Immunometabolic role of long‐chain omega‐3 fatty acids in obesity‐induced inflammation

Inflammation links obesity with the development of insulin resistance. Macrophages and phagocytic immune cells communicate with metabolic tissues to direct an inflammatory response caused by overnutrition and expanding adipose tissue. Marine‐derived omega‐3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), modulate inflammatory signalling events, providing various anti‐inflammatory and cardioprotective benefits. Moreover, EPA and DHA may improve insulin sensitivity by generating proresolving lipid mediators and promoting alternatively activated macrophages. This review will assess the role of EPA and DHA in ameliorating obesity‐induced inflammation, evaluating clinical evidence and mechanisms of action. The pathophysiology of insulin resistance resulting from obesity‐induced inflammation will be discussed, highlighting the relationship between metabolism and immunity, and in particular, how EPA and DHA work with both systems to modulate immunometabolic complications and chronic disease. Copyright © 2013 John Wiley & Sons, Ltd.     

Omega-3 fatty acids supplementation improves endothelial function and arterial stiffness in hypertensive patients with hypertriglyceridemia and high cardiovascular risk

Association between hypertriglyceridemia and cardiovascular (CV) disease is still controversial. The purpose of this study was to compare omega-3 and ciprofibrate effects on the vascular structure and function in low and high CV risk hypertensive patients with hypertriglyceridemia. Twenty-nine adults with triglycerides 150–499 mg/dL were divided into low (<7.5%) and high (≥7.5%) CV risk, randomized to receive omega-3 fatty acids 1800 mg/d or ciprofibrate 100 mg/d for 12 weeks. Treatment was switched after 8-week washout. Clinical evaluation and vascular tests were assessed at baseline and after intervention. Peripheral (131 ± 3 to 125 ± 3 mm Hg, P < .05) and aortic (124 ± 3 to 118 ± 2 mg/dL, P < .05) systolic blood pressure were decreased by ciprofibrate in low-risk patients. In high-risk patients, pulse wave velocity was reduced (10.4 ± 0.4 to 9.4 ± 0.3 m/s, P < .05) and flow-mediated dilation was increased (11.1 ± 1.6 to 13.5 ± 1.2%, P < .05) by omega-3. In conclusion, omega-3 improved arterial stiffness and endothelial function, pointing out the beneficial effect of this therapy on vascular aging, in high-risk patients.     

洛伐他汀与Omega-3脂肪酸对老年混合型高脂血症患者的影响

目的　评价洛伐他汀单用及与Omega 3脂肪酸联合治疗老年混合型高脂血症患者的疗效与安全性。方法　5 3例混合型高脂血症患者随机分为两组。洛伐他汀组 2 6例 ,给予洛伐他汀 2 0mg d ;洛伐他汀 +Omega 3组 2 7例 ,给予洛伐他汀 2 0mg d ,Omega 34.0 5g d ,治疗 8周 ,观察降脂疗效和不良反应。结果　洛伐他汀组总胆固醇 (TC)下降 2 4 .4 5 % ,达标率为 5 0 % ;低密度脂蛋白胆固醇 (LDL C)下降 36 .8% ,达标率为 6 5 .38% ;动脉硬化指数 ((TC HDL C) HDL C)下降 34.16 %。 (以上 3项均为 P <0 .0 0 1) ;甘油三酯 (TG)下降 6 .6 1% (P >0 .0 5 ) ,达标率为 4 2 .31% ;高密度脂蛋白 (HDL C)升高 4 .6 1%。洛伐他汀 +Omega 3组TC下降 2 4 .2 2 % ,达标率为 5 9.2 6 % ;LDL C下降2 1.82 % ,达标率为 70 .37% ;(TC HDL C) HDL C下降 34.90 %。 (以上 3项均为 P <0 .0 0 1) ;同时 ,TG下降 2 7.0 7% ,达标率为 6 2 .96 % ;HDL C升高 5 .38%。结论　洛伐他汀 +Omega 3组降低TG明显优于洛伐他汀组 ,降低TC、LDL C、(TC HDL C) HDL C ,二组差异无显著意义。但达标率洛伐他汀 +Omega 3脂肪酸组均高于洛伐他汀组。两组均未见明显不良反应     

Fat food for a bad mood. Could we treat and prevent depression in Type 2 diabetes by means of ω‐3 polyunsaturated fatty acids? A review of the evidence

AIMS: Evidence strongly suggests that depression is a common complication of Type 2 diabetes mellitus. However, there is considerable room to improve the effectiveness of pharmacological antidepressant agents, as in only 50-60% of the depressed subjects with diabetes does pharmacotherapy lead to remission of depression. The aim of the present paper was to review whether polyunsaturated fatty acids (PUFA) of the omega-3 family could be used for the prevention and treatment of depression in Type 2 diabetes. METHODS: MEDLINE database and published reference lists were used to identify studies that examined the associations between omega-3 PUFA and depression. To examine potential side-effects, such as on glycaemic control, studies regarding the use of omega-3 supplements in Type 2 diabetes were also reviewed. RESULTS: Epidemiological and clinical studies suggest that a high intake of omega-3 PUFA protects against the development of depression. There is also some evidence that a low intake of omega-3 is associated with an increased risk of Type 2 diabetes, but the results are less conclusive. Results from randomized controlled trials in non-diabetic subjects with major depression show that eicosapentaenoic acid is an effective adjunct treatment of depression in diabetes, while docosahexanoic acid is not. Moreover, consumption of omega-3 PUFA reduces the risk of cardiovascular disease and may therefore indirectly decrease depression in Type 2 diabetes, via the reduction of cardiovascular complications. CONCLUSIONS: Supplementation with omega-3 PUFA, in particular eicosapentaenoic acid, may be a safe and helpful tool to reduce the incidence of depression and to treat depression in Type 2 diabetes. Further studies are now justified to test these hypotheses in patients with Type 2 diabetes.     

Omega-3多不饱和脂肪酸代谢产物的动脉粥样硬化拮抗机制

动脉粥样硬化是由内皮细胞的损伤、脂质沉积等引起的慢性炎症反应性病理过程。Omega-3多不饱和脂肪酸(n-3 PUFA)具有重要的动脉粥样硬化保护作用,但其机制仍不明确。多不饱和脂肪酸在环氧化酶、脂氧合酶和细胞色素P450氧化酶的作用下产生具有不同生物活性的类二十烷酸代谢产物。Omega-3多不饱和脂肪酸在自身被代谢为类二十烷酸的同时,也可与花生四烯酸竞争共同的代谢酶,从而也对花生四烯酸来源的类二十烷酸代谢产物水平起调控作用。文章基于代谢的观点,系统地讨论了Omega-3多不饱和脂肪酸通过影响类二十烷酸代谢谱而发挥动脉粥样硬化拮抗作用的机制。     

Comparative cardiometabolic effects of fibrates and omega-3 fatty acids

Even with the aggressive reduction of low-density lipoprotein cholesterol by statin therapy, a high residual risk of cardiovascular events remains substantially and attracts attention to the need for additional preventive therapies. Therefore, effective reductions of residual risk of cardiovascular disease have emerged as therapeutic targets. Fibrates and omega-3 fatty acids have been introduced to reduce triglycerides and to increase high-density lipoprotein cholesterol and have shown anti-atherosclerotic, vascular and metabolic effects. However, some effects are controversial and very recent randomized clinical trials report different results from the earlier ones. In this review, we address the vascular and metabolic effects and the results of recent clinical trials of fibrates and omega-3 fatty acids. We also compared their effects under modern guideline therapy regarding potential drugs to reduce a residual cardiometabolic risk of cardiovascular disease.     

Long‐chain polyunsaturated fatty acid status in obesity: a systematic review and meta‐analysis

Long‐chain polyunsaturated fatty acid (LCPUFA) status has recently been related to the pathogenesis of obesity. Our aims were to systematically review observational studies investigating LCPUFA status from different blood compartments in overweight or obese subjects and to assess the relationship between LCPUFA profile and obesity. The Ovid MEDLINE, Scopus and Cochrane Library CENTRAL databases were searched from inception to January 2014. The meta‐analysis showed significant differences in the LCPUFA composition of total plasma lipids, plasma phospholipids and plasma cholesteryl esters between overweight or obese subjects and controls. Dihomo‐γ‐linolenic acid (DGLA) values were significantly higher in overweight or obese subjects compared with controls in all the investigated biomarkers. In addition, the DGLA/linoleic acid ratio (surrogate parameter for Δ6 desaturase activity) in plasma phospholipids was significantly elevated (mean difference [MD]: 0.05; 95% confidence interval [CI]: 0.02, 0.08; n = 280), while the arachidonic acid/DGLA ratio (surrogate parameter for Δ5 desaturase activity) was significantly decreased (MD: ?0.55; 95% CI: ?0.71, ?0.39; n = 347) in overweight or obese subjects compared with controls. The results of the present meta‐analysis confirm that LCPUFA profile is altered in obesity and suggest that the differences observed in desaturase activities may be responsible for the disturbed LCPUFA metabolism in obesity.     

Circulating n-3 fatty acids and linoleic acid as indicators of dietary fatty acid intake in post-myocardial infarction patients

Background and aims

Population-based studies often use plasma fatty acids (FAs) as objective indicators of FA intake, especially for n-3 FA and linoleic acid (LA). The relation between dietary and circulating FA in cardiometabolic patients is largely unknown. We examined whether dietary n-3 FA and LA were reflected in plasma lipid pools in post-myocardial infarction (MI) patients.

Relationship between circulating n-3 fatty acid concentrations and endothelial function in early adulthood.

AIMS: Fish consumption is inversely associated with cardiovascular mortality, presumably because of n-3 fatty acids in fish. Whether the protection of n-3 fatty acids extends beyond clinical coronary disease to influence the early vascular biology of atherosclerosis remains unclear. This study determined whether circulating levels of n-3 fatty acids are associated with vascular endothelial function in early adulthood. METHODS AND RESULTS: Three hundred and twenty-six adults (157 males, 169 females, aged 20 to 28 years) had high-resolution ultrasound measurements of flow-mediated brachial artery dilatation (FMD) (endothelium-dependent) and arterial response to glyceryl trinitrate (endothelium-independent). Levels of the n-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid in plasma and erythrocyte membranes of subjects were measured. n-3 Fatty acid levels were not related to vascular function in the whole group. In smokers, however, n-3 fatty acids were positively related to flow-mediated dilatation (plasma DHA vs. FMD: 0.045 mm. %(-1), 95% CI 0.011 to 0.079, P=0.01). Flow-mediated dilatation was also associated with n-3 fatty acid levels in subjects in the top third of the insulin, glucose and triglyceride distributions. CONCLUSION: In young smokers and those with higher fasting insulin, glucose or triglyceride concentrations (factors associated with endothelial dysfunction), n-3 fatty acid levels were positively associated with flow-mediated dilatation. This raises the possibility that physiological levels of circulating n-3 fatty acids may protect the endothelium from early adulthood.     

Cardiovascular disease event rates in patients with severe psoriasis treated with systemic anti‐inflammatory drugs: a Danish real‐world cohort study

Objectives

Psoriasis is a chronic inflammatory disorder associated with cardiovascular morbidity and mortality. Systemic anti‐inflammatory drugs, including biological agents, are widely used in the treatment of patients with moderate to severe psoriasis and may attenuate the risk of cardiovascular disease events. We therefore examined the rate of cardiovascular disease events in patients with severe psoriasis treated with systemic anti‐inflammatory drugs.

Design, setting and participants

Individual‐level linkage of nationwide administrative databases was used to assess the event rates associated with use of biological agents, methotrexate or other therapies, including retinoids, cyclosporine and phototherapy, in Denmark from 2007 to 2009.

Main outcome measure

Death, myocardial infarction and stroke.

Results

A total of 2400 patients with severe psoriasis, including 693 patients treated with biological agents and 799 treated with methotrexate, were identified. Incidence rates per 1000 patient‐years and 95% confidence intervals (CIs) for the composite endpoint were 6.0 (95% CI 2.7–13.4), 17.3 (95% CI 12.3–24.3) and 44.5 (95% CI 34.6–57.0) for patients treated with biological agents, methotrexate and other therapies, respectively. Age‐ and sex‐adjusted hazard ratios (HRs) were 0.28 (95% CI 0.12–0.64) and 0.65 (95% CI 0.42–1.00) for patients treated with biological agents and methotrexate, respectively, using other therapies as the reference cohort. Corresponding HRs for a secondary composite endpoint of cardiovascular death, myocardial infarction and stroke were 0.48 (95% CI 0.17–1.38) and 0.50 (95% CI 0.26–0.97).

Conclusion

In this nationwide study of patients with severe psoriasis, systemic anti‐inflammatory treatment with biological agents or methotrexate was associated with lower cardiovascular disease event rates compared to patients treated with other anti‐psoriatic therapies.