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Results for “FATTY ACID METABOLISM”

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PubMed2003

New insight into Phaeodactylum tricornutum fatty acid metabolism. Cloning and functional characterization of plastidial and microsomal delta12-fatty acid desaturases.

In contrast to 16:3 plants like rapeseed (Brassica napus), which contain alpha-linolenic acid (18:3(Delta9,12,15)) and hexadecatrienoic acid (16:3(Delta7,10,13)) as major polyunsaturated fatty acids in leaves, the silica-less diatom Phaeodactylum tricornutum contains eicosapentaenoic acid (EPA; 20:5(Delta5,8,11,14,17)) and a different isomer of hexadecatrienoic acid (16:3(Delta6,9,12)). In this report, we describe the characterization of two cDNAs having sequence homology to Delta12-fatty acid desaturases from higher plants. These cDNAs were shown to code for a microsomal and a plastidial Delta12-desaturase (PtFAD2 and PtFAD6, respectively) by heterologous expression in yeast (Saccharomyces cerevisiae) and Synechococcus, respectively. Using these systems in the presence of exogenously supplied fatty acids, the substrate specificities of the two desaturases were determined and compared with those of the corresponding rapeseed enzymes (BnFAD2 and BnFAD6). The microsomal desaturases were similarly specific for oleic acid (18:1(Delta9)), suggesting that PtFAD2 is involved in the biosynthesis of EPA. In contrast, the plastidial desaturase from the higher plant and the diatom clearly differed. Although the rapeseed plastidial desaturase showed high activity toward the omega9-fatty acids 18:1(Delta9) and 16:1(Delta7), in line with the fatty acid composition of rapeseed leaves, the enzyme of P. tricornutum was highly specific for 16:1(Delta9). Our results indicate that in contrast to EPA, which is synthesized in the microsomes, the hexadecatrienoic acid isomer found in P. tricornutum (16:3(Delta6,9,12)) is of plastidial origin.

Amino Acid Sequence↗

PubMed1980

Effects of alterations of polyunsaturated fatty acid metabolism upon plasma volume loss induced by thermal trauma.

Based upon the prior observation that drugs which reduce sympathetically induced lipolysis also reduce plasma volume loss following thermal trauma, it was postulated that the products of the metabolism of polyunsaturated fatty acids (PUFA) were the substances causing the plasma volume loss. The two major metabolic pathways for PUFA are cyclo-oxygenase transformation to form prostaglandins and lipoxygenase transformation to form fatty acid hydroperoxides. This latter pathway also produces the superoxide anion and metabolism upn plasma volume loss, the effects of indomethacin (a cyclo-oxygenase inhibitor), orgotein (a superoxide dismutase), and catalase (an enzyme which converts hydrogen peroxide to inactive substances) were studied in anesthetized dogs receiving a 15% total body surface area third-degree flame burn. The results of this study showed that indomethacin did nt alter postburn plasma volume loss, orgotein reduced early plasma volume loss but did not reduce continuing loss, and catalase reduced both early and continuing plasma volume loss.

Animals↗

PubMed1984

Adrenoleukodystrophy: very long-chain fatty acid metabolism in fibroblasts.

We studied very long-chain fatty acid (VLFA) metabolism in cultured fibroblasts from patients with adrenoleukodystrophy (ALD). Total hexacosanoate (C26:0) content of ALD fibroblasts was sixfold higher than normal and did not return to normal when cells were grown in lipid-free medium. When normal or ALD fibroblasts were grown in medium containing 10% ALD serum (which is enriched in C26:0), there was no further increase in C26:0 content compared with cells grown in 10% normal human serum. Uptake and loss of 1-14C-palmitate (C16:0) and 1-14C-lignocerate (C24:0) by ALD fibroblasts were similar to normal fibroblasts. Catabolism of exogenous 3H-C26:0 to 3H2O was about 30% of normal. Oxidation of exogenous 1-14C-hexacosanoate, 1-14C-lignocerate, and 1-14C-palmitate in intact ALD fibroblasts was 42%, 27 +/- 13% (SD), and 73 +/- 47%, respectively, of normal. These results are consistent with, but do not conclusively prove, a VLFA oxidation defect in ALD fibroblasts.

Adrenoleukodystrophy↗

PubMed1995

Impaired myocardial fatty acid metabolism detected by 123I-BMIPP in patients with unstable angina pectoris: comparison with perfusion imaging by 99mTc-sestamibi.

The present study was undertaken to determine the potential diagnostic value of 123I-BMIPP scintigraphy for the detection of altered myocardial fatty acid metabolism in patients with unstable angina. Both myocardial metabolic imaging with 123I-BMIPP and perfusion imaging with 99mTc-sestamibi were performed at rest in 28 patients with unstable angina in the pain-free state. The regional uptakes of 123I-BMIPP or 99mTc-sestamibi were scored semiquantitatively (0 = normal, 4 = no activity) and compared with the coronary arteriographic findings. Decreased uptakes of 123I-BMIPP were observed in 18 patients, and 11 patients had abnormal 99mTc-sestamibi images. Defect scores of 123I-BMIPP were larger than those of 99mTc-sestamibi (7.8 +/- 2.1 vs. 5.2 +/- 1.9, p < 0.01). The sensitivity for the detection of patients with unstable angina was higher in 123I-BMIPP than in 99mTc-sestamibi (77% vs. 45%, p < 0.01). The site of the decreased 123I-BMIPP uptake corresponded to the most stenotic coronary artery lesion in all patients. Fatty acid metabolic imaging with 123I-BMIPP was more sensitive for detecting myocardial ischemia than perfusion imaging with 99mTc-sestamibi. 123I-BMIPP may be a clue to define the culprit lesion in unstable angina and be helpful to decide the best treatment and guide coronary angioplasty.

Aged↗

PubMed1995

[Fatty acid metabolism in patients with idiopathic dilated cardiomyopathy: characteristics and prognostic implications].

The characteristics of myocardial fatty acid metabolism in patients with idiopathic dilated cardiomyopathy (DCM) were investigated by myocardial imaging with beta-methyl-p-[123I]iodophenyl-pentadecanoic acid (BMIPP) in 16 patients with DCM, 8 patients with hypertensive heart failure (HHF), and 11 normal subjects. Rest myocardial imaging with BMIPP and 201Tl was performed on another day. The index of myocardial BMIPP uptake, or uptake ratio, was calculated from the percentage uptakes of BMIPP and 201Tl. The index of inhomogeneity of intramyocardial isotope distribution was calculated as the coefficient of variation of BMIPP and 201Tl. The uptake ratio was significantly lower in DCM and HHF patients than in normal subjects (p < 0.01). Uptake ratio correlated well with fractional shortening (r = 0.76, p < 0.01), and left ventricular ejection fraction (r = 0.58, p < 0.01). Although uptake ratio was not different between DCM and HHF patients, defects in BMIPP imaging appeared more frequently in DCM (69%) than in HHF (38%) patients. Furthermore, the extent of the defect in BMIPP imaging in DCM patients was larger than that in 201Tl imaging (p < 0.05), but in HHF patients the extent of the defects in both methods was similar. The coefficient of variation of BMIPP in DCM patients was greater than those in HHF patients and in normal subjects, but those of 201Tl were not different between the three groups. The coefficient of variation of BMIPP in DCM patients correlated well with serum norepinephrine level (r = 0.57, p < 0.01) and atrial natriuretic peptide (r = 0.77, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

[Assessment of myocardial fatty acid metabolism in patients with vasospastic angina using 123I-BMIPP myocardial SPECT].

Myocardial perfusion and fatty acid metabolism may be unpaired in the patients of vasospastic angina (VSA), because abnormal regional wall motion of left ventricle has been shown in some cases of VSA without apparent history of myocardial infarction. To study the clinical utility of 123I-BMIPP scintigraphy in diagnosis of myocardial ischemia in VSA, both 123I-BMIPP (rest) and 201T1 (exercise) SPECT were performed in the 20 patients of VSA diagnosed by coronary angiography. Defect scores were calculated visually from the 17 segments of myocardial images and were compared with patient's anginal history, period from last attack, numbers of attack, left ventricular (LV) ejection fraction and severity of regional LV wall motion abnormality. 123I-BMIPP SPECT images showed decreased tracer uptake in 14 cases of 20 (70%) VSA patients. Exercise 201T1 SPECT images showed decreased tracer uptake in 3 cases of 20 (15%) of patients. Severity of regional LV wall motion abnormality was correlated with defect score of BMIPP. Though total defect score of BMIPP did not correlate with patient's anginal history, number of symptoms and LV ejection fraction, correlated inversely with period from last attack. It was suggested that 123I-BMIPP myocardial SPECT images in VSA patients showed "memories" of myocardial ischemic damages induced by vasospasm. In summary, 123I-BMIPP myocardial SPECT images could be a useful test for diagnosis and evaluation of VSA.

Angina Pectoris, Variant↗

PubMed1995

Synthesis and preliminary evaluation of [1-11C]hexanoate as a PET tracer of fatty acid metabolism.

The potential of [1-11C]hexanoate (11C-HA) as a radiopharmaceutical assessing fatty acid metabolism of the myocardium and brain tissues by PET studies was evaluated. 11C-HA was synthesized by the Grignard reaction of pentylmagnesium bromide and 11CO2. 11C-HA, [1-14C]acetate and [3H]deoxyglucose were simultaneously injected i.v. into mice, and the tissue distribution of the three radionuclides was measured. In the heart, high uptake and rapid clearance of 11C and 14C was found. The brain uptake of 11C was twice as high as that of 14C, and both 11C and 14C decreased slowly compared to the heart. The level of 3H increased with time in both the heart and brain. In fasting conditions, the uptake of 11C by the heart was enhanced and the level of 3H decreased with time. The brain uptake of 11C and 3H was also enhanced. The fasting conditions did not affect the distribution of 14C. The radiation absorbed dose of 11C-HA was also estimated.

Adult↗

PubMed1981

Relationship between structure and fatty acid metabolism in mitochondria isolated from ischemic rat hearts.

We studied mitochondrial structure and intermediates of fatty acid metabolism in mitochondria isolated from ischemic hearts. By electron microscopy, no structural difference was detected between mitochondria isolated from control hearts and from ischemic hearts receiving glucose as the only substrate. However, major differences were observed in mitochondria obtained from control and ischemic hearts receiving both glucose and palmitate. These hearts contained a higher portion of damaged mitochondria. However, measurements of marker enzyme activities failed to show that more mitochondria were lost during the isolation procedure in ischemic than in control hearts. Many densely staining areas (or amorphous densities) were observed in the isolated mitochondria of ischemic hearts. These amorphous densities have an appearance similar to that observed in the intact ischemic heart under the same perfusion conditions. Levels of long-chain acyl-CoA in mitochondria isolated from hearts receiving glucose alone were practically the same for control and ischemic hearts and were only slightly increased in mitochondria of ischemic hearts receiving both glucose and palmitate. On the other hand, levels of long-chain acyl carnitine in mitochondria of ischemic hearts were twice those found in control hearts. The mitochondrial level of long-chain acyl carnitine was approximately four times higher in the ischemic hearts receiving palmitate compared to those receiving no palmitate. This rise in long-chain acyl carnitine levels in mitochondria isolated fom ischemic hearts receiving palmitate may be related to modifications of the mitochondrial structure and to the appearance of amorphous densities.

Animals↗

PubMed1997

Effects of fatty acids and hormones on fatty acid metabolism and gluconeogenesis in bovine hepatocytes.

Primary cultures of hepatocytes were used to study the effects of extracellular oleate concentration and hormones on fatty acid metabolism and gluconeogenesis. Rates of oleate uptake and oxidation to acid-soluble products varied linearly as oleate concentrations increased (0.1 to 2 mM), but rates of triglyceride accumulation varied quadratically. Insulin increased the proportion of oleate that was esterified by 22% without affecting the formation of acid-soluble products. Cells incubated with 2 mM [1-(14)C]oleate for 24 h eliminated 9.6% of the labeled intracellular lipid as acid-soluble products in the following 24 h when no oleate was present during depletion and eliminated 7.7% when 2 mM oleate was present. Insulin reduced labeled triglyceride depletion by 49%. Gluconeogenesis from [2-(14)C] propionate was depressed by 24%, and formation of acid-soluble products was increased by 46% in cells infiltrated with lipid because of previous exposure to 2 mM oleate for 45 h. Rates of gluconeogenesis from propionate were reduced 23% when 2 mM oleate was present during the 3-h period that gluconeogenesis was measured, and the effect was not modified by lipid infiltration. Lipid infiltration influenced hepatic function, and insulin regulated hepatic triglyceride concentration.

Animals↗

PubMedDate not supplied

POSSIBLE ROLE OF VITAMIN E IN UNSATURATED FATTY ACID METABOLISM.

Explore the source record for details and available documents.

Animals↗

PubMed2002

Remnant lipoprotein particles are taken up into myocardium through VLDL receptor--a possible mechanism for cardiac fatty acid metabolism.

The VLDL (very low-density lipoprotein) receptor is a peripheral lipoprotein receptor expressing in fatty acid active tissues abundantly. In the Balb/c fasting mice, VLDL receptor as well as LPL (lipoprotein lipase), FAT (fatty acid translocase)/CD36, H-FABP (heart-type fatty acid-binding protein), ACS (acyl-CoA synthetase) and LCAD (long-chain acyl-CoA dehydrogenase) expressions increased. An electron microscopic examination indicated the lipid droplets that accumulated in the hearts of fasting Balb/c mice. During the development of SD (Sprague-Dawley) rats, VLDL receptor, LPL, FAT/CD36, H-FABP, ACS, and LCAD mRNAs concomitantly increased with growth. However, PK (pyruvate kinase) mRNA expression was negligible. In cultured neonatal rat cardiomyocytes, VLDL receptor expression increased with days in culture. Oil red-O staining showed that cardiomyocytes after 7 days in culture (when the VLDL receptor protein is present) accumulated beta-migrating VLDL. Thereby, we showed that the cardiac VLDL receptor pathway for delivery of remnant lipoprotein particles might be part of a cardiac fatty acid metabolism.

Animals↗

PubMed1996

[Autoradiographic study of myocardial fatty acid metabolism in diabetic mouse using 125I-BMIPP].

The existence of diabetic cardiomyopathy has been substantiated in patients with diabetes mellitus. In this study we evaluated two mice with diabetes mellites (DM) and two control mice to determine whether the fatty acid metabolism of the myocardium is abnormal when 125I-BMIPP is used. 125I-BMIPP of 0.74 MBq (20 microCi) was injected, and 30 min later, the mice were slaughtered. Heart, lungs, liver, spleen and kidneys were removed. After freezing the heart, myocardium was sliced into 20 micron sections using a cryostat. Each slice was placed in contact with an imaging plate for autoradiography. A bioimaging analyzer was used to analyze the data. The percent injected dose/g of heart was lower in the DM group than in the control group (11.6 +/- 0.49 vs 18.3 +/- 1.27). Each slice of the DM group also had fewer counts than slices in the control group (p < 0.05 or p < 0.01). These results indicated that fatty acid metabolism in the myocardium was less in the DM group than in the control group.

Animals↗

PubMed1975

Assessment of myocardial free fatty acid metabolism in humans during heparin infusion.

Free fatty acids (FFA) have been shown to be a major myocardial substrates during the postabsorptive state in humans. In order to document the utilization of these substrates by the heart while heparin was infused, the following study was designed. During heparin infusion, total and individual FFA were measured in arterial and coronary sinus plasma during the postabsorptive state in 13 patients with coronary artery disease and in 4 patients with no evidence of cardiac disease. Oleic-1-14C acid bound to albumin was infused at a constant rate for at least 7 min into the left coronary artery. Left coronary blood flow was determined in all patients. It was assumed the oleic-1-14C acid behaves like endogenous FFA. Arterial FFA concentration was high (mean and SEM: 1 +/- 0.21 mumoles/ml) and varied by less than 10% during the course of the study in 14 of the 17 patients. Oleic acid constituted 44% of all arterial FFA. The relative concentrations of the various individual FFA were similar in arterial and coronary sinus plasma. The average FFA extraction was 19.9 +/- 2.1%. In contrast, the oleic-1-14C acid extraction was relatively more steady during the infusion, and the mean extraction of this tracer was 36.0 +/- 2.1%. Myocardial uptake for the entire group was 52.3 +/- 6.3 mumoles/min. Although a definite plateau for 14CO2 release from oleic-1-14C acid oxidation was not obtained, at least 31.8 +/- 4.3% of the removed FFA was oxidized, representing 49.3 +/- 6.4% of myocardial oxygen consumption. The failure of oleic-1-14C acid oxidation to reach a steady state was not due to delay in the myocardial CO2 pool, since 14CO2 release from infused NaH 14CO3 and lactate-1-14C in 11 other subjects revealed that in equilibrium was obtained within 5 min. These findings indicate that the generation of 14CO2 from oleic-1-14C acid oxidation is relatively slow, and the uptake of labeled FFA is partly matched by release of unlabeled FFA, suggesting that the human heart has important lipid pools.

Adult↗

PubMed2005

Sensing the fat: fatty acid metabolism in the hypothalamus and the melanocortin system.

Recent evidence has demonstrated that circulating long chain fatty acids act as nutrient abundance signals in the hypothalamus. Moreover, pharmacological inhibition of fatty acid synthase (FAS) results in profound decrease in food intake and body weight in rodents. These anorectic actions are mediated by the modulation of hypothalamic neuropeptide systems, such as melanocortins. In this review, we summarize what is known about lipid sensing and fatty acid metabolism in the hypothalamus. Understanding these molecular mechanisms could provide new pharmacological targets for the treatment of obesity and appetite disorders, as well as novel concepts in the nutritional design.

Animals↗

PubMed1992

[Phase 2 study of beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid, a myocardial imaging agent for evaluating myocardial fatty acid metabolism].

A phase 2 study of beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid (123I-BMIPP), a myocardial imaging agent developed for evaluating myocardial fatty acid metabolism, was performed in 197 patients with various heart diseases. The myocardial distribution of 123I-BMIPP did not change from early to late images in 88% of 91 patients with ischemic heart disease (IHD), while washout and/or fill-in were observed in 45% of 55 patients with hypertrophic cardiomyopathy (HCM). In comparison with 201Tl in 165 patients with various heart diseases, the decrease in uptake was more profound with BMIPP in 56% and with 201Tl in only 4%. 123I-BMIPP showed more severely decreased uptake in 83% of the patients with subacute myocardial infarction (15 to 30 days after the onset) and in 73% of the patients with HCM. High-quality SPECT images were obtained with 123I-BMIPP in 93% of 194 patients analyzed. However, the image quality in cardiomyopathy was inferior to that in IHD. The optimal injection dose range and standard dose of 123I-BMIPP were considered to be 74-148 MBq and 111 MBq, respectively. These findings suggest that 123I-BMIPP myocardial imaging is safe and useful for evaluating myocardial fatty acid metabolism in various heart diseases.

Adolescent↗

PubMed1976

Influence of valine deprivation and its reversal on fatty acid metabolism in HeLa cells.

The effects that amino acid starvation and re-supplementation have on fatty acid metabolism in HeLa cells have been studied using radio gas chromatographic techniques. Deprivation of valine for 13.5 h caused fatty acid de novo biosynthesis, elongation and desaturation to cease. This effect was reversed within 5 h by adding valine back to the culture. During deprivation accumulation of triacylglycerol occurred. The return of valine to the culture caused compositional changes in the triacylglycerols and phosphatidylcholines.

Chromatography, Gas↗

PubMed2002

Genetic manipulations of fatty acid metabolism in beta-cells are associated with dysregulated insulin secretion.

Triacylglyceride (TG) accumulation in pancreatic beta-cells is associated with impaired insulin secretion, which is called lipotoxicity. To gain a better understanding of the pathophysiology of lipotoxicity, we generated three models of dysregulated fatty acid metabolism in beta-cells. The overexpression of sterol regulatory element binding protein-1c induced lipogenic genes and TG accumulation. Under these conditions, we observed a decrease in glucose oxidation and upregulation of uncoupling protein-2, which might be causally related to the decreased glucose-stimulated insulin secretion. The overexpression of AMP-activated protein kinase was accompanied by decreased lipogenesis, increased fatty acid oxidation, and decreased glucose oxidation; insulin secretions to glucose and depolarization stimuli were decreased, probably because of the decrease in glucose oxidation and cellular insulin content. It was notable that the secretory response to palmitate was blunted, which would suggest a role of the fatty acid synthesis pathway, but not its oxidative pathway in palmitate-stimulated insulin secretion. Finally, we studied islets of PPAR-gamma(+/-) mice that had increased insulin sensitivity and low TG content in white adipose tissue, skeletal muscle, and liver. On a high-fat diet, glucose-stimulated insulin secretion was decreased in association with increased TG content in the islets, which might be mediated through the elevated serum free fatty acid levels and their passive transport into beta-cells. These results revealed some aspects about the mechanisms by which alterations of fatty acid metabolism affect beta-cell functions.

Adenylate Kinase↗

PubMed1999

Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss.

The current study was undertaken to investigate fatty acid metabolism by skeletal muscle to examine potential mechanisms that could lead to increased muscle triglyceride in obesity. Sixteen lean and 40 obese research volunteers had leg balance measurement of glucose and free fatty acid (FFA) uptake (fractional extraction of [9,10 (3)H]oleate) and indirect calorimetry across the leg to determine substrate oxidation during fasting and insulin-stimulated conditions. Muscle obtained by percutaneous biopsy had lower carnitine palmitoyl transferase (CPT) activity and oxidative enzyme activity in obesity (P < 0.05). During fasting conditions, obese subjects had an elevated leg respiratory quotient (RQ, 0.83 +/- 0.02 vs. 0.90 +/- 0.01; P < 0.01) and reduced fat oxidation but similar FFA uptake across the leg. During insulin infusions, fat oxidation by leg tissues was suppressed in lean but not obese subjects; rates of FFA uptake were similar. Fasting values for leg RQ correlated with insulin sensitivity (r = -0.57, P < 0.001). Thirty-two of the obese subjects were restudied after weight loss (WL, -14.0 +/- 0.9 kg); insulin sensitivity and insulin suppression of fat oxidation improved (P < 0.01), but fasting leg RQ (0.90 +/- 0.02 vs. 0.90 +/- 0.02, pre-WL vs. post-WL) and muscle CPT activity did not change. The findings suggest that triglyceride accumulation in skeletal muscle in obesity derives from reduced capacity for fat oxidation and that inflexibility in regulating fat oxidation, more than fatty acid uptake, is related to insulin resistance.

Adult↗