Therapeutic potential of n-3 polyunsaturated fatty acids in disease (original) (raw)
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Synthesis and Functional Significance of Poly Unsaturated Fatty Acids (PUFA's) in Body
Synthesis and Functional Significance of Poly Unsaturated Fatty Acids (PUFA’s) in Body, 2018
There are 2 types of polyunsaturated acids (PUFA's) namely omega 6 and omega 3 series. PUFA's possess amphipathic properties i.e. hydrophobic head and hydrophilic tail. Such structure besides other properties of unsaturated fatty acids cause biological action especially maintaining cell membrane fluidity inhibiting inflammatory processes, decreasing secretion of proinflammatory cytokines by monocytes and macrophages/reducing susceptibility to ventricular rhythm disorders of the heart, improving functions of the vascular endothelial cells, inhibiting blood platelet aggregation and reducing triglyceride synthesis in the liver. In an organism arachidonic acid (ARA) gets converted to prostanoid series (PGE2, PGI2, TXA2) and leukotrienes (LTB4, LTC4, LTD4) which have proinflammatory potential and can induce platelet aggregation and vasoconstriction. The metabolism of EPA and DHA gives prostanoid series (PGE3, PGI3, TXA3) and leukotriene series (LTB5, LTC5, LTD5), this group of eicosanoids show anti-inflammatory and antiarrhythmic properties.
Polyunsaturated fatty acids in health and disease
Polyunsaturated fatty acids (PUFAs) are necessary for overall health. Two PUFAs families, n-6 and n-3 fatty acids, are physiologically and metabolically distinct. The proportion of PUFAs in serum and erythrocyte phospholipids, which depends on endogenous metabolism controlled by genetic polymorphisms and dietary intake, is an important determinant of both health and disease. Both n-3 and n-6 PUFAs are processed to powerful promoters of eicosanoids synthesis at the cyclooxygenase and lipoxygenase level. Evidence from observational and intervention studies suggest that n-3 PUFAs are cardioprotective, perhaps through their anti-inflammatory, anti-arrhythmic, lipid-lowering and antihypertensive effects. In contrast, dietary n-6 PUFAs have proinflammatory effects. Low n-3 and elevated n-6 PUFAs levels were found in patients with cancer on different sites. The present review focuses on current knowledge related to PUFAs intake and status in health and disease, with reference to the Serbian population.
The role of dietary polyunsaturated fatty acids in inflammation
Serbian Journal of Experimental and Clinical Research, 2013
Low-grade systemic infl ammation is at the base of the most chronic non-communicable diseases, which are reaching epidemic proportions worldwide. Key players in the regulation of infl ammation are n-6 and n-3 polyunsaturated fatty acids (PUFAs), in particular arachidonic acid (n-6) and eicosapentaenoic acid (n-3). Th ey are precursors of eicosanoids-signaling molecules involved in modulating the intensity and duration of infl ammatory responses. Eicosanoids derived from n-6 PUFAs have proinfl ammatory actions, while those derived from n-3 PUFAs act anti-infl ammatory. Th erefore, dietary intake of n-6 and n-3 PUFAs, as well as their ratio, could markedly aff ect the pathogenesis and manifestation of many chronic diseases associated with low-grade infl ammation. Th is review will focus on the relationship between dietary PUFAs and infl ammation, with reference to PUFAs status in plasma phospholipids in Serbian population.
Health benefits of n-3 polyunsaturated fatty acids: eicosapentaenoic acid and docosahexaenoic acid
Advanced Food Nutrition Research, 2012
Obesity is associated with the metabolic syndrome, a significant risk factor for developing type 2 diabetes and cardiovascular diseases. Chronic low-grade inflammation occurring in the adipose tissue of obese individuals is causally linked to the pathogenesis of insulin resistance and the metabolic syndrome. Although the exact trigger of this inflammatory process is unknown, adipose tissue hypoxia, endoplasmic reticular stress, and saturated fatty acid-mediated activation of innate immune processes have been identified as important processes in these disorders. Furthermore, macrophages and T lymphocytes have important roles in orchestrating this immune process. Although energy restriction leading to weight loss is the primary dietary intervention to reverse these obesity-associated metabolic disorders, other interventions targeted at alleviating adipose tissue inflammation have not been explored in detail. In this regard, (n-3) PUFA of marine origin both prevent and reverse high-fat-diet-induced adipose tissue inflammation and insulin resistance in rodents. We provide an update on the pathogenesis of adipose tissue inflammation and insulin resistance in obesity and discuss potential mechanisms by which (n-3) PUFA prevent and reverse these changes and the implications in human health. Adv. Nutr. 2: 304-316, 2011.
Low-grade systemic infl ammation is at the base of the most chronic non-communicable diseases, which are reaching epidemic proportions worldwide. Key players in the regulation of infl ammation are n-6 and n-3 polyunsaturated fatty acids (PUFAs), in particular arachidonic acid (n-6) and ei-cosapentaenoic acid (n-3). Th ey are precursors of eicosanoids-signaling molecules involved in modulating the intensity and duration of infl ammatory responses. Eicosanoids derived from n-6 PUFAs have proinfl ammatory actions, while those derived from n-3 PUFAs act anti-infl ammatory. Th erefore, dietary intake of n-6 and n-3 PUFAs, as well as their ratio, could markedly aff ect the pathogenesis and manifestation of many chronic diseases associated with low-grade infl amma-tion. Th is review will focus on the relationship between dietary PUFAs and infl ammation, with reference to PUFAs status in plasma phospholipids in Serbian population.
Polyunsaturated fatty acids (PUFA) and eicosanoids in human health and pathologies
Linoleic and alpha-linolenic acids, obtained from plant material in the diet are the precursors in tissues of two families with opposing effects which are referred to as "essential fatty acids" (EFA): arachidonic acid (AA) and pentaene (eicosapentaenoic acid: EPA) and hexaene (docosahexaenoic acid: DHA) acids. The role of EFA is crucial, without a source of AA or compounds which can be converted into AA, synthesis of prostaglandins (PGs) by a cyclooxygenase (COX) enzyme would be compromised, and this would seriously affect many normal metabolic processes. COX, also known as prostaglandin endoperoxide synthase (Pghs) or as prostaglandin G/H synthase, is a key membrane bound enzyme responsible for the oxidation of AA to PGs. Two COX isoforms have been identified, COX-1 and COX-2 that form PGH 2 , a common precursor for the biosynthesis of thromboxane A 2 (TxA 2), prostacyclin (PGI 2) and PGs (PGD 2 , PGE 2 , PGF 2α. COX-1 enzyme is expressed constitutively in most cells and tissues. Its expression remains constant under either physiological or pathological conditions controlling synthesis of those PGs primarily involved in the regulation of homeostatic functions. In contrast, COX-2 is an intermediate response gene that encodes a 71-kDa protein. COX-2 is normally absent from most cells but highly inducible in certain cells in response to inflammatory stimuli resulting in enhanced PG release. PGs formed by COX-2 primarily mediate pain and inflammation but have multiple effects that can favour tumorigenesis. They are more abundant in cancers than in normal tissues from which the cancers arise. COX-2 is a participant in the pathway of colon carcinogenesis, especially when mutation of the APC (Adenomatous Polyposis Coli) tumour suppressor gene is the initiating event. In addition, COX-2 up-regulation and elevated PGE 2 levels are involved in breast carcinogenesis. It seems that there is a correlation between COX-2 level of expression and the size of the tumours and their propensity to invade underlying tissue. Inhibition by non-steroidal anti-inflammatory drugs (NSAIDs) of COX enzymes which significantly suppress PGE 2 levels, reduced breast cancer incidence and protected against colorectal cancer. Therefore it is suggested that consumption of a diet enriched in n-3 PUFA (specifically EPA and DHA) and inhibition of COX-2 by NSAIDs may confer cardioprotective effects and provide a significant mechanism for the prevention and treatment of human cancers.
Dietary Polyunsaturated Fatty Acids (PUFAs): Uses and Potential Health Benefits
Current Nutrition Reports
Purpose of Review Polyunsaturated fatty acids (PUFAs) are obtained from various sources, which can be incorporated in the routine diet to maintain the health. They provide protection from several diseases like osteoarthritis, cancer, and autoimmune disorders. Major focus is given to the PUFAs omega-3 (ω-3) and omega-6 (ω-6) fatty acids which are available in both terrestrial and in the marine environment. The main concern of this article is to review the key scientific reports in context with the human health consequences and advantages of the food sources of ω-3 and ω-6 fatty acids. Recent Findings ω-3 and ω-6 fatty acids are consumed by the population globally in the form of foods that are rich in fatty acids. Their nutritional effects have the capability to improve the physical functioning and metabolic rate of the body. Summary These PUFAs contribute in various cellular activities like cell signaling, structural integrity and fluidity of cell membrane, the regulation of blood pressure, glucose level, the nervous system, inflammatory reactions, and hematic clotting. Animal and cell-based models represent that ω-3 and ω-6 PUFAs can regulate the skeletal muscle metabolism. The main concern of this article is to review the key scientific reports in context with the human health consequences and advantages of the food sources of ω-3 and ω-6 fatty acids.
Health Benefits of n-3 Polyunsaturated Fatty Acids
Advances in Food and Nutrition Research, 2012
Obesity is associated with the metabolic syndrome, a significant risk factor for developing type 2 diabetes and cardiovascular diseases. Chronic low-grade inflammation occurring in the adipose tissue of obese individuals is causally linked to the pathogenesis of insulin resistance and the metabolic syndrome. Although the exact trigger of this inflammatory process is unknown, adipose tissue hypoxia, endoplasmic reticular stress, and saturated fatty acid-mediated activation of innate immune processes have been identified as important processes in these disorders. Furthermore, macrophages and T lymphocytes have important roles in orchestrating this immune process. Although energy restriction leading to weight loss is the primary dietary intervention to reverse these obesity-associated metabolic disorders, other interventions targeted at alleviating adipose tissue inflammation have not been explored in detail. In this regard, (n-3) PUFA of marine origin both prevent and reverse high-fat-diet-induced adipose tissue inflammation and insulin resistance in rodents. We provide an update on the pathogenesis of adipose tissue inflammation and insulin resistance in obesity and discuss potential mechanisms by which (n-3) PUFA prevent and reverse these changes and the implications in human health. Adv. Nutr. 2: 304-316, 2011.
N-3 Polyunsaturated Fatty Acids, Body Fat and Inflammation
Obesity Facts, 2013
Background: Based on animal studies, n-3 polyunsaturated fatty acids (PUFAs) have been suggested to lower the risk of obesity and inflammation. We aimed to investigate if, among humans, intake of n-3 PUFAs was associated with i) total body fat, ii) body fat distribution and iii) obesity-related inflammatory markers. Methods: The study population consisted of 1,212 healthy individuals with information on habitual food intake from food frequency questionnaires, six different measures of body fat, and levels of six circulating inflammatory markers. Multiple linear regression analysis of intakes of PUFAs in relation to outcomes were performed and adjusted for potential confounders. Results: Absolute n-3 PUFA intake, but not n-3/n-6, was inversely associated with the different measures of body fat. Among n-3 PUFA derivatives, only α-linolenic acid (ALA) was inversely associated with body fat measures. No significant interactions with the dietary macronutrient composition were observed. Pro-inflammatory cytokines were not associated with absolute PUFA intake, but the macrophage inflammatory protein-1α (MIP-1α) was associated with the n-3/n-6 ratio. Conclusion: In humans, intake of n-3 PUFAs, in particular ALA, is beneficially associated with body fatness. The favourable association is, however, not reflected in systemic levels of pro-inflammatory cytokines, nor is it influenced by macronutrients in the diet.