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A defect in Δ6 and Δ5 desaturases may be a factor in the initiation and progression of insulin resistance, the metabolic syndrome and ischemic heart disease in South Asians
Lipids in Health and Diseasevolume 9, Article number: 130 (2010)
The high incidence of insulin resistance and the metabolic syndrome in South Asians remains unexplained. I propose that a defect in the activity of Δ6 and Δ5 desaturases and consequent low plasma and tissue concentrations of polyunsaturated fatty acids such as γ-linolenic acid (GLA), dihomo-γ-linolenic acid (DGLA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and formation of their anti-inflammatory products prostaglandin E1 (PGE1), prostacyclin (PGI2), PGI3, lipoxins, resolvins, protectins, maresins and nitrolipids could be responsible for the high incidence of insulin resistance, the metabolic syndrome and ischemic heart disease (IHD) in South Asians. This proposal is supported by the observation that South Asian Indians have lower plasma and tissue concentrations of GLA, DGLA, AA, EPA and DHA, the precursors of PGE1, PGI2, PGI3, lipoxins, resolvins, protectins, and nitrolipids, the endogenous molecules that prevent platelet aggregation, vasoconstriction, thrombus formation, leukocyte activation and possess anti-inflammatory action and thus, are capable of preventing the development of insulin resistance, atherosclerosis, hypertension, type 2 diabetes mellitus and premature ischemic heart disease. Genetic predisposition, high carbohydrate intake, lack of exercise, tobacco use and low birth weight due to maternal malnutrition suppress the activity of Δ6 and Δ5 desaturases that leads to low plasma and tissue concentrations of polyunsaturated fatty acids and their products. This implies that adequate provision of polyunsaturated fatty acids and co-factors needed for their metabolism, and efforts to enhance the formation of their beneficial metabolites PGE1, PGI2, PGI3, lipoxins, resolvins, protectins, maresins and nitrolipids could form a novel approach in the prevention and management of these diseases in this high-risk population.
The high prevalence of ischemic heart disease in South Asians has been attributed to abdominal obesity, tobacco use, dyslipidemia, hypertension, diabetes mellitus, abdominal obesity and lack of exercise . All these factors are known to be associated with insulin resistance that could account for the high incidence of ischemic heart disease in South Asians . Almost 60% of the world's heart disease is expected to occur in South Asians. Hence, it is essential that pathophysiology of the disease as to why it is common in South Asians needs to be understood to develop relevant preventive and therapeutic strategies.
In a study that evaluated the differences in postprandial glycemia and insulin sensitivity among young adults of different ethnic origins, it was noted that young South East Asians had the highest postprandial glycemia and lowest insulin sensitivity, whereas European and Arabic Caucasian subjects were the most insulin sensitive and carbohydrate tolerant. These findings suggest that insulin resistance is evident even in lean, young adults of South Asian origin even when they are healthy . In addition, ethnicity appears to be an important risk factor for type 2 diabetes in dysglycaemic persons. In a 2-by-2 factorial double-blind randomized controlled trial that compared the effects of rosiglitazone and ramipril on the primary outcome of diabetes or death in persons meeting criteria for impaired glucose tolerance or impaired fasting glucose, it was noted that South Asians experienced a smaller, and Latinos a larger preventive effect , suggesting that South Asians respond less favorably to the preventive effects of rosiglitazone. But, none of these studies could pinpoint the underlying cause for the higher incidence of insulin resistance in South Asians.
Polyunsaturated fatty acids enhance cell membrane fluidity and decrease Insulin resistance
Insulin resistance is common in obesity, type 2 diabetes mellitus, essential hypertension, hyperlipidemia, ischemic (coronary) heart disease, atherosclerosis, ageing, polycystic ovarian disease and the metabolic syndrome. Increased consumption of energy dense food induces insulin resistance, leads to the development of obesity, the precursor of the metabolic syndrome. Calorie restriction, reduced food intake, increase in energy expenditure in the form of exercise attenuates insulin resistance, decreases the incidence of obesity, type 2 diabetes mellitus, hypertension and the metabolic syndrome.
Insulin has to bind to its receptors on the cell membrane to bring about its actions. Hence, cell membrane structure and its functional integrity influence the properties of the insulin receptor including its affinity to insulin. The properties of cell membrane especially, its fluidity depend on the lipid constitution of the membrane. High saturated fatty acid(s) content of the membrane will render it more rigid (i.e. decrease in fluidity) that leads to a decrease in the number of insulin receptors and the affinity of insulin to its receptors [5–11]. This, in turn, causes insulin resistance and associated hyperinsulinemia. It was reported that an increase in the amount of polyunsaturated fatty acids in the cell membrane may produce a significant increase of the number of high-affinity sites with a concomitant decrease of low-affinity sites for insulin [9, 11].
These in vitro results are supported by in vivo experiments wherein it was observed that feeding animals with diets high in saturated fat induced insulin resistance, and replacing saturated fat isocalorically with polyunsaturated fat, especially long-chain ω-3 fatty acids, prevented the development of insulin resistance in skeletal-muscle tissue. The content of fatty acids in sarcolemmal phospholipid was significantly related to the dietary composition. Insulin binding to intact sarcolemmal vesicles prepared from rats fed on diets high in ω-3 fatty acids increased 14-fold compared with animals fed on the low-ω-3 diet and the former showed increased sarcolemmal insulin binding by 2.3-fold. Increased insulin binding was due to increased receptor number at the low-affinity high-capacity binding site, suggesting that dietary ω-3 and polyunsaturated fatty acids increase insulin binding to sarcolemma by changing the fatty acyl composition of phospholipid surrounding the insulin receptor, an action by which dietary fatty acids seem to modify insulin action .
Mechanisms of anti-atherosclerotic actions of PUFAs
Although the exact mechanism by which PUFAs/EFAs decrease insulin resistance is not known, some of the possibilities include: (a) increase in the number of insulin receptors due to increased membrane fluidity; (b) an increase in GLUT-4 mRNA and protein level in adipocytes ; (c) formation of anti-inflammatory and anti-atherosclerotic molecules such as PGI2, PGE1, lipoxins, resolvins, protectins and maresins [16–21]; (d) suppression of the expression of adhesion molecules [22–24]; (e) inhibition of the formation of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), macrophage migration factor (MIF), high-mobility group box 1 (HMGB1) and interleukin-6 (IL-6) [25–27]; (f) enhancement in the formation of brain-derived neurotrophic factor (BDNF) in the brain and gut that has anti-diabetic actions [28–30]; and that (BDNF), in turn, augments PGI2 synthesis , a potent platelet anti-aggregator, vasodilator and anti-atherosclerotic molecule; (f) enhancement in the synthesis and action of BMPs (bone morphogenetic proteins) that enhance the growth and development of the brain [32, 33]; (g) modulation of the growth and actions of gut bacteria [34–37]; (h) binding to various nuclear receptors and correction of dyslipidemia [38–42]; and (i) regulation of both the secretion and actions of various hypothalamic neurotransmitters and peptides that regulate appetite, satiety, food intake and insulin secretion [43–49]. Furthermore, insulin enhances the activity of Δ6 and Δ5 desaturases  and thus, potentially augments the formation of PUFAs that, in turn, enhance the action of insulin. It is likely that when the intake of PUFAs is adequate (it should be adequate throughout life, especially during the formative periods of various cells and tissues and programming of their functions and responses to various endogenous and exogenous stimuli and stresses including perinatal period), the incorporation of these fatty acids into the cell membrane of endothelial cells will be optimum such that the production of PGI2, PGE1, lipoxins, resolvins, protectins, maresins and nitrolipids will be sufficient both during health and in instances of exposure to adverse stimuli such as shear stress so that the expression of adhesion molecules and the production of pro-inflammatory cytokines will be suppressed to prevent platelet aggregation and initiation and progression of atherosclerosis. Thus, for the maintenance of optimal health of endothelial cells adequate intake of PUFAs though out life both during the perinatal period and adult life is necessary. In the absence of adequate amounts of PUFAs, endothelial cells will not be able to synthesize and release sufficient quantities of PGE1, PGI2, PGI3, lipoxins, resolvins, protectins, maresins and nitrolipids that could lead to endothelial dysfunction, insulin resistance and finally the initiation and progression of the metabolic syndrome and ischemic heart disease.
South Asians are deficient in beneficial PUFAs
If this proposal is true, it implies that South Asians are deficient in PUFAs. Previously, I showed that even healthy Indians have lower concentrations of various PUFAs compared to Canadians and Americans (USA) , suggesting that Indians have low activity of Δ6 and Δ5 desaturases (see Figure 1 for metabolism of essential fatty acids). This, in turn, could lead to decreased formation of PGE1, PGI2, PGI3, lipoxins, resolvins, protectins, maresins and nitrolipids due to precursor PUFA deficiency. This is further supported by the observation that South Asians with IHD have much lower levels of PUFAs in their plasma phospholipid fraction compared to healthy subjects . Furthermore, low activity of Δ6 and Δ5 desaturases could lead to the initiation and progression of insulin resistance and atherosclerosis [53, 54]. These evidences suggest that South Asians are at high risk of developing type 2 diabetes mellitus, the metabolic syndrome, IHD and its associated death and complications due to a defect in the activity of Δ6 and Δ5 desaturases that result in low plasma and tissue concentrations of PUFAs and their products: PGE1, PGI2, PGI3, lipoxins, resolvins, protectins, maresins and nitrolipids that are necessary to prevent platelet aggregation, lower blood pressure, reduce LDL-C, ameliorate the adverse actions of homocysteine, and inhibit ACE (angiotensin converting enzyme) and HMG-CoA enzyme activities [20, 55]. In addition, PUFAs and their beneficial products such as PGI2 and lipoxins have anti-arrhythmic action, enhance wound healing and suppress inflammation [19–21, 56–58].
Folic acid that reduces plasma homocysteine levels augments the metabolism of essential fatty acids such that plasma and tissue levels of various PUFAs are enhanced [59, 60]. Similar potentiating action of vitamin B6 on Δ6 and Δ5 desaturases was also reported [59–62]. Recently it was noted that the gene that encodes the 5-lipoxygenase activating protein (FLAP) and its risk variant results in an almost 2-fold increased risk of IHD by leading to the production of leukotriene B4 (LTB4), a potent chemokine mediators of arterial inflammation [63, 64]. This is supported by the observation that patients with IHD produce more LTB4 than controls, suggesting that LTB pathway is upregulated in IHD. It is interesting to note that lipoxins are potent inhibitors of LTB4 and leukotrienes [65, 66].
These evidences suggest that South Asians are at high risk to develop insulin resistance, type 2 diabetes mellitus, the metabolic syndrome and IHD due to low levels of various PUFAs, LXs, resolvins, protectins, maresins and nitrolipids, and hence could benefit from supplementation of PUFAs. Furthermore, South Asians consume less amounts of ω-3 PUFAs and more of saturated and trans-fats that are known to inhibit the activity of Δ6 and Δ5 desaturases [6, 7, 16–18] which, in turn, further aggravate their tendency to develop insulin resistance and the metabolic syndrome . Since, South Asians have low plasma levels of various PUFAs and consume significantly lower quantities of ω-3 PUFAs; they are more prone to have low-grade systemic inflammation. This is supported by the observation that of 1250 adults of South Asian, Chinese, European and Aboriginal ancestry studied; the age- and sex-adjusted mean CRP was 3.74 ± 0.14 mg/L among Aboriginals, 2.59 mg/L ± 0.12 among South Asians, and 1.18 ± 0.13 mg/L among Chinese compared with 2.06 ± 0.12 mg/L among Europeans (overall P < 0.0001). Differences in the CRP concentration between ethnic groups were substantially diminished, but not abolished, after adjustment for metabolic factors. CRP was independently associated with CVD (cardiovascular diseases) after adjusting for the Framingham risk factors, atherosclerosis, anthropometric measurements, and ethnicity (OR = 1.03 for a 0.1-increase in CRP; P = 0.02). These results clearly indicate that South Asians are more prone to have low-grade systemic inflammation compared to other ethnic groups  that may render them highly susceptible to cardiovascular diseases.
Leukocyte activation and atherosclerosis
One of the major health issues in South Asians is the occurrence of premature atheroslcerosis and consequent IHD that, in turn, is due to insulin resistance. Leukocytes seem to play a major role in the pathobiology of atherosclerosis. Thus, peripheral leukocytes could be used as a marker of insulin resistance and atheroslcerosis by studying the metabolism of essential fatty acids, eicosanoids, lipoxins, resolvins, protectins, maresins, nitrolipids and nitric oxide in these cells. Since leukocytosis is also a marker of inflammation, study of leukocytes and their functions could reflect the underlying pathobiology of low-grade systemic inflammation and its consequences. For instance, higher leukocyte count is associated with a greater cardiovascular risk . This implies that leukocyte myeloperoxidase (MPO) could serve as a biomarker of cardiovascular diseases as reported by Morrow et al .
Infiltration of intima by leukocytes and macrophages is an early event to occur in atherosclerosis, suggesting that leukocyte activation is an early event in atherosclerosis. Since atherosclerotic lesions occur in a patchy manner and develop preferentially at bifurcations, branch points, and inner curvatures of arteries, it suggests that local factors play a significant role in the development of atherosclerosis. Hemodynamic forces induce the expression of pro-inflammatory genes  that initiate and accelerate atherosclerosis at these points of shear stress. Normocholesterolemic C57BL/6 mice and rabbits showed activation of NF-κB and elevated expression of VCAM-1 and ICAM-1, upregulation of pro-inflammatory genes IL-1, IL-6, MCP-1, as well as antioxidant genes glutathione peroxidase and glutathione-S- transferase 2 in endothelial cells in atherosclerosis-susceptible regions of the ascending aorta [53, 71]. Intimal accumulation of LDL and its oxidation products preceded monocyte recruitment into early atherosclerotic lesions, suggesting that lipid accumulation triggers inflammatory response characterized by upregulation of the expression of chemokines and adhesion molecules in the lesion-prone areas in the intima that contributes to leukocyte accumulation and atherosclerotic lesion formation [72–75]. Thus at atheroslcerosis-prone regions of the normal intima, inflammatory response is triggered in response to risk factors that up regulate several proinflammatory genes, which mediate accumulation of leukocytes and initiation and perpetuation of atherosclerosis.
Healthy endothelial cells have the ability to prevent excess expression of adhesion molecules, resist increases in LDL and cholesterol transport and retention, abrogate activation of NF-κB and the induction of expression of pro-inflammatory genes induced by hemodynamic forces at atherosclerosis prone regions due to enhanced infiltration by monocytes, CD68+ leukocytes, and macrophages by elaborating factors/molecules that counter pro-atherosclerotic events. The patchy nature of atherosclerosis suggests that arterial walls undergo regional disturbances of metabolism that include the uncoupling of respiration and oxidative phosphorylation, which may be characteristic of blood vessels being predisposed to the development of atherosclerosis . Oxidative stress, and abnormalities of uncoupling proteins produce smooth muscle contraction and cause hypertension , and respiratory uncoupling is increased in the aortae of experimental animals that are susceptible to atherosclerosis . Bernal-Mizrachi et al  showed that UCP-1 expression in aortic smooth muscle cells causes hypertension and increases atherosclerosis without affecting cholesterol levels. This increase in UCP-1 expression enhanced superoxide anion production and decreased the availability of nitric oxide (NO), suggesting that oxidative stress has been elevated. Thus, inefficient metabolism in blood vessels causes atherosclerosis.
One of the earliest signs of atherosclerosis is the development of abnormal mitochondria in smooth muscle cells . Arteries have marginal oxygenation  and hypoxia reduces the respiratory control ratio. Uncoupled respiration precedes atherosclerosis at lesion-prone sites but not at the sites that are resistant to atherosclerosis . Disease-free aortae have abundant concentrations of the essential fatty acid (EFA)-linoleate and possibly anti-inflammatory lipoxins, resolvins, protectins, maresins and nitrolipids whereas fatty streaks are deficient in EFAs [78, 81, 82]. EFA deficiency promotes respiratory uncoupling [83, 84] and atherosclerosis [53, 78, 85]. Hence, local disturbances of metabolism in the arterial wall are responsible for atherosclerosis and vascular diseases such as IHD.
Aspirin converts arachidonic acid (AA; 20:4 ω-6), eicosapentaenoic acid (EPA; 20:5 ω-3) and docosahexaenoic acid (DHA; 22:6 ω-3) to form aspirin-triggered 15 epimer LXs (ATLs) by activated leukocytes that inhibit acute inflammation (reviewed in 16-18). These 15-epimeric LXs prevent local inflammation on the vessel wall by regulating the motility of PMNs, eosinophils, and monocytes. LXs deficiency leads to an interaction between PMN and endothelial cells that result in endothelial damage, initiation and progression of atherosclerosis . LXs, resolvins and protectins inhibited cytokine generation, leukocyte recruitment, leukocyte diapedesis, exudate formation, suppress the production of pro-inflammatory cytokines. Hence, local deficiency of LXs, resolvins and NPD1 could initiate atheroslcerosis. Furthermore, lipoxins suppress production of MPO from activated leukocytes . Increased generation of MPO by leukocytes could be an indication of decreased formation of lipoxins, resolvins, protectins, maresins and nitrolipids by endothelial cells. This implies that enhancing the formation of endothelial LXs, resolvins, protectins, maresins and nitrolipids may suppress leukocyte activation and MPO generation and prevent IHD.
In this context, it is interesting to note that elevated circulating platelet-monocyte complexes correlated significantly with elevated aortic carotid-femoral pulse wave velocity and platelet-monocyte complexes were higher in subjects with femoral plaques of South Asian descent and Europeans. Higher numbers of platelet-monocyte complexes were independently related to elevated levels of C-reactive protein (CRP), higher carotid-femoral pulse wave velocity, hypertension and smoking in a multivariate model . These results suggest that inflammation as evidence by higher CRP and elevated platelet-monocyte complexes is closely related to the extent of atherosclerosis and indicates that leukocyte activation has an import role in the pathogenesis of atherosclerosis in South Asians. This implies that deficiency or lack of endogenous molecules such as lipoxins that inhibit leukocyte activation could initiate atherosclerosis [53, 86, 87].
Conclusions and therapeutic implications
It is evident from the preceding discussion that one significant factor that could render South Asians highly susceptible to develop insulin resistance, type 2 diabetes mellitus, the metabolic syndrome, IHD and atherosclerosis could be a defect in the activity of Δ6 and Δ5 desaturases and consequent lower plasma and tissue concentrations of PUFAs such as GLA, DGLA, AA, EPA and DHA and reduced formation of anti-inflammatory products PGE1, PGI2, PGI3, lipoxins, resolvins, protectins, maresins and nitrolipids that inhibit leukocyte activation and enhance insulin action. This implies that bypassing block in the activities of Δ6 and Δ5 desaturases by supplementing GLA, DGLA, AA, EPA and DHA and co-factors that are essential for the metabolism of EFAs so that adequate amounts of PUFAs could be formed endogenously such as low-dose aspirin, folic acid, vitamin B6, B2, L-arginine (to decrease asymmetrical dimethyl arginine, ADMA, levels that are increased in patients with IHD, type 2 diabetes mellitus, the metabolic syndrome and hypertension; ADMA also interferes with eNO synthesis), vitamin C and Mg2+ (magnesium is an essential for the normal activity of Δ6 and Δ5 enzymes) will not only improve the plasma and cell/tissue content of various PUFAs but also augment production of beneficial PGE1, PGI2, PGI3, lipoxins, resolvins, protectins, maresins, nitrolipids and endothelial nitric oxide (eNO) and thus, prevent and/or improve insulin resistance, hypertension, type 2 diabetes mellitus, the metabolic syndrome and IHD [5–7, 13, 14, 16–21, 23, 24, 26, 27, 53–62, 83–87, 89–92] (see Figure 2).
Furthermore, previously I and my colleagues showed that AA, EPA and DHA protect pancreatic β cells from chemical-induced cytotoxicity [89–92] and thus preserve their insulin producing capacity. These results are supported by the recent study wherein it was shown that mfat-1 transgenic mice which produce higher amounts of ω-3 PUFAs than the wild type showed increased insulin secretion stimulated by glucose, amino acids and glucagon-like peptide and when challenged with TNF-α, IL-6 and γ-interferon the transgenic islets completely resisted cytokine-induced cell death . These results suggest that certain PUFAs and their products [94, 95] have β cell cytoprotective actions and thus, help in the preservation of insulin secreting capacity. Similar to some PGs, lipoxins, resolvins, protectins, maresins and nitrolipids have been shown to have cytoprotective properties [96–98]
In view of the critical role of Δ6 and Δ5 desaturases in essential fatty acid metabolism, it is important to study their genetic polymorphism in South Asians and correlating these findings with the severity of insulin resistance, type 2 diabetes mellitus and atheroslcerosis in the carotid arteries, peripheral vascular tree, and coronary arteries. It was reported that there is a close correlation between polymorphisms of human Δ6 and Δ5 desaturase genes FADS1 FADS2 and fatty acid composition in serum phospholipids. Eighteen polymorphisms located in this gene cluster located at chromosome 11q12-11q13.1, a region repeatedly found to be linked with atopy and other complex diseases were genotyped in 727 adults [99–101]. Polymorphisms and statistically reconstructed haplotypes of FADS1 and the upstream region of FADS2 showed strongest associations with the level of the direct precursor of inflammatory eicosanoids, the ω-6 fatty acid AA, also strong associations with levels of the ω-6 fatty acids LA, GLA, C20: 2 ω-6, DGLA, C22: 4 ω-6 and of the ω-3 fatty acids ALA, EPA and C22:5 ω-3. Such studies of polymorphisms of human Δ6 and Δ5 desaturase genes in South Asians may give clues to predict and assess the progress of insulin resistance, atherosclerosis and IHD.
Peripheral leukocytes-platelet mixed cultures could be supplemented with AA, EPA and DHA and the formation of lipoxins, resolvins, protectins, maresins, nitrolipids and endothelial nitric oxide could be tested in South Asians to identify those who are unable to form adequate amounts of these lipid mediators and NO. Such subjects need supplementation of various PUFAs, aspirin, glitazones, statins and other co-factors even if they appear to be apparently normal to prevent the development of insulin resistance, atherosclerosis and IHD in future. Retesting such subjects after supplementation of PUFAs, aspirin, glitazones, statins and co-factors to see whether formation of lipoxins, resolvins, protectins, maresins, nitrolipids and eNO has been enhanced will be necessary to ascertain their response to the treatment.
Plasma, RBC, leukocyte and platelet content of various PUFAs, lipoxins, resolvins, protectins, maresins, nitrolipids, NO and other eicosanoids such as PGs, LTs, and TXs (thromboxanes) and activities of Δ6 and Δ5 desaturases could be measured both before and after treatment and used as markers to predict future development and prognostic markers of insulin resistance, the metabolic syndrome, atherosclerosis and IHD. Urinary levels of lipoxins, resolvins, protectins, maresins and nitrolipids and isoprostanes could also be measured and used as biochemical indices of response to treatment and more so in those with diabetic nephropathy.
Development of small molecules that could specifically up regulate the activities of Δ6 and Δ5 desaturases may be useful in the prevention and progression of insulin resistance, the metabolic syndrome, atherosclerosis and IHD. Statins and glitazones modulate the activities of Δ6 and Δ5 desaturases. Hence, development structural analogues of statins and glitazones that specifically target Δ6 and Δ5 desaturases could be attempted. Since Δ6 and Δ5 desaturases are present in many tissues, it is anticipated that drugs that enhance the activities of Δ6 and Δ5 desaturases are likely to have other beneficial actions such as in the treatment of hypertension, dyslipidemia, type 2 diabetes mellitus and Alzheimer's disease. Since PUFAs are naturally occurring endogenous substances, present in almost all tissues and are essential components of all mammalian cells, it is likely that overexpression of Δ6 and Δ5 desaturases is unlikely to have any significant side effects. This is evident from the fact that Eskimos consume large amounts of marine fish that are rich in ω-3 fatty acids EPA and DHA and are not known to suffer from any significant side effects. Similarly, when PUFAs have been administered to different types of patients for long periods of time (from few months to few years) it was noted that there were not any significant side effects. It is also proposed that a defect in the activities of enzymes Δ6 and Δ5 and desaturases and consequent low plasma and tissue levels of GLA, DGLA, AA, EPA and DHA and their products lipoxins, resolvins, resolvins, protectins, maresins and nitrolipids may play a significant role in the development of insulin resistance, atherosclerosis, the metabolic syndrome and IHD in Europeans and other populations.
McKeigue PM, Marmot MG, Syndercombe Court YD, Cottier DE, Rahman S, Riemersma RA: Diabetes, hyperinsulinaemia, and coronary risk factors in Bangladeshis in east London. Br Heart J. 1988, 60: 390-396. 10.1136/hrt.60.5.390
Chandalia M, Abate N, Garg A, Stray-Gundersen J, Grundy SM: Relationship between generalized and upper body obesity to insulin resistance in Asian Indian men. J Clin Endocrinol Metab. 1999, 84: 2329-2335. 10.1210/jc.84.7.2329
Dickinson S, Colagiuri S, Faramus E, Petocz P, Brand-Miller JC: Postprandial hyperglycemia and insulin sensitivity differ among lean young adults of different ethnicities. J Nutr. 2002, 132: 2574-2579.
Boyko EJ, Gerstein HC, Mohan V, Yusuf S, Sheridan P, Anand S, Shaw JE, : Effects of ethnicity on diabetes incidence and prevention: results of the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) trial. Diabetes Med. 2010, 27: 1226-1232. 10.1111/j.1464-5491.2010.03064.x.
Das UN: Insulin resistance and hyperinsulinemia: Are they secondary to an alteration in the metabolism of essential fatty acids?. Med Sci Res. 1994, 22: 243-245.
Das UN: Metabolic Syndrome Pathophysiology: The Role of Essential Fatty Acids. 2010, Wiley-Blackwell, Ames, Iowa,
Das UN: A Perinatal Strategy for Preventing Adult Disease: The Role of Long-Chain Polyunsaturated Fatty Acids. 2002, Kluwer Academic Publishers, Norwell, Massachusetts,
Ginsberg BH, Jabour J, Spector AA: Effect of alterations in membrane lipid unsaturation on the properties of the insulin receptor of Ehrlich ascites cells. Biochim Biophys Acta. 1982, 690: 157-164. 10.1016/0005-2736(82)90318-2
Bruneau C, Staedel-Flaig C, Crémel G, Leray C, Beck JP, Hubert P: Influence of lipid environment on insulin binding in cultured hepatoma cells. Biochim Biophys Acta. 1987, 928: 287-296. 10.1016/0167-4889(87)90188-1
Yorek M, Leeney E, Dunlap J, Ginsberg B: Effect of fatty acid composition on insulin and IGF-I binding in retinoblastoma cells. Invest Ophthalmol Vis Sci. 1989, 30: 2087-2092.
Ginsberg BH, Chatterjee P, Yorek MA: Insulin sensitivity is increased in Friend erythroleukemia cells enriched in polyunsaturated fatty acid. Receptor. 1991, 1: 155-166.
Liu S, Baracos VE, Quinney HA, Clandinin MT: Dietary omega-3 and polyunsaturated fatty acids modify fatty acyl composition and insulin binding in skeletal-muscle sarcolemma. Biochem J. 1994, 299 (Pt 3): 831-837.
Hainault I, Carlotti M, Hajduch E, Guichard C, Lavau M: Fish oil in a high lard diet prevents obesity, hyperlipemia, and adipocyte insulin resistance in rats. Ann N Y Acad Sci. 1993, 683: 98-101. 10.1111/j.1749-6632.1993.tb35696.x
Mori Y, Murakawa Y, Katoh S, Hata S, Yokoyama J, Tajima N, Ikeda Y, Nobukata H, Ishikawa T, Shibutani Y: Influence of highly purified eicosapentaenoic acid ethyl ester on insulin resistance in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous non-insulin-dependent diabetes mellitus. Metabolism. 1997, 46: 1458-1464. 10.1016/S0026-0495(97)90148-7
Peyron-Caso E, Fluteau-Nadler S, Kabir M, Guerre-Millo M, Quignard-Boulange A, Slama G, Rizkalla SW: Regulation of glucose transport and transporter 4 (GLUT-4) in muscle and adipocytes of sucrose-fed rats: effects of N-3 poly- and monounsaturated fatty acids. Horm Metab Res. 2002, 34: 360-366. 10.1055/s-2002-33467
Das UN: Essential fatty acids: Biochemistry, physiology, and pathology. Biotechnology J. 2006, 1: 420-439. 10.1002/biot.200600012.
Das UN: Biological significance of essential fatty acids. J Assoc Physicians India. 2006, 54: 309-319.
Das UN: Essential fatty acids- a review. Current Pharmaceutical Biotechnology. 2006, 7: 467-482. 10.2174/138920106779116856
Merched AJ, Ko K, Gotlinger KH, Serhan CN, Chan L: Atherosclerosis: evidence for impairment of resolution of vascular inflammation governed by specific lipid mediators. FASEB J. 2008, 22: 3595-3606. 10.1096/fj.08-112201
Das UN: Essential fatty acids and their metabolites could function as endogenous HMG-CoA reductase and ACE enzyme inhibitors, anti-arrhythmic, anti-hypertensive, anti-atherosclerotic, anti-inflammatory, cytoprotective, and cardioprotective molecules. Lipids Health Dis. 2008, 7: 37- 10.1186/1476-511X-7-37
Ho KJ, Spite M, Owens CD, Lancero H, Kroemer AH, Pande R, Creager MA, Serhan CN, Conte MS: Aspirin-triggered lipoxin and resolvin E1 modulate vascular smooth muscle phenotype and correlate with peripheral atherosclerosis. Am J Pathol. 2010, 177: 2116-2123. 10.2353/ajpath.2010.091082
Weiss JM, Pilarski KA, Weyl A, Peschen M, Schöpf E, Vestweber D, Vanscheidt W, Simon JC: Prostaglandin E1 inhibits TNF alpha-induced T-cell adhesion to endothelial cells by selective down-modulation of ICAM-1 expression on endothelial cells. Exp Dermatol. 1995, 4: 302-307. 10.1111/j.1600-0625.1995.tb00209.x
Hughes DA, Pinder AC, Piper Z, Johnson IT, Lund EK: Fish oil supplementation inhibits the expression of major histocompatibility complex class II molecules and adhesion molecules on human monocytes. Am J Clin Nutr. 1996, 63: 267-272.
Das UN: Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how?. Prostaglandins Leukot Essent Fatty Acids. 2000, 63: 351-362. 10.1054/plef.2000.0226
Das UN: Interaction(s) between essential fatty acids, eicosanoids, cytokines, growth factors and free radicals: relevance to new therapeutic strategies in rheumatoid arthritis and other collagen vascular diseases. Prostaglandins Leukot Essent Fatty Acids. 1991, 44: 201-210.
Blok WL, Katan MB, van der Meer JW: Modulation of inflammation and cytokine production by dietary (n-3) fatty acids. J Nutr. 1996, 126: 1515-1533.
Das UN: The lipids that matter from infant nutrition to insulin resistance. Prostaglandins Leukot Essent Fatty Acids. 2002, 67: 1-12. 10.1054/plef.2002.0374
Toyomoto M, Ohta M, Okumura K, Yano H, Matsumoto K, Inoue S, Hayashi K, Ikeda K: Prostaglandins are powerful inducers of NGF and BDNF production in mouse astrocyte cultures. FEBS Lett. 2004, 562: 211-215. 10.1016/S0014-5793(04)00246-7
Cole GM, Frautschy SA: DHA may prevent age-related dementia. J Nutr. 2010, 140: 869-874. 10.3945/jn.109.113910
Boesmans W, Gomes P, Janssens J, Tack J, Vanden Berghe P: Brain-derived neurotrophic factor amplifies neurotransmitter responses and promotes synaptic communication in the enteric nervous system. Gut. 2008, 57: 314-322. 10.1136/gut.2007.131839
Santhanam AV, Smith LA, Katusic ZS: Brain-derived neurotrophic factor stimulates production of prostacyclin in cerebral arteries. Stroke. 2010, 41: 350-356. 10.1161/STROKEAHA.109.564492
Paralkar VM, Grasser WA, Mansolf AL, Baumann AP, Owen TA, Smock SL, Martinovic S, Borovecki F, Vukicevic S, Ke HZ, Thompson DD: Regulation of BMP-7 expression by retinoic acid and prostaglandin E(2). J Cell Physiol. 2002, 190: 207-217. 10.1002/jcp.10048
Nakagawa K, Imai Y, Ohta Y, Takaoka K: Prostaglandin E2 EP4 agonist (ONO-4819) accelerates BMP-induced osteoblastic differentiation. Bone. 2007, 41: 543-548. 10.1016/j.bone.2007.06.013
Bomba A, Nemcová R, Gancarcíková S, Herich R, Pistl J, Révajová V, Jonecová Z, Bugarský A, Levkut M, Kasteĺ R, Baran M, Lazar G, Hluchý M, Marsálková S, Posivák J: The influence of omega-3 polyunsaturated fatty acids (omega-3 pufa) on lactobacilli adhesion to the intestinal mucosa and on immunity in gnotobiotic piglets. Berl Munch Tierarztl Wochenschr. 2003, 116: 312-316.
Das UN: Essential fatty acids as possible enhancers of the beneficial actions of probiotics. Nutrition. 2002, 18: 786- 10.1016/S0899-9007(02)00840-7
Kankaanpää PE, Salminen SJ, Isolauri E, Lee YK: The influence of polyunsaturated fatty acids on probiotic growth and adhesion. FEMS Microbiol Lett. 2001, 194: 149-153. 10.1016/S0378-1097(00)00519-X
Kankaanpää P, Yang B, Kallio H, Isolauri E, Salminen S: Effects of polyunsaturated fatty acids in growth medium on lipid composition and on physicochemical surface properties of lactobacilli. Appl Environ Microbiol. 2004, 70: 129-136. 10.1128/AEM.70.1.129-136.2004
Jump DB, Ren B, Clarke S, Thelen A: Effects of fatty acids on hepatic gene expression. Prostaglandins Leukot Essent Fatty Acids. 1995, 52: 107-111. 10.1016/0952-3278(95)90007-1
Wolf G: Fatty acids bind directly to and activate peroxisome proliferator-activated receptors alpha and gamma. Nutr Rev. 1998, 56 (2 Pt 1): 61-63.
Pawar A, Xu J, Jerks E, Mangelsdorf DJ, Jump DB: Fatty acid regulation of liver X receptors (LXR) and peroxisome proliferator-activated receptor alpha (PPARalpha) in HEK293 cells. J Biol Chem. 2002, 277: 39243-39250. 10.1074/jbc.M206170200
Zhao A, Yu J, Lew JL, Huang L, Wright SD, Cui J: Polyunsaturated fatty acids are FXR ligands and differentially regulate expression of FXR targets. DNA Cell Biol. 2004, 23: 519-526. 10.1089/1044549041562267
Uehara Y, Miura S, von Eckardstein A, Abe S, Fujii A, Matsuo Y, Rust S, Lorkowski S, Assmann G, Yamada T, Saku K: Unsaturated fatty acids suppress the expression of the ATP-binding cassette transporter G1 (ABCG1) and ABCA1 genes via an LXR/RXR responsive element. Atherosclerosis. 2007, 191: 11-21. 10.1016/j.atherosclerosis.2006.04.018
Lavialle M, Denis I, Guesnet P, Vancassel S: Involvement of omega-3 fatty acids in emotional responses and hyperactive symptoms. J Nutr Biochem. 2010, 21: 899-905. 10.1016/j.jnutbio.2009.12.005
Lavialle M, Champeil-Potokar G, Alessandri JM, Balasse L, Guesnet P, Papillon C, Pévet P, Vancassel S, Vivien-Roels B, Denis I: An (n-3) polyunsaturated fatty acid-deficient diet disturbs daily locomotor activity, melatonin rhythm, and striatal dopamine in Syrian hamsters. J Nutr. 2008, 138: 1719-1724.
Qu Y, Villacreses N, Murphy DL, Rapoport SI: 5-HT2A/2C receptor signaling via phospholipase A2 and arachidonic acid is attenuated in mice lacking the serotonin reuptake transporter. Psychopharmacology (Berl). 2005, 180: 12-20. 10.1007/s00213-005-2231-5
Basselin M, Chang L, Seemann R, Bell JM, Rapoport SI: Chronic lithium administration to rats selectively modifies 5-HT2A/2C receptor-mediated brain signaling via arachidonic acid. Neuropsychopharmacology. 2005, 30: 461-472. 10.1038/sj.npp.1300611
Delion S, Chalon S, Guilloteau D, Lejeune B, Besnard JC, Durand G: Age-related changes in phospholipid fatty acid composition and monoaminergic neurotransmission in the hippocampus of rats fed a balanced or an n-3 polyunsaturated fatty acid-deficient diet. J Lipid Res. 1997, 38: 680-689.
Delion S, Chalon S, Guilloteau D, Besnard JC, Durand G: Alpha-Linolenic acid dietary deficiency alters age-related changes of dopaminergic and serotoninergic neurotransmission in the rat frontal cortex. J Neurochem. 1996, 66: 1582-1591. 10.1046/j.1471-4159.1996.66041582.x
Felder CC, Kanterman RY, Ma AL, Axelrod J: Serotonin stimulates phospholipase A2 and the release of arachidonic acid in hippocampal neurons by a type 2 serotonin receptor that is independent of inositolphospholipid hydrolysis. Proc Natl Acad Sci USA. 1990, 87: 2187-2191. 10.1073/pnas.87.6.2187
Rimoldi OJ, Finarelli GS, Brenner RR: Effects of diabetes and insulin on hepatic delta 6 desaturase gene expression. Biochem Biophys Res Commun. 2001, 283: 323-326. 10.1006/bbrc.2001.4785
Das UN, Kumar KV, Ramesh G: Essential fatty acid metabolism in South Indians. Prostaglandins Leukot Essen Fatty Acids. 1994, 50: 253-255. 10.1016/0952-3278(94)90163-5.
Das UN: Essential fatty acid metabolism in patients with essential hypertension, diabetes mellitus and coronary heart disease. Prostaglandins Leukot Essen Fatty Acids. 1995, 52: 387-391. 10.1016/0952-3278(95)90066-7.
Das UN: A defect in the activity of Δ6 and Δ5 desaturases may be a factor in the initiation and progression of atherosclerosis. Prostaglandins Leukot Essen Fatty Acids. 2007, 76: 251-268. 10.1016/j.plefa.2007.03.001.
Das UN: A defect in the activity of Δ6 and Δ5 desaturases may be a factor predisposing to the development of insulin resistance syndrome. Prostaglandins Leukot Essen Fatty Acids. 2005, 72: 343-350. 10.1016/j.plefa.2005.01.002.
Das UN: Do polyunsaturated fatty acids behave as endogenous "polypill"?. Med Hypotheses. 2008, 70: 430-434. 10.1016/j.mehy.2007.05.023
Das UN: Prostaglandins and cardiac arrhythmias. Med J Australia. 1981, 2: 157-
Das UN: Prostacyclin as an endogenous anti-arrhythmic agent. Basic Res Cardiol. 1983, 78: 716-719. 10.1007/BF01907219
Das UN: Lipoxin A4 may serve as an endogenous anti-arrhythmic molecule. Med Hypotheses. ,
Bertrandt J, Klos A, Debski B: Content of polyunsaturated fatty acids (PUFAs) in serum and liver of rats fed restricted diets supplemented with vitamins B2, B6 and folic acid. Biofactors. 2004, 22: 189-192. 10.1002/biof.5520220139
Debski B, Bertrandt J, Klos A, Gralak M: Influence of folic acid, vitamin B2 and B6 supplementation on feed intake, body and organs weight, and liver fatty acids composition in rats subjected to severe protein deprivation. Pol J Vet Sci. 2006, 9: 185-190.
Bertrandt J, Klos A, Debski B: Influence of vitamin B6 supplementation on polyunsaturated fatty acids concentration in serum and liver of rats fed a diet restricted in protein. Nahrung. 2004, 48: 99-103. 10.1002/food.200300338
Bertrandt J, Klos A, Debski B: Polyunsaturated fatty acid (PUFA) changes in serum and liver of undernourished rats given dietary vitamin B6 supplementation. J Nutr Sci Vitaminol (Tokyo). 2005, 51: 129-134.
Hakonarson H, Thorvaldsson S, Helgadottir A, Gudbjartsson D, Zink F, Andresdottir M, Manolescu A, Arnar DO, Andersen K, Sigurdsson A, Thorgeirsson G, Jonsson A, Agnarsson U, Bjornsdottir H, Gottskalksson G, Einarsson A, Gudmundsdottir H, Adalsteinsdottir AE, Gudmundsson K, Kristjansson K, Hardarson T, Kristinsson A, Topol EJ, Gulcher J, Kong A, Gurney M, Thorgeirsson G, Stefansson K: Effects of a 5-lipoxygenase-activating protein inhibitor on biomarkers associated with risk of myocardial infarction: a randomized trial. JAMA. 2005, 293: 2245-2256. 10.1001/jama.293.18.2245
Jeng JR: Plasma C-reactive protein and 5-lipoxygenase-activating protein gene promoter poly-A polymorphism in patients with coronary artery disease. Cardiology. 2008, 109: 25-32. 10.1159/000105323
Conti P, Reale M, Barbacana RC, Panara MR, Bongrazio M: Inhibition of leukotriene B4 in neutrophils by lipoxin A4 and B4. Agents Actions. 1991, 32: 85-87. 10.1007/BF01983321
Chiang N, Gronert K, Clish CB, O'Brien JA, Freeman MW, Serhan CN: Leukotriene B4 receptor transgenic mice reveal novel protective roles for lipoxins and aspirin-triggered lipoxins in reperfusion. J Clin Invest. 1999, 104: 309-316. 10.1172/JCI7016
Misra A, Singhal N, Khurana L: Obesity, the metabolic syndrome, and type 2 diabetes in developing countries: role of dietary fats and oils. J Am Coll Nutr. 2010, 29 (3 Suppl): 289S-301S.
Anand SS, Razak F, Yi Q, Davis B, Jacobs R, Vuksan V, Lonn E, Teo K, McQueen M, Yusuf S: C-reactive protein as a screening test for cardiovascular risk in a multiethnic population. Arterioscler Thromb Vasc Biol. 2004, 24: 1509-1515. 10.1161/01.ATV.0000135845.95890.4e
Donoghue MO, Morrow DA, Cannon CP, Wei G, Murphy SA, Gibson CM, Sabatinel MS: Association between baseline neutrophil count, clopidogrel therapy, and clinical and angiographic outcomes in patients with ST-elevation myocardial infarction receiving fibrinolytic therapy. Eur Heart J. 2008, 29: 984-991. 10.1093/eurheartj/ehn112
Morrow DA, Sabatine MS, Brennan ML, de Lemos JA, Murphy SA, Ruff CT, Rifai N, Cannon CP, Hazen SL: Concurrent evaluation of novel cardiac biomarkers in acute coronary syndrome: myeloperoxidase and soluble CD40 ligand and the risk of recurrent ischaemic events in TACTICS-TIMI 18. Eur Heart J. 2008, 29: 1096-1102. 10.1093/eurheartj/ehn071
Brooks AR, Lelkes PI, Rubanyi GM: Gene expression profiling of human aortic endothelial cells exposed to disturbed flow and steady laminar flow. Physiol Genomics. 2002, 9: 27-41.
Napoli D, D'Armiento FP, Mancini FP, Postiglione A, Witztum JL, Palumbo G, Palinski W: Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocytic recruitment into early atherosclerotic lesions. J Clin Invest. 1997, 100: 2680-2690. 10.1172/JCI119813
Shi W, Haberland ME, Jien ML, Shih DM, Lusis AJ: Endothelial responses to oxidized lipoproteins determine genetic susceptibility to atherosclerosis in mice. Circulation. 2000, 102: 75-81.
Cybulsky MI, Won D, Haidari M: Leukocyte recruitment to atherosclerotic lesion. Can J Cardiol. 2004, 20 (Suppl. B): 24B-28B.
Jongstra-Bilen J, Haidari M, Zhu SN, Chen M, Guha D, Cybulsky MI: Low-grade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis. J Exp Med. 2006, 203: 2073-2083. 10.1084/jem.20060245
Santerre RF, Nicolosi RJ, Smith SC: Respiratory control in preatherosclerotic susceptible and resistant pigeon aortas. Exp Mol Pathol. 1974, 20: 397-406. 10.1016/0014-4800(74)90069-0
Petterson G: Effect of dinitrophenol and anoxia on isometric tension in rabbit colon smooth muscle. Acta Pharmacol Toxicol (Copenh). 1985, 57: 184-189.
Bernal-Mizrachi C, Gates AC, Weng S, Imamura T, Knutsen RH, DeSantis P, Coleman T, Townsend RR, Muglia LJ, Semenkovich CF: Vascular respiratory uncoupling increases blood pressure and atherosclerosis. Nature. 2006, 435: 502-506. 10.1038/nature03527.
Watts H: Evolution of the Atherosclerotic Plaque. Edited by: Jones RJ. 1963, 117: Univ Chicago, Chicago,
Levin M, Leppanen O, Evaldsson M, Wiklund O, Bondjers G, Bjornheden T: Mapping of ATP, glucose, glycogen, and lactate concentrations within the arterial wall. Arterioscler Thromb Vasc Biol. 2003, 25: 1801-1807. 10.1161/01.ATV.0000092872.54026.8D.
Smith EB: The effects of age and of early atheromata on the intimal lipids in men. Biochem J. 1962, 84: 49-
Smith EB: Lipids carried by S1 0-12 lipoprotein in normal and hypercholesterolaemic serum. Lancet. 1962, 2: 530-534. 10.1016/S0140-6736(62)90402-6
Klein PD, Johnson RM: Phosphorous metabolism in unsaturated fatty acid-deficient rats. J Biol Chem. 1954, 211: 103-110.
Hayashida T, Portman OW: Swelling of liver mitochondria from rats fed diets deficient in essential fatty acids. Proc Soc Exp Biol Med. 1960, 103: 656-659.
Cornwell DG, Panganamala RV: Atherosclerosis an intracellular deficiency in essential fatty acids. Prog Lipid Res. 1981, 20: 365-376. 10.1016/0163-7827(81)90069-2
Merched AJ, Ko K, Gotlinger KH, Serhan CN, Chan L: Atherosclerosis: evidence for impairment of resolution of vascular inflammation governed by specific lipid mediators. FASEB J. 2008, 22: 3595-3606. 10.1096/fj.08-112201
Takano T, Fiore S, Maddox JF, Brady HR, Petasis NA, Serhan CN: Aspirin-triggered 15-epi-lipoxin A4 and LXA4 stable analogues are potent inhibitors of acute inflammation: evidence for anti-inflammatory receptors. J Exp Med. 1997, 185: 1693-1704. 10.1084/jem.185.9.1693
Dotsenko O, Chaturvedi N, Thom SA, Wright AR, Mayet J, Shore A, Schalkwijk C, Hughes AD: Platelet and leukocyte activation, atherosclerosis and inflammation in European and South Asian men. J Thromb Haemost. 2007, 5: 2036-2042. 10.1111/j.1538-7836.2007.02711.x
Suresh Y, Das UN: Protective action of arachidonic acid against alloxan-induced cytotoxicity and diabetes mellitus. Prostaglandins Leukotrienes Essential Fatty Acids. 2001, 64: 37-52. 10.1054/plef.2000.0236.
Suresh Y, Das UN: Long-chain polyunsaturated fatty acids and chemically-induced diabetes mellitus: Effect of ω-6 fatty acids. Nutrition. 2003, 19: 93-114. 10.1016/S0899-9007(02)00856-0
Suresh Y, Das UN: Long-chain polyunsaturated fatty acids and chemically-induced diabetes mellitus: Effect of ω-3 fatty acids. Nutrition. 2003, 19: 213-228. 10.1016/S0899-9007(02)00855-9
Krishna Mohan I, Das UN: Prevention of chemically-induced diabetes mellitus in experimental animals by polyunsaturated fatty acids. Nutrition. 2001, 17: 126-151. 10.1016/S0899-9007(00)00468-8
Wei D, Li J, Shen M, Jia W, Chen N, Chen T, Su D, Tian H, Zheng S, Dai Y, Zhao A: Cellular production of n-3 PUFAs and reduction of n-6-to-n-3 ratios in the pancreatic beta-cells and islets enhance insulin secretion and confer protection against cytokine-induced cell death. Diabetes. 2010, 59: 471-478. 10.2337/db09-0284
Sailaja Devi MM, Das UN: Effect of prostaglandins against alloxan-induced cytotoxicity to insulin secreting insulinoma RIN cells in vitro. Prostaglandins Leukot Essen Fatty Acids. 2004, 71: 309-318. 10.1016/j.plefa.2004.04.006.
Sailaja MM, Das UN: Effect of prostaglandins against alloxan-induced diabetes mellitus. Prostaglandins Leukot Essen Fatty Acids. 2006, 74: 39-60. 10.1016/j.plefa.2005.09.003.
Gronert K: Lipoxins in the eye and their role in wound healing. Prostaglandins Leukot Essent Fatty Acids. 2005, 73: 221-229. 10.1016/j.plefa.2005.05.009
Brzozowski T, Konturek PC, Pajdo R, Ptak-Belowska A, Kwiecien S, Pawlik M, Drozdowicz D, Sliwowski Z, Brzozowski B, Konturek SJ, Pawlik WW: Physiological mediators in nonsteroidal anti-inflammatory drugs (NSAIDs)-induced impairment of gastric mucosal defense and adaptation. Focus on nitric oxide and lipoxins. J Physiol Pharmacol. 2008, 59 (Suppl 2): 89-102.
Weylandt KH, Kang JX, Wiedenmann B, Baumgart DC: Lipoxins and resolvins in inflammatory bowel disease. Inflamm Bowel Dis. 2007, 13: 797-799. 10.1002/ibd.20109
Malerba G, Schaeffer L, Xumerle L, Klopp N, Trabetti E, Biscuola M, Cavallari U, Galavotti R, Martinelli N, Guarini P, Girelli D, Olivieri O, Corrocher R, Heinrich J, Pignatti PF, Illig T: SNPs of the FADS gene cluster are associated with polyunsaturated fatty acids in a cohort of patients with cardiovascular disease. Lipids. 2008, 43: 289-299. 10.1007/s11745-008-3158-5
Martinelli N, Girelli D, Malerba G, Guarini P, Illig T, Trabetti E, Sandri M, Friso S, Pizzolo F, Schaeffer L, Heinrich J, Pignatti PF, Corrocher R, Olivieri O: FADS genotypes and desaturase activity estimated by the ratio of arachidonic acid to linoleic acid are associated with inflammation and coronary artery disease. Am J Clin Nutr. 2008, 88: 941-949.
Lattka E, Illig T, Heinrich J, Koletzko B: FADS gene cluster polymorphisms: important modulators of fatty acid levels and their impact on atopic diseases. J Nutrigenet Nutrigenomics. 2009, 2: 119-128. 10.1159/000235559
Dr. U N Das is in receipt of Ramalingaswami Fellowship of Department of Biotechnology, India during the tenure of this study.
The authors declare that they have no competing interests.
UND is the sole contributor to this work.