Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Palmitates”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 73 records · Page 4Linked to original sources
PubMed1997

Uptake and metabolism of palmitate by isolated cardiac myocytes from adult rats: involvement of sarcolemmal proteins.

The precise mechanism of uptake of long-chain fatty acids (FA) by cardiac myocytes is incompletely understood. We examined the involvement of sarcolemmal proteins in the initial uptake of FA by isolated rat cardiac myocytes, and the relation between initial uptake and metabolism. Cardiac myocytes were incubated in the presence of 90 microns [1-14C]palmitate complexed to 300 microns bovine serum albumin (BSA), presenting a physiologically relevant condition. During initial palmitate uptake (3 min), 56% of the intracellularly sequestered palmitate was esterified, and an additional 21% converted into oxidation intermediates. Varying the palmitate/BSA molar ratio revealed saturation kinetics with the apparent Km for cellular palmitate uptake (435 micro M) to be comparable to those for esterification (465 micro M) and oxidation (222 micro M). Varying the BSA concentration at a fixed palmitate/BSA molar ratio also showed saturation of uptake at increasing concentrations, with an apparent Km for BSA of 23 micro M. Changes in palmitate metabolism induced by changes in glucose utilization were accompanied by identical effects on palmitate uptake. Addition of lactate also inhibited both oxidation and uptake of palmitate, but had no effect on esterification. Virtually complete inhibition of palmitate oxidation by etomoxir inhibited palmitate uptake for 50%, while decreasing esterification by 33%. In the presence of phloretin and trypsin, palmitate uptake and metabolism were inhibited 76-88%, and in the presence of sulfo-N-succinimidyloleate by 53%. It is concluded that a) the bulk of sarcolemmal palmitate translocation occurs by membrane-associated FA-binding proteins, most likely assisted by albumin binding proteins without regulatory function, and b) palmitate uptake is most likely driven by its rapid intracellular metabolic conversion.

Animals↗
PubMed1995

Effect of nitric oxide on albumin-palmitate binding.

Bovine serum albumin (albumin) was modified by treatment with nitric oxide (NO) to form S-nitrosoalbumin. Analysis of the reduced sulfhydryl groups showed that more than 99% of the albumin was converted to S-nitrosoalbumin. Using a 1:1 molar ratio of protein:palmitate, the unbound palmitate fraction in the presence of S-nitrosoalbumin was determined to be greater (28%) than in the presence of albumin as determined by heptane: water partitioning. NO degradation products neither affected the palmitate heptane:water partition ratio in the absence of binding protein nor the hepatocyte uptake of [3H]palmitic acid. The equilibrium association constants (Ka) for albumin-palmitate and S-nitrosoalbumin-palmitate complexes were determined using the stepwise equilibrium model. The Ka for the first and second palmitate binding sites were (4.6 +/- 1.2) x 10(8) M-1 and (3.3 +/- 0.5) x 10(7) M-1 and (3.1 +/- 0.9) x 10(8) M-1 and (1.3 +/- 0.8) x 10(8) M-1 for albumin and S-nitrosoalbumin, respectively. Thus, the increased unbound fraction of palmitate in the presence of S-nitrosoalbumin was apparently due to a decreased binding affinity at the first high-affinity binding site. Palmitate uptake by hepatocyte suspensions was 27% higher in the presence of S-nitrosoalbumin as compared with albumin. This increase paralleled the increased unbound palmitate fraction. When the albumin concentration was adjusted to account for the increased unbound fraction, there was no difference in the palmitate uptake rates between albumin and S-nitrosoalbumin. Our findings indicate that under conditions where NO concentrations are high (e.g. cirrhosis) and extensive S-nitrosylation of serum albumin occurs, the decreased ligand binding ability of S-nitrosoalbumin may be an important consideration when modeling drug uptake in pathological states.

Animals↗
PubMed1989

Palmitic acid stimulates glucose incorporation in the adipocyte by a mechanism likely involving intracellular calcium.

The effect of palmitic acid on basal and insulin-stimulated incorporation of glucose into rat adipocytes was studied. Palmitic acid (2.40 mM) stimulated basal as well as insulin-stimulated glucose incorporation in rat adipocytes three and twofold, respectively. Similar degrees of stimulation of basal glucose oxidation by palmitate were also observed. The ability of palmitic acid to stimulate glucose uptake was additive with respect to the stimulation induced by insulin and was proportional to the palmitic acid concentration between 0.15 mM and 2.40 mM. Stimulation of glucose incorporation by palmitic acid was inhibited by preincubating the cells with quin2-AM, which accumulates intracellularly yielding the trapped chelator form. quin2, which binds intracellular Ca2+.The concentration of quin2-AM required for half-maximal inhibition of palmitic acid stimulated glucose incorporation was 3.8 +/- 1.2 microM (mean +/- SEM). The inhibition of palmitic acid-stimulated glucose incorporation by quin2-AM (10 microM) was overcome by incubating cells with the Ca2+ ionophore, A23187, in the presence of extracellular Ca2+ (2.6 mM). Chelation of extracellular Ca2+ with EGTA did not significantly affect the magnitude of palmitic acid-stimulated glucose incorporation. Dantrolene (12.5-100 microM) failed to affect basal or palmitic acid-stimulated glucose incorporation. These findings suggest that palmitic acid stimulates incorporation of glucose in the adipocyte by a mechanism dependent upon intracellular but not extracellular Ca2+.

Adipose Tissue↗
PubMed1998

Binding of [3H]palmitate to BSA.

Determination of the BSA-palmitate high-affinity binding constant (Ka) traditionally relied on the heptane-water partitioning technique. We used this technique to calculate Ka for the BSA-[3H]palmitate complex, to determine if Ka was independent of protein concentration, and to determine if the unbound [3H]palmitate concentration is constant at different BSA concentrations using constant BSA-to-palmitate molar ratios (range 1:1 to 1:4). After extensive extraction of non-[3H]palmitate radiolabeled substances, the heptane-to-buffer partition ratio, in the absence of BSA, was 702 +/- 19 (mean +/- SD, n = 6). This value was much lower than the predicted value of 1,376 and was highly dependent on which phase (organic or aqueous) initially contained the [3H]palmitic acid. The data were consistent with the notion of self-association of [3H]palmitate in the aqueous phase. Ka for the BSA-[3H]palmitate complex was determined to be similar (2.2 +/- 0.1) x 10(8) M-1 (mean +/- SD, P > 0.05) at all BSA concentrations studied. At each BSA-to-palmitate molar ratio, the equilibrium unbound ligand concentration was constant only at low BSA concentrations (<10 microM) and at low BSA-to-palmitate molar ratios (i.e., 1:1 and 1:2). At higher BSA concentrations and molar ratios, the unbound ligand concentration increased with an increase in protein concentration. Hepatocyte uptake using the manufacturer-supplied radiolabeled product was significantly higher than with the purified product, suggesting that a non-[3H]palmitate radiolabel is also a substrate for the uptake process.

Animals↗
PubMed1998

Contraction-induced increase in Vmax of palmitate uptake and oxidation in perfused skeletal muscle.

To evaluate the effects of contractions on the kinetics of uptake and oxidation of palmitate in a physiological muscle preparation, rat hindquarters were perfused with glucose (6 mmol/l), albumin-bound [1-14C]palmitate, and varying amounts of albumin-bound palmitate (200-2,200 micro mol/l) at rest and during muscle contractions. When plotted against the unbound palmitate concentration, palmitate uptake and oxidation displayed simple Michaelis-Menten kinetics with estimated maximal velocity (Vmax) and Michaelis-Menten constant (Km) values of 42.8 +/- 3.8 (SE) nmol . min-1 . g-1 and 13.4 +/- 3.4 nmol/l for palmitate uptake and 3.8 +/- 0.4 nmol . min-1 . g-1 and 8.1 +/- 2.9 nmol/l for palmitate oxidation, respectively, at rest. Whereas muscle contractions increased the Vmax for both palmitate uptake and oxidation to 91.6 +/- 10.1 and 16.5 +/- 2.3 nmol . min-1 . g-1, respectively, the Km remained unchanged. Vmax and Km estimates obtained from Hanes-Woolf plots (substrate concentration/velocity vs. substrate concentration) were not significantly different. In the resting perfused hindquarter, an increase in palmitate delivery from 31.9 +/- 0.9 to 48.7 +/- 1.2 micro mol . g-1 . h-1 by increasing perfusate flow was associated with a decrease in the fractional uptake of palmitate so that the rates of uptake and oxidation of palmitate remained unchanged. It is concluded that the rates of uptake and oxidation of long-chain fatty acids (LCFA) saturate with an increase in the concentration of unbound LCFA in perfused skeletal muscle and that muscle contractions, but not an increase in plasma flow, increase the Vmax for LCFA uptake and oxidation. The data are consistent with the notion that uptake of LCFA in muscle may be mediated in part by a transport system.

Animals↗
PubMed2002

Expression profiling of palmitate- and oleate-regulated genes provides novel insights into the effects of chronic lipid exposure on pancreatic beta-cell function.

Chronic lipid exposure is implicated in beta-cell dysfunction in type 2 diabetes. We therefore used oligonucleotide arrays to define global alterations in gene expression in MIN6 cells after 48-h pretreatment with oleate or palmitate. Altogether, 126 genes were altered > or =1.9-fold by palmitate, 62 by oleate, and 46 by both lipids. Importantly, nine of the palmitate-regulated genes are known to be correspondingly changed in models of type 2 diabetes. A tendency toward beta-cell de-differentiation was also apparent with palmitate: pyruvate carboxylase and mitochondrial glycerol 3-phosphate dehydrogenase were downregulated, whereas lactate dehydrogenase and fructose 1,6-bisphosphatases were induced. Increases in the latter (also seen with oleate), along with glucosamine-phosphate N-acetyl transferase, imply upregulation of the hexosamine biosynthesis pathway in palmitate-treated cells. However, palmitate also increased expression of calcyclin and 25-kDa synaptosomal-associated protein (SNAP25), which control distal secretory processes. Consistent with these findings, secretory responses to noncarbohydrate stimuli, especially palmitate itself, were upregulated in palmitate-treated cells (much less so with oleate). Indeed, glucose-stimulated secretion was slightly sensitized by chronic palmitate exposure but inhibited by oleate treatment, whereas both lipids enhanced basal secretion. Oleate and palmitate also induced expression of chemokines (MCP-1 and GRO1 oncogene) and genes of the acute phase response (serum amyloid A3). Increases in transcriptional modulators such as ATF3, CCAAT/enhancer binding protein-beta (C/EBPbeta), C/EBPdelta, and c-fos were also seen. The results highlight links between regulated gene expression and phenotypic alterations in palmitate versus oleate-pretreated beta-cells.

Acute-Phase Proteins↗
PubMed1983

Incorporation of [3H]palmitate into disaturated phosphatidylcholines in alveolar type II cells isolated by centrifugal elutriation.

In order to study synthesis of pulmonary surfactant materials, we measured incorporation of [3H]palmitate into disaturated phosphatidylcholines (PC) in alveolar type II cells isolated by centrifugal elutriation. The time course for this process is not linear and, at high external palmitate levels (1 mM), incorporation is maximal in 4-5 h. Incorporation is dependent on extracellular palmitate with a Vmax (at 1 mM) of 1.66 nmol palmitate incorporated into disaturated PC/4.2 X 10(5) cells per 2 h and a K1/2 of 0.1 mM palmitate. Addition of an optimal amount of extracellular choline (0.05 mM) increases Vmax and decreases K1/2 for palmitate. Incorporation of palmitate is dependent upon cell number, inhibited by extracellular Ca2+ and stimulated by external Mg2+. Cholinergic and beta-adrenergic agonists do not increase incorporation. Pulmonary lavage fluid inhibits incorporation of palmitate into disaturated PC, suggesting there is negative feedback involved. Disaturated PC which has been recently synthesized (i.e., over a 2 h period) is broken down intracellularly by type II cells when they are suspended in palmitate-free medium. These results indicate that (1) several factors, such as substrate levels, cell number, Ca2+, Mg2+ and amount of surfactant present, are involved in the regulation of palmitate incorporation into disaturated PC; (2) disaturated PC which has been recently synthesized may be broken down by type II cells; and (3) surfactant synthesis in freshly isolated cells differs slightly from that reported by other investigators in type II cells maintained in primary cell culture.

Animals↗
PubMed1985

Incorporation of [3H]palmitate and [14C]choline into disaturated phosphatidylcholines in rat alveolar macrophages.

We studied the synthesis of disaturated phosphatidylcholines in rat alveolar macrophages and, in some cases, compared it with that which occurs in isolated alveolar type II cells. Alveolar macrophages suspended in phosphate-buffered medium incorporate palmitate, choline and glycerol into disaturated phosphatidylcholines. The time-course for incorporation of palmitate into disaturated phosphatidylcholines is linear for 20-30 min and reaches a maximum in 2-3 h. Incorporation is dependent on extracellular palmitate with a Vmax (at 1 mM) of 1.53 nmol palmitate incorporated into disaturated phosphatidylcholines per 5 X 10(5) cells per 2 h and a K 1/2 of 0.19 mM palmitate. Exposure of the cells to zymosan particles increases incorporation of palmitate disaturated phosphatidylcholines by almost 2-fold, while cholinergic and beta-adrenergic agonists have no effect. On a per cell basis, alveolar macrophages incorporate only one-third to one-half as much palmitate into disaturated phosphatidylcholines as do type II cells isolated by centrifugal elutriation. The following results suggest there is extensive remodeling of disaturated phosphatidylcholines in alveolar macrophages: (1) palmitate- and choline-labeled disaturated phosphatidylcholines are catabolized by the cells; (2) the products of catabolism are palmitate and water-soluble choline products; (3) addition of unlabeled palmitate and choline to the medium enhances catabolism of the labeled phospholipid. Addition of oleate also enhances catabolism, suggesting that modification of phospholipids is not specific for the saturated variety. Some of the recently labeled disaturated phosphatidylcholines is released from alveolar macrophages into the extracellular space. Several possible functions of alveolar macrophage disaturated phosphatidylcholines are discussed.

Animals↗
PubMed1986

Turnover of palmitate, arachidonate and glycerol in phospholipids of rat rod outer segments.

Rat retinas were intravitreally labeled with [3H]palmitic acid, [3H]arachidonic acid or [3H]glycerol to study the turnover of the component parts of the major phospholipids in rod outer segments at times ranging from 2 hr to 12 days post injection. Rod outer-segment and retinal debris fractions were extracted and the major phospholipids separated by two-dimensional thin-layer chromatography. In darkness, [3H]glycerol rapidly labeled phosphatidylinositol in both rod outer-segment and retinal debris fractions. The label in phosphatidylinositol subsequently decreased dramatically, demonstrating a rapid turnover of phosphatidylinositol with a half-life of less than 1 day. Phosphatidylcholine and phosphatidylethanolamine were maximally labeled by glycerol in the retinal debris at the 2-hr time-point and were maximally labeled in rod outer segments between 1 and 5 days post injection, with somewhat longer residence times in the rod outer segments. Phosphatidylserine showed a lag in initial labeling in both rod outer-segment and retinal debris fractions indicating that this phospholipid is not a major precursor of phosphatidylcholine and phosphatidylethanolamine in rat retinas. [3H]Palmitate and [3H]arachidonate labels were rapidly incorporated into outer-segment phospholipids by 1-2 hr post injection. Eighty per cent of the palmitate label was initially associated with phosphatidylcholine at 2 hr. The total amount of palmitate label in rod outer-segment phosphatidylcholine did not change for 12 days post injection. Outer-segment phosphatidylethanolamine steadily increased in palmitate label throughout the 12-day period, suggesting that phosphatidylethanolamine may be utilized for recapture of palmitate released from breakdown of palmitate esters of rhodopsin or vitamin A or from phospholipids. Arachidonate primarily labeled phosphatidylinositol and phosphatidylcholine of both rod outer segments and retinal debris. The arachidonate label did not decrease dramatically during the first day in phosphatidylinositol as did the glycerol label, indicating that arachidonic acid is reutilized by the retina. Turnover of the individual phospholipids, as measured by a decrease in glycerol labeling of the phospholipid backbone, is more rapid than the loss of palmitate label, indicating that there is extensive reutilization of palmitate in both phosphatidylcholine and phosphatidylethanolamine of the rod outer segment. The data indicate that palmitate derived from many sources could be used by the photoreceptor to acylate rhodopsin.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

A method for examining turnover and synthesis of palmitate-containing brain lipids in vivo.

1. A theoretical three compartment model is presented which gives the rate of incorporation of plasma palmitate into brain, Jpalm, in terms of turnover and synthesis of palmitate-containing lipids, de novo synthesis of palmitate from acetate, and recycling of palmitate within lipids. 2. Jpalm equals 4 h brain radioactivity following intravenous injection of [U-14C]-palmitate (determined with quantitative autoradiography), divided by integrated plasma specific activity of palmitate. Jpalm follows the time course of brain lipid synthesis during development of the rat, but is age-invariant in the adult. 3. At 1-7 days after 5 min of bilateral carotid occlusion in the awake gerbil, intravascular [14C]-palmitate incorporation is reduced in the CA1 pyramidal layer of the hippocampus, consistent with delayed neuronal death, but is elevated in the CA3 and CA4 pyramidal layers and dentate gyrus, suggesting synthesis of new membrane during recovery from the ischaemic insult. 4. Several weeks after unilateral destruction of the cochlea in 11 day old rats, incorporation of [14C]-palmitate from plasma into appropriate central auditory regions is reduced, corresponding to reduced cell size and altered morphology. 5. [14C]-palmitate incorporation into the left hypoglossal nucleus is increased during and following axonal regeneration (up to 23% compared with control side) following transection of the left hypoglossal nerve in Fischer-344 rats, whereas incorporation is decreased 6-7% when regeneration is prevented. Time courses of incorporation in both cases correspond to histological changes. 6. The results show that the palmitate method can be used to examine regional turnover and synthesis of brain lipids following injury, sensory deprivation, development, regeneration and ageing.

Animals↗
PubMed1989

Palmitate oxidation by isolated working fetal and newborn pig hearts.

Palmitate oxidation and the effect of palmitate on glucose and lactate utilization were investigated in isolated, perfused, fetal (0.9 gestation), and neonatal (2 day old) pig hearts. Hearts were perfused under working conditions, developing a mean aortic pressure of 50-55 mmHg, paced at 180 beats/min for 30 min, with Krebs-Henseleit buffer containing 3% albumin, glucose (5 mM), and insulin (100 microU/ml). Palmitate (1 mM) and lactate (5 mM), either individually or in combination, were added to the perfusion buffer. Palmitate oxidation was assessed from 14CO2 production from [U-14C]-palmitate, glucose uptake as 3H2O production from D-[2-3H]-glucose, and lactate metabolism from changes in buffer lactate content. After perfusion, ATP, creatine phosphate, triglycerides, and glycogen were measured. Substantial palmitate oxidation was observed at both ages but was greater in neonatal hearts. Nevertheless, palmitate inhibited lactate utilization and glucose uptake similarly in fetal and neonatal hearts. Lactate also reduced palmitate uptake and oxidation by 40-60% in both fetal and neonatal hearts. During perfusions with palmitate, tissue concentrations of triglycerides increased approximately threefold in fetal hearts and were unaffected by lactate. Thus both palmitate and lactate can act as major energy substrates for the immature heart. Both substrates significantly (P less than 0.01) suppress glucose utilization, and each has suppressive effects on the other's metabolism.

Adenosine Triphosphate↗
PubMed1985

Metabolism of palmitate in cultured rat Sertoli cells.

Isolated rat Sertoli cells were incubated in the presence of [1-14C]palmitate at a cell concentration of 1.54 +/- 0.31 mg protein/flask (n = 7). The oxidation of palmitate was concentration dependent and maximal oxidation was obtained at 0.35 mM-palmitate. At a saturating concentration of palmitate the oxidation was linear for at least 6 h. About 65% of the total amount of palmitate oxidized during 5 h at 0.52 mM-palmitate (109 +/- 44 nmol/flask, n = 5) was recovered as CO2 and the rest as acid-soluble compounds. Almost all radioactive acid-soluble compounds which were secreted by the Sertoli cells were shown to be 3-hydroxybutyrate and acetoacetate. The palmitate recovery in cellular lipids and triacylglycerols was 9.4 +/- 5.1 nmol/flask (n = 5) and 3.5 +/- 2.8 nmol/flask (n = 5) respectively. Addition of glucose had no significant effect on palmitate oxidation but caused a 9-fold increase in esterification of palmitate into triacylglycerols. We conclude that cultured rat Sertoli cells can oxidize palmitate to CO2 and ketone bodies and that fatty acids appear to be a major energy substrate for these cells.

3-Hydroxybutyric Acid↗
PubMed1984

Mechanisms of fatty acid effects on sarcoplasmic reticulum. II. Structural changes induced by oleic and palmitic acids.

The interaction of micromolar concentrations of palmitic and oleic acids with the sarcoplasmic reticulum membrane was studied by electron microscopic techniques in an attempt to define their different effects on ATP-induced calcium sequestration in sarcoplasmic reticulum vesicles. Oleic acid had a concentration-dependent effect on the morphology of sarcoplasmic reticulum vesicles, promoting vesicle fusion and eventual solubilization. Palmitic acid did not alter the morphology of sarcoplasmic reticulum, but its probable site(s) of interaction could be determined. In the presence of palmitic acid, large lamellar structures that formed external to sarcoplasmic reticulum vesicles are probably composed of pure palmitic acid and/or palmitic acid/phospholipid mixed "micelles," but internalization of palmitic acid into sarcoplasmic reticulum vesicles was not detected. Palmitic acid reduced the phospholipid content of sarcoplasmic reticulum membranes with a preservation of the average interparticle protein spacing as observed in freeze-fracture electron micrographs. Thus, palmitic acid appears to be incorporated into the sarcoplasmic reticulum lipid bi-layer. Oleic acid inhibition of ATP-induced calcium sequestration by sarcoplasmic reticulum vesicles is probably caused by net permeability changes of the membrane. A structural mechanism for palmitic acid stimulation of ATP-induced calcium sequestration is proposed in light of the probable insertion of palmitic acid into the sarcoplasmic reticulum lipid bilayer.

Adenosine Triphosphate↗
PubMed2000

Inhibition of insulin gene expression by long-term exposure of pancreatic beta cells to palmitate is dependent on the presence of a stimulatory glucose concentration.

Long-term exposure of pancreatic beta cells to elevated levels of fatty acids (FAs) impairs glucose-induced insulin secretion. However, the effects of FAs on insulin gene expression are controversial. We hypothesized that FAs adversely affect insulin gene expression only in the presence of elevated glucose concentrations. To test this hypothesis, isolated rat islets were cultured for up to 1 week in the presence of 2.8 or 16.7 mmol/L glucose with or without 0.5 mmol/L palmitate. Insulin release, insulin content, and insulin mRNA levels were determined at the end of each culture period. Palmitate increased insulin release at each time point independently of the glucose concentration. In contrast, insulin content was unchanged in the presence of palmitate at 2.8 mmol/L glucose, but was markedly decreased in the presence of 0.5 mmol/L palmitate and 16.7 mmol/L glucose after 2, 3, and 7 days of culture. In the presence of a basal concentration of glucose, insulin mRNA levels were transiently increased by palmitate at 24 hours but were unchanged thereafter. In contrast, palmitate significantly inhibited the stimulatory effects of 16.7 mmol/L glucose on insulin mRNA levels after 2, 3, and 7 days. To determine whether the inhibitory effect of palmitate on glucose-stimulated insulin mRNA levels was associated with decreased insulin promoter activity, HIT-T15 cells were cultured for 24 hours in 11.1 mmol/L glucose in the presence or absence of palmitate, and insulin gene promoter activity was measured in transient transfection experiments using the insulin promoter-reporter construct INSLUC. INSLUC activity was decreased more than 2-fold after 24 hours of exposure to 0.5 mmol/L palmitate. We conclude that long-term exposure of pancreatic beta cells to palmitate decreases insulin gene expression only in the presence of elevated glucose concentrations, in part through inhibition of insulin gene promoter activity.

Animals↗
PubMed2001

Methyl-beta-cyclodextrin: an alternative carrier for intravenous infusion of palmitate during tracer studies in swine (Sus scrofa domestica).

Fatty acid-free albumin has been the standard carrier for intravenous infusion of fatty acids to study in vivo lipid metabolism. However, subjects can have adverse reactions to infusion of albumin. We sought an alternative to albumin as a carrier for intravenous infusion of fatty acids, using the pig as a model. Cyclodextrins are naturally occurring water-soluble molecules that can serve as carriers for lipid-soluble compounds. 13C-palmitate was complexed to either 20% methyl-beta-cyclodextrin, 20% 2-hydroxypropyl-beta-cyclodextrin, or 5% porcine albumin (isotopic purity of infusates: 99.22+/-0.06%). 13C-palmitate-albumin was infused under fed conditions and 13C-palmitate-methyl-beta-cyclodextrin was infused under fasted and fed conditions in 50-kg pigs. Palmitate remained in solution at 4 degrees C in methyl-beta-cyclodextrin, but precipitated at 25-30 degrees C in 2-hydroxypropyl-beta-cyclodextrin. Pigs infused with 13C-palmitate-methyl-beta-cyclodextrin maintained normal body temperature and appetite; those infused with 13C-palmitate-albumin became anorexic and exhibited other negative side effects to albumin. Palmitate oxidation rates under fed conditions were similar using either 13C-palmitate-methyl-beta-cyclodextrin or 13C-palmitate-albumin complexes. Fasting increased 13C-palmitate-methyl-beta-cyclodextrin oxidation by approximately eight-fold. These data suggest that methyl-beta-cyclodextrin may be a suitable substitute for albumin in fatty acid metabolism studies in swine.

Albumins↗
PubMed2002

Cellular cholesterol stimulates acute uptake of palmitate by redistribution of fatty acid translocase in type II pneumocytes.

Cholesterol is an abundant lipid of lung surfactant, where its concentration changes relative to phospholipids in response to certain physiological conditions. We investigated the effect of the cellular cholesterol content on uptake and esterification of palmitic acid, and on cellular distribution of fatty acid translocase (FAT/CD36) in alveolar type II cells. Incubation of type II cells with methyl-beta-cyclodextrin-cholesterol complexes increased the cholesterol content of lamellar bodies. The palmitate uptake of type II cells increased in parallel with the cellular cholesterol content. The content of FAT/CD36 increased in membranes and decreased in cytosol in type II cells. The detergent-insoluble fraction (DIGs), isolated from type II cells, was enriched in FAT/CD36 and caveolin-1 after increasing the cellular cholesterol. The total incorporation of labeled palmitic acid into glycerolipids and cholesterol ester (CE) increased by a factor of about 10 when the amount of unbound (14)C-palmitic acid added to type II cells was increased by a factor of about 1000. Under these conditions, a small but significant increase of the palmitate incorporation into PL occurred. Independent from the amount of added palmitate, palmitate incorporation into triacylglycerol decreased and palmitate incorporation into cholesterol ester increased about 40-65-fold. The beta-oxidation of palmitate significantly decreased. We conclude that alveolar type II cells respond to an increase of the cholesterol level with (i) cellular redistribution of FAT/CD36 into DIGs causing enhanced palmitate uptake and increased cholesterol ester-formation, (ii) storage of cholesterol in lamellar bodies, and (iii) induction of the formation of caveolae-like microdomains in the surface membrane, a structure possibly involved in a lamellar body-independent efflux of free cholesterol via the high-density lipoprotein-specific pathway.

Animals↗
PubMed2005

Stevioside counteracts the alpha-cell hypersecretion caused by long-term palmitate exposure.

Long-term exposure to fatty acids impairs beta-cell function in type 2 diabetes, but little is known about the chronic effects of fatty acids on alpha-cells. We therefore studied the prolonged impact of palmitate on alpha-cell function and on the expression of genes related to fuel metabolism. We also investigated whether the antihyperglycemic agent stevioside was able to counteract these effects of palmitate. Clonal alpha-TC1-6 cells were cultured with palmitate in the presence or absence of stevioside. After 72 h, we evaluated glucagon secretion, glucagon content, triglyceride (TG) content, and changes in gene expression. Glucagon secretion was dose-dependently increased after 72-h culture, with palmitate at concentrations >or=0.25 mM (P< 0.05). Palmitate (0.5 mM) enhanced TG content of alpha-cells by 73% (P< 0.01). Interestingly, stevioside (10(-8) and 10(-6) M) reduced palmitate-stimulated glucagon release by 22 and 45%, respectively (P< 0.01). There was no significant change in glucagon content after 72-h culture with palmitate and/or stevioside. Palmitate increased carnitine palmitoyltransferase I (CPT I) mRNA level, whereas stevioside enhanced CPT I, peroxisome proliferator-activated receptor-gamma, and stearoyl-CoA desaturase gene expressions in the presence of palmitate (P<0.05). In conclusion, long-term exposure to elevated fatty acids leads to a hypersecretion of glucagon and an accumulation of TG content in clonal alpha-TC1-6 cells. Stevioside was able to counteract the alpha-cell hypersecretion caused by palmitate and enhanced the expression of genes involved in fatty acid metabolism. This indicates that stevioside may be a promising antidiabetic agent in treatment of type 2 diabetes.

Acetyl-CoA Carboxylase↗
PubMed2002

Fatty acid binding protein is a major determinant of hepatic pharmacokinetics of palmitate and its metabolites.

Disposition kinetics of [(3)H]palmitate and its low-molecular-weight metabolites in perfused rat livers were studied using the multiple-indicator dilution technique, a selective assay for [(3)H]palmitate and its low-molecular-weight metabolites, and several physiologically based pharmacokinetic models. The level of liver fatty acid binding protein (L-FABP), other intrahepatic binding proteins (microsomal protein, albumin, and glutathione S-transferase) and the outflow profiles of [(3)H]palmitate and metabolites were measured in four experimental groups of rats: 1) males; 2) clofibrate-treated males; 3) females; and 4) pregnant females. A slow-diffusion/bound model was found to better describe the hepatic disposition of unchanged [(3)H]palmitate than other pharmacokinetic models. The L-FABP levels followed the order: pregnant female > clofibrate-treated male > female > male. Levels of other intrahepatic proteins did not differ significantly. The hepatic extraction ratio and mean transit time for unchanged palmitate, as well as the production of low-molecular-weight metabolites of palmitate and their retention in the liver, increased with increasing L-FABP levels. Palmitate metabolic clearance, permeability-surface area product, retention of palmitate by the liver, and cytoplasmic diffusion constant for unchanged [(3)H]palmitate also increased with increasing L-FABP levels. It is concluded that the variability in hepatic pharmacokinetics of unchanged [(3)H]palmitate and its low-molecular-weight metabolites in perfused rat livers is related to levels of L-FABP and not those of other intrahepatic proteins.

Albumins↗