Dietary n-3 PUFA may have potential benefits in preventing peptic ulcer disease (PUD). However, data from observational epidemiological studies are limited. Thus, we conducted a Mendelian randomisation analysis to reveal the causal impact of n-3 PUFA on PUD. Genetic variants strongly associated with plasma levels of total or individual n-3 PUFA including plant-derived α-linolenic acid and marine-derived EPA, DPA and DHA were enrolled as instrumental variables. Effect size estimates of the n-3 PUFA-associated genetic variants with PUD were evaluated using data from the UK biobank. Per one sd increase in the level of total n-3 PUFA in plasma was significantly associated with a lower risk of PUD (OR = 0·91; 95 % CI 0·85, 0·99; P = 0·020). The OR were 0·81 (95 % CI 0·67, 0·97) for EPA, 0·72 (95 % CI 0·58, 0·91) for DPA and 0·87 (95 % CI 0·80, 0·94) for DHA. Genetically predicted α-linolenic acid levels in plasma had no significant association with the risk of PUD (OR = 5·41; 95 % CI 0·70, 41·7). Genetically predicted plasma levels of n-3 PUFA were inversely associated with the risk of PUD, especially marine-based n-3 PUFA. Such findings may have offered an effective and feasible strategy for the primary prevention of PUD.

Cardiovascular diseases (CVDs) are a major health concern for women. Historically there has been a misconception that men are at greater risk because CVD tends to occur earlier in life compared to women. Clinical guidelines for prevention of heart disease are currently the same for both sexes, but accumulating evidence demonstrates that risk profiles diverge. In fact, several CVD risk factors confer an even greater risk in women relative to men, including high blood pressure, obesity, diabetes and raised triglycerides. Furthermore, many female-specific CVD risk factors exist, including early menarche, pregnancy complications, polycystic ovary syndrome, reproductive hormonal treatments and menopause. Little is known about how diet interacts with CVD risk factors at various stages of a woman’s life. Long chain (LC) n-3 polyunsaturated fatty acid (PUFA) intakes are a key dietary factor that may impact risk of CVD throughout the life course differentially in men and women. Oestrogen enhances conversion of the plant n-3 PUFA, alpha-linolenic acid, to LCn-3 PUFA. Increasing the frequency of oily fish consumption or LCn-3 PUFA supplementation may be important for reducing coronary risk during the menopausal transition, during which time oestrogen levels decline and the increase in CVD risk factors is accelerated. Women are under-represented in the evidence base for CVD prevention following LC n-3 PUFA supplementation. Therefore it is not clear whether there are sex differences in response to treatment. Furthermore, there is a lack of evidence on optimal intakes of LC n-3 PUFA across the lifespan for CVD prevention in women.

This study aimed to investigate the association between n-3 PUFA and lung function. First, a cross-sectional study was conducted based on the National Health and Nutrition Examination Survey (NHANES) 2007–2012 data. n-3 PUFA intake was obtained from 24-h dietary recalls. A multivariable linear regression model was used to assess the observational associations of n-3 PUFA intake with lung function. Subsequently, a two-sample Mendelian randomisation (MR) was performed to estimate the potential causal effect of n-3 PUFA on lung function. Genetic instrumental variables were extracted from published genome-wide association studies. Summary statistics about n-3 PUFA was from UK Biobank. Inverse variance weighted was the primary analysis approach. The observational study did not demonstrate a significant association between n-3 PUFA intake and most lung function measures; however, a notable exception was observed with significant findings in the highest quartile for forced vital capacity (FVC) and % predicted FVC. The MR results also showed no causal effect of circulating n-3 PUFA concentration on lung function (forced expiratory volume in one second (FEV1), β = 0·01301, se = 0·01932, P = 0·5006; FVC, β = −0·001894, se = 0·01704, P = 0·9115; FEV1:FVC, β = 0·03118, se = 0·01743, P = 0·07359). These findings indicate the need for further investigation into the impact of higher n-3 PUFA consumption on lung health.

Observational evidence linking dietary n-3 PUFA intake and health outcomes is limited by a lack of robust validation of dietary intake using blood n-3 PUFA levels and potential confounding by fish oil supplement (FOS) use. We investigated the relationship between oily fish intake, FOS use and plasma n-3 PUFA levels in 121 650 UK Biobank (UKBB) participants. Ordinal logistic regression models, adjusted for clinical and lifestyle factors, were used to quantify the contribution of dietary oily fish intake and FOS use to plasma n-3 PUFA levels (measured by NMR spectroscopy). Oily fish intake and FOS use were reported by 38 % and 31 % of participants, respectively. Increasing oily fish intake was associated with a higher likelihood of FOS use (P < 0·001). Oily fish intake ≥ twice a week was the strongest predictor of high total n-3 PUFA (OR 6·7 (95 % CI 6·3, 7·1)) and DHA levels (6·6 (6·3, 7·1). FOS use was an independent predictor of high plasma n-3 PUFA levels (2·0 (2·0, 2·1)) with a similar OR to that associated with eating oily fish < once a week (1·9 (1·8, 2·0)). FOS use was associated with plasma n-3 PUFA levels that were similar to individuals in the next highest oily fish intake category. In conclusion, FOS use is more common in frequent fish consumers and modifies the relationship between oily fish intake and plasma n-3 PUFA levels in UKBB participants. If unaccounted for, FOS use may confound the relationship between dietary n-3 PUFA intake, blood levels of n-3 PUFAs and health outcomes.

Maternal diet influences breast milk nutritional profile; however, it is unclear which nutrients and contaminants are particularly responsive to short- and long-term changes in maternal intake, and the impact of specific exclusion diets, such as vegan or vegetarian. This study systematically reviewed the literature on the effects of maternal nutrient intake, including exclusion diets, on both the nutrient and contaminant content of breast milk. The electronic databases, PubMed, CENTRAL, Web of Science and CINALH were systematically searched until 4 June 2023, with additionally searches of reference lists (PROSPERO, CRD42020221577). The quality of the studies was examined using Cochrane Risk of Bias tool and Newcastle–Ottawa scale. Eighty-eight studies (n 6577) met the search criteria. Due to high heterogeneity, meta-analysis was not possible. There was strong evidence of response to maternal intakes for DHA and EPA, vitamins A, E and K, iodine and Se in breast milk composition, some evidence of response for α-linolenic acid, B vitamins, vitamin C and D, ovalbumin, tyrosine and contaminants, and insufficient evidence to identify the effects arachidonic acid, Cu, Fe, Zn and choline. The paucity of evidence and high heterogeneity among studies reflects the need for more high-quality trials. However, this review identified the importance of maternal intake in the nutritional content of breast milk for a wide range of nutrients and supports the recommendation for supplementation of DHA and vitamin B12 for those on restrictive diets.

The relationship between erythrocyte membrane n-3 PUFA and breast cancer risk is controversial. We aimed to examine the associations of erythrocyte membrane n-3 PUFA with odds of breast cancer among Chinese women by using a relatively large sample size. A case–control study was conducted including 853 newly diagnosed, histologically confirmed breast cancer cases and 892 frequency-matched controls (5-year interval). Erythrocyte membrane n-3 PUFA were measured by GC. Logistic regression and restricted cubic spline were used to quantify the association between erythrocyte membrane n-3 PUFA and odds of breast cancer. Erythrocyte membrane α-linolenic acid (ALA), docosapentaenoic acid (DPA) and total n-3 PUFA were inversely and non-linearly associated with odds of breast cancer. The OR values (95 % CI), comparing the highest with the lowest quartile (Q), were 0·57 (0·43, 0·76), 0·43 (0·32, 0·58) and 0·36 (0·27, 0·49) for ALA, DPA and total n-3 PUFA, respectively. Erythrocyte membrane EPA and DHA were linearly and inversely associated with odds of breast cancer ((EPA: ORQ4 v. Q1 (95 % CI) = 0·59 (0·45, 0·79); DHA: ORQ4 v. Q1 (95 % CI) = 0·50 (0·37, 0·67)). The inverse associations were observed between ALA and odds of breast cancer in postmenopausal women, and between DHA and oestrogen receptor+ breast cancer. This study showed that erythrocyte membrane total and individual n-3 PUFA were inversely associated with odds of breast cancer. Other factors, such as menopause and hormone receptor status, may warrant further investigation when examining the association between n-3 PUFA and odds of breast cancer.

Circulating n-3 PUFA, which integrate endogenous and exogenous n-3 PUFA, can be better used to investigate the relationship between n-3 PUFA and disease. However, studies examining the associations between circulating n-3 PUFA and colorectal cancer (CRC) risk were limited, and the results remained inconclusive. This case–control study aimed to examine the association between serum n-3 PUFA and CRC risk in Chinese population. A total of 680 CRC cases and 680 sex- and age-matched (5-year interval) controls were included. Fatty acids were assayed by GC. OR and 95 % CI were calculated using multivariable logistic regression after adjustment for potential confounders. Higher level of serum α-linolenic acid (ALA), docosapentaenoic acid (DPA), DHA, long-chain n-3 PUFA and total n-3 PUFA were associated with lower odds of CRC. The adjusted OR and 95 % CI were 0·34 (0·24, 0·49, Pfor trend < 0·001) for ALA, 0·57 (0·40, 0·80, Pfor trend < 0·001) for DPA, 0·48 (0·34, 0·68, Pfor trend < 0·001) for DHA, 0·39 (0·27, 0·56, Pfor trend < 0·001) for long-chain n-3 PUFA and 0·31 (0·22, 0·45, Pfor trend < 0·001) for total n-3 PUFA comparing the highest with the lowest quartile. However, there was no statistically significant association between EPA and odds of CRC. Analysis stratified by sex showed that ALA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of CRC in both sexes. This study indicated that serum ALA, DPA, DHA, long-chain n-3 PUFA and total n-3 PUFA were inversely associated with odds of having CRC in Chinese population.

There is now evidence to suggest that there may be an interaction between B vitamins and n-3 PUFA, with suggestions that increasing intake of both nutrients simultaneously may benefit cognition in older adults. The aim of this systematic review was to investigate whether supplementation with a combination of n-3 PUFA and B vitamins can prevent cognitive decline in older adults. Randomised controlled trials conducted in older adults that measured cognitive function were retrieved. The included trials provided a combination of n-3 PUFA and B vitamins alone, or in combination with other nutrients. Trials that provided n-3 PUFA alone and also measured B vitamin status or provided B vitamin supplementation alone and measured n-3 PUFA status were also included. The databases searched were The Cochrane Library, EMBASE, CINAHL, Scopus and MEDLINE. A total of 14 papers were included in the analysis (n 4913; age: 60–70 years; follow-up 24 weeks to 4 years). The meta-analysis results found a significant benefit of nutrient formulas, which included both n-3 PUFA and B vitamins alongside other nutrients, v. placebo on global cognition assessed using composite scores from a neuropsychological test battery (G = 0·23, P = 0·002), global cognition using single measures of cognition (G = 0·28, P = 0·004) and episodic memory (G = 0·32, P = 0·001). The results indicate that providing a combination of n-3 PUFA and B vitamins as part of a multi-nutrient formula benefits cognition in older adults v. a placebo, and the potential for an interaction between these key nutrients should be considered in future experimental work.

Accumulating evidence suggests that supplementation of n-3 PUFA was associated with reduction in risk of major cardiovascular events. This meta-analysis was to systematically evaluate whether daily supplementation and accumulated intake of n-3 PUFA are associated with improved left ventricular (LV) remodelling in patients with chronic heart failure (CHF). Articles were obtained from Pubmed, Clinical key and Web of Science from inception to January 1 in 2021, and a total of twelve trials involving 2162 participants were eligible for inclusion. The sources of study heterogeneity were explained by I2 statistic and subgroup analysis. Compared with placebo groups, n-3 PUFA supplementation improved LV ejection fraction (LVEF) (eleven trials, 2112 participants, weighted mean difference (WMD) = 2·52, 95 % CI 1·25, 3·80, I2 = 87·8 %) and decreased LV end systolic volume (five studies, 905 participants, WMD = –3·22, 95 % CI 3·67, −2·77, I2 = 0·0 %) using the continuous variables analysis. Notably, the high accumulated n-3 PUFA dosage groups (≥ 600 g) presented a prominent improvement in LVEF, while the low and middle accumulated dosage (≤ 300 and 300–600 g) showed no effects on LVEF. In addition, n-3 PUFA supplementation decreased the levels of pro-inflammatory mediators including TNF-α, IL-6 (IL-6) and hypersensitive c-reactive protein. Therefore, the present meta-analysis demonstrated that n-3 PUFA consumption was associated with a substantial improvement of LV function and remodelling in patients subjected to CHF. The accumulated dosage of n-3 PUFA intake is vital for its cardiac protective role.

The brain is rich in long-chain PUFA, which play an essential role in its development and functions. Here, we examined the impact of maternal n-3 PUFA intake deficiency during gestation and lactation on the development of glial cells in the pup’s developing cerebral cortex. In addition, using myelination as indicator and the anti-myelin basic protein as measurement to establish the relationship between the number of glial fibrillary acidic protein (GFAP)-positive cells and the development of oligodendrocytes, we determined the myelination state of the somatosensory cortex at postnatal day 14. Rat dams were fed either a control (Cont) or an n-3 PUFA-deficient (Def) diet for 60 d (acclimatisation: 14 d; gestation: 21 d; and lactation: 21 d). Pups lactated from dams throughout the experiment. The distribution pattern of astrocytes in pups on postnatal day 7 was immunohistochemically analysed using GFAP and brain lipid binding protein (BLBP) as markers for mature astrocytes and astrocyte-specific radial glial cells, respectively. It was observed that, when compared with Cont pups, GFAP-positive cells decreased, BLBP-positive cells increased and myelinated structures were sparser in the somatosensory cortices of Def pups. In the open field test on postnatal day 21, behavioural parameters did not differ between groups. Our results indicated that inhibited maturation of astrocytes caused by maternal n-3 PUFA deficiency hindered the development of brain glial cells of neonatal rats; hence, maternal n-3 PUFA intake during the gestation and lactation periods may have been crucial for the brain cell composition of pups.

Obesity is a major public health problem that predisposes to several diseases and higher mortality in patients with COVID-19. Obesity also generates neuroinflammation, which predisposes to the development of neuropsychiatric diseases. Since there is a lack of effective treatments for obesity, the search for new strategies to reverse its consequences is urgent. In this perspective, the anti-inflammatory properties of omega-3 polyunsaturated fatty acids such as DHA/EPA might reduce the harmful effects of obesity. Here, we used the cafeteria diet (CAF) model to induce obesity in Wistar rats. Animals received ultra-processed food for 20 weeks, and DHA/EPA supplementation (500 mg/kg per d) was performed between the 16th and the 20th week. At the end of the experiment, it was evaluated: body weight, visceral fat deposition, plasma glucose, insulin and triglycerides, and it was also measured the levels of inflammatory cytokines TNF-α and IL-6 in plasma and liver, and TNF-α in the prefrontal cortex. The elevated plus maze test was performed to analyse anxiety-like behaviour. Our results demonstrated that DHA/EPA could not reverse weight and fat gain and did not modify plasma dosages. However, there was a decrease in IL-6 in the liver (DHA/EPA effect: P = 0.023) and TNF-α in the brain (CAF compared with CAF + DHA/EPA, P < 0.05). Also, there was a decrease in the anxiety index in CAF + DHA/EPA compared with the CAF group (P < 0.01). Thus, DHA/EPA supplementation is helpful to reverse the consequences of obesity in the brain.

The results of epidemiological studies involving n-3 PUFA and polycystic ovary syndrome (PCOS) are scarce. This matched case–control study assessed the associations between n-3 PUFA and PCOS prevalence in 325 pairs of PCOS cases and healthy controls. Dietary information was assessed using a 102-item FFQ. Fatty acids in serum phospholipids were measured with a GC method. We found that n-3 PUFA in serum phospholipids were inversely associated with PCOS prevalence, including total, long-chain and individual PUFA (e.g. docosapentaenoic acid (DPA), EPA and DHA). Compared with the lowest tertile (T1), the adjusted OR and their 95% CI for the highest tertile (T3) were 0·63 (0·40, 0·93) for total n-3 PUFA, 0·60 (0·38, 0·92) for long-chain n-3 PUFA, 0·68 (0·45, 1·01) for DHA, 0·70 (0·45, 1·05) for EPA and 0·72 (0·45, 1·08) for DPA. For dietary intake of n-3 PUFA, significant inverse associations were found only for long-chain n-3 PUFA (Ptrend = 0·001), EPA (Ptrend = 0·047) and DHA (Ptrend = 0·030). Both dietary and serum n-3 PUFA, mainly EPA and DPA, were negatively correlated with PCOS-related parameters, such as BMI, fasting insulin, total testosterone and high-sensitivity C-reactive protein, but positively correlated with follicle-stimulating hormone and sex hormone-binding globulin. These results indicated inverse associations between n-3 PUFA, especially long-chain n-3 PUFA, and PCOS prevalence. Higher intakes of n-3 PUFA might be considered a protective factor for PCOS among Chinese females.

Dietary n-3 polyunsaturated fatty acids (PUFAs) present beneficial effects on counteracting inflammation status, displaying a critical anti-inflammatory role and maintaining physiological homeostasis in obesity. The primary objective of this systematic review was to evaluate the effect of n-3 PUFAs intake on the eicosanoid profile of people with obesity and overweight. The search strategy on Embase, Scopus, PubMed, Web of Science, Cochrane Library, Google Scholar and ProQuest was undertaken until November 2019 and updated January 2021. The effect size of n-3 PUFAs on prostaglandins was estimated by Glass's, type 1 in a random-effect model for the meta-analysis. Seven clinical trials met the eligible criteria and a total of 610 subjects were included in this systematic review, and four of seven studies were included in meta-analysis. The intake of n-3 PUFAs promoted an overall reduction in serum pro-inflammatory eicosanoids. Additionally, n-3 PUFAs intake significantly decreased the arachidonic acid COX-derived PG eicosanoid group levels (Glass's Δ −0⋅35; CI −0⋅62, −0⋅07, I2 31⋅48). Subgroup analyses showed a higher effect on periods up to 8 weeks (Glass's Δ −0⋅51; CI −0⋅76, −0⋅27) and doses higher than 0⋅5 g of n-3 PUFAs (Glass's Δ −0⋅46; CI −0⋅72, −0⋅27). Dietary n-3 PUFAs intake contributes to reduce pro-inflammatory eicosanoids of people with obesity and overweight. Subgroup's analysis showed that n-3 PUFAs can reduce the overall arachidonic acid COX-derived PG when adequate dose and period are matched.

The preventability estimate for colorectal cancer (CRC) is approximately 50%, highlighting the huge potential for altering modifiable lifestyle factors (including diet and body fatness) in order to reduce risk of this common malignancy. There is strong evidence that dietary factors (including intake of wholegrains, fibre, red and processed meat and alcohol) affect CRC risk. The lack of positive intervention trials and limited mechanistic understanding likely explain limited public health impact of epidemiological observations, to date. An alternative strategy for nutritional prevention of CRC is use of supplements that provide higher individual nutrient exposure than obtained through the diet (chemoprevention). There are positive data for calcium and/or vitamin D and the n-3 fatty acid EPA from polyp prevention trials using colorectal adenoma as a CRC risk biomarker. Although CRC is an obesity-related malignancy, there remains a paucity of observational data supporting intentional weight loss for CRC risk reduction. Some types of obesity surgeries (Roux-en-Y gastric bypass) might actually increase subsequent CRC risk due to alteration of local intestinal factors. There is intense interest in nutritional therapy of patients after diagnosis of CRC, in order to impact on recurrence and overall survival (now often termed cancer interception). In conclusion, nutritional prevention of CRC continues to hold much promise. Increased mechanistic understanding of the role of individual nutrients (linked to intestinal microbiota), as well as a precision medicine approach to CRC chemoprevention and interception based on both tumour and host factors, should enable translation of nutritional interventions into effective CRC risk reduction measures.

The aim of this work was to study the bioavailability of fatty acids (FA), focusing on n-3 long-chain (LC) PUFA, carried by different molecular lipid species, that is, phospholipids (PL) or TAG, with three formulations based on fish oils or marine PL, providing a similar n-3 LC PUFA amount. The digestive lipolysis was first assessed using an in vitro enzymatic model. Then, intestinal absorption and enterocyte metabolism were investigated in vivo, on male Wistar rats through lymph lipid analysis. The in vitro results showed that the release of n-3 LC PUFA from lipolysis was increased by 48 % when FA were provided as PL rather than TAG. The in vivo results demonstrated that EPA and DHA from both TAG and PL were similarly absorbed and incorporated into lymph lipids. However, DHA was mainly distributed at the sn-1/3 positions of lymph TAG when provided as marine PL, whereas it was equally distributed at the three positions with marine TAG. On the whole, even if the molecular lipid species of n-3 LC PUFA did not greatly modify the in vivo digestion and absorption steps, it modulated the rearrangement of DHA on the glyceride positions of the lymph TAG, which may further impact the DHA metabolic fate and tissue accretion. Consequently, the present study has provided data which may be used to formulate lipid diets rich in DHA in the context of an insufficient consumption of n-3 PUFA in Western countries.

Health effects of fatty acids have been very controversial. Total mortality is inversely associated with the amount of total fat consumed. In contrast, trans fatty acids or SFA intake is positively related to mortality while the inverse is observed with consumption of MUFA or PUFA. Among PUFA, long-chain (LC) n-3 PUFA have many beneficial effects. Dietary intake of some types of fatty acids is specific to Africa. Energy from saturated fat does not exceed 14% and energy from n-6 PUFA does not exceed 8% of total energy intake. Dietary intake of LC n-3 PUFA is less than 100 mg/d whereas international recommendations promote 250–500 mg/d. Consumption of plant n-3 PUFA mainly α-linolenic acid (ALA) is highly variable depending on the country. Both fish and ALA availability are low in several African countries. The prevalence of diabetes and cardiovascular events remain very low in Africa, partly explained by the fact that the whole dietary pattern is globally the best of all continents. One objective of ‘fat for Africa’ could be to increase, as much as possible, the dietary intake of LC n-3 PUFA by promoting sustainable aquaculture and to maintain as much as possible traditional dietary pattern by preventing a tendency to westernisation, provided that the amount of energy and protein is sufficient to fight against wasting and stunting where it still exists.

Marine n-3 PUFA may improve autonomic dysfunction by an increase in heart rate variability (HRV) and may reduce the risk of malignant ventricular arrhythmias. Only a few smaller studies have examined such effects in patients on chronic dialysis, who often have autonomic dysfunction and a high risk of sudden cardiac death, which accounts for almost 30 % of all deaths. This cross-sectional study investigated the association between the plasma phospholipid content of n-3 PUFA and 24-h HRV or ventricular arrhythmias in patients on chronic dialysis. A 48-h Holter monitoring was performed on 169 patients on in-centre dialysis (83 %), home haemodialysis (10 %) or peritoneal dialysis (7 %) obtaining data on arrhythmias (n 152) and 24-h HRV (n 135). The mean overall HRV (standard deviation of normal intervals (SDNN)) was low and 71 % had a reduced overall HRV (SDNN<100 ms) indicating autonomic dysfunction. No significant associations between plasma phospholipid content of total marine n-3 PUFA, EPA (22 : 5n-3) or DHA (22 : 6n-3) and time-domain or frequency-domain HRV were detected in crude or adjusted linear regression analysis. However, a higher plasma phospholipid content of DHA was associated with a significantly lower proportion of patients with ventricular tachycardia (higher DHA-tertile: 9 % v. lower DHA-tertile: 28 %, P=0·02). In conclusion, the content of marine n-3 PUFA in plasma phospholipids was not associated with 24-h HRV, but a higher plasma phospholipid content of DHA was associated with a lower occurrence of ventricular tachycardia suggesting an antiarrhythmic effect of marine n-3 PUFA in patients on chronic dialysis.

The current paradigms of prevention and treatment are unable to curb obesity rates, which indicates the need to explore alternative therapeutic approaches. Obesity leads to several damages to the body and is an important risk factor for a number of other chronic diseases. Furthermore, despite the first alterations in obesity being observed and reported in peripheral tissues, studies indicate that obesity can also cause brain damage. Obesity leads to a chronic low-grade inflammatory state, and the therapeutic manipulation of inflammation can be explored. In this context, the use of n-3 PUFA (especially in the form of fish oil, rich in EPA and DHA) may be an interesting strategy, as this substance is known by its anti-inflammatory effect and numerous benefits to the body, such as reduction of TAG, cardiac arrhythmias, blood pressure and platelet aggregation, and has shown potential to help treat obesity. Thereby, the aim of this narrative review was to summarise the literature related to n-3 PUFA use in obesity treatment. First, the review provides a brief description of the obesity pathophysiology, including alterations that occur in peripheral tissues and at the central nervous system. In the sequence, we describe what are n-3 PUFA, their sources and their general effects. Finally, we explore the main topic linking obesity and n-3 PUFA. Animal and human studies were included and alterations on the whole organism were described (peripheral tissues and brain).

Cell membrane fatty acids influence fundamental properties of the plasma membrane, including membrane fluidity, protein functionality, and lipid raft signalling. Evidence suggests that dietary n-3 PUFA may target the plasma membrane of immune cells by altering plasma membrane lipid dynamics, thereby regulating the attenuation of immune cell activation and suppression of inflammation. As lipid-based immunotherapy might be a promising new clinical strategy for the treatment of inflammatory disorders, we conducted in vitro and in vivo experiments to examine the effects of n-3 PUFA on CD4+ T cell membrane order, mitochondrial bioenergetics and lymphoproliferation. n-3 PUFA were incorporated into human primary CD4+ T cells phospholipids in vitro in a dose-dependent manner, resulting in a reduction in whole cell membrane order, oxidative phosphorylation and proliferation. At higher doses, n-3 PUFA induced unique phase separation in T cell-derived giant plasma membrane vesicles. Similarly, in a short-term human pilot study, supplementation of fish oil (4 g n-3 PUFA/d) for 6 weeks in healthy subjects significantly elevated EPA (20 : 5n-3) levels in CD4+ T cell membrane phospholipids, and reduced membrane lipid order. These results demonstrate that the dynamic reshaping of human CD4+ T cell plasma membrane organisation by n-3 PUFA may modulate down-stream clonal expansion.