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Journal of the American Heart... Jan 2013Few studies have examined the relationship of α-linolenic acid (ALA 18:3n-3), an intermediate-chain essential n-3 polyunsaturated fatty acid derived from plants and...
BACKGROUND
Few studies have examined the relationship of α-linolenic acid (ALA 18:3n-3), an intermediate-chain essential n-3 polyunsaturated fatty acid derived from plants and vegetable oils, with incident atrial fibrillation (AF).
METHODS AND RESULTS
The study population included participants from the Cardiovascular Health Study, a community-based longitudinal cohort of adults aged 65 or older, free of prevalent coronary heart disease and atrial fibrillation. We assessed the associations of plasma phospholipid and dietary ALA with incident AF using Cox regression. The biomarker analysis comprised a total of 2899 participants, and the dietary analysis comprised 4337 participants. We found no association of plasma phospholipid ALA and incident AF. Comparing each of the second, third, and fourth quartiles to the lowest quartile, the hazard ratios for AF were 1.11 (95% CI, 0.90 to 1.37), 1.09 (95% CI, 0.88 to 1.35), and 0.92 (95% CI, 0.74 to 1.15), after adjustment for age, sex, race, clinic, education, smoking, alcohol, body mass index, waist circumference, diabetes, heart failure, stroke, treated hypertension, and physical activity (P trend=0.48). When dietary ALA was considered the exposure of interest, results were similar.
CONCLUSIONS
Results from this prospective cohort study of older adults indicate no association of plasma phospholipid or dietary ALA and incident AF.
Topics: Age Factors; Aged; Aged, 80 and over; Atrial Fibrillation; Biomarkers; Diet; Female; Humans; Incidence; Linear Models; Longitudinal Studies; Male; Nutritional Status; Phospholipids; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; United States; alpha-Linolenic Acid
PubMed: 23525429
DOI: 10.1161/JAHA.112.003814 -
The Journal of Nutrition Sep 2013Analysis 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...
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.
Topics: Animals; Diet; Dietary Fats; Dietary Fats, Unsaturated; Fatty Acids, Monounsaturated; Kidney; Kidney Diseases; Linoleic Acid; Male; Obesity; Oxylipins; Phospholipids; Rapeseed Oil; Rats; Rats, Sprague-Dawley; Safflower Oil; Soybean Oil; alpha-Linolenic Acid
PubMed: 23902961
DOI: 10.3945/jn.113.177360 -
The Journal of Nutrition Mar 2021Diet-induced disordered phospholipid metabolism and disturbed macrophage metabolism contribute to the pathogenesis of metabolic diseases. However, the effects of oleate,...
BACKGROUND
Diet-induced disordered phospholipid metabolism and disturbed macrophage metabolism contribute to the pathogenesis of metabolic diseases. However, the effects of oleate, a main dietary fatty acid, on macrophage phospholipid metabolism are unclear.
OBJECTIVES
We aimed to discover oleate-induced disorders of macrophage phospholipid metabolism and potential therapeutic targets for treating diet-related metabolic diseases.
METHODS
RAW 264.7 cells were exposed to 65 μg oleate/mL, within the blood concentration range of humans and mice, to trigger disorders of phospholipid metabolism. Meanwhile, WY-14643 and pioglitazone, 2 drugs widely used for treating metabolic diseases, were employed to prevent oleate-induced disorders of macrophage phospholipid metabolism. Subsequently, an untargeted metabolomics approach based on liquid chromatography-mass spectrometry was used to discover relevant metabolic disorders and potential therapeutic targets.
RESULTS
We showed that 196 metabolites involved in phospholipid metabolism were altered upon oleate treatment and interventions of WY-14643 and pioglitazone (P < 0.05, 2-tailed Mann-Whitney U test). Notably, most lysophospholipids were decreased, whereas most phospholipids were increased in oleate-treated macrophages. Phosphatidylethanolamines accumulated most among phospholipids, and their acyl chain polyunsaturation increased in oleate-treated macrophages. Additionally, saturated fatty acids were decreased, whereas polyunsaturated fatty acids were increased in oleate-treated macrophages. Furthermore, changes in phosphatidylglycerols, phosphatidylinositols, cardiolipins, phosphatidates, lysophosphatidylglycerols, and acylcarnitines in oleate-treated macrophages could be attenuated or even abolished by WY-14643 and/or pioglitazone treatment.
CONCLUSIONS
Oleate induced accumulation of various phospholipids, increased acyl chain polyunsaturation of phosphatidylethanolamines, and decreased lysophospholipids in RAW 264.7 macrophages. This study suggests macrophage phospholipid and fatty acid metabolism as potential therapeutic targets for intervening diet-related metabolic diseases.
Topics: Animals; Chromatography, Liquid; Lipid Metabolism; Macrophages; Mass Spectrometry; Metabolic Diseases; Metabolomics; Mice; Models, Animal; Oleic Acid; Phospholipids; Pioglitazone; Pyrimidines; RAW 264.7 Cells
PubMed: 33571370
DOI: 10.1093/jn/nxaa411 -
Cell Metabolism Mar 2016Phospholipids are important determinants of membrane biophysical properties, but the impact of membrane acyl chain composition on dietary-lipid absorption is unknown....
Phospholipids are important determinants of membrane biophysical properties, but the impact of membrane acyl chain composition on dietary-lipid absorption is unknown. Here we demonstrate that the LXR-responsive phospholipid-remodeling enzyme Lpcat3 modulates intestinal fatty acid and cholesterol absorption and is required for survival on a high-fat diet. Mice lacking Lpcat3 in the intestine thrive on carbohydrate-based chow but lose body weight rapidly and become moribund on a triglyceride-rich diet. Lpcat3-dependent incorporation of polyunsaturated fatty acids into phospholipids is required for the efficient transport of dietary lipids into enterocytes. Furthermore, loss of Lpcat3 amplifies the production of gut hormones, including GLP-1 and oleoylethanolamide, in response to high-fat feeding, contributing to the paradoxical cessation of food intake in the setting of starvation. These results reveal that membrane phospholipid composition is a gating factor in passive lipid absorption and implicate LXR-Lpcat3 signaling in a gut-brain feedback loop that couples absorption to food intake.
Topics: 1-Acylglycerophosphocholine O-Acyltransferase; Animals; Apolipoproteins; Cholesterol; Diet, High-Fat; Dietary Fats; Female; Glucagon-Like Peptide 1; Intestinal Absorption; Intestinal Mucosa; Intestines; Lipid Metabolism; Male; Membrane Fluidity; Mice, Inbred C57BL; Mice, Knockout; Obesity; Phospholipids; Transcriptional Activation; Triglycerides
PubMed: 26833026
DOI: 10.1016/j.cmet.2016.01.001 -
Cells Dec 2020Lipids are important molecules for human health. The quantity and quality of fats consumed in the diet have important effects on the modulation of both the natural... (Review)
Review
Lipids are important molecules for human health. The quantity and quality of fats consumed in the diet have important effects on the modulation of both the natural biosynthesis and degradation of lipids. There is an important number of lipid-failed associated metabolic diseases and an increasing number of studies suggesting that certain types of lipids might be beneficial to the treatment of many metabolic diseases. The aim of the present work is to expose an overview of biosynthesis, storage, and degradation of lipids in mammalian cells, as well as, to review the published data describing the beneficial effects of these processes and the potential of some dietary lipids to improve metabolic diseases.
Topics: Adipose Tissue; Animals; Biomarkers; Cholesterol; Diet; Dietary Fats; Eicosanoids; GTP Phosphohydrolases; Homeostasis; Humans; Lipid Metabolism; Metabolic Diseases; Mitochondrial Proteins; Phospholipids; Sterols; Triglycerides
PubMed: 33291746
DOI: 10.3390/cells9122605 -
Scientific Reports Jun 2023Alzheimer disease (AD) is the most prevalent cause of dementia in the elderly. Although impaired cognition and memory are the most prominent features of AD,...
Alzheimer disease (AD) is the most prevalent cause of dementia in the elderly. Although impaired cognition and memory are the most prominent features of AD, abnormalities in visual functions often precede them, and are increasingly being used as diagnostic and prognostic markers for the disease. Retina contains the highest concentration of the essential fatty acid docosahexaenoic acid (DHA) in the body, and its deficiency is associated with several retinal diseases including diabetic retinopathy and age related macular degeneration. In this study, we tested the hypothesis that enriching retinal DHA through a novel dietary approach could ameliorate symptoms of retinopathy in 5XFAD mice, a widely employed model of AD. The results show that 5XFAD mice have significantly lower retinal DHA compared to their wild type littermates, and feeding the lysophosphatidylcholine (LPC) form of DHA and eicosapentaenoic acid (EPA) rapidly normalizes the DHA levels, and increases retinal EPA by several-fold. On the other hand, feeding similar amounts of DHA and EPA in the form of triacylglycerol had only modest effects on retinal DHA and EPA. Electroretinography measurements after 2 months of feeding the experimental diets showed a significant improvement in a-wave and b-wave functions by the LPC-diet, whereas the TAG-diet had only a modest benefit. Retinal amyloid β levels were decreased by about 50% by the LPC-DHA/EPA diet, and by about 17% with the TAG-DHA/EPA diet. These results show that enriching retinal DHA and EPA through dietary LPC could potentially improve visual abnormalities associated with AD.
Topics: Mice; Animals; Docosahexaenoic Acids; Eicosapentaenoic Acid; Lysophosphatidylcholines; Alzheimer Disease; Amyloid beta-Peptides; Retina; Retinal Diseases; Diet
PubMed: 37280266
DOI: 10.1038/s41598-023-36268-0 -
Molecular Nutrition & Food Research Oct 2022Colon metabolomes associated with high-fat (H) versus energy-restricted (E) diets in early colorectal cancer (CRC) models have never been directly compared. The...
SCOPE
Colon metabolomes associated with high-fat (H) versus energy-restricted (E) diets in early colorectal cancer (CRC) models have never been directly compared. The objectives of this study are to elucidate metabolites associated with diet, aberrant crypt foci (ACF), and diet:ACF interaction, using a lifetime murine model.
METHODS AND RESULTS
Three-week-old mice consumed control (C), E, or H initiation diets for 18 weeks. ACF formation is initiated weeks 16-21 with azoxymethane injections, followed by progression diet crossover (to C, E, or H) through week 60. Colon extracts are analyzed using ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). Metabolites associated with diet, ACF, or diet:ACF are determined using regression models (FDR-adjusted p-value <0.05). No metabolites are significantly associated with initiation diets, but concentrations of acylcarnitines and phospholipids are associated with C, E, and H progression diets. Purines, taurine, and phospholipids are associated with ACF presence. No significant associations between metabolites and diet:ACF interaction are observed.
CONCLUSIONS
These results suggest that recent, rather than early-life, diet is more closely associated with the colon metabolome, particularly lipid metabolism. Results from this study also provide candidate biomarkers of early CRC development and provide support for the importance of early diet on influencing pre-CRC risk.
Topics: Mice; Animals; Aberrant Crypt Foci; Phospholipids; Taurine; Colonic Neoplasms; Mice, Inbred C57BL; Azoxymethane; Colon; Energy Intake; Diet; Purines; Carcinogens; Precancerous Conditions
PubMed: 35969485
DOI: 10.1002/mnfr.202200180 -
Advances in Nutrition (Bethesda, Md.) Jan 2019Cancer is the second leading cause of mortality worldwide. The role of unresolved inflammation in cancer progression and metastasis is well established.... (Review)
Review
Cancer is the second leading cause of mortality worldwide. The role of unresolved inflammation in cancer progression and metastasis is well established. Platelet-activating factor (PAF) is a key proinflammatory mediator in the initiation and progression of cancer. Evidence suggests that PAF is integral to suppression of the immune system and promotion of metastasis and tumor growth by altering local angiogenic and cytokine networks. Interactions between PAF and its receptor may have a role in various digestive, skin, and hormone-dependent cancers. Diet plays a critical role in the prevention of cancer and its treatment. Research indicates that the Mediterranean diet may reduce the incidence of several cancers in which dietary PAF inhibitors have a role. Dietary PAF inhibitors such as polar lipids have demonstrated inhibitory effects against the physiological actions of PAF in cancer and other chronic inflammatory conditions in vitro and in vivo. In addition, experimental models of radiotherapy and chemotherapy demonstrate that inhibition of PAF as adjuvant therapy may lead to more favorable outcomes. Although promising, there is limited evidence on the potential benefits of dietary PAF inhibitors on cancer prevention or treatment. Therefore, further extensive research is required to assess the effects of various dietary factors and PAF inhibitors and to elucidate the mechanisms in prevention of cancer progression and metastasis at a molecular level.
Topics: Diet; Diet, Mediterranean; Disease Progression; Humans; Neoplasms; Platelet Activating Factor
PubMed: 30721934
DOI: 10.1093/advances/nmy090 -
The Journal of Nutrition Mar 2023It is unclear whether moderate differences in dietary carbohydrate quantity and quality influence plasma FAs in the lipogenic pathway in healthy adults. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
It is unclear whether moderate differences in dietary carbohydrate quantity and quality influence plasma FAs in the lipogenic pathway in healthy adults.
OBJECTIVES
We investigated the effects of different carbohydrate quantities and quality on plasma palmitate concentrations (primary outcome) and other saturated and MUFAs in the lipogenic pathway.
METHODS
Twenty healthy participants were randomly assigned, and 18 (50% women; age: 22-72 y; BMI: 18.2-32.7 kg/m and BMI was measured in kg/m) started the cross-over intervention. During each 3-wk period (separated by a 1-wk washout period), 3 diets were consumed (all foods provided) in random order: low-carbohydrate (LC) (38% energy (E) carbohydrates, 25-35 g fiber/d, 0% E added sugars); high-carbohydrate/high-fiber (HCF) (53% E carbohydrates, 25-35 g fiber/d, 0% E added sugars); and high-carbohydrate/high-sugar (HCS) (53% E carbohydrates, 19-21 g fiber/d, 15% E added sugars). Individual FAs were measured proportionally to total FAs by GC in plasma cholesteryl esters, phospholipids, and TGs. False discovery rate-adjusted repeated measures ANOVA [ANOVA-false discovery rate (FDR)] was used to compare outcomes.
RESULTS
The self-reported intakes of carbohydrates and added- and free sugars were; 30.6% E and 7.4% E in LC, 41.4% E and 6.9% E in HCF, and 45.7% E and 10.3% in HCS. Plasma palmitate did not differ between the diet periods (ANOVA FDR P > 0.43, n = 18). After HCS, myristate concentrations in cholesterol esters and phospholipids were ≥19% higher than LC and ≥22% higher than HCF (P = 0.005). After LC, palmitoleate in TG was 6% lower compared with HCF and 7% compared with HCS (P = 0.041). Body weight differed (≤0.75 kg) between diets before FDR correction.
CONCLUSIONS
Different carbohydrate quantity and quality do not influence plasma palmitate concentrations after 3 wk in healthy Swedish adults, whereas myristate increased after the moderately higher intake of carbohydrate/high-sugar, but not carbohydrate/high-fiber. Whether plasma myristate is more responsive than palmitate to differences in carbohydrate intake requires further study, especially considering that participants deviated from the planned dietary targets. J Nutr 20XX;xx:xx-xx. This trial was registered at clinicaltrials.gov as NCT03295448.
Topics: Humans; Adult; Female; Young Adult; Middle Aged; Aged; Male; Myristates; Dietary Carbohydrates; Diet; Fatty Acids, Monounsaturated; Phospholipids; Sugars; Fatty Acids
PubMed: 36797136
DOI: 10.1016/j.tjnut.2023.01.005 -
Nutrients Oct 2022As centenarians provide a paradigm of healthy aging, investigating the comprehensive metabolic profiles of healthy centenarians is of utmost importance for the pursuit...
The Age-Accompanied and Diet-Associated Remodeling of the Phospholipid, Amino Acid, and SCFA Metabolism of Healthy Centenarians from a Chinese Longevous Region: A Window into Exceptional Longevity.
As centenarians provide a paradigm of healthy aging, investigating the comprehensive metabolic profiles of healthy centenarians is of utmost importance for the pursuit of health and longevity. However, relevant reports, especially studies considering the dietary influence on metabolism, are still limited, mostly lacking the guidance of a model of healthy aging. Therefore, exploring the signatures of the integrative metabolic profiles of the healthy centenarians from a famous longevous region, Bama County, China, should be an effective way. The global metabolome in urine and the short-chain fatty acids (SCFAs) in the feces of 30 healthy centenarians and 31 elderly people aged 60−70 from the longevous region were analyzed by non-targeted metabolomics combined with metabolic target analysis. The results showed that the characteristic metabolites related to longevity were mostly summarized into phosphatidylserine, lyso-phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol, bile acids, and amino acids (p < 0.05). Six metabolic pathways were found significant relevant to longevity. Furthermore, acetic acid, propionic acid, butyric acid, valeric acid, and total SCFA were significantly increased in the centenarian group (p < 0.05) and were also positively associated with the dietary fiber intake (p < 0.01). It was age-accompanied and diet-associated remodeling of phospholipid, amino acid, and SCFA metabolism that expressed the unique metabolic signatures related to exceptional longevity. This metabolic remodeling is suggestive of cognitive benefits, better antioxidant capacity, the attenuation of local inflammation, and health-span-promoting processes, which play a critical and positive role in shaping healthy aging.
Topics: Aged, 80 and over; Aged; Humans; Longevity; Propionates; Amino Acids; Phosphatidylethanolamines; Phospholipids; Centenarians; Phosphatidylserines; Antioxidants; Diet; China; Fatty Acids, Volatile; Butyric Acid; Dietary Fiber; Acetates; Phosphatidylinositols; Bile Acids and Salts; Phosphatidylcholines
PubMed: 36297104
DOI: 10.3390/nu14204420