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.

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 nutrition. PMID:27713780

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.

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.

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.

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.

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

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.

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

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.

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.

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.

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.

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.

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.

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.

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 rights reserved.

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.

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

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.

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

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.

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.

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.

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.

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.

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, however, between MCT proportion and enzyme activity (alkaline phosphatase and sucrase) in the brush border membrane was seen as well as a positive correlation with the concentration of phospholipids in the microvilli. PMID:8125388

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 contribute to lipid peroxidation and GSH depletion. Thus, lipid composition of the diet is an important determinant for the beneficial effect of MCT, with a diet containing a mixture of LCT/MCT being ineffective.

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.

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.

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.

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

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.

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...

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.

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.

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.

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 change brain ketone availability over a prolonged period of time. This trial was registered at clinicaltrials.gov as NCT02409927.

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.

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.

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.

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.

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.

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.

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

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.

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.

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

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)

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.

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.

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 MCT treatment has beneficial effects in alleviating IUGR-induced intestinal morphologic damage, which is associated with improved intestinal energy metabolism.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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

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.

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 operation and may be indicated for associated conditions, such as massive intestinal resection. MCT have also been helpful in patients with defective chylomicron formation due to a-β-lipoproteinaemia. In the congenital and less commonly encountered acquired lymphatic disorders in childhood, MCT have given encouraging results. This group includes patients with gross protein and fat loss due to intestinal lymphangiectasia and others with lymphatic anomalies at other sites. Hyperchylomicronaemia (familial fat-induced hypertriglyceridaemia) responds well to dietary treatment with MCT. PMID:4918706

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

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

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.

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.

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.

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.

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.

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

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.

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®

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.

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.

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

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.

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

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.

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.

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.

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.

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

[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.

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.

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.

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

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.

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.

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 subgroup analyses were consistent with the main analysis. In postsurgical and/or critically ill patients, the administration of STGs vs. MCT/LCTs was significantly associated with improved protein economy, better liver tolerance and a more efficient triglyceride elimination. With regard to clinical outcomes a strong trend towards reduced LOS was observed for STG patients. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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.

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.

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 reducing sepsis-induced liver fat deposition. Preinfusion with MCT before sepsis, however, had no effect on inflammatory-related cytokines or leukotriene in peritoneal lavage fluid. In addition, plasma arginine appears to be a more sensitive indicator than glutamine for septic insult. Copyright 2000 Harcourt Publishers Ltd.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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) (1.5-fold, P = 0.005), but not the plasma total cholesterol (T-Cho) and TG levels. In testes, the MCT replacement diet decreased the number of Oil Red O stain positive vacuoles (-40%, P < 0.001) and increased testis tissue weight (1.1-fold, P = 0.012), total sperm concentration (1.5-fold, P = 0.011) and motile sperm concentration (2.1-fold, P < 0.001) compared to the control group. However, there was no significant change in the sperm survival rate between the two groups. None. One previous study reported that Atgl-deficient male mice were fertile. In most studies heterozygous Atgl(+/-) mice were used to generate homozygous Atgl-deficient Atgl(-/-) mice. Although the same gene targeting mice were used in this study and the formation of vaginal plugs were observed after mating with Atgl(-/-) male mice, there were no pregnant wild-type mice observed after mating with Atgl(-/-) male mice. Local TG metabolism in the male reproductive system could affect spermatogenesis and sperm motility in men. The MCT replacement diet could be an effective therapy for idiopathic non-obstructive oligozoospermia or asthenozoospermia in men with low levels of serum NEFA. This study was supported in part by the Japan Society for the Promotion of Science JSPS KAKENHI Grant (Nos. JP24249080, JP25462557, JP16K11086). The authors declare no conflict of interest. © The Author 2016.Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email:journals.permissions@oup.com

[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.

[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 those in Group B (P < 0.05). With regards to lipid metabolism, protein synthesis and hepatocyte protection, structured triglycerides in parenteral nutrition is advantageous to standard MCT/LCT emulsion in severe hemorrhagic shock patients after resuscitation.

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.

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.

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.

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.

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.

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 that may be clinically advantageous compared with conventional LCT emulsions in certain clinical conditions.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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 of 3500 mg/kg/day), (3) in vitro genotoxicity studies using Salmonella typhimurium and Escherichia coli (negative at 5000 mg/plate), and (4) a four-week, placebo-controlled, double blind, human clinical trial utilizing 20 test subjects (no effects at 42 g MLCT/day). These data are corroborated by other studies published in the peer-reviewed literature on analogous MLCTs.

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 concentrations of these compounds. PMID:23145181

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 concentrations of these compounds.

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.

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

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.

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.

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.

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.

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.

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

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.

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)

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.

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.

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.

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.

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.

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

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.

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 delivered by oral gavage in long-term rodent toxicology studies.

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.

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.

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

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.

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.

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.

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.

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.

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.

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

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.

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.

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

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.

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.

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.

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®

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.

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®

Lipid composition and lidocaine effect on immediate and delayed injection pain following propofol administration.

PubMed

Zirak, Nahid; Bameshki, Alireza; Yazdani, Mohammadjavad; Gilani, Mehryar Taghavi

2016-01-01

Propofol has been used for the induction and maintenance of anesthesia. However, patients experience vascular pain during its injection. The objective of this study was to compare the effect of the lipid type used in propofol preparations and that of lidocaine on the immediate and delayed vascular pain induced by propofol administration. In this double-blinded clinical study, 150 patients at American Society of Anesthesiologists level I-II were randomly divided into three equally sized groups. A propofol with medium and long-chain triglycerides (propofol-MCT/LCT) was administered to the first group. The second group received propofol containing propofol-LCT, and the third group received propofol-LCT and pretreatment lidocaine 20 mg. The incidence and the intensity of immediate (during injection) and delayed injection pain (after 20 s) were evaluated on a verbal analog scale (1-10) until patients' unconsciousness. Sample size was calculated with SigmaPlot version 12.5 software. Data were analyzed with Statistical Package for the Social Sciences (SPSS) version 16, one-way analysis of variance, and post-hoc Tukey. P < 0.05 was considered statistically significant. The demographic parameters of the three groups were similar. The lidocaine group experienced the least immediate vascular pain. The intensity of pain was highest in the propofol-LCT group (P = 0.04). Additionally, the intensity of delayed pain was lowest in the propofol-MCT/LCT group (P = 0.01). The incidence of pain associated with the propofol administration was 26.5, 44, and 18%, respectively, in propofol-MCT/LCT, propofol-LCT, and lidocaine and propofol-LCT groups. The results indicate an effect of the lipid type on delayed pain reduction, especially propofol-MCT/LCT. On the other hand, the lidocaine decreases immediate propofol-LCT vascular pain.

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.

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.

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.

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.

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 structured triglyceride emulsion resulted in an amelioration of nitrogen balance despite no effect on energy expenditure in short term administration over 3 days to ICU patients when compared to a long chain triglyceride emulsion. No side effects linked to medium chain triglycerides were noted. Copyright 2001 Harcourt Publishers Ltd.

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.

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 a mouse xenograft model. Further studies are needed to address the impact of this diet on other tumour-relevant functions such as invasive growth and metastasis. PMID:18447912

Vegetable oil fortified feeds in the nutrition of very low birthweight babies.

PubMed

Vaidya, U V; Hegde, V M; Bhave, S A; Pandit, A N

1992-12-01

Two kinds of oils (i) Polyunsaturated fatty acids (PUFA) rich Safflower oil, and (ii) Medium chain triglyceride (MCT) rich Coconut oil were added to the feeds of 46 very low birthweight (VLBW) babies to see if such a supplementation is capable of enhancing their weight gain. Twenty two well matched babies who received no fortification served as controls. The oil fortification raised the energy density of the feeds from approximately 67 kcal/dl to 79 kcal/dl. Feed volumes were restricted to a maximum of 200 ml/kg/day. The mean weight gain was highest and significantly higher than the controls in the Coconut oil group (19.47 +/- 8.67 g/day or 13.91 g/day). Increase in the triceps skinfold thickness and serum triglycerides were also correspondingly higher in this group. The lead in the weight gain in this group continued in the follow up period (corrected age 3 months). As against this, higher weight gain in Safflower oil group (13.26 +/- 6.58 g/day) as compared to the controls (11.59 +/- 5.33 g/day), failed to reach statistically significant proportions, probably because of increased statistically significant proportions, probably because of increased steatorrhea (stool fat 4+ in 50% of the samples tested). The differences in the two oil groups are presumably because of better absorption of MCT rich coconut oil. However, individual variations in weight gain amongst the babies were wide so that some control babies had higher growth rates than oil fortified ones. The technique of oil fortification is fraught with dangers of intolerance, contamination and aspiration. Long term effects of such supplementation are largely unknown.(ABSTRACT TRUNCATED AT 250 WORDS)

Ten-year single-center experience of the ketogenic diet: factors influencing efficacy, tolerability, and compliance.

PubMed

Wibisono, Cinthya; Rowe, Natalie; Beavis, Erin; Kepreotes, Helen; Mackie, Fiona E; Lawson, John A; Cardamone, Michael

2015-04-01

To evaluate the efficacy, tolerability, and compliance of 3 ketogenic diets, the classical ketogenic diet, medium-chain triglyceride (MCT), and modified Atkins diet. A single-center, retrospective study of 48 children with intractable epilepsy receiving ketogenic diets from 2003 to 2012. Patient demographics, epilepsy history, nutritional management, and side effects were collated. Compliance and tolerability were assessed by recording reasons for diet modification and cessation. The value of potassium citrate supplementation for preventing nephrolithiasis was reviewed. Median age at ketogenic diet initiation was 3.8 years (IQR: 2.3-7 years). The majority had intractable epilepsy, and 33 of the 48 children (69%) had epileptic encephalopathies. Three (6%) patients became seizure free, 35 (73%) reported <50%-90% reduction, and 10 (21%) had 0%-50% reduction during a 2-year period. Diet duration or ketogenic diet type did not predict reduction in seizures (P = .381; P = .272). Constipation (n = 31, 65%) was very common. Food refusal (n = 3, 6%) and poor parental compliance (n = 5, 10%) were common reasons cited for cessation. There were lower rates of side effects for modified Atkins diet. Diet cessation was greatest for MCT; however, 3 patients on MCT ceased therapy because adequate seizure control was achieved. Nephrolithiasis was reported in 1 patient before potassium citrate was used and 2 patients noncompliant with potassium citrate supplementation developed hypercalciuria. The 3 ketogenic diets were comparably effective in seizure control and generally well-tolerated. Potassium citrate supplementation is an effective prophylactic supplement for the prevention of nephrolithiasis. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

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.

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.

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.

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.

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

Lipid composition and lidocaine effect on immediate and delayed injection pain following propofol administration

PubMed Central

Zirak, Nahid; Bameshki, Alireza; Yazdani, Mohammadjavad; Gilani, Mehryar Taghavi

2016-01-01

Background: Propofol has been used for the induction and maintenance of anesthesia. However, patients experience vascular pain during its injection. Aims: The objective of this study was to compare the effect of the lipid type used in propofol preparations and that of lidocaine on the immediate and delayed vascular pain induced by propofol administration. Materials and Methods: In this double-blinded clinical study, 150 patients at American Society of Anesthesiologists level I-II were randomly divided into three equally sized groups. A propofol with medium and long-chain triglycerides (propofol-MCT/LCT) was administered to the first group. The second group received propofol containing propofol-LCT, and the third group received propofol-LCT and pretreatment lidocaine 20 mg. The incidence and the intensity of immediate (during injection) and delayed injection pain (after 20 s) were evaluated on a verbal analog scale (1–10) until patients’ unconsciousness. Statistical Analysis: Sample size was calculated with SigmaPlot version 12.5 software. Data were analyzed with Statistical Package for the Social Sciences (SPSS) version 16, one-way analysis of variance, and post-hoc Tukey. P < 0.05 was considered statistically significant. Results: The demographic parameters of the three groups were similar. The lidocaine group experienced the least immediate vascular pain. The intensity of pain was highest in the propofol-LCT group (P = 0.04). Additionally, the intensity of delayed pain was lowest in the propofol-MCT/LCT group (P = 0.01). The incidence of pain associated with the propofol administration was 26.5, 44, and 18%, respectively, in propofol-MCT/LCT, propofol-LCT, and lidocaine and propofol-LCT groups. Conclusion: The results indicate an effect of the lipid type on delayed pain reduction, especially propofol-MCT/LCT. On the other hand, the lidocaine decreases immediate propofol-LCT vascular pain. PMID:26957686

Dietary triacylglycerol structure and saturated fat alter plasma and tissue fatty acids in piglets.

PubMed

Innis, S M; Dyer, R; Quinlan, P T; Diersen-Schade, D

1996-05-01

Human and pig milk triacylglycerols contain a large proportion of palmitic acid (16:0) which is predominately esterified in the 2-position. Other dietary fats contain variable amounts of 16:0, with unsaturated fatty acids predominantly esterified in the 2-position. These studies determined if the amount or position of 16:0 in dietary fat influences the composition or distribution of liver, adipose tissue, lung, or plasma fatty acids in developing piglets. Piglets were fed to 18 d with sow milk or formula with saturated fat from medium-chain triglyceride (MCT), coconut or palm oil, or synthesized triacylglycerols (synthesized to specifically direct 16:0 to the 2-position) with, in total fatty acids, 30.7, 4.3, 6.5, 27.0, and 29.6% 16:0, and in 2-position fatty acids, 55.3, 0.4, 1.3, 4.4, and 69.9% 16:0, respectively. The percentage of 16:0 in the 2-position of adipose fat from piglets fed sow milk, palm oil, and synthesized triacylglycerols were similar and higher than in piglets fed MCT or coconut oil. Thus, the amount, not the position, of dietary 16:0 determines piglet adipose tissue 16:0 content. The effects of the diets on the plasma and liver triacylglycerols were similar, with significantly lower 16:0 in total and 2-position fatty acids of the MCT and coconut oil groups, and significantly higher 16:0 in the plasma and liver triacylglycerol 2-position of piglets fed the synthesized triacylglycerols rather than sow milk or palm oil. The lung phospholipid total and 2-position 16:0 was significantly lower in the MCT, coconut, and palm oil groups, but similar in the synthesized triacylglycerol group and sow milk group. The lung phospholipid total and 2-position percentage of arachidonic acid (20:4n-6) was significantly lower in all of the formula-fed piglets than in milk-fed piglets. The physiological significance of this is not known.

Antiseizure Effects of Ketogenic Diet on Seizures Induced with Pentylenetetrazole, 4-Aminopyridine and Strychnine in Wistar Rats.

PubMed

Sanya, E O; Soladoye, A O; Desalu, O O; Kolo, P M; Olatunji, L A; Olarinoye, J K

2017-03-06

The ketogenic diet (KD) is a cheap and effective alternative therapy for most epilepsy. There are paucity of experimental data in Nigeria on the usefulness of KD in epilepsy models. This is likely to be responsible for the poor clinical acceptability of the diet in the country. This study therefore aimed at providing experimental data on usefulness of KD on seizure models.  The study used 64 Wistar rats that were divided into two dietary groups [normal diet (ND) and ketogenic diet (KD)]. Animal in each group were fed for 35days. Medium chain triglyceride ketogenic diet (MCT-KD) was used and it consisted of 15% carbohydrate in normal rat chow long with 5ml sunflower oil (25% (v/w). The normal diet was the usual rat chow. Seizures were induced with one of Pentelyntetrazole (PTZ), 4-Aminopyridine (AP) and Strychnine (STR). Fasting glucose, ketosis level and serum chemistry were determined and seizure parameters recorded. Serum ketosis was significantly higher in MCT-KD-fed rats (12.7 ±2.6) than ND-fed (5.17±0.86) rats. Fasting blood glucose was higher in ND-fed rats (5.3±0.9mMol/l) than in MCT-KD fed rats (5.1±0.5mMol/l) with p=0.9. Seizure latency was significantly prolonged in ND-fed compared with MCT-KD fed rats after PTZ-induced seizures (61±9sec vs 570±34sec) and AP-induced seizures (49±11sec vs 483±41sec). The difference after Str-induced seizure (51±7 vs 62±8 sec) was not significan. The differences in seizure duration between ND-fed and MCT-KD fed rats with PTZ (4296±77sec vs 366±46sec) and with AP (5238±102sec vs 480±67sec) were significant (p<0.05), but not with STR (3841±94sec vs 3510±89sec) respectively. The mean serum Na+ was significantly higher in MCT-KD fed (141.7±2.1mMol/l) than ND-fed rats (137±2.3mMol/l). There was no significant difference in mean values of other serum electrolytes between the MCT-KD fed and ND-fed animals. MCT-KD caused increase resistance to PTZ-and AP-induced seizures, but has no effect on STR-induced seizures. This antiseizure property is probably mediated through GABAergic receptors (PTZ effect) and blockade of membrane bound KATP channels (AP effect) with some enhancement by serum ketosis.

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

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

Carbonyl Compounds Produced by Vaporizing Cannabis Oil Thinning Agents.

PubMed

Troutt, William D; DiDonato, Matthew D

2017-11-01

Cannabis use has increased in the United States, particularly the use of vaporized cannabis oil, which is often mixed with thinning agents for use in vaporizing devices. E-cigarette research shows that heated thinning agents produce potentially harmful carbonyls; however, similar studies have not been conducted (1) with agents that are commonly used in the cannabis industry and (2) at temperatures that are appropriate for cannabis oil vaporization. The goal of this study was to determine whether thinning agents used in the cannabis industry produce potentially harmful carbonyls when heated to a temperature that is appropriate for cannabis oil vaporization. Four thinning agents (propylene glycol [PG], vegetable glycerin [VG], polyethylene glycol 400 [PEG 400], and medium chain triglycerides [MCT]) were heated to 230°C and the resulting vapors were tested for acetaldehyde, acrolein, and formaldehyde. Each agent was tested three times. Testing was conducted in a smoking laboratory. Carbonyl levels were measured in micrograms per puff block. Analyses showed that PEG 400 produced significantly higher levels of acetaldehyde and formaldehyde than PG, MCT, and VG. Formaldehyde production was also significantly greater in PG compared with MCT and VG. Acrolein production did not differ significantly across the agents. PG and PEG 400 produced high levels of acetaldehyde and formaldehyde when heated to 230°C. Formaldehyde production from PEG 400 isolate was particularly high, with one inhalation accounting for 1.12% of the daily exposure limit, nearly the same exposure as smoking one cigarette. Because PG and PEG 400 are often mixed with cannabis oil, individuals who vaporize cannabis oil products may risk exposure to harmful formaldehyde levels. Although more research is needed, consumers and policy makers should consider these potential health effects before use and when drafting cannabis-related legislation.

Tumor promotion by dietary fat in azoxymethane-induced colon carcinogenesis in female F344 rats: influence of amount and source of dietary fat.

PubMed

Reddy, B S; Maeura, Y

1984-03-01

The promoting effect of dietary corn oil (CO), safflower oil (SO), olive oil (OO), coconut oil (CC), and medium-chain triglycerides (MCT) on azoxymethane (AOM)-induced colon tumors was studied in female F344 rats. The animals were fed low-fat diets containing 5% CO, 5% SO, or 5% OO 2 weeks before, during, and 1 week after sc injection of 20 mg AOM/kg body weight. One week after the AOM treatment, groups of animals were transferred to high-fat diets containing 23.52% CO, 23.52% SO, 23.52% OO, and 23.52% CC, or 5.88% CO + 17.64% MCT; the remaining animals were continued on 5% fat diets. All animals were fed these diets until the termination of the experiment. Body weights and intakes of calories, protein, and micronutrients were comparable among the various dietary groups. The incidence of colon tumors was increased in rats fed diets containing high-CO and high-SO compared to those fed low-CO and low-SO diets, whereas the diets containing high OO, CC, or MCT had no promoting effect on colon tumor incidence. There was a significant increase in the excretion of fecal deoxycholic acid, lithocholic acid, and 12-ketolithocholic acid in animals fed the high-CO and high-SO diets and no difference in these secondary bile acids excretion in animals fed the high-OO and high-CC diets compared to those animals fed their respective 5% fat diets. This study thus indicates that not only the amount of dietary fat but also the fatty acid composition (type) of fat are important factors in the determination of the promoting effect in colon carcinogenesis.

Coconut oil and beef tallow, but not tricaprylin, can replace menhaden oil in the diet of red drum (Sciaenops ocellatus) without adversely affecting growth or fatty acid composition.

PubMed

Craig, S R; Gatlin, D M

1995-12-01

The ability of juvenile red drum (Sciaenops ocellatus) to utilize medium-chain triglycerides (MCT) and other saturated dietary lipids was investigated in two 6-wk feeding experiments. Diets contained solvent-extracted menhaden fish meal to which menhaden fish oil (control), coconut oil, corn oil, beef tallow or various levels of MCT as tricaprylin (30, 46, 65 and 80% of total lipid) were added. Diets were fed to triplicate groups of juvenile red drum in aquaria containing brackish (6%) water. In the first feeding experiment, red drum fed the control diet had the greatest weight gains and feed efficiencies. Weight gain, but not feed was slightly, of fish fed corn oil and fish fed coconut oil was slightly (P < 0.05) lower. In the second feeding experiment, fish fed coconut oil and those fed beef tallow had significantly higher weight gains and feed efficiencies than did fish fed the control diet. Fish fed the diets containing tricaprylin at all inclusion levels in both feeding experiments had significantly lower weight gains and feed efficiencies and higher levels of beta-hydroxybutyric acid in plasma. Fish fed diets with high levels of MCT also had lower (n-3) and greater (n-6) fatty acid levels in the neutral lipid fraction of muscle tissue compared with fish fed the control diet. Coconut oil and beef tallow consistently resulted in greater liver lipid deposition but had variable effects on other tissue indices. Saturated dietary lipids had variable effects on fatty acid composition of muscle polar and neutral lipid fractions.(ABSTRACT TRUNCATED AT 250 WORDS)

Poor digestibility of fully hydrogenated soybean oil in rats: a potential benefit of hydrogenated fats and oils.

PubMed

Kaplan, R J; Greenwood, C E

1998-05-01

The digestibility and absorption of dietary triacylglycerols are dependent on a number of factors including their fatty acid profile. Data demonstrating poor bioavailability of dietary stearic acid would suggest that hydrogenated oil sources would have lower digestibility coefficients compared with their native oils. To test this hypothesis, postweanling rats were fed one of four diets, formulated to contain 40% of energy as fat (assuming complete bioavailability), for 14 d. The diets only differed by fat type, containing soybean oil (SBO), fully hydrogenated soybean oil (HSB), medium-chain triglyceride oil (MCT), or hydrogenated coconut oil (HCO). Rats fed HSB consumed more food during the last 6 d (155.2 +/- 2.7 g) than those in each of the other groups (MCT: 118.9 +/- 2. 2 g; HCO: 124.7 +/- 3.2 g; SBO: 123.8 +/- 2.3 g), yet, they did not gain more weight. Two-day fecal excretion was almost three times greater in HSB-fed rats than in rats fed any other diet (P < 0.0001) because HSB was very poorly available. The digestibility coefficients (a measure of bioavailability) of the four fats were: HSB (30.9 +/- 1.3%) < HCO (94.5 +/- 0.4%) < SBO (97.0 +/- 0.4%) < MCT (98.7 +/- 0.2%) (P < 0.0007). All rats compensated for the incomplete availability of the fats, as apparent absorbable energy consumed did not differ among diet groups. The present data suggest that HSB only contributes 11.6 kJ/g (most fats contribute approximately 37.7 kJ/g) and that not only manufactured fat substitutes, such as olestra, but also more conventional fats are incompletely available to the body. Foods that currently contain HSB may contribute much less utilizable fat and energy than presently realized.

Infrared Spectroscopy of Bilberry Extract Water-in-Oil Emulsions: Sensing the Water-Oil Interface

PubMed Central

Kiefer, Johannes; Frank, Kerstin; Zehentbauer, Florian M.; Schuchmann, Heike P.

2016-01-01

Water-in-oil (w/o) emulsions are of great interest in many areas of the life sciences, including food technology, bioprocess engineering, and pharmaceuticals. Such emulsions are complex multi-component systems and the molecular mechanisms which lead to a stable emulsion are yet to be fully understood. In this work, attenuated total reflection (ATR) infrared (IR) spectroscopy is applied to a series of w/o emulsions of an aqueous anthocyanin-rich bilberry extract dispersed in a medium chain triglyceride (MCT) oil phase. The content of the emulsifier polyglycerin-polyricinoleat (PGPR) has been varied systematically in order to investigate whether or not its concentration has an impact on the molecular stabilization mechanisms. The molecular stabilization is accessed by a careful analysis of the IR spectrum, where changes in the vibrational frequencies and signal strengths indicate alterations of the molecular environment at the water/oil interface. The results suggest that adding emulsifier in excess of 1% by weight does not lead to an enhanced stabilization of the emulsion. PMID:27089376

Food-grade submicrometer particles from salts prepared using ethanol-in-oil mixtures.

PubMed

Paques, Jerome P; van der Linden, Erik; Sagis, Leonard M C; van Rijn, Cees J M

2012-08-29

A simple method for preparing food-grade particles in the submicrometer range of ethanol soluble salts using ethanol-in-oil (E/O) mixtures is described. Salts CaCl2·2H2O and MgCl2·6H2O were dissolved in ethanol that subsequently was mixed with a medium-chain triglyceride oil phase. It was found that type and concentration of salt have a significant influence on the miscibility of ethanol and oil phase and on the stability of E/O mixtures. The ethanol phase was evaporated from the mixture at elevated temperatures, and salt particles with dimensions in the submicrometer range (6-400 nm) remained suspended in the oil phase. It was found that the concentration of salt and volume fraction of ethanol in MCT oil have a significant influence on the size distribution of salt particles. The size of CaCl2 and MgCl2 submicrometer particles was ascertained by scanning electron microscopy and dynamic light scattering.

Lipidomics profiling of goat milk, soymilk and bovine milk by UPLC-Q-Exactive Orbitrap Mass Spectrometry.

PubMed

Li, Qiangqiang; Zhao, Yan; Zhu, Dan; Pang, Xiumei; Liu, Yue; Frew, Russell; Chen, Gang

2017-06-01

Lipids are very important for human health and milk is a rich dietary source of lipids. In this study, the lipid content in three types of milk (goat, soy and bovine) were determined by using UPLC-Q-Exactive Orbitrap Mass Spectrometry. A total of 13 classes of lipids (including Cer, SM, LPC, PC, PE, DG, TG, PA, PG, PI, PS, LPE, FA) were measured. Moreover, lipid profiles differed significantly between the different milk types. Soymilk is rich in phospholipids including PC, PE, PS, PG, while goat milk is rich in medium chain triglycerides (MCT), USFA, ω-6 FA and ω-3 FA, especially EPA and DHA. Furthermore, a PLS model was established for differentiation of milk types based on the lipid profiles. A total of 14 lipids were identified as biomarkers for differentiation of milk types, thus providing a basis for milk authentication and detection of adulteration. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of supplementation on food intake, body weight and hepatic metabolites in the citrin/mitochondrial glycerol-3-phosphate dehydrogenase double-knockout mouse model of human citrin deficiency.

PubMed

Saheki, Takeyori; Inoue, Kanako; Ono, Hiromi; Katsura, Natsumi; Yokogawa, Mana; Yoshidumi, Yukari; Furuie, Sumie; Kuroda, Eishi; Ushikai, Miharu; Asakawa, Akihiro; Inui, Akio; Eto, Kazuhiro; Kadowaki, Takashi; Sinasac, David S; Yamamura, Ken-Ichi; Kobayashi, Keiko

2012-11-01

The C57BL/6:Slc23a13(-/-);Gpd2(-/-) double-knockout (a.k.a., citrin/mitochondrial glycerol 3-phosphate dehydrogenase double knockout or Ctrn/mGPD-KO) mouse displays phenotypic attributes of both neonatal intrahepatic cholestasis (NICCD) and adult-onset type II citrullinemia (CTLN2), making it a suitable model of human citrin deficiency. In the present study, we show that when mature Ctrn/mGPD-KO mice are switched from a standard chow diet (CE-2) to a purified maintenance diet (AIN-93M), this resulted in a significant loss of body weight as a result of reduced food intake compared to littermate mGPD-KO mice. However, supplementation of the purified maintenance diet with additional protein (from 14% to 22%; and concomitant reduction or corn starch), or with specific supplementation with alanine, sodium glutamate, sodium pyruvate or medium-chain triglycerides (MCT), led to increased food intake and body weight gain near or back to that on chow diet. No such effect was observed when supplementing the diet with other sources of fat that contain long-chain fatty acids. Furthermore, when these supplements were added to a sucrose solution administered enterally to the mice, which has been shown previously to lead to elevated blood ammonia as well as altered hepatic metabolite levels in Ctrn/mGPP-KO mice, this led to metabolic correction. The elevated hepatic glycerol 3-phosphate and citrulline levels after sucrose administration were suppressed by the administration of sodium pyruvate, alanine, sodium glutamate and MCT, although the effect of MCT was relatively small. Low hepatic citrate and increased lysine levels were only found to be corrected by sodium pyruvate, while alanine and sodium glutamate both corrected hepatic glutamate and aspartate levels. Overall, these results suggest that dietary factors including increased protein content, supplementation of specific amino acids like alanine and sodium glutamate, as well as sodium pyruvate and MCT all show beneficial effects on citrin deficiency by increasing the carbohydrate tolerance of Ctrn/mGPD-KO mice, as observed through increased food intake and maintenance of body weight. Copyright © 2012 Elsevier Inc. All rights reserved.

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.

Immediate metabolic effects of different nutritional regimens in critically ill medical patients.

PubMed

Müller, T F; Müller, A; Bachem, M G; Lange, H

1995-07-01

Metabolic effects of different caloric regimens were investigated in nonsurgical, medical patients with multiple-organ failure (MOF). Seven total parenteral nutrition (TPN) regimens were administered, differing in amount (14, 28, and 56 kcal/kg per day, i.e., hypo-, iso-, and hypercaloric nutrition, respectively) and distribution [carbohydrates (COH), amino acids (AA), long-chain and medium-chain triglycerides (LCT/MCT)] of calories. Each regimen was administered over 12 h. Metabolism was monitored by energy expenditure (EE), body temperature (BT), protein breakdown (PB), and blood glucose and serum lactate levels. Measurements were started within 2 days of MOF onset. The study was conducted in a medical intensive care unit. Twenty patients with MOF on mechanical ventilation (mean Apache II score x = 26) were investigated. The mean values of the EE (x = 31 kcal/kg per day), BT (x = 38 degrees C), PB (x = 1.5 g/kg per day), and lactate (x = 2.0 mmol/l) and glucose level (x = 222 mg/dl) parameters were elevated. EE, BT, and lactate and glucose levels were significantly lower under hypocaloric nutrition than during iso- and hypercaloric nutrition (p < 0.01). Differences in the metabolic effects of LCT and MCT were not significant. PB was significantly elevated under hypercaloric nutrition (p < 0.01). Protein balance was positive under hypercaloric nutrition, and negative under iso- and hypocaloric nutrition. In nonsurgical, medical patients neither hypercaloric nor isocaloric nutritional support prevented protein catabolism; in contrast, they enhanced the metabolic burden measured by EE, thermogenesis, urea production rate, and glucose and lactate levels. A hypocaloric regimen is therefore recommended for these patients during the early phase of MOF.

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.

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 illustrate that cardiomyopathy may also develop later in childhood and/or persist into adulthood. Overall, the presented cases suggest a therapeutic effect of triheptanoin in the management of acute cardiomyopathy associated with LC-FAOD. PMID:27590926

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.

Experimental and modeling studies showing the effect of lipid type and level on flavor release from milk-based liquid emulsions.

PubMed

Roberts, Deborah D; Pollien, Philippe; Watzke, Brigitte

2003-01-01

The purpose of this work was to study two key parameters of the lipid phase that influence flavor release-lipid level and lipid type-and to relate the results to a mass balance partition coefficient-based mathematical model. Release of 10 volatile compounds from milk-based emulsions at 10, 25, and 50 degrees C was monitored by 1-min headspace sampling with a solid-phase microextraction fiber, followed by GC-MS analysis. As compared to the observations for milk fat, changing to a lipophilic lipid (medium-chain triglycerides, MCT) and adding a monoglyceride-based surfactant did not influence the volatiles release. However, increasing the solid fat content was found to increase the release. At 25 degrees C, and even more so at 10 degrees C, concurrent with an increase in their solid fat content, hydrogenated palm fat emulsions showed increased flavor release over that observed for emulsions made with coconut oil, coconut oil with surfactant, milk fat, and MCT. However, at 50 degrees C, when hydrogenated palm fat emulsions had zero solid fat content, there was no difference in flavor release from that observed for milk fat emulsions. Varying milk fat at nine levels between 0 and 4.5% showed a systematic dependence of the release on the lipid level, dependent on compound lipophilicity. Close correlations were found between the experimental and model predictions with lipid level and percent liquid lipid as variables.

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

[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.

Nano-emulsions as vehicles for topical delivery of forskolin.

PubMed

Miastkowska, Małgorzata; Sikora, Elżbieta; Lasoń, Elwira; Garcia-Celma, Maria Jose; Escribano-Ferrer, Elvira; Solans, Conxita; Llinas, Meritxell

2017-01-01

Two O/W forskolin-loaded nano-emulsions (0.075% wt.) based on medium chain triglycerides (MCT) and stabilized by a nonionic surfactant (Polysorbate 80 or Polysorbate 40) were studied as forskolin delivery systems. The nano-emulsions were prepared by the PIC method. The mean droplet size of the nano-emulsions with Polysorbate 80 and Polysorbate 40 with oil/surfactant (O/S) ratios of 20/80 and 80% water concentration, measured by Dynamic Light Scattering (DLS), was of 118 nm and 111 nm, respectively. Stability of the formulations, as assessed by light backscattering for 24 h, showed that both nano-emulsions were stable at 25°C. Studies of forskolin in vitro skin permeation from the nano-emulsions and from a triglyceride solution were carried out at 32°C, using Franz-type diffusion cells. A mixture of PBS/ethanol (60/40 v/v) was used as a receptor solution. The highest flux and permeability coefficient was obtained for the system stabilized with Polysorbate 80 (6.91±0.75 µg · cm -2 ·h -1 and 9.21 · 10 -3 ±1.00 · 10 -3 cm · h -1 , respectively) but no significant differences were observed with the flux and permeability coefficient value of forskolin dissolved in oil. The obtained results showed that the nano-emulsions developed in this study could be used as effective carriers for topical administration of forskolin.

Influence of the Oil Phase and Topical Formulation on the Wound Healing Ability of a Birch Bark Dry Extract

PubMed Central

Steinbrenner, Isabel; Houdek, Pia; Pollok, Simone; Brandner, Johanna M.; Daniels, Rolf

2016-01-01

Triterpenes from the outer bark of birch are known for various pharmacological effects including enhanced wound healing (WH). A birch bark dry extract (TE) obtained by accelerated solvent extraction showed the ability to form oleogels when it is suspended in oils. Consistency of the oleogels and the dissolved amount of triterpenes varies largely with the used oil. Here we wanted to know to what extent different oils and formulations (oleogel versus o/w emulsion) influence WH. Looking at the plain oils, medium-chain triglycerides (MCT) enhanced WH (ca. 1.4-fold), while e.g. castor oil (ca.0.3-fold) or light liquid paraffin (LLP; ca. 0.5-fold) significantly decreased WH. Concerning the respective oleogels, TE-MCT showed no improvement although the solubility of the TE was high. In contrast, the oleogel of sunflower oil which alone showed a slight tendency to impair WH, enhanced WH significantly (ca. 1.6-fold). These results can be explained by release experiments where the release rate of betulin, the main component of TE, from MCT oleogels was significantly lower than from sunflower oil oleogels. LLP impaired WH as plain oil and even though it released betulin comparable to sunflower oil it still results in an overall negative effect of the oleogel on WH. As a further formulation option also surfactant free o/w emulsions were prepared using MCT, sunflower oil and LLP as a nonpolar oil phase. Depending on the preparation method (suspension or oleogel method) the distribution of the TE varied markedly and affected also release kinetics. However, the released betulin was clearly below the values measured with the respective oleogels. Consequently, none of the emulsions showed a significantly positive effect on WH. In conclusion, our data show that the oil used as a vehicle influences wound healing not only by affecting the release of the extract, but also by having its own vehicle effect on wound healing. This is also of importance for other applications where drugs have to be applied in non-polar vehicles because these solvents likely influence the outcome of the experiment substantially. PMID:27219110

Preparation and evaluation of a phospholipid-based injectable gel for the long term delivery of leuprolide acetaterrh.

PubMed

Long, Danhong; Gong, Tao; Zhang, Zhirong; Ding, Rui; Fu, Yao

2016-07-01

A phospholipid-based injectable gel was developed for the sustained delivery of leuprolide acetate (LA). The gel system was prepared using biocompatible materials (SPME), including soya phosphatidyl choline (SPC), medium chain triglyceride (MCT) and ethanol. The system displayed a sol state with low viscosity in vitro and underwent in situ gelation in vivo after subcutaneous injection. An in vitro release study was performed using a dialysis setup with different release media containing different percentages of ethanol. The stability of LA in the SPME system was investigated under different temperatures and in the presence of various antioxidants. In vivo studies in male rats were performed to elucidate the pharmacokinetic profiles and pharmacodynamic efficacy. A sustained release of LA for 28 days was observed without obvious initial burst in vivo. The pharmacodynamic study showed that once-a-month injection of LA-loaded SPME (SPME-LA) led to comparable suppression effects on the serum testosterone level as observed in LA solution except for the onset time. These findings demonstrate excellent potential for this novel SPME system as a sustained release delivery system for LA.

Long-Acting Phospholipid Gel of Exenatide for Long-Term Therapy of Type II Diabetes.

PubMed

Hu, Mei; Zhang, Yu; Xiang, Nanxi; Zhong, Ying; Gong, Tao; Zhang, Zhi-Rong; Fu, Yao

2016-06-01

This study aimed to develop a sustained-release formulation of exenatide (EXT) for the long-term therapeutic efficacy in the treatment of type II diabetes. In this study, we present an injectable phospholipid gel by mixing biocompatible phospholipid S100, medium chain triglyceride (MCT) with 85% (w/w) ethanol. A systemic pre-formulation study has been carried out to improve the stability of EXT during formulation fabrication. With the optimized formulation, the pharmacokinetic profiles in rats were studied and two diabetic animal models were employed to evaluate the therapeutic effect of EXT phospholipid gel via a single subcutaneous injection versus repeated injections of normal saline and EXT solution. With optimized formulation, sustained release of exenatide in vivo for over three consecutive weeks was observed after one single subcutaneous injection. Moreover, the pharmacodynamic study in two diabetic models justified that the gel formulation displayed a comparable hypoglycemic effect and controlled blood glucose level compared with exenatide solution treated group. EXT-loaded phospholipid gel represents a promising controlled release system for long-term therapy of type II diabetes.

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 without adversely affecting lipid profiles. However, further research is required by independent research groups using large, well-designed studies to confirm the efficacy of MCT and to determine the dosage needed for the management of a healthy body weight and composition. Copyright © 2015 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

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.

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.

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.

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.

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.

Exercise and postprandial lipemia: effects on vascular health in inactive adults.

PubMed

Ramírez-Vélez, Robinson; Correa-Rodríguez, María; Tordecilla-Sanders, Alejandra; Aya-Aldana, Viviana; Izquierdo, Mikel; Correa-Bautista, Jorge Enrique; Álvarez, Cristian; Garcia-Hermoso, Antonio

2018-04-03

There is evidence to suggest that postprandial lipemia are is linked to the impairment of endothelial function, which is characterized by an imbalance between the actions of vasodilators and vasoconstrictors. The aim of this study was to determine the effects of a 12-week high-intensity training (HIT) and moderate continuous training (MCT) protocol on postprandial lipemia, vascular function and arterial stiffness in inactive adults after high-fat meal (HFM) ingestion. A randomized clinical trial was conducted in 20 healthy, inactive adults (31.6 ± 7.1 years). Participants followed the two exercise protocols for 12 weeks. To induce a state of postprandial lipemia (PPL), all subjects received a HFM. Endothelial function was measured using flow-mediated vasodilation (FMD), normalized brachial artery FMD (nFMD), aortic pulse wave velocity (PWV) and augmentation index (AIx). Plasma total cholesterol, high-density lipoprotein cholesterol (HDL-c), triglycerides and glucose were also measured. The effects of a HFM were evaluated in a fasted state and 60, 120, 180, and 240 min postprandially. A significant decrease in serum glucose between 0 min (fasted state) and 120 min postprandially was found in the HIT group (P = 0.035). Likewise, FMD (%) was significantly different between the fasted state and 60 min after a HFM in the HIT group (P = 0.042). The total cholesterol response expressed as area under curve (AUC) (0-240) was lower following HIT than following MCT, but no significant differences were observed (8%, P > 0.05). Similarly, triglycerides AUC (0-240) was also lower after HIT compared with MCT, which trended towards significance (24%, P = 0.076). The AUC (0-240) for the glucose response was significantly lower following HIT than MCT (10%, P = 0.008). FMD and nFMD AUC (0-240) were significantly higher following HIT than following MCT (46.9%, P = 0.021 and 67.3%, P = 0.009, respectively). PWV AUC (0-240) did not differ following between the two exercise groups (2.3%, P > 0.05). Supervised exercise training mitigates endothelial dysfunction and glucose response induced by PPL. Exercise intensity plays an important role in these protective effects, and medium-term HIT may be more effective than MCT in reducing postprandial glucose levels and attenuating vascular impairment. ClinicalTrials.gov ID: NCT02738385 Date of registration: April 14, 2016.

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

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.

Characterization of orange oil microcapsules for application in textiles

NASA Astrophysics Data System (ADS)

Rossi, W.; Bonet-Aracil, M.; Bou-Belda, E.; Gisbert-Payá, J.; Wilson, K.; Roldo, L.

2017-10-01

The use of orange oil presents as an ecological alternative to chemicals, attracting the attention of the scientific community to the development of eco-friendly antimicrobials. The microencapsulation technology has been used for the application of orange oil to textiles, being an economically viable, fast and efficient method by combining core and shell materials, desirable perceptual and functional characteristics, responsible for properties related to the nature of the product and provides that the wall materials release the functional substances in a controlled manner, in addition to effectively protecting and isolating the core material from the external environment to prevent its volatilization and deterioration, increasing the stability of the oil, such as non-toxicity. Thus, to better exploit the properties of the orange essential oil applied to textile products this study presents a characterization of microcapsules of Melamine formaldehyde obtained by the interfacial polymerization method with variations of proportions of orange oil (volatile) with fixed oil Medium-Chain Triglycerides (MCT) (non-volatile) to assist in the stability of the orange essential oil. Scanning electron microscope (SEM) was used as visualizing tool to characterize microparticles and surface morphology and thermal characteristics of microcapsules were premeditated by mean Differential scanning calorimetry (DSC).

Design of lipid-based formulations for oral administration of poorly water-soluble drug fenofibrate: effects of digestion.

PubMed

Mohsin, Kazi

2012-06-01

Lipid-based drug carriers are likely to have influence on bioavailability through enhanced solubilization of the drug in the gastrointestinal tract. The study was designed to investigate the lipid formulation digestibility in the simulated gastro intestinal media. Fenofibrate was formulated in representative Type II, IIIA, IIIB and IV self-emulsifying/microemulsifying lipid delivery systems (SEDDS and SMEDDS designed for oral administration) using various medium-chain glyceride components, non-ionic surfactants and cosolvents as excipients. Soybean oil was used only as an example of long-chain triglycerides to compare the effects of formulation with their counterparts. The formulations were subjected to in vitro digestion specifically to predict the fate of the drug in the gastro intestinal tract after exposure of the formulation to pancreatic enzymes and bile. In vitro digestion experiments were carried out using a pH-stat maintained at pH 7.5 for 30 min using intestinal fluids simulating the fed and fasted states. The digestion rate was faster and almost completed in Type II and IIIA systems. Most of the surfactants used in the studies are digestible. However, the high concentration of surfactant and/or cosolvent used in Type IIIB or IV systems lowered the rate of digestion. The digestion of medium-chain triglycerides was faster than long-chain triglycerides, but kept comparatively less drug in the post digestion products. Medium-chain mixed glycerides are good solvents for fenofibrate as rapidly digested but to improve fenofibrate concentration in post digestion products the use of long-chain mixed glycerides are suggested for further investigations.

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.

Ketogenic diet therapy for epilepsy during pregnancy: A case series.

PubMed

van der Louw, Elles J T M; Williams, Tanya J; Henry-Barron, Bobbie J; Olieman, Joanne F; Duvekot, Johannes J; Vermeulen, Marijn J; Bannink, Natalja; Williams, Monique; Neuteboom, Rinze F; Kossoff, Eric H; Catsman-Berrevoets, Coriene E; Cervenka, Mackenzie C

2017-02-01

Evaluation of ketogenic diet (KD) therapies for seizure control during pregnancy when safety and appropriate management become considerations. Until now, no information has been available on seizure reduction and human pregnancy related outcomes in women treated with KD therapies. We describe two cases of pregnant women with epilepsy treated with KD therapy either as monotherapy (Case 1) or as adjunctive therapy (Case 2). Case 1: A 27 year old woman, gravida1, started the classic KD with medium chain triglyceride (MCT) emulsion and 75g carbohydrate-restriction, later reduced to 47g. Glucose levels were 4-6mmol/L and blood ketone levels ranged from 0.2 to 1.4mmol/L. Seizure frequency decreased and seizure-free days increased. Mild side effects included intolerance to MCT, reduced serum carnitine and vitamin levels, and mild hyperlipidemia. Fetal and neonatal growth was normal as was growth and development at 12 months. Case 2: A 36 year-old nulliparous woman was treated with a 20 gram carbohydrate-restricted Modified Atkins Diet (MAD) and lamotrigine, resulting in reduction of seizure frequency to once per month prior to pregnancy. Once pregnant, carbohydrates were increased to 30g. When seizures increased, lamotrigine dose was doubled. Urine ketones trended down during second trimester. A male was born with bilateral ear deformities of unknown significance. The child had a normal neurodevelopment at eight months. Non-pharmacological epilepsy therapies like KD and MAD may be effective during human pregnancy. However, safety still has to be established. Further monitoring to identify potential long term side effects is warranted. Copyright © 2017 British Epilepsy Association. All rights reserved.

Influence of membrane material on the production of colloidal emulsions by premix membrane emulsification.

PubMed

Gehrmann, Sandra; Bunjes, Heike

2018-05-01

Premix membrane emulsification is a possibility to produce colloidal emulsions as carrier systems for poorly water soluble drugs. During the extrusion of a coarse pre-emulsion through a porous membrane, the emulsion droplets are disrupted into smaller droplets. The influence of the membrane material on the emulsification success was investigated in dependence on the emulsifier. Premixed medium chain triglyceride (MCT) emulsions stabilized with five different emulsifiers were extruded through seven different hydrophilic polymeric membrane materials with pore sizes of 200nm. The resulting emulsions differed strongly in particle size and particle size distribution with a range of median particle sizes between 0.08μm and 11μm. The particle size of the emulsions did not depend mainly on the structure or thickness of the membrane but on the combination of emulsifier and membrane material. Contact angle measurements indicated that the wetting of the membrane with the continuous phase of the emulsion was decisive for achieving emulsions with colloidal particle sizes. The type of dispersed phase was of minor importance as basically the same results were obtained with peanut oil instead of MCT. To prove the assumption that only sufficiently hydrophilic membrane materials led to emulsions with colloidal particle sizes, two membrane materials were hydrophilized by plasma treatment. After hydrophilization, the emulsifying process led to emulsions with smaller particle sizes. The use of an alumina membrane (Anodisc®) improved the process even more. With this type of membrane, emulsions with a median particle size below 250nm and a narrow particle size distribution could be obtained with all investigated emulsifiers. Copyright © 2016 Elsevier B.V. All rights reserved.

Potential Application of Nanoemulsions for Skin Delivery of Pomegranate Peel Polyphenols.

PubMed

Baccarin, Thaisa; Lemos-Senna, Elenara

2017-11-01

Pomegranate peel and seeds have demonstrated to possess antioxidant compounds with potential application to protect the skin against the ultraviolet radiation damage. However, the photoprotection activity is dependent on the amount of these compounds that reach the viable skin layers. In this paper, we describe the in vitro skin permeation and retention of the major pomegranate peel polyphenols using Franz diffusion cells, after entrapping a ethyl acetate fraction (EAF) from Punica granatum peel extract into nanoemulsions (NEs) prepared with pomegranate seed oil (PSO) or medium chain triglyceride oil (MCT). The in vitro skin permeation of gallic acid (GA), ellagic acid (EA), and punicalagin (PC) was evaluated using a HPLC-DAD validated method. After 8 h of skin permeation, all polyphenol compounds were mostly retained in the skin and did not reach the receptor compartment. However, a 2.2-fold enhancement of the retained amount of gallic acid in the stratum corneum was verified after EAF-loaded NEs are applied, when compared with the free EAF. GA and EA were delivered to the viable epidermis and dermis only when nanoemulsions were applied onto the skin. The mean retained amounts of GA and EA in the EP and DE after applying the EAF-loaded PSO-NE were 1.78 and 1.36 μg cm -2 and 1.10 and 0.97 μg cm -2 , respectively. Similar values were obtained after applying the EAF-loaded MCT-NE. The skin permeation results were supported by the confocal microscopy images. These results evidenced the promising application of nanoemulsions to deliver the pomegranate polyphenols into the deeper skin layers.

Immunomodulatory and Physical Effects of Oil Composition in Vaccine Adjuvant Emulsions

PubMed Central

Fox, Christopher B.; Baldwin, Susan L.; Duthie, Malcolm S.; Reed, Steven G.; Vedvick, Thomas S.

2011-01-01

Squalene-based oil-in-water emulsions have been used for years in some seasonal and pandemic influenza vaccines. However, concerns have been expressed regarding squalene source and potential biological activities. Little information is available regarding the immunomodulatory activity of squalene in comparison with other metabolizable oils in the context of oil-in-water emulsions formulated with vaccines. The present work describes the manufacture and physical characterization of emulsions composed of different classes of oils, including squalene, long chain triglycerides, a medium chain triglyceride, and a perfluorocarbon, all emulsified with egg phosphatidylcholine. Some differences were apparent among the non-squalene oils in terms of emulsion stability, including higher size polydispersity in the perfluorocarbon emulsion, more rapid visual instability at 60 °C for the long-chain triglyceride and perfluorocarbon emulsions, and an increased creaming rate in the medium-chain triglyceride emulsion at 60 °C as detected by laser scattering optical profiling. The biological activity of each of these emulsions was compared when formulated with either a recombinant malaria antigen or a split-virus inactivated influenza vaccine. Overall, vaccines containing the squalene emulsion elicited higher antibody titers and more abundant long-lived plasma cells than vaccines containing emulsions based on other oils. Since squalene-based emulsions show higher adjuvant potency compared to the other oils tested, non-squalene oils may be more suitable as carriers of amphiphilic or hydrophobic immunostimulatory molecules (such as TLR agonists) rather than as stand-alone adjuvants. PMID:21906648

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)

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.

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.

Ketogenic Diets: New Advances for Metabolism-Based Therapies

PubMed Central

Kossoff, Eric H.; Hartman, Adam L.

2014-01-01

Purpose of review Despite myriad anticonvulsants available and in various stages of development, there are thousands of children and adults with epilepsy worldwide still refractory to treatment and not candidates for epilepsy surgery. Many of these patients will now turn to dietary therapies such as the ketogenic diet, medium-chain triglyceride (MCT) diet, modified Atkins diet, and low glycemic index treatment. Recent Findings In the past several years, neurologists are finding new indications to use these dietary treatments, perhaps even as first-line therapy, including infantile spasms, myoclonic-astatic epilepsy (Doose syndrome), Dravet syndrome, and status epilepticus (including FIRES syndrome). Adults are also one of the most rapidly growing populations being treated nowadays; a group of patients previously not typically offered these treatments. In 2009, two controlled trials of the ketogenic diet were published as well as an International Expert Consensus Statement on dietary treatment of epilepsy. Ketogenic diets are also now being increasingly studied for neurologic conditions other than epilepsy, including Alzheimer disease and cancer. Insights from basic science research have helped elucidate the mechanisms by which metabolism-based therapy may be helpful, both in terms of an anticonvulsant and possibly neuroprotective effect. Summary Dietary therapy for epilepsy continues to grow in popularity worldwide, with expanding use for adults and conditions other than epilepsy. PMID:22322415

Effect of lipid viscosity and high-pressure homogenization on the physical stability of "Vitamin E" enriched emulsion.

PubMed

Alayoubi, Alaadin; Abu-Fayyad, Ahmed; Rawas-Qalaji, Mutasem M; Sylvester, Paul W; Nazzal, Sami

2015-01-01

Recently there has been a growing interest in vitamin E for its potential use in cancer therapy. The objective of this work was therefore to formulate a physically stable parenteral lipid emulsion to deliver higher doses of vitamin E than commonly used in commercial products. Specifically, the objectives were to study the effects of homogenization pressure, number of homogenizing cycles, viscosity of the oil phase, and oil content on the physical stability of emulsions fortified with high doses of vitamin E (up to 20% by weight). This was done by the use of a 27-run, 4-factor, 3-level Box-Behnken statistical design. Viscosity, homogenization pressure, and number of cycles were found to have a significant effect on particle size, which ranged from 213 to 633 nm, and on the percentage of vitamin E remaining emulsified after storage, which ranged from 17 to 100%. Increasing oil content from 10 to 20% had insignificant effect on the responses. Based on the results it was concluded that stable vitamin E rich emulsions could be prepared by repeated homogenization at higher pressures and by lowering the viscosity of the oil phase, which could be adjusted by blending the viscous vitamin E with medium-chain triglycerides (MCT).

Role of continuous phase protein, (-)-epigallocatechin-3-gallate and carrier oil on β-carotene degradation in oil-in-water emulsions.

PubMed

Liu, Lei; Gao, Yanxiang; McClements, David Julian; Decker, Eric Andrew

2016-11-01

The chemical instability of β-carotene limits its utilization as a nutraceutical ingredient in foods. In this research, the effect of continuous phase alpha-lactalbumin (α-LA) and (-)-epigallocatechin-3-gallate (EGCG) on β-carotene degradation in medium chain triacylglycerol (MCT)- and corn oil-in-water emulsions was examined. EGCG significantly inhibited β-carotene degradation in both MCT and corn oil-in-water emulsions in a dose dependent manner. α-LA was not able to protect β-carotene in MCT emulsions and the combination of EGCG and α-LA had a similar effect as EGCG alone. EGCG had no effect on lipid oxidation in corn oil-in-water emulsions but can protect β-carotene. β-Carotene was more stable in corn oil emulsions stabilized by α-LA compared to emulsions stabilized by Tween 20. These results show that EGCG is effective at protecting β-carotene in different emulsion systems without negatively impacting lipid oxidation suggesting that it could be utilized to increase the incorporation of β-carotene into food emulsions. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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.

Determination of physicochemical properties and degradation kinetics of triamcinolone acetonide palmitate in vitro.

PubMed

Peng, Cuilian; Liu, Cong; Tang, Xing

2010-12-01

Triamcinolone acetonide palmitate (TAP) is a lipophilic prodrug of triamcinolone acetonide (TAA) to improve the insoluble TAA physicochemical properties for the preparation of emulsions. This investigation has focused on the preformulation study of TAP, including its physicochemical properties and hydrolysis kinetics in vitro. The solubility of TAP in medium-chain triglyceride is about twice greater than that in soybean oil (long-chain triglyceride) (19.17 versus 9.55 mg/g) at 25°C, and in all investigated cases, lecithin (80, 160, and 240 mg/g) as solubilizer provided increased solubility of drugs in medium-chain triglyceride and long-chain triglyceride, whereas the maximum water solubility of TAP was 0.10 μg/mL. The partition coefficient (log P) of TAP was 5.79 irrespective of the pH conditions. The hydrolysis of TAP followed pseudo-first-order kinetics in aqueous solutions, and the stable pH range was from pH 5.0 to 9.0. The in vitro enzymolysis kinetics of TAP in rat plasma and liver homogenate was evaluated by measuring the decrease of TAP as well as the increase of TAA at 37°C for 96 hours. The results demonstrated that the TAP may be hydrolyzed mainly by rat plasma esterase and, to a minor extent, by liver esterase, and the hydrolysis half-life of TAP in 100% rat plasma was 17.53 ± 6.85 hours at pH 7.4. All these results indicated that TAP had successfully obtained higher lipid-soluble property for the preparation of intravenous emulsion and may be an effective prodrug for sustained release of TAA in vivo.

Differential effects of high-fat diets varying in fatty acid composition on the efficiency of lean and fat tissue deposition during weight recovery after low food intake.

PubMed

Dulloo, A G; Mensi, N; Seydoux, J; Girardier, L

1995-02-01

The energetics of body weight recovery after low food intake was examined in the rat during refeeding for 2 weeks with isocaloric amounts of high-fat (HF) diets providing 50% of energy as either lard, coconut oil, olive oil, safflower oil, menhaden fish oil, or a mixture of all these fat types. The results indicate that for both body fat and protein, the efficiency of deposition was dependent on the dietary fat type. The most striking differences were found (1) between diets rich in n-3 and n-6 polyunsaturated fatty acids (PUFA), with the diet high in fish oil resulting in a greater body fat deposition and lower protein gain than the diet high in safflower oil; and (2) between diets rich in long-chain (LCT) and medium-chain triglycerides (MCT), with the diet high in lard resulting in a greater gain in both body fat and protein than the diet high in coconut oil. Furthermore, the diet high in olive oil (a monounsaturated fat) and the mixed-fat diet (containing all fat types) were found to be similar to the fish oil diet in that the efficiency of fat deposition was greater (and that of protein gain lower) than with the diet high in safflower oil. Neither the efficiency of fat gain nor that of protein gain were found to correlate with fasting plasma insulin, the insulin to glucose ratio, or plasma lipids.(ABSTRACT TRUNCATED AT 250 WORDS)

Intestinal Lymphangiectasia: Insights on Management and Literature Review.

PubMed

Alshikho, Mohamad J; Talas, Joud M; Noureldine, Salem I; Zazou, Saf; Addas, Aladdin; Kurabi, Haitham; Nasser, Mahmoud

2016-07-21

BACKGROUND Intestinal lymphangiectasia (IL) is a rare disease characterized by a dilatation of the intestinal lymphatics and loss of lymph fluid into the gastrointestinal tract leading to hypoproteinemia, edema, lymphocytopenia, hypogammaglobinemia, and immunological abnormalities. Iron, calcium, and other serum components (e.g., lipids, fat soluble vitamins) may also be depleted. A literature search revealed more than 200 reported cases of IL. Herein, we report our observations of a patient diagnosed with IL; we also present our conclusion for our review of the published literature. CASE REPORT A 24-year-old male was admitted to Aleppo University Hospital with the complaints of abdominal pain, headache, arthralgia, fever, and rigors. His past medical history was remarkable for frequent episodes of diarrhea, recurrent infections, and swelling in the lower limbs. In addition, he had been hospitalized several times in non-academic hospitals due to edema in his legs, cellulitis, and recurrent infections. In the emergency department, a physical examination revealed a patient in distress. He was weak, dehydrated, pale, and had a high-grade fever. His lower extremities were edematous, swollen, and extremely tender to touch. The overlying skin was erythematous and warm. Moreover, the patient was tachycardic, tacypneic, and moderately hypotensive. The patient was resuscitated with IV fluids, and Tylenol was administered to bring the temperature down. Blood tests showed anemia and high levels of inflammatory markers. The patient's white blood cell count was elevated with an obvious left shift. However, subsequent investigations showed that the patient had IL. Suitable diet modification plans were applied as a long-term management plan. CONCLUSIONS IL is a rare disease of challenging nature due to its systematic effects and lack of comprehensive studies that can evaluate the effectiveness of specific treatments in a large cohort of patients. MCT (medium-chain triglyceride) oils and diet modification strategies are effective in reducing the loss of body proteins and in maintaining near-normal blood levels of immunoglobulins. However, octreotide and MCT oils had no proven role in shrinking edema in our patient.

Intestinal Lymphangiectasia: Insights on Management and Literature Review

PubMed Central

Alshikho, Mohamad J.; Talas, Joud M.; Noureldine, Salem I.; Zazou, Saf; Addas, Aladdin; Kurabi, Haitham; Nasser, Mahmoud

2016-01-01

Patient: Male, 24 Final Diagnosis: Intestinal lymphangiectasia Symptoms: Frequent episodes of diarrhea • recurrent infections • swelling in the lower limbs Medication: Octreotide • MCT oils Clinical Procedure: Endoscopic exam • Doppler ultrasound study • abdominal CT scan Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: Intestinal lymphangiectasia (IL) is a rare disease characterized by a dilatation of the intestinal lymphatics and loss of lymph fluid into the gastrointestinal tract leading to hypoproteinemia, edema, lymphocytopenia, hypogammaglobinemia, and immunological abnormalities. Iron, calcium, and other serum components (e.g., lipids, fat soluble vitamins) may also be depleted. A literature search revealed more than 200 reported cases of IL. Herein, we report our observations of a patient diagnosed with IL; we also present our conclusion for our review of the published literature. Case Report: A 24-year-old male was admitted to Aleppo University Hospital with the complaints of abdominal pain, headache, arthralgia, fever, and rigors. His past medical history was remarkable for frequent episodes of diarrhea, recurrent infections, and swelling in the lower limbs. In addition, he had been hospitalized several times in non-academic hospitals due to edema in his legs, cellulitis, and recurrent infections. In the emergency department, a physical examination revealed a patient in distress. He was weak, dehydrated, pale, and had a high-grade fever. His lower extremities were edematous, swollen, and extremely tender to touch. The overlying skin was erythematous and warm. Moreover, the patient was tachycardic, tacypneic, and moderately hypotensive. The patient was resuscitated with IV fluids, and Tylenol was administered to bring the temperature down. Blood tests showed anemia and high levels of inflammatory markers. The patient’s white blood cell count was elevated with an obvious left shift. However, subsequent investigations showed that the patient had IL. Suitable diet modification plans were applied as a long-term management plan. Conclusions: IL is a rare disease of challenging nature due to its systematic effects and lack of comprehensive studies that can evaluate the effectiveness of specific treatments in a large cohort of patients. Medium-chain triglyceride (MCT) oils and diet modification strategies are effective in reducing the loss of body proteins and in maintaining near-normal blood levels of immunoglobulins. However, octreotide and MCT oils had no proven role in reducing lymphedema in our patient. PMID:27440277

γ-Oryzanol nanoemulsions produced by a low-energy emulsification method: an evaluation of process parameters and physicochemical stability.

PubMed

Zhong, Jinfeng; Liu, Xiong; Wang, Yonghua; Qin, Xiaoli; Li, Zeling

2017-06-21

γ-Oryzanol is a natural antioxidant and nutraceutical compound, which makes it a good candidate for nutraceuticals, food supplements and pharmaceutical preparations. However, the incorporation of γ-oryzanol into aqueous formulations is rather difficult and its bioavailability can be severely decreased because of its water-insoluble property. In this study, γ-oryzanol-enriched nanoemulsion based fish oil and medium-chain triglyceride as carrier oils were proposed. The main objective was to optimize process parameters to form stable nanoemulsions and evaluate their physicochemical stability. The formulations of stable γ-oryzanol nanoemulsions were composed of 10% mixed carrier oils (weight ratio of fish oil to medium-chain triglyceride = 3 : 7) and 10% mixed surfactants (weight ratio of Tween 80 to Span 20 = 3 : 1). The nanoemulsions were stable at a broad pH range of 2-7 and high salt concentrations (≤0.8 mol L -1 ) and sucrose levels (≤16%). The nanoemulsions were much more stable at heating temperatures below 50 °C than at elevated heating temperatures (60 and 70 °C). The nanoemulsions maintained their physical stability at various storage temperatures (5-37 °C) for 18 days. Nanoemulsions at 5 and 23 °C had lower peroxide values and anisidine values than those at an elevated storage temperature (37 °C). These results demonstrate that the low-energy emulsification method can produce γ-oryzanol-enriched nanoemulsions using fish oil and medium-chain triglyceride as carrier oils, and provide useful information for producing bioactive lipids-loaded nanoemulsions for food systems, personal care and pharmaceutical products.

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

PubMed

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

2015-01-01

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

Mechanically Enhanced Liquid Interfaces at Human Body Temperature Using Thermosensitive Methylated Nanocrystalline Cellulose.

PubMed

Scheuble, N; Geue, T; Kuster, S; Adamcik, J; Mezzenga, R; Windhab, E J; Fischer, P

2016-02-09

The mechanical performance of materials at oil/water interfaces after consumption is a key factor affecting hydrophobic drug release. In this study, we methylated the surface of nanocrystalline cellulose (NCC) by mercerization and dimethyl sulfate exposure to produce thermosensitive biopolymers. These methylated NCC (metNCC) were used to investigate interfacial thermogelation at air/water and medium-chain triglyceride (MCT)/water interfaces at body temperature. In contrast to bulk fluid dynamics, elastic layers were formed at room temperature, and elasticity increased significantly at body temperature, which was measured by interfacial shear and dilatational rheology in situ. This unique phenomenon depends on solvent quality, temperature, and polymer concentration at interfaces. Thus, by adjusting the degree of hydrophobicity of metNCC, the interfacial elasticity and thermogelation of the interfaces could be varied. In general, these new materials (metNCC) formed more brittle interfacial layers compared to commercial methylcellulose (MC A15). Thermogelation of methylcellulose promotes attractive intermolecular forces, which were reflected in a change in self-assembly of metNCC at the interface. As a consequence, layer thickness and density increased as a function of temperature. These effects were measured by atomic force microscopy (AFM) images of the displaced interface and confirmed by neutron reflection. The substantial structural and mechanical change of methylcellulose interfaces at body temperature represents a controllable encapsulation parameter allowing optimization of lipid-based drug formulations.

Pickering emulsions stabilized by biodegradable block copolymer micelles for controlled topical drug delivery.

PubMed

Laredj-Bourezg, Faiza; Bolzinger, Marie-Alexandrine; Pelletier, Jocelyne; Chevalier, Yves

2017-10-05

Surfactant-free biocompatible and biodegradable Pickering emulsions were investigated as vehicles for skin delivery of hydrophobic drugs. O/w emulsions of medium-chain triglyceride (MCT) oil droplets loaded with all-trans retinol as a model hydrophobic drug were stabilized by block copolymer nanoparticles: either poly(lactide)-block-poly(ethylene glycol) (PLA-b-PEG) or poly(caprolactone)-block-poly(ethylene glycol) (PCL-b-PEG). Those innovative emulsions were prepared using two different processes allowing drug loading either inside oil droplets or inside both oil droplets and non-adsorbed block copolymer nanoparticles. Skin absorption of retinol was investigated in vitro on pig skin biopsies using the Franz cell method. Supplementary experiments by confocal fluorescence microscopy allowed the visualization of skin absorption of the Nile Red dye on histological sections. Retinol and Nile Red absorption experiments showed the large accumulation of hydrophobic drugs in the stratum corneum for the Pickering emulsions compared to the surfactant-based emulsion and an oil solution. Loading drug inside both oil droplets and block copolymer nanoparticles enhanced again skin absorption of drugs, which was ascribed to the supplementary contribution of free block copolymer nanoparticles loaded with drug. Such effect allowed tuning drug delivery to skin over a wide range by means of a suitable selection of either the formulation or the drug loading process. Copyright © 2017 Elsevier B.V. All rights reserved.

Oil-in-water emulsion impregnated electrospun poly(ethylene terephthalate) fiber mat as a novel tool for optical fiber cleaning.

PubMed

Devlaminck, Dries J G; Rahman, Md Mahbubor; Dash, Mamoni; Samal, Sangram Keshari; Watté, Jan; Van Vlierberghe, Sandra; Dubruel, Peter

2018-06-15

The complete removal of remaining polymer debris after stripping of optical fiber cables is essential for high precision connection between two fibers. It can be anticipated that electrospun porous membranes as cleaning wipes are able to trap and retain polymer debris within their pores. Impregnation of an oil-in-water emulsion as cleaning agent lowers the interfacial tension between debris and the optical fiber thereby enabling the straightforward removal of polymer debris from the optical fiber. Electrospun membranes of poly(ethylene terephthalate) (PET) and cellulose acetate (CA) were obtained with fiber diameters of 0.430 μm and 2 μm respectively. The oil-in-water emulsion was formulated with 10 wt% medium chain triglyceride (MCT) and 10 wt% Tween 80 surfactant in an aqueous phosphate buffer solution. In a scoring range from 0 to 5 for which the score 0 indicated superior cleaning and the score 5 referred to the least efficient cleaning, the electrospun fiber mats (without emulsion) scored within the range of 2-4 while emulsion impregnated electrospun fiber mats revealed the best score of 0. A drastic improvement was thus clearly evident from the obtained results when the cleaning emulsion was applied. The materials developed herein thus represent a new class of soft cleaning agents for optical fibers. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

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 balance when compared with LCT emulsion.

Reformulation of Stmerin(®) D CFC formulation using HFA propellants.

PubMed

Murata, Saburo; Izumi, Takashi; Ito, Hideki

2013-01-01

Stmerin(®) D was reformulated using hydrofluoroalkanes (HFA-134a and HFA-227) as alternative propellants instead of chlorofluorocarbons (CFCs), where the active ingredients were suspended in mixed CFCs (CFC-11/CFC-12/CFC-114). Here, we report the suspension stability and spray performance of the original CFC formulation and a reformulation using HFAs. We prepared metered dose inhalers (MDI) using HFAs with different surfactants and co-solvents, and investigated the effect on suspension stability by visual testing. We found that the drug suspension stability was poor in both HFAs, but was improved, particularly for HFA-227, by adding a middle chain fatty acid triglycerides (MCT) to the formulation. However, the vapor pressure of HFA-227 is higher than a CFC mixture and this increased the fine particle dose (FPD). Spray performance was adjusted by altering the actuator configuration, and the performance of different actuators was tested by cascade impaction. We found the spray performance could be controlled by the configuration of the actuator. A spray performance comparable to the original formulation was obtained with a 0.8 mm orifice diameter and a 90° cone angle. These results demonstrate that the reformulation of Stmerin(®) D using HFA-227 is feasible, by using MCT as a suspending agent and modifying the actuator configuration.

Esterification of free fatty acids in adipocytes: a comparison between octanoate and oleate.

PubMed

Guo, W; Choi, J K; Kirkland, J L; Corkey, B E; Hamilton, J A

2000-07-15

Medium-chain triacylglycerols (MCT) are present in milk, coconut oil and other foods, and are used therapeutically in special diets for certain disorders of lipid and glucose utilization. Recently, it has become apparent that MCT are not only oxidized in the liver, but are also present in lymph and fat tissue, particularly after chronic treatment. To evaluate the influence of MCT on metabolism in fat cells, we compared incorporation of octanoate and oleate into cellular triacylglycerols of 3T3-L1 adipocytes as well as their effects on preadipocyte differentiation. We found that less octanoate than oleate was stored and that more octanoate than oleate was oxidized. Octanoate was esterified to a greater extent at the sn-1,3 position of glyceryl carbons than at the sn-2 position, whereas the opposite was true for oleate. Glycerol release from fat cells pre-treated with octanoate was also greater than from cells pre-treated with oleate, presumably related to the preferential release of octanoate from the sn-1,3 position. Octanoate was not incorporated into lipids in undifferentiated cells and did not induce differentiation in these cells, whereas oleate was readily stored and actually induced differentiation. Incorporation of octanoate into lipids increased as cells differentiated, but reached a maximum of about 10% of the total stored fatty acids. If these effects in vitro also occur in vivo, substitution of octanoate for oleate or other long-chain fatty acids could have the beneficial effect of diminishing fat-cell number and lipid content.

Esterification of free fatty acids in adipocytes: a comparison between octanoate and oleate.

PubMed Central

Guo, W; Choi, J K; Kirkland, J L; Corkey, B E; Hamilton, J A

2000-01-01

Medium-chain triacylglycerols (MCT) are present in milk, coconut oil and other foods, and are used therapeutically in special diets for certain disorders of lipid and glucose utilization. Recently, it has become apparent that MCT are not only oxidized in the liver, but are also present in lymph and fat tissue, particularly after chronic treatment. To evaluate the influence of MCT on metabolism in fat cells, we compared incorporation of octanoate and oleate into cellular triacylglycerols of 3T3-L1 adipocytes as well as their effects on preadipocyte differentiation. We found that less octanoate than oleate was stored and that more octanoate than oleate was oxidized. Octanoate was esterified to a greater extent at the sn-1,3 position of glyceryl carbons than at the sn-2 position, whereas the opposite was true for oleate. Glycerol release from fat cells pre-treated with octanoate was also greater than from cells pre-treated with oleate, presumably related to the preferential release of octanoate from the sn-1,3 position. Octanoate was not incorporated into lipids in undifferentiated cells and did not induce differentiation in these cells, whereas oleate was readily stored and actually induced differentiation. Incorporation of octanoate into lipids increased as cells differentiated, but reached a maximum of about 10% of the total stored fatty acids. If these effects in vitro also occur in vivo, substitution of octanoate for oleate or other long-chain fatty acids could have the beneficial effect of diminishing fat-cell number and lipid content. PMID:10880345

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.

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.

Is the interaction between fatty acids and tryptophan responsible for the efficacy of a ketogenic diet in epilepsy? The new hypothesis of action.

PubMed

Maciejak, P; Szyndler, J; Turzyńska, D; Sobolewska, A; Kołosowska, K; Krząścik, P; Płaźnik, A

2016-01-28

The effects of a ketogenic diet in controlling seizure activity have been proven in many studies, although its mechanism of action remains elusive in many regards. We hypothesize that the ketogenic diet may exert its antiepileptic effects by influencing tryptophan (TRP) metabolism. The aim of this study was to investigate the influence of octanoic and decanoic fatty acids (FAs), the main components in the MCT diet (medium-chain triglyceride diet, a subtype of the ketogenic diet), on the metabolism of TRP, the activity of the kynurenic pathway and the concentrations of monoamines and amino acids, including branched-chain amino acids (BCAA) and aromatic amino acids (AAA) in rats. The acute effects of FA on the sedation index and hippocampal electrical after-discharge threshold were also assessed. We observed that intragastric administration of FA increased the brain levels of TRP and the central and peripheral concentrations of kynurenic acid (KYNA), as well as caused significant changes in the brain and plasma concentrations of BCAA and AAA. We found that the administration of FA clearly increased the seizure threshold and induced sedation. Furthermore, we have demonstrated that blocking TRP passage into the brain abolished these effects of FA but had no similar effect on the formation of ketone bodies. Given that FAs are major components of a ketogenic diet, it is suggested that the anticonvulsant effects of a ketogenic diet may be at least partly dependent on changes in TRP metabolism. We also propose a more general hypothesis concerning the intracellular mechanism of the ketogenic diet. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Multi-omic profiles of hepatic metabolism in TPN-fed preterm pigs

USDA-ARS?s Scientific Manuscript database

New generation lipid emulsions comprised of fish oil or blends of soybean/fish/medium chain triglyceride/olive oil are emerging that result in favorable clinical metabolic outcomes in pediatric populations. Our aim was to characterize the lipidodomic, metabolomic, and transcriptomic profiles these ...

Chronic Cholangitides: Aetiology, Diagnosis, and Treatment*

PubMed Central

Sherlock, Sheila

1968-01-01

A number of different chronic diseases affect the intrahepatic bile radicles or cholangioles. They include primary and secondary sclerosing cholangitis, primary biliary cirrhosis, chronic cholestatic drug jaundice, atresia, and carcinoma. Aetiological factors include infection, immunological changes, hormones, and congenital defects. Patients with chronic cholestasis have decreased bile salts in the intestinal contents and suffer from a bile salt deficiency syndrome. Failure to absorb dietary fat is managed by a low-fat diet and by medium-chain trigly-cerides which are absorbed in the absence of intestinal bile salts. Fat-soluble vitamin deficiencies are prevented by parenteral vitamins A, D, and K1. Calcium absorption is defective, and improvement may follow intramuscular vitamin D, medium-chain triglycerides, a low-fat diet, and oral calcium supplements. In partial intestinal bile salt deficiency the anionic bile-salt-chelating resin cholestyramine controls pruritus though steatorrhoea increases. Pruritus associated with total lack of intestinal bile salts is managed by methyl-testosterone or norethandrolone, though the jaundice increases. PMID:4971054

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.

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.

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

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.

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.

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.

[Effect of glucidic and fat total parenteral nutrition on macrophage phagocytosis in rats].

PubMed

Cukier, C; Waitzberg, D L; Soares, S R; Logullo, A F; Bacchi, C E; Travassos, V H; Saldiva, P H; Torrinhas, R S; de Oliveira, T S

1997-01-01

Fat lipid emulsions in Total Parenteral Nutrition (TPN) have been associated to Mononuclear Phagocytary System (MPS) changes. Intravenous lipid emulsions may alter macrophage membrane composition but there are controversies about their effects on MPS function. The aim of the present investigation was to assess the influence of fat free TPN and fat emulsions TPN on the macrophage phagocytosis. Wistar rats (70) with external jugular vein canulation were divided in seven groups. The rats received, intravenously (i.v.) different isocaloric (1.16 kcal/mL), isonitrogenous (1.5 g/mL), and isolipidic (30 to 32% of non-proteic caloric value) TPN regimens or oral diet: 1) Group OS: oral diet with i.v. infusion of saline; 2) Group GLU: fat-free TPN; 3) Group LCT: TPN with 10% long chain triglecide emulsion (TCL); 6) Group MCT: TPN with 10% lipid emulsion with medium chain triglycerides (TCM-50%) and TCL (50%). After 96 hours of TPN or saline infusion, colloidal carbon was i.v. injected at 1.0 mL/kg body weight. The rats were sacrificed after three hours. Liver, spleen and lung were weighted and studied by immunohistochemistry by the avidine-biotine method. Under light microscopy the total macrophage number (MT) and colloidal carbon phagocytic macrophages number (MF) were established. Phagocytic index was MT/MF x 100. The results were statistically analysed (p < 0.05). The group under oral diet (OS) was the only one to gain weight. There were no differences in organ weight in any group. There were changes in MT, MF and phagocytic index in all TPN groups. Fat free TPN inhibited liver, spleen and lung macrophage phagocytosis. Fat TPN with TCL inhibited liver and lung macrophage phagocytosis. At conclusion fat free TPN or with long chain tryglicerides may inhibit MPS phagocytosis. Further studies are necessary to estabilish the effect of TPN on other MPS function.

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

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.

DEVELOPMENTAL EFFECTS OF TRICHLOROACETONITRILE ADMINISTERED IN CORN OIL TO PREGNANT LONG-EVANS RATS

EPA Science Inventory

Trichloroacetonitrile (TCAN) is a by-product of the chlorine disinfection of water containing natural organic material. When administered by gavage to pregnant Long-Evans rats in a medium-chain triglyceride vehicle, tricaprylin oil (Tricap), at a volume of 10 ml/kg, TCAN induced ...

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.

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.

Effect of feeding diets of varying fatty acid composition on apolipoprotein expression in newborn swine.

PubMed

Wang, H; Hunter, F; Black, D D

1998-10-01

The purpose of this study was to determine the effect of chronic (1 wk) feeding of dietary triacylglycerol (TG) of varying fatty acid composition on small intestinal and hepatic apolipoprotein expression, as well as serum lipid and apolipoprotein concentrations, in newborn swine. Two-day-old female swine were fed one of three diets by gavage with the following lipid composition: medium-chain TG (MCT; MCT oil), intermediate-chain saturated TG (ICST; coconut oil), and long-chain polyunsaturated TG (LCPUT; safflower oil) at 753 kJ . kg-1 . day-1 with 51% of energy from fat. After 1 wk, serum lipids and apolipoprotein concentrations were measured, and jejunal apolipoprotein B (apo B) and apo A-I mass and apo B, apo A-I, apo A-IV, and apo C-III synthesis were measured. Liver was processed for determination of apo B and apo A-I mass and apo B, apo A-I, apo C-III, and beta-actin mRNA abundance by slot blot hybridization. Compared with the MCT and LCPUT groups, the ICST group had higher total serum cholesterol, TG, high-density lipoprotein (HDL)-cholesterol, and apo A-I concentrations. There were no differences among the three groups for intestinal apolipoprotein mass or synthesis. In liver, apo A-I mass was highest in the ICST group. Liver apo A-I and apo C-III mRNA abundance was highest in the ICST group. Among all three groups, hepatic apo A-I mass correlated significantly with plasma HDL-cholesterol concentrations, and serum TG concentrations correlated with hepatic apo C-III mRNA abundance. In conclusion, we found that in the newborn piglet, chronic feeding of ICST increases serum total cholesterol, TG, HDL-cholesterol, and apo A-I concentrations and hepatic expression of apo A-I and apo C-III mRNA, compared with feeding of MCT or LCPUT. We speculate that increased hepatic apo A-I expression may contribute to the higher serum HDL and apo A-I concentrations in the ICST animals. Increased hepatic expression of apo C-III with ICST feeding may contribute to the higher serum TG concentrations by apo C-III-mediated inhibition of the catabolism of triacylglycerol-rich lipoproteins.

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.

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

USDA-ARS?s Scientific Manuscript database

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

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.

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.

Monocarboxylate Transporters Mediate Fluorescein Uptake in Corneal Epithelial Cells.

PubMed

Sun, Yi-Chen; Liou, Hau-Min; Yeh, Po-Ting; Chen, Wei-Li; Hu, Fung-Rong

2017-07-01

To determine the presence of monocarboxylate transporter (MCT) in human and rabbit corneal epithelium and its role in transcellular fluorescein transportation in the cornea. The presence of MCTs in human and rabbit corneal epithelium was determined by RT-PCR and immunohistochemistry. Intracellular fluorescein uptake experiment was performed using cultured human corneal epithelial cells (HCECs). The involvement of MCT in fluorescein uptake was determined by addition of MCT inhibitors to HCECs and acute dry eye model on New Zealand albino rabbits by spectrophotometry, corneal impression cytology, and external eye photographs. MCT-1 and MCT-4 were identified in both human and rabbit corneal epithelia. A longer treatment period and a lower pH value in culture medium increased fluorescein uptake in HCECs. Fluorescein uptake in HCECs was decreased following addition of MCT inhibitors in a concentration-dependent manner. Impression cytology under fluorescent microscopy showed intracellular fluorescein staining in the rabbit cornea with acute dry eye treatment that was decreased following topical treatment of MCT inhibitors. Fluorescein ingress in corneal epithelial cells is mediated by the MCT family. Further study of MCT-mediated transport on HCECs may potentially benefit differential diagnosis and contribute better understandings of ocular surface disorders.

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.

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.

Cirrhosis related chylous ascites successfully treated with TIPS.

PubMed

de Vries, G J; Ryan, B M; de Bièvre, M; Driessen, A; Stockbrugger, R W; Koek, G H

2005-04-01

We describe a patient with chylous ascites, who was extensively investigated for the cause. No malignant or lymphatic disease could be found, but a liver biopsy revealed liver cirrhosis. The chylous ascites was unsuccessfully treated with a sodium restriction diet, diuretics and a medium chain triglyceride diet. After the placement of a transjugular intrahepatic portosystemic shunt the ascites disappeared.

Yield and Water Use Response of Cuphea to Irrigation in the Northern Corn Belt

USDA-ARS?s Scientific Manuscript database

Cuphea (C. viscosissima Jacq. X C. lanceolata W.T. Aiton, PSR23) is a new oilseed crop being developed as a source of medium-chain triglycerides. Cuphea has a sparse, shallow root system and low water use efficiency (WUE) making it potentially susceptible to water stress. Little is known about the y...

In vitro digestion of curcuminoid-loaded lipid nanoparticles

NASA Astrophysics Data System (ADS)

Noack, Andreas; Oidtmann, Johannes; Kutza, Johannes; Mäder, Karsten

2012-09-01

Curcuminoid-loaded lipid nanoparticles were produced by melt homogenization. The used lipid matrices were medium chain triglycerides, trimyristin (TM), and tristearin. The mean particle size of the preparations was between 130 and 180 nm. The incorporated curcuminoids revealed a good stability over a period of 12 months. The curcuminoid-loaded lipid nanoparticles were intended for the oral delivery of curcuminoids. Therefore, the fate of the triglyceride matrix in simulated gastric and simulated intestinal media under the influence of pepsin and pancreatin, respectively, was assessed. The degradation of the triglycerides was monitored by the pH-stat method and with high performance thin layer chromatography in connection with spectrodensitometry to quantify the different lipid fractions. The TM nanoparticles were not degraded in simulated gastric fluid (SGF), but the decomposition of the triglyceride matrix was rapid in the intestinal media. The digestion process was faster in the simulated fed state medium compared to the simulated fasted state medium. Additionally, the stability of the incorporated drug was tested in the respective physiological media. The curcuminoids showed an overall good stability in the different test media. The release of the curcuminoids from the lipid nanoparticles was determined by fluorescence imaging techniques. A slow release of the drug was found in phosphate buffer. In contrast, a more distinct release of the curcuminoids was verifiable in SGF and in simulated intestinal fluids. Overall, it was considered that the transfer of the drug into the outer media was mainly triggered by the lipid degradation and not by drug release.

Tissue-Specific Expression of Monocarboxylate Transporters during Fasting in Mice

PubMed Central

Schutkowski, Alexandra; Wege, Nicole; Stangl, Gabriele I.; König, Bettina

2014-01-01

Monocarboxylates such as pyruvate, lactate and ketone bodies are crucial for energy supply of all tissues, especially during energy restriction. The transport of monocarboxylates across the plasma membrane of cells is mediated by monocarboxylate transporters (MCTs). Out of 14 known mammalian MCTs, six isoforms have been functionally characterized to transport monocarboxylates and short chain fatty acids (MCT1-4), thyroid hormones (MCT8, -10) and aromatic amino acids (MCT10). Knowledge on the regulation of the different MCT isoforms is rare. In an attempt to get more insights in regulation of MCT expression upon energy deprivation, we carried out a comprehensive analysis of tissue specific expression of five MCT isoforms upon 48 h of fasting in mice. Due to the crucial role of peroxisome proliferator-activated receptor (PPAR)-α as a central regulator of energy metabolism and as known regulator of MCT1 expression, we included both wildtype (WT) and PPARα knockout (KO) mice in our study. Liver, kidney, heart, small intestine, hypothalamus, pituitary gland and thyroid gland of the mice were analyzed. Here we show that the expression of all examined MCT isoforms was markedly altered by fasting compared to feeding. Expression of MCT1, MCT2 and MCT10 was either increased or decreased by fasting dependent on the analyzed tissue. MCT4 and MCT8 were down-regulated by fasting in all examined tissues. However, PPARα appeared to have a minor impact on MCT isoform regulation. Due to the fundamental role of MCTs in transport of energy providing metabolites and hormones involved in the regulation of energy homeostasis, we assumed that the observed fasting-induced adaptations of MCT expression seem to ensure an adequate energy supply of tissues during the fasting state. Since, MCT isoforms 1–4 are also necessary for the cellular uptake of drugs, the fasting-induced modifications of MCT expression have to be considered in future clinical care algorithms. PMID:25390336

Improved oral bioavalability of mebudipine upon administration in PhytoSolve and Phosal-based formulation (PBF).

PubMed

Khani, Samira; Keyhanfar, Fariborz

2014-02-01

The aim of this investigation was to examine the efficacy of PhytoSolve and Phosal-based formulation (PBF) to enhance the oral bioavailability of mebudipine, which is a poorly water-soluble calcium channel blocker. The solubility of mebudipine in various oils was determined. PhytoSolve was prepared with a medium-chain triglyceride (MCT) oil (20%), soybean phospholipids (5%), and a 70% fructose solution (75%). The influence of the weight ratio of Phosal 50PG to glycerol in PBF on the mean globule size was studied with dynamic light scattering. The optimized formulation was evaluated for robustness toward dilution, transparency, droplet size, and zeta potential. The in vivo oral absorption of different mebudipine formulations (PhytoSolve, PBF, oily solution, and suspension) were evaluated in rats. The optimized PBF contained Phosal 50PG/glycerol in a 6:4 ratio (w/w). The PBF and PhytoSolve formulations were miscible with water in any ratio and did not demonstrate any phase separation or drug precipitation over 1 month of storage. The mean particle size of PhytoSolve and PBF were 138.5 ± 9.0 and 74.4 ± 2.5 nm, respectively. The in vivo study demonstrated that the oral bioavailability of PhytoSolve and PBF in rats was significantly higher than that of the other formulations. The PhytoSolve and PBF formulations of mebudipine are found to be more bioavailable compared with suspension and oily solutions during an in vivo study in rats. These formulations might be new alternative carriers that increase the oral bioavailability of poorly water-soluble molecules, such as mebudipine.

A comparison of the stability of beverage cloud emulsions formulated with different gum acacia- and starch-based emulsifiers.

PubMed

Reiner, S J; Reineccius, G A; Peppard, T L

2010-06-01

The performance of several hydrocolloids (3 gum acacias, 1 modified gum acacia, and 3 modified starches) in stabilizing beverage emulsions and corresponding model beverages was investigated employing different core materials, emulsifier usage levels, and storage temperatures. Concentrated emulsions were prepared using orange terpenes or Miglyol 812 (comprising medium-chain triglycerides, MCT) weighted 1:1 with ester gum, stored at 25 or 35 degrees C, and analyzed on days 0, 1, and 3. On day 3, model beverages were made from each emulsion, stored at both temperatures, and analyzed weekly for 4 wk. Stability of concentrated emulsions was assessed by measuring mean particle size and by visual observations of ringing; beverage stability was judged similarly and also by loss of turbidity. Particle size measurements showed concentrated emulsions containing gum acacia or modified gum acacia with either core material were stable over 3 d storage at both temperatures whereas those made with modified starches were not, destabilization being faster at 35 degrees C. Beverages based on orange terpenes, in contrast to Miglyol, yielded smaller mean particle sizes, both on manufacture and during storage, regardless of hydrocolloid used. Visual observations of ringing generally supported this finding. Modified gum acacia was evaluated at both recommended and higher usage levels, stability increasing in the latter case. In general, all gum acacia and modified gum acacia emulsifiers were superior in stability to those based on modified starches, at either temperature, for orange terpene-based beverages. In Miglyol-based beverages, similar results were seen, except 1 modified starch performed as well as the gum acacia products.

Design and characterization of Amoitone B-loaded nanostructured lipid carriers for controlled drug release.

PubMed

Luan, Jingjing; Zhang, Dianrui; Hao, Leilei; Li, Caiyun; Qi, Lisi; Guo, Hejian; Liu, Xinquan; Zhang, Qiang

2013-11-01

Amoitone B, a novel compound chemically synthesized as the analogue of cytosporone B, has been proved to own superior affinity with Nur77 than its parent compound and exhibit notable anticancer activity. However, its application is seriously restricted due to the water-insolubility and short biological half-time. The aim of this study was to construct an effective delivery system for Amoitone B to realize sustained release, thus prolong drug circulation time in body and improve the bioavailability. Nanostructured lipid carriers (NLC) act as a new type of colloidal drug delivery system, which offer the advantages of improved drug loading and sustained release. Amoitone B-loaded NLC (AmB-NLC) containing glyceryl monostearate (GMS) and various amounts of medium chain triglycerides (MCT) were successfully prepared by emulsion-evaporation and low temperature-solidification technology with a particle size of about 200 nm and a zeta potential value of about -20 mV. The results of X-ray diffraction and DSC analysis showed amorphous crystalline state of Amoitone B in NLC. Furthermore, the drug entrapment efficacy (EE) was improved compared with solid lipid nanoparticles (SLN). The EE range was from 71.1% to 84.7%, enhanced with the increase of liquid lipid. In vitro drug release studies revealed biphasic drug release patterns with burst release initially and prolonged release afterwards and the release was accelerated with augment of liquid lipid. These results demonstrated that AmB-NLC could be a promising delivery system to control drug release and improve loading capacity, thus prolong drug action time in body and enhance the bioavailability.

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

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.

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 fat than the livers of the control and CAP oil calves. The results of this study demonstrate that the energy demand of the calf to maintain body temperature resulted in increased oxidation of intake energy; thus, overall body composition differences could not be detected. However, the intake of CCO increased the accumulation of lipid in the liver and carcass despite the apparent cold stress conditions. Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Transitions induced by solubilized fat into reverse hexagonal mesophases.

PubMed

Amar-Yuli, Idit; Garti, Nissim

2005-06-25

Lyotropic liquid crystals of glycerol monooleate (GMO) and water binary mixtures have been extensively studied and their resemblance to human membranes has intrigued many scientists. Biological systems as well as food mixtures are composed of lipids and fat components including triacylglycerols (TAGs, triglycerides) that can affect the nature of the assembly of the mesophase. The present study examines the effect of TAGs of different chain lengths (C(2)-C(18)) at various water/GMO compositions, on phase transitions from lamellar or cubic to reverse hexagonal (L(alpha)-H(II) and Q-H(II)). The ability of the triglycerides to promote the formation of an H(II) mesophase is chain length-dependent. It was found that TAG molecules with very short acyl chains (triacetin) can hydrate the head groups of the lipid and do not affect the critical packing parameter (CPP) of the amphiphile; therefore, they do not affect the self-assembly of the GMO in water, and the mesophase remains lamellar or cubic. However, TAGs with medium chain fatty acids will solvate the tails of the lipid, and will affect the CPP of the GMO, and transform the lamellar or cubic phases into hexagonal mesophase. TAGs with long chain fatty acids are very bulky, not very miscible with the GMO, and therefore, kinetically are very slow to solvate the lipid tails of the amphiphile and are difficult to accommodate into the lipophilic parts of the GMO. Their effect on the transitions from a lamellar or cubic phase to hexagonal is detected only after months of equilibration. In order to enhance the effect of the TAG on the phase transitions in the GMO/triglyceride/water systems, temperature and electrolytes effects were examined. In the presence of short and medium chain triglycerides, increasing temperature caused a transition from lamellar or hexagonal to L(2) phase (highest CPP value). However, in the presence of long chain TAGs, increasing temperature to ca. 40 degrees C caused a formation of H(II) mesophase. In addition, it was found that in tricaprylin/GMO/water systems, the increase in temperature caused a decrease in the lattice parameter. The effect of NaCl on the H(II) mesophase revealed interesting results. At low concentration of tricaprylin (5 wt%), the addition of only 0.1 wt% of NaCl was sufficient to cause the formation of well-defined H(II) mesophase, while further addition of electrolyte increased the hexagonal lattice parameters. At higher TAGs concentrations (10 wt%), addition of electrolyte resulted in the formation of H(II) with modifications of the lattice parameter. All the examined effects were more pronounced with increasing water content.

Effects of parenteral structured lipid emulsion on modulating the inflammatory response in rats undergoing a total gastrectomy.

PubMed

Lin, Ming-Tsan; Yeh, Sung-Ling; Tsou, Shung-Sheng; Wang, Ming-Yang; Chen, Wei-Jao

2009-01-01

Structured lipid emulsion improves the nitrogen balance and is rapidly cleared from the blood of moderately catabolic patients. However, the effects of structured lipids on inflammatory reactions during major surgery are not clear. This study investigated the effect of a parenteral structured triacylglycerol emulsion on leukocyte adhesion molecule expression and inflammatory mediator production in rats undergoing a total gastrectomy. Normal rats with internal jugular catheters were assigned to three experimental groups and received total parenteral nutrition. At the same time, a total gastrectomy was performed on the experimental groups. The total parenteral nutrition solutions were isonitrogenous and identical in nutrient compositions except for differences in the composition of the fat emulsion. Group 1 received a conventional fat emulsion with long-chain triacylglycerols (LCTs), group 2 received a physical mixture of medium-chain triacylglycerols (MCTs) and LCTs (MCT/LCT), and group 3 received structured lipids composed of MCTs and LCTs (STG). Half of the rats in each respective group were sacrificed 1 d and the other half 3 d after surgery to examine the analytical parameters. Plasma cholesterol and free fatty acid levels in the STG group were lower than those in the other groups after surgery. The STG group had lower leukocyte CD11a/CD18 expressions than the MCT/LCT group 3 d after surgery, and CD11b/CD18 expressions in the STG group were lower than those in the LCT group on postoperative days. The STG group had higher monocyte chemotactic protein-1 and macrophage inflammatory protein-2 levels in peritoneal lavage fluid than did the other two groups. These results suggest that, compared with the LCT and MCT/LCT groups, rats administered STG had lower plasma lipid concentrations and leukocyte integrin expressions. In addition, STG administration may cause increased recruiting of neutrophils and monocytes at the site of injury and enhance antipathogenicity in rats undergoing a total gastrectomy.

Options for addressing exocrine pancreatic insufficiency in patients receiving enteral nutrition supplementation.

PubMed

Freedman, Steven D

2017-07-01

Patients with exocrine pancreatic insufficiency (EPI) have suboptimal secretion of pancreatic digestive enzymes and experience a range of clinical symptoms related to the malabsorption of fat. In patients with EPI unable to meet their nutritional requirements, enteral nutrition (EN) support is used to augment nutritional status. In addition to protein and carbohydrate, EN formulas contain fats as a calorie source, as well as vitamins and minerals to help prevent nutritional deficiencies related to malabsorption. Semielemental enteral nutrition formulas are advantageous as they contain hydrolyzed protein, shorter chain carbohydrates, and may contain medium chain triglycerides as a fat source. However, severely pancreatic insufficient patients may be unable to absorb complex long-chain triglycerides provided by EN formulas due to insufficient pancreatic lipase; replacement pancreatic enzyme products are recommended for these patients. Currently, none of the FDA-approved pancreatic enzyme replacement therapy (PERT) products are indicated for use in patients receiving enteral nutrition and administration of enzymes by mixing into enteral nutrition formula is not supported by guidelines as this route is associated with risks. RELiZORB (immobilized lipase) is a novel in-line digestive cartridge that has been designed to address the unmet need for PERT in patients receiving enteral nutrition. RELiZORB efficacy and compatibility with a range of commercially available polymeric and semielemental formulas with varying nutrient, caloric content, and triglyceride chain lengths have been demonstrated. In most formulas, RELiZORB efficiently hydrolyzed greater than 90% of fats within the formula into absorbable fatty acids and monoglycerides.

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.

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

Efficient heterologous expression of Fusarium solani lipase, FSL2, in Pichia pastoris, functional characterization of the recombinant enzyme and molecular modeling.

PubMed

Jallouli, Raida; Parsiegla, Goetz; Carrière, Frédéric; Gargouri, Youssef; Bezzine, Sofiane

2017-01-01

The gene coding for a lipase of Fusarium solani, designated as FSL2, shows an open reading frame of 906bp encoding a 301-amino acid polypeptide with a molecular mass of 30kDa. Based on sequence similarity with other fungal lipases, FSL2 contains a catalytic triad, consisting of Ser144, Asp198, and His256. FSL2 cDNA was subcloned into the pGAPZαA vector containing the Saccharomyces cerevisiae α-factor signal sequence and this construct was used to transform Pichia pastoris and achieve a high-level extracellular production of a FSL2 lipase. Maximum lipase activity was observed after 48h. The optimum activity of the purified recombinant enzyme was measured at pH 8.0-9.0 and 37°C. FSL2 is remarkably stable at alkaline pH values up to 12 and at temperatures below 40°C. It has high catalytic efficiency towards triglycerides with short to long chain fatty acids but with a marked preference for medium and long chain fatty acids. FSL2 activity is decreased at sodium taurodeoxycholate concentrations above the Critical Micelle Concentration (CMC) of this anionic detergent. However, lipase activity is enhanced by Ca 2+ and inhibited by EDTA or Cu 2+ and partially by Mg 2+ or K + . In silico docking of medium chain triglycerides, monogalctolipids (MGDG), digalactolipids (DGDG) and long chain phospholipids in the active site of FSL2 reveals structural solutions. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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

2001-08-01

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

Cholesterol oxidation in intravenous lipid emulsions: safety of preparations before and after experimental hyperoxia.

PubMed

Scopesi, Fabio; Zunin, Paola; Bellini, Carlo; Sacchi, Renata; Boggia, Raffaella; Evangelisti, Filippo; Serra, Giovanni

2004-01-01

The aim of this preliminary study was to assess the possible presence of cholesterol oxidation products in 2 i.v. lipidic emulsions with different fatty acid compositions (long-chain triglyceride, medium-chain triglyceride-long-chain triglyceride). Because these emulsions are currently used in neonatal parenteral nutrition, their direct venous introduction might be potentially dangerous because of the possible atherogenic role of cholesterol oxidation products. The emulsions were analyzed when bottles were opened (ie, under normal condition of administration) and after a 12-hour direct experimental exposure to air and high (90%) oxygen concentrations. 7-Ketocholesterol and 5alpha-epoxycholesterol were chosen as markers of cholesterol oxidation and detected by gas chromatography-mass spectrometry of their trimethylsilyl ethers. The detected amounts were always very low and in some cases below the detection limit of the analytical method for the 2 cholesterol oxidation products (COPs; 0.1 and 0.3 microg/g of extracted lipids). Immediately after opening the bottles, their concentrations were lower in the emulsions containing the higher amounts of polyunsaturated fatty acids. Experimental hyperoxic exposure generally determined only a mild increase in the content of cholesterol oxidation biomarker, and after exposure to oxygen, the amounts of COPs were slightly higher than after exposure to air. The results of the present study are undoubtedly reassuring for the safety of neonates, although caution is always required when drawing conclusions from in vitro data.

A novel nutrient sensing mechanism underlies substrate-induced regulation of monocarboxylate transporter-1

PubMed Central

Priyamvada, Shubha; Kumar, Anoop; Natarajan, Arivarasu A.; Gill, Ravinder K.; Alrefai, Waddah A.; Dudeja, Pradeep K.

2012-01-01

Monocarboxylate transporter isoform-1 (MCT1) plays an important role in the absorption of short-chain fatty acids (SCFAs) in the colon. Butyrate, a major SCFA, serves as the primary energy source for the colonic mucosa, maintains epithelial integrity, and ameliorates intestinal inflammation. Previous studies have shown substrate (butyrate)-induced upregulation of MCT1 expression and function via transcriptional mechanisms. The present studies provide evidence that short-term MCT1 regulation by substrates could be mediated via a novel nutrient sensing mechanism. Short-term regulation of MCT1 by butyrate was examined in vitro in human intestinal C2BBe1 and rat intestinal IEC-6 cells and ex vivo in rat intestinal mucosa. Effects of pectin feeding on MCT1, in vivo, were determined in rat model. Butyrate treatment (30–120 min) of C2BBe1 cells increased MCT1 function {p-(chloromercuri) benzene sulfonate (PCMBS)-sensitive [14C]butyrate uptake} in a pertussis toxin-sensitive manner. The effects were associated with decreased intracellular cAMP levels, increased Vmax of butyrate uptake, and GPR109A-dependent increase in apical membrane MCT1 level. Nicotinic acid, an agonist for the SCFA receptor GPR109A, also increased MCT1 function and decreased intracellular cAMP. Pectin feeding increased apical membrane MCT1 levels and nicotinate-induced transepithelial butyrate flux in rat colon. Our data provide strong evidence for substrate-induced enhancement of MCT1 surface expression and function via a novel nutrient sensing mechanism involving GPR109A as a SCFA sensor. PMID:22982338

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.

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.

Monocarboxylate transporter-dependent mechanism confers resistance to oxygen- and glucose-deprivation injury in astrocyte-neuron co-cultures.

PubMed

Gao, Chen; Zhou, Liya; Zhu, Wenxia; Wang, Hongyun; Wang, Ruijuan; He, Yunfei; Li, Zhiyun

2015-05-06

Hypoxic and low-glucose stressors contribute to neuronal death in many brain diseases. Astrocytes are anatomically well-positioned to shield neurons from hypoxic injury. During hypoxia/ischemia, lactate released from astrocytes is taken up by neurons and stored for energy. This process is mediated by monocarboxylate transporters (MCTs) in the central nervous system. In the present study, we investigated the ability of astrocytes to protect neurons from oxygen- and glucose-deprivation (OGD) injury via an MCT-dependent mechanism in vitro. Primary cultures of neurons, astrocytes, and astrocytes-neurons derived from rat hippocampus were subjected to OGD, MCT inhibition with small interfering (si)RNA. Cell survival and expression of MCT4, MCT2, glial fibrillary acidic protein, and neuronal nuclear antigen were evaluated. OGD significantly increased cell death in neuronal cultures and up-regulated MCT4 expression in astrocyte cultures, but no increased cell death was observed in neuron-astrocyte co-cultures or astrocyte cultures. However, neuronal cell death in co-cultures was increased by exposure to MCT4- or MCT2-specific siRNA, and this effect was attenuated by the addition of lactate into the extracellular medium of neuronal cultures prior to OGD. These findings demonstrate that resistance to OGD injury in astrocyte-neuron co-cultures occurs via an MCT-dependent mechanism. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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.

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.

Lipases as biocatalysts for the synthesis of structured lipids.

PubMed

Jala, Ram Chandra Reddy; Hu, Peng; Yang, Tiankui; Jiang, Yuanrong; Zheng, Yan; Xu, Xuebing

2012-01-01

Structured lipids (SL) are broadly referred to as modified or synthetic oils and fats or lipids with functional or pharmaceutical applications. Some structured lipids, such as triglycerides that contain both long-chain (mainly essential) fatty acids and medium- or short-chain fatty acids and also artificial products that mimic the structure of natural materials, namely human milk fat substitutes and cocoa butter equivalents, have been discussed. Further, other modified or synthetic lipids, such as structured phospholipids and synthetic phenolic lipids are also included in this chapter. For all the products described in this chapter, enzymatic production in industry has been already conducted in one way or another. Cocoa butter equivalents, healthy oil containing medium-chain fatty acids, phosphatidyl serine, and phenol lipids from enzyme technology have been reported for commercial operation. As the demand for better quality functional lipids is increasing, the production of structured lipids becomes an interesting area. Thus, in this chapter we have discussed latest developments as well as present industrial situation of all commercially important structured lipids.

Carnitine palmitoyltransferase II deficiency

PubMed Central

Roe, C R.; Yang, B-Z; Brunengraber, H; Roe, D S.; Wallace, M; Garritson, B K.

2008-01-01

Background: Carnitine palmitoyltransferase II (CPT II) deficiency is an important cause of recurrent rhabdomyolysis in children and adults. Current treatment includes dietary fat restriction, with increased carbohydrate intake and exercise restriction to avoid muscle pain and rhabdomyolysis. Methods: CPT II enzyme assay, DNA mutation analysis, quantitative analysis of acylcarnitines in blood and cultured fibroblasts, urinary organic acids, the standardized 36-item Short-Form Health Status survey (SF-36) version 2, and bioelectric impedance for body fat composition. Diet treatment with triheptanoin at 30% to 35% of total daily caloric intake was used for all patients. Results: Seven patients with CPT II deficiency were studied from 7 to 61 months on the triheptanoin (anaplerotic) diet. Five had previous episodes of rhabdomyolysis requiring hospitalizations and muscle pain on exertion prior to the diet (two younger patients had not had rhabdomyolysis). While on the diet, only two patients experienced mild muscle pain with exercise. During short periods of noncompliance, two patients experienced rhabdomyolysis with exercise. None experienced rhabdomyolysis or hospitalizations while on the diet. All patients returned to normal physical activities including strenuous sports. Exercise restriction was eliminated. Previously abnormal SF-36 physical composite scores returned to normal levels that persisted for the duration of the therapy in all five symptomatic patients. Conclusions: The triheptanoin diet seems to be an effective therapy for adult-onset carnitine palmitoyltransferase II deficiency. GLOSSARY ALT = alanine aminotransferase; AST = aspartate aminotransferase; ATP = adenosine triphosphate; BHP = β-hydroxypentanoate; BKP = β-ketopentanoate; BKP-CoA = β-ketopentanoyl–coenzyme A; BUN = blood urea nitrogen; CAC = citric acid cycle; CoA = coenzyme A; CPK = creatine phosphokinase; CPT II = carnitine palmitoyltransferase II; LDL = low-density lipoprotein; MCT = medium-chain triglyceride; PCS = physical composite score; SF-36 = 36-item Short-Form Health Status survey. PMID:18645163

Primary Intestinal Lymphangiectasia Manifested as Unusual Edemas and Effusions: A Case Report.

PubMed

Wang, Xuefeng; Jin, Hong; Wu, Weilu

2016-03-01

Primary intestinal lymphangiectasia (PIL) is a rare disorder of unknown etiology characterized by diffuse or localized dilation and eventual rupture of the enteric lymphatic vessels in mucosa, submucosa, and/or subserosa. Lymph, rich in all kinds of proteins and lymphocytes, leaks into the gastrointestinal tract via the affected lymphatic vessels causing hypoproteinemia and lymphopenia. The main symptom is variable degrees of pitting edemas of bilateral lower limbs. But edemas of any other parts of body, and mild serous effusions may also occur sometimes. PIL occurs in conjunction with a right hemifacial edema, a right upper limb lymphedema, asymmetric bilateral calves edemas, and a unilateral massive pleural effusion seems never to be reported before. In addition, increased enteric protein loss that may cause severe hypoproteinemia usually get overlooked, and the lymphatic system disorders always put the diagnoses in a dilemma.We described a case of a 17-year-old Chinese girl with a history of gradually progressive swellings of right-sided face, right upper limb, and bilateral calves since 3 to 4 months of age. A right-sided massive pleural effusion, a moderate pericardial effusion, and a mild ascites have been proved unchanged by a series of computerized tomography (CT) scans since 5 years ago. The diagnosis of PIL was finally confirmed by severe hypoproteinemia, endoscopic changes, and histology of jejunum biopsy. Further lymphoscintigraphy and lymphangiography also identified lymph leakage in her bowel and several abnormal lymphatic vessels. A high-protein, low-fat diet supplemented with medium-chain triglycerides (MCT) showed some benefit.This case suggested that PIL was a rare but important etiology of hypoproteinemia, effusions, and edemas. PIL, effusions, and lymphedema can be the features of multisegmental generalized lymphatic dysplasia. In addition, both lymphoscintigraphy and intranodal lymphangiography could be considered when lymphatic system disorders are suspected.

Primary Intestinal Lymphangiectasia Manifested as Unusual Edemas and Effusions

PubMed Central

Wang, Xuefeng; Jin, Hong; Wu, Weilu

2016-01-01

Abstract Primary intestinal lymphangiectasia (PIL) is a rare disorder of unknown etiology characterized by diffuse or localized dilation and eventual rupture of the enteric lymphatic vessels in mucosa, submucosa, and/or subserosa. Lymph, rich in all kinds of proteins and lymphocytes, leaks into the gastrointestinal tract via the affected lymphatic vessels causing hypoproteinemia and lymphopenia. The main symptom is variable degrees of pitting edemas of bilateral lower limbs. But edemas of any other parts of body, and mild serous effusions may also occur sometimes. PIL occurs in conjunction with a right hemifacial edema, a right upper limb lymphedema, asymmetric bilateral calves edemas, and a unilateral massive pleural effusion seems never to be reported before. In addition, increased enteric protein loss that may cause severe hypoproteinemia usually get overlooked, and the lymphatic system disorders always put the diagnoses in a dilemma. We described a case of a 17-year-old Chinese girl with a history of gradually progressive swellings of right-sided face, right upper limb, and bilateral calves since 3 to 4 months of age. A right-sided massive pleural effusion, a moderate pericardial effusion, and a mild ascites have been proved unchanged by a series of computerized tomography (CT) scans since 5 years ago. The diagnosis of PIL was finally confirmed by severe hypoproteinemia, endoscopic changes, and histology of jejunum biopsy. Further lymphoscintigraphy and lymphangiography also identified lymph leakage in her bowel and several abnormal lymphatic vessels. A high-protein, low-fat diet supplemented with medium-chain triglycerides (MCT) showed some benefit. This case suggested that PIL was a rare but important etiology of hypoproteinemia, effusions, and edemas. PIL, effusions, and lymphedema can be the features of multisegmental generalized lymphatic dysplasia. In addition, both lymphoscintigraphy and intranodal lymphangiography could be considered when lymphatic system disorders are suspected. PMID:26962779

[Chitosan-coated ophthalmic submicro emulsion for pilocarpine nitrate].

PubMed

Wei, Jun; He, Hong-Liang; Zheng, Chun-Li; Zhu, Jia-Bi

2011-08-01

The study is to design chitosan-coated pilocarpine nitrate submicro emulsion (CS-PN/SE) for the development of a novel mucoadhesive submicro emulsion, aiming to prolong the precorneal retention time and improve the ocular absorption. CS-PN/SE was fabricated in two steps: firstly, pilocarpine nitrate submicro emulsion (PN/SE) was prepared by high-speed shear with medium chain triglycerides (MCT) as oil phase and Tween 80 as the main emulsifier, and then incubated with chitosan (CS) acetic solution. The preparation process was optimized by central composite design-response surface methodology. Besides the particle size, zeta potential, entrapment efficiency and micromorphology were investigated, CS-PN/SE's precorneal residence properties and miotic effect were especially studied using New Zealand rabbits as the animal model. When CS-PN/SE was administered topically to rabbit eyes, the ocular clearance and the mean resident time (MRT) of pilocarpine nitrate were found to be dramatically improved (P < 0.05) compared with PN/SE and pilocarpine nitrate solution (PNs), since the K(CS-PN/SE) was declined to 0.006 4 +/- 0.000 3 min(-1) while MRT was prolonged up to 155.4 min. Pharmacodynamics results showed that the maximum miosis of CS-PN/SE was as high as 46.3%, while the miotic response lasted 480 min which is 255 min and 105 min longer than that of PNs and PN/SE, respectively. A larger area under the miotic percentage vs time curve (AUC) of CS-PN/SE was exhibited which is 1.6 folds and 1.2 folds as much as that of PNs and PN/SE, respectively (P < 0.05). Therefore, CS-PN/SE could enhance the duration of action and ocular bioavailability by improving the precorneal residence and ocular absorption significantly.

New parenteral lipid emulsions for clinical use.

PubMed

Waitzberg, Dan L; Torrinhas, Raquel Susana; Jacintho, Thiago Manzoni

2006-01-01

Routine use of parenteral lipid emulsions (LE) in clinical practice began in 1961, with the development of soybean oil (SO) - based LE. Although clinically safe, experimental reports indicated that SO-based LE could exert a negative influence on immunological functions. Those findings were related to its absolute and relative excess of omega-6 polyunsaturated fatty acids (PUFA) and the low amount of omega-3 PUFA and also to its high PUFA content with an increased peroxidation risk. This motivated the development of new LE basically designed along the reduction of omega-6 PUFA and the omega-3 PUFA addition in order to obtain balanced levels of the omega-6/omega-3 ratio. The new LE for clinical use (available in Europe and South America) are differentiated by their content in polyunsaturated (omega-6 and omega-3), monounsaturated, and saturated fatty acids (FA), as well as FA source of their origin, including soy, coconut, olive, and fish oil. This article presents the new LE nutrition and energy functions but also its biochemical, metabolic, and immunomodulating aspects, according to their FA content. LE at 20% when infused from 1.0 to 2.0 g/kg body weight/day rates, either alone or in association with amino acids and glucose, are safe and well tolerated in routine clinical practice. LE combining SO with medium-chain triglycerides and/or olive oil have less omega-6 PUFA and are better metabolized, with less inflammatory and immunosuppressive effects than in relation to pure SO-based LE. The omega-3 PUFA used alone or as component of a new and complex LE (soy, MCT, olive and fish oil) has demonstrated anti-inflammatory and immunomodulatory effects.

Fat encapsulation enhances dietary nutrients utilization and growth performance of nursery pigs.

PubMed

Yang, F; Zhang, S H; Kim, S W; Ren, C X; Tian, M; Cheng, L; Song, J J; Chen, J; Chen, F; Guan, W T

2018-05-31

Encapsulation of fat may facilitate digestion and absorption of fat in nursery pigs. Two experiments were conducted to evaluate (1) effects of encapsulation of palm oil and coconut oil on growth performance, feed intake, feed efficiency, and blood parameters, and (2) effects of encapsulation of palm oil and coconut oil on apparent total tract digestibility (ATTD) of nutrients, and the activity of digestive enzymes in nursery pigs. In Exp. 1, 540 pigs (28 d of age, 8.23 ± 0.22 kg BW) were allotted to 5 treatments based on a randomized complete block design (as-fed basis). Pigs were fed basal diets with 5 different fat sources: 6.0% soybean oil (SBO), 6.0% palm oil (PO), 6.0% palm oil from encapsulated fat (EPO), 6.0% coconut oil (CO), and 6.0% coconut oil from encapsulated fat (ECO) respectively, with 6 pens per treatment and 18 pigs per pen for a 4-wk feeding trial. Dried casein and whey powder used for encapsulation were included at identical levels in all diets. Pigs fed EPO had increased (PPPad libitum for 4 weeks to measure ATTD of diets weekly and digestive enzyme activity at wk 4. Pigs fed EPO, CO, and ECO had increased (PPPEE) compared to other treatments. Pigs fed PO had greater (PP = 0.073) pancreatic lipase activity compared to other treatments whereas dietary treatments had no effect on pancreatic amylase activity. In conclusion, this study indicates that encapsulation of palm oil improved growth performance and ATTD of diets in nursery pigs, whereas the limited effects of encapsulated coconut oil were likely due to the high digestibility of the medium chain triglycerides (MCT) abundant in coconut oil.

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

PubMed

Ekcharoen, Chanikarn; Tantibhaedhyangkul, Ruangvith

2015-12-01

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

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

Primary intestinal lymphangiectasia: Minireview

PubMed Central

Ingle, Sachin B; Hinge (Ingle), Chitra R

2014-01-01

Primary idiopathic intestinal lymphangiectasia is an unusual disease featured by the presence of dilated lymphatic channels which are located in the mucosa, submucosa or subserosa leading to protein loosing enteropathy.Most often affected were children and generally diagnosed before third year of life but may be rarely seen in adults too. Bilateral pitting oedema of lower limb is the main clinical manifestation mimicking the systemic disease and posing a real diagnostic dilemma to the clinicians to differentiate it from other common systemic diseases like Congestive cardiac failure, Nephrotic Syndrome, Protein Energy Malnutrition, etc. Diagnosis can be made on capsule endoscopy which can localise the lesion but unable to take biopsy samples. Thus, recently double-balloon enteroscopy and biopsy in combination can be used as an effective diagnostic tool to hit the correct diagnosis. Patients respond dramatically to diet constituting low long chain triglycerides and high protein content with supplements of medium chain triglyceride. So early diagnosis is important to prevent untoward complications related to disease or treatment for the sake of accurate pathological diagnosis. PMID:25325063

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.

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.

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

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.

Role of free fatty acid receptors in the regulation of energy metabolism.

PubMed

Hara, Takafumi; Kashihara, Daiji; Ichimura, Atsuhiko; Kimura, Ikuo; Tsujimoto, Gozoh; Hirasawa, Akira

2014-09-01

Free fatty acids (FFAs) are energy-generating nutrients that act as signaling molecules in various cellular processes. Several orphan G protein-coupled receptors (GPCRs) that act as FFA receptors (FFARs) have been identified and play important physiological roles in various diseases. FFA ligands are obtained from food sources and metabolites produced during digestion and lipase degradation of triglyceride stores. FFARs can be grouped according to ligand profiles, depending on the length of carbon chains of the FFAs. Medium- and long-chain FFAs activate FFA1/GPR40 and FFA4/GPR120. Short-chain FFAs activate FFA2/GPR43 and FFA3/GPR41. However, only medium-chain FFAs, and not long-chain FFAs, activate GPR84 receptor. A number of pharmacological and physiological studies have shown that these receptors are expressed in various tissues and are primarily involved in energy metabolism. Because an impairment of these processes is a part of the pathology of obesity and type 2 diabetes, FFARs are considered as key therapeutic targets. Here, we reviewed recently published studies on the physiological functions of these receptors, primarily focusing on energy homeostasis. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

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 infused TG during the steady-state period (r = 0.58; P < .05). In conclusion, the hypertriglyceridemic clamp method was found to give reproducible results and could be considered for comparison of metabolic clearance properties of different types of fat emulsions. The capacity of healthy subjects to eliminate STGs from blood was greater than for LCTs. An increased LPL activity induced by the higher TG infusion rate may have contributed to the increased metabolic clearance of STGs.

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.

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).

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.

Enteral Formula Containing Egg Yolk Lecithin Improves Diarrhea.

PubMed

Akashi, Tetsuro; Muto, Ayano; Takahashi, Yayoi; Nishiyama, Hiroshi

2017-09-01

Diarrhea often occurs during enteral nutrition. Recently, several reports showed that diarrhea improves by adding egg yolk lecithin, an emulsifier, in an enteral formula. Therefore, we evaluated if this combination could improve diarrhea outcomes. We retrospectively investigated the inhibitory effects on watery stools by replacing a polymeric fomula with that containing egg yolk lecithin. Then, we investigated the emulsion stability in vitro. Next, we examined the lipid absorption using different emulsifiers among bile duct-ligated rats and assessed whether egg yolk lecithin, medium-chain triglyceride, and dietary fiber can improve diarrhea outcomes in a rat model of short bowel syndrome. Stool consistency or frequency improved on the day after using the aforementioned combination in 13/14 patients. Average particle size of the egg yolk lecithin emulsifier did not change by adding artificial gastric juice, whereas that of soy lecithin and synthetic emulsifiers increased. Serum triglyceride concentrations were significantly higher in the egg yolk lecithin group compared with the soybean lecithin and synthetic emulsifier groups in bile duct-ligated rats. In rats with short bowels, the fecal consistency was a significant looser the dietary fiber (+) group than the egg yolk lecithin (+) groups from day 6 of test meal feedings. The fecal consistency was also a significant looser the egg yolk lecithin (-) group than the egg yolk lecithin (+) groups from day 4 of test meal feeding. The fecal consistency was no significant difference between the medium-chain triglycerides (-) and egg yolk lecithin (+) groups. Enteral formula emulsified with egg yolk lecithin promotes lipid absorption by preventing the destruction of emulsified substances by gastric acid. This enteral formula improved diarrhea and should reduce the burden on patients and healthcare workers.

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

Mitochondrial fatty acid biosynthesis and muscle fiber plasticity in very long-chain acyl-CoA dehydrogenase-deficient mice.

PubMed

Tucci, Sara; Mingirulli, Nadja; Wehbe, Zeinab; Dumit, Verónica I; Kirschner, Janbernd; Spiekerkoetter, Ute

2018-01-01

The white skeletal muscle of very long-chain acyl-CoA-dehydrogenase-deficient (VLCAD -/- ) mice undergoes metabolic modification to compensate for defective β-oxidation in a progressive and time-dependent manner by upregulating glucose oxidation. This metabolic regulation seems to be accompanied by morphologic adaptation of muscle fibers toward the glycolytic fiber type II with the concomitant upregulation of mitochondrial fatty acid biosynthesis (mFASII) and lipoic acid biosynthesis. Dietary supplementation of VLCAD -/- mice with different medium-chain triglycerides over 1 year revealed that odd-chain species has no effect on muscle fiber switch, whereas even-chain species inhibit progressive metabolic adaptation. Our study shows that muscle may undergo adaptive mechanisms that are modulated by dietary supplementation. We describe for the first time a concomitant change of mFASII in this muscular adaptation process. © 2017 Federation of European Biochemical Societies.

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.

Resistance to Diet-Induced Obesity and Associated Metabolic Perturbations in Haploinsufficient Monocarboxylate Transporter 1 Mice

PubMed Central

Steiner, Nadia; Carneiro, Lionel; Favrod, Céline; Preitner, Frédéric; Thorens, Bernard; Stehle, Jean-Christophe; Dix, Laure; Pralong, François; Magistretti, Pierre J.; Pellerin, Luc

2013-01-01

The monocarboxylate transporter 1 (MCT1 or SLC16A1) is a carrier of short-chain fatty acids, ketone bodies, and lactate in several tissues. Genetically modified C57BL/6J mice were produced by targeted disruption of the mct1 gene in order to understand the role of this transporter in energy homeostasis. Null mutation was embryonically lethal, but MCT1 +/− mice developed normally. However, when fed high fat diet (HFD), MCT1 +/− mice displayed resistance to development of diet-induced obesity (24.8% lower body weight after 16 weeks of HFD), as well as less insulin resistance and no hepatic steatosis as compared to littermate MCT1 +/+ mice used as controls. Body composition analysis revealed that reduced weight gain in MCT1 +/− mice was due to decreased fat accumulation (50.0% less after 9 months of HFD) notably in liver and white adipose tissue. This phenotype was associated with reduced food intake under HFD (12.3% less over 10 weeks) and decreased intestinal energy absorption (9.6% higher stool energy content). Indirect calorimetry measurements showed ∼ 15% increase in O2 consumption and CO2 production during the resting phase, without any changes in physical activity. Determination of plasma concentrations for various metabolites and hormones did not reveal significant changes in lactate and ketone bodies levels between the two genotypes, but both insulin and leptin levels, which were elevated in MCT1 +/+ mice when fed HFD, were reduced in MCT1 +/− mice under HFD. Interestingly, the enhancement in expression of several genes involved in lipid metabolism in the liver of MCT1 +/+ mice under high fat diet was prevented in the liver of MCT1 +/− mice under the same diet, thus likely contributing to the observed phenotype. These findings uncover the critical role of MCT1 in the regulation of energy balance when animals are exposed to an obesogenic diet. PMID:24367518

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.

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.

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.

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.

Transepithelial transport of alpha-lipoic acid across human intestinal Caco-2 cell monolayers.

PubMed

Takaishi, Naoki; Yoshida, Kazutaka; Satsu, Hideo; Shimizu, Makoto

2007-06-27

Alpha-lipoic acid (LA) is used in dietary supplements or food with antioxidative functions. The mechanism for the intestinal absorption of alpha-lipoic acid was investigated in this study by using human intestinal Caco-2 cell monolayers. LA was rapidly transported across the Caco-2 cell monolayers, this transport being energy-dependent, suggesting transporter-mediated transport to be the mechanism involved. The LA transport was strongly dependent on the pH value, being accelerated in the acidic pH range. Furthermore, such monocarboxylic acids as benzoic acid and medium-chain fatty acids significantly inhibited LA transport, suggesting that a proton-linked monocarboxylic acid transporter (MCT) was involved in the intestinal transport of LA. The conversion of LA to the more antioxidative dihydrolipoic acid was also apparent during the transport process.

Structured lipid emulsion as nutritional therapy for the elderly patients with severe sepsis.

PubMed

Chen, Jin; Yan, Jing; Cai, Guo-Long; Xu, Qiang-Hong; Gong, Shi-Jin; Dai, Hai-Wen; Yu, Yi-Hua; Li, Li

2013-06-01

The nutritional support is one of the important therapeutic strategies for the elderly patients with severe sepsis, but there is controversial in choosing a parenteral nutrition formulation. This study was designed to compare the therapeutic effects of structured lipid emulsion, physically mixed medium, and long-chain fat emulsion in the treatment of severe sepsis in elderly patients. A total number of 64 elder patients with severe sepsis were enrolled in the study. After a week of enteral nutritional support, the patients were randomly divided into research (structured lipid emulsion as parenteral alimentation) and control groups (physically mixed medium and long-chain fat emulsion as parenteral alimentation). The alterations of plasma albumin, lipid metabolism, and blood glucose level were recorded after parenteral alimentation and were compared between the two groups. The plasma levels of albumin, prealbumin, cholesterol, and triglyceride were decreased in all the patients after one week of enteral nutritional support treatment (t = 7.78, P = 0.000; t = 10.21, P = 0.000; t = 7.99, P = 0.000; and t = 10.99, P = 0.000). Further parenteral alimentation with different lipid emulsions had significant effects on the serum prealbumin and albumin (t = 3.316, P = 0.002; t = 3.200, P = 0.002), whilst had no effects on the blood glucose and triglyceride level (t = 7.78, P = 0.000; t = 4.228, P = 0.000). In addition, the two groups had a significantly different Apache II score, ventilator time, and hospital stay time (t = -2.213, P = 0.031; t = 2.317, P = 0.024; t = 2.514, P = 0.015). The structured lipid emulsion was safe as parenteral nutrition for elderly patients with severe sepsis. It was demonstrated to be superior to the physically mixed medium and long-chain fat emulsion with respect to the protein synthesis and prognosis.

Lactobacillus acidophilus counteracts enteropathogenic E. coli-induced inhibition of butyrate uptake in intestinal epithelial cells

PubMed Central

Kumar, Anoop; Alrefai, Waddah A.; Dudeja, Pradeep K.

2015-01-01

Butyrate, a key short-chain fatty acid metabolite of colonic luminal bacterial action on dietary fiber, serves as a primary fuel for the colonocytes, ameliorates mucosal inflammation, and stimulates NaCl absorption. Absorption of butyrate into the colonocytes is essential for these intracellular effects. Monocarboxylate transporter 1 (MCT1) plays a major role in colonic luminal butyrate absorption. Previous studies (Tan J, McKenzie C, Potamitis M, Thorburn AN, Mackay CR, Macia L. Adv Immunol 121: 91–119, 2014.) showed decreased MCT1 expression and function in intestinal inflammation. We have previously shown (Borthakur A, Gill RK, Hodges K, Ramaswamy K, Hecht G, Dudeja PK. Am J Physiol Gastrointest Liver Physiol 290: G30–G35, 2006.) impaired butyrate absorption in human intestinal epithelial Caco-2 cells due to decreased MCT1 level at the apical cell surface following enteropathogenic E. coli (EPEC) infection. Current studies, therefore, examined the potential role of probiotic Lactobacilli in stimulating MCT1-mediated butyrate uptake and counteracting EPEC inhibition of MCT1 function. Of the five species of Lactobacilli, short-term (3 h) treatment with L. acidophilus (LA) significantly increased MCT1-mediated butyrate uptake in Caco-2 cells. Heat-killed LA was ineffective, whereas the conditioned culture supernatant of LA (LA-CS) was equally effective in stimulating MCT1 function, indicating that the effects are mediated by LA-secreted soluble factor(s). Furthermore, LA-CS increased apical membrane levels of MCT1 protein via decreasing its basal endocytosis, suggesting that LA-CS stimulation of butyrate uptake could be secondary to increased levels of MCT1 on the apical cell surface. LA-CS also attenuated EPEC inhibition of butyrate uptake and EPEC-mediated endocytosis of MCT1. Our studies highlight distinct role of specific LA-secreted molecules in modulating colonic butyrate absorption. PMID:26272259

Characterization of the Expression of Basigin Gene Products Within the Pineal Gland of Mice.

PubMed

Tokar, Derek; van Ekeris, Leslie; Linser, Paul J; Ochrietor, Judith D

2017-08-01

The expression of Basigin gene products and monocarboxylate transporter-1 (MCT1) has been investigated within the mammalian neural retina and suggests a role for these proteins in cellular metabolism within that tissue. The purpose of the present study was to investigate the expression of these same proteins in the pineal gland of the mouse brain. Mouse pineal gland and neural retina RNA and protein were subjected to quantitative reverse transcription-polymerase chain reaction and immunoblotting analyses. In addition, paraffin-embedded sections of each tissue were analyzed for expression of Basigin gene products and MCT1 via immunohistochemistry. The results indicate that MCT1 and Basigin variant-2, but not Basigin variant-1, are expressed within the mouse pineal gland. The expression of Basigin variant-2 and MCT1 was localized to the capsule surrounding the gland. The position and relative amounts of the gene products suggest that they play a much less prominent role within the pineal gland than in the neural retina.

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

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.

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.

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.

Binding of long-lasting local anesthetics to lipid emulsions.

PubMed

Mazoit, Jean-Xavier; Le Guen, Régine; Beloeil, Hélène; Benhamou, Dan

2009-02-01

Rapid infusion of lipid emulsion has been proposed to treat local anesthetic toxicity. The authors wanted to test the buffering properties of two commercially available emulsions made of long- and of long- and medium-chain triglycerides. Using the shake-flask method, the authors measured the solubility and binding of racemic bupivacaine, levobupivacaine, and ropivacaine to diluted Intralipid (Fresenius Kabi, Paris, France) and Medialipide (B-Braun, Boulogne, France). The apparent distribution coefficient expressed as the ratio of mole fraction was 823 +/- 198 and 320 +/- 65 for racemic bupivacaine and levobupivacaine, and ropivacaine, respectively, at 500 mg in the Medialipide/buffer emulsion; and 1,870 +/- 92 and 1,240 +/- 14 for racemic bupivacaine and levobupivacaine, and ropivacaine, respectively, in the Intralipid/buffer emulsion. Decreasing the pH from 7.40 to 7.00 of the Medialipide/buffer emulsion led to a decrease in ratio of molar concentration from 121 +/- 3.8 to 46 +/- 2.8 for bupivacaine, and to a lesser extent from 51 +/- 4.0 to 31 +/- 1.6 for ropivacaine. The capacity of the 1% emulsions was 871 and 2,200 microM for the 1% Medialipide and Intralipid emulsions, respectively. The dissociation constant was 818 and 2,120 microM for racemic bupivacaine and levobupivacaine, and ropivacaine, respectively. Increasing the temperature from 20 to 37 degrees C led to a greater increase in affinity for ropivacaine (55%) than for bupivacaine (27%). When the pH of the buffer was decreased from 7.40 to 7.00, the affinity was decreased by a factor of 1.68, similar for both anesthetics. The solubility of long-acting local anesthetics in lipid emulsions and the high capacity of binding of these emulsions most probably explain their clinical efficacy in case of toxicity. The long-chain triglyceride emulsion Intralipid appears to be about 2.5 times more efficacious than the 50/50 medium-chain/long-chain Medialipide emulsion. Also, because of their higher hydrophobicity, racemic bupivacaine and levobupivacaine seem to clear more rapidly than ropivacaine.

Histopathological and genetic review of phosphaturic mesenchymal tumours, mixed connective tissue variant.

PubMed

Yamada, Yuichi; Kinoshita, Izumi; Kenichi, Kohashi; Yamamoto, Hidetaka; Iwasaki, Takeshi; Otsuka, Hiroshi; Yoshimoto, Masato; Ishihara, Shin; Toda, Yu; Kuma, Yuki; Setsu, Nokitaka; Koga, Yuki; Honda, Yumi; Inoue, Takeshi; Yanai, Hiroyuki; Yamashita, Kyoko; Ito, Ichiro; Takahashi, Mitsuru; Ohga, Shouichi; Furue, Masutaka; Nakashima, Yasuharu; Oda, Yoshinao

2018-02-01

Phosphaturic mesenchymal tumour, mixed connective tissue variant (PMT-MCT), is a tumour of uncertain differentiation, characterised by 'smudgy/grungy' calcification and vitamin D-resistant phosphaturic osteomalacia. Fibroblast growth factor (FGF)23 is recognised as a reliable marker of PMT-MCT, but quantitative evaluation has never been performed. We reviewed cases of tumour-associated osteomalacia or histologically definitive PMT-MCT without osteomalacia using histological, immunohistochemical and genetic methods and evaluated the diagnostic significance of these findings. A total of 19 tumours from 14 cases diagnosed previously as PMT-MCT were retrieved, on which immunohistochemical staining, reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence in-situ hybridisation (FISH) analysis were performed. Histologically, fibrous capsule, calcification and giant cell reaction tended to be observed in soft-tissue PMT-MCT, while PMT-MCT of bone and multiple PMT-MCT showed an infiltrative growth pattern. The immunohistochemical results were as follows: the tumour cells were positive for FGF23 (nine of 12, 75%), FGFR1 (11 of 11, 100%), CD56 (12 of 14, 85.7%) and E26 oncogene homologue (ERG) (5 of 13, 38.4%). The sole malignant tumour was positive for p53. FGF23 mRNA was detected in seven of 14 formalin-fixed paraffin-embedded (FFPE) specimens and all five frozen specimens by RT-PCR. The level of FGF23 mRNA, which was determined by real-time PCR, varied among the phosphaturic cases. Two of 17 tumours were positive for FGFR1 gene rearrangement. It was considered that PMT-MCT is a histopathological entity with or without phosphaturia, with varying levels of FGF23 mRNA, and with or without fibronectin 1 (FN1)-FGFR1 fusion gene. The authors propose that the histology of PMT-MCT differs depending on its location, such as bone or soft tissue, which could complicate the differential diagnosis. © 2017 John Wiley & Sons Ltd.

Alternative Fuels in Epilepsy and Amyotrophic Lateral Sclerosis.

PubMed

Tefera, Tesfaye W; Tan, Kah Ni; McDonald, Tanya S; Borges, Karin

2017-06-01

This review summarises the recent findings on metabolic treatments for epilepsy and Amyotrophic Lateral Sclerosis (ALS) in honour of Professor Ursula Sonnewald. The metabolic impairments in rodent models of these disorders as well as affected patients are being discussed. In both epilepsy and ALS, there are defects in glucose uptake and reduced tricarboxylic acid (TCA) cycling, at least in part due to reduced amounts of C4 TCA cycle intermediates. In addition there are impairments in glycolysis in ALS. A reduction in glucose uptake can be addressed by providing the brain with alternative fuels, such as ketones or medium-chain triglycerides. As anaplerotic fuels, such as the triglyceride of heptanoate, triheptanoin, refill the TCA cycle C4/C5 intermediate pool that is deficient, they are ideal to boost TCA cycling and thus the oxidative metabolism of all fuels.

[Chylopericardium as a complication of cardiac surgery: report of two cases and review of the literature].

PubMed

Velinović, Milos; Vranes, Mile; Kocica, Mladen; Djukić, Petar; Mikić, Aleksandar; Vukomanović, Vladislav; Kacar, Sasa; Putnik, Svetozar; Marković, Dejan; Seferović, Petar M

2007-01-01

Chylopericardium refers to existing communication between the pericardial sac and the thoracic duct carrying the chyle. The objective of our report was to highlight the specificity of diagnosis and treatment of this rare but tedious condition through the analysis of two case reports. Male patient, aged 63 years, with chylopericardium was diagnosed perioperatively (implantation of artificial aortic--St. Jude No 21 and mitral valve--St. Jude No 29). Etiology of pericardial effusion was established by Sudan III staining of punctate specimen obtained by subxiphoid pericardial puncture. Probable cause of chylopericardium was the lesion of ductus thoracicus during cross-clamping of the superior caval vein with a Cooley clamp. Initial treatment included diet rich in medium-chain triglycerides which resulted in resolution of the effusion. During five-year follow-up, there were no recurrences of pericardial effusion. The second patient was female, 21 years old, with chylopericardium after partial pericardiectomy performed because of the chronic severely symptomatic pericardial effusion, resistant to other forms of treatment. Pericardiocentesis provided 650 ml of yellowish fluid with a high concentration of cholesterol (3.2 mmol/l), triglycerides (16.6 mmol/l), and proteins (64.7 g/l), which verified chylopericardium, most probably as a consequence of the lesion of ductus thoracicus during partial pericardiectomy. Diet rich in medium-chain triglycerides failed to decrease the effusion, after two weeks of treatment (daily secretion 250-350 ml). Lymphography revealed lesion of ductus thoracicus, most probably at Th9/Th10 level, with no direct visualization of extravasal accumulation of contrast media. Surgical ligation of ductus thoracicus was performed through the right thoracotomy. However, postoperative secretion increased to 1000 ml/day. Patient underwent redo surgery comprising the ligation of lymphatic vessels, guided by extravasation of intraoperatively iwected methylene-blue indicator. During one-year follow-up, there were no recurrences of pericardial effusion. In conclusion, intraoperative lymphography significantly contributed to successful surgical treatment of patients with chylopericardium.

Characterization of acetate transport in colorectal cancer cells and potential therapeutic implications

PubMed Central

Ferro, Suellen; Azevedo-Silva, João; Casal, Margarida; Côrte-Real, Manuela; Baltazar, Fatima; Preto, Ana

2016-01-01

Acetate, together with other short chain fatty acids has been implicated in colorectal cancer (CRC) prevention/therapy. Acetate was shown to induce apoptosis in CRC cells. The precise mechanism underlying acetate transport across CRC cells membrane, that may be implicated in its selectivity towards CRC cells, is not fully understood and was addressed here. We also assessed the effect of acetate in CRC glycolytic metabolism and explored its use in combination with the glycolytic inhibitor 3-bromopyruvate (3BP). We provide evidence that acetate enters CRC cells by the secondary active transporters MCT1 and/or MCT2 and SMCT1 as well as by facilitated diffusion via aquaporins. CRC cell exposure to acetate upregulates the expression of MCT1, MCT4 and CD147, while promoting MCT1 plasma membrane localization. We also observed that acetate increases CRC cell glycolytic phenotype and that acetate-induced apoptosis and anti-proliferative effect was potentiated by 3BP. Our data suggest that acetate selectivity towards CRC cells might be explained by the fact that aquaporins and MCTs are found overexpressed in CRC clinical cases. Our work highlights the importance that acetate transport regulation has in the use of drugs such as 3BP as a new therapeutic strategy for CRC. PMID:28874966

The role of monocarboxylate transporters in uptake of lactic acid in HeLa cells.

PubMed

Cheeti, Sravanthi; Warrier, Bharat K; Lee, Chi H

2006-11-15

This study was aimed to identify the monocarboxylate transporters (MCTs) in HeLa cells and to delineate their role in transportation of L-lactic acid. The functional role of MCTs in lactic acid transport was evaluated at various mucosal pHs (4.5-7.4) or in the presence of various loading doses (0.2-2mM) of lactic acid, MCT substrates (nicotinic acid, n-butyric acid, etc.) and inhibitors (alpha-cyano-4-hydroxycinnamate and para-chloromercuribenzoic acid). The molecular properties of MCTs were characterized using reverse transcription-polymerase chain reaction (RT-PCR). The uptake rate of lactic acid by HeLa cells significantly increased from 0.353+/-0.052 to 1.103+/-0.196 micromol/mg protein as the extra-cellular pH changed from 7.4 to 4.5, indicating that activities of MCT were mediated through H(+)-linked mechanism. The uptake profile of lactic acid followed the saturable process with the K(m) value of 0.53 mM. The uptake rate of lactic acid is concentration dependent and is reduced in the presence of MCT inhibitors. MCT isoforms 1, 5 and 6 in HeLa cells were identified by RT-PCR. HeLa cell line can be used as an effective screening tool for intravaginally administered drugs targeted toward MCT.

Applicability of mode-coupling theory to polyisobutylene: a molecular dynamics simulation study.

PubMed

Khairy, Y; Alvarez, F; Arbe, A; Colmenero, J

2013-10-01

The applicability of Mode Coupling Theory (MCT) to the glass-forming polymer polyisobutylene (PIB) has been explored by using fully atomistic molecular dynamics simulations. MCT predictions for the so-called asymptotic regime have been successfully tested on the dynamic structure factor and the self-correlation function of PIB main-chain carbons calculated from the simulated cell. The factorization theorem and the time-temperature superposition principle are satisfied. A consistent fitting procedure of the simulation data to the MCT asymptotic power-laws predicted for the α-relaxation regime has delivered the dynamic exponents of the theory-in particular, the exponent parameter λ-the critical non-ergodicity parameters, and the critical temperature T(c). The obtained values of λ and T(c) agree, within the uncertainties involved in both studies, with those deduced from depolarized light scattering experiments [A. Kisliuk et al., J. Polym. Sci. Part B: Polym. Phys. 38, 2785 (2000)]. Both, λ and T(c)/T(g) values found for PIB are unusually large with respect to those commonly obtained in low molecular weight systems. Moreover, the high T(c)/T(g) value is compatible with a certain correlation of this parameter with the fragility in Angell's classification. Conversely, the value of λ is close to that reported for real polymers, simulated "realistic" polymers and simple polymer models with intramolecular barriers. In the framework of the MCT, such finding should be the signature of two different mechanisms for the glass-transition in real polymers: intermolecular packing and intramolecular barriers combined with chain connectivity.

Role of Monocarboxylate Transporters in Drug Delivery to the Brain

PubMed Central

Vijay, Nisha; Morris, Marilyn E.

2014-01-01

Monocarboxylate transporters (MCTs) are known to mediate the transport of short chain monocarboxylates such as lactate, pyruvate and butyrate. Currently, fourteen members of this transporter family have been identified by sequence homology, of which only the first four members (MCT1- MCT4) have been shown to mediate the proton-linked transport of monocarboxylates. Another transporter family involved in the transport of endogenous monocarboxylates is the sodium coupled MCTs (SMCTs). These act as a symporter and are dependent on a sodium gradient for their functional activity. MCT1 is the predominant transporter among the MCT isoforms and is present in almost all tissues including kidney, intestine, liver, heart, skeletal muscle and brain. The various isoforms differ in terms of their substrate specificity and tissue localization. Due to the expression of these transporters in the kidney, intestine, and brain, they may play an important role in influencing drug disposition. Apart from endogenous short chain monocarboxylates, they also mediate the transport of exogenous drugs such as salicylic acid, valproic acid, and simvastatin acid. The influence of MCTs on drug pharmacokinetics has been extensively studied for γ-hydroxybutyrate (GHB) including distribution of this drug of abuse into the brain and the results will be summarized in this review. The physiological role of these transporters in the brain and their specific cellular localization within the brain will also be discussed. This review will also focus on utilization of MCTs as potential targets for drug delivery into the brain including their role in the treatment of malignant brain tumors. PMID:23789956

The galactolipase activity of Fusarium solani (phospho)lipase.

PubMed

Jallouli, Raida; Othman, Houcemeddine; Amara, Sawsan; Parsiegla, Goetz; Carriere, Frédéric; Srairi-Abid, Najet; Gargouri, Youssef; Bezzine, Sofiane

2015-03-01

The purified (phospho)lipase of Fusarium solani (FSL), was known to be active on both triglycerides and phospholipids. This study aimed at assessing the potential of this enzyme in hydrolyzing galactolipids. FSL was found to hydrolyze at high rates of synthetic medium chains monogalactosyldiacylglycerol (4658±146U/mg on DiC8-MGDG) and digalactosyldiacylglycerol (3785±83U/mg on DiC8-DGDG) and natural long chain monogalactosyldiacylglycerol extracted from leek leaves (991±85U/mg). It is the microbial enzyme with the highest activity on galactolipids identified so far with a level of activity comparable to that of pancreatic lipase-related protein 2. FSL maximum activity on galactolipids was measured at pH8. The analysis of the hydrolysis product of natural MGDG from leek showed that FSL hydrolyzes preferentially the ester bond at the sn-1 position of galactolipids. To investigate the structure-activity relationships of FSL, a 3D model of this enzyme was built. In silico docking of medium chains MGDG and DGDG and phospholipid in the active site of FSL reveals structural solutions which are in concordance with in vitro tests. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

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

Chylous Ascites: Evaluation and Management

PubMed Central

Al-Busafi, Said A.; Ghali, Peter; Deschênes, Marc; Wong, Philip

2014-01-01

Chylous ascites refers to the accumulation of lipid-rich lymph in the peritoneal cavity due to disruption of the lymphatic system secondary to traumatic injury or obstruction. Worldwide, abdominal malignancy, cirrhosis, and tuberculosis are the commonest causes of CA in adults, the latter being most prevalent in developing countries, whereas congenital abnormalities of the lymphatic system and trauma are commonest in children. The presence of a milky, creamy appearing ascitic fluid with triglyceride content above 200 mg/dL is diagnostic, and, in the majority of cases, unless there is a strong suspicion of malignancy, further investigations are not required in patients with cirrhosis. If an underlying cause is identified, targeted therapy is possible, but most cases will be treated conservatively, with dietary support including high-protein and low-fat diets supplemented with medium-chain triglycerides, therapeutic paracentesis, total parenteral nutrition, and somatostatins. Rarely, resistant cases have been treated by transjugular intrahepatic portosystemic shunt, surgical exploration, or peritoneovenous shunt. PMID:27335837

Severe Hypertriglyceridemia in Glut1D on Ketogenic Diet.

PubMed

Klepper, Joerg; Leiendecker, Baerbel; Heussinger, Nicole; Lausch, Ekkehart; Bosch, Friedrich

2016-04-01

High-fat ketogenic diets are the only treatment available for Glut1 deficiency (Glut1D). Here, we describe an 8-year-old girl with classical Glut1D responsive to a 3:1 ketogenic diet and ethosuximide. After 3 years on the diet a gradual increase of blood lipids was followed by rapid, severe asymptomatic hypertriglyceridemia (1,910 mg/dL). Serum lipid apheresis was required to determine liver, renal, and pancreatic function. A combination of medium chain triglyceride-oil and a reduction of the ketogenic diet to 1:1 ratio normalized triglyceride levels within days but triggered severe myoclonic seizures requiring comedication with sultiam. Severe hypertriglyceridemia in children with Glut1D on ketogenic diets may be underdiagnosed and harmful. In contrast to congenital hypertriglyceridemias, children with Glut1D may be treated effectively by dietary adjustments alone. Georg Thieme Verlag KG Stuttgart · New York.

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.

High-fat semielemental diet in the treatment of protracted diarrhea of infancy.

PubMed

Jirapinyo, P; Young, C; Srimaruta, N; Rossi, T M; Cardano, A; Lebenthal, E

1990-12-01

The capacity for greater fat absorption relative to carbohydrate absorption in protracted diarrhea of infancy was studied in a developed and a developing country (Buffalo, NY, and Bangkok, Thailand). Fifty patients with protracted diarrhea in the first year of life (defined as liquid stools of more than 20 mL/kg per day with more than a 14-day duration) were randomly assigned to receive either a standard semielemental diet (Pregestimil) or a high-fat semielemental diet that contained 40% more fat. The increased fat was largely in the form of medium-chain triglycerides, with the new diet providing 60% of the fat as medium-chain triglycerides compared with 40% in the standard diet. Tolerance to both diets was good in both studies. Both groups showed adequate weight gain and an improvement in anthropometric and biochemical parameters. The patients receiving the high-fat diet showed no initial weight loss, however, and their weight gain was initiated earlier. Cumulative weight gain was also higher in the group receiving the high-fat semielemental diet. Fecal fat analyses were performed after 1 week of therapy. There was no difference observed in the coefficient of fat absorption between the groups receiving the two formulas, indicating that infants with protracted diarrhea may be able to tolerate a higher fat intake than is normally provided. As carbohydrate intolerance is known to be a complicating factor when using semielemental enteral feeds for infants with protracted diarrhea, a higher-fat semielemental diet may be the most appropriate way to provide adequate caloric intake.

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.

Application of small-angle neutron scattering to the study of forces between magnetically chained monodisperse ferrofluid emulsion droplets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jain, Dr Nirmesh; Liu, Dr C K; Hawkett, Dr B. S.

2014-01-01

The optical magnetic chaining technique (MCT) developed by Leal-Calderon, Bibette and co-workers in the 1990 s allows precise measurements of force profiles between droplets in monodisperse ferrofluid emulsions. However, the method lacks an in-situ determination of droplet size and therefore requires the combination of separately acquired measurements of droplet chain periodicity versus an applied magnetic field from optical Bragg scattering and droplet diameter inferred from dynamic light scattering (DLS) to recover surface force-distance profiles between the colloidal particles. Compound refractive lens (CRL) focussed small-angle scattering (SANS) MCT should result in more consistent measurements of droplet size (form factor measurements inmore » the absence of field) and droplet chaining period (from structure factor peaks when the magnetic field is applied); and, with access to shorter length scales, extend force measurements to closer approaches than possible by optical measurements. We report on CRL-SANS measurements of monodisperse ferrofluid emulsion droplets aligned in straight chains by an applied field perpendicular to the incident beam direction. Analysis of the scattering from the closely spaced droplets required algorithms that carefully treated resolution and its effect on mean scattering vector magnitudes in order to determine droplet size and chain periods to sufficient accuracy. At lower applied fields scattering patterns indicate structural correlations transverse to the magnetic field direction due to the formation of intermediate structures in early chain growth.« less

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.

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

PubMed

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

2017-03-01

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

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.

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

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.

Antistress and antioxidant effects of virgin coconut oil in vivo.

PubMed

Yeap, Swee Keong; Beh, Boon Kee; Ali, Norlaily Mohd; Yusof, Hamidah Mohd; Ho, Wan Yong; Koh, Soo Peng; Alitheen, Noorjahan Banu; Long, Kamariah

2015-01-01

Virgin coconut oil (VCO) has been consumed worldwide for various health-related reasons and some of its benefits have been scientifically evaluated. Medium-chain fatty acids were found to be a potential antidepressant functional food; however, this effect had not been evaluated in VCO, which is rich in polyphenols and medium-chain fatty acids. The aim of this study was to evaluate the antistress and antioxidant effects of VCO in vivo , using mice with stress-induced injury. The antistress effect of VCO (administered per os , at a dose of 10 ml/kg body weight) was evaluated using the forced swim test and chronic cold restraint stress models. VCO was able to reduce immobility time and restore oxidative stress in mice post-swim test. Furthermore, mice treated with VCO were found to exhibit higher levels of brain antioxidants, lower levels of brain 5-hydroxytryptamine and reduced weight of the adrenal glands. Consequently, the serum cholesterol, triglyceride, glucose and corticosterone levels were also lower in VCO-treated mice. These results suggest the potential value of VCO as an antistress functional oil.

Antistress and antioxidant effects of virgin coconut oil in vivo

PubMed Central

YEAP, SWEE KEONG; BEH, BOON KEE; ALI, NORLAILY MOHD; YUSOF, HAMIDAH MOHD; HO, WAN YONG; KOH, SOO PENG; ALITHEEN, NOORJAHAN BANU; LONG, KAMARIAH

2015-01-01

Virgin coconut oil (VCO) has been consumed worldwide for various health-related reasons and some of its benefits have been scientifically evaluated. Medium-chain fatty acids were found to be a potential antidepressant functional food; however, this effect had not been evaluated in VCO, which is rich in polyphenols and medium-chain fatty acids. The aim of this study was to evaluate the antistress and antioxidant effects of VCO in vivo, using mice with stress-induced injury. The antistress effect of VCO (administered per os, at a dose of 10 ml/kg body weight) was evaluated using the forced swim test and chronic cold restraint stress models. VCO was able to reduce immobility time and restore oxidative stress in mice post-swim test. Furthermore, mice treated with VCO were found to exhibit higher levels of brain antioxidants, lower levels of brain 5-hydroxytryptamine and reduced weight of the adrenal glands. Consequently, the serum cholesterol, triglyceride, glucose and corticosterone levels were also lower in VCO-treated mice. These results suggest the potential value of VCO as an antistress functional oil. PMID:25452773

Chylous ascites: a sequel of pelvic radiation therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sipes, S.L.; Newton, M.; Lurain, J.R.

1985-12-01

Chylous ascites is an unusual condition with many causes. Two cases are presented in which it appeared to be related to whole pelvis irradiation in one patient for carcinoma of the vagina and in another for carcinoma of the vulva. The diagnosis is made by paracentesis and analysis of the fluid. The underlying disease usually requires identification by exploratory laparotomy. Although a malignant process is the most common cause, the only findings in the authors' cases were widespread radiation changes in the intestine. After diagnosis treatment by low-fat diet with medium-chain triglyceride supplements resulted in disappearance of chylous ascites.

GLUT-1 deficiency without epilepsy--an exceptional case.

PubMed

Overweg-Plandsoen, W C G; Groener, J E M; Wang, D; Onkenhout, W; Brouwer, O F; Bakker, H D; De Vivo, D C

2003-01-01

The GLUT-1 deficiency is a metabolic disorder caused by a defect in glucose transport across the blood-brain barrier as a result of a defect in the glucose-transport protein. Patients present with epileptic seizures, delayed development, ataxia and hypotonia, and in many cases acquired microcephaly. In most patients, treatment with a ketogenic diet proved to be successful in controlling the epilepsy. We report a 9-year-old boy with retardation and ataxia, but without epilepsy, caused by GLUT-1 deficiency, proven biochemically and by DNA analysis. Treatment with a medium-chain triglyceride ketogenic diet had a beneficial effect.

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 of Mct8 and exert thyromimetic actions modulating the expression of T3-dependent genes. At the peripheral level, the administration of these TH analogs results in the depletion of circulating T4 and T3. Therefore, sobetirome and Sob-AM2 have the potential to address the cerebral hypothyroidism and the peripheral hyperthyroidism characteristic of MCT8 deficiency.

Solid nanoemulsion as antigen and immunopotentiator carrier for transcutaneous immunization.

PubMed

Gogoll, Karsten; Stein, Pamela; Lee, K D; Arnold, Philipp; Peters, Tanja; Schild, Hansjörg; Radsak, Markus; Langguth, Peter

2016-10-01

Imiquimod, a toll-like receptor 7 (TLR7) agonist, is an active pharmaceutical ingredient (API) established for the topical treatment of several dermal cancerous and precancerous skin lesions. Within this work, the immunostimulatory effect of imiquimod is further exploited in a transcutaneous immunization (TCI) approach based on a solid nanoemulsion (SN) formulation. SN contains a combination of imiquimod with the model peptide antigen SIINFEKL as a novel approach to omit needle and syringe and optimize dermal antigen administration. Excipients including sucrose fatty acid esters and the pharmaceutically acceptable oils MCT (middle chain triglycerides), avocado oil, jojoba wax and squalene are high pressure homogenized together with the antigen SIINFEKL. Freeze drying was performed to eliminate water and to achieve spreadable properties of the formulation for dermal administration. The influence of the different oil components was assessed regarding in vitro drug permeation in a Franz diffusion cell model using a murine skin setup. In vivo performance in terms of cytotoxic T-cell response was assessed in a C57BL/6 mouse model. Whereas Aldara® cream contains imiquimod in a dissolved state, the SN formulations carry the active in a suspended state. This resulted in a reduction of imiquimod permeation across murine skin from the SN when compared to Aldara® cream. In spite of this permeation rate reduction, each SN induced an in vivo immune response by specific T-cell lysis. A stabilized solid nanosuspension containing squalene/tocopherol exhibited a significantly higher performance (p⩽0.05) in comparison with Aldara® cream. MCT based SN exerted an in vivo effect comparable to Aldara®. In conclusion, anhydrous highly dispersed vehicles containing imiquimod in a submicron particle size distribution can represent promising formulations for TCI. The choice of the oil component has a strong influence on SN performance, independent of in vitro drug permeation. Copyright © 2016 Elsevier Inc. All rights reserved.

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.

[Clinical analysis of intestinal lymphangiectasia in 47 children].

PubMed

Guo, S; Song, L; Guan, D X; Mei, T L; Zhou, J; Yu, F H; Wang, G L; Zhang, J; Shen, H Q; Xu, X W

2017-12-02

Objective: To analyze the clinical manifestations, diagnosis, treatment and prognosis of intestinal lymphangiectasia (IL) in children in order to improve the skills of diagnosis and treatment of IL. Method: Clinical manifestations, laboratory findings, gastroscopic findings, histopathological examinations and lymphatic radionuclide imaging assessments were analyzed retrospectively among 47 IL patients who were hospitalized in the Gastroenterology Department of Beijing Children's Hospital Affiliated to Capital Medical University from June 2007 to December 2015. All patients were followed up by telephone. According to the various causes, the patients were divided into the primary intestinal lymphangiectasia (PIL) group and secondary IL group, and their clinical manifestations were compared by t test, Rank sum test or Chi-square test. Result: In 47 IL patients, there were 38 children (81%) younger than 3 years old. There were 43 PIL patients (91%) and 4 secondary IL patients (9%). Between PIL and secondary IL, there were statistical differences in serum albumin ( t=- 3.950, P< 0.005) , globulin( t=- 2.850, P= 0.007), age of onset( U =27.000, P= 0.024), age at diagnosis( U =29.000, P= 0.030) and course of disease( U =26.500, P= 0.023), whereas there were no statistical differences in lymphocyte count, IgG, lymphatic radionuclide imaging, histopathology and gender(all P> 0.05). Edema (44 cases, 94%), diarrhea (42 cases, 89%), accompanied with infection (35 cases, 74%) and ascites (30 cases, 64%) were the main clinical manifestations. In 47 IL patients, 45 patients were done gastroscopy and histopathological examinations, and there were 31 patients' histopathological examinations(69%) were positive. Forty patients were done lymphatic radionuclide imaging, and there was evidence of protein losing from gut via lymphatic radionuclide imaging in 39 patients(98%). Among 47 patients, 35 patients (74%) were followed up, 32 patients had good prognosis, 2 patient failed to show evidence of improvement, 1 patient died and no patient experienced a relapse till the end of the follow-up. In 35 patients, 28 patients were treated with medium chain triglycerides (MCT) dietary therapy, 26 patients showed improvement in symptoms, and 2 patients had no improvement. Among 35 patients with follow-up, there were 6 patients received surgical treatment, and their symptoms were improved. Conclusion: PIL are the majority of IL in children younger than 3 years old. The main clinical manifestations are edema, diarrhea, accompanied with infection and ascites. For the patients without the evidence of lymphangiectasia from duodenum histopathological examination, further consideration of lymphatic radionuclide imaging, clinical manifestations, and laboratory studies are needed to make a final diagnosis. MCT dietary therapy is the cornerstone of IL medical management.

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.

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.

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.

Long-chain omega-3 fatty acids, fibrates and niacin as therapeutic options in the treatment of hypertriglyceridemia: a review of the literature.

PubMed

Ito, Matthew K

2015-10-01

Hypertriglyceridemia affects approximately 33% of the US population. Elevated triglyceride levels are independently associated with cardiovascular disease (CVD) risk, and severe hypertriglyceridemia is a risk factor for acute pancreatitis. Guidelines for the management of severe hypertriglyceridemia (≥5.6 mmol/L [≥500 mg/dL]) recommend immediate use of triglyceride-lowering agents; however, statins remain the first line of therapy for the management of mild to moderate hypertriglyceridemia (1.7-5.6 mmol/L [150-499 mg/dL]). Statins primarily target elevated low-density lipoprotein cholesterol levels, but have also been shown to reduce mean triglyceride levels by up to 18% (or 43% in patients with triglyceride levels≥3.1 mmol/L [≥273 mg/dL]). However, individuals with hypertriglyceridemia may need additional reduction in triglyceride-rich lipoproteins and remnant particles to further reduce residual CVD risk. A number of guidelines recommend the addition of fibrates, niacin, or long-chain omega-3 fatty acids if elevated triglyceride or non-high-density lipoprotein cholesterol levels persist despite the use of high-intensity statin therapy. This review evaluates the impact of fibrates, niacin, and long-chain omega-3 fatty acids on lipid profiles and cardiovascular outcomes in patients with hypertriglyceridemia. It also assesses the adverse effects and drug-drug interactions associated with these triglyceride-lowering agents, because although they have all been shown to effectively reduce triglyceride levels in patients with hypertriglyceridemia, they differ with regard to their associated benefit-risk profiles. Long-chain omega-3 fatty acids may be a well-tolerated and effective alternative to fibrates and niacin, yet further large-scale clinical studies are required to evaluate their effects on cardiovascular outcomes and CVD risk reduction in patients with hypertriglyceridemia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effects of various vehicles on skin hydration in vivo.

PubMed

Wiedersberg, S; Leopold, C S; Guy, R H

2009-01-01

The stratum corneum, the outermost layer of the skin, regulates the passive loss of water to the environment. Furthermore, it is well accepted that drug penetration is influenced by skin hydration, which may be manipulated by the application of moisturizing or oleaginous vehicles. Measurements of transepidermal water loss (TEWL), and of skin hydration using a corneometer, were used to assess the effect of different vehicles on stratum corneum barrier function in vivo in human volunteers. A microemulsion significantly increased skin hydration relative to a reference vehicle based on medium chain triglycerides; in contrast, Transcutol(R) lowered skin hydration. TEWL measurements confirmed these observations. Copyright 2009 S. Karger AG, Basel.

Vitamin A and vitamin E isoforms stability and peroxidation potential of all-in-one admixtures for parenteral nutrition.

PubMed

Guidetti, Mariacristina; Sforzini, Annalisa; Bersani, Germana; Corsini, Catia; Grossi, Gabriele; Zolezzi, Carola; Fasano, Cinzia; Pironi, Loris

2008-05-01

In all-in-one admixtures (AIOs), vitamins can be degraded and lipid can be peroxidized by light exposure, oxygen action, and multiple chemical interactions. We investigated the impact of three commercial lipid emulsions and two multivitamin preparations on vitamin A and vitamin E chemical stability and lipid peroxidation potential of AIOs. A soybean oil (Soy), soybean/medium-chain triacylglycerol oil (MCT), and olive/soybean oil (Olive)-based emulsion (all 20%), and a lyophilized (Lyo) and emulsified (Emu) multivitamin compounds, were tested. Two AIOs for each lipid emulsion were prepared, the former with Lyo and the latter with Emu. The concentrations of retinol palmitate, alpha-gamma-delta-tocopherol, and malondialdehyde were analyzed in AIOs, immediately (T0) and 24 hours (T24) after compounding. Retinol palmitate, and alpha- and gamma-tocopherol were more stable in MCT-AIOs than in both Soy-AIOs and Olive-AIOs (p < 0.013; p < 0.001 respectively). Furthermore alpha-tocopherol was more stable in Lyo-AIOs than in Emu-AIOs (p < 0.004). Malondialdehyde (MDA) increased differently among the admixtures; however the concentrations were similar in all AIOs at T24. The differences in retinol palmitate stability were due both to lipid emulsions per se and to interaction between lipid emulsions and multivitamin preparations. The alpha-gamma-tocopherol stability depended on both lipid emulsions and multivitamin preparations. In tested AIOs there was a different degradation rate of fat-soluble vitamins to keep the same lipid peroxidation level, since MDA concentrations at T24 were similar among AIOs.

Development of Organogel-Derived Capsaicin Nanoemulsion with Improved Bioaccessibility and Reduced Gastric Mucosa Irritation.

PubMed

Lu, Muwen; Cao, Yong; Ho, Chi-Tang; Huang, Qingrong

2016-06-15

Capsaicin (CAP) is the major active component in chili peppers with health-promoting benefits. However, the low bioavailability and irritating quality of CAP greatly limit its applications in functional foods. The objective of this study was to develop a food-grade nanoemulsion to increase the dissolution and bioaccessibility of CAP and to alleviate its irritating effects. To achieve this goal, CAP was first dissolved in medium-chain triacylglycerol (MCT), followed by the addition of sucrose stearate S-370 as organogelator to develop CAP-loaded organogel. The oil-in-water (O/W) emulsion was formed using organogel as the oil phase and Tween 80 as the emulsifier. After ultrasonication treatment, droplet sizes of emulsion were decreased to 168 nm with enhanced dissolution rate and bioaccessibility. In vivo study further confirmed the reduced rat gastric mucosa irritation caused by CAP. The organogel-derived nanoemulsion was proved to be an effective delivery system for CAP-based functional food products.

Fat digestion by lingual lipase: mechanism of lipolysis in the stomach and upper small intestine.

PubMed

Liao, T H; Hamosh, P; Hamosh, M

1984-05-01

Ten to 30% of dietary fat is hydrolyzed in the stomach by lingual lipase, an enzyme secreted from lingual serous glands. We investigated the substrate specificity of this enzyme as well as the potential of lingual lipase to act in the upper small intestine i.e., in the presence of bile salts and lecithin. The data presented show that partially purified preparations of rat lingual lipase and the lipase in gastric aspirates of newborn infants have identical substrate specificity: medium-chain triglycerides were hydrolyzed at rates 5-8-fold higher than long-chain triglycerides; the rat and human enzymes do not hydrolyze the ester bond of lecithin or cholesteryl-ester. In contrast to pancreatic lipase, the hydrolysis of triglycerides by lingual lipase is not inhibited by lecithin. But, similar to pancreatic lipase the activity of lingual lipase is inhibited by bile salts, the extent of inhibition varying with its nature and concentration. This inactivation is not prevented by colipase but is partially averted by lipids and protein, suggesting that lingual lipase can remain active in the duodenum. The pH optimum of the enzyme (2.2-6.5 in the rat and 3.5-6.0 in human gastric aspirates) is compatible with continued activity in the upper small intestine, especially during the neonatal period, when the luminal pH is under 6.5. The marked variation in lipase activity levels in gastric aspirates of newborn infants is probably due to individual variations in enzyme amounts. The characteristics of the lipase are however identical in infants with low, intermediate or high activity levels.(ABSTRACT TRUNCATED AT 250 WORDS)

The Energy Content and Composition of Meals Consumed after an Overnight Fast and Their Effects on Diet Induced Thermogenesis: A Systematic Review, Meta-Analyses and Meta-Regressions

PubMed Central

Quatela, Angelica; Callister, Robin; Patterson, Amanda; MacDonald-Wicks, Lesley

2016-01-01

This systematic review investigated the effects of differing energy intakes, macronutrient compositions, and eating patterns of meals consumed after an overnight fast on Diet Induced Thermogenesis (DIT). The initial search identified 2482 records; 26 papers remained once duplicates were removed and inclusion criteria were applied. Studies (n = 27) in the analyses were randomized crossover designs comparing the effects of two or more eating events on DIT. Higher energy intake increased DIT; in a mixed model meta-regression, for every 100 kJ increase in energy intake, DIT increased by 1.1 kJ/h (p < 0.001). Meals with a high protein or carbohydrate content had a higher DIT than high fat, although this effect was not always significant. Meals with medium chain triglycerides had a significantly higher DIT than long chain triglycerides (meta-analysis, p = 0.002). Consuming the same meal as a single bolus eating event compared to multiple small meals or snacks was associated with a significantly higher DIT (meta-analysis, p = 0.02). Unclear or inconsistent findings were found by comparing the consumption of meals quickly or slowly, and palatability was not significantly associated with DIT. These findings indicate that the magnitude of the increase in DIT is influenced by the energy intake, macronutrient composition, and eating pattern of the meal. PMID:27792142

Improvement of physiochemical properties of the tetrahydroazepinoindole series of farnesoid X receptor (FXR) agonists: beneficial modulation of lipids in primates.

PubMed

Lundquist, Joseph T; Harnish, Douglas C; Kim, Callain Y; Mehlmann, John F; Unwalla, Rayomand J; Phipps, Kristin M; Crawley, Matthew L; Commons, Thomas; Green, Daniel M; Xu, Weixin; Hum, Wah-Tung; Eta, Julius E; Feingold, Irene; Patel, Vikram; Evans, Mark J; Lai, Kehdih; Borges-Marcucci, Lisa; Mahaney, Paige E; Wrobel, Jay E

2010-02-25

In an effort to develop orally active farnesoid X receptor (FXR) agonists, a series of tetrahydroazepinoindoles with appended solubilizing amine functionalities were synthesized. The crystal structure of the previously disclosed FXR agonist, 1 (FXR-450), aided in the design of compounds with tethered solubilizing functionalities designed to reach the solvent cavity around the hFXR receptor. These compounds were soluble in 0.5% methylcellulose/2% Tween-80 in water (MC/T) for oral administration. In vitro and in vivo optimization led to the identification of 14dd and 14cc, which in a dose-dependent fashion regulated low density lipoprotein cholesterol (LDLc) in low density lipoprotein receptor knockout (LDLR(-/-)) mice. Compound 14cc was dosed in female rhesus monkeys for 4 weeks at 60 mg/kg daily in MC/T vehicle. After 7 days, triglyceride (TG) levels and very low density lipoprotein cholesterol (VLDLc) levels were significantly decreased and LDLc was decreased 63%. These data are the first to demonstrate the dramatic lowering of serum LDLc levels by a FXR agonist in primates and supports the potential utility of 14cc in treating dyslipidemia in humans beyond just TG lowering.

Intramolecular proton shuttle supports not only catalytic but also noncatalytic function of carbonic anhydrase II

PubMed Central

Becker, Holger M.; Klier, Michael; Schüler, Christina; McKenna, Robert; Deitmer, Joachim W.

2011-01-01

Carbonic anhydrases (CAs) catalyze the reversible hydration of CO2 to HCO3− and H+. The rate-limiting step in this reaction is the shuttle of protons between the catalytic center of the enzyme and the bulk solution. In carbonic anhydrase II (CAII), the fastest and most wide-spread isoform, this H+ shuttle is facilitated by the side chain of His64, whereas CA isoforms such as carbonic anhydrase III (CAIII), which lack such a shuttle, have only low catalytic activity in vitro. By using heterologous protein expression in Xenopus oocytes, we tested the role of this intramolecular H+ shuttle on CA activity in an intact cell. The data revealed that CAIII, shown in vitro to have ∼1,000-fold reduced activity as compared with CAII, displays significant catalytic activity in the intact cell. Furthermore, we tested the hypothesis that the H+ shuttle in CAII itself can facilitate transport activity of the monocarboxylate transporters 1 and 4 (MCT1/4) independent of catalytic activity. Our results show that His64 is essential for the enhancement of lactate transport via MCT1/4, because a mutation of this residue to alanine (CAII-H64A) abolishes the CAII-induced increase in MCT1/4 activity. However, injection of 4-methylimidazole, which acts as an exogenous H+ donor/acceptor, can restore the ability of CAII-H64A to enhance transport activity of MCT1/4. These findings support the hypothesis that the H+ shuttle in CAII not only facilitates CAII catalytic activity but also can enhance activity of acid-/base-transporting proteins such as MCT1/4 in a direct, noncatalytic manner, possibly by acting as an “H+-collecting antenna.” PMID:21282642

Triheptanoin: long-term effects in the very long-chain acyl-CoA dehydrogenase-deficient mouse[S

PubMed Central

Tucci, Sara; Floegel, Ulrich; Beermann, Frauke; Behringer, Sidney; Spiekerkoetter, Ute

2017-01-01

A rather new approach in the treatment of long-chain fatty acid oxidation disorders is represented by triheptanoin, a triglyceride with three medium-odd-chain heptanoic acids (C7), due to its anaplerotic potential. We here investigate the effects of a 1-year triheptanoin-based diet on the clinical phenotype of very long-chain-acyl-CoA-dehydrogenase-deficient (VLCAD−/−) mice. The cardiac function was assessed in VLCAD−/− mice by in vivo MRI. Metabolic adaptations were identified by the expression of genes regulating energy metabolism and anaplerotic processes using real-time PCR, and the results were correlated with the measurement of the glycolytic enzymes pyruvate dehydrogenase and pyruvate kinase. Finally, the intrahepatic lipid accumulation and oxidative stress in response to the long-term triheptanoin diet were assessed. Triheptanoin was not able to prevent the development of systolic dysfunction in VLCAD−/− mice despite an upregulation of cardiac glucose oxidation. Strikingly, the anaplerotic effects of triheptanoin were restricted to the liver. Despite this, the hepatic lipic content was increased upon triheptanoin supplementation. Our data demonstrate that the concept of anaplerosis does not apply to all tissues equally. PMID:27884962

Exogenous Ketone Supplements Reduce Anxiety-Related Behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk Rats

PubMed Central

Ari, Csilla; Kovács, Zsolt; Juhasz, Gabor; Murdun, Cem; Goldhagen, Craig R.; Koutnik, Andrew P.; Poff, Angela M.; Kesl, Shannon L.; D’Agostino, Dominic P.

2016-01-01

Nutritional ketosis has been proven effective for seizure disorders and other neurological disorders. The focus of this study was to determine the effects of ketone supplementation on anxiety-related behavior in Sprague-Dawley (SPD) and Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. We tested exogenous ketone supplements added to food and fed chronically for 83 days in SPD rats and administered sub-chronically for 7 days in both rat models by daily intragastric gavage bolus followed by assessment of anxiety measures on elevated plus maze (EPM). The groups included standard diet (SD) or SD + ketone supplementation. Low-dose ketone ester (LKE; 1,3-butanediol-acetoacetate diester, ~10 g/kg/day, LKE), high dose ketone ester (HKE; ~25 g/kg/day, HKE), beta-hydroxybutyrate-mineral salt (βHB-S; ~25 g/kg/day, KS) and βHB-S + medium chain triglyceride (MCT; ~25 g/kg/day, KSMCT) were used as ketone supplementation for chronic administration. To extend our results, exogenous ketone supplements were also tested sub-chronically on SPD rats (KE, KS and KSMCT; 5 g/kg/day) and on WAG/Rij rats (KE, KS and KSMCT; 2.5 g/kg/day). At the end of treatments behavioral data collection was conducted manually by a blinded observer and with a video-tracking system, after which blood βHB and glucose levels were measured. Ketone supplementation reduced anxiety on EPM as measured by less entries to closed arms (sub-chronic KE and KS: SPD rats and KSMCT: WAG/Rij rats), more time spent in open arms (sub-chronic KE: SPD and KSMCT: WAG/Rij rats; chronic KSMCT: SPD rats), more distance traveled in open arms (chronic KS and KSMCT: SPD rats) and by delayed latency to entrance to closed arms (chronic KSMCT: SPD rats), when compared to control. Our data indicates that chronic and sub-chronic ketone supplementation not only elevated blood βHB levels in both animal models, but reduced anxiety-related behavior. We conclude that ketone supplementation may represent a promising anxiolytic strategy through a novel means of inducing nutritional ketosis. PMID:27999529

Anxiolytic Effect of Exogenous Ketone Supplementation Is Abolished by Adenosine A1 Receptor Inhibition in Wistar Albino Glaxo/Rijswijk Rats.

PubMed

Kovács, Zsolt; D'Agostino, Dominic P; Ari, Csilla

2018-01-01

Anxiety disorders are one of the most common mental health problems worldwide, but the exact pathophysiology remains largely unknown. It has been demonstrated previously that administration of exogenous ketone supplement KSMCT (ketone salt/KS + medium chain triglyceride/MCT oil) by intragastric gavage for 7 days decreased the anxiety level in genetically absence epileptic Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. To investigate the potential role of the adenosinergic system in the pathomechanism of anxiety we tested whether the inhibition of adenosine A 1 receptors (A 1 Rs) influence the anxiolytic effect of the exogenous ketone supplement. As A 1 Rs may mediate such an effect, in the present study we used a specific A 1 R antagonist, DPCPX (1,3-dipropyl-8-cyclopentylxanthine) to test whether it modulates the anxiolytic effect of sub-chronically (7 days) applied KSMCT in the previously tested animal model by using elevated plus maze (EPM) test. We administered KSMCT (2.5 g/kg/day) alone by intragastric gavage and in combination with intraperitoneally (i.p.) injected of DPCPX in two doses (lower: 0.15 mg/kg, higher: 0.25 mg/kg). Control groups represented i.p saline and water gavage with or without i.p. DPCPX administration (2.5 g/kg/day). After treatments, the level of blood glucose and beta-hydroxybutyrate (βHB), as well as body weight were recorded. KSMCT alone significantly increased the time spent in the open arms and decreased the time spent in the closed arms, supporting our previous results. Injection of lower dose of DPCPX decreased, while higher dose of DPCPX abolished the effect of KSMCT administration on EPM. Blood βHB levels were significantly increased after administration of KSMCT, while DPCPX did not change the KSMCT induced increase in blood βHB levels. These results demonstrate that A 1 R inhibition modified (decreased) the anti-anxiety effect of KSMCT administration implying that the adenosinergic system, likely via A 1 Rs, may modulate the exogenous ketone supplement induced anxiolytic influence.

Alternative lipid emulsions versus pure soy oil based lipid emulsions for parenterally fed preterm infants.

PubMed

Kapoor, Vishal; Glover, Rebecca; Malviya, Manoj N

2015-12-02

The pure soybean oil based lipid emulsions (S-LE) conventionally used for parenteral nutrition (PN) in preterm infants have high polyunsaturated fatty acid (PUFA) content. The newer lipid emulsions (LE) from alternative lipid sources with reduced PUFA content may improve clinical outcomes in preterm infants. To determine the safety and efficacy of the newer alternative LE compared with the conventional S-LE for PN in preterm infants. We used the standard search strategy of the Cochrane Neonatal Review Group (CNRG) to search the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 7), MEDLINE (1946 to 31 July 2015), EMBASE (1947 to 31 July 2015), CINAHL (1982 to 31 July 2015), Web of Science (31 July 2015), conference proceedings, trial registries (clinicaltrials.gov, controlled-trials.com, WHO's ICTRP), and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Randomised or quasi-randomised controlled trials in preterm infants (< 37 weeks), comparing newer alternative LE with S-LE. Data collection and analysis conformed to the methods of the CNRG. We assessed the quality of evidence for important outcomes using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, in addition to reporting the conventional statistical significance of results. Fifteen studies (N = 979 infants) are included in this review. Alternative LE including medium chain triglycerides/long chain triglycerides (MCT/LCT) LE (3 studies; n = 108), MCT-olive-fish-soy oil-LE (MOFS-LE; 7 studies; n = 469), MCT-fish-soy oil-LE (MFS-LE; 1 study; n = 60), olive-soy oil-LE (OS-LE; 7 studies; n = 406), and borage-soy oil-LE (BS-LE; 1 study; n = 34) were compared with S-LE. The different LE were also considered together to compare 'all fish oil containing-LE' versus S-LE (7 studies; n = 499) and 'all alternative LE' versus S-LE (15 studies; n = 979). Some studies had multiple intervention arms and were included in more than one comparison. No study compared pure fish oil-LE or structured-LE to S-LE.The GRADE quality of evidence (GRADE QoE) ranged from 'low' to 'very low.' Evidence came mostly from small single centre studies, many focusing on biochemical aspects as their primary outcomes, with optimal information size not achieved for the important clinical outcomes in any comparison.In the primary outcomes of the review there was a pooled effect towards decreased bronchopulmonary dysplasia (BPD) in OS-LE vs S-LE (4 studies, n = 261) not reaching statistical significance (typical risk ratio (RR) 0.69, 95% confidence interval (CI) 0.46 to 1.04, I² = 32%; typical risk difference (RD) -0.08, 95% CI -0.17 to 0.00, I² = 76%; GRADE QoE: 'very low'). No difference in BPD was observed in any other comparison. There were no statistically significant differences in the primary outcomes of death, growth rate (g/kg/day) or days to regain birth weight in any comparison.Retinopathy of prematurity (ROP) stage 1-2 was reported to be statistically significantly lower in one single centre study (n = 80) in the MOFS-LE group compared with the S-LE group (1/40 vs 12/40, respectively; RR 0.08, 95% CI 0.01 to 0.61; RD -0.27, 95% CI -0.43 to -0.12; number needed to benefit (NNTB) 4, 95% CI 2 to 8). However there were no statistically significant differences in the secondary outcome of ROP ≥ stage 3 in any of the individual studies or in any comparison (GRADE QoE: 'low' to 'very low'). No other study reported on ROP stages 1 and 2 separately.There were no statistically significant differences in the secondary outcomes of sepsis, PN associated liver disease (PNALD)/cholestasis, ventilation duration, necrotising enterocolitis (NEC) ≥ stage 2, jaundice requiring treatment, intraventricular haemorrhage grade III-IV, periventricular leukomalacia (PVL), patent ductus arteriosus (PDA), hypertriglyceridaemia, and hyperglycaemia in any comparison.No study reported on neurodevelopmental outcomes or essential fatty acid deficiency. All lipid emulsions in this review appeared to be safe and were well tolerated in preterm infants. Compared with the pure soy oil based LE, use of MOFS-LE was associated with a decrease in the early stages (1-2) of ROP in one study. However there were no statistically significant differences in clinically important outcomes including death, growth, BPD, sepsis, ROP ≥ stage 3, and PNALD with the use of newer alternative LE versus the conventional pure soy oil based LE (GRADE QoE ranged from 'low' to 'very low'). Currently there is insufficient evidence to recommend any alternative LE over S-LE or vice versa in preterm infants.Larger randomised studies focusing on important clinical outcomes, targeting specific 'at risk' population subgroups (e.g. extreme prematurity, long term PN, etc), and exploring the effect of different proportions of lipid constituents are required to evaluate the effectiveness of newer lipid emulsions compared with the conventional pure soy based LE in preterm infants.

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

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.

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.

Alkyl Chain Ordering of Asymmetric Phosphatidyicholines Adsorbed at a Liquid-Liquid Interface

DTIC Science & Technology

1998-05-30

the blood bind to the PL surface and begin to hydrolyze the triglyceride core and only a small fraction of the phospholipids, such that the core...which surface-adsorbed proteins are able to hydrolyze the triglyceride core has been shown to depend on the acyl chain composition of monolayer PCs...in the commercial use of natural phosphatidylcholines (or lecithins ) as emulsifiers, including their use in delivery of water-insoluble drugs (Davis

L-carnitine and cancer cachexia. I. L-carnitine distribution and metabolic disorders in cancer cachexia.

PubMed

Szefel, Jarosław; Kruszewski, Wiesław Janusz; Ciesielski, Maciej; Szajewski, Mariusz; Kawecki, Krzysztof; Aleksandrowicz-Wrona, Ewa; Jankun, Jerzy; Lysiak-Szydłowska, Wiesława

2012-07-01

Cancer cachexia (CC), a progressive loss of body mass, is associated with decreased energy production. Abnormally low levels of L-carnitine (LC) in skeletal muscle means that mitochondrial β-oxidation of long-chain fatty acids (LCFA) does not occur efficiently in patients with CC. We assessed the influence of CC on LC distribution and the effects of parenteral lipid emulsions on plasma LC levels and urinary excretion. Fifty patients with CC were randomly assigned to total parenteral nutrition (TPN) with long-chain triglycerides (LCTs), or LCTs plus medium-chain triglycerides (MCTs) as 50/50. Patients were further separated into those with body-mass index (BMI) ≤ 19 kg/m(2) and BMI >19 kg/m(2). Plasma concentrations of total LC (TC) and free LC (FC) and their urinary excretion were measured, along with skeletal muscle LC levels. On average, plasma FC and TC were higher than reference values in all patients. Patients with BMI ≤ 19 kg/m(2) had lower plasma FC and TC than those with BMI >19 kg/m(2). Skeletal muscle FC in the BMI ≤ 19 kg/m(2) group was lower than reference value, but within the normal range in others. LC and FC urinary excretion was higher than reference values. Plasma LC and its urinary excretion were higher in patients administered pure LCTs relative to those given MCTs/LCTs. A decrease in skeletal muscle LC in cancer patients with CC (BMI ≤ 19 kg/m(2)) correlates with an increase in its plasma levels and increased renal excretion. A diet of MCTs/LCTs reduces LC release from muscle to plasma and urine more effectively than LCTs.

Waste-to-energy: Dehalogenation of plastic-containing wastes.

PubMed

Shen, Yafei; Zhao, Rong; Wang, Junfeng; Chen, Xingming; Ge, Xinlei; Chen, Mindong

2016-03-01

The dehalogenation measurements could be carried out with the decomposition of plastic wastes simultaneously or successively. This paper reviewed the progresses in dehalogenation followed by thermochemical conversion of plastic-containing wastes for clean energy production. The pre-treatment method of MCT or HTT can eliminate the halogen in plastic wastes. The additives such as alkali-based metal oxides (e.g., CaO, NaOH), iron powders and minerals (e.g., quartz) can work as reaction mediums and accelerators with the objective of enhancing the mechanochemical reaction. The dehalogenation of waste plastics could be achieved by co-grinding with sustainable additives such as bio-wastes (e.g., rice husk), recyclable minerals (e.g., red mud) via MCT for solid fuels production. Interestingly, the solid fuel properties (e.g., particle size) could be significantly improved by HTT in addition with lignocellulosic biomass. Furthermore, the halogenated compounds in downstream thermal process could be eliminated by using catalysts and adsorbents. Most dehalogenation of plastic wastes primarily focuses on the transformation of organic halogen into inorganic halogen in terms of halogen hydrides or salts. The integrated process of MCT or HTT with the catalytic thermal decomposition is a promising way for clean energy production. The low-cost additives (e.g., red mud) used in the pre-treatment by MCT or HTT lead to a considerable synergistic effects including catalytic effect contributing to the follow-up thermal decomposition. Copyright © 2015 Elsevier Ltd. All rights reserved.

Primary intestinal lymphangiectasia (Waldmann's disease).

PubMed

Vignes, Stéphane; Bellanger, Jérôme

2008-02-22

Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. Prevalence is unknown. The main symptom is predominantly bilateral lower limb edema. Edema may be moderate to severe with anasarca and includes pleural effusion, pericarditis or chylous ascites. Fatigue, abdominal pain, weight loss, inability to gain weight, moderate diarrhea or fat-soluble vitamin deficiencies due to malabsorption may also be present. In some patients, limb lymphedema is associated with PIL and is difficult to distinguish lymphedema from edema. Exsudative enteropathy is confirmed by the elevated 24-h stool alpha1-antitrypsin clearance. Etiology remains unknown. Very rare familial cases of PIL have been reported. Diagnosis is confirmed by endoscopic observation of intestinal lymphangiectasia with the corresponding histology of intestinal biopsy specimens. Videocapsule endoscopy may be useful when endoscopic findings are not contributive. Differential diagnosis includes constrictive pericarditis, intestinal lymphoma, Whipple's disease, Crohn's disease, intestinal tuberculosis, sarcoidosis or systemic sclerosis. Several B-cell lymphomas confined to the gastrointestinal tract (stomach, jejunum, midgut, ileum) or with extra-intestinal localizations were reported in PIL patients. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL medical management. The absence of fat in the diet prevents chyle engorgement of the intestinal lymphatic vessels thereby preventing their rupture with its ensuing lymph loss. Medium-chain triglycerides are absorbed directly into the portal venous circulation and avoid lacteal overloading. Other inconsistently effective treatments have been proposed for PIL patients, such as antiplasmin, octreotide or corticosteroids. Surgical small-bowel resection is useful in the rare cases with segmental and localized intestinal lymphangiectasia. The need for dietary control appears to be permanent, because clinical and biochemical findings reappear after low-fat diet withdrawal. PIL outcome may be severe even life-threatening when malignant complications or serous effusion(s) occur.

Primary intestinal lymphangiectasia (Waldmann's disease)

PubMed Central

Vignes, Stéphane; Bellanger, Jérôme

2008-01-01

Primary intestinal lymphangiectasia (PIL) is a rare disorder characterized by dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen and responsible for protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia. PIL is generally diagnosed before 3 years of age but may be diagnosed in older patients. Prevalence is unknown. The main symptom is predominantly bilateral lower limb edema. Edema may be moderate to severe with anasarca and includes pleural effusion, pericarditis or chylous ascites. Fatigue, abdominal pain, weight loss, inability to gain weight, moderate diarrhea or fat-soluble vitamin deficiencies due to malabsorption may also be present. In some patients, limb lymphedema is associated with PIL and is difficult to distinguish lymphedema from edema. Exsudative enteropathy is confirmed by the elevated 24-h stool α1-antitrypsin clearance. Etiology remains unknown. Very rare familial cases of PIL have been reported. Diagnosis is confirmed by endoscopic observation of intestinal lymphangiectasia with the corresponding histology of intestinal biopsy specimens. Videocapsule endoscopy may be useful when endoscopic findings are not contributive. Differential diagnosis includes constrictive pericarditis, intestinal lymphoma, Whipple's disease, Crohn's disease, intestinal tuberculosis, sarcoidosis or systemic sclerosis. Several B-cell lymphomas confined to the gastrointestinal tract (stomach, jejunum, midgut, ileum) or with extra-intestinal localizations were reported in PIL patients. A low-fat diet associated with medium-chain triglyceride supplementation is the cornerstone of PIL medical management. The absence of fat in the diet prevents chyle engorgement of the intestinal lymphatic vessels thereby preventing their rupture with its ensuing lymph loss. Medium-chain triglycerides are absorbed directly into the portal venous circulation and avoid lacteal overloading. Other inconsistently effective treatments have been proposed for PIL patients, such as antiplasmin, octreotide or corticosteroids. Surgical small-bowel resection is useful in the rare cases with segmental and localized intestinal lymphangiectasia. The need for dietary control appears to be permanent, because clinical and biochemical findings reappear after low-fat diet withdrawal. PIL outcome may be severe even life-threatening when malignant complications or serous effusion(s) occur. PMID:18294365

Hepatocellular integrity after parenteral nutrition: comparison of a fish-oil-containing lipid emulsion with an olive-soybean oil-based lipid emulsion.

PubMed

Piper, Swen N; Schade, Ingo; Beschmann, Ralf B; Maleck, Wolfgang H; Boldt, Joachim; Röhm, Kerstin D

2009-12-01

Parenteral nutrition including lipids might be associated with liver disease. The cause leading to parenteral nutrition-related liver dysfunction remains largely unknown but is likely to be multifactorial. The study was performed to assess the effects of a lipid emulsion based on soybean oil, medium-chain triglycerides, olive and fish oil (SMOFlipid20%) compared with a lipid emulsion based on olive and soybean oil on hepatic integrity. In a prospective, randomized, double-blinded trial, 44 postoperative patients with an indication for parenteral nutrition were allocated to one of two regimens: group A (n = 22) received SMOFlipid, group B (n = 22) a lipid emulsion based on olive and soybean oil for 5 days. Aspartate aminotransferase, alanin-aminotransferase, and serum alpha-glutathion S-transferase were measured before the start of parenteral nutrition (d0), at day 2 (d2), and day 5 (d5) after the start of parenteral nutrition. The significance level was defined at a P value of less than 0.05. There was no significant difference at d0, but at d2 and d5, significantly lower aspartate aminotransferase (d2: group A: 27 +/- 13 vs. group B: 47 +/- 36 U l(-1); d5: A: 31 +/- 14 vs. B: 56 +/- 45 U l(-1)), alanin-aminotransferase (d2: A: 20 +/- 12 vs. B: 42 +/- 39 U l(-1); d5: A: 26 +/- 15 vs. B: 49 +/- 44 U l(-1)), and alpha-glutathion S-transferase levels (d2: A: 5 +/- 6 vs. B: 17 +/- 21 U l(-1); d5: A: 6 +/- 7 vs. B: 24 +/- 27 microg l(-1)) were found in soybean oil, medium-chain triglycerides, olive and fish oil group compared with the control group. Hepatic integrity was well retained with the administration of SMOFlipid whereas in patients receiving a lipid emulsion based on olive and soybean oil liver enzymes were elevated indicating a lower liver tolerability.

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.

[Diagnostic reliability and incidence of genital mycoses in pregnant women].

PubMed

Martius, J; Hartmann, A A

1983-01-01

Smears were taken from the anterior and posterior vaginal fornices of 232 women who attended prenatal consultations at Würzburg University Gynecological Clinic. The cultures were compared using Sabouraud's Glucose Agar (S.G.A.) and two commercially available rapid testing media--Nickerson Medium (N.M.) and Microstix Candida (M.C.T.) for saccharomycetes. The presence of saccharomycetes was demonstrated by means of S.G.A. in 23% (52) of the women and with N.M. in 10% (23). If only N.M. had been used, colonization by saccharomycetes would have been overlooked in 32 cases. With regard to the reliability of identification of saccharomycetes in the group, there was no significant difference between N.M. and M.C.T. In women without Candidiasis, negative findings with N.M. and M.C.T. were in agreement in 96% of the cases. Reliable identification of saccharomycetes in genital and gastro-intestinal areas is of special importance in prenatal examinations in view of the risk of infection of the newborn. The investigation reported in the present paper indicates that such reliability can only be achieved with the more costly culture method using Sabouraud's Glucose Agar.

Cardioprotective effects of early and late aerobic exercise training in experimental pulmonary arterial hypertension.

PubMed

Moreira-Gonçalves, Daniel; Ferreira, Rita; Fonseca, Hélder; Padrão, Ana Isabel; Moreno, Nuno; Silva, Ana Filipa; Vasques-Nóvoa, Francisco; Gonçalves, Nádia; Vieira, Sara; Santos, Mário; Amado, Francisco; Duarte, José Alberto; Leite-Moreira, Adelino F; Henriques-Coelho, Tiago

2015-11-01

Clinical studies suggest that aerobic exercise can exert beneficial effects in pulmonary arterial hypertension (PAH), but the underlying mechanisms are largely unknown. We compared the impact of early or late aerobic exercise training on right ventricular function, remodeling and survival in experimental PAH. Male Wistar rats were submitted to normal cage activity (SED), exercise training in early (EarlyEX) and in late stage (LateEX) of PAH induced by monocrotaline (MCT, 60 mg/kg). Both exercise interventions resulted in improved cardiac function despite persistent right pressure-overload, increased exercise tolerance and survival, with greater benefits in EarlyEX+MCT. This was accompanied by improvements in the markers of cardiac remodeling (SERCA2a), neurohumoral activation (lower endothelin-1, brain natriuretic peptide and preserved vascular endothelial growth factor mRNA), metabolism and mitochondrial oxidative stress in both exercise interventions. EarlyEX+MCT provided additional improvements in fibrosis, tumor necrosis factor-alpha/interleukin-10 and brain natriuretic peptide mRNA, and beta/alpha myosin heavy chain protein expression. The present study demonstrates important cardioprotective effects of aerobic exercise in experimental PAH, with greater benefits obtained when exercise training is initiated at an early stage of the disease.

Direct determination of glucose, lactate and triglycerides in blood serum by a tunable quantum cascade laser-based mid-IR sensor

NASA Astrophysics Data System (ADS)

Brandstetter, M.; Volgger, L.; Genner, A.; Jungbauer, C.; Lendl, B.

2013-02-01

This work reports on a compact sensor for fast and reagent-free point-of-care determination of glucose, lactate and triglycerides in blood serum based on a tunable (1030-1230 cm-1) external-cavity quantum cascade laser (EC-QCL). For simple and robust operation a single beam set-up was designed and only thermoelectric cooling was used for the employed laser and detector. Full computer control of analysis including liquid handling and data analysis facilitated routine measurements. A high optical pathlength (>100 μm) is a prerequisite for robust measurements in clinical practice. Hence, the optimum optical pathlength for transmission measurements in aqueous solution was considered in theory and experiment. The experimentally determined maximum signal-to-noise ratio (SNR) was around 140 μm for the QCL blood sensor and around 50 μm for a standard FT-IR spectrometer employing a liquid nitrogen cooled mercury cadmium telluride (MCT) detector. A single absorption spectrum was used to calculate the analyte concentrations simultaneously by using a partial-least-squares (PLS) regression analysis. Glucose was determined in blood serum with a prediction error (RMSEP) of 6.9 mg/dl and triglycerides with an error of cross-validation (RMSECV) of 17.5 mg/dl in a set of 42 different patients. In spiked serum samples the lactate concentration could be determined with an RMSECV of 8.9 mg/dl.

Management of pancreatic exocrine insufficiency: Australasian Pancreatic Club recommendations.

PubMed

Toouli, James; Biankin, Andrew V; Oliver, Mark R; Pearce, Callum B; Wilson, Jeremy S; Wray, Nicholas H

2010-10-18

Pancreatic exocrine insufficiency (PEI) occurs when the amounts of enzymes secreted into the duodenum in response to a meal are insufficient to maintain normal digestive processes. The main clinical consequence of PEI is fat maldigestion and malabsorption, resulting in steatorrhoea. Pancreatic exocrine function is commonly assessed by conducting a 3-day faecal fat test and by measuring levels of faecal elastase-1 and serum trypsinogen. Pancreatic enzyme replacement therapy is the mainstay of treatment for PEI. In adults, the initial recommended dose of pancreatic enzymes is 25,000 units of lipase per meal, titrating up to a maximum of 80,000 units of lipase per meal. In infants and children, the initial recommended dose of pancreatic enzymes is 500 units of lipase per gram of dietary fat; the maximum daily dose should not exceed 10,000 units of lipase per kilogram of bodyweight. Oral pancreatic enzymes should be taken with meals to ensure adequate mixing with the chyme. Adjunct therapy with acid-suppressing agents may be useful in patients who continue to experience symptoms of PEI despite high-dose enzyme therapy. A dietitian experienced in treating PEI should be involved in patient management. Dietary fat restriction is not recommended for patients with PEI. Patients with PEI should be encouraged to consume small, frequent meals and to abstain from alcohol. Medium-chain triglycerides do not provide any clear nutritional advantage over long-chain triglycerides, but can be trialled in patients who fail to gain or to maintain adequate bodyweight in order to increase energy intake.

A critical assessment of transmethylation procedures for n-3 long-chain polyunsaturated fatty acid quantification of lipid classes.

PubMed

Sehl, Anthony; Couëdelo, Leslie; Fonseca, Laurence; Vaysse, Carole; Cansell, Maud

2018-06-15

Lipid transmethylation methods described in the literature are not always evaluated with care so to insure that the methods are effective, especially on food matrix or biological samples containing polyunsaturated fatty acid (PUFA). The aim of the present study was to select a method suitable for all lipid species rich in long chain n-3 PUFA. Three published methods were adapted and applied on individual lipid classes. Lipid (trans)methylation efficiency was characterized in terms of reaction yield and gas chromatography (GC) analysis. The acid-catalyzed method was unable to convert triglycerides and sterol esters, while the method using an incubation at a moderate temperature was ineffective on phospholipids and sterol esters. On the whole only the method using sodium methoxide and sulfuric acid was effective on lipid classes taken individually or in a complex medium. This study highlighted the use of an appropriate (trans)methylation method for insuring an accurate fatty acid composition. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

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.

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

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.

The long N-terminus of the human monocarboxylate transporter 8 is a target of ubiquitin-dependent proteasomal degradation which regulates protein expression and oligomerization capacity.

PubMed

Zwanziger, Denise; Schmidt, Mathias; Fischer, Jana; Kleinau, Gunnar; Braun, Doreen; Schweizer, Ulrich; Moeller, Lars Christian; Biebermann, Heike; Fuehrer, Dagmar

2016-10-15

Monocarboxylate transporter 8 (MCT8) equilibrates thyroid hormones between the extra- and the intracellular sides. MCT8 exists either with a short or a long N-terminus, but potential functional differences between both variants are yet not known. We, therefore, generated MCT8 constructs which are different in N-terminal length: MCT8(1-613), MCT8(25-613), MCT8(49-613) and MCT8(75-613). The M75G substitution prevents translation of MCT8(75-613) and ensures expression of full-length MCT8 protein. The K56G substitution was made to prevent ubiquitinylation. Cell-surface expression, localization and proteasomal degradation were investigated using C-terminally GFP-tagged MCT8 constructs (HEK293 and MDCK1 cells) and oligomerization capacity was determined using N-terminally HA- and C-terminally FLAG-tagged MCT8 constructs (COS7 cells). MCT8(1-613)-GFP showed a lower protein expression than the shorter MCT8(75-613)-GFP protein. The proteasome inhibitor lactacystin increased MCT8(1-613)-GFP protein amount, suggesting proteasomal degradation of MCT8 with the long N-terminus. Ubiquitin conjugation of MCT8(1-613)-GFP was found by immuno-precipitation. A diminished ubiquitin conjugation caused by K56G substitution resulted in increased MCT8(1-613)-GFP protein expression. Sandwich ELISA was performed to investigate if the bands at higher molecular weight observed in Western blot analysis are due to MCT8 oligomerization, which was indeed shown. Our data imply a role of the long N-terminus of MCT8 as target of ubiquitin-dependent proteasomal degradation affecting MCT8 amount and subsequently oligomerization capacity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Impact of fatty acyl composition and quantity of triglycerides on bioaccessibility of dietary carotenoids.

PubMed

Huo, Tianyao; Ferruzzi, Mario G; Schwartz, Steven J; Failla, Mark L

2007-10-31

A carotenoid-rich salad meal with varying amounts and types of triglycerides (TG) was digested using simulated gastric and small intestinal conditions. Xanthophylls (lutein and zeaxanthin) and carotenes (alpha-carotene, beta-carotene, and lycopene) in chyme and micelle fraction were quantified to determine digestive stability and efficiency of micellarization (bioaccessibility). Micellarization of lutein (+zeaxanthin) exceeded that of alpha- and beta-carotenes, which was greater than that of lycopene for all test conditions. Micellarization of carotenes, but not lutein (+zeaxanthin), was enhanced (P < 0.05) by addition of TG (2.5% v/w) to the meal and was dependent on fatty acyl chain length in structured TG (c18:1 > c8:0 > c4:0). The degree of unsaturation of c18 fatty acyl chains in TG added to the salad purée did not significantly alter the efficiency of micellarization of carotenoids. Relatively low amounts of triolein and canola oil (0.5-1%) were required for maximum micellarization of carotenes, but more oil (approximately 2.5%) was required when TG with medium chain saturated fatty acyl groups (e.g., trioctanoin and coconut oil) was added to the salad. Uptake of lutein and beta-carotene by Caco-2 cells also was examined by exposing cells to micelles generated during the simulated digestion of salad purée with either triolein or trioctanoin. Cell accumulation of beta-carotene was independent of fatty acyl composition of micelles, whereas lutein uptake was slightly, but significantly, increased from samples with digested triolein compared to trioctanoin. The results show that the in vitro transfer of alpha-carotene, beta-carotene, and lycopene from chyme to mixed micelles during digestion requires minimal (0.5-1%) lipid content in the meal and is affected by the length of fatty acyl chains but not the degree of unsaturation in TG. In contrast, fatty acyl chain length has limited if any impact on carotenoid uptake by small intestinal epithelial cells. These data suggest that the amount of TG in a typical meal does not limit the bioaccessibility of carotenoids.

Decreasing self-reported cognitive biases and increasing clinical insight through meta-cognitive training in patients with chronic schizophrenia.

PubMed

Gawęda, Łukasz; Krężołek, Martyna; Olbryś, Joanna; Turska, Agnieszka; Kokoszka, Andrzej

2015-09-01

The aim of this study was to assess the impact of meta-cognitive training (MCT) on cognitive biases, symptoms, clinical insight, and general functioning among low-level functioning persons diagnosed with chronic schizophrenia who were attending a daily Community Social Support Group Program; we compared the treatment-as-usual (TAU) condition with the MCT + TAU condition. Forty-four patients diagnosed with chronic schizophrenia were allocated to either the MCT + treatment-as-usual condition or the treatment-as-usual (TAU) condition. Delusion and hallucination severity, cognitive biases, clinical insight, and global functioning were assessed pre- and post-treatment (clinical trial NCT02187692). No significant changes were found in symptom severity as measured with the PSYRATS. Conversely, a medium to large effect size was observed for delusional ideation changes when assessed by the self-report measure (Paranoia Checklist). MCT was found to ameliorate cognitive biases as measured by the self-report scale at large effect size, however, no changes in jumping to conclusions (the Fish Task) and theory of mind deficits ("Reading the Mind in the Eyes" Test) were found in the behavioral tasks. MCT increased insight at large effect size. No changes in global functioning were found between the two conditions. Low intensity intervention. No follow-up assessment was provided. Only PSYRATS was assessed blind to patient allocation. MCT has a beneficial effect on low-functioning chronic schizophrenic patients in ameliorating cognitive biases and increasing clinical insight. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Further characterisation of the 'ileal brake' reflex in man--effect of ileal infusion of partial digests of fat, protein, and starch on jejunal motility and release of neurotensin, enteroglucagon, and peptide YY.

PubMed Central

Spiller, R C; Trotman, I F; Adrian, T E; Bloom, S R; Misiewicz, J J; Silk, D B

1988-01-01

Previous studies have shown that ileal infusion of partially digested triglyceride inhibits jejunal motility. The partial digest used in those studies contained a mixture of glycerol, free fatty acid, mono-, di-, and triglycerides. In Part I of the present study we have separately infused emulsions containing either glycerol 3.1 g (n = 6), oleic acid 9.6 g (n = 6), triolein 10 g (n = 12), or medium chain triglycerides 10 g (n = 6) into the ileum and have recorded the effect this has on jejunal motility. Five further subjects received infusions of partial hydrolysates of corn starch 10 g and lactalbumin 7 g. Marked inhibition of jejunal pressure wave activity was seen after all three lipid infusions, per cent activity falling from a control of 37.7 (7.7) to 6.2 (2.1) and 22.4 (8.2)% 30 min after completing the oleic acid and triolein infusions respectively, and from a control value of 39.5 (4.1) to 17.7 (4.7) after MCTs (all p less than 0.05). No significant fall occurred after infusion of glycerol, protein or carbohydrate. All three lipid infusions raised plasma concentrations of neurotensin, enteroglucagon and peptide YY equally effectively, although only the rise in peptide YY correlated significantly with the inhibition of jejunal pressure wave activity (r = 0.80, n = 6, p less than 0.05). In Part II of this study six subjects received a 3 ml/min jejunal infusion of an isotonic carbohydrate saline solution followed after three hours by a similar infusion of a partial digest of lipid. During each infusion flow and transit time was measured by marker and dye dilution. Jejunal infusion of the carbohydrate-saline solution was associated with low jejunal flow, 4.7 (1.0) ml/min and a mean transit time through the 50 cm study segment of 36.5 (7.1) min. By contrast jejunal infusion of partially digested triglyceride was associated with a markedly increased flow, 9.0 (1.2) ml/min, a fall in mean transit time to 20.3 (2.6) min and significant rises in pancreaticobiliary secretions. Jejunal triglyceride also increased the incidence of prolonged high amplitude jejunal pressure waves in four of six subjects. These studies suggest that there are important differences in the jejunal response to ileal versus jejunal lipid. While long and median chain free fatty acids infused into the ileum exert an inhibitory effect on jejunal motility, when infused directly into the jejunum partially digested triglyceride accelerates transit, increases jejunal flow and subtly alters the pattern of jejunal contractions. PMID:3410330

Effect of cationic lipid composition on properties of oligonucleotide/emulsion complexes: Physico-chemical and release studies.

PubMed

Martini, Erico; Fattal, Elias; de Oliveira, Mônica Cristina; Teixeira, Helder

2008-03-20

This paper describes the influence of cationic lipid composition on physico-chemical properties of complexes formed between oligonucleotides (ON) and cationic emulsions. Formulations containing medium chain triglycerides, egg lecithin, increasing amounts of either oleylamine (OA) or 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and water were prepared by a spontaneous emulsification procedure. ON adsorption on emulsions was evidenced by the inversion of the zeta-potential, the increase in droplet size, and the morphology of the oil droplet examined through transmission electron microscopy. Adsorption isotherms showed a higher amount of ON adsorbed on emulsions containing DOTAP when compared to emulsions containing OA. In a final step, the role of the main parameters, which may in fact influence the ON release rate from emulsions, was investigated. ON were progressively released from emulsions with an increase in dilution ratio and remained quite similar for both OA and DOTAP emulsions over time. Conversely, the effect of the cationic lipid composition was observed upon increasing the charge ratio of complexes. ON release at a same charge ratio was lower from emulsions containing DOTAP (bearing dioleyl chains) than from those containing OA (bearing monoleyl chain).

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.

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.

Nutritional evaluation of structured lipid containing omega 6 fatty acid synthesized from coconut oil in rats.

PubMed

Rao, Reena; Lokesh, Belur R

2003-06-01

Coconut oil is rich in medium chain fatty acids, but deficient in polyunsaturated fatty acids (PUFA). Structured lipids (SL) enriched with omega 6 PUFA were synthesized from coconut oil triglycerides by employing enzymatic acidolysis with free fatty acids obtained from safflower oil. Rats were fed a diet containing coconut oil, coconut oil-safflower oil blend (1:0.7 w/ w) or structured lipid at 10% levels for a period of 60 days. The SL lowered serum cholesterol levels by 10.3 and 10.5% respectively in comparison with those fed coconut oil and blended oil. Similarly the liver cholesterol levels were also decreased by 35.9 and 26.6% respectively in animals fed structured lipids when compared to those fed on coconut oil or the blended oil. Most of the decrease observed in serum cholesterol levels of animals fed structured lipids was found in LDL fraction. The triglyceride levels in serum showed a decrease by 17.5 and 17.4% while in the liver it was reduced by 45.8 and 23.5% in the structured lipids fed animals as compared to those fed coconut oil or blended oil respectively. Differential scanning calorimetric studies indicated that structured lipids had lower melting points and solid fat content when compared to coconut oil or blended oils. These studies indicated that enrichment of coconut oil triglycerides with omega 6 fatty acids lowers its solid fat content. The omega 6 PUFA enriched structured lipids also exhibited hypolipidemic activity.

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.

Vitamin E and selenium treatment of monocrotaline induced hepatotoxicity in rats.

PubMed

Cuce, G; Canbaz, H T; Sozen, M E; Yerlikaya, F H; Kalkan, S

2017-01-01

Monocrotaline (MCT) is a hepatotoxic pyrrolizidine alkaloid that is derived from plants; exposure may occur by consumption of contaminated grains, herbal teas and medicines. MCT can cause liver damage. We investigated the antioxidant effects of selenium (Se) and vitamin E against the toxic effects of MCT. Female Wistar albino rats were divided into four groups: a control group, an MCT group, an MCT + Se group, and an MCT + vitamin E group. Liver tissues were harvested, fixed, processed to paraffin and sections were cut. Anti-von Willebrand factor (vWF) immunohistochemistry, terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL), and hematoxylin and eosin staining were performed. Serum and liver tissue glutathione (GSH), catalase (CAT), and glutathione peroxidase (GPx) levels were measured. Histopathological and TUNEL data showed significantly increased liver damage in the MCT group compared to controls. Histopathological and TUNEL staining indicated significant improvements in the MCT + vitamin E and MCT + Se groups compared to the MCT group. MCT significantly reduced the serum GSH level and GPx activity, and liver GPx activity. Biochemical data indicated a significant improvement in serum GSH level in the MCT + vitamin E group compared to the MCT group. We suggest that vitamin E and Se afford limited protection against MCT hepatotoxicity.

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

A series of lipid-accumulating yeasts was examined for their potential to saccharify xylan and accumulate triglyceride. Of the genera tested, including Candida, Cryptococcus, Lipomyces, Rhodosporidium, Rhodotorula, and Trichosporon, only Crytococcus and Trichosporon isolates saccharified xylan. All of the strains could assimilate xylose and accumuate triglyceride under nitrogen-limiting conditions. Strains of Cryptococcus albidus were found to be especially useful for a one-step saccharification of xylan coupled to triglyceride synthesis. Crytococcus terricolus, a strain constitutive for lipid accumulation, lacked extracellular xylanase, but did assimilate xylose and xylobiose and was able to continuously convert xylan to triglyceride if the culture medium was supplementedmore » with xylanase. 22 references.« less

Transport mechanism for L-lactic acid in human myocytes using human prototypic embryonal rhabdomyosarcoma cell line (RD cells).

PubMed

Kobayashi, Masaki; Fujita, Itaru; Itagaki, Shirou; Hirano, Takeshi; Iseki, Ken

2005-07-01

Monocarboxylate transporter (MCT), which cotransport L-lactic acid and protons across cell membranes, are important for regulation of muscle pH. However, it has not been demonstrated in detail whether MCT isoform contribute to the transport of L-lactic acid in skeletal muscle. The aim of this study was to characterize L-lactic acid transport using an human rhabdomyosarcoma (RD) cell line as a model of human skeletal muscle. mRNAs of MCT 1, 2 and 4 were found to be expressed in RD cells. The [14C] L-lactic acid uptake was concentration-dependent with a Km of 1.19 mM. This Km value was comparable to its Km values for MCT1 or MCT2. MCT1 mRNA was found to be present markedly greater than that MCT2. Therefore, MCT1 most probably acts on L-lactic acid uptake at RD cells. [14C] L-Lactic acid efflux in RD cells was inhibited by alpha-cyano-4-hydroxycinnamate (CHC) but not by butyric acid, a substrate of MCT1. Accordingly, MCT2 or MCT4 is responsible for L-lactic acid efflux by RD cells. MCT4 mRNA was found to be present significantly greater than that MCT2. We conclude that MCT1 is responsible for L-lactic acid uptake and L-lactic acid efflux is mediated by MCT4 in RD cells.

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.

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.

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

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

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.

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.

Commercially marketed supplements for bodybuilding athletes.

PubMed

Grunewald, K K; Bailey, R S

1993-02-01

We conducted a survey of 624 commercially available supplements targeted towards bodybuilding athletes. Over 800 performance claims were made for these supplements. Supplements include amino acids, boron, carnitine, choline, chromium, dibencozide, ferulic acid, gamma oryzanol, medium chain triglycerides, weight gain powders, Smilax compounds and yohimbine. Many performance claims advertised were not supported by published research studies. In some instances, we found no research to validate the claims; in other cases, research findings were extrapolated to inappropriate applications. For example, biological functions of some non-essential compounds were interpreted as performance claims for the supplements. Claims for others were based on their ability to enhance hormonal release or activity. We suggest that more research be conducted on this group of athletes and their nutritional needs. Furthermore, the effectiveness and safety of supplements merit further investigation.

Primary intestinal and thoracic lymphangiectasia: a response to antiplasmin therapy.

PubMed

MacLean, Joanna E; Cohen, Eyal; Weinstein, Michael

2002-06-01

Lymphangiectasia is a congenital or acquired disorder characterized by abnormal, dilated lymphatics with a variable age of presentation. We describe a case of lymphangiectasia with intestinal and pulmonary involvement in an adolescent female, who presented with many of the classic features including chylous pleural effusions, lymphopenia, hypogammaglobinemia, and a protein-losing enteropathy. She also presented with recurrent lower gastrointestinal bleeding, which is infrequently described. The patient did not improve with bowel rest and a low-fat medium-chain triglyceride diet and had little improvement with octreotide acetate therapy. However, she had a clinical response to antiplasmin therapy, trans-4-aminothylcyclohexamine carboxylic acid (tranexamic acid) in terms of serum albumin and gastrointestinal bleeding. She continues to have exacerbations of her condition, as well as persistent lymphopenia and chronic pleural effusions.

Severe Refractory Anemia in Primary Intestinal Lymphangiectasia. A Case Report.

PubMed

Balaban, Vasile Daniel; Popp, Alina; Grasu, Mugur; Vasilescu, Florina; Jinga, Mariana

2015-09-01

Primary intestinal lymphangiectasia (Waldmann's disease) is a rare disease characterized by dilated lymphatics in the small bowel leading to an exudative enteropathy with lymphopenia, hypoalbuminemia and hypogammaglobulinemia. We report the case of a 23 year-old male who presented with chronic anemia and in whom primary intestinal lymphangiectasia was diagnosed. A low-fat diet along with nutritional therapy with medium-chain triglyceride supplementation improved the protein-losing enteropathy, but did not solve the anemia. Octreotide was also unsuccessful, and after attempting angiographic embolization therapy, limited small bowel resection together with antiplasmin therapy managed to correct the anemia and control the exudative enteropathy. Although primary intestinal lymphangiectasia is usually adequately managed by nutritional therapy, complications such as anemia can occur and can prove to be a therapeutic challenge.

Caffeine intake increases plasma ketones: an acute metabolic study in humans.

PubMed

Vandenberghe, Camille; St-Pierre, Valérie; Courchesne-Loyer, Alexandre; Hennebelle, Marie; Castellano, Christian-Alexandre; Cunnane, Stephen C

2017-04-01

Brain glucose uptake declines during aging and is significantly impaired in Alzheimer's disease. Ketones are the main alternative brain fuel to glucose so they represent a potential approach to compensate for the brain glucose reduction. Caffeine is of interest as a potential ketogenic agent owing to its actions on lipolysis and lipid oxidation but whether it is ketogenic in humans is unknown. This study aimed to evaluate the acute ketogenic effect of 2 doses of caffeine (2.5; 5.0 mg/kg) in 10 healthy adults. Caffeine given at breakfast significantly stimulated ketone production in a dose-dependent manner (+88%; +116%) and also raised plasma free fatty acids. Whether caffeine has long-term ketogenic effects or could enhance the ketogenic effect of medium chain triglycerides remains to be determined.

OPTIMIZING DIAGNOSIS AND MANANGEMENT IN MILD-TO-MODERATE ALZHEIMER’S DISEASE

PubMed Central

Galvin, James E.

2012-01-01

Alzheimer’s disease (AD) is characterized by progressive declines in cognitive function and ability to carry out activities of daily living; and the emergence and worsening of behavioral/neuropsychiatric symptoms. While there is no cure for AD, non-pharmacologic interventions and medications that modulate neurotransmission can slow symptomatic progression. Medical foods may also be useful as adjuncts to pharmacologic agents in AD. Medium chain triglycerides aimed at improving cerebral metabolism significantly improve Alzheimer’s Disease Assessment Scale-Cognitive scores when added to ongoing pharmacotherapy in patients with mild-to-moderate AD. Combination of interventions, such as non-pharmacologic treatments, pharmacotherapy, and medical foods, with complementary mechanisms of action may provide a rational approach that may result in maximum preservation of cognitive function in patients with AD. PMID:22973426

One-Step Partially Purified Lipases (ScLipA and ScLipB) from Schizophyllum commune UTARA1 Obtained via Solid State Fermentation and Their Applications.

PubMed

Kam, Yew Chee; Woo, Kwan Kit; Ong, Lisa Gaik Ai

2017-12-08

Lipases with unique characteristics are of value in industrial applications, especially those targeting cost-effectiveness and less downstream processes. The aims of this research were to: (i) optimize the fermentation parameters via solid state fermentation (SSF); and (ii) study the performance in hydrolysis and esterification processes of the one-step partially purified Schizophyllum commune UTARA1 lipases. Lipase was produced by cultivating S. commune UTARA1 on sugarcane bagasse (SB) with used cooking oil (UCO) via SSF and its production was optimized using Design-Expert ® 7.0.0. Fractions 30% ( Sc LipA) and 70% ( Sc LipB) which contained high lipase activity were obtained by stepwise (NH₄)₂SO₄ precipitation. Crude fish oil, coconut oil and butter were used to investigate the lipase hydrolysis capabilities by a free glycerol assay. Results showed that Sc LipA has affinities for long, medium and short chain triglycerides, as all the oils investigated were degraded, whereas Sc LipB has affinities for long chain triglycerides as it only degrades crude fish oil. During esterification, Sc LipA was able to synthesize trilaurin and triacetin. Conversely, Sc LipB was specific towards the formation of 2-mono-olein and triacetin. From the results obtained, it was determined that Sc LipA and Sc LipB are sn -2 regioselective lipases. Hence, the one-step partial purification strategy proved to be feasible for partial purification of S. commune UTARA1 lipases that has potential use in industrial applications.

The value of molecular expression of KIT and KIT ligand analysed using real-time polymerase chain reaction and immunohistochemistry as a prognostic indicator for canine cutaneous mast cell tumours.

PubMed

Costa Casagrande, T A; de Oliveira Barros, L M; Fukumasu, H; Cogliati, B; Chaible, L M; Dagli, M L Z; Matera, J M

2015-03-01

This study investigated the correlation between KIT gene expression determined by immunohistochemistry and real-time polymerase chain reaction (RT-PCR) and the rate of tumour recurrence and tumour-related deaths in dogs affected with mast cell tumour (MCT). Kaplan-Meier curves were constructed to compare tumour recurrence and tumour-related death between patients. The log-rank test was used to check for significant differences between curves. KIT-I, KIT-II and KIT-III staining patterns were observed in 9 (11.11%), 50 (61.73%) and 22 (27.16%) tumours, respectively. Tumour recurrence rates and tumour-related deaths were not associated with KIT staining patterns (P = 0278, P > 0.05), KIT (P = 0.289, P > 0.05) or KIT ligand (P = 0.106, P > 0.05) gene expression. Despite the lack of association between KIT staining pattern and patient survival time, the results suggest a correlation between aberrant KIT localization and increased proliferative activity of MCTs. RT-PCR seems to be a sensible method for quantitative detection of KIT gene expression in canine MCT, although expressions levels are not correlated with prognosis. © 2013 Blackwell Publishing Ltd.

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.

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.

Analysis of the Binding Moiety Mediating the Interaction between Monocarboxylate Transporters and Carbonic Anhydrase II*

PubMed Central

Noor, Sina Ibne; Dietz, Steffen; Heidtmann, Hella; Boone, Christopher D.; McKenna, Robert; Deitmer, Joachim W.; Becker, Holger M.

2015-01-01

Proton-coupled monocarboxylate transporters (MCTs) mediate the exchange of high energy metabolites like lactate between different cells and tissues. We have reported previously that carbonic anhydrase II augments transport activity of MCT1 and MCT4 by a noncatalytic mechanism, while leaving transport activity of MCT2 unaltered. In the present study, we combined electrophysiological measurements in Xenopus oocytes and pulldown experiments to analyze the direct interaction between carbonic anhydrase II (CAII) and MCT1, MCT2, and MCT4, respectively. Transport activity of MCT2-WT, which lacks a putative CAII-binding site, is not augmented by CAII. However, introduction of a CAII-binding site into the C terminus of MCT2 resulted in CAII-mediated facilitation of MCT2 transport activity. Interestingly, introduction of three glutamic acid residues alone was not sufficient to establish a direct interaction between MCT2 and CAII, but the cluster had to be arranged in a fashion that allowed access to the binding moiety in CAII. We further demonstrate that functional interaction between MCT4 and CAII requires direct binding of the enzyme to the acidic cluster 431EEE in the C terminus of MCT4 in a similar fashion as previously shown for binding of CAII to the cluster 489EEE in the C terminus of MCT1. In CAII, binding to MCT1 and MCT4 is mediated by a histidine residue at position 64. Taken together, our results suggest that facilitation of MCT transport activity by CAII requires direct binding between histidine 64 in CAII and a cluster of glutamic acid residues in the C terminus of the transporter that has to be positioned in surroundings that allow access to CAII. PMID:25561737

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.

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

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

Chlorpropamide action on renal concentrating mechanism in rats with hypothalamic diabetes insipidus.

PubMed Central

Kusano, E; Braun-Werness, J L; Vick, D J; Keller, M J; Dousa, T P

1983-01-01

To determine vasopressin (VP)-potentiating effect of chlorpropamide (CPMD), we studied the effect of CPMD in vivo and in vitro in kidneys and in specific tubule segments of rats with hypothalamic diabetes insipidus, homozygotes of the Brattleboro strain (DI rats). Rats on ad lib. water intake were treated with CPMD (20 mg/100 g body wt s.c. daily) for 7 d. While on ad lib. water intake, the urine flow, urine osmolality, urinary excretion of Na +, K +, creatinine, or total solute excretion did not change. However, corticopapillary gradient of solutes was significantly increased in CPMD-treated rats. Higher tissue osmolality was due to significantly increased concentration of Na +, and to a lesser degree urea, in the medulla and papilla of CPMD-treated rats. Consequently, the osmotic gradient between urine and papillary tissue of CPMD-treated rats (delta = 385 +/- 47 mosM) was significantly (P less than 0.001) higher compared with controls (delta = 150 +/- 26 mosM). Minimum urine osmolality after water loading was higher in CPMD-treated DI rats than in controls. Oxidation of [14C]lactate to 14CO2 coupled to NaCl cotransport was measured in thick medullary ascending limb of Henle's loop (MAL) microdissected from control and CPMD-treated rats. The rate of 14CO2 production was higher (delta + 113% +/- 20; P less than 0.01) in CPMD-treated MAL compared with controls, but 14CO2 production in the presence of 10(-3) M furosemide did not differ between MAL from control and from CPMD-treated rats. These observations suggest that CPMD treatment enhances NaCl transport in MAL. Cyclic AMP metabolism was analyzed in microdissected MAL and in medullary collecting tubule (MCT). MCT from control and from CPMD-treated rats did not differ in the basal or VP-stimulated accumulated of cAMP. The increase in cAMP content elicited by 10(-6) M VP in MAL from CPMD-treated rats (delta + 12.0 +/- 1.8 fmol cAMP/mm) was significantly (P less than 0.02) higher compared with MAL from control rats (delta + 5.1 +/- 1.0 fmol cAMP/mm). Preincubation of MAL dissected from Sprague-Dawley rats with 10(-4) M CPMD in vitro increased cAMP accumulation in the presence of VP, but no such enhancement was found in preincubated MCT. Adenylate cyclase activity, basal or stimulated by VP, 5'guanylimidodiphosphate, or by NaF, assayed in isotonic medium did not differ between MAL or MCT from control rats and MAL or MCT from CPMD-treated rats. When assayed in hypertonic medium (800 mosM), the adenylate cyclase activity in the presence of 10(-6) M VP was significantly higher in MAL of CPMD-treated rats. MAL and MCT from control and CPMD-treated rats did not differ in the activities of cAMP phosphodiesterase. The rate of [(14)C]prostaglandin E2 by medullary and papillary microsomes was not different between the control and CPMD-treated rats; likewise, there was no difference in accumulation of immunoreactive prostaglandin E2 in the medium of in vitro incubated medullary or papillary slices prepared from control and CPMD-treated rats. Based on the findings recounted above, we propose a hypothesis that CPMD administration enhances the antidiuretic effect of VP, primarily by increasing medullary and papillary tonicity dye to increased NaCl reabsorption in MAL. There is no evidence that CPMD sensitizes collecting tubules to the action of VP, at least at the camp-generation step. Therefore, increased antidiuretic response to VP in the kidneys of CPMD-treated DI rats is due to enhanced osmotic driving force for water reabsorption (lumen-to-interstitium osmotic gradient) in collecting tubules, rather than due to increased VP-dependent water permeability of tubular epithelium. PMID:6313759

Chlorpropamide action on renal concentrating mechanism in rats with hypothalamic diabetes insipidus.

PubMed

Kusano, E; Braun-Werness, J L; Vick, D J; Keller, M J; Dousa, T P

1983-10-01

To determine vasopressin (VP)-potentiating effect of chlorpropamide (CPMD), we studied the effect of CPMD in vivo and in vitro in kidneys and in specific tubule segments of rats with hypothalamic diabetes insipidus, homozygotes of the Brattleboro strain (DI rats). Rats on ad lib. water intake were treated with CPMD (20 mg/100 g body wt s.c. daily) for 7 d. While on ad lib. water intake, the urine flow, urine osmolality, urinary excretion of Na +, K +, creatinine, or total solute excretion did not change. However, corticopapillary gradient of solutes was significantly increased in CPMD-treated rats. Higher tissue osmolality was due to significantly increased concentration of Na +, and to a lesser degree urea, in the medulla and papilla of CPMD-treated rats. Consequently, the osmotic gradient between urine and papillary tissue of CPMD-treated rats (delta = 385 +/- 47 mosM) was significantly (P less than 0.001) higher compared with controls (delta = 150 +/- 26 mosM). Minimum urine osmolality after water loading was higher in CPMD-treated DI rats than in controls. Oxidation of [14C]lactate to 14CO2 coupled to NaCl cotransport was measured in thick medullary ascending limb of Henle's loop (MAL) microdissected from control and CPMD-treated rats. The rate of 14CO2 production was higher (delta + 113% +/- 20; P less than 0.01) in CPMD-treated MAL compared with controls, but 14CO2 production in the presence of 10(-3) M furosemide did not differ between MAL from control and from CPMD-treated rats. These observations suggest that CPMD treatment enhances NaCl transport in MAL. Cyclic AMP metabolism was analyzed in microdissected MAL and in medullary collecting tubule (MCT). MCT from control and from CPMD-treated rats did not differ in the basal or VP-stimulated accumulated of cAMP. The increase in cAMP content elicited by 10(-6) M VP in MAL from CPMD-treated rats (delta + 12.0 +/- 1.8 fmol cAMP/mm) was significantly (P less than 0.02) higher compared with MAL from control rats (delta + 5.1 +/- 1.0 fmol cAMP/mm). Preincubation of MAL dissected from Sprague-Dawley rats with 10(-4) M CPMD in vitro increased cAMP accumulation in the presence of VP, but no such enhancement was found in preincubated MCT. Adenylate cyclase activity, basal or stimulated by VP, 5'guanylimidodiphosphate, or by NaF, assayed in isotonic medium did not differ between MAL or MCT from control rats and MAL or MCT from CPMD-treated rats. When assayed in hypertonic medium (800 mosM), the adenylate cyclase activity in the presence of 10(-6) M VP was significantly higher in MAL of CPMD-treated rats. MAL and MCT from control and CPMD-treated rats did not differ in the activities of cAMP phosphodiesterase. The rate of [(14)C]prostaglandin E2 by medullary and papillary microsomes was not different between the control and CPMD-treated rats; likewise, there was no difference in accumulation of immunoreactive prostaglandin E2 in the medium of in vitro incubated medullary or papillary slices prepared from control and CPMD-treated rats. Based on the findings recounted above, we propose a hypothesis that CPMD administration enhances the antidiuretic effect of VP, primarily by increasing medullary and papillary tonicity dye to increased NaCl reabsorption in MAL. There is no evidence that CPMD sensitizes collecting tubules to the action of VP, at least at the camp-generation step. Therefore, increased antidiuretic response to VP in the kidneys of CPMD-treated DI rats is due to enhanced osmotic driving force for water reabsorption (lumen-to-interstitium osmotic gradient) in collecting tubules, rather than due to increased VP-dependent water permeability of tubular epithelium.

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.

Co-expression of monocarboxylate transporter 1 (MCT1) and its chaperone (CD147) is associated with low survival in patients with gastrointestinal stromal tumors (GISTs).

PubMed

de Oliveira, Antônio Talvane Torres; Pinheiro, Céline; Longatto-Filho, Adhemar; Brito, Maria Jose; Martinho, Olga; Matos, Delcio; Carvalho, André Lopes; Vazquez, Vinícius Lima; Silva, Thiago Buosi; Scapulatempo, Cristovam; Saad, Sarhan Sydney; Reis, Rui Manuel; Baltazar, Fátima

2012-02-01

Monocarboxylate transporters (MCTs) have been described to play an important role in cancer, but to date there are no reports on the significance of MCT expression in gastrointestinal stromal tumors (GISTs). The aim of the present work was to assess the value of MCT expression, as well as co-expression with the MCT chaperone CD147 in GISTs and evaluate their clinical-pathological significance. We analyzed the immunohistochemical expression of MCT1, MCT2, MCT4 and CD147 in a series of 64 GISTs molecularly characterized for KIT, PDGFRA and BRAF mutations. MCT1, MCT2 and MCT4 were highly expressed in GISTs. CD147 expression was associated with mutated KIT (p = 0.039), as well as a progressive increase in Fletcher's Risk of Malignancy (p = 0.020). Importantly, co-expression of MCT1 with CD147 was associated with low patient's overall survival (p = 0.037). These findings suggest that co-expression of MCT1 with its chaperone CD147 is involved in GISTs aggressiveness, pointing to a contribution of cancer cell metabolic adaptations in GIST development and/or progression.

Localisation of Lactate Transporters in Rat and Rabbit Placentae

PubMed Central

Picut, Catherine A.; Charlap, Jeffrey H.

2016-01-01

The distribution of monocarboxylate transporter (MCT) isoforms 1 and 4, which mediate the plasmalemmal transport of l-lactic and pyruvic acids, has been identified in the placentae of rats and rabbits at different ages of gestation. Groups of three pregnant Sprague-Dawley rats and New Zealand White rabbits were sacrificed on gestation days (GD) 11, 14, 18, or 20 and on GD 13, 18, or 28, respectively. Placentae were removed and processed for immunohistochemical detection of MCT1 and MCT4. In the rat, staining for MCT1 was associated with lakes and blood vessels containing enucleated red blood cells (maternal vessels) while staining for MCT4 was associated with vessels containing nucleated red blood cells (embryofoetal vessels). In the rabbit, staining for MCT1 was associated with blood vessels containing nucleated red blood cells while staining for MCT4 was associated with vessels containing enucleated red blood cells. Strength of staining for MCT1 decreased during gestation in both species, but that for MCT4 was stronger than that for MCT1 and was consistent between gestation days. The results imply an opposite polarity of MCT1 and MCT4 across the trophoblast between rat and rabbit. PMID:27843454

Extraction of ewe's milk cream with supercritical carbon dioxide.

PubMed

González Hierro, M T; Ruiz-Sala, P; Alonso, L; Santa-María, G

1995-04-01

The extraction of ewe's milk cream by supercritical carbon dioxide in the pressure range 9-30 MPa (90-300 bar) and at temperatures of 40 degrees C and 50 degrees C was studied. The solubility of total fat increased with pressure at both temperatures until a plateau was reached. The extraction of cholesterol also increased with pressure until a plateau was reached and it was higher at 50 degrees C than at 40 degrees C when the pressure was > or = 15 MPa (150 bar). The triglyceride composition of each extract, determined by GC, showed that extracts obtained at lower pressures were enriched in short-chain triglycerides and their concentration decreased as the pressure increased. In the other hand, long-chain triglycerides were enriched in the extracts obtained at higher pressures and their concentration rose with increasing pressure.

Investigating the principles of recrystallization from glyceride melts.

PubMed

Windbergs, Maike; Strachan, Clare J; Kleinebudde, Peter

2009-01-01

Different lipids were melted and resolidified as model systems to gain deeper insight into the principles of recrystallization processes in lipid-based dosage forms. Solid-state characterization was performed on the samples with differential scanning calorimetry and X-ray powder diffraction. Several recrystallization processes could be identified during storage of the lipid layers. Pure triglycerides that generally crystallize to the metastable alpha-form from the melt followed by a recrystallization process to the stable beta-form with time showed a chain-length-dependent behavior during storage. With increasing chain length, the recrystallization to the stable beta-form was decelerated. Partial glycerides exhibited a more complex recrystallization behavior due to the fact that these substances are less homogenous. Mixtures of a long-chain triglyceride and a partial glyceride showed evidence of some interaction between the two components as the partial glyceride hindered the recrystallization of the triglyceride to the stable beta-form. In addition, the extent of this phenomenon depended on the amount of partial glyceride in the mixture. Based on these results, changes in solid dosage forms based on glycerides during processing and storage can be better understood.

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.

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.

Genetic disruption of lactate/H+ symporters (MCTs) and their subunit CD147/BASIGIN sensitizes glycolytic tumor cells to phenformin.

PubMed

Marchiq, Ibtissam; Le Floch, Renaud; Roux, Danièle; Simon, Marie-Pierre; Pouyssegur, Jacques

2015-01-01

Rapidly growing glycolytic tumors require energy and intracellular pH (pHi) homeostasis through the activity of two major monocarboxylate transporters, MCT1 and the hypoxia-inducible MCT4, in intimate association with the glycoprotein CD147/BASIGIN (BSG). To further explore and validate the blockade of lactic acid export as an anticancer strategy, we disrupted, via zinc finger nucleases, MCT4 and BASIGIN genes in colon adenocarcinoma (LS174T) and glioblastoma (U87) human cell lines. First, we showed that homozygous loss of MCT4 dramatically sensitized cells to the MCT1 inhibitor AZD3965. Second, we demonstrated that knockout of BSG leads to a decrease in lactate transport activity of MCT1 and MCT4 by 10- and 6-fold, respectively. Consequently, cells accumulated an intracellular pool of lactic and pyruvic acids, magnified by the MCT1 inhibitor decreasing further pHi and glycolysis. As a result, we found that these glycolytic/MCT-deficient cells resumed growth by redirecting their metabolism toward OXPHOS. Third, we showed that in contrast with parental cells, BSG-null cells became highly sensitive to phenformin, an inhibitor of mitochondrial complex I. Phenformin addition to these MCT-disrupted cells in normoxic and hypoxic conditions induced a rapid drop in cellular ATP-inducing cell death by "metabolic catastrophe." Finally, xenograft analysis confirmed the deleterious tumor growth effect of MCT1/MCT4 ablation, an action enhanced by phenformin treatment. Collectively, these findings highlight that inhibition of the MCT/BSG complexes alone or in combination with phenformin provides an acute anticancer strategy to target highly glycolytic tumors. This genetic approach validates the anticancer potential of the MCT1 and MCT4 inhibitors in current development. ©2014 American Association for Cancer Research.

Parenteral and enteral metabolism of anaplerotic triheptanoin in normal rats. II. Effects on lipolysis, glucose production, and liver acyl-CoA profile

PubMed Central

Gu, Lei; Zhang, Guo-Fang; Kombu, Rajan S.; Allen, Frederick; Kutz, Gerd; Brewer, Wolf-Ulrich; Roe, Charles R.

2010-01-01

The anaplerotic odd-medium-chain triglyceride triheptanoin is used in clinical trials for the chronic dietary treatment of patients with long-chain fatty acid oxidation disorders. We previously showed (Kinman RP, Kasumov T, Jobbins KA, Thomas KR, Adams JE, Brunengraber LN, Kutz G, Brewer WU, Roe CR, Brunengraber H. Am J Physiol Endocrinol Metab 291: E860–E866, 2006) that the intravenous infusion of triheptanoin increases lipolysis traced by the turnover of glycerol. In this study, we tested whether lipolysis induced by triheptanoin infusion is accompanied by the potentially harmful release of long-chain fatty acids. Rats were infused with heptanoate ± glycerol or triheptanoin. Intravenous infusion of triheptanoin at 40% of caloric requirement markedly increased glycerol endogenous Ra but not oleate endogenous Ra. Thus, the activation of lipolysis was balanced by fatty acid reesterification in the same cells. The liver acyl-CoA profile showed the accumulation of intermediates of heptanoate β-oxidation and C5-ketogenesis and a decrease in free CoA but no evidence of metabolic perturbation of liver metabolism such as propionyl overload. Our data suggest that triheptanoin, administered either intravenously or intraduodenally, could be used for intensive care and nutritional support of metabolically decompensated long-chain fatty acid oxidation disorders. PMID:19903863

Interaction between basigin and monocarboxylate transporter 2 in the mouse testes and spermatozoa

PubMed Central

Chen, Cheng; Maekawa, Mamiko; Yamatoya, Kenji; Nozaki, Masami; Ito, Chizuru; Iwanaga, Toshihiko; Toshimori, Kiyotaka

2016-01-01

Basigin is a member of the immunoglobulin superfamily and plays various important roles in biological events including spermatogenesis. To examine the basigin molecular variants during spermatogenesis and sperm maturation in the mouse, immunoprecipitated basigin samples from testis and epididymal spermatozoa were analyzed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The results demonstrated that basigin molecules from the testis and spermatozoa were separable into two major bands and that the differences in the molecular sizes were possibly because of an endoproteolytic cleavage. Since basigin is known to be a chaperone for the monocarboxylate transporter 1 (MCT1), the localization of basigin, MCT1 and MCT2 was examined during postnatal testicular development. Immunohistochemical studies showed different expression patterns of MCT1 and MCT2. MCT1 was localized on the surface of spermatogonia, spermatocytes, and spermatids. In contrast, MCT2 appeared on the principal piece of spermatozoa in the testis, where basigin was also observed. In mature epididymal spermatozoa, MCT2 was located on the midpiece, where basigin co-localized with MCT2 but not with MCT1. Furthermore, MCT2 was immunoprecipitated with basigin in mouse testes and sperm. These results suggest that basigin has a functional role as a binding partner with MCT2 in testicular and epididymal spermatozoa. PMID:26208397

Influence of nutrition on liver oxidative metabolism.

PubMed

Jorquera, F; Culebras, J M; González-Gallego, J

1996-06-01

The liver plays a major role in the disposition of the majority of drugs. This is due to the presence of several drug-metabolizing enzyme systems, including a group of membrane-bound mixed-function oxidative enzymes, mainly the cytochrome P450 system. Hepatic oxidative capacity can be assessed by changes in antipyrine metabolism. Different drugs and other factors may induce or inhibit the cytochrome P450-dependent system. This effect is important in terms of the efficacy or toxicity of drugs that are substrates for the system. Microsomal oxidation in animals fed with protein-deficient diets is depressed. The mixed-function oxidase activity recovers after a hyperproteic diet or the addition of lipids. Similar findings have been reported in patients with protein-calorie malnutrition, although results in the elderly are conflicting. Different studies have revealed that microsomal oxidation is impaired by total parenteral nutrition and that this effect is absent when changing the caloric source from carbohydrates to a conventional amino acid solution or after lipid addition, especially when administered as medium-chain/long-chain triglyceride mixtures. Peripheral parenteral nutrition appears to increase antipyrine clearance.

Donkey's milk detailed lipid composition.

PubMed

Gastaldi, Daniela; Bertino, Enrico; Monti, Giovanna; Baro, Cristina; Fabris, Claudio; Lezo, Antonela; Medana, Claudio; Baiocchi, Claudio; Mussap, Michele; Galvano, Fabio; Conti, Amedeo

2010-01-01

Donkey's milk (DM) has recently aroused scientific interest, above all among paediatric allergologists. A deeper knowledge of both proteins and fats in donkey's milk is necessary to evaluate the immunological, physiological and nutritional properties. By using the most refined techniques for fatty acids analysis, the paper offers a detailed comparative analysis of the lipid fractions of DM as well as of human and cow milk, also indicating the distribution of fatty-acid moieties among sn-1/3 and sn-2 positions of the glycerol backbone. In DM the position of fatty acids on glycerol backbone, above all of long chain saturated fatty acids, is very similar to that of human milk: this fact, in conjunction with the relatively high contents of medium-chain triglycerides, makes the lipids in DM, through quantitatively reduced, highly bioavailable. The high PUFA n-3 content of donkey's milk, and especially its low n-6/n-3 ratio, acquires particular interest in subjects affected by cow's milk protein allergy. Whole DM might also constitute the basis for formulas suitable for subjects in the first year of life.

Altered K+ fluxes and insulin release in pancreatic islets from omega3 fatty acid-depleted rats.

PubMed

Sener, Abdullah; Zhang, Ying; Louchami, Karim; Oguzhan, Berrin; Courtois, Philippe; Portois, Laurence; Chardigny, Jean-Michel; Carpentier, Yvon A; Malaisse, Willy J

2006-10-01

A low intake of long-chain polyunsaturated omega3 fatty acid often prevails in Western populations. Its consequences in terms of the control of fuel homeostasis led us to explore functional events in pancreatic islets isolated from either normal or omega3-depleted rats (second generation). In the latter rats, the inflow of K+ by both ouabain-sensitive and ouabain-resistant modalities was decreased, this coinciding with an impaired insulin secretory response to ouabain. The intravenous injection of a medium-chain triglyceride:fish oil emulsion to omega3-depleted rats 2 h before sacrifice restored a normal value for the inflow of K+ by the ouabainsensitive modality, i.e., that linked to the activity of the Na,K-ATPase, but failed to correct the entry of K+ by the ouabain-resistant modality and the defect of the insulin secretory response to ouabain. In conclusion, an impaired activity of the Na,K-ATPase in insulin-producing cells apparently represents a key determinant of altered islet function in omega3-depleted rats.

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.

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

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

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.

Formulation and development of bicontinuous nanostructured liquid crystalline particles of efavirenz.

PubMed

Avachat, Amelia M; Parpani, Shreekrishna S

2015-02-01

Efavirenz is a lipophilic non-nucleoside reverse transcriptase inhibitor used in the first-line pediatric therapeutic cocktail. Due to its high lipophilicity (logP = 5.4) and poor aqueous solubility (intrinsic water solubility = 8.3 μg/mL) efavirenz has low bioavailability. A 30 mg/mL solution in a medium-chain triglyceride vehicle is the only pediatric formulation available with an oral bioavailability 20% lower than the solid form. The current work was aimed at formulating and characterizing liquid crystal nanoparticles for oral delivery of efavirenz to improve oral bioavailability, provide sustained release, minimize side effects and drug resistance. Formulation of cubosomes was done by two methods; sonication and spray drying. Sonication gave highest entrapment efficiency and least particle size. Further, monoolein was substituted with phytantriol as monoolein gets degraded in the presence of lipase when administered orally with consequent loss of liquid crystalline structure. It was confirmed that there was no difference in particle size, entrapment efficiency and nature of product formed by using monoolein or phytantriol. The best formulation was found to be F9, having particle size 104.19 ± 0.21 nm and entrapment efficiency 91.40 ± 0.10%. In vitro release at the end of 12h was found to be 56.45% and zeta potential to be -23.14 mV which stabilized the cubic phase dispersions. It was further characterized for TEM, small angle X-ray scattering (SAXS), DSC and stability studies. SAXS revealed Pn3m space group, indicating a diamond cubic phase which was further confirmed by TEM. Pharmacokinetics of EFV was studied in male Wistar rats. EFV-loaded cubosome dispersions exhibited 1.93 and 1.62-fold increase in peak plasma concentration (Cmax) and 1.48 and 1.42-fold increase in AUC in comparison to that of a suspension prepared with the contents of EFV capsules suspended in 1.5% carboxymethylcellulose PBS solution (pH 5.0), and an EFV solution in medium-chain triglyceride respectively. Thus, stable cubosomes of efavirenz with increased bioavailability providing sustained release effect could be prepared successfully using phytantriol and poloxamer 407. Copyright © 2014 Elsevier B.V. All rights reserved.

Enhancing oxidative stability in heated oils using core/shell structures of collagen and α-tocopherol complex.

PubMed

Gim, Seo Yeong; Hong, Seungmi; Kim, Jisu; Kwon, YongJun; Kim, Mi-Ja; Kim, GeunHyung; Lee, JaeHwan

2017-11-15

In this study, collagen mesh structure was prepared by carrying α-tocopherol in the form of core/shell complex. Antioxidant properties of α-tocopherol loaded carriers were tested in moisture added bulk oils at 140°C. From one gram of collagen core/shell complex, 138mg α-tocopherol was released in medium chain triacylglycerol (MCT). α-Tocopherol was substantially protected against heat treatment when α-tocopherol was complexed in collagen core/shell. Oxidative stability in bulk oil was significantly enhanced by added collagen mesh structure or collagen core/shell complex with α-tocopherol compared to that in control bulk oils (p<0.05), although no significant difference was observed between oils containing collagen mesh structure and collagen core/shell with α-tocopherol (p>0.05). Results of DPPH loss in methanol demonstrated that collagen core/shell with α-tocopherol had significantly (p<0.05) higher antioxidant properties than collagen mesh structure up to a certain period. Therefore, collagen core/shell complex is a promising way to enhance the stability of α-tocopherol and oxidative stability in oil-rich foods prepared at high temperature. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

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.

Detailed faecal fat analysis using Fourier transform infrared spectroscopy: Exploring the possibilities.

PubMed

De Koninck, Anne-Sophie; Nys, Karen; Vandenheede, Brent; Van Biervliet, Stephanie; Speeckaert, Marijn M; Delanghe, Joris R

2016-11-01

Fourier transform infrared (FTIR) spectroscopic determination of faecal fat is a simple and elegant alternative for the classical Van De Kamer approach. Besides quantification of the total amount of fat, analysis of the lipase hydrolysis efficiency (fatty acid/triglyceride ratio), fatty acid chain length and trans-unsaturated fatty acids could provide a better monitoring of dietary treatment. Stool samples (26 routine samples and 36 cystic fibrosis patients) were analysed with the Perkin Elmer Spectrum Two® spectrometer (3500-450cm -1 ). Fatty acid/triglyceride ratio was calculated using the absorbance ratio at 2855:1746cm -1 . To estimate lipase hydrolysis efficiency, sample ratios were compared with the ratio of butter and pure free fatty acids. Mean fatty acid chain length was calculated using the absorbance ratio at 2855:1709cm -1 . The absorbance at 966cm -1 was used to trace the presence of trans-type unsaturated fatty acids. Butter showed a low fatty acid/triglyceride ratio (1.21) and pure free fatty acids a high fatty acid/triglyceride ratio (6.76). Mean fatty acid/triglyceride ratio of routine stool samples was 4.16±1.01. The applicability of fatty acid/triglyceride ratios was also tested in cystic fibrosis patients under treatment with a mean of 4.92±0.98. Relative absorbance contribution per carbon atom was 0.06 (ratio 1.06 for C18 standard, 0.91 for C16 standard). The mean ratio of the stool samples was 1.12 (mean acyl chain length of C19), with values ranging from 0.73 (C12) to 1.68 (C28). The presence of traceable amounts of trans-unsaturated fatty acids was also demonstrated. For the analysis of faecal material, FTIR provides unique information, difficult to obtain using other techniques. These findings offer perspectives for diet monitoring in patients with (non-)pancreatic malabsorption. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

A model for the origin of Himalayan anatexis and inverted metamorphism

NASA Astrophysics Data System (ADS)

Harrison, T. Mark; Grove, Marty; Lovera, Oscar M.; Catlos, E. J.

1998-11-01

The origin of the paired granite belts and inverted metamorphic sequences of the Himalaya has generally been ascribed to development of the Main Central Thrust (MCT). Although a variety of models have been proposed that link early Miocene anatexis with inverted metamorphism, recent dating studies indicate that recrystallization of elements of the MCT footwall occurred in the central Himalaya as recently as ˜6 Ma. The recognition that hanging wall magmatism and footwall metamorphism are not spatially and temporally related renders unnecessary the need for exceptional physical conditions to explain generation of the High Himalayan leucogranites and North Himalayan granites, which differ in age, petrogenesis, and emplacement style. We suggest that their origin is linked to shear heating on a continuously active thrust that cuts through Indian supracrustal rocks that had previously experienced low degrees of partial melting. Numerical simulations assuming a shear stress of 30 MPa indicate that continuous slip on the Himalayan decollement beginning at 25 Ma could trigger partial melting reactions leading to formation of the High Himalayan granite chain between 25 and 20 Ma and the North Himalayan belt between 17 and 8 Ma. The ramp-flat geometry we apply to model the Himalayan thrust system requires that the presently exposed rocks of the hanging wall resided at middle crustal levels above the decollement throughout the early and middle Miocene. Late Miocene, out-of-sequence thrusting within the broad shear zone beneath the MCT provides a mechanism to bring these rocks to the surface in their present location (i.e., well to the north of the present tectonic front) and has the additional benefit of explaining how the inverted metamorphic sequences formed beneath the MCT. We envision that formation of the MCT Zone involved successive accretion of tectonic slivers of the Lesser Himalayan Formations to the hanging wall and incorporate these effects into the model. The model predicts continued anatexis up to 400 km north of the Himalayan range, consistent with the timing and geochemistry of leucogranites exhumed on the flank of a south Tibetan rift.

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.

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.

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.

The history of N-methanocarbathymidine: the investigation of a conformational concept leads to the discovery of a potent and selective nucleoside antiviral agent.

PubMed

Marquez, Victor E; Hughes, Stephen H; Sei, Shizuko; Agbaria, Riad

2006-09-01

Conformationally locked (North)-methanocarbathymidine (N-MCT) and (South)-methanocarbathymidine (S-MCT) have been used to investigate the conformational preferences of kinases and polymerases. The herpes kinases show a distinct bias for S-MCT, while DNA polymerases almost exclusively incorporate the North 5'-triphosphate (N-MCT-TP). Only N-MCT demonstrated potent antiviral activity against herpes simplex viruses (HSV-1 and 2) and Kaposi's sarcoma-associated herpesvirus (KSHV). The activity of N-MCT depends on its metabolic transformation to N-MCT-TP by the herpes kinases (HSV-tk or KSHV-tk), which catalyze the mono and diphosphorylation steps; cellular kinases generate the triphosphate. N-MCT at a dose of 5.6 mg/kg was totally protective for mice inoculated intranasally with HSV-1. Tumor cells that are not responsive to antiviral therapy became sensitive to N-MCT if the cells expressed HSV-tk. N-MCT given twice daily (100 mg/kg) for 7 days completely inhibited the growth of MC38 tumors derived from cells that express HSV-tk in mice while exhibiting no effect on tumors derived from non-transduced cells. After i.p. administration, N-MCT was rapidly absorbed and distributed in all organs examined with slow penetration into brain and testes. N-MCT-TP was also a potent inhibitor of HIV replication in human osteosarcoma (HOS) cells expressing HSV-tk.

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.

Association between Metabolite Profiles, Metabolic Syndrome and Obesity Status.

PubMed

Allam-Ndoul, Bénédicte; Guénard, Frédéric; Garneau, Véronique; Cormier, Hubert; Barbier, Olivier; Pérusse, Louis; Vohl, Marie-Claude

2016-05-27

Underlying mechanisms associated with the development of abnormal metabolic phenotypes among obese individuals are not yet clear. Our aim is to investigate differences in plasma metabolomics profiles between normal weight (NW) and overweight/obese (Ov/Ob) individuals, with or without metabolic syndrome (MetS). Mass spectrometry-based metabolite profiling was used to compare metabolite levels between each group. Three main principal components factors explaining a maximum of variance were retained. Factor 1's (long chain glycerophospholipids) metabolite profile score was higher among Ov/Ob with MetS than among Ov/Ob and NW participants without MetS. This factor was positively correlated to plasma total cholesterol (total-C) and triglyceride levels in the three groups, to high density lipoprotein -cholesterol (HDL-C) among participants without MetS. Factor 2 (amino acids and short to long chain acylcarnitine) was positively correlated to HDL-C and negatively correlated with insulin levels among NW participants. Factor 3's (medium chain acylcarnitines) metabolite profile scores were higher among NW participants than among Ov/Ob with or without MetS. Factor 3 was negatively associated with glucose levels among the Ov/Ob with MetS. Factor 1 seems to be associated with a deteriorated metabolic profile that corresponds to obesity, whereas Factors 2 and 3 seem to be rather associated with a healthy metabolic profile.

Apoptosis and Inflammation Associated Gene Expressions in Monocrotaline-Induced Pulmonary Hypertensive Rats after Bosentan Treatment

PubMed Central

Hong, Young Mi; Kwon, Jung Hyun; Choi, Shinkyu

2014-01-01

Background and Objectives Vascular wall remodeling in pulmonary hypertension can be caused by an aberration in the normal balance between proliferation and apoptosis of endothelial cell in the pulmonary artery. The objective of this study was to evaluate the effect of bosentan on apoptosis in monocrotaline (MCT)-induced pulmonary hypertension. Materials and Methods Sprague-Dawley rats were divided into three groups: control (C) group, M group (MCT 60 mg/kg) and B group (MCT 60 mg/kg plus bosentan 20 mg/day orally). Gene expressions of Bcl (B cell leukemia/lymphoma)-2, caspase-3, complement component (C)-6, vascular endothelial growth factor (VEGF), interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) were analyzed by real time polymerase chain reaction and western blot analysis. Results The messenger ribonucleic acid (mRNA) expressions of caspase-3 and VEGF were significantly increased in the M group compared with the C group, and significantly decreased in the B group compared with the M group in week 4. mRNA expression of IL-6 was significantly decreased in weeks 1, 2, and 4 in the B group compared with the M group. mRNA expression of TNF-α was significantly decreased on day 5 and in weeks 1 and 2 in the B group compared with the M group. Conclusion Bosentan may have potential for preventing apoptosis and inflammation. PMID:24653739

Zebrafish as a model for monocarboxyl transporter 8-deficiency.

PubMed

Vatine, Gad David; Zada, David; Lerer-Goldshtein, Tali; Tovin, Adi; Malkinson, Guy; Yaniv, Karina; Appelbaum, Lior

2013-01-04

Allan-Herndon-Dudley syndrome (AHDS) is a severe psychomotor retardation characterized by neurological impairment and abnormal thyroid hormone (TH) levels. Mutations in the TH transporter, monocarboxylate transporter 8 (MCT8), are associated with AHDS. MCT8 knock-out mice exhibit impaired TH levels; however, they lack neurological defects. Here, the zebrafish mct8 gene and promoter were isolated, and mct8 promoter-driven transgenic lines were used to show that, similar to humans, mct8 is primarily expressed in the nervous and vascular systems. Morpholino-based knockdown and rescue experiments revealed that MCT8 is strictly required for neural development in the brain and spinal cord. This study shows that MCT8 is a crucial regulator during embryonic development and establishes the first vertebrate model for MCT8 deficiency that exhibits a neurological phenotype.

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.

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].

Dai-kenchu-to attenuates rat sinusoidal obstruction syndrome by inhibiting the accumulation of neutrophils in the liver.

PubMed

Narita, Masato; Hatano, Etsuro; Tamaki, Nobuyuki; Yamanaka, Kenya; Yanagida, Atsuko; Nagata, Hiromitsu; Asechi, Hiroyuki; Takada, Yasutsugu; Ikai, Iwao; Uemoto, Shinji

2009-06-01

Sinusoidal obstruction syndrome (SOS) is drug-induced liver injury that occurs in patients who receive hematopoietic cell transplantation and oxaliplatin-contained chemotherapy. The aim of study was to investigate the pharmacological treatment of SOS using a traditional Japanese medicine, Dai-kenchu-to (DKT). Male Sprague-Dawley rats were treated with monocrotaline (MCT) to induce SOS. The rats were divided into three groups: control, MCT and MCT+DKT groups. In the MCT+DKT group, DKT was gavaged at 12 h after MCT treatment and given every 12 h until the end of the protocol. The rats of MCT group were treated with water instead of DKT. At 48 h after MCT treatment, blood and liver samples were collected. In the MCT+DKT group, the macroscopic and histological findings revealed liver congestion, sinusoidal alteration and the destruction of sinusoidal lining, which were comparable with those of the MCT group. However, the area of hepatic necrosis and serum AST levels significantly decreased in the MCT+DKT group compared with those of the MCT group. Treatment with DKT resulted in the reduction of neutrophil accumulation, myeloperoxidase activity and the expression of cytokine-induced neutrophil chemoattractant (CINC) and intracellular adhesion molecule-1 (ICAM-1) mRNA in the liver compared with those of the MCT group. Treatment with processed ginger, one of the ingredients in DKT, resulted in similar effects to those shown by DKT. Dai-kenchu-to attenuates MCT-induced liver injury by preventing neutrophil-induced liver injury through blockage of upregulation of CINC and ICAM-1 mRNA level.

Monocarboxylate transporter 1 contributes to growth factor-induced tumor cell migration independent of transporter activity

PubMed Central

Gray, Alana L.; Coleman, David T.; Shi, Runhua; Cardelli, James A.

2016-01-01

Tumor progression to metastatic disease contributes to the vast majority of incurable cancer. Understanding the processes leading to advanced stage cancer is important for the development of future therapeutic strategies. Here, we establish a connection between tumor cell migration, a prerequisite to metastasis, and monocarboxylate transporter 1 (MCT1). MCT1 transporter activity is known to regulate aspects of tumor progression and, as such, is a clinically relevant target for treating cancer. Knockdown of MCT1 expression caused decreased hepatocyte growth factor (HGF)-induced as well as epidermal growth factor (EGF)-induced tumor cell scattering and wound healing. Western blot analysis suggested that MCT1 knockdown (KD) hinders signaling through the HGF receptor (c-Met) but not the EGF receptor. Exogenous, membrane-permeable MCT1 substrates were not able to rescue motility in MCT1 KD cells, nor was pharmacologic inhibition of MCT1 able to recapitulate decreased cell motility as seen with MCT1 KD cells, indicating transporter activity of MCT1 was dispensable for EGF- and HGF-induced motility. These results indicate MCT1 expression, independent of transporter activity, is required for growth factor-induced tumor cell motility. The findings presented herein suggest a novel function for MCT1 in tumor progression independent of its role as a monocarboxylate transporter. PMID:27127175

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.

Preventive effect of sildenafil on right ventricular function in rats with monocrotaline-induced pulmonary arterial hypertension

PubMed Central

Yoshiyuki, Rieko; Tanaka, Ryo; Fukushima, Ryuji; Machida, Noboru

2016-01-01

The present study aimed to evaluate the preventive effect of sildenafil treatment on pulmonary hypertension (PH) induced by monocrotaline (MCT) in rats. Fifty-four 12-week-old male Sprague–Dawley rats were injected with MCT or saline solution (MCT-injected rats: n=36; saline: n=18). Serial echocardiography and right ventricular systolic pressure (RVSP) measurements via a cardiac catheter were performed at 2, 4 and 6 weeks after the injection. After injection of MCT, rats received oral sildenafil (MCT/sildenafil group: n=18) or no treatment (MCT group: n=18) until undergoing echocardiography and cardiac catheterization. RVSP in the MCT/sildenafil group was lower than that in the MCT group at 4 (P<0.001) and 6 weeks (P<0.001). The septal curvature was improved in the MCT/sildenafil group compared with the MCT group. This finding showed that sildenafil prevented flattening of the interventricular septum because of right ventricular pressure overload. The ratio of peak trans-tricuspid early diastolic wave velocity to active filling with atrial systolic velocity showed that sildenafil improved diastolic function. Tricuspid annular plane systolic excursion and tricuspid annular systolic velocity in the MCT/sildenafil group did not show preserved myocardial contraction after administration of sildenafil. Administration of sildenafil leads to a reduction in RVSP and improvement in cardiac function in rats with PH induced by MCT. The vasodilatory action of sildenafil improves right ventricular diastolic function, but the intrinsic, positive, inotropic effect of sildenafil is minimal. PMID:26876436

Activity of the Monocarboxylate Transporter 1 inhibitor AZD3965 in Small Cell Lung Cancer

PubMed Central

Polański, Radosław; Hodgkinson, Cassandra L.; Fusi, Alberto; Nonaka, Daisuke; Priest, Lynsey; Kelly, Paul; Trapani, Francesca; Bishop, Paul W.; White, Anne; Critchlow, Susan E.; Smith, Paul D.; Blackhall, Fiona

2013-01-01

Purpose The monocarboxylate transporter 1 (MCT1) inhibitor AZD3965 is undergoing Phase I evaluation in the UK. AZD3965 is proposed, via lactate transport modulation, to kill tumor cells reliant on glycolysis. We investigated the therapeutic potential of AZD3965 in small cell lung cancer (SCLC) seeking rationale for clinical testing in this disease and putative predictive biomarkers for trial use. Experimental Design AZD3965 sensitivity was determined for 7 SCLC cell lines, in normoxia and hypoxia, and for a tumor xenograft model. Proof of mechanism was sought via changes in intracellular/tumor lactate. Expression of MCT1 and related transporter MCT4 were assessed by western blot. Drug resistance was investigated via MCT4 siRNAi and overexpression. The expression and clinical significance of MCT1 and MCT4 were explored in a tissue microarray from 78 SCLC patients. Results AZD3965 sensitivity varied in vitro and was highest in hypoxia. Resistance in hypoxia was associated with increased MCT4 expression. In vivo, AZD3965 reduced tumor growth and increased intra-tumor lactate. In the tissue microarray, high MCT1 expression was associated with worse prognosis (p=0.014). MCT1 and hypoxia marker CA IX expression in the absence of MCT4 was observed in 21% of SCLC tumors. Conclusions This study provides a rationale to test AZD3965 in SCLC patients. Our results suggest that patients with tumors expressing MCT1 and lacking in MCT4 are most likely to respond. PMID:24277449

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.

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.

Prevalence and risk factors for mast cell tumours in dogs in England.

PubMed

Shoop, Stephanie Jw; Marlow, Stephanie; Church, David B; English, Kate; McGreevy, Paul D; Stell, Anneliese J; Thomson, Peter C; O'Neill, Dan G; Brodbelt, David C

2015-01-01

Mast cell tumour (MCT) appears to be a frequent tumour type in dogs, though there is little published in relation to its frequency in dogs in the UK. The current study aimed to investigate prevalence and risk factors for MCTs in dogs attending English primary-care veterinary practices. Electronic patient records from practices participating in the VetCompass animal surveillance project between July 2007 and June 2013 were searched for MCT diagnosis. Various search terms and standard diagnostic terms (VeNom codes) identified records containing MCT diagnoses, which were evaluated against clinical criteria for inclusion to the study. MCT prevalence for the entire dataset and specific breed types were calculated. Descriptive statistics characterised MCT cases and multivariable logistic regression methods evaluated risk factors for association with MCT (P < 0.05). Within a population of 168,636 dogs, 453 had MCT, yielding a prevalence of 0.27% (95% confidence interval (CI) 0.24% - 0.29%). The highest breed type specific prevalences were for the Boxer at 1.95% (95% CI 1.40% - 2.51%), Golden Retriever at 1.39% (0.98% - 1.81%) and Weimaraner at 0.85% (95% CI 0.17% to 1.53%). Age, insurance status, neuter status, weight and breed type were associated with MCT diagnosis. Of dogs of specific breed type, the Boxer, Pug and Staffordshire Bull Terrier showed greater odds of MCT diagnosis compared with crossbred dogs. Conversely, the German Shepherd Dog, Border Collie, West Highland White Terrier, Springer Spaniel and Cocker Spaniel had reduced odds of MCT diagnosis compared with crossbred dogs. No association was found between MCT diagnosis and sex. This study highlights a clinically significant prevalence of MCT and identifies specific breed types with predisposition to MCT, potentially aiding veterinarian awareness and facilitating diagnosis.

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.

Enhancement of Muscle Mitochondrial Oxidative Capacity and Alterations in Insulin Action Are Lipid Species Dependent

PubMed Central

Turner, Nigel; Hariharan, Krit; TidAng, Jennifer; Frangioudakis, Georgia; Beale, Susan M.; Wright, Lauren E.; Zeng, Xiao Yi; Leslie, Simon J.; Li, Jing-Ya; Kraegen, Edward W.; Cooney, Gregory J.; Ye, Ji-Ming

2009-01-01

OBJECTIVE Medium-chain fatty acids (MCFAs) have been reported to be less obesogenic than long-chain fatty acids (LCFAs); however, relatively little is known regarding their effect on insulin action. Here, we examined the tissue-specific effects of MCFAs on lipid metabolism and insulin action. RESEARCH DESIGN AND METHODS C57BL6/J mice and Wistar rats were fed either a low-fat control diet or high-fat diets rich in MCFAs or LCFAs for 4–5 weeks, and markers of mitochondrial oxidative capacity, lipid levels, and insulin action were measured. RESULTS Mice fed the MCFA diet displayed reduced adiposity and better glucose tolerance than LCFA-fed animals. In skeletal muscle, triglyceride levels were increased by the LCFA diet (77%, P < 0.01) but remained at low-fat diet control levels in the MCFA-fed animals. The LCFA diet increased (20–50%, P < 0.05) markers of mitochondrial metabolism in muscle compared with low-fat diet–fed controls; however; the increase in oxidative capacity was substantially greater in MCFA-fed animals (50–140% versus low-fat–fed controls, P < 0.01). The MCFA diet induced a greater accumulation of liver triglycerides than the LCFA diet, likely due to an upregulation of several lipogenic enzymes. In rats, isocaloric feeding of MCFA or LCFA high-fat diets induced hepatic insulin resistance to a similar degree; however, insulin action was preserved at the level of low-fat diet–fed controls in muscle and adipose from MCFA-fed animals. CONCLUSIONS MCFAs reduce adiposity and preserve insulin action in muscle and adipose, despite inducing steatosis and insulin resistance in the liver. Dietary supplementation with MCFAs may therefore be beneficial for preventing obesity and peripheral insulin resistance. PMID:19720794

De novo synthesis of milk triglycerides in humans

PubMed Central

Mohammad, Mahmoud A.; Sunehag, Agneta L.

2014-01-01

Mammary gland (MG) de novo lipogenesis contributes significantly to milk fat in animals but little is known in humans. Objective: To test the hypothesis that the incorporation of 13C carbons from [U-13C]glucose into fatty acids (FA) and glycerol in triglycerides (TG) will be greater: 1) in milk than plasma TG, 2) during a high-carbohydrate (H-CHO) diet than high-fat (H-FAT) diet, and 3) during feeding than fasting. Seven healthy, lactating women were studied on two isocaloric, isonitrogenous diets. On one occasion, subjects received diets containing H-FAT or H-CHO diet for 1 wk. Incorporation of 13C from infused [U-13C]glucose into FA and glycerol was measured using GC-MS and gene expression in RNA isolated from milk fat globule using microarrays. Incorporation of 13C2 into milk FA increased with increased FA chain length from C2:0 to C12:0 but progressively declined in C14:0 and C16:0 and was not detected in FA>C16. During feeding, regardless of diets, enrichment of 13C2 in milk FA and 13C3 in milk glycerol were ∼3- and ∼7-fold higher compared with plasma FA and glycerol, respectively. Following an overnight fast during H-CHO and H-FAT diets, 25 and 6%, respectively, of medium-chain FA (MCFA, C6–C12) in milk were derived from glucose but increased to 75 and 25% with feeding. Expression of genes involved in FA or glycerol synthesis was unchanged regardless of diet or fast/fed conditions. The human MG is capable of de novo lipogenesis of primarily MCFA and glycerol, which is influenced by the macronutrient composition of the maternal diet. PMID:24496312

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.

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 MCT1 inhibitors.

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.

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.