1-O-alkyl-glycerols from Squid Berryteuthis magister Reduce Inflammation and Modify Fatty Acid and Plasmalogen Metabolism in Asthma Associated with Obesity.

Asthma associated with obesity is considered the most severe phenotype and can be challenging to manage with standard medications. Marine-derived 1-O-alkyl-glycerols (AGs), as precursors for plasmalogen synthesis, have high biological activity, making them a promising substance for pharmacology. This study aimed to investigate the effect of AGs from squid Berryteuthis magister on lung function, fatty acid and plasmalogen levels, and cytokine and adipokine production in obese patients with asthma. The investigational trial included 19 patients with mild asthma associated with obesity who received 0.4 g of AGs daily for three months in addition to their standard treatment. The effects of AGs were evaluated at one and three months of treatment. The results of the study demonstrated that intake of AGs increased the FEV1 and FEV1/VC ratios, and significantly decreased the ACQ score in 17 of the 19 patients after three months of treatment. The intake of AGs increased concentration of plasmalogen and n-3 PUFA in plasma, and modified leptin/adiponectin production by adipose tissue. The supplementation of AGs decreased the plasma levels of inflammatory cytokines (TNF-α, IL-4, and IL-17a), and oxylipins (TXB2 and LTB4), suggesting an anti-inflammatory property of AGs. In conclusion, 1-O-alkyl-glycerols could be a promising dietary supplement for improving pulmonary function and reducing inflammation in obese asthma patients, and a natural source for plasmalogen synthesis. The study highlighted that the beneficial effects of AG consumption can be observed after one month of treatment, with gradual improvement after three months of supplementation.

Thermosensory Transient Receptor Potential Ion Channels and Asthma.

Asthma is a widespread chronic disease of the bronchopulmonary system with a heterogeneous course due to the complex etiopathogenesis. Natural-climatic and anthropogenic factors play an important role in the development and progression of this pathology. The reception of physical and chemical environmental stimuli and the regulation of body temperature are mediated by thermosensory channels, members of a subfamily of transient receptor potential (TRP) ion channels. It has been found that genes encoding vanilloid, ankyrin, and melastatin TRP channels are involved in the development of some asthma phenotypes and in the formation of exacerbations of this pathology. The review summarizes modern views on the role of high and low temperatures in airway inflammation in asthma. The participation of thermosensory TRP channels (vanilloid, ankyrin, and melastatin TRP channels) in the reaction to high and low temperatures and air humidity as well as in the formation of bronchial hyperreactivity and respiratory symptoms accompanying asthma is described. The genetic aspects of the functioning of thermosensory TRP channels are discussed. It is shown that new methods of treatment of asthma exacerbations caused by the influence of temperature and humidity should be based on the regulation of channel activity.

Lipid-Induced Mechanisms of Metabolic Syndrome.

Metabolic syndrome (MetS) has a worldwide tendency to increase and depends on many components, which explains the complexity of diagnosis, approaches to the prevention, and treatment of this pathology. Insulin resistance (IR) is the crucial cause of the MetS pathogenesis, which develops against the background of abdominal obesity. In light of recent evidence, it has been shown that lipids, especially fatty acids (FAs), are important signaling molecules that regulate the signaling pathways of insulin and inflammatory mediators. On the one hand, the lack of n-3 polyunsaturated fatty acids (PUFAs) in the body leads to impaired molecular mechanisms of glucose transport, the formation of unresolved inflammation. On the other hand, excessive formation of free fatty acids (FFAs) underlies the development of oxidative stress and mitochondrial dysfunction in MetS. Understanding the molecular mechanisms of the participation of FAs and their metabolites in the pathogenesis of MetS will contribute to the development of new diagnostic methods and targeted therapy for this disease. The purpose of this review is to highlight recent advances in the study of the effect of fatty acids as modulators of insulin response and inflammatory process in the pathogenesis and treatment for MetS.

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma.

The complexity of the pathogenetic mechanisms of the development of chronic inflammation in asthma determines its heterogeneity and insufficient treatment effectiveness. Nuclear transcription factors, which include peroxisome proliferator-activated receptors, that is, PPARs, play an important role in the regulation of initiation and resolution of the inflammatory process. The ability of PPARs to modulate not only lipid homeostasis but also the activity of the inflammatory response makes them an important pathogenetic target in asthma therapy. At present, special attention is focused on natural (polyunsaturated fatty acids (PUFAs), endocannabinoids, and eicosanoids) and synthetic (fibrates, thiazolidinediones) PPAR ligands and the study of signaling mechanisms involved in the implementation of their anti-inflammatory effects in asthma. This review summarizes current views on the structure and function of PPARs, as well as their participation in the pathogenesis of chronic inflammation in asthma. The potential use of PPAR ligands as therapeutic agents for treating asthma is under discussion.

Pro-Resolving Lipid Mediators in the Pathophysiology of Asthma.

Asthma is one of the most important medical and social problems of our time due to the prevalence and the complexity of its treatment. Chronic inflammation that is characteristic of asthma is accompanied by bronchial obstruction, which involves various lipid mediators produced from n-6 and n-3 polyunsaturated fatty acids (PUFAs). The review is devoted to modern ideas about the PUFA metabolites-eicosanoids (leukotrienes, prostaglandins, thromboxanes) and specialized pro-resolving lipid mediators (SPMs) maresins, lipoxins, resolvins, protectins. The latest advances in clinical lipidomics for identifying and disclosing the mechanism of synthesis and the biological action of SPMs have been given. The current views on the peculiarities of the inflammatory reaction in asthma and the role of highly specialized metabolites of arachidonic, eicosapentaenoic and docosahexaenoic acids in this process have been described. The possibility of using SPMs as therapeutic agents aimed at controlling the resolution of inflammation in asthma is discussed.

Molecular Targets of Fatty Acid Ethanolamides in Asthma.

Asthma is a common allergic pathology of the respiratory tract that requires the study of mechanisms underlying it, due to severe forms of the disease, which are refractory to therapy. The review is devoted to the search for molecular targets of fatty acid ethanolamides in asthma, in particular palmitoylethanolamide (PEA), which has been successfully used in the treatment of chronic inflammatory and neurodegenerative diseases, in the pathogenesis of which the nervous and immune systems are involved. Recently, the potentially important role of neuro-immune interactions in the development of allergic reactions has been established. Many of the clinical symptoms accompanying allergic airway inflammation are the result of the activation of neurons in the airways, so the attention of researchers is currently focused on neuro-immune interactions, which can play an important role in asthma pathophysiology. A growing number of scientific works confirm that the key molecule in the implementation of these inter-systemic interactions is nerve growth factor (NGF). In addition to its classic role in nervous system physiology, NGF is considered as an important factor associated with the pathogenesis of allergic diseases, particularly asthma, by regulating of mast cell differentiation. In this regard, NGF can be one of the targets of PEA in asthma therapy. PEA has a biological effect on the nervous system, and affects the activation and the degranulation of mast cells.

The influence of weather and climate on patients with respiratory diseases in Vladivostok as a global health implication.

PURPOSE: To identify the formation of meteopathic reactions in patients with respiratory diseases under the influence of extreme weather changes in Vladivostok. METHODS: The short-term meteopathic reaction in patients with respiratory diseases to the impact of "Weather Complex", consisting of nine weather parameters, on the day of patient's examination and on 1 and 2 days before the examination, was assessed. 146 acclimatized residents of Vladivostok (29 patients with chronic bronchitis, 51 patients with controlled asthma, 39 patients with uncontrolled asthma and 27 healthy volunteers) were examined. Pulmonary function (PF) was studied by spirography and by body plethysmography. RESULTS: The adaptive-compensatory response of PF in patients with respiratory diseases to weather decreases depending on the disease severity, resulting in the development of meteodependence. The impact of "Weather Complex" on a human body is primarily reflected in PF, and the reaction of metabolic parameters is manifested with a 1-2 days time lag. Glutathione peroxidase and glutathione reductase, key factors in maintaining oxidative cell balance, play the most important role in the formation of a compensatory response to weather. In the light of the global health implication, recommendations are suggested to adjust the treatment of patients with respiratory pathology in specific conditions of abruptly changeable weather. CONCLUSIONS: The maritime monsoon climate creates an additional strain on both respiratory system and systems that ensure the peroxidation balance worsening bronchopulmonary pathology.

The Mechanisms of the Regulation of Immune Response in Patients with Comorbidity of Chronic Obstructive Pulmonary Disease and Asthma.

Background. Comorbidity of chronic obstructive pulmonary disease (COPD) and asthma (asthma COPD overlap syndrome, ACOS) is a significant problem in pulmonary practice, whose pathogenetic issues are not clarified yet. Objective. To study the features of the regulation of immune response in patients with comorbid COPD and asthma. Methods. We assessed the levels of CD3+, CD4+, CD8+, CD4+/CD8+, CD19+, CD25+, HLA-DR, total IgE, TNF-α, IL-4, IFN-γ, TXB2, and LTB4 in patients with comorbid COPD and asthma. Results. The study involved 44 people with COPD, 39 people with asthma, and 12 people with comorbid COPD and asthma. The specific features in comorbid COPD and asthma were lymphocytosis, increased absolute count of T-helper cells, increased cytotoxic T-lymphocytes in relative and absolute count, increased relative and absolute numbers of B-lymphocytes, and high levels of total IgE. The elevated levels of TNF-α and IL-4 and inhibition of IFN-γ production were detected. The content of LTB4 was maximal; TXB2 levels were higher than in control group but lower than in COPD and asthma. Conclusion. In comorbid COPD and asthma inflammation increased even during stable period. High levels of eicosanoids, low production of Th1-type cytokines, and active synthesis of opposition IL-4, along with increased IgE, indicate the activation of Th2-type immune response.

Effect of the prolonged high-fat diet on the fatty acid metabolism in rat blood and liver.

BACKGROUND: Contradictory data on consequences of prolonged high-fat diet requires a detailed study of the influence of nutritional high-fat load mechanisms on the peculiarity of lipid metabolism in blood and liver. The present study was undertaken to investigate the fatty acid composition of polar and neutral lipids of the blood plasma, erythrocytes and liver in Wistar rats under the conditions of a prolonged high-fat diet. METHODS: The study was conducted on 60 adult white male Wistar rats. The animals were fed on a high-fat diet consisted of the beef fat and cholesterol (19% and 2% of the total diet, respectively) up to 180 days. The fatty acid composition of the polar and neutral lipids of plasma, erythrocytes and liver were analyzed by the gas chromatography. Statistical data processing was performed by the methods of descriptive statistics with Statistica 6.0. RESULTS: The prolonged unbalanced diet rich in cholesterol and saturated fatty acids resulted in compensatory biosynthesis of the fatty acids in the rat's liver, the inhibition of synthesis of apoproteins and lipoproteins, disruption of the active transport of fatty acids to tissue cells. This launched the accumulation of 20:4n-6, 20:5n-3, 22:5n-3, and 22:6n-3 in the liver and blood plasma and deficiency of 18:2n-6, 20:5n-3 and 22:6n-3 in the erythrocytes. CONCLUSIONS: Adaptive adjustment of lipid metabolism un0064er conditions of the high-fat diet induced inhibition of the formation of lipoproteins (VLDL cholesterol) in the liver, compensatory synthesis of 18:1n-9, 20:5n-3, and 20:3n-6 with primary esterification of PUFA n-3 series to neutral lipids.

Modification of the fatty acid composition of the erythrocyte membrane in patients with chronic respiratory diseases.

BACKGROUND: Early preclinical diagnosis of COPD is urgent. We proposed that fatty acid composition of red blood cells may serve as a prognostic test for the complications in the chronic respiratory diseases. Fatty acid composition of the erythrocyte membranes in patients with chronic respiratory diseases (chronic bronchitis, CB, and stable chronic obstructive pulmonary disease, COPD) was studied. It was established that modification of the fatty acid composition in the erythrocyte membranes was unidirectional in both groups of patients. METHODS: Patients with CB and stable COPD (group A, GOLD 1) (15 subjects in each group) were studied in clinic. The activity of the inflammatory process was evaluated by the phagocytic activity of neutrophils, cytokine levels and cytokine receptors in the blood serum (TNFα, sTNF-RI, bFGF, TGF-ß, IL-8). Fatty acid (FA) composition of the erythrocyte membranes was analyzed by gas liquid chromatography. Statistical data processing was performed by the methods of descriptive statistics with Statistica 6.0. RESULTS: In both groups (CB and COPD), a significant accumulation of the saturated FAs (14:0, 15:0, 18:0) was established. The amount of the arachidonic acid (20:4n-6) was increased by 13% (р < 0.05) in CB patients and by 41% (р < 0.001) in COPD patients, as compared with healthy persons. The elevated level of the PUFA n-6 in the erythrocytes membranes in patients with chronic respiratory diseases confirms that proinflammatory (leukotriene B4) and bronchospasm (prostaglandin D2) mediator substrates is increased. The level of the eicosapentaenoic acid (20:5n-3) was decreased by 32% (р < 0.05) in CB patients and 2-fold (р < 0.001) in COPD patients. The observed increase in the 20:4n-6/20:5n-3 ratio--1.5-fold (р < 0.001) in CB patients and 3-fold in COPD patients--can be a specific marker of the adverse course of the respiratory pathology and the chronic inflammatory development. CONCLUSIONS: Chronic respiratory disease development is associated with the disturbance of the fatty acid composition in erythrocyte membranes and disbalance of the ratio between precursor of pro- and antiinflammatory eicosanoids.

Composition of fatty acids in plasma and erythrocytes and eicosanoids level in patients with metabolic syndrome.

BACKGROUND: Disturbances of the fatty acids composition in plasma and red blood cells and eicosanoid synthesis play an important role in the metabolic syndrome (MS) formation. METHODS: The observation group included 61 people with metabolic syndrome (30 patients with MS and normal levels of insulin, 31 people with MS and insulin resistance--IR). The parameters of carbohydrate and lipid metabolism in blood serum were examined. The composition of nonesterified fatty acids (NEFA), fatty acid (FA) of red blood cells lipids was analyzed by gas-liquid chromatography. Eicosanoids level in MS patients blood serum was studied by enzyme immunoassay. RESULTS: In MS patients in the absence of glucose-insulin homeostasis disturbances and in patients with IR the accumulation of polyunsaturated fatty acids (18:2 n6, 18:3 n3, 22:4 n6) and lower pool of saturated FA (12:0, 14:0, 16: 0, 17:0) in plasma were discovered. A deficit of polyunsaturated FA (18:3 n3, 20:4 n6) with a predominance of on-saturated FA (14:0, 18:0) in erythrocyte membranes was revealed. In MS patients regardless of the carbohydrate metabolism status high levels of leukotriene B4 and 6-keto-prostaglandin-F1α in serum were found. The development of IR in MS patients leads to increased synthesis of thromboxane A2. CONCLUSION: The results revealed a disturbance in nonesterified fatty acids of plasma lipids and red blood cells, eicosanoid synthesis in MS patients. The breach of the plasma and cell membranes fatty acids compositions, synthesis of vasoactive and proinflammatory eicosanoids is an important pathogenetic part of the MS development.

Modification of fatty acids composition in erythrocytes lipids in arterial hypertension associated with dyslipidemia.

BACKGROUND: Modification of fatty acids (FA) composition in erythrocytes lipids as an early indicator of the development of arterial hypertension (AH) and lipid disorders. METHODS: We included 34 patients with arterial hypertension and 11 healthy individuals. Each patient was examined the lipid composition of serum. From erythrocytes by gas chromatography were identified fatty acids. The quantitative composition of the erythrocyte lipids FA in patients with AH presented with saturated and polyunsaturated monoenic acids with carbon chain lengths from C12 to C22. RESULTS: In all hypertensive patients is disturbed lipid FA composition of erythrocytes. The patients with a normal level of serum lipids revealed deficiency of polyunsaturated acids n6-linoleic (18:2 n6), arachidonic (20:4 n6), dokozatetraenic 14.4% (22:4 n6). The patients with dislipidemia installed more profound restructuring of the lipid matrix of the membrane of erythrocytes. A decrease in polyunsaturated fatty acids family n3: dokozapentaenovoy (22:5 n3), docosahexaenoic PUFA (22:6 n3), the total value of n3 PUFA in 1,3 times was revealed. CONCLUSION: Thus, modification of erythrocyte FA are fairly subtle indicator of pathology of lipid metabolism, which manifest themselves much earlier than changes in the lipoprotein of blood plasma.