A tutorial on fatty acid biology

Fatty acids are an extraordinarily diverse set of molecules that serve as sources of fuel, key components of cell structure, and parent molecules for bioactive second messengers. The metabolism of fatty acids is part of a delicate homeostasis that is fundamental to normal functioning and the response to pathophysiologic insult. The growing body of evidence on nutrition demonstrates that we truly "are what we eat," and the fatty acid content of our diets has far-reaching physiologic implications, many of which we are only beginning to understand. As the gap between basic science and patient care becomes increasingly narrow, clinicians should have a working knowledge of fatty acid biology. This tutorial provides an overview of fatty acid biology with the goal of increasing comfort in discussing how these heterogeneous molecules are classified and metabolized, in addition to how fatty acid content influences basic cellular processes.     

Alterations in circulating fatty acid composition in patients with systemic lupus erythematosus: a pilot study

Introduction: Circulating fatty acids (FAs) may play a role in the disease pathogenesis of patients with systemic lupus erythematosus (SLE). Objectives: To compare red blood cell (RBC) and plasma FA composition: (1) between female SLE patients and age‐matched healthy female (HF) controls and in SLE with history of cardiovascular disease (CVD) and those with no history (SLE+CVD vs SLE–CVD); and (2) between SLE patients who were or were not receiving prednisone treatment at the time of blood sampling. Methods: This cross‐sectional study consisted of 33 female patients with SLE (11 SLE+CVD, 22 SLE?CVD) and 20 HF controls. Demographics, CVD risk, medication profile, blood biochemistry, and FA composition of RBC and plasma total lipids were determined. Results: Waist circumference and body mass index were higher in SLE patients than in HF controls. These variables along with serum triglycerides, blood glucose, and systolic blood pressure were higher in SLE+CVD than SLE?CVD patients. RBC FA composition showed lower eicosapentaenoic acid (EPA, ω‐3 active metabolite) and ω‐3 index (EPA+ docosahexaenoic acid) in SLE patients compared with HF controls. The ratio of the RBC inflammatory metabolite, arachidonic acid, to the anti‐inflammatory metabolite EPA was also significantly higher in SLE patients than in HF controls. No differences were seen in plasma FA between SLE and HF groups. However, SLE?CVD patients had a more favorable lipid profile than SLE+CVD patients. In SLE patients, the use of prednisone resulted in alteration of both RBC and plasma FA composition. Conclusion: SLE patients, regardless of their history of CVD, have altered plasma and RBC FA composition favoring inflammation. The use of prednisone was associated with differences in FA profile.     

Eicosapentaenoic acid and docosahexaenoic acid synergistically attenuate bile acid-induced hepatocellular apoptosis

Background: Clinical studies have demonstrated improvement of parenteral nutrition (PN)–associated liver disease (PNALD) with ω3 polyunsaturated fatty acid (ω3PUFA) supplementation containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Experiments were designed to test the following hypotheses: (1) therapeutic effects of ω3PUFA are due to attenuation of cellular apoptosis induced by hydrophobic bile acid exposure, which occurs in cholestasis, and (2) attenuation of apoptosis by EPA and DHA is additive or synergistic. Methods: Cultured HepG2 cells were treated with 50–200 µM chenodeoxycholic acid (CDCA) in the presence and absence of EPA, DHA, or EPA + DHA. Apoptosis was evaluated using cell staining with fluorescence microscopy and the Apo‐ONE Homogeneous Caspase‐3/7 assay. Specific apoptotic mediators were evaluated with quantitative RT‐PCR. Results: Treatment with EPA alone and DHA alone resulted in 22% and 9% attenuation of caspase‐3/7 activity, respectively. Caspase‐3/7 activity was attenuated by 52% when cells were treated with a combination of EPA and DHA (P = .0034). Treatment with EPA alone, DHA alone, and the combination of EPA and DHA all resulted in equal attenuation of apoptotic mediator gene expression. Conclusions: The combination of EPA and DHA resulted in a synergistic attenuation of bile acid–induced hepatocellular apoptosis, as assessed by caspase‐3/7 activity, compared to EPA and DHA separately. The combination of EPA and DHA did not result in a synergistic attenuation of the upregulation of Fas or TRAIL‐R2. These data suggest that EPA and DHA may be working via multiple intracellular pathways to attenuate bile acid–induced apoptosis.     

Enrichment of n‐3 fatty acids and conjugated linoleic acid in beef: ProSafeBeef

ProSafeBeef is a 5‐year integrated project funded by the European Commission under the sixth Framework Programme. The overall aim is to advance beef safety and quality across Europe and the work programme spans seven integrated “pillars”. Pillar 3 is concerned with producing safe beef and beef products with enhanced nutritional and eating quality characteristics. A particular focus is on the development of strategies to enhance the concentrations in beef of those fatty acids considered to be of benefit to human health, without causing a detrimental effect on the appearance, shelf‐life or eating quality of the beef. There is accumulating evidence of the importance of long‐chain n‐3 (omega‐3) polyunsaturated fatty acids (PUFAs) for human health and disease prevention, and also evidence from experimental studies that has shown anticarcinogenic, antiatherogenic, and anti‐obesity effects of two isomers of conjugated linoleic acid (CLA). Based on this evidence, the major focus of research efforts to improve the nutritional value of beef has been on increasing the concentration of the n‐3 PUFAs and CLA. Considerable progress has been made within pillar 3 of ProSafeBeef to meet this aim, primarily by manipulating the diet of cattle. Fundamental information on ruminal lipid metabolism and on the control and/or prevention of ruminal hydrogenation of dietary lipids arising from research within ProSafeBeef will facilitate the production of beef with a ‘healthier’ fatty acid profile. Moreover, strategies will be defined for industry on how to optimise nutritional and sensory properties and oxidative quality of beef products, by combining the nutritional enhancement made in the live animal together with target levels of functional ingredients to be added during processing.     

Role for fatty acid binding protein in the regulation of hepatic lipogenesis by dietary linoleic acid

The effect of added dietary ethyl palmitate or ethyl linoleate on hepatic lipogenic enzymes and the amount of hepatic fatty acid binding protein was examined in meal-fed rats. Dietary linoleate reduced the activities of fatty acid synthetase, glucose-6-phosphate dehydrogenase, NADP-malic enzyme, ATP-citrate lyase, and the amount of fatty acid binding protein compared to rats fed a fat-free or palmitate supplemented diet. The possible role of fatty acid biding protein in the regulation of lipogenesis by dietary fat is discussed.     

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。     

不同年龄阶段小鼠脑聚集二十二碳六烯酸及脂肪酸去饱和酶的变化

【目的】 探讨生命早期不同年龄阶段脑摄取、聚集二十二碳六烯酸(DHA)(C22:6n-3)及相关去饱和酶的变化。 【方法】 使用6~8周龄清洁级C57BL/6J雌性小鼠,分别给予n-3 多不饱和脂肪酸(n-3 PUFAs)缺乏饲料和含n-3 PUFAs饲料喂养6周,然后雌雄合笼交配繁殖,新生仔鼠分别于生后7、21 d和42 d时取血、脑和肝脏。采用甲酯化-气相色谱分析对血浆、脑和肝脏中脂肪酸谱进行分析;采用荧光定量PCR方法对脑和肝脏中脂肪酸去饱和酶1(FADS1)和脂肪酸去饱和酶2(FADS2)基因mRNA表达进行检测。 【结果】 对不同年龄小鼠组织脂肪酸的比较发现,脑中DHA和总n-3 PUFAs含量在两种不同饲料组均随年龄增加而升高;而肝中的含量则随年龄增加而降低。与n-3 PUFAs缺乏组相比,饲料中添加n-3 PUFAs可使仔鼠生后7、21 d和42 d时脑和肝脏中DHA和总n-3 PUFAs含量均显著升高;升高的程度在脑组织中随年龄增加而降低,而在肝脏组织中则不随年龄变化。对不同年龄段FADS表达的比较发现,FADS1和FADS2 mRNA在脑组织中的表达量于42 d时显著高于7 d和21 d,而在肝组织中的表达量于各年龄段之间无显著性差异。与n-3 PUFAs缺乏组相比,饲料中添加n-3 PUFAs可使仔鼠生后7 d和21 d时脑组织FADS1和FADS2表达水平显著降低,而42 d时的表达无变化;肝组织中这两种酶mRNA水平在7 d和21 d时无变化,42 d时FADS1显著降低。 【结论】 发育期脑对DHA的聚集需求随着年龄增大而逐渐减少;FADS在脑中的表达水平随年龄增大而升高。同时,饲料n-3 PUFAs缺乏状态对脑聚集DHA以及FADS的影响在年龄小时更明显。     

Update on alpha-linolenic acid

Consumption of omega 3 fatty acids is known to have health benefits. For many years, the importance of the only member of the omega 3 family considered to be essential, alpha-linolenic acid (ALA), has been overlooked. Current research indicates that ALA, along with its longer chain metabolites, may play an important role in many physiological functions. Potential benefits of ALA include cardioprotective effects, modulation of the inflammatory response, and a positive impact on both central nervous system function and behavior. Recommended levels for ALA intake have been set, yet the possible advantages of its consumption are just being revealed.     

Effect of Dietary Fatty Acid Composition on Th1/Th2 Polarization in Lymphocytes

Background: It has become increasingly clear that polyunsaturated fatty acids (PUFAs) have immunomodulatory effects. However, the intake of these fatty acids used in animal studies often greatly exceeds dietary human intake. Whether differences in the composition of fatty acids that are consumed in amounts consistent with normal dietary intake can influence immune function remains uncertain. Methods: We manufactured 3 types of liquid diet, related to modified fatty acid composition (ω‐6/ω‐3 = 0.25, 2.27 and 42.9), but excluding eicosapentaenoic acid and docosahexaenoic acid, based upon a liquid diet used clinically in humans. We assessed CD3‐stimulated cytokine production of splenocytes in female BALB/c mice (n = 4 per group) fed 1 of 3 liquid diets for 4 weeks. We also measured the cytokine production of peripheral blood mononuclear cells stimulated with phorbol myristate acetate and ionomycin in humans at the end of a 4‐week period of consumption of 2 different liquid diets (ω‐6/ω‐3 = 3 and 44). Results: We found that the ratio of interfero ω‐γ (IFN‐γ) / interleukin‐4 (IL‐4) was significantly higher in mice fed theω ‐3 rich diet than in others. In humans, IFN‐γ / IL‐4 was significantly higher after the ω‐3 versus the ω‐6 enhanced diet. Conclusions: Differences in the composition of ω‐3 andω ‐6 PUFAs induces a shift in the Th1/Th2 balance in both mouse and human lymphocytes, even when ingested in normal dietary amounts. An ω‐3 rich diet containing α‐linolenic acid modulates immune function.     

孕期不同膳食模式对膳食脂肪酸含量及母初乳脂肪酸组成的影响

【目的】研究中国两种不同膳食模式地区膳食脂肪酸(fatty acid,FA)含量的差异,并探讨这种差异对母初乳脂肪酸组成的影响。【方法】对传统内陆膳食(常州)和海洋膳食(温州)地区孕晚期孕妇进行7d膳食调查,根据《2002中国食物成份数据》中的食物脂肪酸含量数据计算出膳食脂肪酸含量;并通过随访这些孕妇收集5d母初乳样本,采用高效毛细气相色谱分析技术检测5d母初乳的脂肪酸组成。【结果】常州与温州两地孕母摄入的膳食种类存在差异,温州地区孕母摄入的海洋食品远大于常州地区。常州地区孕母膳食脂肪酸中亚油酸(linoleic acid,LA)和α-亚麻酸(α-linolenic acid,ALA)含量均高于温州地区;而二十二碳六烯酸(docosahexaenoic acid,DHA)和二十碳五烯酸(eicosap-entaenoic acid,EPA)含量均低于温州地区;花生四稀酸(arachidonic acid,AA)含量则未见显著差异。两地膳食脂肪酸组成中LA、ALA、AA以及DHA的差异同样反应在5d母初乳中,但两地5d母初乳中的EPA含量差异无显著性。【结论】膳食模式不同的两个地区,其孕母的膳食脂肪酸含量存在差异,且这种差异可在母初乳脂肪酸组成中得到体现。     

Comparative evaluation of essential fatty acid composition of mothers' milk of some urban and suburban regions of West Bengal,India

This study investigated the fatty acid composition of lipid present in breast milk of mothers residing in urban and suburban regions of West Bengal with special emphasis on n-6 and n-3 polyunsaturated fatty acids, which played a crucial role in the growth and development of neonates. Milk samples collected from 135 mothers of middle income group (average monthly income around ‘Rs 10,000/-’) were analysed by gas liquid chromatography after extraction and transmethylation to determine fatty acid composition. Information about the dietary intake of individual mothers was obtained through food frequency questionnaire. The fractions of n-6 and n-3 polyunsaturated fatty acids available in milk of urban mothers were 13.59 ± 0.94 and 3.65 ± 0.49, respectively, and in suburban mothers 12.74 ± 0.89 and 4.36 ± 0.39, respectively. The green leafy vegetables, fishes and vegetable oils were the major sources of essential fatty acids in the diet of the experimental groups of Bengali mothers. This study revealed a relationship between the alimentary habits of mothers and the concentration of essential fatty acids in breast milk of Bengali mothers.     

Linseed oil and marine oil as sources of (n-3) fatty acids in rat heart

Rats were fed a fat mixture containing a low level of (n-3) polyunsaturated fatty acids, linseed oil or marine oil. The arachidonic acid in cardiac tissue was depressed by (n-3) linolenic acid and further depressed by (n-3) polyunsaturated fatty acids of marine oil. Docosahexaenoic acid was the principal replacement for arachidonic acid.     

Nutrition and the patient requiring mechanical ventilatory support.

Respiratory function in mechanically ventilated patients (VP) is adversely affected by starvation and hypermetabolic stress. These patients are more successfully managed and extubated if proper nutritional support is provided. The features of metabolism and respiratory function in VP require moderation in glucose, fat, and protein administration. In delivering energy to VP, attention must be given to nearby tracheostomy sites complicating the parenteral route and airway-cuff problems that may inhibit effective enteral feeding.     

Dietary conjugated linoleic acid and long-chain n-3 fatty acids in mammary and prostate cancer protection: a review

The role of dietary fatty acids on cancer is still controversial. To examine the current literature on the protective role of conjugated linoleic acid (CLA) and marine long-chain fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] and the risk of breast and prostate cancer, data from 41 case-control and cohort studies and relevant in vitro and animal experiments were included in this 2000–2010 revision. Epidemiological studies on CLA intake or its tissue concentration related to breast and prostate tumorigenesis are not conclusive; EPA and DHA intake have shown important inverse associations just in some studies. Additional research on the analysed association is required.     

Dietary carnosic acid suppresses hepatic steatosis formation via regulation of hepatic fatty acid metabolism in high-fat diet-fed mice

In this study, we examined the hepatic anti-steatosis activity of carnosic acid (CA), a phenolic compound of rosemary (Rosmarinus officinalis) leaves, as well as its possible mechanism of action, in a high-fat diet (HFD)-fed mice model. Mice were fed a HFD, or a HFD supplemented with 0.01% (w/w) CA or 0.02% (w/w) CA, for a period of 12 weeks, after which changes in body weight, blood lipid profiles, and fatty acid mechanism markers were evaluated. The 0.02% (w/w) CA diet resulted in a marked decline in steatosis grade, as well as in homeostasis model assessment of insulin resistance (HOMA-IR) index values, intraperitoneal glucose tolerance test (IGTT) results, body weight gain, liver weight, and blood lipid levels (P < 0.05). The expression level of hepatic lipogenic genes, such as sterol regulating element binding protein-1c (SREBP-1c), liver-fatty acid binding protein (L-FABP), stearoyl-CoA desaturase 1 (SCD1), and fatty acid synthase (FAS), was significantly lower in mice fed 0.01% (w/w) CA and 0.02% (w/w) CA diets than that in the HFD group; on the other hand, the expression level of β-oxidation-related genes, such as peroxisome proliferator-activated receptor α (PPAR-α), carnitine palmitoyltransferase 1 (CPT-1), and acyl-CoA oxidase (ACO), was higher in mice fed a 0.02% (w/w) CA diet, than that in the HFD group (P < 0.05). In addition, the hepatic content of palmitic acid (C16:0), palmitoleic acid (C16:1), and oleic acid (C18:1) was significantly lower in mice fed the 0.02% (w/w) CA diet than that in the HFD group (P < 0.05). These results suggest that orally administered CA suppressed HFD-induced hepatic steatosis and fatty liver-related metabolic disorders through decrease of de novo lipogenesis and fatty acid elongation and increase of fatty acid β-oxidation in mice.     

Nutrition modulation of gastrointestinal toxicity related to cancer chemotherapy: from preclinical findings to clinical strategy

Chemotherapy‐induced gut toxicity is a major dose‐limiting toxicity for many anticancer drugs. Gastrointestinal (GI) complications compromise the efficacy of chemotherapy, promote overall malnutrition, aggravate cancer cachexia, and may contribute to worsened prognosis. The GI tract is an attractive target for nutrition modulation, owing to its direct exposure to the diet, participation in uptake and metabolism of nutrients, high rate of cell turnover, and plasticity to nutrition stimuli. Glutamine, ω‐3 polyunsaturated fatty acids, and probiotics/prebiotics are therapeutic factors that potentially modulate GI toxicity related to cancer treatments. Preclinical and clinical evidence are reviewed to critically define plausible benefits of these factors and their potential development into adjuncts to cancer chemotherapy. Mechanisms underlying the action of these nutrients are being unraveled in the laboratory. Optimal strategies to translate these findings into clinical care still remain to be elucidated. Key questions that remain to be answered include the following: which nutrient or combination of nutrients is selected for which patient and chemotherapy regimen? What mechanisms are responsible for modulation, and how are nutrient(s) administered in a clinically optimal manner? Research exploring interactions between different nutrients in GI protection is ongoing and demands further understanding. How nutrition preparations given to chemotherapy‐treated patients are formulated in terms of component selection and dose optimization should be carefully studied and justified.     

Dietary polyunsaturated fatty acid intake during late pregnancy affects fatty acid composition of mature breast milk

ObjectiveThe aim of this study was to investigate how maternal polyunsaturated fatty acid intake at different periods during pregnancy affects the composition of polyunsaturated fatty acids in mature human milk.MethodsA prospective study was conducted involving 45 pregnant women, aged between 18 and 35 y, who had full-term pregnancies and practiced exclusive or predominant breast-feeding. Mature breast milk samples were collected after the 5th postpartum week by manual expression; fatty acid composition was determined by gas chromatography. Fatty acid intake during pregnancy and puerperium was estimated through multiple 24-h dietary recalls. Linear regression models, adjusted by postpartum body mass index and deattenuated, were used to determine associations between estimated fatty acids in maternal diet during each trimester of pregnancy and fatty acid content in mature human milk.ResultsA positive association was identified between maternal intake of eicosapentaenoic acid (β, 1.873; 95% confidence interval [CI], 0.545, 3.203) and docosahexaenoic acid (β, 0.464; 95% CI, 0.212–0.714) during the third trimester of pregnancy, as well as the maternal dietary ω-3 to ω-6 ratio (β, 0.093; 95% CI, 0.016–0.170) during the second and third trimesters and postpartum period, with these fatty acids content in mature breast milk.ConclusionsThe maternal dietary docosahexaenoic acid and eicosapentaenoic acid content during late pregnancy may affect the fatty acid composition of mature breast milk. Additionally, the maternal dietary intake of ω-3 to ω-6 fatty acid ratio, during late pregnancy and the postpartum period, can affect the polyunsaturated fatty acid composition of breast milk.