Myristic acid reduces skin inflammation and nociception.

This study evaluated the inhibitory effect of myristic acid (MA) on models of inflammation and nociception. The in vitro anti-inflammatory activities of MA were assessed on LPS-stimulated macrophages, membrane stabilization assay, and inhibition of protein denaturation, whereas the inhibitory activity of MA on in vivo inflammation was assessed on TPA-induced ear edema using acute and chronic assays in mice. The inhibitory effect of MA on nociception was assessed using three in vivo models. MA exerted in vitro anti-inflammatory activity by the increase (58%) in the production of IL-10 in LPS-stimulated macrophages. In the in vivo assay, MA showed good anti-inflammatory effects on the acute (ED50 = 62 mg/kg) and chronic (ED50 = 77 mg/kg) TPA-induced ear edema. The antinociceptive activity of MA was related to the participation of the nitrergic system in the formalin-induced paw licking test. PRACTICAL APPLICATIONS: Previous studies with different plant extracts containing MA, as one of their major components, have demonstrated anti-inflammatory and antinociceptive actions. However, the anti-inflammatory and antinociceptive actions of myristic acid have not been previously reported. The results suggest that MA induced anti-inflammatory effects in LPS-stimulated macrophages through the participation of IL-10. The antinociceptive effects of MA are attributed to the participation of the nitrergic system.

Saturated fatty acids induce development of both metabolic syndrome and osteoarthritis in rats.

The predominant saturated fatty acids (SFA) in human diets are lauric acid (LA, C12:0), myristic acid (MA, C14:0), palmitic acid (PA, C16:0) and stearic acid (SA, C18:0). The aim of this study was to investigate whether diets containing individual SFA together with excess simple carbohydrates induce osteoarthritis (OA)-like changes in knee joints and signs of metabolic syndrome in rats. Rats were given either a corn starch diet or a diet composed of simple carbohydrates together with 20% LA, MA, PA, SA or beef tallow for 16 weeks. Rats fed beef tallow, SA, MA or PA diets developed signs of metabolic syndrome, and also exhibited cartilage degradation and subchondral bone changes similar to OA. In contrast, replacement of beef tallow with LA decreased signs of metabolic syndrome together with decreased cartilage degradation. Furthermore, PA and SA but not LA increased release of matrix sulphated proteoglycans in cultures of bovine cartilage explants or human chondrocytes. In conclusion, we have shown that longer-chain dietary SFA in rats induce both metabolic syndrome and OA-like knee changes. Thus, diets containing SFA are strongly relevant to the development or prevention of both OA and metabolic syndrome.

Plasma free fatty acid levels influence Zn(2+) -dependent histidine-rich glycoprotein-heparin interactions via an allosteric switch on serum albumin.

BACKGROUND: Histidine-rich glycoprotein (HRG) regulates coagulation through its ability to bind and neutralize heparins. HRG associates with Zn(2+) to stimulate HRG-heparin complex formation. Under normal conditions, the majority of plasma Zn(2+) associates with human serum albumin (HSA). However, free fatty acids (FFAs) allosterically disrupt Zn(2+) binding to HSA. Thus, high levels of circulating FFAs, as are associated with diabetes, obesity, and cancer, may increase the proportion of plasma Zn(2+) associated with HRG, contributing to an increased risk of thrombotic disease. OBJECTIVES: To characterize Zn(2+) binding by HRG, examine the influence that FFAs have on Zn(2+) binding by HSA, and establish whether FFA-mediated displacement of Zn(2+) from HSA may influence HRG-heparin complex formation. METHODS: Zn(2+) binding to HRG and to HSA in the presence of different FFA (myristate) concentrations were examined by isothermal titration calorimetry (ITC) and the formation of HRG-heparin complexes in the presence of different Zn(2+) concentrations by both ITC and ELISA. RESULTS AND CONCLUSIONS: We found that HRG possesses 10 Zn(2+) sites (K' = 1.63 × 10(5) ) and that cumulative binding of FFA to HSA perturbed its ability to bind Zn(2+) . Also Zn(2+) binding was shown to increase the affinity with which HRG interacts with unfractionated heparins, but had no effect on its interaction with low molecular weight heparin (~ 6850 Da). [Correction added on 1 December 2014, after first online publication: In the preceding sentence, "6850 kDa" was corrected to "6850 Da".] Speciation modeling of plasma Zn(2+) based on the data obtained suggests that FFA-mediated displacement of Zn(2+) from serum albumin would be likely to contribute to the development of thrombotic complications in individuals with high plasma FFA levels.

Ceramide synthase 5 mediates lipid-induced autophagy and hypertrophy in cardiomyocytes.

Diabetic cardiomyopathy (DbCM), which consists of cardiac hypertrophy and failure in the absence of traditional risk factors, is a major contributor to increased heart failure risk in type 2 diabetes patients. In rodent models of DbCM, cardiac hypertrophy and dysfunction have been shown to depend upon saturated fatty acid (SFA) oversupply and de novo sphingolipid synthesis. However, it is not known whether these effects are mediated by bulk SFAs and sphingolipids or by individual lipid species. In this report, we demonstrate that a diet high in SFA induced cardiac hypertrophy, left ventricular systolic and diastolic dysfunction, and autophagy in mice. Furthermore, treatment with the SFA myristate, but not palmitate, induced hypertrophy and autophagy in adult primary cardiomyocytes. De novo sphingolipid synthesis was required for induction of all pathological features observed both in vitro and in vivo, and autophagy was required for induction of hypertrophy in vitro. Finally, we implicated a specific ceramide N-acyl chain length in this process and demonstrated a requirement for (dihydro)ceramide synthase 5 in cardiomyocyte autophagy and myristate-mediated hypertrophy. Thus, this report reveals a requirement for a specific sphingolipid metabolic route and dietary SFAs in the molecular pathogenesis of lipotoxic cardiomyopathy and hypertrophy.

Fat intake and asthma in Spanish schoolchildren.

OBJECTIVES: To study the relationship between lipid, fatty acid and lipid-rich food intake and current asthma in a group of Spanish schoolchildren. SUBJECTS/METHODS: The subjects of this cross-sectional study were 638 Spanish schoolchildren (8-13 years of age). The weight and height of all the subjects were recorded. A questionnaire, completed by the subjects' parents, was used to obtain personal and health information. Current asthma was established when the children had ever had asthma, if they had been diagnosed with asthma by a doctor and if they had been treated with medications at some time in the previous 12 months. Food intake was monitored using a 3-day food record. All foods consumed were converted into energy and nutrients. RESULTS: The energy derived from lipids, saturated fatty acids (SFAs) and myristic and palmitic acids was independently associated with current asthma (Odds Ratio (OR) third tertile 2.85 (1.01-8.07) P=0.049, 10.00 (0.89-111.97) P=0.002, 11.21 (1.36-92.24) P=0.002, 7.58 (1.40-41.03) P=0.022, respectively), as was the intake of butter (OR third tertile 2.97 (1.01-8.68) P=0.001). No relationship was seen between this condition and the intake of any other fatty acid, the n-6/n-3 ratio, nor the consumption of margarine, milk products, fish, meat, eggs or vegetable oils. CONCLUSIONS: Increased intakes of SFAs, myristic and palmitic acids and butter seem to be related to the risk of current asthma in children.