PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “FATTY ACID METABOLISM”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23Linked to original sources
PubMed2006

A Mediator subunit, MDT-15, integrates regulation of fatty acid metabolism by NHR-49-dependent and -independent pathways in C. elegans.

The Caenorhabditis elegans Nuclear Hormone Receptor NHR-49 coordinates expression of fatty acid (FA) metabolic genes during periods of feeding and in response to fasting. Here we report the identification of MDT-15, a subunit of the C. elegans Mediator complex, as an NHR-49-interacting protein and transcriptional coactivator. Knockdown of mdt-15 by RNA interference (RNAi) prevented fasting-induced mRNA accumulation of NHR-49 targets in vivo, and fasting-independent expression of other NHR-49 target genes, including two FA-Delta9-desaturases (fat-5, fat-7). Interestingly, mdt-15 RNAi affected additional FA-metabolism genes (including the third FA-Delta9-desaturase, fat-6) that are regulated independently of NHR-49, suggesting that distinct unidentified regulatory factors also recruit MDT-15 to selectively modulate metabolic gene expression. The deregulation of FA-Delta9-desaturases by knockdown of mdt-15 correlated with dramatically decreased levels of unsaturated FAs and multiple deleterious phenotypes (short life span, sterility, uncoordinated locomotion, and morphological defects). Importantly, dietary addition of specific polyunsaturated FAs partially suppressed these pleiotropic phenotypes. Thus, failure to properly govern FA-Delta9-desaturation contributed to decreased nematode viability. Our findings imply that a single subunit of the Mediator complex, MDT-15, integrates the activities of several distinct regulatory factors to coordinate metabolic and hormonal regulation of FA metabolism.

Animals↗
PubMed1995

Protein-energy malnutrition during gestation and lactation in rats affects growth rate, brain development and essential fatty acid metabolism.

The influence of feeding a low protein diet to rat dams during gestation and lactation on lipid metabolism in pups was studied. Wistar rats were fed 5, 10, 15 and 25% dietary protein during gestation and lactation. Pup growth was monitored until weaning, and brain weight, protein concentration, proteolipid concentration and total lipid phosphorus concentration of brain were analyzed. The levels of fatty acids in dam milk as well as in pup liver phospholipids and brain prosphatidylcholine and phosphatidylethanolamine were determined. The progressive deprivation of maternal dietary protein produced a reduction in the total saturated fatty acid concentration of dam milk and an increment in the concentration of nonmetabolized linoleic acid. Pup body and brain weights as well as proteolipid, protein and total lipid phosphorus concentrations in brain were reduced in proportion to the degree of dietary protein deficiency. The products:precursor ratio of (n-6) fatty acids in liver phospholipids revealed an impairment in the elongation-desaturation pathway due to maternal protein deficiency. Both (n-6) and (n-3) polyunsaturated fatty acids within brain phosphatidylethanolamine were decreased by reduced maternal dietary protein intake, whereas only the linoleic acid-derived products were similarly affected in the corresponding phosphatidylcholine fraction. These results demonstrate the widespread and profound deleterious effects of low protein levels of maternal diet on the growth rate, brain development and fatty acid metabolism in rat pups.

Analysis of Variance↗
PubMed1991

Fatty acid metabolism and contractile function in the reperfused myocardium. Multinuclear NMR studies of isolated rabbit hearts.

The hypothesis that substrate availability can alter contractile function in reperfused myocardium after global ischemia was investigated in this study. Isolated rabbit hearts were placed in a dual tuned (31P/13C) NMR probe with a 9.4-T magnet and perfused with the following substrates given individually or in combination: 10 mM glucose, 2 mM palmitate, and 2.5 mM [3-13C]pyruvate. Glucose was the sole substrate present for all groups of hearts before the onset of 10 or 20 minutes of zero-flow ischemia. Contractility (dP/dt) was significantly higher in hearts reperfused with glucose compared with hearts reperfused with palmitate or the combination. In addition, myocardial oxygen consumption/unit of work at reperfusion was more efficient with glucose than with palmitate. ATP content during reperfusion was similar with glucose and palmitate and did not account for improved function with glucose. To determine if inhibition of pyruvate metabolism by palmitate might result in altered postischemic function, additional hearts were reperfused with 2.5 mM [3-13C]pyruvate provided alone or in combination with palmitate. Using 13C NMR spectroscopy, it was shown that with the addition of palmitate, pyruvate oxidation was decreased in control and 10-minute ischemic hearts as is consistent with inhibition of pyruvate dehydrogenase by fatty acids. However, palmitate/pyruvate did not worsen postischemic function as compared with palmitate or pyruvate alone. Tricarboxylic acid cycle activity was slowed in reperfused pyruvate hearts, but no further reduction was observed when palmitate was present. In conclusion, palmitate reduces the mechanical function of the reperfused isolated rabbit heart as compared with glucose. This effect of palmitate does not appear to be caused by suppression of pyruvate oxidation or by a change in high energy phosphate content.

Animals↗
PubMed1979

In vitro lipid metabolism in the rat pancreas. II. Effects of secretagogues on fatty acid metabolism, net lipolysis and ATP levels.

1. The concentration of carbamylcholine, bombesin, pancreozymin, pentagastrin and secretin evoking a similar 4--5-fold maximal increase in amylase secretion from rat pancreatic fragments were 3.10(-6), 10(-7), 10(-8), 3.10(-6), and 3.10(-6) M, respectively. The maximal concentration of vasoactive intestinal peptide tested (3.10(-6) M) increased amylase secretion by 250%. The six secretagogues could be separated into two groups according to their effects on lipid metabolism and ATP levels. 2. When used at their optimal concentrations, carbamylcholine, bombesin, pancreozymin, and pentagastrin lowered pancreatic ATP levels by 18-26% and increased net release of free fatty acids by 68-105%. 3. The effects of 3.10(-6) M carbamylcholine and 10(-8) M pancreozymin on the metabolism of 3H2O, D-[U-14C]glucose and [1-14C]acetate were similar; the incorporation of radioactivity in the fatty acid moiety of glycerolipids decreased by 20--50% whereas the incorporation of 3H from 3H2O and of 14C from [U-14C]glucose increased by 20--35% in the glycerol moiety. In addition, the oxidation of [U-14C]glucose, [1-14C]acetate and [1-14C]palmitate to 14CO2 increased by 15--32% while the esterification of [1-14C]palmitate, [1-14C]-linoleate, and [1-14C]arachidonate was inhibited by 14--23%. The spectrum of fatty acids labeled with [1-14C]acetate indicated an inhibition of the malonic acid pathway whereas the elongation of polyenoic fatty acids was unaltered.

Acetyl Coenzyme A↗
PubMed1991

Regulation of fatty acid metabolism and gluconeogenesis by growth hormone and insulin in sheep hepatocyte cultures. Effects of lactation and pregnancy.

Primary monolayer hepatocyte cultures derived from non-mated, pregnant and lactating sheep were used to investigate the interactions between the effects of growth hormone and insulin on (i) the partitioning of fatty acid metabolism between oxidation and esterification, and (ii) the rate of gluconeogenesis. In hepatocytes from lactating sheep the rates of gluconeogenesis, ketogenesis and very-low-density lipoprotein secretion were approx. 2-fold higher than in cells from non-mated or pregnant animals. There was no apparent difference in the rates of fatty acid uptake between the three groups of sheep cells. Growth hormone stimulated gluconeogenesis only in hepatocytes from non-mated sheep. It has no effect on the flux of fatty acid towards ketone body formation. Growth hormone inhibited intracellular accumulation of acylglycerol from exogenous fatty acid. Insulin alone had no such effect, but it blunted the effect of growth hormone when the two hormones were present together. The data suggest that major differences may exist between ruminants and non-ruminants in the response of liver metabolism both to lactation per se and to the effects of growth hormone and insulin.

Animals↗
PubMed1993

Cholesterol and fatty acid metabolism in piglets fed sow milk or infant formula with or without addition of cholesterol.

Several studies have reported that plasma cholesterol and phospholipid (PL) levels of arachidonic acid (20:4n-6) are lower and PL levels of linoleic acid (18:2n-6) are higher in infants fed formula than in infants fed human milk. Plasma cholesterol level and possibly the dietary intake of cholesterol could be related to plasma PLn-6 fatty acid metabolism because plasma PL 18:2n-6 is used for esterification of plasma free cholesterol. Whether the low cholesterol content of infant formula as compared with human milk is related to the difference in plasma n-6 fatty acid levels between infants fed human milk and infants fed formula is not known. This study determined the effect of feeding formula with 0.05 mmol cholesterol/L, formula with 1.09 mmol cholesterol/L, or sow milk with 0.34 mmol cholesterol/L on plasma, liver, and bile lipid fatty acid levels and liver low-density lipoprotein (LDL) receptor mass in piglets. Liver microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity and plasma lathosterol were assayed as indices of liver and body cholesterol synthesis, respectively. Formula with or without cholesterol added, or sow milk, was fed from birth to 18 days of age. Providing cholesterol in the formula did not correct the significantly lower plasma cholesterol or plasma and liver PL 20:4n-6 levels associated with formula feeding. The liver total cholesterol and cholesteryl esters (CE), biliary bile acid, and PL concentrations were significantly higher and the liver HMG CoA reductase activity and plasma lathosterol:cholesterol ratio were significantly lower in piglets fed the formula with cholesterol than in piglets fed the formula without cholesterol added.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Human placenta metabolizes fatty acids: implications for fetal fatty acid oxidation disorders and maternal liver diseases.

The role of fat metabolism during human pregnancy and in placental growth and function is poorly understood. Mitochondrial fatty acid oxidation disorders in an affected fetus are associated with maternal diseases of pregnancy, including preeclampsia, acute fatty liver of pregnancy, and the hemolysis, elevated liver enzymes, and low platelets syndrome called HELLP. We have investigated the developmental expression and activity of six fatty acid beta-oxidation enzymes at various gestational-age human placentas. Placental specimens exhibited abundant expression of all six enzymes, as assessed by immunohistochemical and immunoblot analyses, with greater staining in syncytiotrophoblasts compared with other placental cell types. beta-Oxidation enzyme activities in placental tissues were higher early in gestation and lower near term. Trophoblast cells in culture oxidized tritium-labeled palmitate and myristate in substantial amounts, indicating that the human placenta utilizes fatty acids as a significant metabolic fuel. Thus human placenta derives energy from fatty acid oxidation, providing a potential explanation for the association of fetal fatty acid oxidation disorders with maternal liver diseases in pregnancy.

Adult↗
PubMed1991

Recurrent acute encephalopathy due to fatty acid metabolic defect--report of two cases.

An increasing number of reports indicate that patients with some inherited metabolic diseases may have symptoms resembling those of Reye's syndrome. We describe 2 patients who developed Reye-like syndrome at the age of 7 months respectively. Conscious disturbance, hepatomegaly, impaired liver function, hyperammonemia, and nonketotic hypoglycemia were noted during acute episode. Blood lactate level was normal in both cases. Liver and muscle biopsy of both patients showed macrovesicular fatty change. Increased density of matrix in hepatocyte mitochondria was noted in patient 1. Stacking of cristae was shown in patient 2. The first patient had another episode of hyperammonemia at 2 years of age. The second patient was admitted three more times due to recurrent vomiting and conscious change at the age of 7 months, 10 months and 13 months respectively. Fatty acid metabolic defect should be considered in children or infants with recurrent Reye-like syndrome.

Acute Disease↗
PubMed2005

Acute valproate poisoning: pharmacokinetics, alteration in fatty acid metabolism, and changes during therapy.

The clinical features, complications, and pharmacokinetics of intentional acute valproic acid (VPA) overdoses are described. Alteration in fatty acid metabolism is evaluated and therapy-induced changes are discussed. Central nervous system features were the predominant clinical manifestations (6/6), followed by respiratory failure (5/6) and multiorgan failure (2/6). Mechanical ventilation was required in 5 of 6 patients because of respiratory depression or deep coma. Hemodialysis was applied in 4/6 of the cases due to hyperammonemia, worsening neurologic condition, or organ dysfunction. Cerebral edema and hemorrhagic pancreatitis ensued in 2/6 of the patients and ICU mortality was 2/6. VPA peak levels ranged from 520 to 1700 mg/L with a mean of 1127 mg/L. Ammonia was elevated in all cases with a mean of 550 microg/dL. All patients showed signs of impaired mitochondrial beta-oxidation with increase of medium- and long-chain acylcarnitines in serum. Severe VPA overdose is associated with a high mortality rate requiring early medical interventions. Beside supportive intensive care, hemodialysis can be considered as an adjunctive measure.

Anticonvulsants↗
PubMed2005

Changes in expression levels of genes involved in fatty acid metabolism: upregulation of all three members of the PPAR family (alpha, gamma, delta) and the newly described adiponectin receptor 2, but not adiponectin receptor 1 during neonatal cardiac development of the rat.

UNLABELLED: During neonatal cardiac development, the heart changes its substrate preference from glucose to fatty acids. The aim of this study was to investigate the changes in mRNA expression levels of genes involved in the control of cardiac fatty acid metabolism in the transition from neonatal to adult life. METHODS: mRNA expression levels for peroxisome proliferator activated receptor (PPAR) alpha, gamma and delta, PPARgamma co-factor 1 alpha and beta (PGC-1 alpha and beta), 9-cis retinoc-acid-activated receptor alpha, beta and gamma (RXR alpha, beta, gamma), 5'-AMP activated protein kinase (AMPK) alpha1 and alpha2, adiponectin receptor 1 and 2 (AR 1 and AR 2) were measured in heart tissue of neonatal 0-day, 7-day and 21- day old rats. RESULTS: mRNA expression of all three members of the PPAR family were upregulated significantly from day 0 to day 21 (alpha +117%, gamma +133%, delta +203%). In addition, m-RNA expression of all RXR isoforms increased from day 0 to day 7 (alpha +125%, beta +69%; gamma +41%). AR 2 exhibited a small but significant increase in mRNA expression (+ 46%). CONCLUSIONS: We were able to demonstrate for the first time that in addition to PPARalpha, also PPARgamma and delta, as well as all RXR isoforms and AR 2 are upregulated in the heart during neonatal development.

Animals↗
PubMed1997

Effect of endurance training on fatty acid metabolism: local adaptations.

Older studies of humans seem to suggest a correlation between free fatty acid (FFA) turnover and oxidation on the one hand and plasma FFA concentration on the other hand during submaximal exercise. However, recent studies, in which higher concentrations of plasma FFA have been reached during prolonged submaximal exercise, have revealed a levelling off in net uptake in spite of increasing plasma FFA concentrations. Furthermore, this relationship between FFA concentration and FFA uptake and oxidation is altered by endurance training. These recent findings in humans support the notion from other cell types that transmembrane fatty acid transport is not only by simple diffusion, but predominantly carrier-mediated. During prolonged submaximal knee-extension exercise it has been demonstrated that the total oxidation of fatty acids was approximately 60% higher in trained subjects than in nontrained subjects. The training-induced adaptations responsible for this increased utilization of plasma fatty acids by the muscle could be located at several steps from the mobilization of fatty acids to skeletal muscle metabolism in the mitochondria. In this paper regulation at the transport steps and also at various metabolic steps is discussed.

Biological Transport↗
PubMed1999

Muscle contractile activity increases fatty acid metabolism and transport and FAT/CD36.

We have examined whether 1) fatty acid (FA) uptake, 2) FA transporter expression, and 3) FA metabolism are increased when the oxidative capacity of skeletal muscle is increased. The oxidative capacities of red and white tibialis anterior and extensor digitorum longus muscles were increased via chronic stimulation (10 Hz, 24 h/day for 7 days). The contralateral muscles served as controls. After 7 days of increased muscle activity 1) palmitate uptake by giant sarcolemmal vesicles was increased twofold (P < 0.05), 2) the expression of FA translocase (FAT)/CD36 was increased at both the mRNA (3.2- to 10-fold) and protein (3.4-fold) levels, and 3) palmitate oxidation and esterification into triacylglycerols and phospholipids were increased 1.5-, 2.7-, and 1.7-fold, respectively (P < 0.05). These data show that when the oxidative capacity of muscle is increased, there is a parallel increase in the rate of FA transport and FA transporters at the sarcolemmal membrane, which is associated with the enhanced expression of the membrane transporter FAT/CD36.

Animals↗
PubMed2006

Randomly interesterified triacylglycerol containing medium- and long-chain fatty acids stimulates fatty acid metabolism in white adipose tissue of rats.

We have reported previously that randomly interesterified triacylglycerol containing medium- and long-chain fatty acids in the same glycerol molecule (MLCT) resulted in significantly lower body fat accumulation and higher hepatic fatty acid oxidation than from long-chain triacylglycerol (LCT) in rats. To understand the metabolic changes occurring in white adipose tissue, the fatty acid oxidation and synthesis, and the adipocytokine level were measured in rats fed with MLCT or LCT for 2 weeks. In comparison with LCT, MLCT lowered not only the fatty acid synthase and glycerol-3-phosphate dehydrogenase activities in perirenal adipose tissue, but also the serum insulin and leptin levels, in addition to significantly reducing the body fat accumulation. In contrast, fatty acid oxidation measured as the carnitine palmitoyltransferase activity in the tissue was significantly higher in the MLCT-fed rats than in the LCT-fed rats. It seems that the altered fatty acid metabolism in adipose tissue per se was also responsible for the lower adiposity by dietary MLCT.

Adipose Tissue, White↗
PubMed2006

Modulation of fatty acid metabolism as a potential approach to the treatment of obesity and the metabolic syndrome.

Increased de novo lipogenesis and reduced fatty acid oxidation are probable contributors to adipose accretion in obesity. Moreover, these perturbations have a role in leading to non-alcoholic steatohepatitis, dyslipidemia, and insulin resistance--via "lipotoxicity"-related mechanisms. Research in this area has prompted an effort to evaluate several discrete enzymes in these pathways as targets for future therapeutic intervention. Acetyl-CoA carboxylase 1 (ACC1) and ACC2 regulate fatty acid synthesis and indirectly control fatty acid oxidation via a key product, malonyl CoA. Based on mouse genetic and preclinical pharmacologic evidence, inhibition of ACC1 and/or ACC2 may be a useful approach to treat obesity and metabolic syndrome. Similarly, available data suggest that inhibition of other enzymes in this pathway, including fatty acid synthase, stearoyl CoA desaturase, and diacylglycerol acytransferase 1, will have beneficial effects. AMP-activated protein kinase is a master regulator of nutrient metabolism, which controls several aspects of lipid metabolism. Activation of AMPK in selected tissues is also a potential therapeutic approach. Inhibition of hormone-sensitive lipase is another possible approach. The rationale for modulating the activity of these enzymes and their relative merits (and downsides) as possible therapeutic targets are further discussed.

AMP-Activated Protein Kinases↗
PubMed1992

Assessment of iodohexadecenoic acid as a tracer of fatty acid metabolism by external detection: a study on isolated rat heart.

Labelled fatty acids have been proposed to explore cardiac metabolism. For the analysis of the external detection curve obtained with 16-iodo 9-hexadecenoic acid (IHA), we developed a mathematical 4-compartment model with compartments 0, 1, 2 and 3 representing vascular IHA, intracellular IHA, esterified forms and iodide, respectively. This model, used here for isolated rat hearts perfused in a recirculating system, is validated by an intracellular analysis, then tested in various metabolic conditions. Thus, the mathematical analysis of the external detection curve gives us numerical data on IHA metabolism, especially the distribution between degradation and storage. Our results confirm the suitability of IHA for assessing myocardial metabolism.

Animals↗