Palmitic Acid Metabolism Research Articles

PAM, OLA, and LNA are Differentially Taken Up and Trafficked Via Different Metabolic Pathways in Porcine Adipocytes.

Dietary fatty acids have different effects on fat deposition in pigs. To clarify the underlying mechanisms of this difference, we compared the metabolism of palmitic (PAM, saturated), oleic (OLA, monounsaturated) and linoleic acid (LNA, polyunsaturated) in porcine adipocytes treated with 100μM PAM, OLA or LNA. We observed that the adipocytes incubated with LNA accumulated more lipids compared with those treated with PAM and OLA. We then probed the metabolism of these fatty acids in porcine adipocytes by using isotope-labelled fatty acids. The results showed that 42% of the [1-14C] LNA, 34% of the [1-14C] PAM and 28% of the [1-14C] OLA were recovered in the cellular lipids. The gene expression analyses showed that LNA significantly increased the expression of adipogenesis- and oxidation-related genes including PPARγ, C/EBPα, ap2 and NRF1. In addition, the cells incubated with LNA showed a decreased Ser112 phosphorylation in PPARγ compared to those incubated with PAM and OLA. Furthermore, when PPARγ Ser112 phosphorylation was inhibited, no significant difference in the triacylglycerol contents in the adipocytes was observed. These results showed the dietary fatty acids had different metabolism pathways in porcine adipocytes, and LNA significantly promoted lipid accumulation, probably by regulating PPARγ phosphorylation in adipocytes.

HDL inhibits saturated fatty acid mediated augmentation of innate immune responses in endothelial cells by a novel pathway

Background and aimsPeripheral insulin resistance is associated with several metabolic abnormalities, including elevated serum fatty acids that contribute to vascular injury and atherogenesis. Our goals were to examine whether saturated fatty acids can modify innate immune responses to subclinical concentrations of lipopolysaccharide (LPS) in endothelial cells, and to explore the underlying pathway and determine whether it is modified by high density lipoprotein (HDL) and other factors commonly altered in insulin resistance. MethodsPhysiologic concentrations of palmitic acid were added to human aortic endothelial cells with and without a variety of inhibitors or HDL and measures of cell inflammation and function assessed. ResultsPalmitic acid significantly amplified human aortic endothelial cell inflammatory responses to LPS. Similar results were obtained from lipolysis products of triglyceride rich lipoproteins. Metabolism of palmitic acid to ceramide and subsequent activation of PKC-ζ, MAPK and ATF3 appeared critical in amplifying LPS induced inflammation. The amplified response to palmitic acid/LPS was decreased by HDL, dose dependently, and this inhibition was dependent on activation of PI3K/AKT and reduction in ATF3. ConclusionsThese results indicate that endothelial cell innate immune responses are modified by metabolic abnormalities commonly present in insulin resistance and provide evidence for a novel mechanism by which HDL may reduce vascular inflammation.

GC-TOF/MS-based metabolomic strategy for combined toxicity effects of deoxynivalenol and zearalenone on murine macrophage ANA-1 cells

The actual health risk from exposure to combined mycotoxins is unknown, and few studies have focused on changes to cellular biological systems (e.g., metabolomics) caused by combined mycotoxic effects. To evaluate the combined mycotoxic effects of deoxynivalenol (DON) and zearalenone (ZEN) on the level of cellular biological systems, gas chromatographic, time-of-flight mass spectroscopy (GC-TOF/MS) of the complete murine macrophage ANA-1 cell metabolome was implemented in this study. Using optimized chromatography and mass spectrometry parameters, the metabolites detected by GC-TOF/MS were identified and processed using multivariate statistical analysis, including principal component analysis (PCA) and orthogonal projection on latent-structures discriminant analysis (OPLS-DA). The metabolite sets were screened for further pathway analysis under rules of t-test (P) value < 0.05, VIP value > 1, and similarity value > 500. The mainly interfered metabolism pathways were categorized into two dominant types: amino acid metabolism and glycometabolism. Four metabolites, palmitic acid, 1-monopalmitin, ribose-5-phosphate and 2-deoxy-D-galactose, occur only under combined “DON + ZEN” treatment, indicating abnormal metabolism in ANA-1 cells. The metabolic state of ANA-1 cells under induction by combined “DON + ZEN” illustrates that DON may inhibit the estrogenic effects of ZEN. Thus, the combined effect of “DON + ZEN” may exacerbate toxicity in the pentose phosphate pathway, while palmitic acid metabolism is likely a new pathway effected by the combination, “DON + ZEN.”

Astrocyte arachidonate and palmitate uptake and metabolism is differentially modulated by dibutyryl-cAMP treatment

Astrocytes play a vital role in brain lipid metabolism; however the impact of the phenotypic shift in astrocytes to a reactive state on arachidonic acid metabolism is unknown. Therefore, we determined the impact of dibutyryl-cAMP (dBcAMP) treatment on radiolabeled arachidonic acid ([1-14C]20:4n-6) and palmitic acid ([1-14C]16:0) uptake and metabolism in primary cultured murine cortical astrocytes. In dBcAMP treated astrocytes, total [1-14C]20:4n-6 uptake was increased 1.9-fold compared to control, while total [1-14C]16:0 uptake was unaffected. Gene expression of long-chain acyl-CoA synthetases (Acsl), acyl-CoA hydrolase (Acot7), fatty acid binding protein(s) (Fabp) and alpha-synuclein (Snca) were determined using qRT-PCR. dBcAMP treatment increased expression of Acsl3 (4.8-fold) and Acsl4 (1.3-fold), which preferentially use [1-14C]20:4n-6 and are highly expressed in astrocytes, consistent with the increase in [1-14C]20:4n-6 uptake. However, expression of Fabp5 and Fabp7 were significantly reduced by 25% and 45%, respectively. Acot7 (20%) was also reduced, suggesting dBcAMP treatment favors acyl-CoA formation. dBcAMP treatment enhanced [1-14C]20:4n-6 (2.2-fold) and [1-14C]16:0 (1.6-fold) esterification into total phospholipids, but the greater esterification of [1-14C]20:4n-6 is consistent with the observed uptake through increased Acsl, but not Fabp expression. Although total [1-14C]16:0 uptake was not affected, there was a dramatic decrease in [1-14C]16:0 in the free fatty acid pool as esterification into the phospholipid pool was increased, which is consistent with the increase in Acsl3 and Acsl4 expression. In summary, our data demonstrates that dBcAMP treatment increases [1-14C]20:4n-6 uptake in astrocytes and this increase appears to be due to increased expression of Acsl3 and Acsl4 coupled with a reduction in Acot7 expression.

The positional isomers of palmitic and oleic triglycerides, lipolysis, conformation of apoB-100, formation of apoE/B-100 ligand and absorption of lipoproteins of very low density by insulin-dependent cells under action of statins.

The study was carried out to trace back quantitative alterations of positional isomers, oleic and palmitic triglycerides and individual fatty acids in blood serum. After two weeks of taking of Simvastatin (40, 80 mg), analysis of blood serum established decreasing of content of Рhosphatidylcholine and more reliable decreasing of amount of non-etherized alcohol cholesterol. No alterations of content of particular fatty acids were detected. In apoB-100, Рhosphatidylcholine and non-etherized alcohol cholesterol form polar mono-layer; it covers mass of oleic and palmitic triglycerides that was bound by apoB-100 in oleic and palmitic lipoproteins of very low density disturbing bio-availability of substrate (oleic and palmitic triglycerides) for post-heparin lipase. This very pool of non-etherized alcohol cholesterol is inhibited by statins activating lipolysis in oleic and palmitic lipoproteins of very low density. In blood was detected amount of palmitic positional isomersin oleic and palmitic triglycerides (palmitoyl-palmitoyl-palmitate and palmitol-palmitoyl-oleate) and oleic positional isomers (oleyl-oleyl-palmitate and oleyl-oleyl-oleate). The significant difference was marked in content of positional isomers both of oleyl-oleyl-oleate and oleyl-oleyl-palmitate; their content is less in blood of patients of experimental group as compared with healthy people. In case of treatment with Simvastatin (40 mg) the level of palmitic positional isomers and palmitol-palmitoyloleate is decreased. In case of treatment with Simvastatin (80 mg) significant decreasing of positional isomers-palmitolpalmitoyl-oleate and oleyl-oleyl-palmitate as compared with data before treatment. The detection of content of positional isomers triglycerides permits: a) to characterize disorders of metabolism of palmitic fatty acid, oleic fatty acid, oleic and palmitic triglycerides and oleic and palmitic lipoproteins of very low density of the same name; b) to form individual diet therapy; c) to obtain objective information concerning compliance of prescribed recommendations b y patient. The basis of primary prevention of atherosclerosis and atheromatosis is in decreasing up to physiological level in food the content of longchained saturated fatty acids mainly palmitic acid.

Utility of Fatty Acid Profile of Erythrocyte Membrane in Identifying Diagnostic Markers of Crohnʼs Disease

Introduction: We often experience cases of Crohn's disease (CD) that are hard to distinguish from other inflammatory bowel diseases (IBDs), such as ulcerative colitis (UC) and indeterminate colitis, making diagnosis difficult. We have previously reported that the erythrocyte membrane phospholipid fatty acid profile is very specific in patients with initial IBD, particularly CD. This suggests that the activity of enzymes involved in the metabolism of linoleic acid (LA) and palmitic acid (PA), namely, delta 6 desaturase and elongase 6, is expected to be higher than that of healthy individuals. In this study, we evaluated the utility of delta 6 desaturation index (Δ6di), elongation index (EI), and various fatty acids as diagnostic markers of CD. Methods: Ninety-five IBD patients (70 with CD and 25 with UC) and controls (90 healthy individuals) were enrolled in this study. We analyzed the erythrocyte membrane phospholipid fatty acid concentrations in each of these groups. As indexes of enzyme activity, we calculated the Δ6di using the percentage weights of LA, dihomo-γ-linoleic acid (DGLA), and arachidonic acid (AA), i.e., Δ6di=(DGLA+AA)/LA, and EI using the percentage weights of PA, stearic acid (SA), and oleic acid (OA), i.e., EI=(SA+OA)/PA. Results: In CD patients, the percentage weights of SA, DGLA, and AA were significantly higher, and those of PA and LA were significantly lower (p < 0.001), in comparison with those of UC patients and controls. Similarly, Δ6di and EI were significantly higher (p < 0.001). The areas under the receiver operating characteristic curve of Δ6di and SA were the highest at 0.920 and 0.922, respectively. When cut-off values of 1.325 and 13.27 were chosen for Δ6di and SA, respectively, the sensitivity and specificity for CD patients versus UC patients and controls were 91.4 and 87.8% for Δ6di and 82.9 and 99.1% for SA, respectively. Conclusion: In CD patients, the percentage weights of LA and PA were significantly lower, and those of AA and SA were significantly higher as compared to those of UC patients and controls. In addition, Δ6di and SA could be excellent diagnostic markers of CD.Figure 1

What Are n-7 Fatty Acids and Are There Health Benefits Associated with Them?

What Are n-7 Fatty Acids and Are There Health Benefits Associated with Them?

Metabolomics changes in a rat model of obstructive jaundice: mapping to metabolism of amino acids, carbohydrates and lipids as well as oxidative stress.

The study examined the global metabolic and some biochemical changes in rats with cholestasis induced by bile duct ligation (BDL). Serum samples were collected in male Wistar rats with BDL (n = 8) and sham surgery (n = 8) at day 3 after surgery for metabolomics analysis using a combination of reversed phase chromatography and hydrophilic interaction chromatography (HILIC) and quadrupole-time-of-flight mass spectrometry (Q-TOF MS). The serum levels of malondialdehyde (MDA), total antioxidative capacity (T-AOC), glutathione (GSH) and glutathione disulfide (GSSG), the activities of superoxide dismutase (SOD) and glutathion peroxidase (GSH-Px) were measured to estimate the oxidative stress state. Key changes after BDL included increased levels of l-phenylalanine, l-glutamate, l-tyrosine, kynurenine, l-lactic acid, LysoPCc (14:0), glycine and succinic acid and decreased levels of l-valine, PCb (19:0/0:0), taurine, palmitic acid, l-isoleucine and citric acid metabolism products. And treatment with BDL significantly decreased the levels of GSH, T-AOC as well as SOD, GSH-Px activities, and upregulated MDA levels. The changes could be mapped to metabolism of amino acids and lipids, Krebs cycle and glycolysis, as well as increased oxidative stress and decreased antioxidant capability. Our study indicated that BDL induces major changes in the metabolism of all 3 major energy substances, as well as oxidative stress.

Hepatocellular toxicity of benzbromarone: effects on mitochondrial function and structure.

Benzbromarone is an uricosuric structurally related to amiodarone and a known mitochondrial toxicant. The aim of the current study was to improve our understanding in the molecular mechanisms of benzbromarone-associated hepatic mitochondrial toxicity. In HepG2 cells and primary human hepatocytes, ATP levels started to decrease in the presence of 25-50μM benzbromarone for 24-48h, whereas cytotoxicity was observed only at 100μM. In HepG2 cells, benzbromarone decreased the mitochondrial membrane potential starting at 50μM following incubation for 24h. Additionally, in HepG2 cells, 50μM benzbromarone for 24h induced mitochondrial uncoupling,and decreased mitochondrial ATP turnover and maximal respiration. This was accompanied by an increased lactate concentration in the cell culture supernatant, reflecting increased glycolysis as a compensatory mechanism to maintain cellular ATP. Investigation of the electron transport chain revealed a decreased activity of all relevant enzyme complexes. Furthermore, treatment with benzbromarone was associated with increased cellular ROS production, which could be located specifically to mitochondria. In HepG2 cells and in isolated mouse liver mitochondria, benzbromarone also reduced palmitic acid metabolism due to an inhibition of the long-chain acyl CoA synthetase. In HepG2 cells, benzbromarone disrupted the mitochondrial network, leading to mitochondrial fragmentation and a decreased mitochondrial volume per cell. Cell death occurred by both apoptosis and necrosis. The study demonstrates that benzbromarone not only affects the function of mitochondria in HepG2 cells and human hepatocytes, but is also associated with profound changes in mitochondrial structure which may be associated with apoptosis.

Saturated long-chain fatty acids activate inflammatory signaling in astrocytes.

This study describes the effects of long-chain fatty acids on inflammatory signaling in cultured astrocytes. Data show that the saturated fatty acid palmitic acid, as well as lauric acid and stearic acid, trigger the release of TNFα and IL-6 from astrocytes. Unsaturated fatty acids were unable to induce cytokine release from cultured astrocytes. Furthermore, the effects of palmitic acid on cytokine release require Toll-like receptor 4 rather than CD36 or Toll-like receptor 2, and do not depend on palmitic acid metabolism to palmitoyl-CoA. Inhibitor studies revealed that pharmacologic inhibition of p38 or p42/44 MAPK pathways prevents the pro-inflammatory effects of palmitic acid, whereas JNK and PI3K inhibition does not affect cytokine release. Depletion of microglia from primary astrocyte cultures using the lysosomotropic agent l-leucine methyl ester revealed that the ability of palmitic acid to trigger cytokine release is not dependent on the presence of microglia. Finally, data show that the essential ω-3 fatty acid docosahexaenoic acid acts in a dose-dependent manner to prevent the actions of palmitic acid on inflammatory signaling in astrocytes. Collectively, these data demonstrate the ability of saturated fatty acids to induce astrocyte inflammation in vitro. These data thus raise the possibility that high levels of circulating saturated fatty acids could cause reactive gliosis and brain inflammation in vivo, and could potentially participate in the reported adverse neurologic consequences of obesity and metabolic syndrome.

ROS-activated p38 MAPK/ERK-Akt cascade plays a central role in palmitic acid-stimulated hepatocyte proliferation

In the past years, free fatty acids (FFAs) and obesity have been reported to play an important role in cancer development. Palmitic acid (PA) is the most prevalent saturated FFA in circulation. However, the mechanism underlying the effect of PA on cell proliferation is still to be elucidated. In this report, we, for the first time, investigate the signaling pathway in human normal hepatocytes (QZG) responsible for PA-induced proliferation. The results demonstrate that PA promotes cell cycle progression, accelerates cell proliferation, and induces a transient and sequential activation of a series of kinases. The employment of several inhibitors and antioxidants indicates that a ROS-induced stress-sensitive p38 MAPK/ERK-Akt cascade plays a critical role in the regulation of PA on cell cycle and cell proliferation. Moreover, PA dose and time dependently activates Nrf2 and this activation relies on ROS-induced stimulation of p38 MAPK/ERK-Akt signaling, demonstrating that Nrf2 activation may be associated with the regulation of PA on cell cycle transition and proliferation. In conclusion, our study elucidates the importance of PA metabolism on cell proliferation, and suggests that PA stimulates hepatocyte proliferation through activating the ROS-p38 MAPK/ERK-Akt cascade which is intersected with the activation of Nrf2 and that the effect of ROS on signal transduction is in a dose- and time-dependent manner. All the above noted provide a new clue for the central role of ROS in cell proliferation and tumorigenesis.

Differential Utilization of Saturated Palmitate and Unsaturated Oleate

We recently described a primarily reduced palmitate oxidation in myotubes established from type 2 diabetic subjects, whereas triacylglycerol (TAG) accumulation seemed to be adaptive. However, it is still uncertain whether these changes are similar for saturated and unsaturated fatty acids and whether high concentrations of glucose and/or insulin may change this picture. Studies of palmitic acid and oleic acid metabolism in human myotubes established from control and type 2 diabetic subjects under conditions of acute high concentrations of insulin and/or glucose may solve these questions. Total oleic acid and palmitic acid uptake in myotubes was increased during acute insulin stimulation (P < 0.01) but not under acute, high-glucose concentrations, and no differences were found between the groups. Type 2 diabetic myotubes expressed a reduced palmitic acid oxidation to carbon dioxide (P </= 0.04), whereas oleic acid oxidation showed no differences between myotubes from both groups. High glucose concentrations decreased oleic acid oxidation (P </= 0.03). Lipid distribution was not different in diabetic and control myotubes when palmitic acid and oleic acid incorporation into cellular lipids was compared. Myotubes that were exposed to palmitic acid showed an increased palmitic acid incorporation into diacylglycerol (DAG) and TAG compared with myotubes that were exposed to oleic acid (P < 0.05) expressing an increased intracellular free fatty acid (FFA) level (P < 0.05). Lipid distribution was not affected by high glucose, whereas insulin increased FFAs, DAG, and TAG (P < 0.05). De novo lipid synthesis from glucose in both diabetic and control myotubes was of the same magnitude independent of glucose and insulin concentrations. These results indicate that palmitic acid and oleic acid are utilized in the same pattern in diabetic and control myotubes even though palmitic acid oxidation is primarily reduced in diabetic cells. Palmitic acid and oleic acid are handled differently by myotubes: Palmitic acid seems to accumulate as DAG and TAG, whereas oleic acid accumulates as intracellular FFAs. These observations indicate that oleic acid is preferable as fatty acid as it accumulates to a lesser extent as DAG and TAG than palmitic acid. Neither acute hyperglycemia nor de novo lipid synthesis from glucose seems central to the TAG accumulation in obesity or type 2 diabetes.

Palmitic acid metabolism in the soleus muscle in vitro in hypo- and hyperthyroid rats.

The aim of this study was to establish whether the rate of fatty acid (FA) incorporation and its utilization by the isolated soleus muscle is modified under conditions of thyroid hormone deficit or excess. The rate of palmitic acid (PA) uptake, oxidation and incorporation into intramuscular lipids with increasing PA concentration (0.5-1.5 mM) in the incubation medium were determined. In hypothyroid rats intramuscular triacylglycerol (TG) synthesis was increased, while the rate of PA oxidation to CO2 and incorporation into mono- and diacylglycerols (MG/DG) and phospholipids (PL) remained unchanged. In rats with triiodothyronine (T3) excess the rate of all processes studied was enhanced, although the percentage incorporation of PA into different classes of intramuscular lipids was fairly constant and, independently of thyroid state and FA concentration in the medium, was 56-66% for TG, 9-14% for MG/DG and 24-32% for PL. Our results thus indicate that even short-term T3 excess accelerates the rate of FA uptake and metabolism in the oxidative soleus muscle, whereas in hypothyroid rats only intramuscular TG synthesis is affected.

Effects of conjugated linoleic acid isomers on lipid metabolism and gluconeogenesis in monolayer cultures of bovine hepatocytes.

The objective was to determine the effects of linoleic acid and different isomers of conjugated linoleic acid (CLA) at different concentrations on hepatic lipid and glucose metabolism in the bovine. Monolayer cultures of hepatocytes obtained from 7- to 10-d-old Holstein bull calves were exposed to treatments from 16 to 64 h after plating. The treatments included 1.0 mM palmitic acid plus either 0.1 or 1.0 mM of cis-9, cis-12 linoleic acid, cis-9, trans-11 CLA, or trans-10, cis-12 CLA. Metabolism of palmitic acid to cellular triacylglycerol (TAG) was decreased when media contained cis-9, trans-11 compared with trans-10, cis-12 CLA. Total cellular TAG content was increased for the CLA isomers compared to cis-9, cis-12 linoleic acid. Both CLA isomers increased palmitic acid incorporation into phospholipids, cholesterol, and media triacylglycerol compared with cis-9, cis-12 linoleic acid at a concentration of 1.0 mM. Increasing the concentration of treatment fatty acids from 0.1 to 1.0 mM decreased oxidation of palmitic acid to acid-soluble products, but no effects of fatty acids were observed. There was no treatment effect on rates of gluconeogenesis from propionic acid. Overall, CLA isomers elicited changes in palmitic acid metabolism to cellular and media triacylglycerol, and cellular phospholipids and cholesterol, but had little or no effect on other measured pathways of lipid metabolism or gluconeogenesis in bovine hepatocytes.

Effects of Long Chain Fatty Acids on Lipid and Glucose Metabolism in Monolayer Cultures of Bovine Hepatocytes

The objectives were to determine the long-term (48h) effects of specific long chain fatty acids on hepatic lipid and glucose metabolism in monolayer cultures of bovine hepatocytes. From 16 to 64h after plating, hepatocytes from three 7- to 10-d-old calves were exposed to one of the following treatments: 1mM palmitic acid (1mM C16:0), 2mM palmitic acid (2mM C16:0), or 1mM palmitic acid plus 1mM of either stearic (C18:0), oleic (C18:1), linoleic (C18:2), linolenic (C18:3), eicosapentaenoic (C20:5), or docosahexaenoic (C22:6) acid, or 0.5mM each of eicosapentaenoic and docosahexaenoic acid (C20:5 + C22:6). The two treatments containing 2mM of saturated fatty acids, 2mM C16:0 and 1mM C16:0 plus 1mM C18:0, increased β-hydroxybutyrate concentrations in the medium and [1-14C]palmitic acid oxidation to acid-soluble products compared with all other treatments. The treatment containing C22:6 increased total cellular triglyceride content and incorporation of [1-14C]palmitic acid into cellular triglycerides. The treatments containing C22:6 or C20:5 + C22:6 increased [1-14C]palmitic acid metabolism to phospholipids and cholesterol. The presence of C22:6 in the medium decreased metabolism of [2-14C]propionic acid either to glucose in the medium or to cellular glycogen. Overall, fatty acids differed in their effects on lipid and glucose metabolism in monolayer cultures of bovine hepatocytes with C22:6 eliciting the most profound changes.

Metabolic Fate of Long-Chain Unsaturated Fatty Acids and Their Effects on Palmitic Acid Metabolism and Gluconeogenesis in Bovine Hepatocytes

The objectives were to determine the metabolic fate of different long-chain fatty acids, and their effects on palmitic acid metabolism and gluconeogenesis in bovine hepatocytes. Hepatocytes were isolated from four ruminating calves and exposed in suspension for 3h to one of the following treatments: 1mM palmitic acid (1C16), 2mM palmitic acid (2C16), or 1mM palmitic acid plus either 1mM oleic (C18:1), linoleic (C18:2), linolenic (C18:3), eicosapentaenoic (C20:5), or docosahexaenoic acid (C22:6). Oxidation of [1-14C]palmitic acid or one of the [1-14C]-labeled treatment fatty acids to CO2 or incorporation into cellular triglycerides (TG), phospholipids, cholesterol, and cholesterol esters were measured. Rates of oxidation to CO2 were 3- to 4-fold higher for C22:6 than for other fatty acids, with the exception of C20:5, which had intermediate rates of oxidation to CO2. In general, treatments 2C16 and C18:1 yielded the highest rates of incorporation into most cellular lipids, whereas the polyunsaturated fatty acids were poor substrates for incorporation into cellular lipids. The most pronounced change was a large reduction of polyunsaturated fatty acid incorporation into cellular TG compared to 1C16, 2C16, and C18:1. The unsaturated fatty acids also influenced palmitic acid metabolism. The addition of C20:5 yielded the highest rates of palmitic acid oxidation to CO2 followed by addition of C18:1 and C22:6. Treatments containing polyunsaturated fatty acids decreased palmitic acid metabolism to TG and total cellular lipids compared with treatments 2C16 and C18:1. Rates of gluconeogenesis from propionate were significantly higher for the treatment containing C18:1. Long-chain fatty acids vary in their routes of metabolism and influence palmitic acid metabolism and gluconeogenesis in bovine hepatocytes.

The Effect of β-Chloro D-Alanine and L-Cycloserine on The Serine, Phosphorus and Palmitic Acid Uptake and Metabolism of Tetrahymena Lipids

The serine palmitoyltransferase inhibitors beta-chloro-D-alanine and L-cycloserine resulted in the uptake and metabolism of 3H-serine, 3H-palmitic acid and 32P significant alterations in the unicellular Tetrahymena pyriformis GL as compared to the untreated cells. In contrast with the higher eukariotic cells, by these treatments - except 5 mM L-cycloserine - the ceramide formation were not inhibited in Tetrahymena. L-cycloserine inhibited the conversion of phosphatidylserine (PS) to phosphatidyl-ethanolamine (PE) by decarboxylation, and the conversion of PE to phosphatidylcoline (PC) by methylation. The shorter L-cycloserine treatments caused lower, and the longer treatments higher label in glycerophospholipids. beta-chloro-D-alanine resulted in the glycerophospholids higher lipid precursor incorporation both in the shorter and longer treatments. Presumably beta-chloro-D-alanine treatments inhibit the transaminase activity, and the higher concentration (5 and 10 mM) proved to be toxic for Tetrahymena. We found differences between the metabolism of serine and palmitic acid labeled lipids in the beta-chloro-D-alanine and L-cycloserine treated groups. This phenomenon is probably due to a difference in the uptake of phospholipid head group component serine and hydrophobic tail precursor palmitic acid: the incorporation of palmitic acid in Tetrahymena is extremely quick, on the other hand, the uptake of serine is slower, a clear time dependence was measured.

In vivo stable isotope studies in three patients affected with mitochondrial fatty acid oxidation disorders: Limited diagnostic use of 1-13C fatty acid breath test using bolus technique

The in vivo oxidation of fatty acids (FA) of different chain length was investigated in three patients with documented mitochondrial FA oxidation disorders: one patient with mild multiple acyl-CoA dehydrogenase deficiency (MADM), one with medium chain acyl-CoA dehydrogenase deficiency (MCAD), and one with carnitine palmitoyltransferase I deficiency (CPT I). Breath tests were performed after oral administration of 1-13C butyric, 1-13C octanoic, and 1-13C palmitic acids. 13C/12C ratio in the expired oxidative end product CO2 was measured. The cumulative 13C elimination was calculated and expressed as a percentage of the administered dose. In the MADM patient the influence of carnitine therapy (or deprivation) on the utilization of 1-13C palmitic acid was also examined. In the MCAD and CPT I patients, the 1-13C butyric, 1-13C octanoic and 1-13C palmitic acids in vivo oxidation were similar to five healthy controls. In the MADM patient, the oxidation of 1-13C butyric and 1-13C octanoic acids were normal, whereas the metabolism of 1-13C palmitic acid ranged from 33% to 66% of controls. In this patient the serum carnitine level decreased from 60 to 27 μmol/l without carnitine supplementation. Clinically there was mild hypotonia. 1-13C palmitic acid oxidation compared to controls was 50%. After 2 further weeks of carnitine deprivation the serum carnitine was 10–15 μmol/l. Clinically he was very hypotonic and had a large liver. 1-13C Palmitic acid oxidation was 33%. After 6 weeks of readministration of carnitine (l-carnitine 100 mg/kg/day p.o.) the serum carnitine was 60 μmol/l and the patient was in good clinical condition. 1-13C palmitic acid oxidation was 66% compared to controls. Our study implies that this simple fatty acid breath test is not of diagnostic use for detection of enzymatic defects in FA oxidation disorders. The carnitine dependent 1-13C palmitic acid oxidation indicates that this test might be of some value in cases with primary or secondary carnitine deficiencies.

Metabolic fate of oleic acid, palmitic acid and stearic acid in cultured hamster hepatocytes.

Unlike other saturated fatty acids, dietary stearic acid does not appear to raise plasma cholesterol. The reason for this remains to be established, although it appears that it must be related to inherent differences in the metabolism of the fatty acid. In the present study, we have looked at the metabolism of palmitic acid and stearic acid, in comparison with oleic acid, by cultured hamster hepatocytes. Stearic acid was taken up more slowly and was poorly incorporated into both cellular and secreted triacylglycerol. Despite this, stearic acid stimulated the synthesis and secretion of triacylglycerol to the same extent as the other fatty acids. Incorporation into cellular phospholipid was lower for oleic acid than for palmitic acid and stearic acid. Desaturation of stearic acid, to monounsaturated fatty acid, was found to be greater than that of palmitic acid. Oleic acid produced from stearic acid was incorporated into both triacylglycerol and phospholipid, representing 13% and 6% respectively of the total after a 4 h incubation. Significant proportions of all of the fatty acids were oxidized, primarily to form ketone bodies, but by 8 h more oleic acid had been oxidized compared with palmitic acid and stearic acid.

Transport and Metabolism of Alanine and Palmitic Acid by Field-Collected Larvae of Tedania ignis (Porifera, Demospongiae): Estimated Consequences of Limited Label Translocation

The epidermis of larvae of Tedania ignis (Porifera, Demospongiae) is uniformly ciliated except for the posterior pole. The epidermal cells are long, columnar, and monociliate; each cilium arises from an epidermal crypt; symbiotic bacteria were not observed in larval cells. These lecithotrophic ("nonfeeding") larvae can feed by assimilating dissolved organic materials (DOM) from seawater. Larvae transported both the amino acid alanine (mean = 2.73 pmol larva-1 h-1; [S] = 1 {mu}M) and the fatty acid palmitic acid (mean = 16.27 pmol larva-1 h-1; [S] = 1 {mu}M) from seawater. Following assimilation, the label from alanine was recovered primarily in small molecular weight compounds; the label from palmitic acid was localized chiefly in the lipid fraction. Estimates of the contribution of transport to metabolism (mean respiration rate = 940.7 pmol O2 larva-1 h-1) reveal that alanine transport is energetically insignificant. Palmitic acid transport, in contrast, could account for 21%-55% of larval metabolism. Autoradiographic analysis of the distribution of the label in larvae suggests that epidermal cells are the chief recipients of the assimilated materials. Thus, the contribution of transport to whole-larva metabolism may underestimate the tissue-specific value. At palmitic acid concentrations of 1 and 0.25 {mu}M, the contribution of transport to the estimated metabolism of the epidermis would be 131% and 33% of energy requirements. Thus, the potential benefits of DOM to larvae are dependent not only on the nature of the epidermal transporters and the solute concentration, but also the degree to which materials are distributed among tissues.