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Sample records for medium-chain triglycerides mct

  1. 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.

  2. 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

  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. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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

  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-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. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 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.

  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. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  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. 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.

  12. 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.

  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. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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

  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. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  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. 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.

  11. Studies on self-nanoemulsifying drug delivery system of flurbiprofen employing long, medium and short chain triglycerides.

    PubMed

    Daar, Junaid; Khan, Ahmad; Khan, Jallat; Khan, Amjad; Khan, Gul Majid

    2017-03-01

    The aim of the study was to successfully design, formulate and evaluate self-nanoemulsifying drug delivery system (SNEDDS) of poorly aqueous soluble drug viz. flurbiprofen using long (LCT), medium (MCT) and short chain triglycerides (SCT). The SNEDDS are thermodynamically stable lipid based drug delivery systems which consist of mixture of oil, surfactant and co-surfactant. Upon aqueous dilution, this mixture produces nano-emulsion spontaneously on slight agitation. The excipients intended to be used were screened for their potential to dissolve the drug and to form clear dispersion upon aqueous dilution. Labrafil M 1944 CS, capryol-90 and triacetin were selected as long, medium and short chain triglycerides, respectively, as lipids while tween-80 and polyethylene glycol-400 (PEG-400)/ethanol (3:1 ratio) were selected as surfactant and co-surfactant, respectively. The excipients were studied at every possible combination ratios using pseudo-ternary diagram. The LCT, MCT and SCT-SNEDDS were optimized using thermodynamic studies, percentage transmittance value, viscosity, refractive index (RI), electrical conductivity, globule size analysis and in-vitro drug release studies. The drug release profiles of optimized SNEDDS were then compared with market product at different pH mediums. The LCT-SNEDDS was considered to be superior for enhancement of the drug bioavailability when compared with other SNEDDS formulations and market product.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  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. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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

  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. 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.

  10. 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.

  11. 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

  12. 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®

  13. 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.

  14. 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.

  15. 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)

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  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. 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

  11. 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.

  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. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. [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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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...

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  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. 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)

  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. 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

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. [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.

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

    PubMed Central

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

    2002-01-01

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

  20. 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

  1. 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.

  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. 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

  4. Tissue-specific strategies of the very-long chain acyl-CoA dehydrogenase-deficient (VLCAD-/-) mouse to compensate a defective fatty acid β-oxidation.

    PubMed

    Tucci, Sara; Herebian, Diran; Sturm, Marga; Seibt, Annette; Spiekerkoetter, Ute

    2012-01-01

    Very long-chain acyl-CoA dehydrogenase (VLCAD)-deficiency is the most common long-chain fatty acid oxidation disorder presenting with heterogeneous phenotypes. Similar to many patients with VLCADD, VLCAD-deficient mice (VLCAD(-/-)) remain asymptomatic over a long period of time. In order to identify the involved compensatory mechanisms, wild-type and VLCAD(-/-) mice were fed one year either with a normal diet or with a diet in which medium-chain triglycerides (MCT) replaced long-chain triglycerides, as approved intervention in VLCADD. The expression of the mitochondrial long-chain acyl-CoA dehydrogenase (LCAD) and medium-chain acyl-CoA dehydrogenase (MCAD) was quantified at mRNA and protein level in heart, liver and skeletal muscle. The oxidation capacity of the different tissues was measured by LC-MS/MS using acyl-CoA substrates with a chain length of 8 to 20 carbons. Moreover, in white skeletal muscle the role of glycolysis and concomitant muscle fibre adaptation was investigated. In one year old VLCAD(-/-) mice MCAD and LCAD play an important role in order to compensate deficiency of VLCAD especially in the heart and in the liver. However, the white gastrocnemius muscle develops alternative compensatory mechanism based on a different substrate selection and increased glucose oxidation. Finally, the application of an MCT diet over one year has no effects on LCAD or MCAD expression. MCT results in the VLCAD(-/-) mice only in a very modest improvement of medium-chain acyl-CoA oxidation capacity restricted to cardiac tissue. In conclusion, VLCAD(-/-) mice develop tissue-specific strategies to compensate deficiency of VLCAD either by induction of other mitochondrial acyl-CoA dehydrogenases or by enhancement of glucose oxidation. In the muscle, there is evidence of a muscle fibre type adaptation with a predominance of glycolytic muscle fibres. Dietary modification as represented by an MCT-diet does not improve these strategies long-term.

  5. 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.

  6. Comparison of diet-induced thermogenesis of foods containing medium- versus long-chain triacylglycerols.

    PubMed

    Kasai, Michio; Nosaka, Naohisa; Maki, Hideaki; Suzuki, Yoshie; Takeuchi, Hiroyuki; Aoyama, Toshiaki; Ohra, Atsushi; Harada, Youji; Okazaki, Mitsuko; Kondo, Kazuo

    2002-12-01

    The purpose of this study was to investigate the effect of 5-10 g of medium-chain triacylglycerols (MCT) on diet-induced thermogenesis in healthy humans. The study compared diet-induced thermogenesis after ingestion of test foods containing MCT and long-chain triacylglycerols (LCT), using a double-blind, crossover design. Eight male and eight female subjects participated in study 1 and study 2, respectively. In both studies, the LCT was a blend of rapeseed oil and soybean oil. In study 1, the liquid meals contained 10 g MCT (10M), a mixture of 5 g MCT and 5 g LCT (5M5L), and 10 g LCT (10L). In study 2, the subjects were given a meal (sandwich and clear soup) with the mayonnaise or margarine containing 5 g of MCT or LCT. Postprandial energy expenditure was measured by indirect calorimetry before and during the 6 h after ingestion of the test meals. Diet-induced thermogenesis was significantly greater after 5M5L and 10M Ingestion as compared to 10L ingestion. Ingestion of the mayonnaise or margarine containing 5 g MCT caused significantly larger diet-induced thermogenesis as compared to that of LCT. These results suggest that, in healthy humans, the intake of 5-10 g of MCT causes larger diet-induced thermogenesis than that of LCT, irrespective of the form of meal containing the MCT.

  7. 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.

  8. 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.

  9. 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.

  10. Branched-chain ketoacids secreted by glioblastoma cells via MCT1 modulate macrophage phenotype.

    PubMed

    Silva, Lidia Santos; Poschet, Gernot; Nonnenmacher, Yannic; Becker, Holger M; Sapcariu, Sean; Gaupel, Ann-Christin; Schlotter, Magdalena; Wu, Yonghe; Kneisel, Niclas; Seiffert, Martina; Hell, Rüdiger; Hiller, Karsten; Lichter, Peter; Radlwimmer, Bernhard

    2017-12-01

    Elevated amino acid catabolism is common to many cancers. Here, we show that glioblastoma are excreting large amounts of branched-chain ketoacids (BCKAs), metabolites of branched-chain amino acid (BCAA) catabolism. We show that efflux of BCKAs, as well as pyruvate, is mediated by the monocarboxylate transporter 1 (MCT1) in glioblastoma. MCT1 locates in close proximity to BCKA-generating branched-chain amino acid transaminase 1, suggesting possible functional interaction of the proteins. Using in vitro models, we demonstrate that tumor-excreted BCKAs can be taken up and re-aminated to BCAAs by tumor-associated macrophages. Furthermore, exposure to BCKAs reduced the phagocytic activity of macrophages. This study provides further evidence for the eminent role of BCAA catabolism in glioblastoma by demonstrating that tumor-excreted BCKAs might have a direct role in tumor immune suppression. Our data further suggest that the anti-proliferative effects of MCT1 knockdown observed by others might be related to the blocked excretion of BCKAs. © 2017 The Authors.

  11. 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.

  12. 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.

  13. 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.

  14. [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

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

    PubMed

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

    1993-03-01

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

  16. 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.

  17. 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.

  18. Dietary intake of the short-chain triglyceride triacetin vs. long-chain triglycerides decreases adipocyte diameter and fat deposition in rats.

    PubMed

    Lynch, J W; Bailey, J W

    1995-05-01

    Diets containing either triacetin (the water-soluble triglyceride of acetate) or long-chain triglycerides (LCT) were fed to rats for 30 d to determine the effect on body weight gain and adipose tissue cellularity. Male Sprague-Dawley rats were allowed free access to one of three diets: a control diet containing 5% of energy as fat or one of two experimental diets that contained 30% triglyceride (by energy). The source of the triglyceride in the two experimental groups was either 100% LCT or 95% triacetin + 5% LCT. Within the experimental groups receiving 30% fat, the source of dietary triglyceride (LCT vs. triacetin) did not affect total energy consumption. There were no significant differences in body weight at the onset of the study; however, animals fed 100% LCT weighed significantly more than the other two groups at the end of the study. In all three fat pads studied, animals fed triacetin had significantly lower pad mass than did animals fed LCT. Mean fat cell size was smaller in fat depots of animals fed short-chain triglyceride. Provision of dietary energy as the short-chain triglyceride triacetin in lieu of LCT resulted in lower weight gain and fat deposition. These data demonstrate the impact of dietary triglyceride composition on body weight regulation.

  19. Structured triglyceride for parenteral nutrition: meta-analysis of randomized controlled trials.

    PubMed

    Zhou, Yong; Wu, Xiao-Ting; Li, Ni; Zhuang, Wen; Liu, Guanjian; Wu, Taixiang; Wei, Mao-Ling

    2006-01-01

    This study assessed the safety and efficacy of structured triglyceride (ST) for parenteral nutrition. A meta-analysis of all the relevant randomized controlled trials (RCTs) was performed. Clinical trials were identified from the following electronic databases: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, Chinese Bio-medicine Database. The search was undertaken in March 2005. Language was restricted to Chinese and English. Literature references were checked at the same time. Only RCTs were extracted and evaluated by two reviewers independently of each other. The statistical analysis was performed by RevMan4.2 software which was provided by the Cochrane Collaboration. A P value of <0.05 was considered statistically significant. Ten RCTs involving 236 patients were included. Eight of them compared ST with the long-chain triglyceride (LCT), and the combined results showed that the ST had significant effect on resting energy expenditure (weighted mean difference [WMD] =1.54, 95%CI [ 1.26, 1.82], p<0.00001), plasma glycerol (WMD = 0.14, 95%CI [0.06, 0.22], P= 0.0007), free fatty acids (WMD=0.24, 95%CI [0.10, 0.37], P=0.0006), and beta-hydroxybutyric acid (WMD=0.14, 95%CI [0.06, 0.22], P=0.0007), but no differences was found regarding nitrogen balance (standardized mean difference [SMD] = 0.64, 95%CI [-0.30, 1.59], P=0.18), respiratory quotient (WMD =-0.02, 95%CI [-0.04, 0.01], P= 0.18), and plasma triglycerides (WMD = -0.10, 95%CI [-0.30, 0.10], P=0.32). Only two RCTs compared ST with the physical mixture of medium- and long-chain triglyceride (MCT/LCT), data from trials were not combined due to clinical differences between trials, and conclusions can not be drew from the present data. ST appeared to be safe and well tolerated. Further trials are required, especially compared with the MCT/LCT, with sufficient size and rigorous design.

  20. 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.

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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.

  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. 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.

  8. A polymorphism in the gene encoding procolipase produces a colipase, Arg92Cys, with decreased function against long-chain triglycerides

    PubMed Central

    D’Silva, Sheryl; Xiao, Xunjun; Lowe, Mark E.

    2013-01-01

    Type 2 diabetes mellitus is a multifactorial and polygenic disorder with increasing prevalence. Recently, a polymorphism in the gene encoding procolipase, a cysteine for arginine substitution at position 92, was associated with type 2 diabetes in two human populations. Because procolipase plays a critical role in dietary fat metabolism, polymorphisms that affect the function of procolipase could influence the development of type 2 diabetes. We hypothesized that the Arg92Cys polymorphism has functional consequences. To test our hypothesis, we expressed recombinant cysteine 92 (Cys92) procolipase in a yeast expression system and compared the function and stability of purified Cys92 with that of the more common arginine 92 (Arg92) procolipase. Cys92 fully restored the activity of bile-salt inhibited lipase with short- and medium-chain triglycerides but only had 50% of Arg92 function with long-chain triglycerides. After storage at 4°C, Cys92 lost the ability to restore pancreatic triglyceride lipase activity with medium- and long-chain triglycerides. The loss of function correlated with the inability of Cys92 to anchor lipase on an emulsion surface and oxidation of the cysteine. No detectable degradation or intramolecular disulfide formation occurred in Cys92 after storage. Our findings demonstrate that the Arg92Cys polymorphism decreases the function of Cys92 colipase. This change may contribute to the development of type 2 diabetes. PMID:17715423

  9. Solubilisation of poorly water-soluble drugs during in vitro lipolysis of medium- and long-chain triacylglycerols.

    PubMed

    Christensen, Janne Ørskov; Schultz, Kirsten; Mollgaard, Birgitte; Kristensen, Henning Gjelstrup; Mullertz, Anette

    2004-11-01

    The partitioning of poorly soluble drugs into an aqueous micellar phase was exploited using an in vitro lipid digestion model, simulating the events taking place during digestion of acylglycerols in the duodenum. The aqueous micellar phase was isolated after ultracentrifugation of samples obtained at different degrees of triacylglycerol hydrolysis. Flupentixol, 1'-[4-[1-(4-fluorophenyl)-1-H-indol-3-yl]-1-butyl]spiro[iso-benzofuran-1(3H), 4' piperidine] (LU 28-179) and probucol were studied. The effect of the alkyl chain length of the triacylglycerol was studied using a medium-chain triacylglycerol (MCT) and a long-chain triacylglycerol (LCT), respectively. In general, an oil solution was used as the lipid source in the model. Samples were analysed in regard to micellar size, lipid composition and drug concentration. During lipolysis, the content of lipolytic products in the aqueous micellar phase increased. The micellar size (R(H) approximately 3 nm) only increased when long-chain lipolytic products were incorporated in the mixed micelles (R(H) approximately 7.8 nm). Flupentixol was quickly transferred to the mixed micelles due to high solubility in this phase (100% released). A tendency towards higher solubilisation of LU 28-179, when it was administered in the LCT (approximately 24% released) compared to when it was administered in the MCT (approximately 15% released) at 70% hydrolysis, and a lagphase was observed. There was no difference in the solubilisation of probucol using MCT or LCT ( approximately 20% released), respectively. Differences in the physicochemical properties of the drugs resulted in differences in their distribution between the phases arising during lipolysis.

  10. 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

  11. 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.

  12. 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.

  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. 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.

  15. Feasibility and Efficacy of Defatted Human Milk in the Treatment for Chylothorax After Cardiac Surgery in Infants.

    PubMed

    Fogg, Kristi L; DellaValle, Diane M; Buckley, Jason R; Graham, Eric M; Zyblewski, Sinai C

    2016-08-01

    Chylothorax is a well-described complication after cardiothoracic surgery in children. Medical nutritional therapy for chylothorax includes medium-chain triglyceride (MCT) formulas and reduction in enteral long-chain triglyceride intake to reduce chyle production. Human milk is usually eliminated from the diet of infants with chylothorax because of its high long-chain triglyceride content. However, given the immunologic properties of human milk, young infants with chylothorax may benefit from using human milk over human milk substitutes. We performed a retrospective cohort study to describe the feasibility and efficacy of defatted human milk (DHM) for the treatment for chylothorax in infants after cardiac surgery and to compare growth outcomes between infants treated with DHM (n = 14) versus MCT formula (n = 21). There were no differences in mortality or length of hospital stay between the DHM and MCT formula treatment groups. The DHM treatment group had a significantly higher weight-for-age z-score at hospital discharge compared to the MCT formula group with median z-scores of -1 (-2 to 0.5) and -1.5 (-2 to 0), respectively (p = 0.02). In infants with chylothorax after cardiac surgery, DHM is a safe and feasible medical nutritional treatment and may have potential benefits for improved nutrition and growth.

  16. 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.

  17. Relief from Back Pain Through Postural Adjustment: a Controlled Clinical Trial of the Immediate Effects of Muscular Chains Therapy (MCT).

    PubMed

    Rosario, Jose L

    2014-09-01

    Back pain can be one of the most common health problems, causing suffering, disabilities, and financial losses. Postural models for pain treatment state that poor posture alters the joint position and causes pain, such as back pain. Muscular Chain Therapy (MCT) is a technique that is used to treat posture pathologies, among others. The aim of the present study was to assess the efficiency of a single session of Muscular Chain Therapy (MCT) on complaints of undiagnosed musculoskeletal spinal pain. Physical therapy clinic of the University of Center-West (Guarapuava, Brazil). 100 subjects, aged between 20 and 39 years, with complaints of spinal musculoskeletal pain. Randomized controlled trial. The participants were randomly assigned by a non-care provider into two groups: The MCT Group that received Muscular Chain Treatment and the Control Group that received a placebo treatment of 15 minutes turned off ultrasound therapy. All volunteers were assessed before and after treatment using an analog pain scale. A score of 0 indicated no pain and 10 was the maximum degree of pain on the scale. Degree of pain measured by analog scale. The chi-square goodness of fit test was used to compare gender distribution among groups displayed a p value = .25. Subject age had differences analyzed using the unpaired t test (p = .44). Pain assessment for treatment and placebo control groups was analyzed using a paired t test and unpaired t test. The paired t test was used for intragroup before/after treatment comparison (MCT p = .00001; Control Group p = .0001). The unpaired t test was used for comparing the difference of the pain level before and after treatment between groups (p = .0001). A priori statistical significance was set a p = .05. It is possible to conclude that one MCT session is an effective treatment of undiagnosed spinal musculoskeletal pain.

  18. Fatty acid chain length, postprandial satiety and food intake in lean men.

    PubMed

    Poppitt, S D; Strik, C M; MacGibbon, A K H; McArdle, B H; Budgett, S C; McGill, A-T

    2010-08-04

    High-fat diets are associated with obesity, and the weak satiety response elicited in response to dietary lipids is likely to play a role. Preliminary evidence from studies of medium (MCT) and long chain triglycerides (LCT) supports greater appetite suppression on high-MCT diets, possibly a consequence of direct portal access, more rapid oxidation and muted lipaemia. No data is as yet available on high-SCT diets which also have direct hepatic access. In this study SCT- (dairy fats), MCT- (coconut oil) and LCT-enriched (beef tallow) test breakfasts (3.3 MJ) containing 52 g lipid (58 en% fat) were investigated in a randomized, cross-over study in 18 lean men. All participants were required to complete the 3 study days in randomised order. Participants rated appetite sensations using visual analogue scales (VAS), and energy intake (EI) was measured by covert weighing of an ad libitum lunch meal 3.5 h postprandially. Blood samples were collected by venous cannulation. There were no detectable differences between breakfasts in perceived pleasantness, visual appearance, smell, taste, aftertaste and palatability (P>0.05). There was no significant effect of fatty acid chain length on ratings of hunger, fullness, satisfaction or current thoughts of food, nor did energy (mean, sem: SCT: 4406, 366 kJ; MCT: 4422, 306 kJ; LCT: 4490, 324 kJ; P>0.05) or macronutrient intake at lunch differ between diets. The maximum difference in EI between diets was less than 2%. Postprandial lipaemia also did not differ significantly. We conclude that there was no evidence that fatty acid chain length has an effect on measures of appetite and food intake when assessed following a single high-fat test meal in lean participants. Copyright 2010 Elsevier Inc. All rights reserved.

  19. 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.

  20. Structured versus long-chain triglycerides: a safety, tolerance, and efficacy randomized study in colorectal surgical patients.

    PubMed

    Bellantone, R; Bossola, M; Carriero, C; Malerba, M; Nucera, P; Ratto, C; Crucitti, P; Pacelli, F; Doglietto, G B; Crucitti, F

    1999-01-01

    After trauma or surgery, researchers have suggested that medium-chain triglycerides have metabolic advantages, although they are toxic in large doses. To try to reduce this potential toxicity, structured lipids, which provide a higher oxidation rate, faster clearance from blood, improved nitrogen balance, and less accumulation in the reticuloendothelial system, could be used. Therefore, we evaluated, through a blind randomized study, the safety, tolerance, and efficacy of structured triglycerides, compared with long-chain triglycerides (LCT), in patients undergoing colorectal surgery. Nineteen patients were randomized to receive long-chain or structured triglycerides as a lipid source. They received the same amount of calories (27.2/kg/d), glucose (4 g/kg/d), protein (0.2 g/kg/d), and lipids (11.2 kcal/kg/d). Patients were evaluated during and after the treatment for clinical and laboratory variables, daily and cumulative nitrogen balance, urinary excretion of 3-methyl-histidine, and urinary 3-methylhistidine/creatinine ratio. No adverse effect that required the interruption of the treatment was observed. Triglyceride levels and clinical and laboratory variables were similar in the two groups. A predominantly positive nitrogen balance was observed from day 2 until day 5 in the LCT group and from day 1 until day 4 in the structured triglycerides group. The cumulative nitrogen balance (in grams) for days 1 to 3 was 9.7+/-5.2 in the experimental group and 4.4+/-11.8 in the control group (p = .2). For days 1 to 5 it was 10.7+/-10.5 and 6.5+/-17.9 (p = .05), respectively. The excretion of 3-methylhistidine was higher in the control group but decreased in the following days and was similar to the experimental group on day 5. This study represents the first report in which structured triglycerides are administered in postoperative patients to evaluate safety, tolerance, and efficacy. It suggests that Fe73403 is safe, well tolerated, and efficacious in terms of nitrogen

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. Lipid emulsions differentially affect LPS-induced acute monocytes inflammation: in vitro effects on membrane remodeling and cell viability.

    PubMed

    Boisramé-Helms, Julie; Delabranche, Xavier; Klymchenko, Andrey; Drai, Jocelyne; Blond, Emilie; Zobairi, Fatiha; Mely, Yves; Hasselmann, Michel; Toti, Florence; Meziani, Ferhat

    2014-11-01

    The aim of this study was to assess how lipid emulsions for parenteral nutrition affect lipopolysaccharide (LPS)-induced acute monocyte inflammation in vitro. An 18 h long LPS induced human monocyte leukemia cell stimulation was performed and the cell-growth medium was supplemented with three different industrial lipid emulsions: Intralipid(®), containing long-chain triglycerides (LCT--soybean oil); Medialipid(®), containing LCT (soybean oil) and medium-chain triglycerides (MCT--coconut oil); and SMOFlipid(®), containing LCT, MCT, omega-9 and -3 (soybean, coconut, olive and fish oils). Cell viability and apoptosis were assessed by Trypan blue exclusion and flow cytometry respectively. Monocyte composition and membrane remodeling were studied using gas chromatography and NR12S staining. Microparticles released in supernatant were measured by prothrombinase assay. After LPS challenge, both cellular necrosis and apoptosis were increased (threefold and twofold respectively) and microparticle release was enhanced (sevenfold) after supplementation with Medialipid(®) compared to Intralipid(®), SMOFlipid(®) and monocytes in the standard medium. The monocytes differentially incorporated fatty acids after lipid emulsion challenge. Finally, lipid-treated cells displayed microparticles characterized by disrupted membrane lipid order, reflecting lipid remodeling of the parental cell plasma membrane. Our data suggest that lipid emulsions differentially alter cell viability, monocyte composition and thereby microparticle release. While MCT have deleterious effects, we have shown that parenteral nutrition emulsion containing LCT or LCT and MCT associated to n-3 and n-9 fatty acids have no effect on endotoxin-induced cell death and inflammation.

  8. 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.

  9. 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.

  10. Olive Oil-Based Lipid Emulsions Do Not Influence Platelet Receptor Expression in Comparison to Medium and Long Chain Triglycerides In vitro.

    PubMed

    Stoetzer, Carsten; Nickel, Katja; Weißig, Annette; Großheim, Marieke; Scheinichen, Dirk; Doll, Thorben; Jüttner, Björn

    2016-11-01

    Lipid emulsions influence platelet aggregation and receptor expression. However, the effect on platelet function is not fully explained. Therefore, the aim of this study was to examine the influence of the lipids Lipofundin ® , Lipidem ® and ClinOleic ® on surface expressions of P-selectin, GPIb and GPIIb/IIIa on platelets in vitro. Whole blood was incubated in two different concentrations (0.06 and 0.6 mg/ml) of LCT/MCT, n-3/LCT/MCT and LCT-MUFA for 30 min, followed by activation with TRAP-6 or ADP for flow-cytometric assay. Rates of P-selectin, GPIb and GPIIb/IIIa expression were analyzed. There was a significant increase in GPIIb/IIIa- and P-selectin-expression after incubation with LCT/MCT and n-3/LCT/MCT at the concentration of 0.6 mg/ml, without and after stimulation with TRAP-6 and ADP. GPIb was significantly decreased. Accordingly, LCT-MUFA had no effect on receptor expression of platelets in vitro. We demonstrated that LCT-MUFA did not activate receptor expression of platelets whereas LCT/MCT significantly increased platelet aggregation in vitro. This finding should be noted for parenteral nutrition of intensive care patients and, in the future, might provide further insight into the pathogenic pathways of acute thromboembolic events. However, prospectively designed clinical studies are needed to support our results.

  11. Fats infused intraduodenally affect the postprandial secretion of the exocrine pancreas and the plasma concentration of cholecystokinin but not of peptide YY in growing pigs.

    PubMed

    Jakob, S; Mosenthin, R; Zabielski, R; Rippe, C; Winzell, M S; Gacsalyi, U; Laubitz, D; Grzesiuk, E; Pierzynowski, S G

    2000-10-01

    In pigs, the spontaneous secretion of the exocrine pancreas and the release of cholecystokinin (CCK) and peptide YY (PYY) after intraduodenal infusion of fully saturated synthetic fats differing in chain length was studied. Growing pigs (n = 6) were prepared with pancreatic duct catheters, duodenal T-cannulas and catheters placed in the jugular vein. The pigs were fed 2 g/100 g body twice daily. Beginning with the morning feeding, a medium-chain triglyceride (MCT: glycerol tricaprylate), a long-chain triglyceride (LCT: glycerol tristearate) or saline was infused at a rate of 0.1 g/100 g body. Pancreatic juice was collected, beginning 1 h preprandially until 3 h postprandially. Blood samples were obtained 15 min preprandially and 15, 45, 90 and 150 min postprandially. The infusion of MCT evoked a change in the trend of the curve for the volume of secretion of pancreatic juice, lipase and colipase concentrations and outputs. The trend of the curve did not change over time for CCK and PYY. Differences between the trends of the curves for the saline and MCT treatment were observed for volume of secretion, protein output, lipase content and output, trypsin and colipase output. Differences in the trends of the curves between MCT and LCT were obtained for the outputs of protein, lipase and colipase. Plasma CCK levels were lower as a result of the MCT treatment compared with the saline and LCT treatments. The results suggest an immediate, distinguished response of the porcine exocrine pancreas to fats differing in chain length.

  12. 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

  13. 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.

  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. Nanoemulsion delivery systems for oil-soluble vitamins: Influence of carrier oil type on lipid digestion and vitamin D3 bioaccessibility.

    PubMed

    Ozturk, Bengu; Argin, Sanem; Ozilgen, Mustafa; McClements, David Julian

    2015-11-15

    The influence of carrier oil type on the bioaccessibility of vitamin D3 encapsulated within oil-in-water nanoemulsions prepared using a natural surfactant (quillaja saponin) was studied using a simulated gastrointestinal tract (GIT) model: mouth; stomach; small intestine. The rate of free fatty acid release during lipid digestion decreased in the following order: medium chain triglycerides (MCT) > corn oil ≈ fish oil > orange oil > mineral oil. Conversely, the measured bioaccessibility of vitamin D3 decreased in the following order: corn oil ≈ fish oil > orange oil > mineral oil > MCT. These results show that carrier oil type has a considerable impact on lipid digestion and vitamin bioaccessibility, which was attributed to differences in the release of bioactives from lipid droplets, and their solubilization in mixed micelles. Nanoemulsions prepared using long chain triglycerides (corn or fish oil) were most effective at increasing vitamin bioaccessibility. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. 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.

  17. Effect of acute feeding of diets of varying fatty acid composition on intestinal apolipoprotein expression in the newborn swine.

    PubMed

    Wang, H; Zhan, R; Hunter, F; Du, J; Black, D

    1996-06-01

    The purpose of this study was to determine the effects of dietary fatty acids of varying chain lengths and degrees of saturation on intestinal apolipoprotein (apo) B and A-I expression in the newborn piglet. Two-day-old female piglets received one of three isocaloric formulas containing 48% of total calories (120 kcal/kg/24 h) as medium-chain triglycerides (MCT) from MCT oil, intermediate-chain saturated triglycerides (ICST) from coconut oil, or long-chain polyunsaturated triglycerides (LCPUT) from safflower oil by continuous duodenal infusion for 24 h. After in situ radiolabeling, jejunal and ileal mucosal apo B-48 and A-I were immunoprecipitated, and synthesis was expressed as percentage of total protein synthesis. Mucosal apo B and A-I mass was measured by ELISA as nanograms of apoprotein/microgram of total protein. Fifty percent less apo B jejunal synthesis was present in the ICST group versus the MCT and LCPUT groups (0.67 +/- 0.07, 1.19 +/- 0.20, and 1.25 +/- 0.15, respectively, mean +/- SEM, p < 0.05). Jejunal apo B mass was lower in the MCT group versus the ICST and LCPUT groups (0.10 +/- 0.02, 0.21 +/- 0.03, and 0.16 +/- 0.03, respectively, p < 0.05). Ileal apo B synthesis was lowest in the ICST group. No differences were found in ileal apo B mass. Two-fold higher jejunal apo A-I synthesis was found in the LCPUT group versus the MCT and ICST groups (14.18 +/- 1.69, 7.56 +/- 2.63, and 6.36 +/- 0.58, respectively, p < 0.01). No differences were found for jejunal apo A-I mass. In the ileum, the only difference was a higher apo A-I mass in the LCPUT group (p < 0.05). We conclude that in the newborn piglet intestinal apo B and A-I expression is acutely and differentially regulated by dietary lipid varying in fatty acid chain length and saturation. The patterns of regulation are complex and vary among specific apolipoproteins and regions of the small intestine and include co- and posttranslational mechanisms.

  18. 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.

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

    PubMed Central

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

    2016-01-01

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

  20. Total parenteral nutrition with short- and long-chain triglycerides: triacetin improves nitrogen balance in rats.

    PubMed

    Bailey, J W; Barker, R L; Karlstad, M D

    1992-09-01

    Little is known about the long-term metabolic effects of parenteral administration of short-chain triglycerides. These studies were undertaken to investigate triacetin, the water-soluble triglyceride of acetate when it is incorporated into nutritionally balanced total parenteral nutrition formulas. Male Sprague-Dawley rats (n = 22) were fed an isovolemic, isocaloric and isonitrogenous diet for 7 d. The lipid energy represented 30% of the nonprotein energy with short-chain triglycerides representing 0, 50 or 90% of the lipid energy. Plasma acetate concentration was determined as well as indicators of protein metabolism: daily and cumulative nitrogen balance, whole body leucine kinetics and rectus muscle and liver fractional protein synthetic rates. No overt toxic effects were observed at any point during the study. As the proportion of short-chain triglycerides in the diet increased from 0 to 50 or 90% of the lipid energy, cumulative nitrogen balance increased 50 or 120%, respectively (P less than 0.05). Whole-body and tissue leucine kinetics (determined during the last 2.5 h of the 7-d study) were unaffected by the lipid composition of the diet. Plasma acetate concentration was not significantly different among groups. These results indicate that incorporation of the short-chain triglyceride, triacetin, in nutritionally balanced total parenteral nutrition formulas improves nitrogen balance with no overt toxic effects. These data indicate that triacetin may have a future role as a parenteral nutrient, and that further studies of its use are warranted.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. The hypertriglyceridemic clamp technique. Studies using long-chain and structured triglyceride emulsions in healthy subjects.

    PubMed

    Nordenström, Jörgen; Thörne, Anders; Aberg, Wiveca; Carneheim, Claes; Olivecrona, Thomas

    2006-11-01

    In a randomized crossover study, plasma kinetics of 2 different types of fat emulsions were studied in 8 healthy volunteers by using a hypertriglyceridemic clamp technique. The method involves the stabilization of serum triglyceride (TG) concentration during 180 minutes at a predetermined level (4 mmol/L) by adjustment of TG infusion rate by repeated online measurements of serum TG concentration. The fat emulsions under study were a long-chain fatty acid triglyceride (LCT) emulsion (Intralipid 20%, Fresenius Kabi, Sweden) and a structured triglyceride (STG) emulsion (Structolipid 20%, Fresenius Kabi) where medium- and long-chain fatty acids have been interesterified within a TG molecule. The hypertriglyceridemic clamp was found to have acceptable reproducibility when tested in 3 healthy individuals on 2 different occasions, as similar steady-state TG levels were obtained by infusing similar amounts of fat. The average (+/-SEM) TG concentration during the 180-minute clamp was similar for STGs and LCTs (4.0 +/- 0.1 vs 3.9 +/- 0.1 mmol/L; not significant), but the amount of fat that had to be infused was significantly higher during STG than during LCT clamping (0.31 +/- 0.04 vs 0.21 +/- 0.02 g TG per minute; P < .05). Higher serum levels of free fatty acids (1.80 +/- 0.13 vs 0.96 +/- 0.09 mmol/L; P < .05), free glycerol (1.30 +/- 0.07 vs 0.76 +/- 0.08 mmol/L; P < .001), and beta-OH butyrate (1.61 +/- 0.44 vs 1.17 +/- 0.23 mmol/L; not significant) were obtained at the end of the clamp during infusion of STGs compared with LCTs. During infusion of STGs the medium-chain fatty acids octanoic (C:8) and decanoic acid (C:10) constituted approximately half of circulating fatty acids that correspond to the compositional ratio of the emulsion. Plasma lipoprotein lipase (LPL) concentration was higher during STG than during LCT clamping (6.06 +/- 0.62 vs 3.15 +/- 0.40 mU/mL; P < .05), and there was a positive correlation between the mean LPL concentration and the amount of

  6. 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

  7. Dietary fat sources differentially modulate intestinal barrier and hepatic inflammation in alcohol-induced liver injury in rats

    PubMed Central

    Zhong, Wei; Li, Qiong; Xie, Guoxiang; Sun, Xiuhua; Tan, Xiaobing; Sun, Xinguo; Jia, Wei

    2013-01-01

    Endotoxemia is a causal factor in the development of alcoholic liver injury. The present study aimed at determining the interactions of ethanol with different fat sources at the gut-liver axis. Male Sprague-Dawley rats were pair fed control or ethanol liquid diet for 8 wk. The liquid diets were based on a modified Lieber-DeCarli formula, with 30% total calories derived from corn oil (rich in polyunsaturated fatty acids). To test the effects of saturated fats, corn oil in the ethanol diet was replaced by either cocoa butter (CB, rich in long-chain saturated fatty acids) or medium-chain triglycerides (MCT, exclusively medium-chain saturated fatty acids). Ethanol feeding increased hepatic lipid accumulation and inflammatory cell infiltration and perturbed hepatic and serum metabolite profiles. Ethanol feeding with CB or MCT alleviated ethanol-induced liver injury and attenuated ethanol-induced metabolic perturbation. Both CB and MCT also normalized ethanol-induced hepatic macrophage activation, cytokine expression, and neutrophil infiltration. Ethanol feeding elevated serum endotoxin level, which was normalized by MCT but not CB. In accordance, ethanol-induced downregulations of intestinal occludin and zonula occludens-1 were normalized by MCT but not CB. However, CB normalized ethanol-increased hepatic endotoxin level in association with upregulation of an endotoxin detoxifying enzyme, argininosuccinate synthase 1 (ASS1). Knockdown ASS1 in H4IIEC3 cells resulted in impaired endotoxin clearance and upregulated cytokine expression. These data demonstrate that the protection of saturated fats against alcohol-induced liver injury occur via different actions at the gut-liver axis and are chain length dependent. PMID:24113767

  8. 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.

  9. Functional analysis of human aromatic amino acid transporter MCT10/TAT1 using the yeast Saccharomyces cerevisiae.

    PubMed

    Uemura, Satoshi; Mochizuki, Takahiro; Kurosaka, Goyu; Hashimoto, Takanori; Masukawa, Yuki; Abe, Fumiyoshi

    2017-10-01

    Tryptophan is an essential amino acid in humans and an important serotonin and melatonin precursor. Monocarboxylate transporter MCT10 is a member of the SLC16A family proteins that mediates low-affinity tryptophan transport across basolateral membranes of kidney, small intestine, and liver epithelial cells, although the precise transport mechanism remains unclear. Here we developed a simple functional assay to analyze tryptophan transport by human MCT10 using a deletion mutant for the high-affinity tryptophan permease Tat2 in Saccharomyces cerevisiae. tat2Δtrp1 cells are defective in growth in YPD medium because tyrosine present in the medium competes for the low-affinity tryptophan permease Tat1 with tryptophan. MCT10 appeared to allow growth of tat2Δtrp1 cells in YPD medium, and accumulate in cells deficient for Rsp5 ubiquitin ligase. These results suggest that MCT10 is functional in yeast, and is subject to ubiquitin-dependent quality control. Whereas growth of Tat2-expressing cells was significantly impaired by neutral pH, that of MCT10-expressing cells was nearly unaffected. This property is consistent with the transport mechanism of MCT10 via facilitated diffusion without a need for pH gradient across the plasma membrane. Single-nucleotide polymorphisms (SNPs) are known to occur in the human MCT10 coding region. Among eight SNP amino acid changes in MCT10, the N81K mutation completely abrogated tryptophan import without any abnormalities in the expression or localization. In the MCT10 modeled structure, N81 appeared to protrude into the putative trajectory of tryptophan. Plasma membrane localization of MCT10 and the variant proteins was also verified in human embryonic kidney 293T cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Patient Workload Profile: National Naval Medical Center (NNMC), Bethesda, MD.

    DTIC Science & Technology

    1980-06-01

    Diets Sucrose-Fructose Elimination Diet Medium-Chain Triglyceride (MCT) Barium Enema Preparation Diet Ketogenic Diet 125 mg Calcium Test Diet ...Traditional Ketogenic Diet 150 gm and 300 gm Carbohydrate Sodium Restricted Diets Test Diets Sodium Restricted, Calorie Restricted Fat Free Test Diet Diets 100...Rations Served - NNMC, Bethesda 89 7-2 Regular and Therapeutic Diets - NNMC, Bethesda 91 7-3 Regular and Therapeutic Rations Served

  11. 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.

  12. 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.

  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. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Effects of Shiitake Intake on Serum Lipids in Rats Fed Different High-Oil or High-Fat Diets.

    PubMed

    Asada, Norihiko; Kairiku, Rumi; Tobo, Mika; Ono, Akifumi

    2018-04-27

    Shiitake (Lentinula edodes) extract, eritadenine, has been shown to reduce cholesterol levels, and its hypocholesterolemic actions are involved in the metabolism of methionine. However, the mechanisms by which eritadenine affects cholesterol metabolism in animals fed a high-fat diet containing different sources of lipids have not yet been elucidated in detail. This study was conducted to investigate the effects of shiitake supplementation on serum lipid concentrations in rats fed a diet including a high amount of a plant oil (HO [high oil] and HOS [high oil with shiitake] groups), animal fat (HF [high fat] and HFS [high fat with shiitake] groups), or MCT- (medium-chain triglyceride-) rich plant oil (HM [high MCT] and HMS [high MCT with shiitake] groups). Rats in the HOS, HFS, and HMS groups were fed shiitake. When rats were fed a diet containing shiitake, serum triglyceride, cholesterol levels, and LCAT (lecithin-cholesterol acyltransferase) activities were lower in rats given MCT-rich plant oil than in those that consumed lard. The lipid type in the diet with shiitake also affected serum cholesterol levels and LCAT activities. The diet containing MCT-rich plant oil showed the greatest rates of decrease in all serum lipid profiles and LCAT activities. These results suggest that shiitake and MCT-rich plant oil work together to reduce lipid profiles and LCAT activity in serum.

  20. 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).

  1. 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.

  2. Effect of chronic alcohol consumption on Hepatic SIRT1 and PGC-1{alpha} in rats

    SciTech Connect

    Lieber, Charles S.; Department of Medicine, Mount Sinai School of Medicine, New York, NY; Leo, Maria A.

    2008-05-23

    The nuclear genes, NAD-dependent deacetylase Sirtuis 1 (SIRT1) and the peroxisome proliferator-activated receptor-{gamma} coactivator1{alpha} (PGC-1{alpha}) are regulators of energy metabolism. Here, we studied the role of alcohol consumption in expression of these sensing molecules. Alcohol significantly reduced hepatic SIRT1 mRNA by 50% and PGC-1{alpha} mRNA by 46% and it significantly inhibited the protein expression of SIRT1 and PGC-1{alpha}, while the transcription factor PPAR-{gamma} remained unchanged. However, when the lipid composition of the alcohol diet was changed by replacing long-chain triglycerides (LCT) with medium chain triglycerides (MCT), SIRT1 and PGC-1{alpha} mRNA were restored to near control levels. This study demonstrates thatmore » alcohol reduces key energy sensing proteins and that replacement of LCT by MCT affects the transcription of these genes. Since there is a pathophysiological link between SIRT1 and PGC-1{alpha} and mitochondrial energy, the implication of the study is that mitochondrial dysfunction due to alcohol abuse can be treated by dietary modifications.« less

  3. Structural and mechanical properties of organogels: Role of oil and gelator molecular structure.

    PubMed

    Cerqueira, Miguel A; Fasolin, Luiz H; Picone, Carolina S F; Pastrana, Lorenzo M; Cunha, Rosiane L; Vicente, António A

    2017-06-01

    This work aims at evaluating the influence of oil and gelator structure on organogels' properties through rheological measurements, polarized microscopy and small-angle X-ray scattering (SAXS). Four different food-grade gelators (glyceryl tristearate - GT; sorbitan tristearate - ST; sorbitan monostearate - SM and glyceryl monostearate - GM) were tested in medium-chain triglyceride and high oleic sunflower (MCT and LCT, respectively) oil phases. Organogels were prepared by mixing the oil phase and gelator at different concentrations (5, 10, 15, 20 and 25%) at 80°C during 30min. All organogels presented birefringence confirming the formation of a crystalline structure that changed with the increase of the gelator concentration. Through the evaluation of SAXS peaks it has been confirmed that all structures were organized as lamellas but with different d-spacing values. These particularities at micro- and nanoscale level lead to differences in rheological properties of organogels. Results showed that the oil type (i.e. medium- and long-chain triglyceride) and hydrophilic head of gelators (i.e. sorbitan versus glyceryl) exert influence on the organogels physical properties, but the presence of monostearate leads to the formation of stronger organogels. Moreover, gels produced with LCT were stronger and gelled at lower organogelator concentration than MCT. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Effect of Acylglycerol Composition and Fatty Acyl Chain Length on Lipid Digestion in pH-Stat Digestion Model and Simulated In Vitro Digestion Model.

    PubMed

    Qi, Jin F; Jia, Cai H; Shin, Jung A; Woo, Jeong M; Wang, Xiang Y; Park, Jong T; Hong, Soon T; Lee, K-T

    2016-02-01

    In this study, a pH-stat digestion model and a simulated in vitro digestion model were employed to evaluate the digestion degree of lipids depending on different acylglycerols and acyl chain length (that is, diacylglycerol [DAG] compared with soybean oil representing long-chain triacylglycerol compared with medium-chain triacylglycerol [MCT]). In the pH-stat digestion model, differences were observed among the digestion degrees of 3 oils using digestion rate (k), digestion half-time (t1/2 ), and digestion extent (Φmax). The results showed the digestion rate order was MCT > soybean oil > DAG. Accordingly, the order of digestion half-times was MCT < soybean oil < DAG. In simulated in vitro digestion model, digestion rates (k') and digestion half-times (t'1/2 ) were also obtained and the results showed a digestion rate order of MCT (k' = 0.068 min(-1) ) > soybean oil (k' = 0.037 min(-1) ) > DAG (k' = 0.024 min(-1) ). Consequently, the order of digestion half-times was MCT (t'1/2 = 10.20 min) < soybean oil (t'1/2 = 18.74 min) < DAG (t'1/2 = 29.08 min). The parameters obtained using the 2 models showed MCT was digested faster than soybean oil, and that soybean oil was digested faster than DAG. © 2015 Institute of Food Technologists®

  10. 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.

  11. Low density of neutral hydrogen and helium in the local interstellar medium: Extreme Ultraviolet Explorer photometry of the Lyman continuum of the hot white dwarfs MCT 0501-2858, MCT 0455-2812, HZ 43, and GD 153

    NASA Technical Reports Server (NTRS)

    Vennes, Stephane; Dupuis, Jean; Bowyer, Stuart; Fontaine, Gilles; Wiercigroch, Alexandria; Jelinsky, Patrick; Wesemael, Francois; Malina, Roger

    1994-01-01

    The first comprehensive sky survey of the extreme ultraviolet (EUV) spectral range performed by the Extreme Ultraviolet Explorer (EUVE) has uncovered a handful of very bright sources at wavelengths longer than the He I 504 A photoionization edge. Among these objects are four white dwarfs with exceptionally low interstellar medium (ISM) column densities along the line of sight. Analysis of EUV photometry of the He-rich DO white dwarf MCT 0501-2858 and the H-rich DA white dwarf MCT 0455-2812 along one line of sight and of the DA white dwarfs HZ 43 and GD 153 near the north Galactic pole indicates that the overall minimum column density of the neutral material centered on the Sun is N(H I) = 0.5-1.0 x 10(exp 18)/sq cm. In the case of MCT 0501-2858, EUV photometric measurements provide a clear constraint to the effective temperature (60,000-70,000 K). Given these neutral hydrogen columns, the actual contribution to the density of neutral species from the immediate solar environment (the 'local fluff') would only cover a distance of approximately equals 2-3 pc (assuming an average density n(H I) = 0.1/cu cm) leaving these lines of sight almost entirely within the hot phase of the ISM. A preliminary examination of the complete EUVE long-wavelength survey indicates that these lines of sight are exceptional and set a minimum column density in the solar environment.

  12. Parenteral nutrition combined with rice soup can be a safe and effective intervention for congenital chylous ascites.

    PubMed

    Cao, Yi; Yan, Weihui; Lu, Lina; Tao, Yijing; Lu, Wei; Chen, Yingwei; Tang, Qingya; Cai, Wei

    2016-01-01

    Congenital chylous ascites in the neonatal period is a rare entity. Total parenteral nutrition (TPN), medium chain triglyceride (MCT)-based diet, octreotide and repeated paracentesis are regarded as appropriate medical treatment for congenital chylous ascites, and surgery is recommended when conservative therapy has failed. We present two cases in which ascites were confirmed via an abdominal sonogram and diagnostic paracentesis. In our clinical experience, rice soup combined with PN can be a safe and effective intervention.

  13. 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.

  14. Prompt inhibition of fMLP-induced Ca2+ mobilization by parenteral lipid emulsions in human neutrophils.

    PubMed

    Wanten, Geert; Rops, Angelique; van Emst-De Vries, Sjenet E; Naber, Ton; Willems, Peter H G M

    2002-04-01

    It remains unclear whether modulation of immune system functions by lipids contributes to the increased infection rate observed in patients treated with parenteral nutrition. We therefore evaluated the effects of lipid emulsions derived from fish oil [very long chain triglycerides (VLCT)], olive oil [long-chain triglycerides- mono-unsaturated fatty acid (LCT-MUFA)], soya oil [long-chain triglycerides (LCT)], or a physical mixture of coconut and soya oil [mixed long- and medium-chain triglycerides (LCT-MCT)] on neutrophil activation. N-formyl-methionyl-leucyl-phenylalanine (fMLP) evoked an immediate increase of the cytosolic Ca2+ concentration ([Ca2+](i,av)) in a suspension of neutrophils. When added 3 min before fMLP, however, all four lipid emulsions reduced the hormone-induced increase in [Ca2+](i,av) with the same efficacy but with different potency. Half-maximal inhibition was reached at emulsion concentrations of 0.24 mM VLCT, 0.32 mM LCT-MCT, 0.52 mM LCT, and 0.82 mM LCT-MUFA. Similarly to the lipids, the protein kinase C (PKC) activator PMA markedly reduced the fMLP-induced increase in [Ca2+](i,av). PMA inhibition was abolished by the PKC inhibitor staurosporine. In contrast, however, this drug did not interfere with the inhibitory lipid effect, indicating that the lipids act primarily in a PKC-independent manner. In summary, this study shows that nutritional lipids can evoke a prompt and significant attenuation of hormone-induced neutrophil stimulation and that the emulsions based on fish oil and a mixture of coconut oil and soya oil are among the most potent ones in this respect.

  15. 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.

  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. [Congenital intestinal lymphangiectasia: a rare differential diagnosis in hypoproteinemia in infants].

    PubMed

    Möller, A; Kalhoff, H; Reuter, T; Friedrichs, N; Wagner, N

    2006-01-01

    Congenital intestinal lymphangiectasia is a rare disease in childhood, which may already cause protein-losing enteropathy in newborns. This is a case report of an infant with generalized edema and protein-losing enteropathy, in whom intestinal lymphangiectasia was diagnosed at the age of two months. Following repetitive intravenous albumin und gamma globulin infusions, the elimination of long-chain fats from the diet and the substitution with medium-chain triglycerides (MCT) led to an improvement of the protein-losing enteropathy. In newborns with low level of serum protein and edema protein-losing enteropathy caused by congenital lymphangiectasia might be considered as a differential diagnosis.

  18. The effects of different lipid emulsions on the lipid profile, fatty acid composition, and antioxidant capacity of preterm infants: A double-blind, randomized clinical trial.

    PubMed

    Wang, Ying; Feng, Yi; Lu, Li-Na; Wang, Wei-Ping; He, Zhen-Juan; Xie, Li-Juan; Hong, Li; Tang, Qing-Ya; Cai, Wei

    2016-10-01

    Olive oil (OO), medium-chain triglycerides (MCT)/long-chain triglycerides (LCT) mixture and soybean oil (SO) lipid emulsions are currently used for preterm infants in China. The aim of our study was to compare the lipid profile, fatty acid composition, and antioxidant capacity of preterm infants administered OO, MCT/LCT, or SO lipid emulsions. In this study, 156 preterm infants (birth weight < 2000 g and gestational age < 37 weeks) received parenteral nutrition (PN) containing OO, MCT/LCT, or SO lipid emulsions for a minimum of 14 d. On days 0, 7, and 14, the lipid profile, fatty acid composition and antioxidant capacity were analyzed. On day 7, HDL levels in the MCT/LCT group were significantly lower than in the OO (1.06 ± 0.40 mmol/L) or SO groups. LDL levels were higher in the OO group than in the MCT/LCT or SO groups on day 7. A-I/B was higher in MCT/LCT than in OO or SO groups. Myristic acid (C14:0) levels on days 7 and 14 increased in MCT/LCT compared to the OO and SO groups. The OO group had higher oleic acid (C18:1n9) levels than the two other groups. Linoleic acid (C18:2n6), linolenic acid (C18:3n3), and eicosapentaenoic acid (20:5n3) were significantly lower in the OO group than in MCT/LCT or SO groups. Monounsaturated fatty acid levels decreased, and ω-6 polyunsaturated fatty acid and essential fatty acids levels increased in MCT/LCT and SO groups. No significant differences were obtained in SOD, MDA, GSH-Px, and T-AOC among the groups. The three lipid emulsions were safe and well tolerated in preterm infants. Oleic acid (C18:1n9) levels increased and LA (C18:2n6), ALA (C18:3n3), and EPA (C20:5n23) levels decreased in OO compared to MCT/LCT or SO. NCT01683162, https://register.clinicaltrials.gov/. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  19. Acute anticonvulsant effects of capric acid in seizure tests in mice.

    PubMed

    Wlaź, Piotr; Socała, Katarzyna; Nieoczym, Dorota; Żarnowski, Tomasz; Żarnowska, Iwona; Czuczwar, Stanisław J; Gasior, Maciej

    2015-03-03

    Capric acid (CA10) is a 10-carbon medium-chain fatty acid abundant in the medium-chain triglyceride ketogenic diet (MCT KD). The purpose of this study was to characterize acute anticonvulsant effects of CA10 across several seizure tests in mice. Anticonvulsant effects of orally (p.o.) administered CA10 were assessed in the maximal electroshock seizure threshold (MEST), 6-Hz seizure threshold, and intravenous pentylenetetrazole (i.v. PTZ) seizure tests in mice. Acute effects of CA10 on motor coordination were assessed in the grip and chimney tests. Plasma and brain concentrations of CA10 were measured. Co-administration studies with CA10 and another abundant medium-chain fatty acid, caprylic acid (CA8) were performed. CA10 showed significant and dose-dependent anticonvulsant properties by increasing seizure thresholds in the 6-Hz and MEST seizure tests; it was ineffective in the i.v. PTZ seizure test. At higher doses than those effective in the 6-Hz and MEST seizure tests, CA10 impaired motor performance in the grip and chimney tests. An enhanced anticonvulsant response in the 6-Hz seizure test was produced when CA8 and CA10 were co-administered. An acute p.o. administration of CA10 resulted in dose-proportional increases in its plasma and brain concentrations. CA10 exerted acute anticonvulsant effects at doses that produce plasma exposures comparable to those reported in epileptic patients on the MCT KD. An enhanced anticonvulsant effect is observed when CA10 and the other main constituent of the MCT KD, CA8, were co-administered. Thus, acute anticonvulsant properties of CA10 and CA8 may influence the overall clinical efficacy of the MCT KD. Copyright © 2014. Published by Elsevier Inc.

  20. Post-natal changes in MCT1 expression in the forestomach of calves.

    PubMed

    Pfannkuche, H; Taifour, F; Steinhoff-Wagner, J; Hammon, H M; Gäbel, G

    2014-02-01

    The monocarboxylate transporter 1 (MCT1) has been demonstrated to be involved in the transfer of short-chain fatty acids (SCFA) and/or their intraepithelial metabolites from the rumen to the blood. As MCT1 plays a role in SCFA transfer, it is assumed that SCFA are the main substrates influencing its expression. However, there are hints that MCT1 may also be expressed during the early life of the animal when SCFA are not released in the forestomach. To figure out whether MCT1 expression in the forestomach is influenced independently of SCFA during that period, we studied post-natal MCT1 expression immunohistochemically in the epithelia of omasum, atrium ruminis, saccus dorsalis ruminis, saccus ventralis ruminis and reticulum of calves born preterm and at term. The calves were nourished by colostrum or by milk-based formula diet. MCT1 could be found in all the forestomach compartments tested, even in preterm calves. The protein was mainly oriented to the luminal side in the immature epithelium 24 h after birth. Orientation to the blood side of the cells developed during the first 4 days after birth. In the rumen epithelia (but not in the other forestomach compartments tested), orientation of MCT1 to the blood side of the cells was paralleled by an increase in the overall expression rate during the first 4 days after birth. As lactate levels were very high directly after birth, a lactate-dependent substrate induction may have been the underlying mechanism. However, non-specific changes due to general differential processes might also be the cause. Both early upregulation of MCT1 and high blood lactate levels may provide the epithelia with lactate as energy source. © 2013 Blackwell Verlag GmbH.

  1. 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.

  2. 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.

  3. They say coconut oil can aid weight loss, but can it really?

    PubMed

    Clegg, M E

    2017-10-01

    There has in recent years, been much media speculation and consumer interest in the beneficial satiating properties of consuming coconut oil and its potential to aid weight loss. However, the media has primarily cited studies using medium-chain triglycerides (MCT) oil. The current perspective looks at the research that is available on coconut oil. It examines if and how MCT-related research can be applied to coconut oil and if there is potential for coconut oil to aid weight loss. The current report indicates a lack of consistent evidence on the topic of coconut oil, satiety and weight loss. Given both the publicity and the increased consumption of coconut oil further research, particularly long-term clinical trials, in this area are warranted.

  4. 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.

  5. Anaplerotic Treatment of Long-Chain Fat Oxidation Disorders with Triheptanoin: Review of 15 years Experience

    PubMed Central

    Roe, Charles R.; Brunengraber, Henri

    2015-01-01

    Background The treatment of long-chain mitochondrial β-oxidation disorders (LC-FOD) with a low fat-high carbohydrate diet, a diet rich in medium-even-chain triglycerides (MCT), or a combination of both has been associated with high morbidity and mortality for decades. The pathological tableau appears to be caused by energy deficiency resulting from reduced availability of citric acid cycle (CAC) intermediates required for optimal oxidation of acetyl-CoA. This hypothesis was investigated by diet therapy with carnitine and anaplerotic triheptanoin (TH). Methods Fifty-two documented LC-FOD patients were studied in this investigation (age range: birth to 51 years). Safety monitoring included serial quantitative measurements of routine blood chemistries, blood levels of carnitine and acylcarnitines, and urinary organic acids. Results The average frequency of serious clinical complications were reduced from ~ 60 % with conventional diet therapy to 10 % with TH and carnitine treatment and mortality decreased from ~ 65 % with conventional diet therapy to 3.8 %. Carnitine supplementation was uncomplicated. Conclusion The energy deficiency in LC-FOD patients was corrected safely and more effectively with the triheptanoin diet and carnitine supplement than with conventional diet therapy. Safe intervention in neonates and infants will permit earlier intervention following pre-natal diagnosis or diagnosis by expanded newborn screening. PMID:26547562

  6. Regulation of Mct1 by cAMP-dependent internalization in rat brain endothelial cells.

    PubMed

    Smith, Jeffrey P; Uhernik, Amy L; Li, Lun; Liu, Zejian; Drewes, Lester R

    2012-10-22

    In the cerebrovascular endothelium, monocarboxylic acid transporter 1 (Mct1) controls blood-brain transport of short chain monocarboxylic and keto acids, including pyruvate and lactate, to support brain energy metabolism. Mct1 function is acutely decreased in rat brain cerebrovascular endothelial cells by β-adrenergic signaling through cyclic adenosine monophosphate (cAMP); however, the mechanism for this acute reduction in transport capacity is unknown. In this report, we demonstrate that cAMP induces the dephosphorylation and internalization of Mct1 from the plasma membrane into caveolae and early endosomes in the RBE4 rat brain cerebrovascular endothelial cell line. Additionally, we provide evidence that Mct1 constitutively cycles through clathrin vesicles and recycling endosomes in a pathway that is not dependent upon cAMP signaling in these cells. Our results are important because they show for the first time the regulated and unregulated vesicular trafficking of Mct1 in cerebrovascular endothelial cells; processes which have significance for better understanding normal brain energy metabolism, and the etiology and potential therapeutic approaches to treating brain diseases, such as stroke, in which lactic acidosis is a key component. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Regulation of Mct1 by cAMP-dependent internalization in rat brain endothelial cells

    PubMed Central

    Smith, Jeffrey P.; Uhernik, Amy L.; Li, Lun; Liu, Zejian; Drewes, Lester R.

    2012-01-01

    In the cerebrovascular endothelium, monocarboxylic acid transporter 1 (Mct1) controls blood-brain transport of short chain monocarboxylic and keto acids, including pyruvate and lactate, to support brain energy metabolism. Mct1 function is acutely decreased in rat brain cerebrovascular endothelial cells by β-adrenergic signaling through cyclic adenosine monophosphate (cAMP); however, the mechanism for this acute reduction in transport capacity is unknown. In this report, we demonstrate that cAMP induces the dephosphorylation and internalization of Mct1 from the plasma membrane into caveolae and early endosomes in the RBE4 rat brain cerebrovascular endothelial cell line. Additionally, we provide evidence that Mct1 constitutively cycles through clathrin vesicles and recycling endosomes in a pathway that is not dependent upon cAMP signaling in these cells. Our results are important because they show for the first time the regulated and unregulated vesicular trafficking of Mct1 in cerebrovascular endothelial cells; processes which have significance for better understanding normal brain energy metabolism, and the etiology and potential therapeutic approaches to treating brain diseases, such as stroke, in which lactic acidosis is a key component PMID:22925948

  8. 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.

  9. Carbon and Acyl Chain Flux during Stress-induced Triglyceride Accumulation by Stable Isotopic Labeling of the Polar Microalga Coccomyxa subellipsoidea C169*

    PubMed Central

    Allen, James W.; DiRusso, Concetta C.; Black, Paul N.

    2017-01-01

    Deriving biofuels and other lipoid products from algae is a promising future technology directly addressing global issues of atmospheric CO2 balance. To better understand the metabolism of triglyceride synthesis in algae, we examined their metabolic origins in the model species, Coccomyxa subellipsoidea C169, using stable isotopic labeling. Labeling patterns arising from [U-13C]glucose, 13CO2, or D2O supplementation were analyzed by GC-MS and/or LC-MS over time courses during nitrogen starvation to address the roles of catabolic carbon recycling, acyl chain redistribution, and de novo fatty acid (FA) synthesis during the expansion of the lipid bodies. The metabolic origin of stress-induced triglyceride was found to be a continuous 8:2 ratio between de novo synthesized FA and acyl chain transfer from pre-stressed membrane lipids with little input from lipid remodeling. Membrane lipids were continually synthesized with associated acyl chain editing during nitrogen stress, in contrast to an overall decrease in total membrane lipid. The incorporation rates of de novo synthesized FA into lipid classes were measured over a time course of nitrogen starvation. The synthesis of triglycerides, phospholipids, and galactolipids followed a two-stage pattern where nitrogen starvation resulted in a 2.5-fold increase followed by a gradual decline. Acyl chain flux into membrane lipids was dominant in the first stage followed by triglycerides. These data indicate that the level of metabolic control that determines acyl chain flux between membrane lipids and triglycerides during nitrogen stress relies primarily on the Kennedy pathway and de novo FA synthesis with limited, defined input from acyl editing reactions. PMID:27903654

  10. Carbon and Acyl Chain Flux during Stress-induced Triglyceride Accumulation by Stable Isotopic Labeling of the Polar Microalga Coccomyxa subellipsoidea C169.

    PubMed

    Allen, James W; DiRusso, Concetta C; Black, Paul N

    2017-01-06

    Deriving biofuels and other lipoid products from algae is a promising future technology directly addressing global issues of atmospheric CO 2 balance. To better understand the metabolism of triglyceride synthesis in algae, we examined their metabolic origins in the model species, Coccomyxa subellipsoidea C169, using stable isotopic labeling. Labeling patterns arising from [U- 13 C]glucose, 13 CO 2 , or D 2 O supplementation were analyzed by GC-MS and/or LC-MS over time courses during nitrogen starvation to address the roles of catabolic carbon recycling, acyl chain redistribution, and de novo fatty acid (FA) synthesis during the expansion of the lipid bodies. The metabolic origin of stress-induced triglyceride was found to be a continuous 8:2 ratio between de novo synthesized FA and acyl chain transfer from pre-stressed membrane lipids with little input from lipid remodeling. Membrane lipids were continually synthesized with associated acyl chain editing during nitrogen stress, in contrast to an overall decrease in total membrane lipid. The incorporation rates of de novo synthesized FA into lipid classes were measured over a time course of nitrogen starvation. The synthesis of triglycerides, phospholipids, and galactolipids followed a two-stage pattern where nitrogen starvation resulted in a 2.5-fold increase followed by a gradual decline. Acyl chain flux into membrane lipids was dominant in the first stage followed by triglycerides. These data indicate that the level of metabolic control that determines acyl chain flux between membrane lipids and triglycerides during nitrogen stress relies primarily on the Kennedy pathway and de novo FA synthesis with limited, defined input from acyl editing reactions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. 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

  12. Chylous ascites following abdominal aortic surgery.

    PubMed

    Panieri, E; Kussman, B D; Michell, W L; Tunnicliffe, J A; Immelman, E J

    1995-03-01

    Chylous ascites is an extremely rare complication of abdominal aortic surgery. A case with a successful outcome is presented, followed by a review of the 17 published cases. Chylous ascites can result in nutritional imbalance, immunological deficit and respiratory dysfunction. Paracentesis confirms the diagnosis and provides symptomatic relief. Conservative management, beginning with a low-fat diet and medium-chain triglyceride (MCT) supplementation, is recommended, changing to total parenteral nutrition if unsuccessful. Failure of non-operative treatment may necessitate the need for laparotomy and ligation of leaking lymphatics or peritoneovenous shunting.

  13. 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.

  14. 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.

  15. 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

  16. Fat emulsions based on structured lipids (1,3-specific triglycerides): an investigation of the in vivo fate.

    PubMed

    Hedeman, H; Brøndsted, H; Müllertz, A; Frokjaer, S

    1996-05-01

    Structured lipids (1,3-specific triglycerides) are new chemical entities made by enzymatic transesterification of the fatty acids in the 1,3 positions of the triglyceride. The purpose of this study is to characterize structured lipids with either short chain fatty acids or medium chain fatty acids in the 1,3 positions with regard to their hydrophobicity, and investigate the in vivo fate in order to evaluate the potential of structured lipids as core material in fat emulsions used as parenteral drug delivery system. The lipids were characterized by employing reversed phase high performance liquid chromatography. The biodistribution of radioactively labeled emulsions was studied in rats. By employing high performance liquid chromatography a rank order of the hydrophobicities of the lipids could be given, with the triglycerides containing long chain fatty acids being the most hydrophobic and the structured lipid with short chain fatty acids in the 1,3 positions the least. When formulated as fat emulsions, the emulsion based on structured lipids with short fatty acids in the 1,3 positions was removed slower from the general blood circulation compared to emulsions based on lipids with long chain fatty acids in the 1,3 positions. The type of core material influences the in vivo circulation time of fat emulsions.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Carbon chain abundance in the diffuse interstellar medium

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  3. Microcapsules with a pH responsive polymer: influence of the encapsulated oil on the capsule morphology.

    PubMed

    Wagdare, Nagesh A; Marcelis, Antonius T M; Boom, Remko M; van Rijn, Cees J M

    2011-11-01

    Microcapsules were prepared by microsieve membrane cross flow emulsification of Eudragit FS 30D/dichloromethane/edible oil mixtures in water, and subsequent phase separation induced by extraction of the dichloromethane through an aqueous phase. For long-chain triglycerides and jojoba oil, core-shell particles were obtained with the oil as core, surrounded by a shell of Eudragit. Medium chain triglyceride (MCT oil) was encapsulated as relatively small droplets in the Eudragit matrix. The morphology of the formed capsules was investigated with optical and SEM microscopy. Extraction of the oil from the core-shell capsules with hexane resulted in hollow Eudragit capsules with porous shells. It was shown that the differences are related to the compatibility of the oils with the shell-forming Eudragit. An oil with poor compatibility yields microcapsules with a dense Eudragit shell on a single oil droplet as the core; oils having better compatibility yield porous Eudragit spheres with several oil droplets trapped inside. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Influence of lipid type on gastrointestinal fate of oil-in-water emulsions: In vitro digestion study.

    PubMed

    Zhang, Ruojie; Zhang, Zipei; Zhang, Hui; Decker, Eric Andrew; McClements, David Julian

    2015-09-01

    The potential gastrointestinal fate of oil-in-water emulsions containing lipid phases from different sources was examined: vegetable oils (corn, olive, sunflower, and canola oil); marine oils (fish and krill oil); flavor oils (orange and lemon oil); and, medium chain triglycerides (MCT). The lowest rates and extents of lipid digestion were observed for emulsified flavor oil, followed by emulsified krill oil. There was no appreciable difference between the final amounts of free fatty acids released for emulsified digestible oils. Differences in the digestibility of emulsions prepared using different oils were attributed to differences in their compositions, e.g., fatty acid chain length and unsaturation. The particle size distribution, particle charge, microstructure, and macroscopic appearance of the emulsions during passage through the simulated GIT depended on oil type. The results of this study may facilitate the design of functional foods that control the digestion and absorption of triglycerides, as well as the bioaccessibility of hydrophobic bioactives. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. 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.

  6. Preparation and physicochemical properties of surfactant-free emulsions using electrolytic-reduction ion water containing lithium magnesium sodium silicate.

    PubMed

    Okajima, Masahiro; Wada, Yuko; Hosoya, Takashi; Hino, Fumio; Kitahara, Yoshiyasu; Shimokawa, Ken-ichi; Ishii, Fumiyoshi

    2013-04-01

    Surfactant-free emulsions by adding jojoba oil, squalane, olive oil, or glyceryl trioctanoate (medium chain fatty acid triglycerides, MCT) to electrolytic-reduction ion water containing lithium magnesium sodium silicate (GE-100) were prepared, and their physiochemical properties (thixotropy, zeta potential, and mean particle diameter) were evaluated. At an oil concentration of 10%, the zeta potential was ‒22.3 ‒ ‒26.8 mV, showing no marked differences among the emulsions of various types of oil, but the mean particle diameters in the olive oil emulsion (327 nm) and MCT emulsion (295 nm) were smaller than those in the other oil emulsions (452-471 nm). In addition, measurement of the hysteresis loop area of each type of emulsion revealed extremely high thixotropy of the emulsion containing MCT at a low concentration and the olive emulsion. Based on these results, since surfactants and antiseptic agents markedly damage sensitive skin tissue such as that with atopic dermatitis, surfactant- and antiseptic-free emulsions are expected to be new bases for drugs for external use.

  7. 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.

  8. 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.

  9. 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.

  10. Regulation of monocarboxylate transporter 1 (MCT1) promoter by butyrate in human intestinal epithelial cells: involvement of NF-kappaB pathway.

    PubMed

    Borthakur, Alip; Saksena, Seema; Gill, Ravinder K; Alrefai, Waddah A; Ramaswamy, Krishnamurthy; Dudeja, Pradeep K

    2008-04-01

    Butyrate, a short chain fatty acid (SCFA) produced by bacterial fermentation of undigested carbohydrates in the colon, constitutes the major fuel for colonocytes. We have earlier shown the role of apically localized monocarboxylate transporter isoform 1 (MCT1) in transport of butyrate into human colonic Caco-2 cells. In an effort to study the regulation of MCT1 gene, we and others have cloned the promoter region of the MCT1 gene and identified cis elements for key transcription factors. A previous study has shown up-regulation of MCT1 expression, and activity by butyrate in AA/C1 human colonic epithelial cells, however, the detailed mechanisms of this up-regulation are not known. In this study, we demonstrate that butyrate, a substrate for MCT1, stimulates MCT1 promoter activity in Caco-2 cells. This effect was dose dependent and specific to butyrate as other predominant SCFAs, acetate, and propionate, were ineffective. Utilizing progressive deletion constructs of the MCT1 promoter, we showed that the putative butyrate responsive elements are in the -229/+91 region of the promoter. Butyrate stimulation of the MCT1 promoter was found to be independent of PKC, PKA, and tyrosine kinases. However, specific inhibitors of the NF-kappaB pathway, lactacystein (LC), and caffeic acid phenyl ester (CAPE) significantly reduced the MCT1 promoter stimulation by butyrate. Also, butyrate directly stimulated NF-kappaB-dependent luciferase reporter activity. Histone deacetylase (HDAC) inhibitor trichostatin A (TSA) also stimulated MCT1 promoter activity, however, unlike butyrate, this stimulation was unaltered by the NF-kappaB inhibitors. Further, the combined effect of butyrate, and TSA on MCT1 promoter activity was additive, indicating that their mechanisms of action were independent. Our results demonstrate the involvement of NF-kappaB pathway in the regulation of MCT1 promoter activity by butyrate. 2007 Wiley-Liss, Inc.

  11. 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

  12. Triheptanoin Treatment in Patients with Pediatric Cardiomyopathy Associated with Long Chain-Fatty Acid Oxidation Disorders

    PubMed Central

    Vockley, J; Charrow, J; Ganesh, J; Eswara, M; Diaz, GA; McCracken, E; Conway, R; Enns, GM; Starr, J; Wang, R; Abdenur, JE.; Sanchez-de-Toledo, J; Marsden, DL

    2016-01-01

    Long-chain fatty acid oxidation disorders (LC-FAOD) can cause cardiac hypertrophy and cardiomyopathy, often presenting in infancy, typically leading to death or heart transplant despite ongoing treatment. Previous data on triheptanoin treatment of cardiomyopathy in LC-FAOD suggested a clinical benefit on heart function during acute failure. An additional series of LC-FAOD patients with critical emergencies associated with cardiomyopathy were treated with triheptanoin under emergency treatment or compassionate use protocols. Case reports from 10 patients (8 infants) with moderate or severe cardiomyopathy associated with LC-FAOD are summarized. The majority of these patients were detected by newborn screening, with follow up confirmatory testing, including mutation analysis; all patients were managed with standard treatment, including medium chain triglyceride (MCT) oil. While on this regimen, they presented with acute heart failure requiring hospitalization and cardiac support (ventilation, ECMO, vasopressors) and, in some cases, resuscitation. The patients discontinued MCT oil and began treatment with triheptanoin, an investigational drug. Triheptanoin is expected to provide anaplerotic metabolites, to replace deficient TCA cycle intermediates and improve effective energy metabolism. Cardiac function was measured by echocardiography and ejection fraction (EF) was assessed. EF was moderately to severely impaired prior to triheptanoin treatment, ranging from 12–45%. Improvements in EF began between 2 and 21 days following initiation of triheptanoin, and peaked at 33–71%, with 9 of 10 patients achieving EF in the normal range. Continued treatment was associated with longer-term stabilization of clinical signs of cardiomyopathy. The most common adverse event observed was gastrointestinal distress. Of the 10 patients, 7 have continued on treatment, 1 elected to discontinue due to tolerability issues, and 2 patients died from other causes. Two of the case histories

  13. 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.

  14. 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…

  15. 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.

  16. Association Between MCT1 A1470T Polymorphism and Fat-Free Mass in Well-Trained Young Soccer Players.

    PubMed

    Massidda, Myosotis; Eynon, Nir; Bachis, Valeria; Corrias, Laura; Culigioni, Claudia; Cugia, Paolo; Scorcu, Marco; Calò, Carla M

    2016-04-01

    The aim of this study was to investigate the association between the MCT1 A1470T polymorphism and fat-free mass in young Italian elite soccer players. Participants were 128 Italian male soccer players. Fat-free mass was estimated for each of the soccer player using age- and gender-specific formulas with plicometry. Genotyping for the MCT1 A1470T polymorphism was performed using polymerase chain reaction. The MCT1 A1470T genotypes were in agreement with the Hardy-Weinberg equilibrium distribution. The percentage of fat-free mass was significantly higher in soccer players with the TT genotype and in the T-allele-dominant model group (TT + AT) compared with the soccer players with the AA genotype. The MCT1 T allele is associated with the percentage of fat-free mass in young elite male soccer players. Elucidating the genetic basis of body composition in athletes could potentially be used as an additional tool for strength and conditioning professionals in planning and adjusting training. However, these results are preliminary and need to be replicated in more cohorts.

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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].

  2. Sobetirome and its Amide Prodrug Sob-AM2 Exert Thyromimetic Actions in Mct8-Deficient Brain.

    PubMed

    Bárez-López, Soledad; Hartley, Meredith D; Grijota-Martínez, Carmen; Scanlan, Thomas S; Guadaño-Ferraz, Ana

    2018-06-29

    Loss of function mutations in the thyroid hormone (TH)-specific cell membrane transporter, the monocarboxylate transporter 8 (MCT8), lead to profound psychomotor retardation and abnormal TH serum levels, with low thyroxine (T4) and high triiodothyronine (T3). Several studies point to impaired TH transport across brain barriers as a crucial pathophysiological mechanism resulting in cerebral hypothyroidism. Treatment options for MCT8-deficient patients are limited and are focused on overcoming the brain barriers. The aim of this study was to evaluate the ability of the TH analog sobetirome and its prodrug Sob-AM2 to access the brain and exert thyromimetic actions in the absence of Mct8. Juvenile wild-type (Wt) mice and mice lacking Mct8 and deiodinase type 2 (Mct8/Dio2KO) were treated systemically with daily injections of vehicle, 1 mg of sobetirome/kg body weight/day, or 0.3 mg of Sob-AM2/kg body weight/day for seven days. Sobetirome content was measured using liquid chromatography-tandem mass spectrometry, and T4 and T3 levels by specific radioimmunoassays. The effect of sobetirome treatment in the expression of T3-dependent genes was measured in the heart, liver, and cerebral cortex by real-time polymerase chain reaction. Sob-AM2 treatment in Mct8/Dio2KO animals led to 1.8-fold more sobetirome content in the brain and 2.5-fold less in plasma in comparison to the treatment with the parent drug sobetirome. Both sobetirome and Sob-AM2 treatments in Mct8/Dio2KO mice greatly decreased plasma T4 and T3 levels. Dio1 and Ucp2 gene expression was altered in the liver of Mct8/Dio2KO mice and was not affected by the treatments. In the heart, Hcn2 but not Atp2a2 expression was increased after treatment with the analogs. Interestingly, both sobetirome and Sob-AM2 treatments increased the expression of several T3-dependent genes in the brain such as Hr, Abcd2, Mme, and Flywch2 in Mct8/Dio2KO mice. Sobetirome and its amide prodrug Sob-AM2 can access the brain in the absence

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

    NASA Astrophysics Data System (ADS)

    Lorenz, Christian; Stevens, Mark; Wool, Richard

    2003-03-01

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

  4. 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.

  5. How to treat the untreated: effectiveness of a self-help metacognitive training program (myMCT) for obsessive-compulsive disorder

    PubMed Central

    Moritz, Steffen; Jelinek, Lena; Hauschildt, Marit; Naber, Dieter

    2010-01-01

    Despite advances in the understanding and treatment of obsessive-compulsive disorder (OCD), many patients undergoing interventions display incomplete symptom reduction. Our research group has developed a self-help manual entitled “My Metacognitive Training for OCD” (myMCT) aimed at raising patients' awareness about cognitive biases that seem to subserve OCD. The training is particularly intended for patients currently unable or unwilling to attend standard therapy, or in cases where such a treatment option is not available. For the present study, 86 individuals suffering from OCD were recruited over the Internet. Following the initial assessment participants were either immediately emailed the myMCT manual or allocated to a waitlist group. After 4 weeks, a second assessment was performed. The myMCT group showed significantly greater improvement for OCD symptoms according to the Y-BOCS total score compared with the waitlist group (d =.63), particularly for obsessions (d=.69). Medium to strong differences emerged for the OCI-R (d =.70) and the BDI-SF (d =.50). The investigation provides the first evidence for the effectiveness of the myMCT for OCD. PMID:20623925

  6. 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.

  7. 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

  8. 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

  9. Influence of Polysorbate 60 on Formulation Properties and Bioavailability of Morin-Loaded Nanoemulsions with and without Low-Saponification-Degree Polyvinyl Alcohol.

    PubMed

    Ikeuchi-Takahashi, Yuri; Kobayashi, Ayaka; Ishihara, Chizuko; Matsubara, Takumi; Matsubara, Hiroaki; Onishi, Hiraku

    2018-01-01

    The aim of the present study was to investigate the influence of polysorbate 60 (Tween 60) on the development of morin-loaded nanoemulsions to improve the oral bioavailability of morin. Nanoemulsions were prepared using Tween 60 and polyvinyl alcohol (PVA) as emulsifiers, and medium chain triglycerides (MCT) as the lipid base. Low-saponification-degree PVA (LL-810) was also added to stabilize dispersed droplets. MCT-LL810 nanoemulsion containing LL-810 was prepared with a reduced amount of Tween 60. However, the area under the blood concentration-time curve (AUC) of MCT-LL810 (0.18) nanoemulsion containing a small amount of Tween 60 did not increase because the absorption of morin was limited by P-glycoprotein (P-gp)-mediated efflux. MCT-LL810 (0.24) nanoemulsion containing a large amount of Tween 60 showed the highest AUC, dispersed droplets containing Tween 60 may have been transported into epithelial cells in the small intestine, and P-gp transport activity appeared to be suppressed by permeated Tween 60. Based on the plasma concentration profile, dispersed droplets in MCT-LL810 (0.24) nanoemulsion permeated more rapidly through the mucus layer and the intestinal membrane than MCT (0.24) nanoemulsion without LL-810. In conclusion, a novel feature of Tween 60 incorporated into the dispersed droplets of a nanoemulsion interacting with P-gp was demonstrated herein. Dispersed droplets in MCT-LL810 (0.24) nanoemulsion containing LL-810 permeated rapidly through the mucus layer and intestinal membrane, and Tween 60 incorporated in dispersed droplets interacted with P-gp-mediated efflux, increasing the bioavailability of morin.

  10. Structured triglyceride vehicles for oral delivery of halofantrine: examination of intestinal lymphatic transport and bioavailability in conscious rats.

    PubMed

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

    2002-09-01

    To compare the influence of triglyceride vehicle intramolecular structure on the intestinal lymphatic transport and systemic absorption of halofantrine in conscious rats. Conscious, lymph cannulated and nonlymph cannulated rats were dosed orally with three structurally different triglycerides; sunflower oil, and two structured triglycerides containing different proportion and position of medium-(M) and long-chain (L) fatty acids on the glycerol backbone. The two structured triglycerides were abbreviated MLM and LML to reflect the structural position on the glycerol. The concentration of halofantrine in blood and lymph samples was analyzed by HPLC. Both the lymphatic transport and the total absorption of halofantrine were enhanced by the use the MLM triglyceride. The estimated total absorption of halofantrine in the lymph cannulated animals was higher than in the nonlymph cannulated animals, and this was most pronounced for the animals dosed with the structured triglycerides. Using MLM as vehicle increases the portal absorption of halofantrine and results in similar lymphatic transport levels when compared to sunflower oil. Total absorption when assessed as absorption in the blood plus lymphatic transport for halofantrine after administration in the MLM triglyceride was higher than after administration in sunflower oil.

  11. 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.

  12. 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.

  13. A coconut oil-rich meal does not enhance thermogenesis compared to corn oil in a randomized trial in obese adolescents

    PubMed Central

    LaBarrie, Janna; St-Onge, Marie-Pierre

    2017-01-01

    Background Consumption of medium chain triglycerides (MCT) in overweight adults increases thermogenesis and improves weight management. Coconut oil is a rich natural source of MCT, but its thermogenic effect is unknown. Our study evaluated the effects of a test oil enriched in coconut oil, on energy expenditure, satiety, and metabolic markers in a randomized, double blind, cross-over study. Methods and findings Fifteen children, age 13-18 years, body mass index >85th percentile for age and sex, were enrolled. Two test meals, containing 20 g of fat from either corn oil or a coconut oil-enriched baking fat (1.1 g of fatty acids with chain lengths ≤ 10C), were administered. A fasting blood sample was taken before breakfast and at 30, 45, 60, 120, and 180 min post-meal for measurement of metabolites. Thermic effect of food (TEF) was assessed over 6 h using indirect calorimetry. Satiety was measured using visual analog scales (VAS). There was no significant effect of fat type, time, or fat type × time interaction on TEF, appetite/satiety, glucose, and insulin area under the curve. There was a significant effect of fat type on leptin (P=0.027), triglycerides (P=0.020) and peptide YY (P=0.0085); leptin and triglyceride concentrations were lower and peptide YY concentrations were higher with corn oil consumption. Conclusion A coconut oil-enriched baking fat does not enhance thermogenesis and satiety in children. Given that this is the only current study of its kind, more research is needed into the use of coconut oil as a tool in weight management in overweight and obese children. PMID:28758166

  14. A coconut oil-rich meal does not enhance thermogenesis compared to corn oil in a randomized trial in obese adolescents.

    PubMed

    LaBarrie, Janna; St-Onge, Marie-Pierre

    2017-01-01

    Consumption of medium chain triglycerides (MCT) in overweight adults increases thermogenesis and improves weight management. Coconut oil is a rich natural source of MCT, but its thermogenic effect is unknown. Our study evaluated the effects of a test oil enriched in coconut oil, on energy expenditure, satiety, and metabolic markers in a randomized, double blind, cross-over study. Fifteen children, age 13-18 years, body mass index >85th percentile for age and sex, were enrolled. Two test meals, containing 20 g of fat from either corn oil or a coconut oil-enriched baking fat (1.1 g of fatty acids with chain lengths ≤ 10C), were administered. A fasting blood sample was taken before breakfast and at 30, 45, 60, 120, and 180 min post-meal for measurement of metabolites. Thermic effect of food (TEF) was assessed over 6 h using indirect calorimetry. Satiety was measured using visual analog scales (VAS). There was no significant effect of fat type, time, or fat type × time interaction on TEF, appetite/satiety, glucose, and insulin area under the curve. There was a significant effect of fat type on leptin (P=0.027), triglycerides (P=0.020) and peptide YY (P=0.0085); leptin and triglyceride concentrations were lower and peptide YY concentrations were higher with corn oil consumption. A coconut oil-enriched baking fat does not enhance thermogenesis and satiety in children. Given that this is the only current study of its kind, more research is needed into the use of coconut oil as a tool in weight management in overweight and obese children.

  15. 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.

  16. The lowering effect of dietary glucose versus starch on fat digestibility in rats is dependent on the type of fat in the diet.

    PubMed

    Vissia, G H; Beynen, A C

    2000-07-01

    The aim of the study was to determine whether the type of dietary fat influences the effect of dietary glucose on lipid digestibility. Earlier work had shown that glucose, when compared with starch, reduced fat digestibility in rats fed rations containing animal fat as fat source. Male rats (n = 6/group) were fed for two weeks on purified diets containing either 62% (w/w) starch or glucose and either 8% (w/w) palm oil, coconut fat, soybean oil or medium-chain triglycerides (MCT) as the main source of fat. The diets had no differential effect on growth. Glucose significantly depressed apparent lipid digestibility in rats fed the diets containing either palm oil or coconut fat, but not in rats given the diets containing either soybean oil or MCT. Thus, the inhibitory effect of glucose on lipid digestibility in rats is dependent on the dietary lipid source. This observation may contribute to understanding the mechanism by which dietary glucose inhibits fat digestion.

  17. Autophagy promotes metastasis and glycolysis by upregulating MCT1 expression and Wnt/β-catenin signaling pathway activation in hepatocellular carcinoma cells.

    PubMed

    Fan, Qing; Yang, Liang; Zhang, Xiaodong; Ma, Yingbo; Li, Yan; Dong, Lei; Zong, Zhihong; Hua, Xiangdong; Su, Dongming; Li, Hangyu; Liu, Jingang

    2018-01-19

    Autophagy is a dynamic physiological process that can generate energy and nutrients for cell survival during stress. Autophagy can regulate the migration and invasive ability in cancer cells. However, the connection between autophagy and metabolism is unclear. Monocarboxylate transporter 1 (MCT1) plays an important role in lactic acid transport and H + clearance in cancer cells, and Wnt/β-catenin signaling can increase cancer cell glycolysis. We investigated whether autophagy promotes glycolysis in hepatocellular carcinoma (HCC) cells by activating the Wnt/β-catenin signaling pathway, accompanied by MCT1 upregulation. Autophagic activity was evaluated using western blotting, immunoblotting, and transmission electron microscopy. The underlying mechanisms of autophagy activation on HCC cell glycolysis were studied via western blotting, and Transwell, lactate, and glucose assays. MCT1 expression was detected using quantitative reverse transcription-PCR (real-time PCR), western blotting, and immunostaining of HCC tissues and the paired adjacent tissues. Autophagy promoted HCC cell glycolysis accompanied by MCT1 upregulation. Wnt/β-catenin signaling pathway activation mediated the effect of autophagy on HCC cell glycolysis. β-Catenin downregulation inhibited the autophagy-induced glycolysis in HCC cells, and reduced MCT1 expression in the HCC cells. MCT1 was highly expressed in HCC tissues, and high MCT1 expression correlated positively with the expression of microtubule-associated protein light chain 3 (LC3). Activation of autophagy can promote metastasis and glycolysis in HCC cells, and autophagy induces MCT1 expression by activating Wnt/β-catenin signaling. Our study describes the connection between autophagy and glucose metabolism in HCC cells and may provide a potential therapeutic target for HCC treatment.

  18. Enhancing Nutraceutical Bioavailability from Raw and Cooked Vegetables Using Excipient Emulsions: Influence of Lipid Type on Carotenoid Bioaccessibility from Carrots.

    PubMed

    Zhang, Ruojie; Zhang, Zipei; Zou, Liqiang; Xiao, Hang; Zhang, Guodong; Decker, Eric Andrew; McClements, David Julian

    2015-12-09

    The influence of the nature of the lipid phase in excipient emulsions on the bioaccessibility and transformation of carotenoid from carrots was investigated using a gastrointestinal tract (GIT) model. Excipient emulsions were fabricated using whey protein as an emulsifier and medium-chain triglycerides (MCT), fish oil, or corn oil as the oil phase. Changes in particle size, charge, and microstructure were measured as the carrot-emulsion mixtures were passed through simulated mouth, stomach, and small intestine regions. Carotenoid bioaccessibility depended on the type of lipids used to form the excipient emulsions (corn oil > fish oil ≫ MCT), which was attributed to differences in the solubilization capacity of mixed micelles formed from different lipid digestion products. The transformation of carotenoids was greater for fish oil and corn oil than for MCT, which may have been due to greater oxidation or isomerization. The bioaccessibility of the carotenoids was higher from boiled than raw carrots, which was attributed to greater disruption of the plant tissue facilitating carotenoid release. In conclusion, excipient emulsions are highly effective at increasing carotenoid bioaccessibility from carrots, but lipid type must be optimized to ensure high efficacy.

  19. Nonessential fatty acids in formula fat blends influence essential fatty acid metabolism and composition in plasma and organ lipid classes in piglets.

    PubMed

    Wall, K M; Diersen-Schade, D; Innis, S M

    1992-12-01

    The n-6 and n-3 fatty acid status of developing organs is the cumulative result of the diet lipid composition and many complex events of lipid metabolism. Little information is available, however, on the potential effects of the saturated fatty acid chain length (8:0-16:0) or oleic acid (18:1) content of the diet on the subsequent metabolism of the essential fatty acids 18:2n-6 and 18:3n-3 and their elongated/desaturated products. The effects of feeding piglets formulas with fat blends containing either coconut oil (12:0 + 14:0) or medium chain triglycerides (MCT, 8:0 + 10:0) but similar levels of 18:1, 18:2n-6 and 18:3n-3, or MCT with high or low 18:1 but constant 18:2n-6 and 18:3n-3 on the fatty acid composition of plasma, liver and kidney triglycerides, phospholipids and cholesteryl esters, and of brain total lipid, were studied. Diet-induced changes in the fatty acid composition of lipid classes were generally similar for plasma, liver and kidney. Dietary 18:1 content was reflected in tissue lipids and was inversely associated with levels of 18:2n-6. Lower percentage of 18:2n-6, however, was not associated with lower levels of its elongated/desaturated product 20:4n-6 but was associated with higher levels of 22:6n-3. Feeding coconut oil vs. MCT resulted in lower 18:1 levels in all lipids, and higher percentages of 20:4n-6 in tissue phospholipid. Increasing the dietary n-6/n-3 ratio from 5 to 8 significantly increased tissue percentage of 18:2n-6 and decreased phospholipid 22:6n-3.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. 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.

  1. Chinese hypertriglycerideamic subjects of different ages responded differently to consuming oil with medium- and long-chain fatty acids.

    PubMed

    Xue, Changyong; Liu, Yinghua; Wang, Jin; Zheng, Zixin; Zhang, Yuehong; Zhang, Yong; Zhang, Rongxin; Yu, Xiaoming; Jin, Hongjiang; Nosaka, Naohisa; Arai, Chie; Kasai, Michio; Aoyama, Toshiaki; Wu, Jian

    2009-08-01

    Two groups of Chinese hypertriacylglycerolemic subjects were recruited and randomized to medium- and long-chain triacylglycerols (MLCT) oil or long-chain triacylglycerols (LCT) oil. Two subgroups were divided by age at less or more 60 years in both groups. Both oils were consumed at 25-30 g daily for 8 weeks. Anthropometry, blood biochemicals, and computed tomography (CT) scanning were done at the initial and final times. In subjects of age less than 60 years on MLCT, the body weight, body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-hip ratio (WHR), body fat, total fat area, and subcutaneous fat area were significantly lower than those of the initial values, and the change values in these indicators and visceral fat area lowered significantly as compared with those on LCT. The levels of apoB, apoA2, apoC2, and apoC3 decreased significantly, and the change in values in the levels of triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), apoA1, apoB, apoA2, apoC2, apoC3 were significantly lower on MLCT of age under 60 years as compared with those on LCT.

  2. 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.

  3. 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.

  4. 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.

  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. 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.

  7. 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.

  8. 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

  9. 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

  10. Biophysical elucidation of the mechanism of enhanced drug release and topical delivery from polymeric film-forming systems.

    PubMed

    Garvie-Cook, Hazel; Frederiksen, Kit; Petersson, Karsten; Guy, Richard H; Gordeev, Sergey N

    2015-08-28

    The effect of incorporating the lipidic medium-chain triglyceride (MCT) into polymeric film-forming systems (FFS) for topical drug delivery has been evaluated. First, the in vitro release of betamethasone-17-valerate (BMV), a representative dermatological drug, was determined from FFS comprising either hydrophobic polyacrylate co-polymers, or hydrophilic hydroxypropyl cellulose, with and without MCT. Release was enhanced from both polymers in the presence of MCT. Atomic force microscopy imaging and nanoindentation of FFS with MCT revealed two-phase structured films with softer inclusions (0.5 to 4μm in diameter) surrounded by a more rigid structure. Chemical mapping with Raman micro-spectroscopy showed that MCT was primarily confined to the inclusions within the polymer, which predominated in the surrounding film. BMV was distributed throughout the film but was more concentrated outside the inclusions. Furthermore, while BMV dissolved better into the hydrophobic films, it was more soluble in the MCT inclusions in hydrophilic films, suggesting its increased availability for diffusion from these softer regions of the polymer and explaining the release enhancement observed. Second, ex vivo skin penetration studies clearly revealed that uptake of BMV was higher from hydrophobic FFS than that from the more hydrophilic polymer due, at least in part, to the superior anti-nucleation efficiency of the former. Drug was quickly taken up into the SC from which it then diffused continuously over a sustained period into the lower, viable skin layers. In the presence of MCT, the overall uptake of BMV was increased and provides the basis for further optimisation of FFS as simple, convenient and sustained formulations for topical therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. Effects of miglyol 812 on rats after 4 weeks of gavage as compared with methylcellulose/tween 80.

    PubMed

    Sellers, Rani S; Antman, M; Phillips, J; Khan, K N; Furst, S M

    2005-01-01

    Miglyol 812 is a medium-chain triglyceride used in toxicology studies as an excipient to improve test compound solubility/absorption. As part of a larger toxicology study, 15 Wistar Han IGS rats/sex/group were dosed by oral gavage for 4 weeks with 10 mL kg(-1) day(-1) of 100% Miglyol 812 or 0.5% methylcellulose/0.1% Tween 80 in water (MC-T) followed by 4 weeks without treatment to evaluate the potential effects of this excipient in long-term toxicology studies relative to a traditional excipient such as MC-T. Clinical signs evident during the dosing phase included soft and/or mucoid stool in 12/15 males and 11/15 females treated with Miglyol 812 but in no animals treated with MC-T. Animals treated with Miglyol 812 had a 6-7% statistically significant reduction in body weight gain as compared to MC-T-treated animals. Statistically significant changes in clinical chemistry parameters as compared to MC-T included decreased blood urea nitrogen (50% and 29% in males and females, respectively), increased cholesterol (1.6-fold and 1.5-fold in males and females, respectively), decreased total protein (6% and 8% in males and females, respectively), decreased globulins (15% and 11% in males and females, respectively), and increased triglycerides (2.8-fold and 1.7-fold in males and females, respectively). Absolute and relative thymic weights decreased 28% and 24%, respectively, in males, and 18% and 17%, respectively, in females without histological alterations. Histopathology revealed increased alveolar histiocytosis with focal interstitial inflammation in lungs in 5/10 males and 7/10 females treated with Miglyol 812 compared to only 1/10 males and 1/10 females treated with MC-T. All effects were reversible during the recovery period. Results of this study indicate that 100% miglyol 812 produces reversible gastrointestinal effects and decreases in body weight gains along with changes in several serum chemistry parameters. Therefore, it should not be considered innocuous when

  16. 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.

  17. 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.

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

    NASA Astrophysics Data System (ADS)

    Yan, Mengguo; Cochran, Eric

    2014-03-01

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

  19. 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.

  20. Differential effects of dietary fats on sympathetic nervous system activity in the rat.

    PubMed

    Young, J B; Walgren, M C

    1994-01-01

    Fat feeding stimulates sympathetic nervous system (SNS) activity in rats. To determine if fats vary in their potency as stimulants of the SNS, [3H]norepinephrine ([3H]NE) turnover was measured in heart and interscapular brown adipose tissue (IBAT) of animals fed lab chow diets supplemented with safflower oil, coconut oil, or medium-chain triglycerides (MCT). At 5 days, all three fats accelerated [3H]NE turnover in heart and did so equally, but only when the fat supplement represented an increase in energy intake. However, after 14 days, safflower oil and coconut oil but not MCT increased [3H]NE turnover in heart compared with turnover rates obtained in animals fed isoenergetic amounts of chow. Furthermore, the stimulatory effect of safflower oil on [3H]NE turnover was statistically greater than that seen in animals fed equivalent amounts of coconut oil. In vivo synthesis of NE assessed by accumulation of dopamine (DA) in heart following inhibition of dopamine-beta-hydroxylase (D beta H) was likewise highest in safflower oil-fed rats and lowest in those fed MCT. Thus, sympathetic activation by dietary fat varies among different fats, suggesting a role for fatty acid intake in dietary regulation of the SNS.

  1. 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.

  2. Triglyceride accumulation protects against fatty acid-induced lipotoxicity

    PubMed Central

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

    2003-01-01

    Excess lipid accumulation in non-adipose tissues is associated with insulin resistance, pancreatic β-cell apoptosis and heart failure. Here, we demonstrate in cultured cells that the relative toxicity of two common dietary long chain fatty acids is related to channeling of these lipids to distinct cellular metabolic fates. Oleic acid supplementation leads to triglyceride accumulation and is well tolerated, whereas excess palmitic acid is poorly incorporated into triglyceride and causes apoptosis. Unsaturated fatty acids rescue palmitate-induced apoptosis by channeling palmitate into triglyceride pools and away from pathways leading to apoptosis. Moreover, in the setting of impaired triglyceride synthesis, oleate induces lipotoxicity. Our findings support a model of cellular lipid metabolism in which unsaturated fatty acids serve a protective function against lipotoxicity though promotion of triglyceride accumulation. PMID:12629214

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

    PubMed

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

    1994-01-01

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

  4. Model studies on the release of aroma compounds from structured and nonstructured oil systems using proton-transfer reaction mass spectrometry.

    PubMed

    Landy, Pascale; Pollien, Philippe; Rytz, Andreas; Leser, Martin E; Sagalowicz, Laurent; Blank, Imre; Spadone, Jean-Claude

    2007-03-07

    Relative retention, volatility, and temporal release of volatile compounds taken from aldehyde, ester, and alcohol chemical classes were studied at 70 degrees C in model systems using equilibrium static headspace analysis and real time dynamic headspace analysis. These systems were medium-chain triglycerides (MCT), sunflower oil, and two structured systems, i.e., water-in-oil emulsion and L2 phase (water-in-oil microemulsion). Hydrophilic domains of the emulsion type media retained specifically the hydrophilic compounds and alcohols. Four kinetic parameters characterizing the concentration- and time-dependent releases were extracted from the aroma release curves. Most of the kinetic parameter values were higher in structured systems than in oils particularly when using MCT. The oil nature was found to better control the dynamic release profiles than the system structures. The release parameters were well-related (i) to the volatile hydrophobicity as a function of the oil used and (ii) to the retention data in the specific case of the L2 phase due to a specific release behavior of alcohols.

  5. Expression of lactate/H⁺ symporters MCT1 and MCT4 and their chaperone CD147 predicts tumor progression in clear cell renal cell carcinoma: immunohistochemical and The Cancer Genome Atlas data analyses.

    PubMed

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

    2015-01-01

    Clear cell renal cell carcinomas (ccRCCs) have inactivation of the von Hippel-Lindau protein, leading to the accumulation of hypoxia-inducible factor-α (HIF-α). HIF-1α induces aerobic glycolysis, the Warburg effect, whereas HIF-2α functions as an oncoprotein. Lactate transport through monocarboxylate transporters (MCTs) and the chaperone CD147 is essential for high glycolytic cancer cell survival. To elucidate the clinical significance of MCT1, MCT4, and CD147 expression, we investigated their expressions by immunohistochemistry in ccRCC specimens and validated the results by an open-access The Cancer Genome Atlas data analysis. Overexpression of MCT1, MCT4, and CD147 was observed in 49.4% (89/180), 39.4% (71/180), and 79.4% (143/180) of ccRCC patients, respectively. High MCT1 expression was associated with older age (P = .017), larger tumor size (P = .015), and advanced TNM stage (P = .012). However, MCT4 overexpression was not related to any variables. CD147 overexpression correlated with high grade (P = .005), tumor necrosis (P = .016), and larger tumor size (P = .038). In univariate analysis, high expression of MCT1 (P < .001), MCT4 (P = .016), and CD147 (P = .02) was linked to short progression-free survival. In multivariate analysis, high MCT1 expression was associated with worse progression-free survival (P = .001). In conclusion, high expression of MCT1 and CD147 is associated with poor prognostic factors. Overexpression of MCT1, MCT4, and CD147 predicts tumor progression. Reversing the Warburg effect by targeting the lactate transporters may be a useful strategy to prevent ccRCC progression. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. 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.

  7. 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

  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. 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. 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.

  11. Differences in MCT1 A1470T polymorphism prevalence between runners and swimmers.

    PubMed

    Ben-Zaken, S; Eliakim, A; Nemet, D; Rabinovich, M; Kassem, E; Meckel, Y

    2015-06-01

    Skeletal muscle is the major producer and user of lactate in the body. Therefore, transport of lactate across cells' membrane is of considerable importance. Lactate transport is mediated by proton-linked monocarboxylate transporter (MCT1). The A1470T polymorphism (rs1049434) in MCT1 gene influences lactate transport, with T allele associated with reduction of lactate transport rate and elevation in blood lactate levels. The aim of the current study was to compare allelic and genotype frequencies of MCT1 A1470T polymorphism among Israeli track-and-field athletes, swimmers, and non-athletes. Genomic DNA was extracted from 173 track-and-field athletes (age 17-50), 80 swimmers (age 16-49), and 128 non-athletes (age 19-29). Track-and-field athletes were assigned to three subgroups: long-distance runners, middle-distance runners, and power event athletes. Swimmers were assigned to two subgroups: long-distance swimmers and short-distance swimmers. Genotyping was performed using polymerase chain reaction. T-allele frequency was significantly higher among long-distance swimmers (45%) compared with long- and middle-distance runners (27% and 30%, respectively; P < 0.01). In addition, T-allele frequency was significantly higher among short-distance swimmers (40%) compared with power event athletes (25%, P < 0.01). Overall, T-allele frequency was significantly higher among swimmers (42%) compared with runners (27%, P < 0.001). More research is needed to clarify whether this polymorphism displays advantage for swimming performance. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Enhanced rectal absorption of amphotericin B lyophilized with glycyrrhizinate in rabbits.

    PubMed

    Tanaka, M; Kuwahara, E; Takahashi, M; Koyama, O; Takahashi, N; Yotsuyanagi, T

    1998-08-01

    The influence of bases and additives in the formulation for rectal absorption of amphotericin B (AMB) lyophilized with dipotassium glycyrrhizinate (GLYK) was investigated using rabbits in relation to an in vitro release test. The release of AMB from the fatty base of Witepsol or a medium chain triglyceride (MCT) was markedly faster than that from the hydrophilic base of macrogol. The addition of polyoxyethylene (2) lauryl ether (POE(2)LE) into the fatty bases led to a marked increase in the release rate, whereas POE(9)LE or sodium lauryl sulfate resulted in a significantly lower release rate. Animals received rectally each of seven AMB formulations of Witepsol H-15, macrogol, MCT with surfactants and aqueous solution. The absorption of the AMB lyophilized mixture with GLYK at a 1:9 molar ratio from a MCT base was significantly superior to that from macrogol. The addition of POE(2)LE into the MCT base resulted in a marked increase in bioavailability, showing the highest bioavailability of 4.9%. High serum levels of over 100 ng/ml of serum were maintained for 24 h following administration. The lowest bioavailability was 0.32% for the macrogol suppository. There was a good correlation between the release rate of AMB from the formulations and bioavailability. These results suggest that an AMB rectal formulation may provide a promising therapeutic alternative to infusion, taking into account the serum level of AMB exceeding the minimal inhibitory concentration of the infecting organism.

  13. 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

  14. A common polymorphism of the MCT1 gene and athletic performance.

    PubMed

    Fedotovskaya, Olga N; Mustafina, Leysan J; Popov, Daniil V; Vinogradova, Olga L; Ahmetov, Ildus I

    2014-01-01

    In red skeletal muscle, monocarboxylate transporter 1 (MCT1) is required for lactate to enter the myocytes for oxidation. The A1470T polymorphism (rs1049434) in the MCT1 gene was shown to be associated with lactate transport rates in human skeletal muscles. The aim of the study was to compare genotype and allele frequencies of the MCT1 gene polymorphism in 323 Russian athletes and 467 nonathletic controls and to investigate the association of the MCT1 gene A1470T polymorphism with maximal oxygen consumption and maximal lactate concentration in rowers (n = 79). Genotyping for the A1470T MCT1 polymorphism was performed by PCR-RFLP method. Physiological measurements of 79 Russian rowers of national competitive standard were determined during an incremental test to exhaustion on a rowing ergometer. Frequencies of the A allele (71.8% vs 62.5%, P < .0001) and AA genotype (59.8% vs 39.4%, P < .0001) were significantly higher in endurance-oriented athletes (n = 142) than in the control group. Mean blood lactate concentration was higher in male rowers with the T allele (AT+TT 10.26 ± 1.89 mmol/L, AA 8.75 ± 1.69 mmol/L, P = .005). MCT1 gene A1470T polymorphism is associated with endurance athlete status and blood lactate level after intensive exercise.

  15. Revisiting the metabolism and physiological functions of caprylic acid (C8:0) with special focus on ghrelin octanoylation.

    PubMed

    Lemarié, Fanny; Beauchamp, Erwan; Legrand, Philippe; Rioux, Vincent

    2016-01-01

    Caprylic acid (octanoic acid, C8:0) belongs to the class of medium-chain saturated fatty acids (MCFAs). Dairy products and specific oils like coconut oil are natural sources of dietary C8:0 but higher intakes of this fatty acid can be provided with MCT (Medium-Chain Triglycerides) oil that consists in 75% of C8:0. MCFAs have physical and metabolic properties that are distinct from those of long-chain saturated fatty acids (LCFAs ≥ 12 carbons). Beneficial physiological effects of dietary C8:0 have been studied for a long time and MCT oil has been used as a special energy source for patients suffering from pancreatic insufficiency, impaired lymphatic chylomicron transport and fat malabsorption. More recently, caprylic acid was also shown to acylate ghrelin, the only known peptide hormone with an orexigenic effect. Through its covalent binding to the ghrelin peptide, caprylic acid exhibits an emerging and specific role in modulating physiological functions themselves regulated by octanoylated ghrelin. Dietary caprylic acid is therefore now suspected to provide the ghrelin O-acyltransferase (GOAT) enzyme with octanoyl-CoA co-substrates necessary for the acyl modification of ghrelin. This review tries to highlight the discrepancy between the formerly described beneficial effects of dietary MCFAs on body weight loss and the C8:0 newly reported effect on appetite stimulation via ghrelin octanoylation. The subsequent aim of this review is to demonstrate the relevance of carrying out further studies to better understand the physiological functions of this particular fatty acid. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  16. 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

  17. 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

  18. 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.

  19. Phytonadione Content in Branded Intravenous Fat Emulsions.

    PubMed

    Forchielli, Maria Luisa; Conti, Matteo; Motta, Roberto; Puggioli, Cristina; Bersani, Germana

    2017-03-01

    Intravenous fat emulsions (IVFE) with different fatty acid compositions contain vitamin E as a by-product of vegetable and animal oil during the refining processes. Likewise, other lipid-soluble vitamins may be present in IVFE. No data, however, exist about phytonadione (vitamin K1) concentration in IVFE information leaflets. Therefore, our aim was to evaluate the phytonadione content in different IVFE. Analyses were carried out in triplicate on 6 branded IVFE as follows: 30% soybean oil (100%), 20% olive-soybean oil (80%-20%), 20% soybean-medium-chain triglycerides (MCT) coconut oil (50%-50%), 20% soybean-olive-MCT-fish oil (30%-25%-30%-15%), 20% soybean-MCT-fish oil (40%-50%-10%), and 10% pure fish oil (100%). Phytonadione was analyzed and quantified by a quali-quantitative liquid chromatography-mass spectrometry (LC-MS) method after its extraction from the IVFE by an isopropyl alcohol-hexane mixture, reverse phase-liquid chromatography, and specific multiple-reaction monitoring for phytonadione and vitamin d3 (as internal standard). This method was validated through specificity, linearity, and accuracy. Average vitamin K1 content was 500, 100, 90, 100, 95, and 70 µg/L in soybean oil, olive-soybean oil, soybean-MCT coconut oil, soybean-olive-MCT-fish oil, soybean-MCT-fish oil, and pure fish oil intravenous lipid emulsions (ILEs), respectively. The analytical LC-MS method was extremely effective in terms of specificity, linearity ( r = 0.99), and accuracy (coefficient of variation <5%). Phytonadione is present in IVFE, and its intake varies according to IVFE type and the volume administered. It can contribute to daily requirements and become clinically relevant when simultaneously infused with multivitamins during long-term parenteral nutrition. LC-MS seems adequate in assessing vitamin K1 intake in IVFE.

  20. 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.

  1. Role of Medium- and Short-Chain L-3-Hydroxyacyl-CoA Dehydrogenase in the Regulation of Body Weight and Thermogenesis

    PubMed Central

    Schulz, Nadja; Himmelbauer, Heinz; Rath, Michaela; van Weeghel, Michel; Houten, Sander; Kulik, Wim; Suhre, Karsten; Scherneck, Stephan; Vogel, Heike; Kluge, Reinhart; Wiedmer, Petra; Joost, Hans-Georg

    2011-01-01

    Dysregulation of fatty acid oxidation plays a pivotal role in the pathophysiology of obesity and insulin resistance. Medium- and short-chain-3-hydroxyacyl-coenzyme A (CoA) dehydrogenase (SCHAD) (gene name, hadh) catalyze the third reaction of the mitochondrial β-oxidation cascade, the oxidation of 3-hydroxyacyl-CoA to 3-ketoacyl-CoA, for medium- and short-chain fatty acids. We identified hadh as a putative obesity gene by comparison of two genome-wide scans, a quantitative trait locus analysis previously performed in the polygenic obese New Zealand obese mouse and an earlier described small interfering RNA-mediated mutagenesis in Caenorhabditis elegans. In the present study, we show that mice lacking SCHAD (hadh−/−) displayed a lower body weight and a reduced fat mass in comparison with hadh+/+ mice under high-fat diet conditions, presumably due to an impaired fuel efficiency, the loss of acylcarnitines via the urine, and increased body temperature. Food intake, total energy expenditure, and locomotor activity were not altered in knockout mice. Hadh−/− mice exhibited normal fat tolerance at 20 C. However, during cold exposure, knockout mice were unable to clear triglycerides from the plasma and to maintain their normal body temperature, indicating that SCHAD plays an important role in adaptive thermogenesis. Blood glucose concentrations in the fasted and postprandial state were significantly lower in hadh−/− mice, whereas insulin levels were elevated. Accordingly, insulin secretion in response to glucose and glucose plus palmitate was elevated in isolated islets of knockout mice. Therefore, our data indicate that SCHAD is involved in thermogenesis, in the maintenance of body weight, and in the regulation of nutrient-stimulated insulin secretion. PMID:21990309

  2. 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.

  3. 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.

  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. Effects of a Series of Acidic Drugs on L-Lactic Acid Transport by the Monocarboxylate Transporters MCT1 and MCT4.

    PubMed

    Leung, Yat H; Belanger, Francois; Lu, Jennifer; Turgeon, Jacques; Michaud, Veronique

    2017-01-01

    Drug-induced myopathy is a serious side effect that often requires removal of a medication from a drug regimen. For most drugs, the underlying mechanism of drug-induced myopathy remains unclear. Monocarboxylate transporters (MCTs) mediate L-lactic acid transport, and inhibition of MCTs may potentially lead to perturbation of L-lactic acid accumulation and muscular disorders. Therefore, we hypothesized that L-lactic acid transport may be involved in the development of drug-induced myopathy. The aim of this study was to assess the inhibitory potential of 24 acidic drugs on L-lactic acid transport using breast cancer cell lines Hs578T and MDA-MB-231, which selectively express MCT1 and MCT4, respectively. The influx transport of L-lactic acid was minimally inhibited by all drugs tested. The efflux transport was next examined: loratadine (IC50: 10 and 61 µM) and atorvastatin (IC50: 78 and 41 µM) demonstrated the greatest potency for inhibition of L-lactic acid efflux by MCT1 and MCT4, respectively. Acidic drugs including fluvastatin, cerivastatin, simvastatin acid, lovastatin acid, irbesartan and losartan exhibited weak inhibitory potency on L-lactic acid efflux. Our results suggest that some acidic drugs, such as loratadine and atorvastatin, can inhibit the efflux transport of L-lactic acid. This inhibition may cause an accumulation of intracellular L-lactic acid leading to acidification and muscular disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. 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

  7. Short term and dosage influences of palm based medium- and long-chain triacylglycerols on body fat and blood parameters in C57BL/6J mice.

    PubMed

    Lee, Yee-Ying; Tang, Teck-Kim; Ab Karim, Nur Azwani; Alitheen, Noorjahan Banu Mohamed; Lai, Oi-Ming

    2014-01-01

    Structured lipid medium- and long-chain triacylglycerols (MLCT) are claimed to be able to manage obesity. The present study investigated the body fat influence of enzymatically interesterifed palm-based medium- and long-chain triacylglycerols (P-MLCT) on diet-induced obesity (DIO) C57BL/6J mice compared with commercial MLCT oil (C-MLCT) and a control, which was the non enzymatically modified palm kernel and palm oil blend (PKO-PO blend). It also investigated the low fat and high fat effects of P-MLCT. DIO C57BL/6J mice were fed ad libitum with low fat (7%) and high fat (30%) experimental diets for 8 weeks before being sacrificed to obtain blood serum for analysis. From the results, there is a trend that P-MLCT fed mice were found to have the lowest body weight, body weight gain, total fat pad accumulation (perirenal, retroperitoneal, epididymal and mesenteric), total triglyceride levels and efficiency in controlling blood glucose level, compared with C-MLCT and the PKO-PO blend in both low fat and high fat diets. Nevertheless, the PKO-PO blend and P-MLCT caused significantly (P < 0.05) higher total cholesterol levels compared to C-MLCT. P-MLCT present in low fat and high fat dosage were shown to be able to suppress body fat accumulation. This effect is more prominent with the low fat dosage.

  8. Simulated glass-forming polymer melts: dynamic scattering functions, chain length effects, and mode-coupling theory analysis.

    PubMed

    Frey, S; Weysser, F; Meyer, H; Farago, J; Fuchs, M; Baschnagel, J

    2015-02-01

    We present molecular-dynamics simulations for a fully flexible model of polymer melts with different chain length N ranging from short oligomers (N = 4) to values near the entanglement length (N = 64). For these systems we explore the structural relaxation of the supercooled melt near the critical temperature T c of mode-coupling theory (MCT). Coherent and incoherent scattering functions are analyzed in terms of the idealized MCT. For temperatures T > T c we provide evidence for the space-time factorization property of the β relaxation and for the time-temperature superposition principle (TTSP) of the α relaxation, and we also discuss deviations from these predictions for T ≈ T c. For T larger than the smallest temperature where the TTSP holds we perform a quantitative analysis of the dynamics with the asymptotic MCT predictions for the late β regime. Within MCT a key quantity, in addition to T c, is the exponent parameter λ. For the fully flexible polymer models studied we find that λ is independent of N and has a value (λ = 0.735 ) typical of simple glass-forming liquids. On the other hand, the critical temperature increases with chain length toward an asymptotic value T c (∞) . This increase can be described by T c (∞) - T c(N) ∼ 1/N and may be interpreted in terms of the N dependence of the monomer density ρ, if we assume that the MCT glass transition is ruled by a soft-sphere-like constant coupling parameter Γ c = ρ c T c (-1/4), where ρ c is the monomer density at T c. In addition, we also estimate T c from a Hansen-Verlet-like criterion and MCT calculations based on structural input from the simulation. For our polymer model both the Hansen-Verlet criterion and the MCT calculations suggest T c to decrease with increasing chain length, in contrast to the direct analysis of the simulation data.

  9. Clinically relevant HIF-1α-dependent metabolic reprogramming in oropharyngeal squamous cell carcinomas includes coordinated activation of CAIX and the miR-210/ISCU signaling axis, but not MCT1 and MCT4 upregulation

    PubMed Central

    Sáenz-de-Santa-María, Inés; Bernardo-Castiñeira, Cristóbal; Secades, Pablo; Bernaldo-de-Quirós, Sandra; Rodrigo, Juan Pablo; Astudillo, Aurora; Chiara, María-Dolores

    2017-01-01

    Metabolic reprogramming is a very heterogeneous phenomenon in cancer. It mostly consists on increased glycolysis, lactic acid formation and extracellular acidification. These events have been associated to increased activity of the hypoxia inducible factor, HIF-1α. This study aimed at defining the metabolic program activated by HIF-1α in oropharyngeal squamous cell carcinomas (SCC) and assessing its clinical impact. Global gene/miRNA expression was analyzed in SCC-derived cells exposed to hypoxia. Expression of HIF-1α, the carbonic anhydrase CAIX, and the lactate/H+ transporters MCT1 and MCT4 were analyzed by immunohistochemistry in 246 SCCs. Cell-based analysis revealed that HIF-1α-driven metabolic program includes over-expression of glycolytic enzymes and the microRNA miR-210 coupled to down-regulation of its target, the iron-sulfur cluster assembly protein, ISCU. pH-regulator program entailed over-expression of CAIX, but not MCT1 or MCT4. Accordingly, significant overlapping exists between over-expression of HIF-1α and CAIX, but not HIF-1α and MCT1 or MCT4, in tumor cells. Increased miR-210 and concomitant decreased ISCU RNA levels were found in ~40% of tumors and this was significantly associated with HIF-1α and CAIX, but not MCT1 or MCT4, over-expression. HIF-1α and/or CAIX over-expression was associated with high recurrence rate and low overall survival of surgically treated patients. By contrast, clinically significant correlations were not found in tumors with MCT1 or MCT4 over-expression. This is the first study that provides in vivo evidences of coordinated activation of HIF-1α, CAIX, miR-210 and ISCU in carcinoma and association with poor prognosis, a finding with important implications for the development of metabolic-targeting therapies against hypoxia. PMID:28099149

  10. Clinically relevant HIF-1α-dependent metabolic reprogramming in oropharyngeal squamous cell carcinomas includes coordinated activation of CAIX and the miR-210/ISCU signaling axis, but not MCT1 and MCT4 upregulation.

    PubMed

    Sáenz-de-Santa-María, Inés; Bernardo-Castiñeira, Cristóbal; Secades, Pablo; Bernaldo-de-Quirós, Sandra; Rodrigo, Juan Pablo; Astudillo, Aurora; Chiara, María-Dolores

    2017-02-21

    Metabolic reprogramming is a very heterogeneous phenomenon in cancer. It mostly consists on increased glycolysis, lactic acid formation and extracellular acidification. These events have been associated to increased activity of the hypoxia inducible factor, HIF-1α. This study aimed at defining the metabolic program activated by HIF-1α in oropharyngeal squamous cell carcinomas (SCC) and assessing its clinical impact. Global gene/miRNA expression was analyzed in SCC-derived cells exposed to hypoxia. Expression of HIF-1α, the carbonic anhydrase CAIX, and the lactate/H+ transporters MCT1 and MCT4 were analyzed by immunohistochemistry in 246 SCCs. Cell-based analysis revealed that HIF-1α-driven metabolic program includes over-expression of glycolytic enzymes and the microRNA miR-210 coupled to down-regulation of its target, the iron-sulfur cluster assembly protein, ISCU. pH-regulator program entailed over-expression of CAIX, but not MCT1 or MCT4. Accordingly, significant overlapping exists between over-expression of HIF-1α and CAIX, but not HIF-1α and MCT1 or MCT4, in tumor cells. Increased miR-210 and concomitant decreased ISCU RNA levels were found in ~40% of tumors and this was significantly associated with HIF-1α and CAIX, but not MCT1 or MCT4, over-expression. HIF-1α and/or CAIX over-expression was associated with high recurrence rate and low overall survival of surgically treated patients. By contrast, clinically significant correlations were not found in tumors with MCT1 or MCT4 over-expression. This is the first study that provides in vivo evidences of coordinated activation of HIF-1α, CAIX, miR-210 and ISCU in carcinoma and association with poor prognosis, a finding with important implications for the development of metabolic-targeting therapies against hypoxia.

  11. 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

  12. 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

  13. 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.

  14. State-of-the-art MCT photodiodes for cutting-edge sensor applications by AIM

    NASA Astrophysics Data System (ADS)

    Figgemeier, H.; Hanna, S.; Eich, D.; Fries, P.; Mahlein, K.-M.; Wenisch, J.; Schirmacher, W.; Beetz, J.; Breiter, R.

    2017-02-01

    For about 30 years, AIM has been ranking among the leading global suppliers for high-performance MCT infrared detectors, with its portfolio spanning the photosensitivity cut-off range from the SWIR to the VLWIR and from 1st generation to 3rd generation FPA devices. To meet the market demands for SWaP-C- and IR-detectors with additional functionalities such as multicolor detection, AIM employs both LPE and MBE technology. From AIḾs line of highest-performance single color detectors fabricated by LPE, we will present our latest excellent results of 5.3 μm cut-off MWIR MCT detectors with 1024x768 pixels and a 10 μm pixel pitch. AIM's powerful low dark current LWIR and VLWIR p-on-n device technology on LPE-grown MCT has now been extended to the MWIR spectral range. A comparison of results from n-on-p and p-on-n MWIR MCT planar photodiode arrays is presented. Operating temperatures of 160 K and higher, in conjunction with low defect density and excellent thermal sensitivity (NETD) are attained. The results achieved for LPE MWIR are compared to MBE MWIR data. For both the cost-efficient production of MWIR single color MCT detectors, as well as 3rd generation multicolor MCT detectors, AIM makes use of MBE growth of MCT on large-area GaAs substrates. The now-available AIM MWIR single color MBE MCT detectors grown on GaAs are qualified, delivered, and have reached a maturity fully meeting customers' requirements. Representing AIM's multicolor detector development, latest test results on a 640x512 pixels with a 20 μm pitch design will be presented. The MWIR/MWIR diodes demonstrate high QE, very low color cross talk, and excellent NETD in conjunction with low defect densities.

  15. 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.

  16. Cerebral Cortex Hyperthyroidism of Newborn Mct8-Deficient Mice Transiently Suppressed by Lat2 Inactivation

    PubMed Central

    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. PMID:24819605

  17. 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.

  18. 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.

  19. Good response of low-fat/high-protein diet in a patient with chyluria.

    PubMed

    Triffoni-Melo, Andresa T; Diez-Garcia, Rosa Wanda; Barros Silva, Gyl Eanes; Garcia Caldas, Fernando de Freitas; Wichert-Ana, Lauro; Corte Denardi, Rafaela; Kato, Mery; Júnior Lucca, Leandro; Dantas, Márcio

    2014-04-01

    Chyluria is an inappropriate urinary excretion of chyle that turns the urine milky. A nutritional approach based on low-fat/high-protein content diet associated or not with medium-chain triglyceride (MCT) showed to be an efficient conservative treatment to improve the milky urine appearance in a patient with chyluria. A 30-year-old female patient was admitted with chyluria of unknown etiology. An ureteropyeloscopy revealed a single lesion in each kidney, both with linear aspect and measuring 5 mm in extension. These lesions were located close to the renal papillae and were leaking a cloudy and milky fluid. Both lesions were laser cauterized followed by improvement of the milky urine. However, the chyluria relapsed after few months and a low-fat/high-protein content diet with 10 g of soybean oil to meet the requirements essential fatty acids (EFA) and with MCT from coconut oil as alternative to prepare foods was started. Few weeks later the patient returned reporting consistent improvement of the milky urine appearance related with the use of the diet. However since the diet was tasteless and time consuming to prepare, she reported low compliance to diet with MCT and the milky urine relapsed. The MCT was discontinued and the diet with EFA source was maintained with better compliance. Since then the chyluria remains in remission. In conclusion, the dramatic improvement of the milky urine with low-fat/high-protein diet with EFA source observed in our patient demonstrates that this nutritional approach is efficient with fast results to treat chyluria during long term.

  20. Disulfiram-loaded mixed nanoparticles with high drug-loading and plasma stability by reducing the core crystallinity for intravenous delivery.

    PubMed

    Zhuo, Xuezhi; Lei, Tian; Miao, Linlin; Chu, Wei; Li, Xiaowen; Luo, Lifeng; Gou, Jingxin; Zhang, Yu; Yin, Tian; He, Haibing; Tang, Xing

    2018-05-30

    To develop an injectable formulation and improve the stability of disulfiram (DSF), DSF was encapsulated into mixed nanoparticles (DSF-NPs) through a high-pressure homogenization method. The Flory-Huggins interaction parameters (χ FH ) were calculated to predict the miscibility between DSF and the hydrophobic core, resulting in PCL 5000 selected as the hydrophobic block to encapsulate the DSF, as PCL 5000 had a lower χ FH 3.39 and the drug loading of the nanoparticles prepared by mPEG 5000 -PCL 5000 was relatively higher. mPEG 5000 -PCL 5000 and PCL 5000 were blended to reduce the leakage of DSF during preparation, as well as increase the stability of the nanoparticles. The cargo-loading capacity of the nanoparticles was improved from 3.35% to 5.50% by reducing the crystallinity of the PCL nanoparticle core, and the crystallinity decreased from 51.13% to 25.15% after adding medium chain triglyceride (MCT). The DSF-NPs prepared by the above method had a small particle size of 98.1 ± 10.54 nm, with a polydispersity index (PDI) of 0.036, as well as drug loading of 5.50%. Furthermore, DSF-NPs containing MCT showed higher stability than DSF-NPs without MCT and DSF-sol (DSF dissolved in Cremophor EL and ethanol) in water and 90% plasma-containing PBS. The pharmacokinetics proved that DSF-NPs containing MCT enhanced the DSF concentration in the blood. Finally, DSF-NPs effectively inhibited H22 xenograft tumor growth in vivo. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. 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.

  2. Influence of flavor solvent on flavor release and perception in sugar-free chewing gum.

    PubMed

    Potineni, Rajesh V; Peterson, Devin G

    2008-05-14

    The influence of flavor solvent [triacetin (TA), propylene glycol (PG), medium chained triglycerides (MCT), or no flavor solvent (NFS)] on the flavor release profile, the textural properties, and the sensory perception of a sugar-free chewing gum was investigated. Time course analysis of the exhaled breath and saliva during chewing gum mastication indicated that flavor solvent addition or type did not influence the aroma release profile; however, the sorbitol release rate was statistically lower for the TA formulated sample in comparison to those with PG, MCT, or NFS. Sensory time-intensity analysis also indicated that the TA formulated sample was statistically lower in perceived sweetness intensity, in comparison with the other chewing gum samples, and also had lower cinnamon-like aroma intensity, presumably due to an interaction between sweetness intensity on aroma perception. Measurement of the chewing gum macroscopic texture by compression analysis during consumption was not correlated to the unique flavor release properties of the TA-chewing gum. However, a relationship between gum base plasticity and retention of sugar alcohol during mastication was proposed to explain the different flavor properties of the TA sample.

  3. A novel nanoscale-dispersed eye ointment for the treatment of dry eye disease

    NASA Astrophysics Data System (ADS)

    Zhang, Wenjian; Wang, Yan; Lee, Benjamin Tak Kwong; Liu, Chang; Wei, Gang; Lu, Weiyue

    2014-03-01

    A novel nanoscale-dispersed eye ointment (NDEO) for the treatment of severe evaporative dry eye has been successfully developed. The excipients used as semisolid lipids were petrolatum and lanolin, as used in conventional eye ointment, which were coupled with medium-chain triglycerides (MCT) as a liquid lipid; both phases were then dispersed in polyvinyl pyrrolidone solution to form a nanodispersion. Single-factor experiments were conducted to optimize the formulations. A transmission electron micrograph showed that the ointment matrix was entrapped in the nanoemulsion of MCT, with a mean particle size of about 100 nm. The optimized formulation of NDEO was stable when stored for six months at 4 °C, and demonstrated no cytotoxicity to human corneal epithelial cells when compared with commercial polymer-based artificial tears (Tears Natural® Forte). The therapeutic effects of NDEO were evaluated on a mouse model with ‘dry eye’. Both the tear break-up time and fluorescein staining demonstrated therapeutic improvement, displaying a trend of positive correlation with higher concentrations of ointment matrix in the NDEO formulations compared to a marketed product. Histological evaluation demonstrated that the NDEO restored the normal corneal and conjunctival morphology and is safe for ophthalmic application.

  4. Caprylic Triglyceride as a Novel Therapeutic Approach to Effectively Improve the Performance and Attenuate the Symptoms Due to the Motor Neuron Loss in ALS Disease

    PubMed Central

    Zhao, Wei; Varghese, Merina; Vempati, Prashant; Dzhun, Anastasiya; Cheng, Alice; Wang, Jun; Lange, Dale; Bilski, Amanda; Faravelli, Irene; Pasinetti, Giulio Maria

    2012-01-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and finally death. ALS patients suffer from asthenia and their progressive weakness negatively impacts quality of life, limiting their daily activities. They have impaired energy balance linked to lower activity of mitochondrial electron transport chain enzymes in ALS spinal cord, suggesting that improving mitochondrial function may present a therapeutic approach for ALS. When fed a ketogenic diet, the G93A ALS mouse shows a significant increase in serum ketones as well as a significantly slower progression of weakness and lower mortality rate. In this study, we treated SOD1-G93A mice with caprylic triglyceride, a medium chain triglyceride that is metabolized into ketone bodies and can serve as an alternate energy substrate for neuronal metabolism. Treatment with caprylic triglyceride attenuated progression of weakness and protected spinal cord motor neuron loss in SOD1-G93A transgenic animals, significantly improving their performance even though there was no significant benefit regarding the survival of the ALS transgenic animals. We found that caprylic triglyceride significantly promoted the mitochondrial oxygen consumption rate in vivo. Our results demonstrated that caprylic triglyceride alleviates ALS-type motor impairment through restoration of energy metabolism in SOD1-G93A ALS mice, especially during the overt stage of the disease. These data indicate the feasibility of using caprylic acid as an easily administered treatment with a high impact on the quality of life of ALS patients. PMID:23145119

  5. Caprylic triglyceride as a novel therapeutic approach to effectively improve the performance and attenuate the symptoms due to the motor neuron loss in ALS disease.

    PubMed

    Zhao, Wei; Varghese, Merina; Vempati, Prashant; Dzhun, Anastasiya; Cheng, Alice; Wang, Jun; Lange, Dale; Bilski, Amanda; Faravelli, Irene; Pasinetti, Giulio Maria

    2012-01-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and finally death. ALS patients suffer from asthenia and their progressive weakness negatively impacts quality of life, limiting their daily activities. They have impaired energy balance linked to lower activity of mitochondrial electron transport chain enzymes in ALS spinal cord, suggesting that improving mitochondrial function may present a therapeutic approach for ALS. When fed a ketogenic diet, the G93A ALS mouse shows a significant increase in serum ketones as well as a significantly slower progression of weakness and lower mortality rate. In this study, we treated SOD1-G93A mice with caprylic triglyceride, a medium chain triglyceride that is metabolized into ketone bodies and can serve as an alternate energy substrate for neuronal metabolism. Treatment with caprylic triglyceride attenuated progression of weakness and protected spinal cord motor neuron loss in SOD1-G93A transgenic animals, significantly improving their performance even though there was no significant benefit regarding the survival of the ALS transgenic animals. We found that caprylic triglyceride significantly promoted the mitochondrial oxygen consumption rate in vivo. Our results demonstrated that caprylic triglyceride alleviates ALS-type motor impairment through restoration of energy metabolism in SOD1-G93A ALS mice, especially during the overt stage of the disease. These data indicate the feasibility of using caprylic acid as an easily administered treatment with a high impact on the quality of life of ALS patients.

  6. The effect of structured triglycerides on the kinetic stability of total nutrient admixtures.

    PubMed

    Balogh, Judit; Bubenik, Júlia; Dredán, Judit; Csempesz, Ferenc; Kiss, Dorottya; Zelkó, Romána

    2005-10-05

    The physical stability of two types of total parenteral nutrient (TPN) admixtures was studied as a function of storage time and temperature. One of them contained only structured triglycerides and the other exclusively long-chain triglycerides as lipid components. Droplet size of the mixtures was followed by photon correlation spectroscopy for 10 days. Zeta potential and dynamic surface tension measurements were carried out to evaluate the possible changes in the charge and interfacial surface tension of the emulsion droplets during the storage. pH values were monitored in order to follow the possible decomposition processes in the course of storage. Droplet size of emulsions prepared with lipids containing exclusively long-chain triglycerides showed remarkable increase after 4 days of storage in contrast with that of the mixtures containing structured lipids. The obtained results indicate that besides the advantageous metabolic effects of structured triglycerides, their application is recommended to improve the physical stability of TPN admixtures.

  7. 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.

  8. 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

  9. PyMCT: A Very High Level Language Coupling Tool For Climate System Models

    NASA Astrophysics Data System (ADS)

    Tobis, M.; Pierrehumbert, R. T.; Steder, M.; Jacob, R. L.

    2006-12-01

    At the Climate Systems Center of the University of Chicago, we have been examining strategies for applying agile programming techniques to complex high-performance modeling experiments. While the "agile" development methodology differs from a conventional requirements process and its associated milestones, the process remain a formal one. It is distinguished by continuous improvement in functionality, large numbers of small releases, extensive and ongoing testing strategies, and a strong reliance on very high level languages (VHLL). Here we report on PyMCT, which we intend as a core element in a model ensemble control superstructure. PyMCT is a set of Python bindings for MCT, the Fortran-90 based Model Coupling Toolkit, which forms the infrastructure for the inter-component communication in the Community Climate System Model (CCSM). MCT provides a scalable model communication infrastructure. In order to take maximum advantage of agile software development methodologies, we exposed MCT functionality to Python, a prominent VHLL. We describe how the scalable architecture of MCT allows us to overcome the relatively weak runtime performance of Python, so that the performance of the combined system is not severely impacted. To demonstrate these advantages, we reimplemented the CCSM coupler in Python. While this alone offers no new functionality, it does provide a rigorous test of PyMCT functionality and performance. We reimplemented the CPL6 library, presenting an interesting case study of the comparison between conventional Fortran-90 programming and the higher abstraction level provided by a VHLL. The powerful abstractions provided by Python will allow much more complex experimental paradigms. In particular, we hope to build on the scriptability of our coupling strategy to enable systematic sensitivity tests. Our most ambitious objective is to combine our efforts with Bayesian inverse modeling techniques toward objective tuning at the highest level, across model

  10. PCSK9 Induces CD36 Degradation and Affects Long-Chain Fatty Acid Uptake and Triglyceride Metabolism in Adipocytes and in Mouse Liver.

    PubMed

    Demers, Annie; Samami, Samaneh; Lauzier, Benjamin; Des Rosiers, Christine; Ngo Sock, Emilienne Tudor; Ong, Huy; Mayer, Gaetan

    2015-12-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the low-density lipoprotein receptor thereby elevating plasma low-density lipoprotein cholesterol levels and the risk of coronary heart disease. Thus, the use of PCSK9 inhibitors holds great promise to prevent heart disease. Previous work found that PCSK9 is involved in triglyceride metabolism, independently of its action on low-density lipoprotein receptor, and that other yet unidentified receptors could mediate this effect. Therefore, we assessed whether PCSK9 enhances the degradation of CD36, a major receptor involved in transport of long-chain fatty acids and triglyceride storage. Overexpressed or recombinant PCSK9 induced CD36 degradation in cell lines and primary adipocytes and reduced the uptake of the palmitate analog Bodipy FL C16 and oxidized low-density lipoprotein in 3T3-L1 adipocytes and hepatic HepG2 cells, respectively. Surface plasmon resonance, coimmunoprecipitation, confocal immunofluorescence microscopy, and protein degradation pathway inhibitors revealed that PCSK9 directly interacts with CD36 and targets the receptor to lysosomes through a mechanism involving the proteasome. Importantly, the level of CD36 protein was increased by >3-fold upon small interfering RNA knockdown of endogenous PCSK9 in hepatic cells and similarly increased in the liver and visceral adipose tissue of Pcsk9(-/-) mice. In Pcsk9(-/-) mice, increased hepatic CD36 was correlated with an amplified uptake of fatty acid and accumulation of triglycerides and lipid droplets. Our results demonstrate an important role of PCSK9 in modulating the function of CD36 and triglyceride metabolism. PCSK9-mediated CD36 degradation may serve to limit fatty acid uptake and triglyceride accumulation in tissues, such as the liver. © 2015 American Heart Association, Inc.

  11. 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

  12. 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.

  13. A curly-tail modifier locus, mct1, on mouse chromosome 17

    SciTech Connect

    Letts, V.A.; Schork, N.J.; Frankel, W.N.

    1995-10-10

    The major gene for neural tube defects, ct, in the curly-tail (CT) mouse strain was mapped previously to mouse chromosome 4 by combining linkage data from several backcrosses. The penetrance of the neural tube trait, already incomplete in the CT strain, was further reduced in several of these backcrosses, suggesting the existence of recessive modifiers or strain-specific susceptibility alleles. Here we describe the mapping of a curly-tail modifier locus, mct1, to chromosome 17 in moderate and low penetrance crosses of CT with BALB/cByJ and Mus spretus. No effect of mct1 was seen in a higher penetrance cross with the BXD-8/Tymore » strain, confirming that ct is the major gene in the model. Homozygosity at both ct and mct1 loci was sufficient to account for all of the affected individuals in the BALB/cByJ cross and most of the affected individuals in the M. spretus cross and was the preferred model overall. No evidence was found for epistatic interaction between ct and mct1. 30 refs., 2 figs., 3 tabs.« less

  14. CD147 and MCT1-potential partners in bladder cancer aggressiveness and cisplatin resistance.

    PubMed

    Afonso, Julieta; Santos, Lúcio L; Miranda-Gonçalves, Vera; Morais, António; Amaro, Teresina; Longatto-Filho, Adhemar; Baltazar, Fátima

    2015-11-01

    The relapsing and progressive nature of bladder tumors, and the heterogeneity in the response to cisplatin-containing regimens, are the major concerns in the care of urothelial bladder carcinoma (UBC) patients. The metabolic adaptations that alter the tumor microenvironment and thus contribute to chemoresistance have been poorly explored in UBC setting. We found significant associations between the immunoexpressions of the microenvironment-related molecules CD147, monocarboxylate transporters (MCTs) 1 and 4, CD44 and CAIX in tumor tissue sections from 114 UBC patients. The presence of MCT1 and/or MCT4 expressions was significantly associated with unfavorable clinicopathological parameters. The incidence of CD147 positive staining significantly increased with advancing stage, grade and type of lesion, and occurrence of lymphovascular invasion. Similar associations were observed when considering the concurrent expression of CD147 and MCT1. This expression profile lowered significantly the 5-year disease-free and overall survival rates. Moreover, when selecting patients who received platinum-based chemotherapy, the prognosis was significantly worse for those with MCT1 and CD147 positive tumors. CD147 specific silencing by small interfering RNAs (siRNAs) in UBC cells was accompanied by a decrease in MCT1 and MCT4 expressions and, importantly, an increase in chemosensitivity to cisplatin. Our results provide novel insights for the involvement of CD147 and MCTs in bladder cancer progression and resistance to cisplatin-based chemotherapy. We consider that the possible cooperative role of CD147 and MCT1 in determining cisplatin resistance should be further explored as a potential theranostics biomarker. © 2014 Wiley Periodicals, Inc.

  15. Loss of caveolin-1 and gain of MCT4 expression in the tumor stroma

    PubMed Central

    Martins, Diana; Beça, Francisco F; Sousa, Bárbara; Baltazar, Fátima; Paredes, Joana; Schmitt, Fernando

    2013-01-01

    The progression from in situ to invasive breast carcinoma is still an event poorly understood. However, it has been suggested that interactions between the neoplastic cells and the tumor microenvironment may play an important role in this process. Thus, the determination of differential tumor-stromal metabolic interactions could be an important step in invasiveness. The expression of stromal Caveolin-1 (Cav-1) has already been implicated in the progression from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). Additionally, stromal Cav-1 expression has been associated with the expression of stromal monocarboxylate transporter 4 (MCT4) in invasive breast cancer. However, the role of stromal MCT4 in invasiveness has never been explored, neither the association between Cav-1 and MCT4 in the transition from breast DCIS to IDC. Therefore, our aim was to investigate in a series of breast cancer samples including matched in situ and invasive components, if there was a relationship between stromal Cav-1 and MCT4 in the progression from in situ to invasive carcinoma. We found loss of stromal Cav-1 in the progression to IDC in 75% of the cases. In contrast, MCT4 stromal expression was acquired in 87% of the IDCs. Interestingly, a concomitant loss of Cav-1 and gain of MCT4 was observed in the stroma of 75% of the cases, when matched in situ and invasive carcinomas were compared. These results suggest that alterations in Cav-1 and MCT4 may thus mark a critical point in the progression from in situ to invasive breast cancer. PMID:23907124

  16. 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.

  17. Thyroid Hormone Transporters MCT8 and OATP1C1 Control Skeletal Muscle Regeneration.

    PubMed

    Mayerl, Steffen; Schmidt, Manuel; Doycheva, Denica; Darras, Veerle M; Hüttner, Sören S; Boelen, Anita; Visser, Theo J; Kaether, Christoph; Heuer, Heike; von Maltzahn, Julia

    2018-06-05

    Thyroid hormone (TH) transporters are required for the transmembrane passage of TH in target cells. In humans, inactivating mutations in the TH transporter MCT8 cause the Allan-Herndon-Dudley syndrome, characterized by severe neuromuscular symptoms and an abnormal TH serum profile, which is fully replicated in Mct8 knockout mice and Mct8/Oatp1c1 double-knockout (M/O DKO) mice. Analysis of tissue TH content and expression of TH-regulated genes indicate a thyrotoxic state in Mct8-deficient skeletal muscles. Both TH transporters are upregulated in activated satellite cells (SCs). In M/O DKO mice, we observed a strongly reduced number of differentiated SCs, suggesting an impaired stem cell function. Moreover, M/O DKO mice and mice lacking both transporters exclusively in SCs showed impaired skeletal muscle regeneration. Our data provide solid evidence for a unique gate-keeper function of MCT8 and OATP1C1 in SC activation, underscoring the importance of a finely tuned TH signaling during myogenesis. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  18. 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.

  19. 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.

  20. Nuclear factor E2-related factor-2 has a differential impact on MCT1 and MCT4 lactate carrier expression in colonic epithelial cells: a condition favoring metabolic symbiosis between colorectal cancer and stromal cells.

    PubMed

    Diehl, K; Dinges, L-A; Helm, O; Ammar, N; Plundrich, D; Arlt, A; Röcken, C; Sebens, S; Schäfer, H

    2018-01-04

    Malignant tumors, such as colorectal cancer (CRC), are heterogeneous diseases characterized by distinct metabolic phenotypes. These include Warburg- and reverse Warburg phenotypes depending on differential distribution of the lactate carrier proteins monocarboxylate transporter-4 and -1 (MCT4 and MCT1). Here, we elucidated the role of the antioxidant transcription factor nuclear factor E2-related factor-2 (Nrf2) as the key regulator of cellular adaptation to inflammatory/environmental stress in shaping the metabolism toward a reverse Warburg phenotype in malignant and premalignant colonic epithelial cells. Immunohistochemistry of human CRC tissues revealed reciprocal expression of MCT1 and MCT4 in carcinoma and stroma cells, respectively, accompanied by strong epithelial Nrf2 activation. In colorectal tissue from inflammatory bowel disease patients, MCT1 and Nrf2 were coexpressed as well, relating to CD68+inflammatory infiltrates. Indirect coculture of human NCM460 colonocytes with M1- but not M2 macrophages induces MCT1 as well as G6PD, LDHB and TALDO expression, whereas MCT4 expression was decreased. Nrf2 knockdown or reactive oxygen species (ROS) scavenging blocked these coculture effects in NCM460 cells. Likewise, Nrf2 knockdown inhibited similar effects of tBHQ-mediated Nrf2 activation on NCM460 and HCT15 CRC cells. M1 coculture or Nrf2 activation/overexpression greatly altered the lactate uptake but not glucose uptake and mitochondrial activities in these cells, reflecting the reverse Warburg phenotype. Depending on MCT1-mediated lactate uptake, Nrf2 conferred protection from TRAIL-induced apoptosis in NCM460 and HCT15 cells. Moreover, metabolism-dependent clonal growth of HCT15 cells was induced by Nrf2-dependent activation of MCT1-driven lactate exchange. These findings indicate that Nrf2 has an impact on the metabolism already in premalignant colonic epithelial cells exposed to inflammatory M1 macrophages, an effect accompanied by growth and survival

  1. Stability and Oil Migration of Oil-in-Water Emulsions Emulsified by Phase-Separating Biopolymer Mixtures.

    PubMed

    Yang, Nan; Mao, Peng; Lv, Ruihe; Zhang, Ke; Fang, Yapeng; Nishinari, Katsuyoshi; Phillips, Glyn O

    2016-08-01

    Oil-in-water (O/W) emulsions with varying concentration of oil phase, medium-chain triglyceride (MCT), were prepared using phase-separating gum arabic (GA)/sugar beet pectin (SBP) mixture as an emulsifier. Stability of the emulsions including emulsion phase separation, droplet size change, and oil migration were investigated by means of visual observation, droplet size analysis, oil partition analysis, backscattering of light, and interfacial tension measurement. It was found that in the emulsions prepared with 4.0% GA/1.0% SBP, when the concentration of MCT was greater than 2.0%, emulsion phase separation was not observed and the emulsions were stable with droplet size unchanged during storage. This result proves the emulsification ability of phase-separating biopolymer mixtures and their potential usage as emulsifiers to prepare O/W emulsion. However, when the concentration of MCT was equal or less than 2.0%, emulsion phase separation occurred after preparation resulting in an upper SBP-rich phase and a lower GA-rich phase. The droplet size increased in the upper phase whereas decreased slightly in the lower phase with time, compared to the freshly prepared emulsions. During storage, the oil droplets exhibited a complex migration process: first moving to the SBP-rich phase, then to the GA-rich phase and finally gathering at the interface between the two phases. The mechanisms of the emulsion stability and oil migration in the phase-separated emulsions were discussed. © 2016 Institute of Food Technologists®

  2. 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.

  3. STAT3:FOXM1 and MCT1 drive uterine cervix carcinoma fitness to a lactate-rich microenvironment.

    PubMed

    Silva, Lidia Santos; Goncalves, Luis Gafeira; Silva, Fernanda; Domingues, Germana; Maximo, Valdemar; Ferreira, Joana; Lam, Eric W-F; Dias, Sergio; Felix, Ana; Serpa, Jacinta

    2016-04-01

    Uterine cervix cancer is the second most common malignancy in women worldwide with human papillomavirus (HPV) as the etiologic factor. The two main histological variants, squamous cell carcinomas (SCC) and adenocarcinomas (AC), resemble the cell morphology of exocervix and endocervix, respectively. Cancer metabolism is a cancer hallmark conditioned by the microenvironment. As uterine cervix homeostasis is dependent on lactate, we hypothesized lactate plays a role in uterine cervix cancer progression. Using in vitro (SiHa-SCC and HeLa-AC) and BALB-c/SCID models, we demonstrated that lactate metabolism is linked to histological types, with SCC predominantly consuming and AC producing lactate. MCT1 is a key factor, allowing lactate consumption and being regulated in vitro by lactate through the FOXM1:STAT3 pathway. In vivo models showed that SCC (SiHa) expresses MCT1 and is dependent on lactate to grow, whereas AC (HeLa) expresses MCT1 and MCT4, with higher growth capacities. Immunohistochemical analysis of tissue microarrays (TMA) from human cervical tumors showed that MCT1 expression associates with the SCC type and metastatic behavior of AC, whereas MCT4 expression concomitantly increases from in situ SCC to invasive SCC and is significantly associated with the AC type. Consistently, FOXM1 expression is statistically associated with MCT1 positivity in SCC, whereas the expression of FOXO3a, a FOXM1 functional antagonist, is linked to MCT1 negativity in AC. Our study reinforces the role of the microenvironment in the metabolic adaptation of cancer cells, showing that cells that retain metabolic features of their normal counterparts are positively selected by the organ's microenvironment and will survive. In particular, MCT1 was shown to be a key element in uterine cervix cancer development; however, further studies are needed to validate MCT1 as a suitable therapeutic target in uterine cervix cancer.

  4. 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.

  5. Deficiency in Monocarboxylate Transporter 1 (MCT1) in Mice Delays Regeneration of Peripheral Nerves following Sciatic Nerve Crush

    PubMed Central

    Morrison, Brett M.; Tsingalia, Akivaga; Vidensky, Svetlana; Lee, Youngjin; Jin, Lin; Farah, Mohamed H.; Lengacher, Sylvain; Magistretti, Pierre J.; Pellerin, Luc; Rothstein, Jeffrey D.

    2014-01-01

    Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence and MCT1 tdTomato BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves in MCT1 heterozygous null mice are crushed and peripheral nerve regeneration quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21 days in wild-type mice to greater than 38 days in MCT1 heterozygote null mice. In fact, half of the MCT1 heterozygote null mice have no recovery of CMAP at 42 days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42 days post-crush in the MCT1 heterozygote null mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote null mice at 4 weeks and tibial mixed sensory and motor nerve at 3 weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly through failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush. PMID:25447940

  6. 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.

  7. Evaluation of MCT1, MCT4 and CD147 Genes in Peripheral Blood Cells of Breast Cancer Patients and Their Potential Use as Diagnostic and Prognostic Markers.

    PubMed

    Luz, Maria Cláudia de B; Perez, Matheus M; Azzalis, Ligia A; Sousa, Luiz Vinícius de A; Adami, Fernando; Fonseca, Fernando L A; Alves, Beatriz da C A

    2017-03-23

    Patients with breast cancer-the deadliest cancer among women-are at constant risk of developing metastasis. Oxidative stress and hypoxia are common feature of tumor cells that can proliferate even in a resultant metabolic acidosis. Despite the low extracellular pH, intracellular pH of tumor cells remains relatively normal, or even more alkaline due to the action of a membrane protein family known as monocarboxylate transporters (MCTs). The objective of this study was to verify the diagnostic and prognostic value of MCT1 , MCT4 and CD147 in tumor and peripheral blood samples of patients with breast cancer undergoing chemotherapic treatment. Differential expression of MCT1 , MCT4 and CD147 obtained by qPCR was determined by 2 -ΔΔ C q method between biological samples (tumor and serial samples of peripheral) of patients ( n = 125) and healthy women ( n = 25). tumor samples with higher histological grades have shown higher expression of these markers; this higher expression was also observed in blood samples obtained at diagnosis of patients when compared to healthy women and in patients with positive progression of the disease (metastasis development). markers studied here could be a promising strategy in routine laboratory evaluations as breast cancer diagnosis and prognosis.

  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. 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.

  10. 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.

  11. 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

  12. 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.

  13. MCT1 A1470T: a novel polymorphism for sprint performance?

    PubMed

    Sawczuk, Marek; Banting, Lauren K; Cięszczyk, Paweł; Maciejewska-Karłowska, Agnieszka; Zarębska, Aleksandra; Leońska-Duniec, Agata; Jastrzębski, Zbigniew; Bishop, David J; Eynon, Nir

    2015-01-01

    The A1470T polymorphism (rs1049434) in the monocarboxylate (lactate/pyruvate) transporter 1 gene (MCT1) has been suggested to influence athletic performance in the general population. We compared genotype distributions and allele frequencies of the MCT1 gene A1470T polymorphism between endurance athletes, sprint/power athletes and matched controls. We also examined the association between the MCT1 A1470T and the athletes' competition level ('elite' and 'national' level). The study involved endurance athletes (n=112), sprint/power athletes (n=100), and unrelated sedentary controls (n=621), all Caucasians. Genomic DNA was extracted from buccal epithelium using a standard protocol. We conducted Fisher's exact tests and multinomial logistic regression analyses to assess the association between MCT1 genotype and athletic status/competition level. Sprint/power athletes were more likely than controls to possess the minor T allele (TT genotype compared to the AA [p<0.001]; TT or AT compared to the AA [p=0.007]; TT compared to both AA and AT genotypes [p<0.001]). Likewise, sprint/power athletes were more likely than endurance athletes to have the TT genotype compared to the AA (p=0.029) and the TT compared to both AA and AT genotypes (p=0.027). Furthermore, elite sprint/power athletes were more likely than national-level athletes to have the TT genotype compared to the AA (p=0.044), and more likely to have the TT genotype compared to both AA and AT genotypes (recessive model) (p=0.045). The MCT1 TT genotype is associated with elite sprint/power athletic status. Future studies are encouraged to replicate these findings in other elite athlete cohorts. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  14. Downregulation of MCT1 inhibits tumor growth, metastasis and enhances chemotherapeutic efficacy in osteosarcoma through regulation of the NF-κB pathway.

    PubMed

    Zhao, Zhiqiang; Wu, Man-Si; Zou, Changye; Tang, Qinglian; Lu, Jinchang; Liu, Dawei; Wu, Yuanzhong; Yin, Junqiang; Xie, Xianbiao; Shen, Jingnan; Kang, Tiebang; Wang, Jin

    2014-01-01

    Monocarboxylate transporter isoform 1 (MCT1) is an important member of the proton-linked MCT family and has been reported in an array of human cancer cell lines and primary human tumors. MCT1 expression is associated with developing a new therapeutic approach for cancer. In this study, we initially showed that MCT1 is expressed in a variety of human osteosarcoma cell lines. Moreover, we evaluated the therapeutic response of targeting MCT1 using shRNA or MCT1 inhibitor. Inhibiting MCT1 delayed tumor growth in vitro and in vivo, including in an orthotopic model of osteosarcoma. Targeting MCT1 greatly enhanced the sensitivity of human osteosarcoma cells to the chemotherapeutic drugs adriamycin (ADM). In addition, we observed that MCT1 knockdown significantly suppressed the metastatic activity of osteosarcoma, including wound healing, invasion and migration. Further mechanistic studies revealed that the antitumor effects of targeting MCT1 might be related to the NF-κB pathway. Immunochemistry assay showed that MCT1 was an independent positive prognostic marker in osteosarcoma patients. In conclusion, our data, for the first time, demonstrate that MCT1 inhibition has antitumor potential which is associated with the NF-κB pathway, and high MCT1 expression predicates poor overall survival in patients with osteosarcoma. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. 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.

  16. Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush.

    PubMed

    Morrison, Brett M; Tsingalia, Akivaga; Vidensky, Svetlana; Lee, Youngjin; Jin, Lin; Farah, Mohamed H; Lengacher, Sylvain; Magistretti, Pierre J; Pellerin, Luc; Rothstein, Jeffrey D

    2015-01-01

    Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence in wild-type mice and tdTomato fluorescence in MCT1 BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves of MCT1 heterozygous null mice are crushed and peripheral nerve regeneration was quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21 days in wild-type mice to greater than 38 days in MCT1 heterozygote null mice. In fact, half of the MCT1 heterozygote null mice have no recovery of CMAP at 42 days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42 days post-crush in the MCT1 heterozygote null mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote null mice at 4 weeks and tibial mixed sensory and motor nerve at 3 weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly due to failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. 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…

  18. Curcuminoids-loaded lipid nanoparticles: novel approach towards malaria treatment.

    PubMed

    Nayak, Aditya P; Tiyaboonchai, Waree; Patankar, Swati; Madhusudhan, Basavaraj; Souto, Eliana B

    2010-11-01

    In the present work, curcuminoids-loaded lipid nanoparticles for parenteral administration were successfully prepared by a nanoemulsion technique employing high-speed homogenizer and ultrasonic probe. For the production of nanoparticles, trimyristin, tristerin and glyceryl monostearate were selected as solid lipids and medium chain triglyceride (MCT) as liquid lipid. Scanning electron microscopy (SEM) revealed the spherical nature of the particles with sizes ranging between 120 and 250 nm measured by photon correlation spectroscopy (PCS). The zeta potential of the particles ranged between -28 and -45 mV depending on the nature of the lipid matrix produced, which also influenced the entrapment efficiency (EE) and drug loading capacity (LC) found to be in the range of 80-94% and 1.62-3.27%, respectively. The LC increased reciprocally on increasing the amount of MCT as confirmed by differential scanning calorimetry (DSC). DSC analyses revealed that increasing imperfections within the lipid matrix allowed for increasing encapsulation parameters. Nanoparticles were further sterilized by filtration process which was found to be superior over autoclaving in preventing thermal degradation of thermo-sensitive curcuminoids. The in vivo pharmacodynamic activity revealed 2-fold increase in antimalarial activity of curcuminoids entrapped in lipid nanoparticles when compared to free curcuminoids at the tested dosage level. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  19. Utilizing biotechnology in producing fats and oils with various nutritional properties.

    PubMed

    Flickinger, Brent D

    2007-01-01

    The role of dietary fat in health and wellness continues to evolve. In today's environment, trans fatty acids and obesity are issues that are impacted by dietary fat. In response to new information in these areas, changes in the amount and composition of edible fats and oils have occurred and are occurring. These compositional changes include variation in fatty acid composition and innovation in fat structure. Soybean, canola, and sunflower are examples of oilseeds with varied fatty acid composition, including mid-oleic, high-oleic, and low-linolenic traits. These trait-enhanced oils are aimed to displace partially hydrogenated vegetable oils primarily in frying applications. Examples of oils with innovation in fat structure include enzyme interesterified (EIE) fats and oils and diacylglycerol oil. EIE fats are a commercial edible fat innovation, where a lipase is used to modify the fat structure of a blend of hard fat and liquid oil. EIE fats are aimed to displace partially hydrogenated vegetable oils in baking and spread applications. Diacylglycerol and medium-chain triglyceride (MCT)-based oils are commercial edible oil innovations. Diacylglycerol and MCT-based oils are aimed for individuals looking to store less of these fats as body fat when they are used in place of traditional cooking and salad oils.

  20. Development of a self-emulsifying formulation that reduces the food effect for torcetrapib.

    PubMed

    Perlman, M E; Murdande, S B; Gumkowski, M J; Shah, T S; Rodricks, C M; Thornton-Manning, J; Freel, D; Erhart, L C

    2008-03-03

    Torcetrapib is a highly lipophilic (Clog P=7.45) and water insoluble cholesteryl ester transfer protein (CETP) inhibitor developed for the treatment of atherosclerosis. Self-emulsifying drug delivery system (SEDDS) formulations have been developed to reduce the food effect observed in early clinical trials using medium chain triglyceride (MCT) softgels and to increase the dose per capsule. MCT/Triacetin/Polysorbate 80/Capmul MCM (20/30/20/30) (MTPC) increased fasted exposure and thus reduced the food effect from 5- to 3-fold in dogs at a dose of 90 mg. Self-emulsifying formulations also accelerated absorption and generally decreased variability. Use of the lipophilic, GRAS cosolvent triacetin allowed a 2-fold increase in the dose per capsule. For the three formulations evaluated in dogs that showed significant differences in absorption, emulsion droplet size did not appear to play a significant role. Absorption did increase with Cremophor RH40 content, and at 50% Cremophor RH40 there was no food effect (at 30 mg). High polar surfactant content also resulted in poor dose proportionality, while there was good dose proportionality for MTPC. Studies of in vitro lipolysis are being conducted to aid in understanding the in vitro/in vivo relationships for torcetrapib SEDDS absorption.

  1. 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

  2. Engineering E. coli for triglyceride accumulation through native and heterologous metabolic reactions.

    PubMed

    Rucker, Joanna; Paul, Julie; Pfeifer, Blaine A; Lee, Kyongbum

    2013-03-01

    Triglycerides, traditionally sourced from plant oils, are heavily used in both industrial and healthcare applications. Commercially significant products produced from triglycerides include biodiesel, lubricants, moisturizers, and oils for cooking and dietary supplements. The need to rely upon plant-based production, however, raises concerns of increasing demand and sustainability. The reliance on crop yields and a strong demand for triglycerides provides motivation to engineer production from a robust microbial platform. In this study, Escherichia coli was engineered to synthesize and accumulate triglycerides. Triglycerides were produced from cell wall phospholipid precursors through engineered expression of two enzymes, phosphatidic acid phosphatase (PAP) and diacylglycerol acyltransferase (DGAT). A liquid chromatography-mass spectrometry (LC-MS) method was developed to analyze the production of triglycerides by the engineered E. coli strains. This proof-of-concept study demonstrated a yield of 1.1 mg/L triglycerides (2 g/L dry cell weight) in lysogeny broth medium containing 5 g/L glucose at 8 h following induction of PAP and DGAT expression. LC-MS results also demonstrated that the intracellular triglyceride composition of E. coli was highly conserved. Triglycerides containing the fatty acid distributions 16:0/16:0/16:1, 16:0/16:0/18:1, and 18:1/16:0/16:1 were found in highest concentrations and represent ∼70 % of triglycerides observed.

  3. Triglycerides and carotid intima-media thickness in ischemic stroke patients.

    PubMed

    Batluk, Jana; Leonards, Christopher O; Grittner, Ulrike; Lange, Kristin Sophie; Schreiber, Stephan J; Endres, Matthias; Ebinger, Martin

    2015-11-01

    Common carotid artery intima-media thickness (CCA-IMT) is an established marker for atherosclerosis. The role of triglycerides in CCA-IMT remains controversial. We sought to determine if elevated fasting and post-challenge triglycerides are associated with CCA-IMT. All acute ischemic stroke patients who participated in the Berlin "Cream & Sugar" study in the Charité Virchow and Charité Mitte Campuses between January 2009 and January 2014 and underwent carotid artery ultrasound studies were eligible for inclusion. A combined oral glucose and triglyceride tolerance test was performed 3-7 days after first ever ischemic stroke. Patients were classified according to triglyceride metabolism-namely, (1) patients reaching a maximum triglyceride levels 3 h post-challenge ("fast metabolizers," n = 37), (2) patients with increasing triglycerides 4 (medium metabolizers, n = 64), and (3) 5 h post-challenge ("slow metabolizers," n = 44; 13 missing). We included 158 patients (34% female; mean age 63 years, SD 14). Absolute non-fasting triglyceride levels were positively associated with CCA-IMT. A final multiple regression model revealed that older age, more severe strokes, and higher levels of fasting triglycerides were significantly and independently associated with higher mean CCA-IMT. Older age, higher waist-to-hip ratio, and higher levels of thyroid-stimulating hormone were independently associated with higher maximum CCA-IMT. Fasting triglycerides but not post-challenge triglycerides associate with CCA-IMT. An oral fat challenge may not add information on atherosclerotic status in ischemic stroke patients. The Berlin "Cream & Sugar" study is registered with EudraCT (2009-010356-97) and clinicaltrials.gov (NCT 01378468). Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. MCT1 Inhibitor AZD3965 Increases Mitochondrial Metabolism, Facilitating Combination Therapy and Noninvasive Magnetic Resonance Spectroscopy.

    PubMed

    Beloueche-Babari, Mounia; Wantuch, Slawomir; Casals Galobart, Teresa; Koniordou, Markella; Parkes, Harold G; Arunan, Vaitha; Chung, Yuen-Li; Eykyn, Thomas R; Smith, Paul D; Leach, Martin O

    2017-11-01

    Monocarboxylate transporters (MCT) modulate tumor cell metabolism and offer promising therapeutic targets for cancer treatment. Understanding the impact of MCT blockade on tumor cell metabolism may help develop combination strategies or identify pharmacodynamic biomarkers to support the clinical development of MCT inhibitors now in clinical trials. In this study, we assessed the impact of the MCT1 inhibitor AZD3965 on cancer cell metabolism in vitro and in vivo Exposing human lymphoma and colon carcinoma cells to AZD3965 increased MCT4-dependent accumulation of intracellular lactate, inhibiting monocarboxylate influx and efflux. AZD3965 also increased the levels of TCA cycle-related metabolites and 13 C-glucose mitochondrial metabolism, enhancing oxidative pyruvate dehydrogenase and anaplerotic pyruvate carboxylase fluxes. Increased mitochondrial metabolism was necessary to maintain cell survival under drug stress. These effects were counteracted by coadministration of the mitochondrial complex I inhibitor metformin and the mitochondrial pyruvate carrier inhibitor UK5099. Improved bioenergetics were confirmed in vivo after dosing with AZD3965 in mouse xenograft models of human lymphoma. Our results reveal new metabolic consequences of MCT1 inhibition that might be exploited for therapeutic and pharmacodynamic purposes. Cancer Res; 77(21); 5913-24. ©2017 AACR . ©2017 American Association for Cancer Research.

  5. 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.

  6. Optimal dietary therapy of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency

    PubMed Central

    Gillingham, Melanie B.; Connor, William E.; Matern, Dietrich; Rinaldo, Piero; Burlingame, Terry; Meeuws, Kaatje; Harding, Cary O.

    2009-01-01

    Current dietary therapy for long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency consists of fasting avoidance, and limiting long-chain fatty acid (LCFA) intake. This study reports the relationship of dietary intake and metabolic control as measured by plasma acylcarnitine and organic acid profiles in 10 children with LCHAD or TFP deficiency followed for 1 year. Subjects consumed an average of 11% of caloric intake as dietary LCFA, 11% as MCT, 12% as protein, and 66% as carbohydrate. Plasma levels of hydroxypalmitoleic acid, hydroxyoleic, and hydroxylinoleic carnitine esters positively correlated with total LCFA intake and negatively correlated with MCT intake suggesting that as dietary intake of LCFA decreases and MCT intake increases, there is a corresponding decrease in plasma hydroxyacylcarnitines. There was no correlation between plasma acylcarnitines and level of carnitine supplementation. Dietary intake of fat-soluble vitamins E and K was deficient. Dietary intake and plasma levels of essential fatty acids, linoleic and linolenic acid, were deficient. On this dietary regimen, the majority of subjects were healthy with no episodes of metabolic decompensation. Our data suggest that an LCHAD or TFP-deficient patient should adhere to a diet providing age-appropriate protein and limited LCFA intake (10% of total energy) while providing 10–20% of energy as MCT and a daily multi-vitamin and mineral (MVM) supplement that includes all of the fat-soluble vitamins. The diet should be supplemented with vegetable oils as part of the 10% total LCFA intake to provide essential fatty acids. PMID:12809642

  7. 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.