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 505 records · Page 28Linked to original sources
PubMed1975

Application of tracers in studying free fatty acid metabolism of various organs in vivo.

A few selected examples are given of the application of radio-labeled fatty acids in studying substrate utilization under in vivo conditions. The flux of free fatty acids (FFA) may be calculated by the constant infusion technique of Armstrong et al. using either labeled palmitic or oleic acid. Utilization of FFA by the myocardium is conveniently studied by the constant infusion of 14C-labeled palmitate or oleate. The extraction ratio of these two fatty acids is very similar both in the case of myocardium and of several other tissues investigated. Using this technique not only the removal and oxidation of FFA may be calculated but also competition between the major substrates (FFA, lactate, ketone bodies) can be studied. Arterial FFA concentration, rate of coronary blood flow, and myocardial work are mentioned as some of the important factors influencing the rate of myocardial FFA utilization. The study of skeletal muscle metabolism employing labeled fatty acids is of great importance since release as well as uptake of FFA takes place across most muscle beds and thus net arteriovenous differences may be misleading. A somewhat similar situation also exists in the splanchnic region. Labeled fatty acids have also been utilized to investigate both the oxidation of FFA and their incorporation into brain lipids. Both the uptake and release of FFA may be followed in the adipose tissue by the use of labeled palmitate or oleate.

Adipose Tissue↗
PubMed1984

Influence of beta-hydroxybutyrate infusion on glucose and free fatty acid metabolism in dogs.

We have investigated the effect of infusion of DL-beta-hydroxybutyrate (BOHB) (30 mumol X kg-1 X min-1) on glucose and free fatty acid (FFA) metabolism by means of the primed constant infusion of [U-14C]glucose and [1,2-13C]palmitic acid. The role of the hormonal response to the ketone infusion was assessed by controlling the hormone levels pharmacologically. In one group hormones were not controlled, while in the other two groups insulin and glucagon were maintained at constant levels by infusion of somatostatin, insulin, and glucagon at constant rates. In one of these hormonally controlled groups, combined alpha- and beta-adrenergic blockade was also employed. BOHB infusion increased total ketone concentration approximately 10-fold and, when hormones were not controlled, induced a significant increase in glucagon concentration. Regardless of hormonal status, elevation of the ketone levels decreased the rate of glucose production and FFA appearance. Glucose oxidation decreased in proportion to the reduction in the rate of glucose uptake in all groups. When sympathetic activity was not blocked an increase in the percent of FFA uptake oxidized enabled the percent CO2 production from FFA oxidation to remain constant despite the decrease in FFA uptake. However, when sympathetic activity was blocked the increase in the percent of FFA uptake oxidized observed in the other groups was prevented. We conclude from these studies that an elevation in ketone levels directly affects glucose and FFA metabolism independent of changes in insulin and glucagon levels and sympathetic activity.

3-Hydroxybutyric Acid↗
PubMed1984

Effect of 4-(4'-chlorobenzyloxy)benzyl nicotinate (KCD-232) on triglyceride and fatty acid metabolism in rats.

The effects of KCD-232, a new hypolipidemic agent with a structure of 4-(4'-chlorobenzyloxy) benzyl nicotinate, on triglyceride (TG) and fatty acid (FA) metabolism were studied in rats. KCD-232 dose-dependently reduced both liver and serum TG levels. From in vivo and in vitro studies, the hypotriglyceridemic action of KCD-232 was shown to be based on the inhibition of hepatic TG synthesis due to both decreased FA synthesis and increased FA oxidation in the liver. Of two metabolites of KCD-232, i.e. 4-(4'-chlorobenzyloxy)benzoic acid (MII) and nicotinic acid, MII was found to be responsible for the decreased synthesis and increased oxidation of FA in the liver, the latter apparently being due to increased mitochondrial oxidation activated by MII. MII was demonstrated to form a xenobiotic TG in which one fatty acid moiety was substituted by MII and to form a thioester with CoA by rat liver microsomes. This thioester, MII-CoA, inhibited fatty acid syntheses from [14C]acetate, [14C] acetyl-CoA and [14C]malonyl-CoA in cell-free enzyme systems from rat liver both with and without an NADPH-generating system, whereas MII as such showed no effect. MII-CoA were therefore considered to be a chemical entity for the inhibition of hepatic fatty acid synthesis by KCD-232 and was suggested to inhibit fatty acid synthetase directly.

Acetates↗
PubMed1988

Abnormal myocardial fatty acid metabolism in dilated cardiomyopathy detected by iodine-123 phenylpentadecanoic acid and tomographic imaging.

The radioidinated synthetic fatty acid iodine-123 phenylpentadecanoic acid (IPPA) has proven useful in the identification of regional abnormalities of cardiac metabolism in patients with myocardial ischemia. The present study was performed to test the hypothesis that the myocardial distribution and turnover of fatty acids, assessed noninvasively with IPPA, are altered in patients with cardiomyopathy. Nine normal volunteers and 19 patients with dilated cardiomyopathy of various etiologies underwent cardiac imaging with single-photon emission computed tomography (SPECT) after intravenous injection of IPPA. Apical short-axis and basal short-axis sections were reconstructed and quantitatively analyzed for relative IPPA activity distribution and washout. Patients with congestive cardiomyopathy demonstrated significantly greater heterogeneity of IPPA uptake than normal subjects (maximal percent variation of activity 27 +/- 11 vs 18 +/- 4, p less than 0.01). They also demonstrated a more rapid percent washout rate than control subjects (24 +/- 8 vs 17 +/- 6 for the apical short-axis section, p less than 0.05; 26 +/- 7 vs 18 +/- 5 for the basal short-axis section, p less than 0.01). These abnormalities of fatty acid distribution and turnover were independent of the etiology of the cardiomyopathy. The degree of heterogeneity of IPPA uptake was significantly related to the patients' New York Heart Association functional class (r = 0.64, p less than 0.01). Thus, compared with normal myocardium, the myocardium of patients with congestive cardiomyopathy demonstrates a more heterogeneous distribution of fatty acid uptake, which parallels the clinical severity of the disease. Furthermore, patients with congestive cardiomyopathy demonstrate a more rapid myocardial clearance of the labeled fatty acid, as assessed with SPECT imaging.

Adult↗
PubMed1975

Modulation of fatty acid metabolism by glucagon in man. I. Effects in normal subjects.

This investigation was designed to examine the contribution of glucagon to the regulation of free fatty acid (FFA) metabolism in man. The acute effects of exogenous glucagon upon the concentration of plasma FFA and its metabolites: acetoacetic acid (AcAc), beta hydroxybutyric acid (BOH), and triglyceride (TG) were assessed in five normal male subjects. The threshold of response was determined by administering intravenous glucagon in a graded dose-response fashion, andassessing the magnitude of change in FFA and its metabolites. A prompt rise in FFA concentration occurred after glucagon injection, and was associated with a synchronous elevation in both AcAc and BOH concentration in plasma. The rise in FFA concentration was maximal with the glucagon dosage of 0.5 mug./kg. with no greater FFA response seen athigher hormone dosage. In contrast, the rise in plasma ketones was linearly related to thedosage of glucagon but not to the corresponding rise in FFA concentration. The behavior of plasma triglyceride concentration following glucagon challenge also contrasted with the linear rise in ketone concentration. At the lowest dosage of glucagon, TG concentration rose transiently, while at the highest two dosages the concentration of TG was reduced. The transitional dosage of hormone at which no change in TG concentration was observed was approximately 0.5 mug./kg. Comparing our in vivo data with the conclusions reached from published liver perfusion studies, it can be suggested that in the dosages employed, glucagon acutely elevates plasma FFA concentration and modulates their metabolism by augmenting conversion to AcAc and BOH while tending to reduce conversion to TG in man.

Acetoacetates↗
PubMed1980

Effect of methyl 2-hexadecynoate on hepatic fatty acid metabolism.

Normal and hepatoma bearing rats were fed a low level of methyl 2-hexadecynoate in a low fat diet for one month. The effect of the acetylenic acid on lipid metabolism as derived from mass analysis of lipid classes, fatty acids and positional monoene isomers isolated from the major lipid classes of liver and hepatoma has been assessed. Methyl 2-hexadecynoate caused a 25% decrease in body weight and the appearance of essential fatty acid deficiency symptoms within one week. Non-tumor-bearing animals contained a seven-fold increase in all neutral lipid classes, except cholesterol, while host animals did not contain fatty livers. The apparent protective effect of the host animal by the hepatoma also resulted in only marginal changes in the fatty acid and positional monoene isomers from host liver and hepatoma lipids. In contrast to host liver and hepatoma, methyl 2-hexadecynoate caused a massive accumulation of palmitate and hexadecenoates with a concomitant decrease in stearate and octadecenoates in most of the lipid classes from non-tumor-bearing animals. These changes were accompanied by a shift from the higher molecular weight triglycerides to lower molecular weights corresponding to carbon number 48. The high concentrations of hexadecenoates consisted predominantly of the delta 9 isomer. Despite the high concentrations of cis delta 9 hexadecenoate, precursor of cis delta 11 octadecenoate (vaccenate), total vaccenate levels of the five major lipid classes were lower than control values. All of these data strongly suggest that long-chain 2-ynoic acids inhibit elongation of saturated and monoene fatty acids.

Animals↗
PubMedDate not supplied

The regulation of prostaglandin biosynthesis by the manipulation of essential fatty acid metabolism.

Two of the most widely used groups of drugs in medical practice are the non-steroidal anti-inflammatory agents and the steroids. Both act by modulating the conversion of essential fatty acids to prostaglandins, leukotrienes and related substances. The actions of these drugs are therefore likely to be modified by variations in the levels of substrates, notably arachidonic acid and dihomogammalinolenic acid, available for metabolism by lipoxygenase and cyclo-oxygenase enzymes. Yet most doctors who use the drugs and many scientists who carry out research on them seem unaware of the factors which determine the concentrations of the substrate essential fatty acids. This paper reviews in detail the metabolism of essential fatty acids and the interactions between nutrient intake and subsequent metabolism which determine the concentrations of the individual fatty acids. It is concluded that the efficacy of drug therapy as far as the steroids and the non-steroidal anti-inflammatory drugs are concerned could be substantially enhanced by greater knowledge of the factors which determine the availability of substrates to the key enzymes.

Animals↗
PubMed1997

The effect of dietary lipid on polyunsaturated fatty acid metabolism in Atlantic salmon (Salmo salar) undergoing parr-smolt transformation.

The aim of this study was to measure the changes in lipid metabolism which occur during smoltification and seawater transfer in Atlantic salmon (Salmo salar). Duplicate groups of Atlantic salmon parr were fed diets containing either fish oil (FO) or a blend of linseed and rapeseed oils, vegetable oil (VO), from October (week 0) to seawater transfer in May (week 26). From May to August (weeks 26-43), all fish were fed a fish oil-containing diet. Fatty acyl desaturation and elongation activity were followed in isolated hepatocytes incubated with radioactive 18:3n-3 and 18:2n-6. Metabolism of 18:3n-3 was consistently around 5-fold greater than metabolism of 18:2n-6, and total metabolism of both substrate polyunsaturated fatty acids (PUFA) was increased in fish fed both VO and FO up to seawater transfer after which desaturation activities were reduced. Desaturation activities with both 18:3n-3 and 18:2n-6 were significantly greater in fish fed VO, compared to fish fed FO, at 22 and 26 wk. Arachidonic acid (20:4n-6; AA) in liver polar lipids (PL) of fish fed VO increased consistently from weeks 0-22 but varied after seawater transfer. In fish fed FO, AA in liver PL remained constant up to week 17 before increasing at seawater transfer and leveling off thereafter. Eicosapentaenoic acid (20:5n-3; EPA) in liver PL of fish fed VO decreased significantly from week 0-22 before rising at seawater transfer and increasing rapidly posttransfer. EPA in liver PL of fish fed FO showed a similar trend except EPA was always greater in the freshwater phase compared to fish fed VO. Docosahexaenoic acid (DHA) levels in liver PL of fish fed VO remained constant in the seawater phase before increasing following seawater transfer. In fish fed FO, DHA in liver PL increased from weeks 0-17 reducing and leveling off postseawater transfer. The levels of PGF(2 alpha) and PGF(3 alpha) were measured in isolated gill cells stimulated with calcium ionophore A23187. PGF(2 alpha) production in fish fed VO increased significantly between 0-7 wk before decreasing toward seawater transfer. After transfer, PGF(2 alpha), production increased to a peak at 35 wk. PGF(2 alpha) production in fish fed FO was not significantly altered during the trial period. The changes in PGF(3 alpha) production were broadly similar to those occurring with PGF(2 alpha), but the latter was always in excess of the former (2- to 4-fold). Plasma chloride concentrations in fish subjected to seawater challenge at 20 wk were significantly lower in fish fed VO compared to those fed FO. This study has provided new information on the changes in lipid metabolism which accompany parr-smolt transformation and suggests that diets which have a fatty acid composition more similar to that in aquatic invertebrates may be beneficial in effecting successful seawater adaptation.

Animals↗
PubMed2002

Intramuscular fatty acid metabolism in contracting and non-contracting human skeletal muscle.

The present study was undertaken to investigate the fate of blood-borne non-esterified fatty acids (NEFA) entering contracting and non-contracting knee extensor muscles of healthy young individuals. [U-(13)C]-palmitate was infused into a forearm vein during 5 h of one-legged knee extensor exercise at 40 % of maximal work capacity and the NEFA kinetics, oxidation and rate of incorporation into intramuscular triacylglycerol (mTAG) were determined for the exercising and the non-exercising legs. During 4 h of one-legged knee extensor exercise, mTAG content decreased by 30 % (P < 0.05) in the contracting muscle, whereas it was unchanged in the non-contracting muscle. The uptake of plasma NEFA, as well as the proportion directed towards oxidation, was higher in the exercising compared to the non-exercising leg, whereas the rate of palmitate incorporation into mTAG was fourfold lower (0.70 +/- 0.14 vs. 0.17 +/- 0.04 micromol (g dry wt)(-1) h(-1); P < 0.05), resulting in fractional synthesis rates of 1.0 +/- 0.2 and 3.8 +/- 0.9 % h(-1) (P < 0.01) for the contracting and non-contracting muscle, respectively. These findings demonstrate that mTAG in human skeletal muscle is continuously synthesised and degraded and that the metabolic fate of plasma NEFA entering the muscle is influenced by muscle contraction, so that a higher proportion is directed towards oxidation at the expense of storage in mTAG.

Adult↗
PubMed2005

Cardiac fatty acid metabolism is preserved in the compensated hypertrophic rat heart.

Cardiac hypertrophy and failure are associated with alterations in cardiac substrate metabolism. It remains to be established, however, whether genomically driven changes in cardiac glucose and fatty acid (FA) metabolism represent a key event of the hypertrophic remodeling process. Accordingly, we investigated metabolic gene expression and substrate metabolism during compensatory hypertrophy, in relation to other cardiac remodeling processes. Thereto, cardiac hypertrophy was induced in rats by supra-renal aortic constriction to various degrees, resulting in increased heart/body weight ratios of 22% (Aob-1), 24% (Aob-2) and 32% (Aob-3) (p < 0.005) after 4 weeks. The unaltered ejection fraction in all groups indicated that the hypertrophy was still compensatory in nature. beta-Myosin Heavy Chain protein and ANF mRNA levels were increased in all groups. Only in Aob-3 rats were SERCA2a mRNA levels markedly reduced. In this group, glycolytic capacity was modestly elevated (+ 25%; p < 0.01). Notwithstanding these phenotypical changes, the expression of genes involved in FA metabolism and FA oxidation rate in cardiac homogenates was completely preserved, irrespective of the degree of hypertrophy. These findings indicate that cardiac FA oxidative capacity is preserved during compensatory hypertrophy, and that a decline in metabolic gene expression does not represent a hallmark of the development of hypertrophy.

Animals↗
PubMed2003

Red blood cell membrane essential fatty acid metabolism in early psychotic patients following antipsychotic drug treatment.

A role of indices of oxidative stress, oxidative injury, and abnormal membrane phospholipid, specifically the phospholipid essential polyunsaturated fatty acids (EPUFAs) metabolism has been suggested based on studies in separate groups of patients with or without medication. The current study investigated the relationship between these biochemical measures in first-episode psychotic patients (N=16) at baseline and after 6 months of antipsychotic treatment (N=5 each with risperidone and olanzapine) and compared them to matched normal subjects. The indices of oxidative stress included: antioxidant enzymes; superoxide dismutase, glutathione peroxidase and catalase; and the oxidative injury as the levels of plasma lipid peroxides. The key membrane EPUFA's been; linolenic acid, arachidonic acid, nervonic acid, docosapentaenoic acid and docosahexaenoic acid. Furthermore, the changes in these biochemical measures were correlated with clinical symptomatology. Data indicated that, at baseline, reduced levels of antioxidant enzymes were associated with increased plasma lipid peroxides and reduced membrane EPUFAs, particularly omega-3 fatty acids. Furthermore, these biochemical measures normalized after 6 months of antipsychotic treatment. Parallel-improved psychopathology indicated that membrane EPUFA status might be partly affected by oxidative damage, which together may contribute to the pathophysiology and thereby, psychopathology of schizophrenia. These data also support the augmentation of antipsychotic treatment by supplementation with a combination of antioxidants and omega-3 fatty acids.

Adult↗
PubMed1986

Growth and fatty acid metabolism in experimental intrauterine growth retardation: effect of postnatal nutrition in rat.

Rats, 3 1/2 to 4 d of age, were used to study weight gain and fatty acid (FA) metabolism as a function of degree of intrauterine growth retardation (IUGR) and of postnatal nutrition. The IUGR, quantified postnatally as mild and severe, was produced by uterine artery ligation on d 17 of gestation, and controls were shamoperated. Food intake was manipulated by varying the litter size; i.e., pup number per dam was 4 or 5 for overfeeding, 8-10 for normal feeding and 13-15 for underfeeding. Fatty acid synthesis rate (FASR) (determined by tritiated water incorporation in FA) and contents were determined in selected organs at 84 to 96 h of age. The initial weights (grams) at 2 to 12 h of age were: 5.88 +/- 0.74 (mean +/- SD) for controls, 5.18 +/- 0.11 for mild IUGR and 4.18 +/- 0.24 for severe IUGR. During the first 96 h of life, weight gain was less in underfed control pups while overfeeding resulted in the same weight gain as in normally fed pups. Pups with mild IUGR showed the same effect of under- or overfeeding as control pups. In the severe IUGR groups, weight gains were similar in all three feeding groups. In the carcass, the fatty acid content was reduced as a result of both prenatal and postnatal undernutrition. Although the underfed control group had a high FASR, underfeeding had no effect on the FASR of groups with IUGR. In the liver, the FA content was also lower in the underfed controls and in IUGR groups, without any difference in FASR. Feeding did not influence the FASR of liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

Free fatty acid metabolism in human skeletal muscle is regulated by PPARgamma and RXR agonists.

Free fatty acid (FFA) oxidation in human skeletal muscle cells can be stimulated, both independently and in a synergistic manner, by agonists for PPARgamma and RXR. Increased FFA disposal in muscle through augmented oxidation could reduce intramyocellular lipid accumulation. The abilities of such agents to improve glucose tolerance and insulin action may thus involve effects on both glucose and FFA metabolism.

Fatty Acids, Nonesterified↗