stearates and elaidic-acid

The dietary intake of elaidate (elaidic acid), a trans-fatty acid, is associated with the development of various diseases. Since elaidate is a C18 unsaturated fatty acid with a steric structure similar to that of a C18 saturated fatty acid (stearate), we previously revealed that insulin-dependent glucose uptake was impaired in adipocytes exposed to elaidate prior to and during differentiation similar to stearate. However, it is still unknown whether the mechanism of impairment of insulin-dependent glucose uptake due to elaidate is similar to that of stearate. Here, we indicate that persistent exposure to elaidate has particular effects on insulin signaling and GLUT4 dynamics. Insulin-induced accumulation of Akt at the plasma membrane (PM) and elevations of phosphorylated Akt and AS160 levels in whole cells were suppressed in adipocytes persistently exposed to 50 μM elaidate. Interestingly, persistent exposure to the same concentration of stearate has no effect on the phosphorylated Akt and AS160 levels. When cells were exposed to these fatty acids, elaidate suppressed insulin-induced fusion, but not translocation, of GLUT4 storage vesicles in the PM, whereas stearate did not suppress the fusion and translocation of GLUT4 storage, indicating that elaidate has suppressive effects on the accumulation of Akt and fusion of GLUT4 storage vesicles and that both elaidate and stearate vary in the mechanisms by which they impair insulin-dependent glucose uptake.

Topics: 3T3-L1 Cells; Adipocytes; Animals; Carbohydrate Metabolism; Cell Membrane; Glucose; Glucose Transporter Type 4; Insulin; Mice; Oleic Acids; Phosphorylation; Protein Transport; Proto-Oncogene Proteins c-akt; Signal Transduction; Stearates; Transport Vesicles

Pentalinon andrieuxii Muell Arg is a Mexican-Central American plant anciently used by local people to treat cutaneous leishmaniasis. We evaluated a hexane extract of the root we called PAE for its chemical content and for its immunochemical and in vitro activity against Leishmania donovani and healing of experimental Kala-azar. Chemical analysis using gas chromatography coupled to mass spectrometry (GC-MS) identified hexadecanoic acid, hexadecanoic acid ethyl ester, 9, 12-octadecadienoic acid ethyl ester, octadecanoic acid ethyl ester, 9-octadecenoic acid ethyl ester and diethyl phthalate as the main compounds present in PAE. We also demonstrated PAE kills promastigotes and amastigotes in vitro and significantly reduces parasite loads in liver and spleen of infected Balb/c mice. PAE induces expression of NFkB/AP-1 transcription factors and production of IL-2 and IFN-γ by spleen cells of PAE treated but not in the untreated control mice. Furthermore, there were not IL-6, IL-10 nor TNF production in macrophages treated in vitro with PAE. We developed an affordable extract of P. andrieuxii effective to treat experimental Kala-azar in Balb/c mice.

Topics: Animals; Apocynaceae; Fatty Acids, Unsaturated; Gas Chromatography-Mass Spectrometry; Interferon-gamma; Interleukin-2; Leishmania donovani; Leishmaniasis, Cutaneous; Leishmaniasis, Visceral; Liver; Macrophages; Mice; Mice, Inbred BALB C; NF-kappa B; Oleic Acid; Oleic Acids; Parasite Load; Phthalic Acids; Plant Extracts; Spleen; Stearates; Transcription Factor AP-1

Consumption of trans-unsaturated fatty acids promotes atherosclerosis, but whether degradation of fats in macrophages is altered by trans-unsaturated fatty acids is unknown. We compared the metabolism of oleate (C18:1Δ9-10 cis; (Z)-octadec-9-enoate), elaidate (C18:Δ9-10 trans; (E)-octadec-9-enoate), and stearate (C18:0, octadecanoate) in adherent peripheral human macrophages. Metabolism was followed by measurement of acylcarnitines in cell supernatants by MS/MS, determination of cellular fatty acid content by GC/MS, and assessment of β-oxidation rates using radiolabeled fatty acids. Cells incubated for 44 h in 100 µM elaidate accumulated more unsaturated fatty acids, including both longer- and shorter-chain, and had reduced C18:0 relative to those incubated with oleate or stearate. Both C12:1 and C18:1 acylcarnitines accumulated in supernatants of macrophages exposed to trans fats. These results suggested β-oxidation inhibition one reaction proximal to the trans bond. Comparison of [1-(14)C]oleate to [1-(14)C]elaidate catabolism showed that elaidate completed the first round of fatty acid β-oxidation at rates comparable to oleate. Yet, in competitive β-oxidation assays with [9,10-(3)H]oleate, tritium release rate decreased when unlabeled oleate was replaced by the same quantity of elaidate. These data show specific inhibition of monoenoic fat catabolism by elaidate that is not shared by other atherogenic fats.

Topics: Carnitine; Cells, Cultured; Fatty Acids; Humans; Macrophages; Oleic Acid; Oleic Acids; Oxidation-Reduction; Plant Oils; Stearates; Tandem Mass Spectrometry

Fatty acids have both stimulatory and inhibitory effects on insulin secretion. Long-term exposure to fatty acids results in impaired insulin secretion whilst acute exposure has generally been found to enhance insulin release. However, there are conflicting data in the literature as to the relative efficacy of various fatty acids and on the glucose dependency of the stimulatory effect. Moreover, there is little information on the responses of human islets in vitro to fatty acids. We have therefore studied the acute effects of a range of fatty acids on insulin secretion from rat and human islets of Langerhans at different glucose concentrations. Fatty acids (0.5 mM) acutely stimulated insulin release from rat islets of Langerhans in static incubations in a glucose-dependent manner. The greatest effect was seen at high glucose concentration (16.7 mM) and little or no response was elicited at 3.3 or 8.7 mM glucose. Long-chain fatty acids (palmitate and stearate) were more effective than medium-chain (octanoate). Saturated fatty acids (palmitate, stearate) were more effective than unsaturated (palmitoleate, linoleate, elaidate). Stimulation of insulin secretion by fatty acids was also studied in perifused rat islets. No effects were observed at 3.3 mM glucose but fatty acids markedly potentiated the effect of 16.7 mM glucose. The combination of fatty acid plus glucose was less effective when islets had been first challenged with glucose alone. The insulin secretory responses to fatty acids of human islets in static incubations were similar to those of rat islets. In order to examine whether the responses to glucose and to fatty acids could be varied independently we used an animal model in which lactating rats are fed a low-protein diet during early lactation. Islets from rats whose mothers had been malnourished during lactation were still able to respond effectively to fatty acids despite a lowered secretory response to glucose. These data emphasise the complex interrelationships between nutrients in the control of insulin release and support the view that fatty acids play an important role in glucose homeostasis during undernutrition.

Topics: Animals; Caprylates; Cells, Cultured; Fatty Acids; Fatty Acids, Monounsaturated; Female; Glucose; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Lactation; Linoleic Acid; Models, Animal; Nutrition Disorders; Oleic Acid; Oleic Acids; Palmitates; Rats; Rats, Wistar; Stearates; Stimulation, Chemical