Distinct effects of α-linolenic acid and docosahexaenoic acid on the expression of genes related to cholesterol metabolism and the response to infection in THP-1 monocytes and immune cells of obese humans.

BACKGROUND: Monocytes play a large role in chronic inflammatory conditions such as obesity, atherosclerosis and infection. Marine-derived omega-3 fatty acids such as docosahexaenoic acid (DHA) beneficially alter immune function and attenuate chronic inflammation in part by modifying gene expression. Comparisons with plant-derived omega-3 α-linolenic acid (ALA) on immune cell gene expression and function are limited. METHODS: Transcriptome analysis was performed on THP-1 human monocytes treated with ALA, DHA or vehicle for 48 hr using fold change analysis, principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), variable importance analysis (VIP), and ingenuity pathway analysis (IPA). Candidate genes were validated by qPCR. Functional assays evaluated the transcriptomic predictions. Expression of candidate transcripts identified in THP-1 cells were examined in PBMC from clinical trial (OXBIO; NCT03583281) participants consuming ALA- or DHA-rich oil supplements. FINDINGS: ALA and DHA-treated monocytes presented distinct transcriptomic profiles as per VIP and PLS-DA. Both fatty acids were predicted to reduce cellular cholesterol content, while ALA would uniquely increase response to infection and chemotactic signals. Functional assays revealed ALA and DHA decreased cholesterol content. DHA significantly decreased the response to infection and chemotaxis, but ALA had no effect. Candidate transcripts responded similarly in PBMC from n-3 PUFA supplemented women with obesity. CONCLUSION: ALA and DHA differentially alter the transcription profiles and functions associated with the response to infection, chemotaxis, and cholesterol metabolism in mononuclear immune cells. Thus, they may uniquely affect related disease processes contributing to obesity, atherosclerosis, and the response to infection.

Long Chain N3-PUFA Decreases ACE2 Protein Levels and Prevents SARS-CoV-2 Cell Entry.

Angiotensin-converting enzyme 2 (ACE2) is a target of interest for both COVID-19 and cardiovascular disease management. Even though lower ACE2 levels may be beneficial in SARS-CoV-2 infectivity, maintaining the ACE1/ACE2 balance is also crucial for cardiovascular health. So far, reports describing conditions capable of altering ACE2 protein levels, especially via dietary components, are limited. In this study, the effects of omega-3 polyunsaturated fatty acids (n3-PUFA) on the protein levels of ACE1 and ACE2 in rodent tissues, human endothelial and kidney cell lines, and human plasma were examined. The ability of n3-PUFA to affect the entry of the SARS-CoV-2 pseudovirus into cells was also tested. Docosahexaenoic acid (DHA), and in some cases eicosapentaenoic acid (EPA), but not α-linoleic acid (ALA), reduced both ACE1 and ACE2 (non-glycosylated p100 and glycosylated p130 forms) in the heart, aorta, and kidneys of obese rats, as well as in human EA.hy926 endothelial and HEK293 kidney cells. Dietary supplementation with either DHA or ALA had no effect on plasma soluble ACE2 levels in humans. However, treatment of HEK293 cells with 80 and 125 µM DHA for 16 h inhibited the entry of the SARS-CoV-2 pseudovirus. These results strongly suggest that DHA treatment may reduce the ability of SARS-CoV-2 to infect cells via a mechanism involving a decrease in the absolute level of ACE2 protein as well as its glycosylation. Our findings warrant further evaluation of long-chain n3-PUFA supplements as a novel option for restricting SARS-CoV-2 infectivity in the general population.

Effects of Diets Enriched with Conventional or High-Oleic Canola Oils on Vascular Endothelial Function: A Sub-Study of the Canola Oil Multi-Centre Intervention Trial 2 (COMIT-2), a Randomized Crossover Controlled Feeding Study.

Partial replacement of saturated fatty acids (SFA) with unsaturated fatty acids is recommended to reduce cardiovascular disease (CVD) risk. Monounsaturated fatty acids (MUFA), including oleic acid, are associated with lower CVD risk. Measurement of flow-mediated dilation of the brachial artery (FMD) is the gold standard for measuring endothelial function and predicts CVD risk. This study examined the effect of partially replacing SFA with MUFA from conventional canola oil and high-oleic acid canola oil on FMD. Participants (n = 31) with an elevated waist circumference plus ≥1 additional metabolic syndrome criterion completed FMD measures as part of the Canola Oil Multi-Centre Intervention Trial 2 (COMIT-2), a multi-center, double-blind, three-period crossover, controlled feeding randomized trial. Diet periods were 6 weeks, separated by ≥4-week washouts. Experimental diets were provided during all feeding periods. Diets only differed by the fatty acid profile of the oils: canola oil (CO; 17.5% energy from MUFA, 9.2% polyunsaturated fatty acids (PUFA), 6.6% SFA), high-oleic acid canola oil (HOCO; 19.1% MUFA, 7.0% PUFA, 6.4% SFA), and a control oil blend (CON; 11% MUFA, 10% PUFA, 12% SFA). Multilevel models were used to examine the effect of the diets on FMD. No significant between-diet differences were observed for average brachial artery diameter (CO: 6.70 ± 0.15 mm, HOCO: 6.57 ± 0.15 mm, CON: 6.73 ± 0.14 mm; p = 0.72), peak brachial artery diameter (CO: 7.11 ± 0.15 mm, HOCO: 7.02 ± 0.15 mm, CON: 6.41 ± 0.48 mm; p = 0.80), or FMD (CO: 6.32 ± 0.51%, HOCO: 6.96 ± 0.49%, CON: 6.41 ± 0.48%; p = 0.81). Partial replacement of SFA with MUFA from CO and HOCO had no effect on FMD in participants with or at risk of metabolic syndrome.

Polymorphisms in the stearoyl-CoA desaturase gene modify blood glucose response to dietary oils varying in MUFA content in adults with obesity.

Diets varying in SFA and MUFA content can impact glycaemic control; however, whether underlying differences in genetic make-up can influence blood glucose responses to these dietary fatty acids is unknown. We examined the impact of dietary oils varying in SFA/MUFA content on changes in blood glucose levels (primary outcome) and whether these changes were modified by variants in the stearoyl-CoA desaturase (SCD) gene (secondary outcome). Obese men and women participating in the randomised, crossover, isoenergetic, controlled-feeding Canola Oil Multicenter Intervention Trial II consumed three dietary oils for 6 weeks, with washout periods of ˜6 weeks between each treatment. Diets studied included a high SFA/low MUFA Control oil (36·6 % SFA/28·2 % MUFA), a conventional canola oil (6·2 % SFA/63·1 % MUFA) and a high-oleic acid canola oil (5·8 % SFA/74·7 % MUFA). No differences in fasting blood glucose were observed following the consumption of the dietary oils. However, when stratified by SCD genotypes, significant SNP-by-treatment interactions on blood glucose response were found with additive models for rs1502593 (P = 0·01), rs3071 (P = 0·02) and rs522951 (P = 0·03). The interaction for rs3071 remained significant (P = 0·005) when analysed with a recessive model, where individuals carrying the CC genotype showed an increase (0·14 (sem 0·09) mmol/l) in blood glucose levels with the Control oil diet, but reductions in blood glucose with both MUFA oil diets. Individuals carrying the AA and AC genotypes experienced reductions in blood glucose in response to all three oils. These findings identify a potential new target for personalised nutrition approaches aimed at improving glycaemic control.

Oils Rich in α-Linolenic Acid or Docosahexaenoic Acid Have Distinct Effects on Plasma Oxylipin and Adiponectin Concentrations and on Monocyte Bioenergetics in Women with Obesity.

BACKGROUND: Omega-3 fatty acids, including DHA and α-linolenic acid (ALA), are proposed to improve metabolic health by reducing obesity-associated inflammation. Their effects are mediated in part by conversion to oxylipins. ALA is relatively understudied, and direct comparisons to other omega-3 fatty acids are limited. OBJECTIVES: We compared the effects of equal doses of ALA and DHA on plasma oxylipins and markers of metabolic health in women with obesity. METHODS: We carried out a randomized, double-blind, crossover clinical trial where women aged 20-51 with a BMI of 30-51 kg/m2 were supplemented with 4 g/day of ALA or DHA for 4 weeks in the form of ALA-rich flaxseed oil or DHA-rich fish oil. The primary outcome, the plasma oxylipin profile, was assessed at Days 0 and 28 of each phase by HPLC-MS/MS. Plasma fatty acids, inflammatory markers, and the monocyte glucose metabolism were key secondary outcomes. Data were analyzed using a mixed model. RESULTS: Compared to the baseline visit, there were higher plasma levels of nearly all oxylipins derived from DHA (3.8-fold overall; P < 0.001) and EPA (2.7-fold overall; P < 0.05) after 28 days of fish-oil supplementation, while there were no changes to oxylipins after flaxseed-oil supplementation. Neither supplement altered plasma cytokines; however, adiponectin was increased (1.1-fold; P < 0.05) at the end of the fish-oil phase. Compared to the baseline visit, 28 days of flaxseed-oil supplementation reduced ATP-linked oxygen consumption (0.75-fold; P < 0.05) and increased spare respiratory capacity (1.4-fold; P < 0.05) in monocytes, and countered the shift in oxygen consumption induced by LPS. CONCLUSIONS: Flaxseed oil and fish oil each had unique effects on metabolic parameters in women with obesity. The supplementation regimens were insufficient to reduce inflammatory markers but adequate to elicit increases in omega-3 oxylipins and adiponectin in response to fish oil and to alter monocyte bioenergetics in response to flaxseed oil. This trial was registered at clinicaltrials.gov as NCT03583281.

Rationale and design of a randomized controlled trial examining the effects of marine- and plant-sourced omega-3 fatty acid supplements on octadecanoid profiles and inflammation in females with obesity (OXBIO trial).

INTRODUCTION: Consumption of omega-3 polyunsaturated fatty acids (n-3 PUFAs) has been reported to provide health benefits, but it remains unknown whether the fatty acids themselves or their oxygenated metabolites, oxylipins, are responsible for the beneficial effects. PURPOSE: This paper describes the design and rationale of a randomized, double-blinded, cross-over study comparing the effects of α-linolenic acid (ALA)-rich flax oil and docosahexaenoic acid (DHA)-rich fish oil supplementation on circulating oxylipin profiles in females with obesity, in relation to obesity-induced inflammation. METHODS AND ANALYSIS: Pre-menopausal females (n = 24) aged 20-55 with a BMI ≥30, will consume capsules containing flaxseed oil (4 g ALA/day) or fish oil (4 g DHA + 0.8 g EPA/day) during 4-week supplementation phases, with a minimum 4-week washout. The primary outcome is alterations in plasma oxylipin profiles. Secondary outcomes include effects of supplementation on circulating markers of inflammation, adipokines, plasma fatty acid composition, blood lipid profile, anthropometrics, oxylipin and cytokine profiles of stimulated immune cells, monocyte glucose metabolism, blood pressure and pulse wave velocity. ETHICS AND SIGNIFICANCE: This trial has been approved by the University of Manitoba Biomedical Research Ethics Board and the St. Boniface Hospital Research Review Committee. The study will provide information regarding the effects of ALA and DHA supplementation on oxylipin profiles in obese but otherwise healthy females. Additionally, it will improve our understanding of the response of circulating inflammatory mediators originating from immune cells, adipose tissue and the liver to n-3 PUFA supplementation in relation to the metabolic features of obesity.

Time Course and Sex Effects of α-Linolenic Acid-Rich and DHA-Rich Supplements on Human Plasma Oxylipins: A Randomized Double-Blind Crossover Trial.

BACKGROUND: Differences in health effects of dietary α-linolenic acid (ALA) and DHA are mediated at least in part by differences in their effects on oxylipins. OBJECTIVES: Time course and sex differences of plasma oxylipins in response to ALA- compared with DHA-rich supplements were examined. METHODS: Healthy men and women, aged 19-34 y and BMI 18-28 kg/m2, were provided with capsules containing ∼4 g/d of ALA or DHA in a randomized double-blind crossover study with >6-wk wash-in and wash-out phases. Plasma PUFA and oxylipin (primary outcome) concentrations at days 0, 1, 3, 7, 14, and 28 of supplementation were analyzed by GC and HPLC-MS/MS, respectively. Sex differences, supplementation and time effects, and days to plateau were analyzed. RESULTS: ALA supplementation doubled ALA concentrations, but had no effects on ALA oxylipins after 28 d, whereas DHA supplementation tripled both DHA and its oxylipins. Increases in DHA oxylipins were detected as early as day 1, and a plateau was reached by days 5-7 for 11 of 12 individual DHA oxylipins and for total DHA oxylipins. Nine individual DHA oxylipins reached a plateau in females with DHA supplementation, compared with only 4 in males. A similar time course and sex difference pattern occurred with EPA and its oxylipins with DHA supplementation. DHA compared with ALA supplementation also resulted in higher concentrations of 4 individual arachidonic acids, 1 linoleic acid, and 1 dihomo-γ-linolenic acid oxylipin, despite not increasing the concentrations of these fatty acids, further demonstrating that oxylipins do not always reflect their precursor PUFA. CONCLUSIONS: DHA compared with a similar dose of ALA has greater effects on both n-3 and n-6 oxylipins in young, healthy adults, with differences in response to DHA supplementation occurring earlier and being greater in females. These findings can help explain differences in dietary effects of ALA and DHA.This study was registered at clinicaltrials.gov as NCT02317588.

Spleen Oxylipin and Polyunsaturated Fatty Acid Profiles are Altered by Dietary Source of Polyunsaturated Fatty Acid and by Sex.

As the largest secondary lymphoid organ, the spleen plays an important role in immune responses. The role of arachidonic acid (ARA) and its 20-carbon eicosanoids in modulating immune function has long been of interest. However, recent advances have enabled the identification of numerous other n-6 and n-3 polyunsaturated fatty acid (PUFA)-derived oxylipins. Here, we investigate the effects of diet and sex on the spleen nonesterified oxylipin profiles and phospholipid and neutral lipid PUFA composition in Sprague-Dawley rats supplemented with oils rich in α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or linoleic acid. Dietary ALA, EPA, and DHA resulted in lower levels of ARA and ARA oxylipins. Oxylipins derived from other n-6 PUFA were also reduced despite no or opposite effect on their PUFA levels. Each diet also resulted in higher levels of oxylipins almost exclusively derived from the supplemented PUFA, despite PUFA in the same biosynthetic pathway also often being increased. Further, while oxylipin differences often reflected changes to phospholipid PUFA, there were instances where they corresponded more closely to changes in neutral lipid PUFA. With respect to sex effects, >50% of lipoxygenase ARA-derived oxylipins were higher in males in at least one diet group, while multiple DHA oxylipins were lower in males only in rats provided the DHA diet. This fundamental description of oxylipin composition in the spleen, including the influence of diet and sex and the relationship to PUFA composition, will help inform future studies examining the functions of these oxylipins under physiological and pathological conditions.

Alpha-linolenic acid enhances the phagocytic and secretory functions of alternatively activated macrophages in part via changes to the oxylipin profile.

Alternatively activated macrophages are innate immune cells that contribute to resolution of inflammation and maintenance of homeostasis. Modulation of available fatty acid sources is thought to affect cellular physiology through a variety of mechanisms, including through alterations to the profile of oxygenated free fatty acid metabolites, called oxylipins, produced in a cell type specific manner. Here, we investigated how treatment with the plant-sourced omega-3 fatty acid α-linolenic acid (ALA) affects the oxylipin profile and functional capacity of a cell culture model of human alternatively activated (M2a-like) macrophages. In a targeted but unbiased screen, ALA enhanced the production of oxylipins from all polyunsaturated fatty acid (PUFA) precursors, with oxylipins derived from ALA being enhanced the most. Consistently, ALA treatment enhanced the expression of both cytoplasmic and calcium-independent phospholipase A2. At a functional level, ALA treatment increased phagocytic activity and altered production of the chemokine MCP-1 by M2a-like cells in a manner dependent on the time of treatment. ALA treatment during polarization increased MCP-1 secretion, which was sensitive to pharmacological inhibition of 15-LOX-1 by ML351. Thus, ALA modulates the phenotype of alternatively activated macrophages, likely through its own LOX-derived oxylipins and/or through general modulation of oxylipin biosynthesis. These effects likely contribute to the overall anti-inflammatory benefit observed with ALA supplementation.

Diets Enriched with Conventional or High-Oleic Acid Canola Oils Lower Atherogenic Lipids and Lipoproteins Compared to a Diet with a Western Fatty Acid Profile in Adults with Central Adiposity.

BACKGROUND: Novel oils high in monounsaturated fatty acids (MUFAs) and low in saturated fatty acids (SFAs) are an alternative to partially hydrogenated oils high in trans-unsaturated fatty acids. There is widespread use of high-MUFA oils across the food industry; however, limited knowledge of their cardiovascular impact exists. OBJECTIVES: We investigated the effects of diets containing canola oil, high-oleic acid canola oil (HOCO), and a control oil blend (diet formulated to emulate a Western fat profile) on lipids, lipoproteins, and apolipoproteins (apos), as secondary outcomes of the trial. METHODS: In a multi-center, double-blind, randomized, 3-period crossover, controlled feeding trial, men (n = 44) and women (n = 75) with a mean age of 44 y, mean body mass index (BMI; in kg/m2) of 31.7, and an increased waist circumference plus ≥1 metabolic syndrome criteria consumed prepared, weight-maintenance diets containing canola oil [17.5% MUFAs, 9.2% polyunsaturated fatty acids (PUFAs), 6.6% SFAs], HOCO (19.1% MUFAs, 7.0% PUFAs, 6.4% SFAs), or control oil (10.5% MUFAs, 10.0% PUFAs, 12.3% SFAs) for 6 wk with ≥4-wk washouts. Fasting serum lipids were assessed at baseline and 6 wk. Diet effects were examined using a repeated measures mixed model. RESULTS: Compared with the control, canola and HOCO diets resulted in lower endpoint total cholesterol (TC; -4.2% and -3.4%; P < 0.0001), LDL cholesterol (-6.6% and -5.6%; P < 0.0001), apoB (-3.7% and -3.4%; P = 0.002), and non-HDL cholesterol (-4.5% and -4.0%; P = 0.001), with no differences between canola diets. The TC:HDL cholesterol and apoB:apoA1 ratios were lower after the HOCO diet than after the control diet (-3.7% and -3.4%, respectively). There were no diet effects on triglyceride, HDL cholesterol, or apoA1 concentrations. CONCLUSIONS: HOCO, with increased MUFAs at the expense of decreased PUFAs, elicited beneficial effects on lipids and lipoproteins comparable to conventional canola oil and consistent with reduced cardiovascular disease risk in adults with central adiposity. This trial was registered at www.clinicaltrials.gov as NCT02029833.

Distinct effects of dietary ALA, EPA and DHA on rat adipose oxylipins vary by depot location and sex.

Dietary EPA and DHA given together alter oxylipins in adipose tissue. To compare the separate effects of individual dietary n-3 PUFA on oxylipins in different adipose depots (gonadal, mesenteric, perirenal, subcutaneous) in males and females, rats were provided diets containing higher levels of α-linolenic acid (ALA), EPA or DHA. Each n-3 PUFA enhanced its respective oxylipins the most, while effects on other n-3 oxylipins varied. For example: in perirenal and subcutaneous depots, more DHA oxylipins were higher with dietary ALA than with EPA; dietary EPA uniquely decreased 14-hydroxy-docosahexaenoic acid, in contrast to increasing many other DHA oxylipins. The n-3 PUFAs also reduced oxylipins from n-6 PUFAs in order of effectiveness: DHA > EPA > ALA. Diet by sex interactions in all depots except the perirenal depot resulted in higher oxylipins in males given DHA, and higher oxylipins in females given the other diets. Diet and sex effects on oxylipins did not necessarily reflect effects on either their tissue phospholipid or neutral lipid PUFA precursors. These varying diet and sex effects on oxylipins in the different adipose sites indicate that they may have distinct effects on adipose function.

Trans-10,cis-12 conjugated linoleic acid (t10-c12 CLA) treatment and caloric restriction differentially affect adipocyte cell turnover in obese and lean mice.

Caloric restriction (CR) is one of the most promising strategies for weight loss but is associated with loss of lean mass, whereas compounds such as trans-10,cis-12 conjugated linoleic acid (t10-c12 CLA) have been promoted as antiobesity agents. To compare the mechanisms of weight reduction by CR and t10-c12 CLA, body composition, glucose control, and characteristics of adipose tissue with respect to cell turnover (stem cells and preadipocytes, apoptosis and autophagy) and Tbx-1 localization were examined in obese db/db mice and lean C57BL/6J mice undergoing CR or fed CLA isomers (0.4% w/w c9-t11 or t10-c12) for 4 weeks. Our findings show that the t10-c12 CLA reduced whole-body fat mass by decreasing all fat depots (visceral, inguinal, brown/interscapular), while CR lowered both whole-body fat and lean mass in obese mice. t10-c12 CLA elevated blood glucose in both obese and lean mice, while glycemia was not altered by CR. The adipocyte stem cell population remained unchanged; however, t10-c12 CLA reduced and CR elevated the proportion of immature adipocytes in obese mice, suggesting differential effects on adipocyte maturation. t10-c12 CLA reduced apoptosis (activated caspase-3) in both obese and lean mice but did not alter autophagy (LC3II/LC3I). Nuclear Tbx-1, a marker of metabolically active beige adipocytes, was greater in the adipose of t10-c12 CLA-fed animals. Thus, weight loss achieved via t10-c12 CLA primarily involves fat loss and more cells with Tbx-1 localized to the nucleus, while CR operates through a mechanism that reduces both lean and fat mass and blocks adipocyte differentiation.

Chlorogenic acid from coffee beans: evaluating the evidence for a blood pressure-regulating health claim.

The consumption of coffee has been associated with a number of health benefits, including a reduced risk of cardiovascular disease. Hypertension is an important risk factor for adverse cardiovascular events. Coffee may help reduce blood pressure (BP) in humans, which might be attributable to its polyphenolic compound, chlorogenic acid. The high incidence of hypertension among Canadians underscores the need for new and effective strategies to reduce BP. Dietary interventions may constitute such a strategy, but consumers need to be informed about which foods are most effective for regulating BP. To guide healthy eating, Health Canada permits the use of health claims on the labels of foods that confer health benefits. Currently, there is only one health claim for BP regulation. Additional health claims for foods that assist in BP regulation are therefore warranted. This review provides background information on chlorogenic acid and examines the evidence regarding the use of chlorogenic acid for BP regulation in the context of Health Canada's health claims framework.

Canola oil rich in oleic acid improves diastolic heart function in diet-induced obese rats.

Obesity is a leading cause of cardiovascular disease. It directly affects heart structure and function and contributes to heart failure. Diet is a major factor involved in the development of obesity along with genetic factors. We examined the effects of monounsaturated and polyunsaturated fatty acid-rich oils on cardiac structure and function in the diet-induced rodent model of obesity (DIO). Obese prone (OP) rats were fed a high-fat diet (HF; 55% of kcal) for 12 weeks; Sprague-Dawley rats fed commercial chow served as control. Echocardiography was performed to assess the cardiac structure and function in all rats at 12 weeks. OP rats fed the HF diet showed significant impairment in diastolic function compared to control rats. The HF diet containing high oleic canola oil significantly improved diastolic function of OP rats compared to the HF diet with lard. In conclusion, canola oil rich in oleic acid, when incorporated into an HF diet, prevents the development of diastolic dysfunction in DIO rats.

Trans-10,cis-12-conjugated linoleic acid worsens renal pathology and alters cyclooxygenase derived oxylipins in obesity-associated nephropathy.

Dietary conjugated linoleic acid (CLA) reduces indicators of early renal disease progression and the associated elevated cyclooxygenase (COX) levels in young obese rats with obesity-associated nephropathy (OAN). Therefore, renal function and injury and COX and its metabolites were assessed in obese fa/fa Zucker rats with more advanced renal disease. Obese rats at 16 weeks of age were provided with either cis(c)9, trans(t)11 (fa/fa-9,11) or t10,c12 (fa/fa-10,12) CLA for 8 weeks, and compared to lean (lean-CTL) and obese (fa/fa-CTL) rats provided the control diet without CLA. Obese rats displayed significantly reduced renal function and increased renal injury compared to lean rats. In the obese rat groups, glomerular hypertrophy was reduced in both CLA-supplemented groups. While all other measures of renal function or injury were not different in fa/fa-9,11 compared to fa/fa-CTL rats, the fa/fa-10,12 rats had greater renal hypertrophy, glomerular fibrosis, fibrosis, tubular casts and macrophage infiltration compared to the fa/fa-CTL and fa/fa-9,11 groups. The fa/fa-10,12 group also had elevated levels of renal COX1, which was associated with increased levels of two oxylipins produced by this enzyme, 6-keto-prostaglandin F(1α), and thromboxane B2. Renal linoleic acid and its lipoxygenase products also were lower in obese compared to lean rats, but CLA supplementation had no effect on these or any other lipoxygenase oxylipins. In summary, supplementation with c9,t11 CLA did not improve more advanced OAN and t10,c12 CLA worsened the renal pathology. Altered production of select COX1 derived oxylipins was associated with the detrimental effect of the t10,c12 isomer.

The impact of omega-3 polyunsaturated fatty acid supplementation on the incidence of cardiovascular events and complications in peripheral arterial disease: a systematic review and meta-analysis.

BACKGROUND: Individuals with peripheral arterial disease are at higher risk for cardiovascular events than the general population. While supplementation with omega-3 polyunsaturated fatty acids (PUFA) has been shown to improve vascular function, it remains unclear if supplementation decreases serious clinical outcomes. We conducted a systematic review and meta-analysis to determine whether omega-3 PUFA supplementation reduces the incidence of cardiovascular events and complications in adults with peripheral arterial disease. METHODS: We searched five electronic databases (MEDLINE, EMBASE, CENTRAL, Scopus and the International Clinical Trials Registry Platform) from inception to 6 December 2013 to identify randomized trials of omega-3 PUFA supplementation (from fish or plant oils) that lasted ≥12 weeks in adults with peripheral arterial disease. No language filters were applied. Data on trial design, population characteristics, and health outcomes were extracted. The primary outcome was major adverse cardiac events; secondary outcomes included myocardial infarction, cardiovascular death, stroke, angina, amputation, revascularization procedures, maximum and pain-free walking distance, adverse effects of the intervention, and quality of life. Trial quality was assessed using the Cochrane Risk of Bias tool. RESULTS: Of 741 citations reviewed, we included five trials enrolling 396 individuals. All included trials were of unclear or high risk of bias. There was no evidence of a protective association of omega-3 PUFA supplementation against major adverse cardiac events (pooled risk ratio 0.73, 95% CI 0.22 to 2.41, I2 75%, 2 trials, 288 individuals) or other serious clinical outcomes. Adverse events and compliance were poorly reported. CONCLUSIONS: Our results showed that insufficient evidence exists to suggest a beneficial effect of omega-3 PUFA supplementation in adults with peripheral arterial disease with regard to cardiovascular events and other serious clinical outcomes.

Lentil-based diets attenuate hypertension and large-artery remodelling in spontaneously hypertensive rats.

Hypertension is a major risk factor for CVD, the leading cause of mortality worldwide. The prevalence of hypertension is expected to continue increasing, and current pharmacological treatments cannot alleviate all the associated problems. Pulse crops have been touted as a general health food and are now being studied for their possible effects on several disease states including hypertension, obesity and diabetes. In the present study, 15-week-old spontaneously hypertensive rats (SHR) were fed diets containing 30% w/w beans, peas, lentils, chickpeas, or mixed pulses or a pulse-free control diet for 4 weeks. Normotensive Wistar-Kyoto (WKY) rats were placed on a control diet. Pulse wave velocity (PWV) was measured weekly, while blood pressure (BP) was measured at baseline and week 4. Fasting serum obtained in week 4 of the study was analysed for circulating lipids. A histological analysis was carried out on aortic sections to determine vascular geometry. Of all the pulse varieties studied, lentils were found to be able to attenuate the rise in BP in the SHR model (P< 0·05). Lentils were able to decrease the media:lumen ratio and media width of the aorta. The total cholesterol (TC), LDL-cholesterol (LDL-C) and HDL-cholesterol levels of rats fed the pulse-based diets were found to be lower when compared with those of the WKY rat and SHR controls (P< 0·05). Although all pulses reduced circulating TC and LDL-C levels in the SHR, only lentils significantly reduced the rise in BP and large-artery remodelling in the SHR, but had no effect on PWV. These results indicate that the effects of lentils on arterial remodelling and BP in the SHR are independent of circulating LDL-C levels.

A diet high in α-linolenic acid and monounsaturated fatty acids attenuates hepatic steatosis and alters hepatic phospholipid fatty acid profile in diet-induced obese rats.

This study investigated the efficacy of the plant-based n-3 fatty acid, α-linolenic acid (ALA), a dietary precursor of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for modulating hepatic steatosis. Rats were fed high fat (55% energy) diets containing high oleic canola oil, canola oil, a canola/flax oil blend (C/F, 3:1), safflower oil, soybean oil, or lard. After 12 weeks, C/F and weight-matched (WM) groups had 20% less liver lipid. Body mass, liver weight, glucose and lipid metabolism, inflammation and molecular markers of fatty acid oxidation, synthesis, desaturation and elongation did not account for this effect. The C/F group had the highest total n-3 and EPA in hepatic phospholipids (PL), as well as one of the highest DHA and lowest arachidonic acid (n-6) concentrations. In conclusion, the C/F diet with the highest content of the plant-based n-3 ALA attenuated hepatic steatosis and altered the hepatic PL fatty acid profile.

Dietary linoleic acid and α-linolenic acid differentially affect renal oxylipins and phospholipid fatty acids in diet-induced obese rats.

Analysis of oxylipins derived from fatty acids may provide insight into the biological effects of dietary lipids beyond their effects on tissue fatty acid profiles. We have previously observed that diets with higher amounts of α-linolenic acid (ALA; 18:3n3) are associated with reduced obesity-related glomerulopathy (ORG). Therefore, to examine the renal oxylipin profile, the effects of dietary linoleic acid (LA; 18:2n6) and ALA on oxylipins and renal phospholipid fatty acid composition, and the relationship between oxylipins and ORG, diet-induced obese rats displaying ORG were fed 8 different diets for 8 wk as follows (oil/oil = combination of two oils) [shown as ALA/LA (in g) per 100 g oil]: canola/flax (20/18), canola (8/18), soy (9/53), high-oleic canola/canola (5/16), high-oleic canola (2/15), lard/soy (1/8), and safflower (0.2/73). Targeted lipidomic analysis by HPLC-tandem mass spectrometry revealed that LA and ALA oxylipins comprised 60% of the total renal oxylipin profile examined. Of the >60 oxylipins screened, only those derived either directly or indirectly from ALA were associated with less glomerulomegaly, indicative of reduced ORG progression. Both the amount and ratio of dietary LA and ALA influenced renal polyunsaturated fatty acids (PUFAs); in contrast, only fatty acid amount altered oxylipins derived from these fatty acids, but there was no apparent competition by LA or ALA on their formation. Dietary LA incorporation into renal phospholipids was higher than for ALA, but ALA oxylipin:ALA ratios were higher than the analogous LA ratios for select lipoxygenase reactions. This indicates that the effect of dietary ALA on renal oxylipins exceeded what was reflected in renal PUFA composition. In conclusion, dietary LA and ALA have differential effects on renal oxylipins and PUFAs, and ALA-derived oxylipins are associated with renoprotection in this model of ORG.

Consumption of buckwheat modulates the post-prandial response of selected gastrointestinal satiety hormones in individuals with type 2 diabetes mellitus.

PURPOSE: In healthy participants and those with diet-controlled type 2 diabetes (T2DM), to (1) compare the acute 3-hour post-prandial response of glucose, insulin and other gastrointestinal hormones known to influence food intake and glucose metabolism after consumption of a food product made from whole grain buckwheat flour versus rice flour; (2) determine the effect of daily consumption of a food product made from whole grain buckwheat flour on fasting glucose, lipids and apolipoproteins. METHODS: Healthy participants or those with T2DM consumed either buckwheat or rice crackers. Blood samples were collected at baseline and 15, 30, 45, 60, 120 and 180minutes after consumption. In a second phase of the study, participants consumed one serving of buckwheat crackers daily for 1week; fasting blood samples from day 1 and day 7 were analyzed. RESULTS: Post-prandial plasma glucagon-like peptide-1, glucose-dependent insulinotropic peptide and pancreatic polypeptide were altered after consuming buckwheat versus rice crackers. Interestingly, changes in these hormones did not lead to changes in post-prandial glucose, insulin or C-peptide concentrations. Significant correlations were observed between both fasting concentrations and post-prandial responses of several of the hormones examined. Interestingly, certain correlations were present only in the healthy participant group or the T2DM group. There was no effect of consuming buckwheat for one week on fasting glucose, lipids or apolipoproteins in either the healthy participants or those with T2DM. CONCLUSIONS: Although the buckwheat cracker did not modify acute glycemia or insulinemia, it was sufficient to modulate gastrointestinal satiety hormones.