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Simon Eaton

Publications and source records attributed to Simon Eaton.

At least 37 records · Page 2Linked to original sources
PubMed2004

Melatonin protects from, but does not reverse, the effects of mediators of sepsis on liver bioenergetics.

BACKGROUND: Reactive oxygen species (ROS) have been reported to play a significant role in the pathogenesis of sepsis and liver dysfunction. In particular, neonates are at risk for sepsis and have less protection against oxidation. Melatonin has been reported to reduce the oxidative stress status in neonates with sepsis. Little is known about the effect of melatonin on liver bioenergetics. The aim of this study was to investigate the protective effect of melatonin on hepatocyte oxidative energy metabolism against hydrogen peroxide (H2O2), a free radical mediator of septic damage. METHODS: Hepatocytes were isolated from neonatal suckling rats (11-15 days old). The cells, respiring on palmitate, were exposed to H2O2 at the concentration of 2 mmol/l, melatonin alone at 1 micromol/l or 10 micromol/l, or H2O2 plus melatonin at each of the two concentrations. Oxygen consumption was measured polarographically. In subsequent experiments, melatonin was added after the hydrogen peroxide. RESULTS: Hydrogen peroxide significantly reduced hepatocyte oxygen consumption ( p<0.001), but melatonin added at the same time was able to prevent this effect ( p<0.001). However, melatonin at a low dose significantly inhibited hepatocyte oxygen consumption ( p<0.001), an effect which has not been previously described. When melatonin was added to cells after they had been exposed to hydrogen peroxide, a beneficial effect was not observed, indicating that melatonin is not able to reverse the effects of hydrogen peroxide. CONCLUSION: Melatonin has a protective effect on hepatocyte oxidative metabolism, improving mitochondrial function by counteracting oxidative stress.

Animals↗
PubMed2004

Heart energy metabolism after intestinal ischaemia and reperfusion.

BACKGROUND/PURPOSE: Multiple organ failure subsequent to intestinal ischaemia and reperfusion (I/R) includes cardiac failure, but little is known about heart energy metabolism in this setting. This study investigates the effects of intestinal I/R on heart energy metabolism and evaluates the effects of moderate hypothermia. METHODS: Adult rats underwent intestinal ischaemia for 60 minutes followed by 120 minutes of reperfusion. Animals were maintained at either normothermia (36 degrees to 38 degrees C) or moderate hypothermia (30 degrees to 32 degrees C). In experiment A, 2 groups were studied: (1) sham at normothermia; (2) I/R at normothermia. After death, the heart was removed. Cardiac phosphoenergetics were assessed by 31P magnetic resonance spectroscopy; data are expressed as micromoles per gram. In experiment B, 4 groups were studied: (1) sham at normothermia, (2) I/R at normothermia, (3) sham at hypothermia, (4) I/R at hypothermia. At the end of the experiment, the heart was harvested. The activity of carnitine palmitoyl transferase I (CPT I), an important enzyme in the control of fatty acid oxidation, was measured; data are expressed as nanomoles per minute per unit citrate synthase. Results are expressed as mean +/- SEM. RESULTS: In experiment A, there were no differences between the 2 study groups in cardiac phosphocreatine, inorganic phosphate, adenosine triphosphate (ATP), or in the ratio of inorganic phosphate to ATP. In experiment B, CPT I activity was decreased significantly after I/R at normothermia compared with normothermic sham, but this enzyme inhibition was prevented by hypothermia (3.9 +/- 0.2; v I/R). CONCLUSIONS: These results suggest that although cardiac ATP supply was maintained during intestinal I/R at normothermia, the balance of substrate utilisation was shifted from fatty acid oxidation to carbohydrate utilisation. However, moderate hypothermia modified these changes. The beneficial effect of moderate hypothermia on cardiac metabolism during intestinal I/R has potential clinical application in various surgical conditions.

Adenosine Triphosphate↗
PubMed2004

Mitochondrial beta-oxidation.

Mitochondrial beta-oxidation is a complex pathway involving, in the case of saturated straight chain fatty acids of even carbon number, at least 16 proteins which are organized into two functional subdomains; one associated with the inner face of the inner mitochondrial membrane and the other in the matrix. Overall, the pathway is subject to intramitochondrial control at multiple sites. However, at least in the liver, carnitine palmitoyl transferase I exerts approximately 80% of control over pathway flux under normal conditions. Clearly, when one or more enzyme activities are attenuated because of a mutation, the major site of flux control will change.

Animals↗
PubMed2004

Intestinal ischemia reperfusion injury and multisystem organ failure.

Intestinal ischemia-reperfusion is a common pathway for many diseases in infants, children, and adults, and this may lead to multiple organ dysfunction syndrome and death. While several studies have investigated reperfusion injury in cardiac, cerebral, and hepatic disease, limited work has been published on intestinal ischemia-reperfusion and its multiorgan effects. The authors have developed models of intestinal ischemia-reperfusion in rats and have demonstrated that intestinal reperfusion causes liver energy failure at normothermia. This is followed by 100% mortality within 4 hours of reperfusion. Moderate hypothermia (32 degrees C to 33 degrees C) induced throughout ischemia and reperfusion prevents liver energy failure, intestinal damage, and neutrophil infiltration in the lungs. Moderate hypothermia in this model of intestinal ischemia and reperfusion prevents mortality. Further studies are needed to establish whether therapeutic hypothermia is a useful intervention in the treatment of infants and children with intestinal injuries caused by ischemia and reperfusion.

Adenosine Triphosphate↗
PubMed2003

Early full blood count and severity of disease in neonates with necrotizing enterocolitis.

Thrombocytopaenia occurs during necrotizing enterocolitis (NEC), and nadir platelet count is associated with extent of disease. In paediatric meningococcal disease, the product of neutrophil and platelet count at admission is prognostically useful. We therefore aimed to determine whether the first full blood count (FBC) after diagnosis of NEC is useful as a score for poor outcome and severity of disease. Between 1987 to 2001, neutrophils (N), platelets (P) and their product (PN) was available in 187 neonates treated for NEC at our institution. Neonates with NEC were grouped according to the extent of disease (no gangrene, focal, multifocal and pan-intestinal). Data were not normally distributed so Mann-Whitney U test or analysis of variance (ANOVA) on logged data were used ( p<0.05 was considered significant). Receiver operating characteristics (ROC) curves were used to examine the relationship between specificity and sensitivity. A perfect test would have an ROC curve area of 1. Initial P count and PN product of non-survivors were both significantly lower than in survivors ( p<0.0001), whereas N was not different ( p<0.08). Low Log(10)PN was significantly associated with greater extent of disease (ANOVA; no gangrene vs multifocal, p<0.01, vs panintestinal, p<0.0005), suggesting that the initial FBC could be prognostically useful. Area under the ROC survival curve for neutrophils was 0.58, for platelets 0.75 and for PN product 0.71; thus, although no test performed extremely well, initial platelet count and NP product could be useful in evaluating disease severity in neonates with NEC and for further monitoring.

Blood Cell Count↗
PubMed2003

Neonatal endotoxemia affects heart but not kidney bioenergetics.

PURPOSE: The aim was to determine the effects of early and late endotoxemia on neonatal cardiac and renal mitochondrial energetics. METHODS: Suckling rats received intraperitoneal 300 microgram/kg lipopolysaccharide; controls received saline. Heart and kidney mitochondria were isolated after 2 hours (early) or 6 hours (late sepsis). State 3 (maximum mitochondrial flux) and 4 O(2) consumption and complex I activity were measured. Results, expressed as mean +/- SEM normalized to citrate synthase (CS), were compared using paired t tests. RESULTS: Mortality rate was zero within 2 hours, 2.7% between 2 and 6 hours of endotoxemia, and 100% 6 to 8 hours; therefore, we consider that 2 hours and 6 hours represent early and late endotoxemia, respectively. Endotoxic heart mitochondria had unaltered O(2) consumption at 2 hours but significantly decreased state 3 after 6 hours, resulting in significantly decreased respiratory control ratio. Complex I activity, which could affect O(2) consumption, was decreased significantly at 6 hours (9.8 +/- 0.6 mU/U CS; n = 15) versus controls (11.3 +/- 0.8, n = 15; P =.04), but not at 2 hours. There were no differences in these measurements at either 2 hours or 6 hours in kidney mitochondria. CONCLUSIONS: The respiratory chain is affected late in endotoxemia. Neither early nor late endotoxemia affects oxidative function of kidney mitochondria.

Animals↗
PubMed2003

Cardiac and renal mitochondria respond differently to hydrogen peroxide in suckling rats.

BACKGROUND: Overwhelming septicemia with multiple organ failure is one of the main causes of mortality with neonatal surgery. Liver, kidney, and heart are organs for which oxidative metabolism is particularly important. Hydrogen peroxide (H(2)O(2)), a major mediator of sepsis, inhibits liver metabolism. Our aim was to determine the effects of H(2)O(2) on neonatal renal and cardiac oxidative metabolism. MATERIALS AND METHODS: Mitochondria were isolated from the heart and kidney of 11 to 15-day-old rats. Oxygen consumption was measured polarographically in mitochondria incubated with different concentrations of H(2)O(2). State 3 oxygen consumption, which represents maximum mitochondrial oxidative flux, was measured in the presence of adenosine diphosphate. State 4 oxygen consumption, which represents oxygen consumption that is wasted and not used for adenosine triphosphate (ATP) generation, was measured after all adenosine diphosphate was used. beta-Oxidation flux and carnitine palmitoyltransferase I activity were measured radiochemically with increased levels of H(2)O(2). RESULTS: H(2)O(2) impaired state 3 oxygen consumption at all concentrations tested in cardiac and renal mitochondria. H(2)O(2) had no significant effect on heart mitochondrial state 4 oxygen consumption but significantly increased that of kidney. Heart, but not kidney, beta-oxidation flux was inhibited by H(2)O(2). Neither cardiac nor renal carnitine palmitoyltransferase I activity was affected by H(2)O(2). CONCLUSIONS: H(2)O(2) inhibits maximal rates of ATP generation by heart and kidney mitochondria but has a more severe effect on kidney mitochondria because more oxygen is wasted and not used for ATP generation. This decrease in ATP generation may be a factor in the dysfunction of these organs during sepsis.

Adenosine Triphosphate↗
PubMed2003

Body temperature and heat production in suckling rat endotoxaemia: beneficial effects of glutamine.

BACKGROUND/PURPOSE: Sepsis is an important cause of neonatal mortality. The aim of the study was to investigate the metabolism of endotoxic neonatal rats and the potential beneficial effect of glutamine. METHODS: Suckling rats received intraperitoneal saline (control; C), endotoxin (300 microg/g LPS; E), saline+glutamine (2 mmol/g; CG), endotoxin+glutamine (EG), saline+leucine (2 mmol/g; CL) or endotoxin+leucine (EL). Sepsis score (0-8) and rectal temperature were monitored. Hypothermia was defined as rectal temperature less than 32 degrees C. Oxygen consumption (VO2, mL/kg/h), a determinant of heat production, was measured by indirect calorimetry. Data (mean +/- SEM) were compared by analysis of variance (ANOVA), paired t test or Fisher's Exact test. RESULTS: Endotoxic (E) rats had significantly lower VO2 than C rats from 90 minutes postinjection to the end of the experiment, 210 minutes (VO2 from 150 to 210 minutes: C 671 +/- 45; E 429 +/- 36, P <.0004; n = 8; paired t test). VO2 of CL or CG rats was elevated between 90 and 210 minutes compared with control, but significantly (P <.01) only in the L group (C 706 +/- 31; CG 871 +/- 63; CL 984 +/- 31; n = 7-9, ANOVA). VO2 was significantly higher (P <.05) in EG rats than E rats (E 460 +/- 29; EG 654 +/- 68; n = 9-10). In the EL group, VO2 was raised but was not significantly different from E (E 460 +/- 29; EL 637 +/- 52; n = 8-10). EG rats were significantly less hypothermic between 90 and 210 minutes (58 of 132 measurements) compared with E (95 of 147; P =.0007, Fisher's Exact test), whereas the EL group were similarly hypothermic (74 of 120) to E (P =.7). Sepsis score was significantly lower in the EG group than both E and EL groups (E 4.9 +/- 0.3; EG 3.6 +/- 0.3; EL 5.0 +/- 0.3; n = 40; P <.01; ANOVA). CONCLUSIONS: Neonatal endotoxaemia lowers VO2, heat production, and body temperature. Glutamine and leucine both cause nutrient-induced thermogenesis in control animals and restore VO2 of endotoxic animals. Glutamine additionally increases rectal temperature, reduces incidence of hypothermia, and improves clinical signs of endotoxic rats. This suggests that glutamine may be beneficial for nutrition in neonatal sepsis.

Animals↗
PubMed2003

Hypothermia throughout intestinal ischaemia-reperfusion injury attenuates lung neutrophil infiltration.

BACKGROUND/PURPOSE: Secondary organ damage to the lungs is an important consequence of intestinal ischaemia reperfusion (IIR) injury. Moderate hypothermia ameliorates gut necrosis and liver energy failure after IIR but potential beneficial effects on lung neutrophil infiltration after reperfusion of ischaemic bowel have not been investigated. METHODS: Adult Sprague-Dawley rats underwent 60 minutes intestinal ischaemia followed by 120 minutes of reperfusion. The animals were maintained at either normothermia (36 degrees to 38 degrees C) or moderate hypothermia (30 degrees to 32 degrees C). Four groups were studied: (A) sham normothermia; (B) IIR normothermia; (C) sham hypothermia; and (D) IIR hypothermia. Lungs and terminal ileum were removed for measurement of myeloperoxidase activity (a marker of neutrophil infiltration). Results are expressed as milliunits per milligrams protein, mean +/- SEM, and one-way analysis of variance (ANOVA) with Tukey post-test was used for group comparisons. RESULTS: Lungs: IIR at normothermia significantly increased lung neutrophil infiltration assessed by myeloperoxidase activity compared with sham-operated controls (normothermia sham 4.6 +/- 1.0, n = 8; normothermia IIR 37.7 +/- 13.8, n = 8; P =.011). Moderate hypothermia during IIR significantly attenuated lung neutrophil infiltration (7.2 +/- 2.1, n = 9) compared with normothermia IIR (P =.016) such that myeloperoxidase activity was similar to that found in sham normothermia (4.6 +/- 1.0, n = 8) and sham hypothermia (3.1 +/- 1.3, n = 8). Intestine: Gut myeloperoxidase activity was 0.9 +/- 0.5 in sham normothermia (n = 9) and 2.3 +/- 0.6 after normothermic IIR (n = 8). After IIR at hypothermia gut myeloperoxidase activity (0.5 +/- 0.2; n = 8) was significantly less than normothermic IIR (P =.035) and higher than sham hypothermia (0.2 +/- 0.1, n = 9; P =.01). CONCLUSIONS: These results indicate that moderate hypothermia may prevent damage to another distant organ, ie the lungs, by preventing recruitment of neutrophils. This may be of benefit in decreasing distal organ damage in diseases in which intestinal ischaemia-reperfusion is implicated in the pathogenesis.

Animals↗
PubMed2003

Carbon dioxide elimination during laparoscopy in children is age dependent.

UNLABELLED: The absorption of carbon dioxide (CO2) used for positive pressure pneumoperitoneum may lead to an increased CO2 load. CO2 elimination during laparoscopy has not been investigated previously in paediatrics. The aim of this study was to characterise the pattern of CO2 elimination during laparoscopic surgery in infants and children. METHODS: Twenty children undergoing laparoscopy and 19 children undergoing laparotomy for elective abdominal operations were studied. Pneumoperitoneum was achieved using insufflation of unheated CO2. CO2 elimination (metabolically produced + absorbed; milliliters per kilogram per minute) was measured minute by minute during the operation by indirect calorimetry. End-tidal CO2 (kPa) was recorded every 10 minutes. The above variables were assessed before CO2 insufflation, during pneumoperitoneum, and after desufflation. RESULTS: Before insufflation, CO2 elimination was 4.6 +/- 0.3 ml/kg/min and increased after 15 minutes of pneumoperitoneum to 5.2 +/- 0.3 (P <.001). Post desufflation, CO2 elimination decreased toward preinsufflation values, but did not return to baseline by the end of operation (5.8 +/- 0.3; P <.001). End-tidal CO2 was 4.7 +/- 0.2 preinsufflation, peaked at 1 hour (5.3 +/- 0.2; P <.001) and subsequently decreased in response to ventilatory adjustments. The total amount of CO2 insufflated was positively correlated with patient age (r2 = 0.27; P <.01). CO2 elimination was age related, as indicated by multilevel model analysis and by negative correlations between maximum increase in CO2 elimination and both age (r2 = 0.27; P <.01) and weight (r2 = 0.29; P <.01). These data suggest that the younger or smaller the child, the larger the increase in CO2 elimination. Seven patients (35%) responded to desufflation with a sharp transient increase in CO2 elimination, which did not appear to be related to patient age, length of pneumoperitoneum, abdominal pressure, or type of operation. CONCLUSIONS: During pneumoperitoneum, younger children absorb proportionately more CO2 than older individuals. The short-lived increase in CO2 elimination postdesufflation may be related to an increase in venous return from the lower limbs after release of the abdominal pressure. These findings suggest that small children warrant close monitoring during laparoscopy and during the immediate postoperative period.

Adolescent↗
PubMed2003

Impaired energy metabolism during neonatal sepsis: the effects of glutamine.

Neonatal sepsis is an important cause of morbidity and mortality as a result of multiple organ system failure, particularly in neonates requiring total parenteral nutrition. Suitable therapies and support are needed both to prevent sepsis and to prevent multiple organ failure. After bacterial infection, pro-inflammatory cytokines trigger the antimicrobial activity of macrophages and neutrophils, resulting in production of reactive species such as H2O2, NO, superoxide and peroxynitrite. However, excess production can lead to host tissue damage. Incubation of either hepatocytes or heart mitochondria from neonatal rats with these reactive species, or with cytokines, leads to impairment of mitochondrial oxidative function, and in an animal model of neonatal sepsis similar results to the in vitro findings have been demonstrated. Recent in vivo studies, using indirect calorimetry of suckling rat pups, show that during endotoxaemia there is a profound hypometabolism, associated with hypothermia. Having determined that cellular oxidative function may be impaired during sepsis, it is of great importance to try to identify therapeutic measures. Much interest has been shown in glutamine, which may become essential during sepsis. It has been shown that hepatic glutamine is rapidly depleted during endotoxaemia. When hepatocytes from endotoxaemic rats were incubated with glutamine, there was a restoration of mitochondrial structure and metabolism. In vivo, intraperitoneal injection of glutamine into endotoxic suckling rats partially reversed hypometabolism, markedly reduced the incidence of hypothermia and improved clinical status. These results suggest that glutamine has a beneficial effect during sepsis in neonates.

Animals↗
PubMed2002

Control of mitochondrial beta-oxidation flux.

The control of mitochondrial beta-oxidation, including the delivery of acyl moieties from the plasma membrane to the mitochondrion, is reviewed. Control of beta-oxidation flux appears to be largely at the level of entry of acyl groups to mitochondria, but is also dependent on substrate supply. CPTI has much of the control of hepatic beta-oxidation flux, and probably exerts high control in intact muscle because of the high concentration of malonyl-CoA in vivo. beta-Oxidation flux can also be controlled by the redox state of NAD/NADH and ETF/ETFH(2). Control by [acetyl-CoA]/[CoASH] may also be significant, but it is probably via export of acyl groups by carnitine acylcarnitine translocase and CPT II rather than via accumulation of 3-ketoacyl-CoA esters. The sharing of control between CPTI and other enzymes allows for flexible regulation of metabolism and the ability to rapidly adapt beta-oxidation flux to differing requirements in different tissues.

Acyl Coenzyme A↗
PubMed2002

Hepatic glutamine metabolism during endotoxemia in neonatal rats.

OBJECTIVES: The liver plays a central role during endotoxemia. We investigated the biochemical changes that occur in neonatal liver during early stages of endotoxemia. METHODS: Twenty neonatal rats (10 to 15 d; n = 10/group) were studied. Endotoxemic rats received intraperitoneal injections of 300 microg/kg of 12.5 mg/L of lipopolysaccharide and control rats received isovolemic normal saline. Two hours after injection, all lipopolysaccharide-injected animals exhibited signs of endotoxemia. Livers were removed and extracted into 12% perchloric acid. 1H and 31P magnetic resonance spectroscopy measured hepatic levels of glutamine, glutamate, alanine, lactate, glucose, beta-hydroxybutyrate, adenosine triphosphate, and adenosine diphosphate. Unpaired t test compared groups. RESULTS: No mortality occurred during the first 2 h after injection. Endotoxemia significantly decreased hepatic levels of glutamine (P < 0.001), glucose (P = 0.047), and beta-hydroxybutyrate (P < 0.001). There was no difference in hepatic levels of glutamate (P = 0.050), alanine (P = 0.165), lactate (P = 0.478), adenosine triphosphate (P = 0.165), and adenosine diphosphate (P = 0.136) between groups. CONCLUSIONS: Early endotoxemia caused significant changes in the hepatic metabolism of glutamine, glucose, and beta-hydroxybutyrate. These findings increase our understanding of the pathophysiology of neonatal endotoxemia.

Animals↗
PubMed2002

Fatty acid oxidation in neonatal hepatocytes: effects of sepsis and glutamine.

OBJECTIVE: Little is known about fat use during sepsis during the neonatal period. Intramitochondrial O(2) consumption is inhibited in isolated hepatocytes from suckling septic rats and this impairment is reversed by glutamine. We investigated the effect of neonatal sepsis on fat oxidation and whether glutamine can directly affect fatty acid oxidation. METHODS: Suckling Wistar rats (11 d) received an intraperitoneal injection of 300 microg/kg of lipopolysaccharide (Escherichia coli 055:B5); controls received normal saline. At 2 h, hepatocytes were isolated. Hepatocytes were incubated at 37 degrees C with 0.5 mM [1-(14)C]palmitate or 0.5 mM [1-(14)C]palmitate plus 10 mM glutamine. After 1 h, the perchloric acid-soluble (14)C-radioactivity (representing mainly ketone bodies) and (14)CO(2) were measured. Hepatocyte O(2) consumption from 0.5 mM palmitate was measured with and without 2.5 ng/mL myxothiazol to estimate intramitochondrial O(2) consumption. RESULTS: There were no significant differences in fatty acid oxidation between control and endotoxemic hepatocytes measured as acid-soluble radioactivity (which represents mainly ketogenesis, plus Krebs cycle intermediates), as (14)CO(2) production, or as the sum of acid-soluble radioactivity plus (14)CO(2) generation. Glutamine significantly increased fatty acid oxidation (acid-soluble radioactivity plus (14)CO(2)) in hepatocytes from control and endotoxic animals. CONCLUSIONS: The finding of no significant difference in fatty acid oxidation between hepatocytes from control and endotoxemic rats is surprising given that intramitochondrial O(2) consumption from palmitate is decreased. This may reflect altered use of acetyl-coenzyme A to ketone bodies and Krebs cycle intermediates. Glutamine enhanced fatty acid oxidation from control and endotoxemic hepatocytes, suggesting that it may promote substrate oxidation during endotoxemia.

Animals↗
PubMed2002

Differential effects of neonatal endotoxemia on heart and kidney carnitine palmitoyl transferase I.

BACKGROUND/PURPOSE: The heart and kidney are both affected in sepsis-related multiple organ failure. Both utilize fatty acid substrates during the neonatal period, and impairment of oxidative metabolism during sepsis could lead to bioenergetic failure. The enzyme carnitine palmitoyl transferase I (CPT I) is important in the control of fat oxidation in the neonatal period. The aim of this study was to determine the effects of sepsis on neonatal cardiac and renal CPT I. METHODS: Suckling rats received 300 microgram/kg lipopolysaccharide intraperitoneally. Mitochondria were isolated from the heart and kidney after 2 hours. CPT I and II activity were measured radiochemically. Protein levels of M- and L- isoforms of CPT I, both of which are present in heart, were determined by Western blotting. RESULTS: CPT I activity was decreased significantly in the heart but not in the kidney by endotoxemia, whereas CPT II activity was the same in each organ. To investigate the mechanism of this decrease, we carried out Western blotting of the CPT I isoforms in heart mitochondria. Neither M- nor L- isoform was decreased in amount. To determine whether free-radical attack could directly inhibit CPT I activity, control heart mitochondria were incubated with free-radical generating systems. Although hydrogen peroxide had no effect on CPT I activity, the reactive oxygen species nitric oxide, superoxide, and peroxynitrite, all of which are generated in the heart during sepsis, significantly inhibited CPT I activity. CONCLUSIONS: The activity of CPT I, a rate-controlling step of fat oxidation, is significantly impaired in heart but not in kidney during neonatal sepsis. This may be caused by direct attack by free radicals, suggesting that antioxidant strategies could be of use in preventing sepsis-related cardiac damage.

Animals↗
PubMed2002

The metabolic response to intravenous medium-chain triglycerides in infants after surgery.

OBJECTIVE: The aim of this study was to determine if administration of mixed medium-chain triglycerides (MCT)/long chain triglycerides (LCT) fat emulsion would increase net fat oxidation and if carbohydrate intake would influence net fat oxidation. STUDY DESIGN: Stable infants receiving total parenteral nutrition were studied after surgery. Respiratory gas exchange was measured by indirect calorimetry and urinary nitrogen excretion by the micro-Kjeldahl method. Intravenous fat (4 g/kg/day) was given as either pure LCT fat emulsion or 50/50 MCT/LCT fat emulsion. Carbohydrate intake was either "high" (15 g/kg/day) or "low" (10 g/kg/day). Four groups of patients were studied: group 1 = LCT and high-carbohydrate; group 2 = LCT and low-carbohydrate; group 3 = MCT/LCT and high-carbohydrate; group 4 = MCT/LCT and low-carbohydrate. RESULTS: At a carbohydrate intake of 15 g/kg/day, the calories available from glucose exceeded the measured resting energy expenditure (REE), and no differences were seen in either energy expenditure or net fat oxidation between patients receiving LCT and MCT/LCT fat emulsions. However, at a carbohydrate intake of 10 g/kg/day, when glucose calories were less than REE, net fat oxidation was significantly higher in patients receiving MCT/LCT (median, 1.94; range, 1.05-2.24 g/kg/day) compared with patients receiving LCT (median, 0.60; range, -0.09 to 1.35; P =.03). CONCLUSION: Providing that carbohydrate calories do not exceed REE, partial replacement of LCT by MCT in intravenous fat emulsions can increase net fat oxidation in infants after surgery.

Dietary Carbohydrates↗
PubMed2002

Mitochondrial fatty acid beta-oxidation in the retinal pigment epithelium.

Pigmentary retinopathy is an important feature of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, a disorder of mitochondrial fatty acid beta-oxidation. Pathogenesis of this complication remains unknown. The retinal pigment epithelium (RPE) is affected early in this retinopathy. We wanted to determine whether there is evidence of mitochondrial fatty acid beta-oxidation in the RPE cells. Fatty acid oxidation was measured from cultured porcine RPE cells by incubating them with [U-13C]-hexadecanoic acid. Acylcarnitine esters were analyzed by tandem mass spectrometry. The activity of LCHAD and carnitine uptake capacity were measured from the cultured cells. Antibodies to the human mitochondrial trifunctional protein (MTP) containing LCHAD activity were used to analyze the expression of the MTP in the cultured RPE cell lysate and in human retinal sections by immunoblotting and immunohistochemistry. Fatty acid oxidation analysis showed normal chain shortening of hexadecanoic acid and production of acetylcarnitine in cultured RPE cells. Immunoblotting revealed expression of the MTP and enzyme assay showed the activity of LCHAD in the RPE cells. RPE cells were also capable of carnitine uptake. Positive labeling to the MTP antibodies was detected in the RPE, photoreceptors, and ganglion cells. The results give strong in vitro evidence for the presence of mitochondrial fatty acid beta-oxidation in RPE cells and the expression of the MTP in the RPE and other layers of the retina. Further studies are required to clarify whether this pathway acts also in vivo in the retina.

Animals↗