Long-chain polyunsaturated fatty acids and chemically induced diabetes mellitus. Effect of omega-3 fatty acids

In a previous study, we showed that prior oral feeding of oils rich in omega-3 eicosapentaenoic acid and docosahexaenoic acid and omega-6 gamma-linolenic acid and arachidonic acid prevent the development of alloxan-induced diabetes mellitus in experimental animals. We also observed that 99% pure omega-6 fatty acids gamma-linolenic acid and arachidonic acid protect against chemically induced diabetes mellitus. Here we report the results of our studies with omega-3 fatty acids. Alloxan-induced in vitro cytotoxicity and apoptosis in an insulin-secreting rat insulinoma cell line, RIN, was prevented by prior exposure of these cells to alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid. Prior oral supplementation with alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid prevented alloxan-induced diabetes mellitus. alpha-Linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid not only attenuated chemical-induced diabetes mellitus but also restored the anti-oxidant status to normal range in various tissues. These results suggested that omega-3 fatty acids can abrogate chemically induced diabetes in experimental animals and attenuate the oxidant stress that occurs in diabetes mellitus.     

Long-chain polyunsaturated fatty acids and chemically induced diabetes mellitus: effect of omega-6 fatty acids

OBJECTIVE: We previously showed that prior oral supplementation of oils rich in omega-3, eicosapentaenoic acid and docosahexaenoic acid, and omega-6, gamma-linolenic acid and arachidonic acid, can prevent the development of alloxan-induced diabetes mellitus in experimental animals. But the effect of individual fatty acids on chemically induced diabetes mellitus is not known. We report the results of our studies with omega-6 fatty acids. METHODS: Alloxan-induced in vitro cytotoxicity and apoptosis in an insulin-secreting rat insulinoma cell line, RIN, was prevented by prior exposure of these cells to linoleic acid, gamma-linolenic acid, and arachidonic acid (AA) but not to dihomo-gamma-linolenic acid. Cyclo-oxygenase and lipoxygenase inhibitors did not block this protective action of AA. Prior oral supplementation with gamma-linolenic acid and pre- and simultaneous treatments with AA prevented alloxan-induced diabetes mellitus. RESULTS: Even though pretreatment with linoleic acid and dihomo-gamma-linolenic acid and simultaneous treatment with linoleic acid, gamma-linolenic acid, and dihomo-gamma-linolenic acid did not prevent the development of diabetes mellitus, the severity of diabetes was much less. The saturated fatty acid stearic acid and the monounsaturated fatty acid oleic acid were ineffective in preventing alloxan-induced diabetes mellitus. gamma-Linolenic acid and AA not only attenuated chemically induced diabetes mellitus but also restored the antioxidant status to normal range in various tissues. Changes in the concentrations of various fatty acids of the phospholipid fraction of plasma that occurred as a result of alloxan-induced diabetes mellitus also reverted to normal in the AA-treated animals. CONCLUSIONS: These results suggest that polyunsaturated fatty acids can prevent chemically induced diabetes in experimental animals and attenuate the oxidant stress that occurs in diabetes mellitus.     

孕中期血浆n-6多不饱和脂肪酸水平与妊娠期糖尿病的关联

目的  探讨中国西南地区孕妇孕中期血浆n-6多不饱和脂肪酸(polyunsaturated fatty acids, PUFAs)水平与妊娠期糖尿病(gestational diabetes mellitus, GDM)的关联。方法  本研究基于同济-双流出生队列,于2017-2019年在成都市双流区妇幼保健院围产保健门诊纳入18~40岁的6 143名单胎妊娠孕妇。通过问卷调查收集孕妇基本信息和孕期健康状况,并对其进行体格测量和血液样本收集。根据孕24~28周孕妇75 g口服葡萄糖耐量试验(oral glucose tolerance test, OGTT)结果,选取269名符合GDM诊断标准的孕妇作为病例组。在非GDM的孕妇中按照孕妇年龄(±3岁)、基线孕周(±4周)进行1∶2匹配,选取538名非GDM孕妇作为对照组。采用气相色谱-质谱联用的方法检测孕妇孕中期血浆多种n-6 PUFAs水平。采用多变量校正的条件Logistic回归分析模型评估孕中期血浆各n-6 PUFAs类别和总n-6 PUFAs与GDM患病风险的关联,并利用错误发现率(false discovery rate, FDR)法校正多重检验。采用敏感性分析探讨其稳健性。结果  807名研究对象的年龄为(27.8±3.9)岁,孕周为(24.8±1.1)周,孕前BMI为(21.5±3.1) kg/m²。孕中期血浆亚油酸(linoleic acid, LA)、γ-亚油酸(gamma-linolenic acid, GLA)、二十碳二烯酸(eicosadienoic acid, EDA)和花生四烯酸(arachidonic acid, AA)水平每增加一个标准差,GDM的患病风险的OR值分别为0.83(95% CI：0.69~0.99, P=0.039)、0.82(95% CI：0.69~0.99, P=0.037)、0.63(95% CI：0.50~0.79, P < 0.001)和1.20(95% CI：1.02~1.42, P=0.032),而多重校正后LA、GLA和AA与GDM患病风险关联无统计学意义(均有P > 0.05)。敏感性分析结果显示EDA与GDM患病风险的关联稳定。结论  孕中期血浆n-6 PUFAs中EDA与GDM患病风险有关,此结论需进一步在大样本人群中进行验证。     

Synthesis of long-chain polyunsaturated fatty acids in preterm newborns fed formula with long-chain polyunsaturated fatty acids

BACKGROUND: Docosahexaenoic acid (DHA) and arachidonic acid (AA) are long-chain polyunsaturated fatty acids (LCPs) that play pivotal roles in growth and neurodevelopment. OBJECTIVE: We aimed to quantify the synthesis of LCPs in preterm infants fed infant formula containing LCPs. DESIGN: Twenty-two preterm infants were randomly assigned to either the no-LCP group (fed formula without LCPs; n = 11) or the LCP group (fed formula with LCPs; n = 11). Dietary LCPs had higher (13)C content than did the endogenously synthesized LCPs, which were derived from linoleic and alpha-linolenic acids. The (13)C content of major selected plasma fatty acids was measured by using gas chromatography-isotope ratio mass spectrometry at birth and at age 1, 3, and 7 mo. Absolute LCP synthesis and the percentage of LCP synthesis relative to dietary intake were calculated. RESULTS: Percentage AA synthesis was 67.2 +/- 7.8%, 35.9 +/- 9.8%, and 29.0 +/- 10.3%, and that of DHA was 41.7 +/- 14.9%, 10.5 +/- 8.1%, and 7.4 +/- 6.2% at 1, 3, and 7 mo old, respectively. Absolute AA synthesis was 26.7 +/- 4.2, 14.4 +/- 3.9, and 11.6 +/- 4.1 mg x kg(-1) x d(-1) and that of DHA was 12.6 +/- 4.5, 3.2 +/- 2.5, and 2.3 +/- 1.9 mg x kg(-1) . d(-1) at 1, 3, and 7 mo old, respectively. AA and DHA synthesis decreased significantly (P < 0.01) with time, and AA synthesis was significantly (P < 0.01) greater than DHA synthesis. CONCLUSIONS: By this novel approach, we measured endogenous LCP synthesis in infants receiving dietary LCPs over long periods. By age 7 mo, LCP synthesis was dramatically lower in preterm infants fed LCPs.     

Maternal plasma phospholipid polyunsaturated fatty acids in pregnancy with and without gestational diabetes mellitus: relations with maternal factors.

BACKGROUND: The fatty acids arachidonic acid (AA; 20:4n-6) and docosahexaenoic acid (DHA; 22:6n-3) are essential for fetal growth and development, but their metabolism may be altered in insulin resistance. OBJECTIVES: The objectives were to determine maternal plasma phospholipid polyunsaturated fatty acid concentrations in pregnant women receiving dietary therapy for gestational diabetes mellitus (GDM) and to identify maternal factors associated with plasma phospholipid AA and DHA concentrations in the third trimester. DESIGN: Fasting plasma phospholipid fatty acids were determined in women with GDM (n = 15) receiving dietary therapy only and in healthy, pregnant women without GDM (control group, n = 15) at 27-30, 33-35, and 36-39 wk gestation. RESULTS: Maternal plasma phospholipid (as % by wt of total fatty acids and mg/L) linoleic acid (18:2n-6), AA, and 22:5n-6 concentrations did not differ significantly between women with GDM and control subjects. The other n-6 long-chain polyunsaturated fatty acids (% by wt) were lower in GDM subjects than in control subjects. Plasma phospholipid (expressed as % by wt and mg/L) linolenic acid (18:3n-3) and summed precursors of DHA were lower and DHA (% by wt and mg/L), adjusted for dietary DHA intake, was 13% higher in GDM subjects than in control subjects. Maternal blood hemoglobin A1C was inversely related to plasma phospholipid AA (% by wt) (r = -0.56, P = 0.03) in control subjects and positively associated with plasma phospholipid AA (% by wt) in women with GDM (r = 0.76, P = 0.001). Pregravid body mass index was negatively associated with plasma phospholipid DHA (% by wt) in control subjects (r = -0.55, P = 0.04) and in women with GDM with a body mass index (in kg/m2) <30 (r = -0.76, P = 0.007). CONCLUSIONS: This is the first report documenting alterations in maternal plasma phospholipid PUFAs in pregnant women receiving dietary therapy for GDM. In pregnant woman, both with and without GDM, maternal glycemic control and pregravid BMI appear to be significant predictors of plasma phospholipid AA and DHA, respectively, during the third trimester. Additionally, dietary DHA significantly affects phospholipid DHA concentrations.     

脂肪酸对糖尿病模型大鼠血磷脂脂肪谱的影响

目的　观察富含n - 6和n - 3多不饱和脂肪酸 (PUFA)饲料对自发性 2型糖尿病模型OtsukaLong -E vansTokushimaFatty(OLETF)大鼠糖代谢及血清磷脂 (S -PL)中脂肪酸 (FA)组成的影响。 方法　将 2 0只 14周龄雄性OLETF大鼠随机分为 2组。两组大鼠饲料总能量相同 ,其中饱和脂肪酸 (SFA)、单不饱和脂肪酸 (MUFA)和PU FA的百分含量亦相同 ,但分别富含n - 6PUFA〔4 1 6mol/ (10 0mol·脂肪 )〕和n - 3PUFA〔2 0 4mol/ (10 0mol·脂肪 )〕 ,饮食干预 10周。第 2 4周时实施口服糖耐量试验 (OGTT)、胰岛素水平测定和S -PL中FA组成测定。结果　干预期间 ,两组大鼠总进食量及体重增长无显著性差异 ;干预后OGTT及胰岛素水平测定表明 ,n - 3组相对于n - 6组具有较好的胰岛素敏感性。n - 3组大鼠S -PL中 18∶1(n - 9)、MUFA总量、18∶2 (n - 6 )、各n - 3系PUPA百分含量较n- 6组高 ,n - 6PUFA总量、2 0∶4 (n - 6 )百分含量较低。结论　n - 3PUFA的摄入相对于n - 6PUFA对OLETF大鼠的糖代谢有益 ,OLETF大鼠S -PL的FA组成受到饲料中FA的影响 ,但并不是其直接反应。     

n-3 long-chain polyunsaturated fatty acids in type 2 diabetes: a review

Historically, epidemiologic studies have reported a lower prevalence of impaired glucose tolerance and type 2 diabetes in populations consuming large amounts of the n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) found mainly in fish. Controlled clinical studies have shown that consumption of n-3 LC-PUFAs has cardioprotective effects in persons with type 2 diabetes without adverse effects on glucose control and insulin activity. Benefits include lower risk of primary cardiac arrest; reduced cardiovascular mortality, particularly sudden cardiac death; reduced triglyceride levels; increased high-density lipoprotein levels; improved endothelial function; reduced platelet aggregability; and lower blood pressure. These favorable effects outweigh the modest increase in low-density lipoprotein levels that may result from increased n-3 LC-PUFA intake. Preliminary evidence suggests increased consumption of n-3 LC-PUFAs with reduced intake of saturated fat may reduce the risk of conversion from impaired glucose tolerance to type 2 diabetes in overweight persons. Reported improvements in hemostasis, slower progression of artery narrowing, albuminuria, subclinical inflammation, oxidative stress, and obesity require additional confirmation. Expected health benefits and public health implications of consuming 1 to 2 g/day n-3 LC-PUFA as part of lifestyle modification in insulin resistance and type 2 diabetes are discussed.     

Plasma phospholipid polyunsaturated fatty acids and homocysteine in Chinese type 2 diabetes patients

The main aim of the present study was to investigate the plasma phospholipids (PL) fatty acids status and its association with plasma Hcy in patients with type 2 diabetes mellitus (T2DM). One hundred and four T2DM (aged 57.3±13.4 y) and 150 healthy subjects (aged 48.4±8.7 y) were recruited. Plasma Hcy and PL fatty acids were determined by standard methods. Plasma Hcy concentration in T2DM was significantly higher than that in healthy subjects (p<0.001). The prevalence of hyperhomocysteinemia was significantly higher in T2DM (36.54%) than that in healthy subjects (17.32%) (p=0.012). Plasma PL 20:4n-6 (r=0.303, p=0.012), 22:5n-3 (r=0.312, p=0.01), total PUFA (r=0.303, p=0.012), n-6 PUFA (r=0.261, p=0.032) were significantly positively associated with plasma Hcy concentration in T2DM. While, plasma PL n-3:n-6 PUFA (r=-0.400, p=0.046) was negatively associated with plasma Hcy in T2DM. In healthy subjects, plasma PL 22:6n-3 (r=-0.201, p=0.042) was negatively associated with plasma Hcy. In addition, plasma PL 22:6n-3 (r=0.193, p=0.044) and 22:5n-6 (r=0.234, p=0.038) were significantly negatively associated with plasma vitamin B-12 in healthy subjects. Our results suggested that increased plasma Hcy levels in T2DM associated with low n-3:n-6 ratio intake. We suggest that T2DM increase their long chain n-3 PUFA intake from fish or fish oil while decrease n-6 PUFA intake.     

Dietary polyunsaturated fatty acids reduce retinal stress induced by an elevation of intraocular pressure in rats

N-6 and n-3 polyunsaturated fatty acids (PUFAs) have been shown to prevent tissue release of inflammatory molecules. We have shown that a combination of n-6 and n-3 PUFAs is more efficient than single supplementations on the long-term consequences of intraocular pressure elevation. We hypothesized that such an association is also more effective during early retinal stress by modifying retinal proinflammatory prostaglandin and cytokine productions. Rats were supplemented for 3 months with n-6 PUFAs, n-3 PUFAs, or both n-6 and n-3 PUFAs. After 3 months, a surgical elevation of intraocular pressure was induced. Retinal morphometry and glial cell activation were evaluated 24 hours after laser treatment. The retinal levels of prostaglandin E₁ (PGE₁) and prostaglandin E₂ (PGE₂) and the messenger RNA levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α were measured. Retinal glial cell activation after laser treatment was partly prevented by dietary n-6, n-3, and n-6 and n-3 PUFAs. Retinal PGE₁ was unaffected by the laser treatment or by the diet. Dietary n-6 and/or n-3 PUFAs prevented the increase in PGE₂ levels observed in laser-treated retinas without affecting the induction of interleukin-1β, interleukin-6, and tumor necrosis factor-α messenger RNAs. This study shows that not only a combination of n-6 and n-3 PUFAs but also single supplementations can preserve the retina from early glial cell activation and PGE₂ release. The protective effect is not mediated by changes in cytokine expression but may be related to modifications in retinal prostaglandin metabolism.     

n-3及n-6多不饱和脂肪酸与乳腺癌关系的Meta分析

目的 系统评价n-3多不饱和脂肪酸(n-3PUFAs)、n-6多不饱和脂肪酸(n-6PUFAs)及其比例与乳腺癌发病风险的关系。方法 系统检索Pubmed、Embase、Web of Science、知网、万方等数据库截止至2022年1月1日有关n-3及n-6多不饱和脂肪酸与乳腺癌关系的研究,对最终纳入的文献进行数据提取与质量评价,采用Stata 15.1软件进行Meta分析。结果 共纳入33项针对n-3及n-6PUFAs和乳腺癌发病风险关联的观察性流行病学研究,其中队列研究14项,病例对照研究20项,共纳入研究对象1 077 178例,患者19 207例。Meta分析结果显示:n-3多不饱和脂肪酸(OR=0.933,95%CI:0.858～1.014)、n-6多不饱和脂肪酸(OR=1.018,95%CI:0.914～1.133)与乳腺癌发病风险无统计学关联(P>0.05),而较高的n-6/n-3PUFAs比值会显著增加乳腺癌的发病风险(OR=1.166,95%CI:1.047～1.299,P=0.005)。结论 n-6/n-3多不饱和脂肪酸的比值与乳腺癌的发病风险呈正相关,提示合理的膳食脂肪摄入比可能会降低乳腺癌的患病风险。而n-3及n-6多不饱和脂肪酸与乳腺癌发病风险的单独效应关系尚不明确,仍需更多前瞻性实验流行病学证据进行支持。     

Desirable intakes of polyunsaturated fatty acids in Indonesian adults

A Indonesian Advisory Group on Fatty Acid Nutrition and Health was established in 2004 to consider the increasing incidence of nutritionally-related cardiovascular disease in Indonesia. Emerging international recommendations, often focused on dietary fat and may not have been relevant to the national situation. Traditional dietary patterns were apparently protective against ischaemic heart disease often with fat derived dominantly from a particular source like coconut, soy, peanut or fish. These fats were used in ways which promoted the use of potentially cardioprotective foods like legumes, vegetables, fruits and aquatic food. Optimal intakes of polyunsaturated fatty acids in Indonesia are likely to reflect both absolute intakes and the relationships between n-3 and n-6 fatty acids of longer chain lengths. This leaves some issues for active and continuing review, like the intakes of trans fatty acids, and the regulatory and food labelling implications. Some studies underway and others which need implementation will enable the Advisory Group to prepare a second report with more basis in Indonesian evidence. In the meantime, the Advisory Group has recommended that the AHA (American Heart Association) and ISSFAL (International Society for the Study of Fatty Acids and Lipids) recommendations obtain until the end of 2007.