert E.; Davies, Fiona K.

    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

  10. Discovery and Characterization of a Novel Small-Molecule Agonist for Medium-Chain Free Fatty Acid Receptor G Protein-Coupled Receptor 84.

    PubMed

    Zhang, Qing; Yang, Hui; Li, Jing; Xie, Xin

    2016-05-01

    G protein-coupled receptor 84 (GPR84) is a free fatty acid receptor activated by medium-chain free fatty acids with 9-14 carbons. It is expressed mainly in the immune-related tissues, such as spleen, bone marrow, and peripheral blood leukocytes. GPR84 plays significant roles in inflammatory processes and may represent a novel drug target for the treatment of immune-mediated diseases. However, the lack of potent and specific ligands for GPR84 hindered the study of its functions and the development of potential clinical applications. Here, we report the screen of 160,000 small-molecule compounds with a calcium mobilization assay using a human embryonic kidney 293 cell line stably expressing GPR84 and Gα16, and the identification of 2-(hexylthio)pyrimidine-4,6-diol (ZQ-16) as a potent and selective agonist of GPR84 with a novel structure. ZQ-16 activates several GPR84-mediated signaling pathways, including calcium mobilization, inhibition of cAMP accumulation, phosphorylation of extracellular signal-regulated protein kinase 1/2, receptor desensitization and internalization, and receptor-β-arrestin interaction. This compound may be a useful tool to study the functions of GPR84 and a potential candidate for further structural optimization. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  11. Dispersion of Short- and Medium-Chain Chlorinated Paraffins (CPs) from a CP Production Plant to the Surrounding Surface Soils and Coniferous Leaves.

    PubMed

    Xu, Jiazhi; Gao, Yuan; Zhang, Haijun; Zhan, Faqiang; Chen, Jiping

    2016-12-06

    Chlorinated paraffin (CP) production is one important emission source for short- and medium-chain CPs (SCCPs and MCCPs) in the environment. In this study, 48 CP congener groups were measured in the surface soils and coniferous leaves collected from the inner and surrounding environment of a CP production plant that has been in operation for more than 30 years to investigate the dispersion and deposition behavior of SCCPs and MCCPs. The average concentrations of the sum of SCCPs and MCCPs in the in-plant coniferous leaves and surface soils were 4548.7 ng g -1 dry weight (dw) and 3481.8 ng g -1 dw, which were 2-fold and 10-fold higher than those in the surrounding environment, respectively. The Gaussian air pollution model explained the spatial distribution of CPs in the coniferous leaves, whereas the dispersion of CPs to the surrounding surface soils fits the Boltzmann equation well. Significant fractionation effect was observed for the atmospheric dispersion of CPs from the production plant. CP congener groups with higher octanol-air partitioning coefficients (K OA ) were more predominant in the in-plant environment, whereas the ones with lower K OA values had the elevated proportion in the surrounding environment. A radius of approximately 4 km from the CP production plant was influenced by the atmospheric dispersion and deposition of CPs.

  12. Quantification of short- and medium-chain chlorinated paraffins in environmental samples by gas chromatography quadrupole time-of-flight mass spectrometry.

    PubMed

    Gao, Wei; Wu, Jing; Wang, Yawei; Jiang, Guibin

    2016-06-24

    Chlorinated paraffins (CPs) are technical products produced and used in bulk for a number of purposes. However, the analysis of CPs is challenging, as they are complex mixtures of compounds and isomers. We herein report the development of an analytical method for the analysis of short-chain CPs (SCCPs) and medium-chain CPs (MCCPs) using quadrupole time-of-flight high-resolution mass spectrometry (GC-NCI-qTOF-HRMS). This method employs gas chromatography with a chemical ionization source working in negative mode. The linear relationship between chlorination and the CP total response factors was applied to quantify the CP content and the congener group distribution patterns. In a single injection, 24 SCCP formula groups and 24 MCCP formula groups were quantified. Extraction of accurate masses using qTOF-HRMS allowed the SCCPs and MCCPs to be distinguished, with interference from other chemicals (e.g., PCBs) being largely avoided. The SCCP and MCCP detection limits were 24-81ng/mL and 27-170ng/mL, respectively. Comparison of the obtained results with analytical results from gas chromatography coupled with electron capture negative ionization low-resolution mass spectrometry (GC-ECNI-LRMS) indicate that the developed technique is a more accurate and convenient method for the analysis of CPs in samples from a range of matrices. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Increase of medium-chain fatty acid ethyl ester content in mixed H. uvarum/S. cerevisiae fermentation leads to wine fruity aroma enhancement.

    PubMed

    Hu, Kai; Jin, Guo-Jie; Mei, Wen-Chao; Li, Ting; Tao, Yong-Sheng

    2018-01-15

    Medium-chain fatty acid (MCFA) ethyl esters, as yeast secondary metabolites, significantly contribute to the fruity aroma of foods and beverages. To improve the MCFA ethyl ester content of wine, mixed fermentations with Hanseniaspora uvarum Yun268 and Saccharomyces cerevisiae were performed. Final volatiles were analyzed by gas solid phase microextraction-chromatography-mass spectrometry, and aroma characteristics were quantitated by sensory analysis. Results showed that mixed fermentation increased MCFA ethyl ester content by 37% in Cabernet Gernischt wine compared to that obtained by pure fermentation. Partial least-squares regression analysis further revealed that the improved MCFA ethyl esters specifically enhanced the temperate fruity aroma of wine. The enhancement of MCFA ethyl esters was attributed to the increased contents of MCFAs that could be induced by the presence of H. uvarum Yun268 in mixed fermentation. Meanwhile, the timing of yeast inoculations significantly affected the involving biomass of each strain and the dynamics of ethanol accumulation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. In Silico and Wet Lab Studies Reveal the Cholesterol Lowering Efficacy of Lauric Acid, a Medium Chain Fat of Coconut Oil.

    PubMed

    Lekshmi Sheela, Devi; Nazeem, Puthiyaveetil Abdulla; Narayanankutty, Arunaksharan; Manalil, Jeksy Jos; Raghavamenon, Achuthan C

    2016-12-01

    The coconut oil (CO) contains 91 % of saturated fatty acids in which 72 % are medium chain fatty acids (MCFAs) like lauric, capric and caprylic acids. In contrast to animal fat, coconut oil has no cholesterol. Despite this fact, CO is sidelined among other vegetable oils due to the health hazards attributed to the saturated fatty acids. Though various medicinal effects of CO have been reported including the hypolipidemic activity, people are still confused in the consumption of this natural oil. In silico analyses and wet lab experiments have been carried out to identify the hypolipidemic properties of MCFAs and phenolic acids in CO by using different protein targets involved in cholesterol synthesis. The molecular docking studies were carried out using CDOCKER protocol in Accelery's Discovery Studio, by taking different proteins like HMG- CoA reductase and cholesterol esterase as targets and the different phytocompounds in coconut as ligands. Molecular docking highlighted the potential of lauric acid in inhibiting the protein targets involved in hyperlipidemics. Further, validation of in silico results was carried out through in vivo studies. The activity of key enzymes HMG- CoA reductase and lipoprotein lipase were found reduced in animals fed with lauric acid and CO.

  15. Cloning of a coconut endosperm cDNA encoding a 1-acyl-sn-glycerol-3-phosphate acyltransferase that accepts medium-chain-length substrates.

    PubMed Central

    Knutzon, D S; Lardizabal, K D; Nelsen, J S; Bleibaum, J L; Davies, H M; Metz, J G

    1995-01-01

    Immature coconut (Cocos nucifera) endosperm contains a 1-acyl-sn-glycerol-3-phosphate acyltransferase (LPAAT) activity that shows a preference for medium-chain-length fatty acyl-coenzyme A substrates (H.M. Davies, D.J. Hawkins, J.S. Nelsen [1995] Phytochemistry 39:989-996). Beginning with solubilized membrane preparations, we have used chromatographic separations to identify a polypeptide with an apparent molecular mass of 29 kD, whose presence in various column fractions correlates with the acyltransferase activity detected in those same fractions. Amino acid sequence data obtained from several peptides generated from this protein were used to isolate a full-length clone from a coconut endosperm cDNA library. Clone pCGN5503 contains a 1325-bp cDNA insert with an open reading frame encoding a 308-amino acid protein with a calculated molecular mass of 34.8 kD. Comparison of the deduced amino acid sequence of pCGN5503 to sequences in the data banks revealed significant homology to other putative LPAAT sequences. Expression of the coconut cDNA in Escherichia coli conferred upon those cells a novel LPAAT activity whose substrate activity profile matched that of the coconut enzyme. PMID:8552723

  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.; ...

    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. High levels of medium-chain chlorinated paraffins and polybrominated diphenyl ethers on the inside of several household baking oven doors.

    PubMed

    Gallistl, Christoph; Sprengel, Jannik; Vetter, Walter

    2018-02-15

    Fat obtained by wipe tests on the inner surface of 21 baking ovens from Stuttgart (Germany) were analyzed for halogenated flame retardants (HFRs), namely polybrominated diphenyl ethers (PBDEs), decabromodiphenyl ethane (DBDPE), dechlorane plus (DP), short- and medium-chain chlorinated paraffins (SCCPs, MCCPs), as well as polychlorinated biphenyls (PCBs). In ~50% of the samples chlorinated paraffins (CPs) were present in the mg/g fat range, i.e. three to four orders of magnitude higher concentrated than the sum of all other target compounds. In contrast the remaining ~50% of the samples were free of CPs, while the other HFRs were comparable in CP-positive and CP-negative samples. The exceptionally high concentrations and exclusive presence of CPs in half of the samples produced strong evidence that these compounds were released from the baking oven itself. This hypothesis was supported by detection of MCCPs at even higher concentrations in the inner components of one dismantled baking oven. The release of substantial amounts of HFRs from the oven casing during its use may contribute to human exposure to these compounds, especially MCCPs and SCCPs. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Feature construction can improve diagnostic criteria for high-dimensional metabolic data in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency.

    PubMed

    Ho, Sirikit; Lukacs, Zoltan; Hoffmann, Georg F; Lindner, Martin; Wetter, Thomas

    2007-07-01

    In newborn screening with tandem mass spectrometry, multiple intermediary metabolites are quantified in a single analytical run for the diagnosis of fatty-acid oxidation disorders, organic acidurias, and aminoacidurias. Published diagnostic criteria for these disorders normally incorporate a primary metabolic marker combined with secondary markers, often analyte ratios, for which the markers have been chosen to reflect metabolic pathway deviations. We applied a procedure to extract new markers and diagnostic criteria for newborn screening to the data of newborns with confirmed medium-chain acyl-CoA dehydrogenase deficiency (MCADD) and a control group from the newborn screening program, Heidelberg, Germany. We validated the results with external data of the screening center in Hamburg, Germany. We extracted new markers by performing a systematic search for analyte combinations (features) with high discriminatory performance for MCADD. To select feature thresholds, we applied automated procedures to separate controls and cases on the basis of the feature values. Finally, we built classifiers from these new markers to serve as diagnostic criteria in screening for MCADD. On the basis of chi(2) scores, we identified approximately 800 of >628,000 new analyte combinations with superior discriminatory performance compared with the best published combinations. Classifiers built with the new features achieved diagnostic sensitivities and specificities approaching 100%. Feature construction methods provide ways to disclose information hidden in the set of measured analytes. Other diagnostic tasks based on high-dimensional metabolic data might also profit from this approach.

  19. Spatial and temporal trends of short- and medium-chain chlorinated paraffins in sediments off the urbanized coastal zones in China and Japan: A comparison study.

    PubMed

    Zeng, Lixi; Lam, James C W; Horii, Yuichi; Li, Xiaolin; Chen, Weifang; Qiu, Jian-Wen; Leung, Kenneth M Y; Yamazaki, Eriko; Yamashita, Nobuyoshi; Lam, Paul K S

    2017-05-01

    To examine the impacts of urbanization and industrialization on the coastal environment, and assess the effectiveness of control measures on the contamination by chlorinated paraffins (CPs) in East Asia, surface and core sediments were sampled from the urbanized coastal zones in China and Japan (i.e., Pearl River Delta (PRD), Hong Kong waters and Tokyo Bay) and analyzed for short-chain (SCCPs) and medium-chain CPs (MCCPs). Much higher concentrations of CPs were found in the industrialized PRD than in adjacent Hong Kong waters. Significant correlation between CP concentration and population density in the coastal district of Hong Kong was observed (r 2  = 0.72 for SCCPs and 0.55 for MCCPs, p < 0.05), highlighting the effect of urbanization. By contrast, a relatively lower pollution level of CPs was detected in Tokyo Bay. More long-chain groups within SCCPs in the PRD than in Hong Kong waters and Tokyo Bay implied the effect of industrialization. Comparison of temporal trends between Hong Kong outer harbor with Tokyo Bay shows the striking difference in historical deposition of CPs under different regulatory situations in China and Japan. For the first time, the declining CP concentrations in Tokyo Bay, Japan, attest to the effectiveness of emissions controls. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Binding of the human "electron transferring flavoprotein" (ETF) to the medium chain acyl-CoA dehydrogenase (MCAD) involves an arginine and histidine residue.

    PubMed

    Parker, Antony R

    2003-10-01

    The interaction between the "electron transferring flavoprotein" (ETF) and medium chain acyl-CoA dehydrogenase (MCAD) enables successful flavin to flavin electron transfer, crucial for the beta-oxidation of fatty acids. The exact biochemical determinants for ETF binding to MCAD are unknown. Here we show that binding of human ETF, to MCAD, was inhibited by 2,3-butanedione and diethylpyrocarbonate (DEPC) and reversed by incubation with free arginine and hydroxylamine respectively. Spectral analyses of native ETF vs modified ETF suggested that flavin binding was not affected and that the loss of ETF activity with MCAD involved modification of one ETF arginine residue and one ETF histidine residue respectively. MCAD and octanoyl-CoA protected ETF against inactivation by both 2,3-butanedione and DEPC indicating that the arginine and histidine residues are present in or around the MCAD binding site. Comparison of exposed arginine and histidine residues among different ETF species, however, indicates that arginine residues are highly conserved but that histidine residues are not. These results lead us to conclude that this single arginine residue is essential for the binding of ETF to MCAD, but that the single histidine residue, although involved, is not.

  1. Extensive domain motion and electron transfer in the human electron transferring flavoprotein.medium chain Acyl-CoA dehydrogenase complex.

    PubMed

    Toogood, Helen S; van Thiel, Adam; Basran, Jaswir; Sutcliffe, Mike J; Scrutton, Nigel S; Leys, David

    2004-07-30

    The crystal structure of the human electron transferring flavoprotein (ETF).medium chain acyl-CoA dehydrogenase (MCAD) complex reveals a dual mode of protein-protein interaction, imparting both specificity and promiscuity in the interaction of ETF with a range of structurally distinct primary dehydrogenases. ETF partitions the functions of partner binding and electron transfer between (i) the recognition loop, which acts as a static anchor at the ETF.MCAD interface, and (ii) the highly mobile redox active FAD domain. Together, these enable the FAD domain of ETF to sample a range of conformations, some compatible with fast interprotein electron transfer. Disorders in amino acid or fatty acid catabolism can be attributed to mutations at the protein-protein interface. Crucially, complex formation triggers mobility of the FAD domain, an induced disorder that contrasts with general models of protein-protein interaction by induced fit mechanisms. The subsequent interfacial motion in the MCAD.ETF complex is the basis for the interaction of ETF with structurally diverse protein partners. Solution studies using ETF and MCAD with mutations at the protein-protein interface support this dynamic model and indicate ionic interactions between MCAD Glu(212) and ETF Arg alpha(249) are likely to transiently stabilize productive conformations of the FAD domain leading to enhanced electron transfer rates between both partners.

  2. Dietary Intake of Structured Lipids with Different Contents of Medium-Chain Fatty Acids on Obesity Prevention in C57BL/6J Mice.

    PubMed

    Zhou, Shengmin; Wang, Yueqiang; Jiang, Yuanrong; Zhang, Zhongfei; Sun, Xiangjun; Yu, Liangli Lucy

    2017-08-01

    Three medium- and long-chain triacylglycerols (MLCT) with different contents of medium-chain fatty acids (MCFA) (10% to 30%, w/w) were prepared and evaluated for their anti-obesity potential in C57BL/6J mice. The group fed with a high fat diet of MLCT containing 30% (w/w) MCFA showed significantly decreased body weight and fat mass (P < 0.05) relative to the control mice fed an obesity-inducing high fat rapeseed oil diet. In addition, serum parameters including triacylglycerols, total cholesterol, glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 and apolipoprotein B in the treatment group fed with 30% (w/w) MCFA were close to those of mice fed with a low fat rapeseed oil diet, but significantly different (P < 0.05) from those of the obesity control group. Moreover, the intake of MLCT with high content of MCFA reduced the size of adipocytes. In addition, the visceral fat and liver weights, as well as the liver triacylglycerol for 3 treatment groups were lower than those of the obesity control group. These results demonstrate the great potential of MLCT with high content of MCFA in weight loss. © 2017 Institute of Food Technologists®.

  3. 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

    2014-05-06

    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.

  4. Elevated Medium-Chain Acylcarnitines Are Associated With Gestational Diabetes Mellitus and Early Progression to Type 2 Diabetes and Induce Pancreatic β-Cell Dysfunction.

    PubMed

    Batchuluun, Battsetseg; Al Rijjal, Dana; Prentice, Kacey J; Eversley, Judith A; Burdett, Elena; Mohan, Haneesha; Bhattacharjee, Alpana; Gunderson, Erica P; Liu, Ying; Wheeler, Michael B

    2018-05-01

    Specific circulating metabolites have emerged as important risk factors for the development of diabetes. The acylcarnitines (acylCs) are a family of metabolites known to be elevated in type 2 diabetes (T2D) and linked to peripheral insulin resistance. However, the effect of acylCs on pancreatic β-cell function is not well understood. Here, we profiled circulating acylCs in two diabetes cohorts: 1 ) women with gestational diabetes mellitus (GDM) and 2 ) women with recent GDM who later developed impaired glucose tolerance (IGT), new-onset T2D, or returned to normoglycemia within a 2-year follow-up period. We observed a specific elevation in serum medium-chain (M)-acylCs, particularly hexanoyl- and octanoylcarnitine, among women with GDM and individuals with T2D without alteration in long-chain acylCs. Mice treated with M-acylCs exhibited glucose intolerance, attributed to impaired insulin secretion. Murine and human islets exposed to elevated levels of M-acylCs developed defects in glucose-stimulated insulin secretion and this was directly linked to reduced mitochondrial respiratory capacity and subsequent ability to couple glucose metabolism to insulin secretion. In conclusion, our study reveals that an elevation in circulating M-acylCs is associated with GDM and early stages of T2D onset and that this elevation directly impairs β-cell function. © 2018 by the American Diabetes Association.

  5. 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.

  6. Immunohistochemical analysis of MCT1 and CD147 in equine skeletal muscle fibres.

    PubMed

    Mykkänen, A K; Hyyppä, S; Pösö, A R; Ronéus, N; Essén-Gustavsson, B

    2010-12-01

    Monocarboxylate transporter 1 (MCT1) and its ancillary protein CD147 facilitate efflux of lactate from the muscle. Expression of MCT1 and CD147 were studied with immunohistochemistry in type I, IIA, IIAB and IIB fibres of equine gluteal muscle. Staining intensity of MCT1 in the cytoplasm as well as in the membranes of fibre types decreased in the order I=IIA>IIAB>IIB and correlated with the oxidative capacity. Capillaries were pronounced in the MCT1 staining. CD147 antibody stained plasma membranes of all fibre types evenly, whereas the staining in the cytoplasm followed that of MCT1. In the middle gluteal muscle the expression of MCT1 follows the oxidative capacity of muscle fibres, but the expression of CD147 in sarcolemma does not vary among fibre types. The use of horse specific MCT1 and CD147 antibodies can in future studies help to evaluate lactate efflux from different muscle fibre types. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Inhibition effect of flavonoids on monocarboxylate transporter 1 (MCT1) in Caco-2 cells.

    PubMed

    Shim, Chang-Koo; Cheon, Eun-Pa; Kang, Keon Wook; Seo, Ki-Soo; Han, Hyo-Kyung

    2007-11-01

    This study aimed to investigate the inhibition effect of flavonoids on monocarboxylate transporter 1 (MCT1) in Caco-2 cells. The cellular uptake of benzoic acid was examined in the presence and the absence of naringin, naringenin, morin, silybin and quercetin in Caco-2 cells. All the tested flavonoids except naringin significantly inhibited (P<0.05) the cellular uptake of [(14)C]-benzoic acid. Particularly, naringenin and silybin exhibited strong inhibition effects with IC50 values of 23.4 and 30.2 microM, respectively. Kinetic analysis indicated that the inhibition mode of naringenin and silybin on MCT1 activity was competitive with a Ki of 15-20 microM. The effect of flavonoids on the gene expression of MCT1 was also examined by using RT-PCR and western blot analysis. Results indicated that the expression level of MCT1 was not affected by the treatment with naringenin or silybin. The cellular accumulation of naringenin in Caco-2 cells was not changed in the presence of benzoic acid or L-lactic acid, implying that naringenin might not be a substrate of MCT1. In conclusion, some flavonoids appeared to be competitive inhibitors of MCT1, suggesting the potential for diet-drug interactions between flavonoids and MCT1 substrates.

  8. Strain softening along the MCT zone from the Sikkim Himalaya: Relative roles of Quartz and Micas

    NASA Astrophysics Data System (ADS)

    Bhattacharyya, Kathakali; Mitra, Gautam

    2011-06-01

    In the Darjeeling - Sikkim Himalaya, two distinct faults form the Main Central thrust (MCT), the structurally higher MCT1 and the lower MCT2; each has accommodated translation greater than 100 km. The lower MCT2 places Greater Himalayan amphibolite grade Paro-Lingtse gneiss over Lesser Himalayan greenschist grade Daling metapelites. The MCT2 is folded by the underlying Lesser Himalayan duplex and is exposed at different structural positions of the fold. At Pelling, the MCT2 zone is exposed as a ˜373 m thick NW dipping fault zone that exposes ˜19 m of hanging wall mylonitized Lingtse gneiss. The Lingtse protolith shows evidence of amphibolite grade plastic deformation features in quartz and feldspar. Within the hanging wall mylonite zone (HWMZ), quartz and feldspar have undergone grain-size reduction by different deformation mechanisms and feldspars are sericitized suggesting the presence of fluids during deformation. We estimate a temperature of ˜300 °C within the fault zone during fluid-assisted retrogression and deformation. Reaction softening of feldspars produced a large proportion of intrinsically weak matrix. This, in combination with development of a strong foliation defined by parallel mica grains, resulted in strain softening along the MCT2 zone, and concentrated the deformation along a thin zone or zones.

  9. Increased densities of monocarboxylate transporter MCT1 after chronic hyperglycemia in rat brain.

    PubMed

    Canis, Martin; Maurer, Martin H; Kuschinsky, Wolfgang; Duembgen, Lutz; Duelli, Roman

    2009-02-27

    The brain is capable of taking up monocarboxylates as energy substrates. Under physiological conditions, plasma levels of monocarboxylates are very low and glucose is the primary energy substrate in brain metabolism. However, given conditions such as hyperglycemia and ketosis, levels of circulating monocarboxylates such as lactate and pyruvate are elevated. Previous studies reported an increased expression of monocarboxylate transporter MCT1 in brain following ketotic diet. The major aim of the present study was to answer the question whether chronic hyperglycemia is likewise sufficient to change local densities of MCT1 in the brain. Moreover, chronic hyperglycemia increases local cerebral glucose utilization (LCGU) in particular brain areas. Glucose hereby enters the brain parenchyma via glucose transporters and is partially metabolised by astrocytes, which then release lactate to meet the energetic demands of surrounding neurons. Streptozotocin was given intravenously to induce chronic hyperglycemia and local densities of MCT1 were measured by immunoautoradiographic methods in cryosections of rat brains. The density of monocarboxylate transporter MCT1 was significantly increased in 10 of 24 brain structures investigated (median increase 11.7+/-3.4 %). Immunocytochemical stainings of these substructures revealed an expression of MCT1 within endothelial cells and astrocytes. A comparison of MCT1 densities with LCGU measured in a previous study under normo- and hyperglycemic conditions revealed a partial correlation between both parameters and under both conditions. Four out of 10 brain areas, which showed a significant increase in MCT1 density due to hyperglycemia, also showed a significant increase in LCGU. In summary, our data show that chronic hyperglycemia induces a moderate increase of local and global density of MCT1 in several brain structures. However, in terms of brain topologies and substructures this phenomenon did only partially match with increased

  10. Regulation of Acetate Utilization by Monocarboxylate Transporter 1 (MCT1) in Hepatocellular Carcinoma (HCC).

    PubMed

    Jeon, Jeong Yong; Lee, Misu; Whang, Sang Hyun; Kim, Jung-Whan; Cho, Arthur; Yun, Mijin

    2018-01-19

    Altered energy metabolism is a biochemical fingerprint of cancer cells. Hepatocellular carcinoma (HCC) shows reciprocal [18F]fluorodeoxyglucose (FDG) and [11C]acetate uptake, as revealed by positron emission tomography/computed tomography (PET/CT). Previous studies have focused on the role of FDG uptake in cancer cells. In this study, we evaluated the mechanism and roles of [11C]acetate uptake in human HCCs and cell lines. The expression of monocarboxylate transporters (MCTs) was assessed to determine the transporters of [11C]acetate uptake in HCC cell lines and human HCCs with different [11C]acetate uptake. Using two representative cell lines with widely different [11C]acetate uptake (HepG2 for high uptake and Hep3B for low uptake), changes in [11C]acetate uptake were measured after treatment with an MCT1 inhibitor or MCT1-targeted siRNA. To verify the roles of MCT1 in cells, oxygen consumption rate and the amount of lipid synthesis were measured. HepG2 cells with high [11C]acetate uptake showed higher MCT1 expression than other HCC cell lines with low [11C]acetate uptake. MCT1 expression was elevated in human HCCs with high [11C]acetate uptake compared to those with low [11C]acetate uptake. After blocking MCT1 with AR-C155858 or MCT1 knockdown, [11C]acetate uptake in HepG2 cells was significantly reduced. Additionally, inhibition of MCT1 suppressed mitochondrial oxidative phosphorylation, lipid synthesis, and cellular proliferation in HCC cells with high [11C]acetate uptake. MCT1 may be a new therapeutic target for acetate-dependent HCCs with high [11C]acetate uptake, which can be selected by [11C]acetate PET/CT imaging in clinical practice.

  11. Increased densities of monocarboxylate transport protein MCT1 after chronic administration of nicotine in rat brain.

    PubMed

    Canis, Martin; Mack, Brigitte; Gires, Olivier; Maurer, Martin H; Kuschinsky, Wolfgang; Duembgen, Lutz; Duelli, Roman

    2009-08-01

    Chronic administration of nicotine is followed by a general stimulation of brain metabolism that results in a distinct increase of glucose transport protein densities for Glut1 and Glu3, and local cerebral glucose utilization (LCGU). This increase of LCGU might be paralleled by an enhanced production of lactate. Therefore, the question arose as to whether chronic nicotine infusion is accompanied by increased local densities of monocarboxylate transporter MCT1 in the brain. Secondly, we inquired whether LCGU might be correlated with local densities of MCT1 during normal conditions and after chronic nicotine infusion. Nicotine was given subcutaneously for 1 week by osmotic mini-pumps and local densities of MCT1 were measured by immunoautoradiographic methods in cryosections of rat brains. MCT1 density was significantly increased in 21 of 32 brain structures investigated (median increase 15.0+/-3.6%). Immunohistochemical stainings of these substructures revealed an over-expression of MCT1 within endothelial cells and astrocytes of treated animals. A comparison of 23 MCT1 densities with LCGU measured in the same structures in a previous study revealed a partial correlation between both parameters under control conditions and after chronic nicotine infusion. 10 out of 23 brain areas, which showed a significant increase of MCT1 density due to chronic nicotine infusion, also showed a significant increase of LCGU. In summary, our data show that chronic nicotine infusion induces a moderate increase of local and global density of MCT1 in defined brain structures. However, in terms of brain topologies and substructures this phenomenon did partially match with increased LCGU. It is concluded that MCT1 transporters were upregulated during chronic nicotine infusion at the level of brain substructures and, at least partially, independently of LCGU.

  12. Characterization of monocarboxylate transporter 1 (MCT1) binding affinity for Basigin gene products and L1cam.

    PubMed

    Howard, John; Finch, Nicole A; Ochrietor, Judith D

    2010-07-01

    The purpose of this study was to determine the binding affinities of Basigin gene products and neural cell adhesion molecule L1cam for monocarboxylate transporter-1 (MCT1). ELISA binding assays were performed in which recombinant proteins of the transmembrane domains of Basigin gene products and L1cam were incubated with MCT1 captured from mouse brain. It was determined that Basigin gene products bind MCT1 with moderate affinity, but L1cam does not bind MCT1. Despite a high degree of sequence conservation between Basigin gene products and L1cam, the sequences are different enough to prevent L1cam from interacting with MCT1.

  13. MCT Detectors and ROICS for Various Format MWIR and LWIR Arrays

    DTIC Science & Technology

    2009-10-01

    ABSTRACT Silicon ROICs for MCT LWIR (4x288, 6x576) and MWIR (128x128) diode matrix arrays were designed, manufactured and tested. MCT layers...of polysilicon and two metallization levels. MCT Detectors and ROICs for Various Format MWIR and LWIR Arrays RTO-MP-SET-151 7 - 1...Format MWIR and LWIR Arrays 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f

  14. Novel polymeric materials from triglycerides

    USDA-ARS?s Scientific Manuscript database

    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 ...

  15. Meta-analysis of structured triglyceride versus other lipid emulsions for parenteral nutrition.

    PubMed

    Zhu, Mengbai; Li, Xueliang

    2013-06-01

    Structured triglyceride (STG) is a new emulsion synthesized from long-chain fatty acids and medium-chain fatty acids bound to the same glycerol backbone. We performed a meta-analysis to examine the safety, efficacy, and tolerability of STG for parenteral nutrition. We searched MEDLINE, EMBASE, and the Chinese Biomedicine Database, with the last search done in May 2012. Only randomized controlled trials in humans published in Chinese or English were included. Search terms included structured triglyceride and structural lipid. Methodologic quality was evaluated using the Jadad Scale. Meta-analysis was conducted using Review Manager 5.0.24 to calculate the weighted mean difference (WMD) and standardized mean difference (SMD) with 95% confidence intervals. Twenty-one studies (833 participants) published in English or Chinese were included in the analysis. STG significantly affected plasma triglycerides (WMD = -0.15; 95% confidence interval [CI], -0.29 to -0.01; P = 0.04), plasma glycerol (WMD = 0.21; 95% CI, 0.01-0.41; P = 0.04), free fatty acids (WMD = 0.21; 95% CI, 0.03-0.39; P = 0.02), nitrogen balance (SMD = 1.13; 95% CI, 0.26-1.99; P = 0.01), AST (WMD = -5.97; 95% CI, -7.17 to -4.76; P < 0.00001), and glucose (WMD = -0.18; 95% CI, -0.30 to -0.06; P = 004), but not respiratory quotient, resting energy expenditure, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, bilirubin, cholesterol, serum creatinine, or vital signs. STG is rapidly metabolized without harming the liver, and positively affects nitrogen balance. STG is at least as safe and effective for parenteral nutrition as other triglycerides. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. De novo synthesis of milk triglycerides in humans

    PubMed Central

    Mohammad, Mahmoud A.; Sunehag, Agneta L.

    2014-01-01

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

  17. Occurrence, homologue patterns and source apportionment of short- and medium-chain chlorinated paraffins in suburban soils of Shanghai, China.

    PubMed

    Wang, Xue-Tong; Xu, Si-Yue; Wang, Xi-Kui; Hu, Bao-Ping; Jia, Hao-Hao

    2017-08-01

    In order to systematically investigate the spatial distribution, homologue profiles, and sources of short- and medium-chain chlorinated paraffins (SCCPs and MCCPs) in suburban soils in Shanghai, SCCPs and MCCPs in soils were analyzed using gas chromatography coupled with low resolution mass spectrometry in electron capture negative ion (ECNI) mode (GC-ECNI-MS). The CP concentrations in soils were between not detected (ND) - 697 ng g -1 with a median value of 3.52 ng g -1 for SCCPs, and ND - 666 ng g -1 with a median value of 15.3 ng g -1 for MCCPs, respectively. The concentrations of MCCPs in most soils were higher than that of SCCPs. The total CP concentrations (sum of SCCPs and MCCPs) in soils varied from ND to 964 ng g -1 with a median value of 20.5 ng g -1 . The concentration of MCCPs was higher than that of SCCPs in most soils. The levels of SCCPs and MCCPs in suburban soils in Shanghai were at the medium level when compared to other areas around the world. No significant correlation was observed between soil CP concentrations and total organic carbon contents (p > 0.05). For different use type of soils, the median concentrations of CPs in soils were found higher in greenland than that in other areas probably due to busy traffic, sewage sludge application and/or wastewater irrigation. All soils were divided into two groups by hierarchical cluster analysis (HCA) both for SCCPs and MCCPs. Three discharge sources of CPs in suburban soil of Shanghai were identified by PMF model. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. 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

    2015-10-06

    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.

  19. Cellular and Molecular Responses of Dunaliella tertiolecta by Expression of a Plant Medium Chain Length Fatty Acid Specific Acyl-ACP Thioesterase

    PubMed Central

    Lin, Huixin; Shen, Hui; Lee, Yuan K.

    2018-01-01

    Metabolic engineering of microalgae to accumulate high levels of medium chain length fatty acids (MCFAs) has met with limited success. Traditional approaches employ single introduction of MCFA specific acyl-ACP thioesterases (TEs), but our current research in transgenic Dunaliella tertiolecta line has highlighted that, there is no single rate-limiting approach that can effectively increase MCFA levels. Here, we explore the accumulation of MCFAs in D. tertiolecta after transgenic expression of myristic acid biased TE (C14TE). We observe that the MCFA levels were negatively correlated to the fatty acid (FA) synthesis genes, ketoacyl-ACP synthase II (KASII), stearoyl-CoA-9-desaturase (Δ9D), and oleoyl-CoA-12-desaturase (Δ12D). To further examine the molecular mechanism of MCFA accumulation in microalgae, we investigate the transcriptomic dynamics of the MCFA producing strain of D. tertiolecta. At the transcript level, enhanced MCFA accumulation primarily involved up-regulation of photosynthetic genes and down-regulation of genes from central carbon metabolic processes, resulting in an overall decrease in carbon precursors for FA synthesis. We additionally observe that MCFA specific peroxisomal β-oxidation gene (ACX3) was greatly enhanced to prevent excessive build-up of unusual MCFA levels. Besides, long chain acyl-CoA synthetase gene (LACS) was down-regulated, likely in attempt to control fatty acyl supply flux to FA synthesis cycle. This article provides a spatial regulation model of unusual FA accumulation in microalgae and a platform for additional metabolic engineering targeting pathways from FA synthesis, FA transport, and peroxisomal β-oxidation to achieve microalgae oils with higher levels of MCFAs. PMID:29670594

  20. Functional role of a distal (3'-phosphate) group of CoA in the recombinant human liver medium-chain acyl-CoA dehydrogenase-catalysed reaction.

    PubMed Central

    Peterson, K L; Srivastava, D K

    1997-01-01

    The X-ray crystallographic structure of medium-chain acyl-CoA dehydrogenase (MCAD)-octenoyl-CoA complex reveals that the 3'-phosphate group of CoA is confined to the exterior of the protein structure [approx. 15 A (1.5 nm) away from the enzyme active site], and is fully exposed to the outside solvent environment. To ascertain whether such a distal (3'-phosphate) fragment of CoA plays any significant role in the enzyme catalysis, we investigated the recombinant human liver MCAD (HMCAD)-catalysed reaction by using normal (phospho) and 3'-phosphate-truncated (dephospho) forms of octanoyl-CoA and butyryl-CoA substrates. The steady-state kinetic data revealed that deletion of the 3'-phosphate group from octanoyl-CoA substrate increased the turnover rate of the enzyme to about one-quarter, whereas that from butyryl-CoA substrate decreased the turnover rate of the enzyme to about one-fifth; the Km values of both these substrates were increased by 5-10-fold on deletion of the 3'-phosphate group from the corresponding acyl-CoA substrates. The transient kinetics for the reductive half-reaction, oxidative half-reaction and the dissociation 'off-rate' (of the reaction product from the oxidized enzyme site) were all found to be affected by deletions of the 3'-phosphate group from octanoyl-CoA and butyryl-CoA substrates. A cumulative account of these results reveals that, although the 3'-phosphate group of acyl-CoA substrates might seem 'useless' on the basis of the structural data, it has an essential functional role during HMCAD catalysis. PMID:9271097

  1. Short- and medium-chain chlorinated paraffins in sediments from the middle reaches of the Yangtze River: Spatial distributions, source apportionment and risk assessment.

    PubMed

    Qiao, Lin; Gao, Lirong; Xia, Dan; Huang, Huiting; Zheng, Minghui

    2017-01-01

    Chlorinated paraffins (CPs) are easily adsorbed into sediments where they pose potential risks to the ecosystem and human health. Few studies have investigated short- and medium-chain CPs (SCCPs and MCCPs) in sediments. The aim of the present study was to comprehensively investigate contamination levels, spatial distributions, sources and risks posed by CPs in sediments from the middle reaches of the Yangtze River. The sediment samples were analyzed by two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC×GC-TOFMS). The concentrations of SCCPs and MCCPs ranged from 4.19 to 41.6ng/g dry weight (dw) and not detected to 14.6ng/g dw, respectively. No significant correlation was found between the total organic carbon contents and CP concentrations (P>0.05). The spatial distributions showed that CP contamination levels in the sediments were related to local human activities. The dominant congener groups were C 10-11 Cl 6-7 for SCCPs, and C 14 Cl 7-8 for MCCPs. Correspondence analysis revealed that likely sources of SCCPs were the production and use of CP-42 and CP-52. Principal component analysis indicated that SCCPs and MCCPs in the sediments may come from different sources. Moreover, CPs with nine carbon atoms were quantitated for the first time in sediment samples, and the results indicated they should not be neglected in future analyses. Risk assessments indicated that CPs in the sediments did not pose a great ecological risk currently. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Occurrences, sources and risk assessment of short- and medium-chain chlorinated paraffins in sediments from the middle reaches of the Yellow River, China.

    PubMed

    Qiao, Lin; Xia, Dan; Gao, Lirong; Huang, Huiting; Zheng, Minghui

    2016-12-01

    Chlorinated paraffins (CPs), one class of hydrophobic and toxic compounds, are easily adsorbed into sediments and then pose potential risks to the ecosystem and human health. However, few researches on short- and medium-chain CPs (SCCPs and MCCPs) in sediments have been performed. In order to comprehensively investigate the spatial distributions, sources, and ecological risks of CPs, sediments collected from the middle reaches of the Yellow River were analyzed by two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC × GC-TOFMS). The concentrations of SCCPs and MCCPs ranged from 11.6 to 9.76 × 10 3  ng/g dry weight (dw) and from 8.33 to 168 ng/g dw, respectively. No significant correlation was found between total organic carbon (TOC) and CP concentrations (P > 0.05). The spatial distributions showed that contamination levels of CPs were relevant to human activities. In addition, two types of sediment samples were classified by hierarchical cluster analysis (HCA) and results indicated the predominant congener groups were C 10 Cl 6-7 for SCCPs and C 14 Cl 7-8 for MCCPs. Principal component analysis (PCA) revealed that SCCPs and MCCPs in the sediments may have different sources, and SCCPs are likely to come from the production and use of CP-42 and CP-52. Moreover, complex environmental processes, including long-range transportation via the atmosphere and/or river, deposition and degradation of CPs, resulted in increased abundances of short chain and low chlorinated congeners in sediment samples compared with commercial mixtures, and different homolog patterns among samples. The significant negative correlation between SCCP concentrations and MCCP/SCCP ratios could be related to long-range transport of CPs. A preliminary risk assessment indicated that CPs at current levels posed no significant ecological risk. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Health risks posed to infants in rural China by exposure to short- and medium-chain chlorinated paraffins in breast milk.

    PubMed

    Xia, Dan; Gao, Li-Rong; Zheng, Ming-Hui; Li, Jing-Guang; Zhang, Lei; Wu, Yong-Ning; Qiao, Lin; Tian, Qi-Chang; Huang, Hui-Ting; Liu, Wen-Bin; Su, Gui-Jin; Liu, Guo-Rui

    2017-06-01

    Chlorinated paraffins (CPs) are complex mixtures of synthetic chemicals found widely in environmental matrices. Short-chain CPs (SCCPs) are candidate persistent organic pollutants under the Stockholm Convention. There should be great concern about human exposure to SCCPs. Data on CP concentrations in human breast milk is scarce. This is the first study in which background SCCP and medium-chain CP (MCCP) body burdens in the general rural population of China have been estimated and health risks posed to nursing infants by CPs in breast milk assessed. The concentrations of 48 SCCP and MCCP formula congeners were determined in 24 pooled human milk samples produced from 1412 individual samples from eight provinces in 2007 and 16 provinces in 2011. The samples were analyzed by comprehensive two-dimensional gas chromatography electron capture negative ionization high-resolution time-of-flight mass spectrometry. The median SCCP and MCCP concentrations were 303 and 35.7ngg -1 lipid weight, respectively, for the 2007 samples and 360 and 45.4ngg -1 lipid weight, respectively, for the 2011 samples. The C 10 and C 14 homologs were the dominant CP carbon-chain-length groups, contributing 51% and 82% of the total SCCP and MCCP concentrations, respectively. There are probably multiple CP sources to the general Chinese population and numerous exposure pathways. The median estimated daily SCCP and MCCP intakes for nursing infants were 1310 and 152ngkg -1 d -1 , respectively, in 2007 and 1520 and 212ngkg -1 d -1 , respectively, in 2011. SCCPs do not currently pose significant risks to infants in China. However, it is necessary to continuously monitor CP concentrations and health risks because CP concentrations in Chinese human breast milk are increasing. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. The health system impact of false positive newborn screening results for medium-chain acyl-CoA dehydrogenase deficiency: a cohort study.

    PubMed

    Karaceper, Maria D; Chakraborty, Pranesh; Coyle, Doug; Wilson, Kumanan; Kronick, Jonathan B; Hawken, Steven; Davies, Christine; Brownell, Marni; Dodds, Linda; Feigenbaum, Annette; Fell, Deshayne B; Grosse, Scott D; Guttmann, Astrid; Laberge, Anne-Marie; Mhanni, Aizeddin; Miller, Fiona A; Mitchell, John J; Nakhla, Meranda; Prasad, Chitra; Rockman-Greenberg, Cheryl; Sparkes, Rebecca; Wilson, Brenda J; Potter, Beth K

    2016-02-03

    There is no consensus in the literature regarding the impact of false positive newborn screening results on early health care utilization patterns. We evaluated the impact of false positive newborn screening results for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in a cohort of Ontario infants. The cohort included all children who received newborn screening in Ontario between April 1, 2006 and March 31, 2010. Newborn screening and diagnostic confirmation results were linked to province-wide health care administrative datasets covering physician visits, emergency department visits, and inpatient hospitalizations, to determine health service utilization from April 1, 2006 through March 31, 2012. Incidence rate ratios (IRRs) were used to compare those with false positive results for MCADD to those with negative newborn screening results, stratified by age at service use. We identified 43 infants with a false positive newborn screening result for MCADD during the study period. These infants experienced significantly higher rates of physician visits (IRR: 1.42) and hospitalizations (IRR: 2.32) in the first year of life relative to a screen negative cohort in adjusted analyses. Differences in health services use were not observed after the first year of life. The higher use of some health services among false positive infants during the fir