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PubMed2004

Betaine improves growth, but does not induce whole body or hepatic palmitate oxidation in swine (Sus scrofa domestica).

Dietary betaine may reduce carcass fat in growing pigs. We explored the effects of betaine on short-term growth and in vivo and in vitro fatty acid oxidation. Pigs were housed in metabolism crates and fed diets containing either 0% (control), 0.125% or 0.5% betaine at 80% of ad libitum energy intake. Fatty acid oxidation was measured during intravenous infusions of 1-(13)C-palmitate and in hepatocytes incubated in the presence or absence of betaine and carnitine. CO2 and palmitate isotopic enrichments were determined by mass spectrometry. Pigs consuming 0.125% and 0.5% betaine for at least 9 days had growth rates that were 38% and 12% greater than controls, respectively. Feed efficiency was also improved with betaine. Fasting increased palmitate oxidation rates 7-8-fold (P < 0.01), but betaine had no effect in either the fed or fasted state (P > 0.1). For hepatocytes, carnitine but not betaine enhanced palmitate oxidation. This response suggests that previously observed reduction in adipose accretion must be via a mechanism other than oxidation. Betaine had no effect on plasma non-esterified fatty acids or urea nitrogen. Under the confinement conditions in this study, dietary betaine improved animal growth responses, but it had no apparent effect on either whole body or hepatic fatty acid oxidation.

Animal Nutritional Physiological Phenomena↗
PubMed2005

Topical use of liposomal copper palmitate formulation blocks porphyrin-induced photosensitivity in rats.

Photodynamic therapy (PDT) is a new treatment modality that uses porphyrin derivatives and visible light, especially for the treatment of cancer. However, PDT with certain photosensitisers can cause prolonged skin photosensitization. This is particularly true for Photofrin II (Photofrin)-mediated PDT where patients are required to avoid direct exposure to sunlight for a period of 4-6 weeks. This is the only long-term adverse reaction to the drug. Recent studies have shown that topical copper treatment avoids this type of inflammatory reaction. In this study, we have tested the efficiency of the liposomal formulation of copper palmitate on porphyrin-photosensitized rats. Initially, adult male Sprague-Dawley rats were rendered photosensitive either by administration of Photofrin or aminolevulinic acid (ALA), a precursor of protoporphyrin IX (PpIX). Prior to this, their dorsal skin was shaved and treated topically with a cream consisting of either empty or copper palmitate-encapsulated liposomal formulation. After being kept in a dimmed light environment, the rats were exposed to visible light, and inflammatory responses were inspected. Histological studies revealed that no inflammatory cells were present at the skin sites treated with liposomal cream containing copper palmitate in the Photofrin-sensitized group while no reduction in the number of inflammatory cells was observed at the skin samples treated with the empty liposomes. In conclusion, the data demonstrate the significant protective effect of topically-applied liposome-encapsulated copper palmitate against both Photofrin and ALA-induced PpIX photosensitivity.

Administration, Topical↗
PubMed2003

High glucose potentiates palmitate-induced NO-mediated cytotoxicity through generation of superoxide in clonal beta-cell HIT-T15.

Prolonged exposure to free fatty acids induces beta-cell cytotoxicity. We investigated whether this fatty-acid-induced cytotoxicity is affected by high glucose levels. In clonal beta-cell HIT-T15, palmitate-induced cytotoxicity was potentiated depending on elevated glucose concentrations due to increased apoptosis without cytotoxic effects of high glucose per se. This palmitate cytotoxicity was blocked by NO synthase inhibitors, and palmitate actually increased cellular NO production. The potentiation of palmitate cytotoxicity under high glucose was reversed by decreasing superoxide production, suggesting that superoxide overproduction under high glucose enhances NO-mediated cytotoxicity in beta-cells, which may explain the mechanism of synergistic deterioration of pancreatic beta-cells by free fatty acids and high glucose.

Animals↗
PubMed1999

Variations in serum cholesteryl ester transfer and phospholipid transfer activities in healthy women and men consuming diets enriched in lauric, palmitic or oleic acids.

Cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) activities were measured in sera from 32 normolipidemic women and men consuming diets enriched in lauric, palmitic, or oleic acids. Serum CETP activity, measured as the rate of radiolabeled cholesteryl esters transferred from HDL toward serum apo B-containing lipoproteins, was higher with the palmitic acid diet (25.1+/-2.5%) than with the lauric acid (23.7+/-2.4%) and the oleic acid (24.0+/-2.7%) diets (P = 0.0028 and 0.0283, respectively). CETP mass concentrations, as measured with an enzyme-linked immunosorbent assay were increased after the lauric acid diet (2.57+/-0.63 mg/l) and the palmitic acid diet (2.49+/-0.64 mg/l) as compared with the oleic acid diet (2.34+/-0.45 mg/l) (P = 0.0035 and 0.0249, respectively). In contrast with CETP, serum PLTP activity, as measured as the rate of radiolabeled phosphatidylcholine transferred from liposomes toward serum HDL, was significantly higher with the lauric acid diet (23.5+/2.6%) than with the palmitic acid diet (22.5+/-2.5%) (P = 0.0013), while no significant differences were noted when comparing the saturated diets versus the oleic acid diet (23.0+/-2.3%). No significant alterations in the mean apparent diameter of LDL, and in the relative proportions of individual HDL subpopulations were observed from one dietary period to another. Nevertheless, lipid transfer activities correlated significantly with the relative abundance of HDL2b, HDL2a, HDL3b, and HDL3c, with opposite tendencies being observed for cholesteryl ester transfer and phospholipid transfer activities. In general, serum CETP activity correlated negatively with HDL cholesterol, but positively with triglyceride concentrations after the dietary interventions, and the relations with serum lipids were just the opposite for PLTP activity. In addition, CETP and PLTP activities correlated negatively when subjects consumed the standardized diets (P < 0.05 in all cases), but not when subjects consumed their habitual diet. It is concluded that serum lipid transfer activities in normolipidemic subjects can be significantly affected by the fatty acid content of the diet, with differential effects on CETP and PLTP activities.

Adult↗
PubMed2003

Linoleic acid and antioxidants protect against DNA damage and apoptosis induced by palmitic acid.

Polyunsaturated fats are the main target for lipid peroxidation and subsequent formation of mutagenic metabolites, but diets high in saturated fats are more strongly associated with adverse health effects. We show that the common saturated fatty acid, palmitic acid, is a potent inducer of DNA damage in an insulin-secreting cell line, and in primary human fibroblasts. Damage is not associated with upregulation of inducible nitric oxide synthase, but is prevented by two different antioxidants, alpha-lipoic acid and 3,3'-methoxysalenMn(III) (EUK134), which also partly prevent palmitic acid-induced apoptosis and growth inhibition. Since mutagenic metabolites can be formed from peroxidation of polyunsaturated fatty acids, co-administration of palmitic and a polyunsaturated fatty acid might be particularly harmful. Palmitic acid-induced DNA damage is instead prevented by linoleic acid, which is acting here as a protective agent against oxidative stress, rather than as a source of mutagenic metabolites. These results illustrate the complexity of the relationship of dietary fat intake to genotoxicity.

Antioxidants↗
PubMed1999

High density lipoprotein (HDL), and not albumin, is the major palmitate binding protein in New Zealand long-finned (Anguilla dieffenbachii) and short-finned eel (Anguilla australis schmidtii) plasma.

Plasma from two members of the teleost Anguillidae family, the New Zealand long-finned (Anguilla dieffenbachii) and short-finned eels (Anguilla australis schmidtii), were examined. Agarose gel electrophoresis showed both species had a major anionic diffuse protein band migrating at approximately the same position as human albumin, and autoradiography showed this protein bound [14C]palmitic acid, but not 63Ni2+. Cellulose acetate electrophoresis followed by Oil Red O staining suggested that this band was a lipoprotein. Two-dimensional electrophoresis of plasma showed the absence of a significant albumin band at approx. 65 kDa, and that the palmitate binding band appeared to be composed of at least three proteins, with the major protein running at 30 kDa. N-Terminal sequencing of the palmitate binding band indicated major sequences of DAPAPP(S)QLED- for long-finned eel and DAPAPPSQLEHV- for short-finned eel, confirming their identities as apo-AI, the major apolipoprotein of high density lipoprotein (HDL). When ultracentrifugation was used to separate the lipoproteins of each species, the anionic palmitate binding protein was found solely in the lipoprotein fractions. There was no evidence of albumin in plasma from either eel, and it appears that in its absence HDL takes on the role of fatty acid transport.

Anguilla↗
PubMed2002

The oxygen-substituted palmitic acid analogue, 13-oxypalmitic acid, inhibits Lck localization to lipid rafts and T cell signaling.

Palmitoylation of cysteines 3 and 5 is necessary for targeting Lck to lipid rafts and is needed for Lck function in T cell receptor (TCR) signaling. Point mutations of cysteines 3 and 5 result in a form of Lck that fails to associate with the plasma membrane, which limits the usefulness of this genetic approach to address the role of palmitoylation in the distribution of Lck within the plasma membrane. To circumvent this problem, we sought to identify a palmitic acid analogue that would enable plasma membrane association of Lck, but not facilitate its localization within lipid rafts. Here we examined the effects of the heteroatom-substituted analogue of palmitic acid, 13-oxypalmitic acid (13-OP), on Lck subcellular localization and function. 13-OP is similar in chain length to palmitic acid, but possesses reduced hydrophobicity. We found that treatment of cells with 13-OP inhibited incorporation of omega-[(125)I]iodopalmitate into Lck. 13-OP inhibited localization of Lck to lipid rafts without altering its membrane localization. Consistent with the dissociation of Lck from rafts, treatment with 13-OP abolished Lck association with the GPI-anchored protein, CD48, but not the transmembrane glycoprotein CD4. Jurkat T cells treated with 13-OP showed marked reduction in tyrosine phosphorylation and activation of mitogen-activated protein kinase upon TCR stimulation. In conclusion, the less hydrophobic analogue of palmitate, 13-OP, alters the normal acylation of Lck that provides Lck with the necessary hydrophobicity and tight packing order required for inclusion in lipid rafts.

Antigens, CD↗
PubMed1999

A simple screening test for fatty acid oxidation defects using whole-blood palmitate oxidation.

We report that measurement of whole-blood palmitate oxidation is a rapid and inexpensive screening test for fatty acid oxidation defects. The assay has been adapted from published assays using cultured fibroblasts or isolated white blood cells. Micro whole-blood samples are incubated with tritiated palmitic acid as substrate. The tritiated water produced is proportional to the mitochondrial beta-oxidation of palmitic acid. Patients with confirmed beta-oxidation defects show low whole-blood palmitate oxidation.

Adolescent↗
PubMed1996

Comparison of pharmacokinetic parameters of a polypeptide, the Bowman-Birk protease inhibitor (BBI), and its palmitic acid conjugate.

PURPOSE: The alteration of the pharmacokinetic parameters of the polypeptide BBI through conjugation with palmitic acid was examined. METHODS: 125I-BBI or 125I-Pal-BBI was administered iv to 6 week old CF-1 mice at a dose of 3 mg/kg. The mice were sacrificed at 5, 10, 20, 60, 120, 240, 360, and 480 min and the total radioactivity was determined for blood and each organ. The blood was analyzed on a Sephadex G-50 size-exclusion column to determine the amount of intact polypeptide present in the blood. From the amount of intact polypeptide at each time point, the pharmacokinetic parameters were determined. RESULTS: By conjugating three palmitic acids to each BBI molecule, the area under the curve (AUC) and mean residence time (MRT) increase by a factor of 10.8 and 2.8, respectively. There was also a difference in the organ distribution between the two treatments; while 125I-BBI was rapidly cleared from the kidneys, 125I-Pal-BBI was predominantly to the liver. Subsequent studies suggested that the binding of the conjugate to non-albumin serum proteins was most likely the cause of the altered pharmacokinetics. CONCLUSIONS: The residence time in the blood and the lipophilicity of BBI were increased upon conjugation with palmitic acid through a reversible disulfide linkage. Pharmacokinetic studies showed an increase in the AUC and a decrease in kidney clearance in palmitic acid conjugates, indicating a potential increase of the therapeutic efficacy of the polypeptide drug.

Animals↗
PubMed2004

Fatty acid protection from palmitic acid-induced apoptosis is lost following PI3-kinase inhibition.

We have previously shown that saturated fatty acids induce DNA damage and cause apoptotic cell death in insulin-producing beta-cells. Here we examine further the effects of single or combined dietary fatty acids on RINm5F survival or cell death signalling. Palmitate and stearate, but not linoleate, oleate or palmitoylmethyl ester, induced growth inhibition and increased apoptosis in RINm5F cells following 24 h exposure. Co-incubation with inhibitors of ceramide synthesis, myriocin or fumonisin B(1), did not improve viability of palmitic acid treated RINm5F cells. The inhibitor of inducible nitric oxide synthase, 1400 W, similarly had no protective effect. However, linoleic acid protected against palmitic acid-induced apoptotic and necrotic cell death. The specific pharmacological inhibitors of phosphatidylinositol 3-kinase, LY294002 and wortmannin, abolished the protective effect of linoleic acid on apoptosis but not on necrosis. These data show that the growth inhibitory and apoptosis-inducing effect of the saturated fatty acid palmitate on RINm5F cells is prevented by co-incubation with the polyunsaturated fatty acid linoleate but not inhibitors of ceramide or nitric oxide generation. A key role for phosphatidylinositol 3-kinase in mediating the linoleic-acid reduction in apoptosis is suggested.

Androstadienes↗
PubMed1998

The effect of age and gender on the metabolic disposal of [1-13C] palmitic acid.

OBJECTIVE: To examine the effect of age and gender on the metabolic disposal of [1-13C]palmitic acid. DESIGN: Cross-sectional. SETTING: Clinical Nutrition and Metabolism Unit at Southampton General Hospital, Institute of Human Nutrition, University of Southampton. SUBJECTS AND MEASUREMENTS: Twelve children (5 boys and 7 girls; aged 5-10 y) and six men (BMI 23.3 +/- 2.6 kg/m2; aged 20-30 y) were recruited. Following oral administration of a bolus dose of [1-13C]palmitic acid (10 mg/kg body weight) consumed with a test meal (1667 kJ) the excretion of 13C-label was measured on breath as 13CO2 over 24 h and in stool over 5 d to account for differences in absorption of [1-13C]palmitic acid. The 13C-enrichment of samples was determined by continuous flow-isotope ratio mass spectrometry. Net substrate oxidation was estimated from gaseous exchange measurements in the postabsorptive state and over 6 h postprandially. RESULTS: The excretion of 13CO2 on breath varied between subjects both in the pattern and amount excreted over 24 h. Breath 13CO2 was not different between boys (61.0 +/- 22.4% of absorbed dose) and girls (54.2 +/- 17.9% of absorbed dose). The excretion of breath 13CO2 was less in the men (35.1 +/- 9.3% of absorbed dose; P = 0.005) and that observed previously by our group in women (30.7 +/- 6.7% of absorbed dose; P = 0.005) than in the children. Net fat oxidation was greater in the children in both the postabsorptive (2.43 +/- 0.78 g/h) and postprandial (11.89 +/- 3.13 g/6 h) states than in the men (0.93 g/h +/- 1.50; P = 0.016; 9.86 +/- 10.53 g/6 h; NS) and women studied previously (0.53 +/- 0.68 g/h; P = 0.003; 0.03 +/- 3.21 g/6 h; P = 0.001). CONCLUSIONS: Our observations that children oxidised nearly twice the amount of [1-13C]palmitic acid than adults in conjunction with greater net fat oxidation in children than adults in both the postabsorptive and postprandial states should be considered before current UK dietary recommendations for fat and saturated fats, developed for adults, are applied to growing children. For dietary recommendations to be developed further more information is required, particularly in groups of infants and the elderly, about the factors that influence the postprandial handling of dietary fat.

Absorption↗
PubMed1968

Formation of ketone bodies from [14C]palmitate and [14C]glycerol by tissues from ketotic sheep.

Labelled ketone bodies were produced readily from [U-(14)C]palmitate, [2-(14)C]palmitate and [1-(14)C]glycerol by sheep rumen-epithelial and liver tissues in vitro. On a tissue-nitrogen basis, both tissues had similar capacities for ketogenesis. Palmitate was a ketogenic substrate in both rumen-epithelial tissue and liver, and more of its (14)C appeared in ketone bodies than in the (14)CO(2) liberated. Glycerol was actively metabolized to ketone bodies, but more readily underwent complete oxidation to carbon dioxide; this complete oxidation was most pronounced in rumen-epithelial tissue from ketotic ewes. These experiments with labelled compounds confirm earlier observations that rumen-epithelial tissue, like liver, actively forms ketone bodies from long-chain fatty acids and show further that normal rumen-epithelial tissue can convert palmitate into ketone bodies as readily as into carbon dioxide. Free glycerol, which is metabolized only by liver tissue in non-ruminants, is also metabolized by rumen epithelium. The rumen epithelium thus has unique metabolic capacity among extrahepatic tissues.

Acidosis↗
PubMed1968

The carnitine-independent oxidation of palmitate plus malate by moth flight-muscle mitochondria.

Mitochondria isolated from the flight muscle of the southern armyworm moth, Prodenia eridania, can oxidize palmitate+malate very rapidly. Added carnitine had no effect on the rate of oxidation of palmitate+malate by flight-muscle mitochondria from two species of moths, and carnitine palmitoyltransferase could not be detected in Prodenia by direct assay. Palmitoylcarnitine was not oxidized by moth mitochondria, but when added in low concentrations it reversibly suppressed the oxidation of palmitate. The evidence indicates that carnitine is not involved in fatty acid degradation by moth flight muscle. Added thiols, including CoA, also suppressed palmitate+malate oxidation. An ATP-dependent fatty acyl-CoA synthetase is present in moth mitochondria.

Animals↗
PubMed1995

Comparative effects of recombinant human insulin-like growth factor I and insulin on whole-body and forearm palmitate metabolism in man.

1. The effects of intravenous infusions of recombinant human insulin-like growth factor I and insulin on palmitate kinetics, lipolysis and on serum triacylglycerol were compared. Overnight-fasted normal subjects received high doses of insulin-like growth factor I (30 micrograms h-1 kg-1) and insulin (0.23 nmol h-1 kg-1; group 1), low doses of insulin-like growth factor I (5 micrograms h-1 kg-1) and insulin (0.04 nmol h-1 kg-1; group 2) or saline (control group). The doses of insulin-like growth factor I and insulin were equipotent with regard to increases in glucose uptake during 8 h euglycaemic clamping. 2. Whole-body palmitate flux (measured by continuous infusions of [2,2-D2]palmitate) was lowered dose-dependently by 68% +/- 6% during insulin-like growth factor I and by 82% +/- 2% during insulin after 8 h of infusions of high doses (insulin-like growth factor I versus insulin; not significant). Plasma palmitate, glycerol and triacylglycerol concentrations had decreased to a similar extent at the end of the infusions of both peptides at either dose. 3. The present results demonstrate that insulin-like growth factor I and insulin infused at doses which result in identical increases in glucose uptake during euglycaemic clamping are equipotent inhibitors of lipolysis.

Adult↗
PubMed1999

Cross-talk mechanisms in the development of insulin resistance of skeletal muscle cells palmitate rather than tumour necrosis factor inhibits insulin-dependent protein kinase B (PKB)/Akt stimulation and glucose uptake.

Insulin resistance in skeletal muscle is one of the earliest symptoms associated with non-insulin-dependent diabetes mellitus (NIDDM). Tumour necrosis factor (TNF) and nonesterified fatty acids have been proposed to be crucial factors in the development of the insulin-resistant state. We here show that, although TNF downregulated insulin-induced insulin receptor (IR) and IR substrate (IRS)-1 phosphorylation as well as phosphoinositide 3-kinase (PI3-kinase) activity in pmi28 myotubes, this was, unlike in adipocytes, not sufficient to affect insulin-induced glucose transport. Rather, TNF increased membrane expression of GLUT1 and glucose transport in these muscle cells. In contrast, the nonesterified fatty acid palmitate inhibited insulin-induced signalling cascades not only at the level of IR and IRS-1 phosphorylation, but also at the level protein kinase B (PKB/Akt), which is thought to be directly involved in the insulin-induced translocation of GLUT4, and inhibited insulin-induced glucose uptake. Palmitate also abrogated TNF-dependent enhancement of basal glucose uptake, suggesting that palmitate has the capacity to render muscle cells resistant not only to insulin but also to TNF with respect to glucose transport by GLUT4 and GLUT1, respectively. Our data illustrate the complexity of the mechanisms governing insulin resistance of skeletal muscle, questioning the role of TNF as a direct inhibitor of glucose homoeostasis in this tissue and shedding new light on an as yet unrecognized multifunctional role for the predominant nonesterified fatty acid palmitate in this process.

Animals↗
PubMed2000

The origin of 1H NMR-visible triacylglycerol in human neutrophils. Highfatty acid environments result in preferential sequestration of palmitic acid into plasma membrane triacylglycerol.

Human neutrophils incubated for 1 h in vitro with 10% commercial pooled, human serum containing high levels of free fatty acids (1141 microM) displayed a distinct lipid signal, typical of triacylglycerol, in the 1H NMR spectrum. Concurrently their plasma membrane triacylglycerol mass increased 4.6-fold with a selective rise in the content of palmitic and linoleic acids. Although qualitatively similar, these effects were much greater than those observed after incubating neutrophils with 50 microg.mL-1 of lipopolysaccharide in the presence of 10% AB serum with normal free fatty acid content (345 microM, LPS/S). Incubation of neutrophils with an artificial mixture of free fatty acids at concentrations found in commercial serum, or with the fatty acid fraction isolated from commercial serum increased the 1H NMR-detectable triacylglycerol. The signal intensity of the 1H NMR-detectable triacylglycerol depended on the triacylglycerol composition, and correlated with increased membrane triacylglycerol mass. Cellular uptake of 3H-labelled palmitic or oleic acids increased in the presence of commercial serum but not with LPS/S, with little contribution in either case to the triacylglycerol pool that increased in mass. Pulse-chase experiments demonstrated that with LPS/S and commercial serum, radiolabelled palmitic acid was preferentially incorporated into triacylglycerol located in the plasma membrane. This process could occur at the plasma membrane, as cytoplasts efficiently convert exogenous fatty acids into triacylglycerol. We propose that LPS/S and serum containing high levels of free fatty acid, important in conditions of sepsis and inflammation, may facilitate the sequestration of palmitic acid into triacylglycerol by different pathways. This triacylglycerol originates from exogenous and endogenous free fatty acids, is 1H NMR-visible, and may have a role in regulating apoptosis.

Arachidonic Acid↗
PubMed2003

Palmitic and stearic fatty acids induce caspase-dependent and -independent cell death in nerve growth factor differentiated PC12 cells.

Apoptotic cell death has been proposed to play a role in the neuronal loss observed following traumatic injury in the CNS and PNS. The present study uses an in vitro tissue culture model to investigate whether free fatty acids (FFAs), at concentrations comparable to those found following traumatic brain injury, trigger cell death. Nerve growth factor (NGF)-differentiated PC12 cells exposed to oleic and arachidonic acids (2 : 1 ratio FFA/BSA) showed normal cell survival. However, when cells were exposed to stearic and palmitic acids, there was a dramatic loss of cell viability after 24 h of treatment. The cell death induced by stearic acid and palmitic acid was apoptotic as assessed by morphological analysis, and activation of caspase-8 and caspase-3-like activities. Western blotting showed that differentiated PC12 cells exposed to stearic and palmitic acids exhibited the signature apoptotic cleavage fragment of poly (ADP-ribose) polymerase (PARP). Interestingly, blockade of caspase activities with the pan-caspase inhibitor z-VAD-fmk failed to prevent the cell death observed induced by palmitic or stearic acid. RT-PCR and RNA blot experiments showed an up-regulation of the Fas receptor and ligand mRNA. These findings are consistent with our hypothesis that FFAs may play a role in the cell death associated with trauma in the CNS and PNS.

Amino Acid Chloromethyl Ketones↗
PubMed2003

Skeletal muscle cells from insulin-resistant (non-diabetic) individuals are susceptible to insulin desensitization by palmitate.

We recently demonstrated that in vivo insulin resistance is not retained in cultured skeletal muscle cells. In the present study, we tested the hypothesis that treating cultured skeletal muscle cells with fatty acids has an effect on insulin action which differs between insulin-sensitive and insulin-resistant subjects. Insulin effects were examined in myotubes from 8 normoglycemic non-obese insulin-resistant and 8 carefully matched insulin-sensitive subjects after preincubation with or without palmitate, linoleate, and 2-bromo-palmitate. Insulin-stimulated glycogen synthesis decreased by 27 +/- 5 % after palmitate treatment in myotubes from insulin-resistant, but not from insulin-sensitive subjects (1.50 +/- 0.08-fold over basal vs. 1.81 +/- 0.09-fold, p = 0.042). Despite this observation, we did not find any impairment in the PI 3-kinase/PKB/GSK-3 pathway. Furthermore, insulin action was not affected by linoleate and 2-bromo-palmitate. In conclusion, our data provide preliminary evidence that insulin resistance of skeletal muscle does not necessarily involve primary defects in insulin action, but could represent susceptibility to the desensitizing effect of fatty acids and possibly other environmental or adipose tissue-derived factors.

Adult↗