Palmitate Utilization Research Articles

Inpatient prescribing patterns of long-acting injectables and their oral or short-acting injectable equivalent formulations.

Background: Long-acting injectable (LAI) antipsychotics (APs) each have an oral equivalent formulation, while aripiprazole, olanzapine, and ziprasidone each also have a short-acting injectable (SAI) equivalent formulation. Inpatient prescribing patterns of LAIs and their oral/SAI equivalents are less characterized in populations other than Medicaid, Medicare, and Veterans Affairs populations. Mapping out inpatient prescribing patterns remains an important first step to ensure appropriate use of antipsychotics during this critical juncture of patient care prior to discharge. This study determined inpatient prescribing patterns of first- (FGA) and second-generation antipsychotic (SGA) LAIs and their oral/SAI formulations. Methods: This was a large retrospective study using the Cerner Health Facts® database. Hospital admissions due to schizophrenia, schizoaffective disorder, or bipolar disorder from 2010 to 2016 were identified. AP utilization was defined as the proportion of inpatient stays during which at least 1 AP was administered to the total number of inpatient visits over the observed period. Descriptive analyses were used to determine prescribing patterns for APs. Chi-square tests were used to determine utilization differences across years. Results: 94,989 encounters were identified. Encounters during which oral/SAI of SGA LAIs were administered were most common (n = 38,621, 41%). Encounters during which FGA LAIs or SGA LAIs were administered were the least common (n = 1,047, 1.1%). Prescribing patterns differed across years (p < 0.05) within the SGA LAI subgroup analysis (N = 6,014). Paliperidone palmitate (63%, N = 3,799) and risperidone (31%, N = 1,859) were the most frequently administered. Paliperidone palmitate utilization increased from 30% to 72% (p < 0.001), while risperidone utilization decreased from 70% to 18% (p < 0.001). Conclusions: Compared with their oral or SAI formulations, LAIs were underutilized from 2010 to 2016. Among SGA LAIs, the prescribing patterns of paliperidone palmitate and risperidone changed significantly.

No effect of triheptanoin in patients with phosphofructokinase deficiency

Phosphofructokinase deficiency (PFKD) is a rare disorder of glycogen metabolism. The lack of phosphofructokinase activity blocks the oxidative pathway from glucose and glycogen to pyruvate. Patients suffer from myopathy, exercise intolerance, and myoglobinuria. Currently, there is no specific treatment for PFKD. We hypothesized that 2 weeks treatment with triheptanoin could improve oxidative metabolism during exercise by bypassing the blocked pyruvate generation in PFKD. The study was a randomized, double-blind, placebo-controlled crossover study. Three genetically verified patients completed two treatment periods of 14 days each with triheptanoin (0.3–1 g × kg−1 × day−1) or placebo liquid. Primary outcomes were heart rate, fatty acid and total oxidation measured via stable isotope and indirect calorimetry methodology during submaximal exercise. Triheptanoin did not improve the primary outcome heart rate during submaximal exercise compared to placebo. Palmitate oxidation was increased during submaximal exercise in one patient but did not increase in the two other patients during triheptanoin treatment. Palmitate production and palmitate utilization increased during exercise and increased to a greater extent with triheptanoin treatment in all three patients. This study suggests that triheptanoin treatment has no effect on heart rate or exercise performance despite increased palmitate production and utilization in patients with PFKD.

Muscle glycogen synthesis and breakdown are both impaired in glycogenin-1 deficiency.

To study fat and carbohydrate metabolism during exercise in patients with glycogenin-1 (GYG1) deficiency, and to study whether IV glucose supplementation can alleviate exercise intolerance in these patients. This is a case-control study with 4 patients with GYG1 deficiency and 4 healthy controls. Patients performed 1 hour of cycling at 50% of their maximal workload capacity, while controls cycled at the same absolute workloads as patients. Heart rate was measured continuously, and production and utilization of fat and glucose was assessed by stable isotope technique. The following day, patients repeated the exercise, this time receiving an IV 10% glucose supplement. Glucose utilization during exercise was similar in patients and controls, while palmitate utilization was greater in patients compared to controls. However, exercise-induced increases in lactate were attenuated to about half normal in patients. This was also the case during a handgrip exercise test. Glucose infusion improved exercise tolerance in patients, and lowered heart rate by on average 11 beats per minute during exercise. The findings suggest that patients with GYG1 deficiency not only have abnormal formation of glycogen, but also have impaired muscle glycogenolysis, as suggested by impaired lactate production during exercise and improved exercise tolerance with glucose infusion.

Short-Term Cigarette Smoke Exposure Leads to Metabolic Alterations in Lung Alveolar Cells

Cigarette smoke (CS)-induced alveolar destruction and energy metabolism changes are known contributors to the pathophysiology of chronic obstructive pulmonary disease (COPD). This study examines the effect of CS exposure on metabolism in alveolar type II cells. Male A/J mice (8 wk old) were exposed to CS generated from a smoking machine for 4 or 8 weeks, and a recovery group was exposed to CS for 8 weeks and allowed to recover for 2 weeks. Alveolar type II cells were isolated from air- or CS- exposed mice. Acute CS exposure led to a reversible airspace enlargement in A/J mice as measured by the increase in mean linear intercept, indicative of alveolar destruction. The effect of CS exposure on cellular respiration was studied using the XF Extracellular Flux Analyzer. A decrease in respiration while metabolizing glucose was observed in the CS-exposed group, indicating altered glycolysis that was compensated by an increase in palmitate utilization; palmitate utilization was accompanied by an increase in the expression of CD36 and carnitine-palmitoyl transferase 1 in type II alveolar cells for the transport of palmitate into the cells and into mitochondria, respectively. The increase in palmitate use for energy production likely affects the surfactant biosynthesis pathway, as evidenced by the decrease in phosphatidylcholine levels and the increase in phospholipase A2 activity after CS exposure. These findings help our understanding of the mechanism underlying the surfactant deficiency observed in smokers and provide a target to delay the onset of COPD.

Carnitine-Palmitoyltransferase-1 Deficiency Impairs Skeletal Muscle Fatty Acid Oxidation, But Preserves Insulin Sensitivity

Carnitine-deficiency syndromes are often associated with alterations in lipid metabolism and cardiac function. The present study was designed to determine whether this is also seen in an experimental model of carnitine deficiency. Carnitine deficiency was induced in male Sprague-Dawley rats supplemented with sodium pivalate for 26 to 28 weeks. This treatment resulted in nearly a 60% depletion of myocardial total carnitine content as compared with control hearts. When isolated working hearts from these animals were perfused with 5.5 mmol/L glucose and 1.2 mmol/L palmitate and subjected to incremental increases in left-atrial filling pressures, cardiac function remained dramatically depressed. The effects of carnitine deficiency on glucose and palmitate utilization were also assessed in hearts perfused at increased workload conditions. At this workload, function was depressed in carnitine-deficient hearts, as were rates of 1.2-mmol/L [U-14C]-palmitate oxidation, when compared with control hearts (544 ± 37 v 882 ± 87 nmol/g dry weight · min, P < .05). However, glucose oxidation rates from 5.5 mmol/L [U-14C]-glucose were slightly increased in carnitine-deficient hearts. To determine whether the depressed fatty acid oxidation rates were a result of reduced mechanical function in carnitine-deficient hearts, the workload of hearts was reduced. Under these conditions, mechanical function was similar among control and carnitine-deficient hearts. Palmitate oxidation rates were also similar in these hearts (526 ± 69 v 404 ± 47 nmol/g dry weight · min for control and carnitine-deficient hearts, respectively). Our results show that work performed by hearts from carnitine-deficient animals is rate-limiting in the oxidation of palmitate. Despite this, our findings suggest that the sodium pivalate model of carnitine deficiency may prove to be useful for the investigation of functional and metabolic aspects of carnitine deficiency.

A 13C isotopomer model for NMR and GC‐MS analysis

13C NMR spectroscopy and GC‐MS, in combination with stable isotope tracer molecules, offer a unique opportunity in studying metabolic regulation. Accurate quantification of fluxes through different metabolic pathways requires comprehensive analysis of isotopomer distribution. In this study, a mathematical model that describes 13C isotopomer distribution in TCA cycle intermediates was developed and applied to the analysis of NMR and GC‐MS data for quantification of substrate utilization and anaplerosis. Rat hearts were perfused with buffer containing 5.5 mM glucose and 0.6 mM [U‐13C] palmitate. 13C NMR and GC‐MS of tissue extracts were performed for positional isotopomer distribution (PID) of glutamate and mass isotopomer distribution (MID) of key TCA cycle intermediates. Relative palmitate utilization (VFA) and relative anaplerosis (y) were determined by fitting the model to PID or MID. The two methods yielded similar VFA: 0.76±0.09, 0.76±0.09. y determined from MID fitting was higher than from PID fitting: 0.13±0.03 vs 0.08±0.02. Compare to model simulated MID using parameters from PID fitting, GC‐MS measured MID showed a large fraction of M0 isotopmer: 18±4% vs 9±4%. Our results suggest that NMR and GC‐MS are similar in determining substrate utilization. However, the cause of discrepancy in determining anaplerosis needs further investigation.This work is supported by NIH R0173315 and R01HL086935.

ATP Production and TCA Activity are Stimulated by Propionyl-L-Carnitine in the Diabetic Rat Heart

The beneficial effect of propionyl-L-carnitine (PLC) on cardiac function in diabetes mellitus is well documented. This study was designed to determine whether the improvement in cardiac function mediated by PLC in the diabetic rat heart is associated with an increase in ATP production and tricarboxylic acid (TCA) cycle activity. Diabetes was induced by an intravenous injection of streptozotocin (60 mg/kg). Following diagnosis of diabetes, treatment was initiated by supplementing the drinking water with PLC at a concentration of 1 g/L for a period of 6 weeks. ATP production and TCA cycle activity were determined from oxidative rates of glucose and palmitate measured in isolated working hearts from control and diabetic animals. The effect of diabetes was associated with a decrease in heart function, expressed as rate-pressure product (RPP), and in rates of myocardial glucose oxidation. Rates of palmitate oxidation in diabetic hearts were similar to those of control hearts. In PLC-treated diabetic hearts, rates of both glucose and palmitate oxidation were increased and a significant improvement in RPP was observed. As a result, overall ATP production and TCA cycle activity from glucose and palmitate oxidation were increased in diabetic hearts. Our results indicate that the depression in RPP in the diabetic rat heart can be prevented with chronic PLC treatment. Increases in glucose and palmitate utilization with resultant increases in ATP production and TCA cycle activity may explain the benefit of PLC on diabetic rat heart function.

Lack of Myoglobin Causes a Switch in Cardiac Substrate Selection

Myoglobin is an important intracellular O2 binding hemoprotein in heart and skeletal muscle. Surprisingly, disruption of myoglobin in mice (myo-/-) resulted in no obvious phenotype and normal cardiac function was suggested to be mediated by structural alterations that tend to steepen the oxygen pressure gradient from capillary to mitochondria. Here we report that lack of myoglobin causes a biochemical shift in cardiac substrate utilization from fatty acid to glucose oxidation. Proteome and gene expression analysis uncovered key enzymes of mitochondrial beta-oxidation as well as the nuclear receptor PPAR to be downregulated in myoglobin-deficient hearts. Using FDG-PET we showed a substantially increased in vivo cardiac uptake of glucose in myo-/- mice (6.7+/-2.3 versus 0.8+/-0.5% of injected dose in wild-type, n=5, P<0.001), which was associated with an upregulation of the glucose transporter GLUT4. The metabolic switch was confirmed by 13C NMR spetroscopic isotopomer studies of isolated hearts which revealed that [1,6-13C2]glucose utilization was increased in myo-/- hearts (38+/-8% versus 22+/-5% in wild-type, n=6, P<0.05), and concomitantly, [U-13C16]palmitate utilization was decreased in the myoglobin-deficient group (42+/-6% versus 63+/-11% in wild-type, n=6, P<0.05). Because of the O2-sparing effect of glucose utilization, the observed shift in substrate metabolism benefits energy homoeostasis and therefore represents a molecular adaptation process allowing to compensate for lack of the cytosolic oxygen carrier myoglobin. Furthermore, our data suggest that an altered myoglobin level itself may be a critical determinant for substrate selection in the heart. The full text of this article is available online at http://circres.ahajournals.org.

Conditional-dependent effects of CVT-4325, a novel fatty acid oxidation inhibitor, on palmitate utilization

Conditional-dependent effects of CVT-4325, a novel fatty acid oxidation inhibitor, on palmitate utilization

Electrostimulation enhances FAT/CD36-mediated long-chain fatty acid uptake by isolated rat cardiac myocytes.

We investigated palmitate uptake and utilization by contracting cardiac myocytes in suspension to explore the link between long-chain fatty acid (FA) uptake and cellular metabolism, in particular the role of fatty acid translocase (FAT)/CD36-mediated transsarcolemmal FA transport. For this, an experimental setup was developed to electrically stimulate cardiomyocytes in multiple parallel incubations. Electrostimulation at voltages > or =170 V resulted in cellular contraction with no detrimental effect on cellular integrity. At 200 V and 4 Hz, palmitate uptake (measured after 3-min incubation) was enhanced 1.5-fold. In both quiescent and contracting myocytes, after their uptake, palmitate was largely and rapidly esterified, mainly into triacylglycerols. Palmitate oxidation (measured after 30 min) contributed to 22% of palmitate taken up by quiescent cardiomyocytes and, after stimulation at 4 Hz, was increased 2.8-fold to contribute to 39% of palmitate utilization. The electrostimulation-mediated increase in palmitate uptake was blocked in the presence of either verapamil, a contraction inhibitor, or sulfo-N-succinimidyl-FA esters, specific inhibitors of FAT/CD36. These data indicate that, in contracting cardiac myocytes, palmitate uptake is increased due to increased flux through FAT/CD36.

Role of iron in the potentiation of anthracycline cardiotoxicity: Identification of heart cell mitochondria as a major site of iron-anthracycline interaction

The role of iron in anthracycline toxicity was studied in rats in vivo in intact animals and in vitro in heart cell cultures. In animals treated with 8 mg/kg doxorubicin, iron loading resulted in severe weight loss and a twofold increase in rate of mortality. Studies in cultured heart cells aimed at defining the subcellular target of interaction between iron and anthracycline toxicity showed no evidence of anthracycline-induced damage to sarcolemmal thiolic enzymes represented by 5′-nucleotidase and only a limited increase in lysosomal fragility as monitored by an increase in β-hexosaminidase activity in cell homogenates and its release into the culture medium. By contrast, doxorubicin treatment resulted in a marked inhibition of mitochondrial function as monitored by a decrease in carbon 14-labeled palmitate utilization, to 33% ± 4% of controls, and prior iron loading resulted in a further decrease in palmitate utilization, to 18% ± 3% of controls. Conversely, iron-chelation treatment by either deferoxamine or deferiprone (L1) eliminated the harmful effects of iron loading and resulted in a partial inhibition of doxorubicin toxicity in both normal and iron-loaded cells. Our studies represent the first demonstration in intact animals of the potentiation of anthracycline toxicity by iron overload. They also indicate that mitochondria represent an important target of combined iron-anthracycline toxicity. These observations provide new insights into the mechanism of anthracycline cardiotoxicity and may be useful in developing better strategies for tumor therapy.

Fatty acid oxidation and cardiac function in the sodium pivalate model of secondary carnitine deficiency

Carnitine-deficiency syndromes are often associated with alterations in lipid metabolism and cardiac function. The present study was designed to determine whether this is also seen in an experimental model of carnitine deficiency. Carnitine deficiency was induced in male Sprague-Dawley rats supplemented with sodium pivalate for 26 to 28 weeks. This treatment resulted in nearly a 60% depletion of myocardial total carnitine content as compared with control hearts. When isolated working hearts from these animals were perfused with 5.5 mmol/L glucose and 1.2 mmol/L palmitate and subjected to incremental increases in left-atrial filling pressures, cardiac function remained dramatically depressed. The effects of carnitine deficiency on glucose and palmitate utilization were also assessed in hearts perfused at increased workload conditions. At this workload, function was depressed in carnitine-deficient hearts, as were rates of 1.2-mmol/L [U- 14C]-palmitate oxidation, when compared with control hearts (544 ± 37 v 882 ± 87 nmol/g dry weight · min, P < .05). However, glucose oxidation rates from 5.5 mmol/L [U- 14C]-glucose were slightly increased in carnitine-deficient hearts. To determine whether the depressed fatty acid oxidation rates were a result of reduced mechanical function in carnitine-deficient hearts, the workload of hearts was reduced. Under these conditions, mechanical function was similar among control and carnitine-deficient hearts. Palmitate oxidation rates were also similar in these hearts (526 ± 69 v 404 ± 47 nmol/g dry weight · min for control and carnitine-deficient hearts, respectively). Our results show that work performed by hearts from carnitine-deficient animals is rate-limiting in the oxidation of palmitate. Despite this, our findings suggest that the sodium pivalate model of carnitine deficiency may prove to be useful for the investigation of functional and metabolic aspects of carnitine deficiency.

Myocardial function and metabolism in pig hearts after relief from chronic partial coronary stenosis

Metabolic behavior was compared during acute extracorporeal reperfusion after removal of a chronic 4-day partial coronary stenosis in eight pig hearts (RCS group) and during comparable extracorporeal perfusion in seven chronically prepared hearts (Sham group). Coronary stenosis in RCS hearts was induced in the left anterior descending (LAD) artery by partial inflation of a hydraulic occluder to restrict LAD peak phasic velocity by approximately 50%. Regional mechanical shortening was decreased in RCS compared with Sham hearts after 4 days of chronic coronary stenosis [diminished systolic shortening (P < 0.066) with systolic expansion (P < 0.015)] but was comparable to Sham hearts after relief from stenosis. At analogous workloads (left ventricular pressure and heart rate) during reperfusion, metabolic behavior was distinctive between groups. Specifically, compared with Sham hearts, myocardial O2 consumption was selectively increased in RCS hearts (+ 49 delta %, P < 0.026) as was fatty acid oxidation estimated from 14CO2 production from [U-14C]palmitate (+ 60 delta %, P < 0.061) and exogenous glucose utilization measured from the release of 3H2O from [5-3H]glucose (+ 517 delta %, P < 0.025). At the conclusion of the studies, triphenyltetrazolium chloride staining showed no gross evidence of macroinfarction in RCS or Sham hearts, and there was an essentially unremarkable histological survey of anterior myocardium for microscopic necrosis in either group. The level of O2 consumption and preservation of preferred fatty acid utilization indicate that metabolism remains or regains its aerobic pattern of activity in early recovery immediately after removal of chronic partial coronary stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibitory action of palmitic acid on the growth of Saccharomyces cerevisiae.

High concentrations of long-chain fatty acids have been found to be harmful to mammalian cells and prokaryotic organisms. This effect was investigated in Saccharomyces cerevisiae. Addition of 3 mmol/L palmitate to a yeast extract-peptone medium caused a significant inhibition of cell growth during the first 2 d of incubation, followed by renewed growth and palmitate utilization. Inhibition was also observed with palmitate concentrations down to 0.1 mmol/L. As inferred from catalase activity determinations, this effect was found to correlate with the absence of peroxisome proliferation. Finally, no inhibition was observed in exponential-phase cultures or in the presence of 0.1 g/L glucose, this suggesting that the physiological state of the cell may determine whether its growth will be inhibited by fatty acids.

Palmitate utilization by isolated mitochondria from chromically-overloaded rat hearts

Palmitate utilization by isolated mitochondria from chromically-overloaded rat hearts

Fatty acid metabolism by the porcine placenta

Two experiments were performed to determine whether esterification is a major pathway of fatty acid utilization within porcine placenta and to determine what metabolic parameters may limit fatty acid transfer to the fetal pig. Maternal (endometrium) and fetal (chorioallantois) placenta were obtained by Caesarean section at d 110 of gestation in both experiments. Eight gilts were used in the first experiment. Tissue sections were incubated with palmitate at concentrations ranging from .25 to 2.0 mM. Maternal placenta metabolized palmitate at a higher rate than fetal placenta, although fetal placenta was more efficient in esterifying palmitate. Esterification composed the majority of palmitate utilization within fetal and maternal placenta. The second experiment evaluated the effect of dietary lipid on placental fatty acid metabolism and evaluated the ability of placenta to mobilize lipids. Fourteen gilts were divided into two groups of seven and fed a diet containing 15% tallow diet or a diet not supplemented with tallow (control) from d 90 to 110 of gestation. Dietary lipid had no detectable effects on lipoprotein lipase activity, [14C]palmitate metabolism, or lipolysis by the maternal or fetal placenta. Lipolytic activity of placental tissues was minimally affected by incubation with various proposed lipolytic activity of placental tissues was minimally affected by incubation with various proposed lipolytic agents. The data indicate that supply of fatty acids to the fetal pig may be limited by transfer of plasma fatty acids into the cytoplasm of placental cells or by regulatory enzymes for intermediate esterification; both types of limitations have been proposed to be influenced by fatty-acid binding proteins.

Change from aerobic to anaerobic metabolism after brain death, and reversal following triiodothyronine therapy.

Brain-dead organ donors are depleted of circulating triiodothyronine (T3) and show features suggestive generally of anaerobic metabolism at the tissue level, accompanied by deteriorating hemodynamic function. The principle of single-bolus kinetics with labeled carbon compounds (14C-R), with subsequent measurement of both plasma activity and of exhaled 14C O2 has therefore been used to study glucose, pyruvate, and palmitate utilization under conditions of (1) sedation, (2) brain death, and (3) brain death with T3 therapy in the baboon. Serum lactate and plasma-free fatty acid concentrations were also measured. There was a major change in metabolic oxidative processes following brain death. The rate of glucose, pyruvate, and palmitate utilization was markedly reduced, and there was an accumulation of lactate and free fatty acids in the plasma, indicating a general change from aerobic to anaerobic metabolism. The administration of T3 to the brain-dead baboon resulted in a dramatic increase in the rate of metabolite utilization, and a reduction in the plasma concentrations of plasma lactate and free fatty acids, indicating an apparent reversal from tissue anaerobic to aerobic metabolism. We suggest that T3 should be administered to all brain-dead potential organ donors to correct and maintain a more physiologic metabolic status and thus to improve organ function.

Inhibition of long-chain fatty acid oxidation by methylglyoxal bis(guanylhydrazone)

Methylglyoxal bis(guanylhydrazone) (MGBG), an inhibitor of spermidine and spermine biosynthesis and clinically used anti-cancer drug, powerfully inhibited carnitine-dependent fatty acid oxidation in heart muscle homogenates. Equipotent inhibition was also produced by spermine whereas spermidine and putrescine were less effective. MGBG appeared to act as a competitive inhibitor in respect to carnitine. Even though MGBG and spermine equally effectively depressed palmitate oxidation in muscle homogenates in vitro, a striking difference existed between the compounds as regards their effects on fatty acid oxidation in cultured tumor cells. Micromolar concentrations of MGBG distinctly impaired palmitate utilization also in cultured L 1210 leukemia cells, whereas similar concentrations of spermine markedly enhanced the oxidation of the fatty acid. The inhibitory effect of MGBG in cultured tumor cells was, at least partly, reversed upon addition of exogenous carnitine. The finding indicating that MGBG impairs fatty acid utilization may be an explanation for the known hypoglycemic effect produced by the drug in most animal species as well as for some of the side-effects associated with its clinical use, most notably severe myalgia.

The control of fatty acid metabolism in liver cells from fed and starved sheep.

Isolated liver cells prepared from starved sheep converted palmitate into ketone bodies at twice the rate seen with cells from fed animals. Carnitine stimulated palmitate oxidation only in liver cells from fed sheep, and completely abolished the difference between fed and starved animals in palmitate oxidation. The rates of palmitate oxidation to CO2 and of octanoate oxidation to ketone bodies and CO2 were not affected by starvation or carnitine. Neither starvation nor carnitine altered the ratio of 3-hydroxybutyrate to acetoacetate or the rate of esterification of [1-14C]palmitate. Propionate, lactate, pyruvate and fructose inhibited ketogenesis from palmitate in cells from fed sheep. Starvation or the addition of carnitine decreased the antiketogenic effectiveness of gluconeogenic precursors. Propionate was the most potent inhibitor of ketogenesis, 0.8 mM producing 50% inhibition. Propionate, lactate, fructose and glycerol increased palmitate esterification under all conditions examined. Lactate, pyruvate and fructose stimulated oxidation of palmitate and octanoate to CO2. Starvation and the addition of gluconeogenic precursors stimulated apparent palmitate utilization by cells. Propionate, lactate and pyruvate decreased cellular long-chain acylcarnitine concentrations. Propionate decreased cell contents of CoA and acyl-CoA. It is suggested that propionate may control hepatic ketogenesis by acting at some point in the beta-oxidation sequence. The results are discussed in relation to the differences in the regulation of hepatic fatty acid metabolism between sheep and rats.

Effects of lactate and glutamine on palmitate metabolism in rat kindey cortex

Rat renal cortical slices were incubated with [1-(14)C]palmitate bound to 2.5% albumin. The following effects were found: a)1 mM palmitate utilization or oxidation to CO(2) varied according to the concentration of lactate in the media, it increased at 0.8 and 3.2 mM, was unchanged at 8 mM, and decreased at 16 mM. Esterification was stimulated at 3.2 mM lactate. b) Addition of glutamine (0.1 mM) instead of lactate stimulated incomplete and complete oxidation of palmitate (1 mM), whereas high medium glutamine (10 mM) inhibited palmitate (1 mM) utilization, esterification, and oxidation to CO(2) but increased its incomplete oxidation. The low rate of exogenous palmitate oxidation observed in this study and the finding that exogenous palmitate oxidation is only partially inhibited at very high concentrations of exogenous lactate or glutamine are consistent with the view that these exogenous substrates contribute little to the oxidative metabolism of rat renal cortex in vitro, which probably depends on the supply of substrates endogenous to the tissue.