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FASEB Journal : Official Publication of... Jul 2023The phospholipase A and acyltransferase (PLAAT) family is composed of three isoforms in mice (PLAAT1, 3, and 5), all of which function as phospholipid-metabolizing...
The phospholipase A and acyltransferase (PLAAT) family is composed of three isoforms in mice (PLAAT1, 3, and 5), all of which function as phospholipid-metabolizing enzymes exhibiting phospholipase A /A and acyltransferase activities. Plaat3-deficient (Plaat3 ) mice were previously reported to show lean phenotype and remarkable hepatic fat accumulation under high-fat diet (HFD) feeding, while Plaat1 mice have not been analyzed. In the present study, we generated Plaat1 mice and investigated the effects of PLAAT1 deficiency on HFD-induced obesity, hepatic lipid accumulation, and insulin resistance. After HFD treatment, PLAAT1 deficiency caused a lower body weight gain compared to wild-type mice. Plaat1 mice also showed reduced liver weight with negligible hepatic lipid accumulation. In accordance with these findings, PLAAT1 deficiency improved HFD-induced hepatic dysfunction and lipid metabolism disorders. Lipidomics analysis in the liver revealed that in Plaat1 mice, the levels of various glycerophospholipids tended to increase, while all classes of lysophospholipids examined tended to decrease, suggesting that PLAAT1 functions as phospholipase A /A in the liver. Interestingly, the HFD treatment of wild-type mice significantly increased the mRNA level of PLAAT1 in the liver. Furthermore, the deficiency did not appear to elevate the risk of insulin resistance in contrast to PLAAT3 deficiency. These results suggested that the suppression of PLAAT1 improves HFD-induced overweight and concomitant hepatic lipid accumulation.
Topics: Animals; Mice; Diet, High-Fat; Insulin Resistance; Lipid Metabolism; Liver; Phospholipids; Phospholipases; Acyltransferases; Mice, Inbred C57BL
PubMed: 37330992
DOI: 10.1096/fj.202201033R -
Neuroscience and Biobehavioral Reviews Apr 2020Chronic stress and ageing are two of the most important factors that negatively affect cognitive processes such as learning and memory across the lifespan. To date,... (Review)
Review
Chronic stress and ageing are two of the most important factors that negatively affect cognitive processes such as learning and memory across the lifespan. To date, pharmacological agents have been insufficient in reducing the impact of both on brain health, and thus, novel therapeutic strategies are required. Recent research has focused on nutritional interventions to modify behaviour and reduce the deleterious consequences of both stress and ageing. In this context, emerging evidence indicate that phospholipids, a specific type of fat, are capable of improving a variety of cognitive processes in both animals and humans. The mechanisms underlying these positive effects are actively being investigated but as of yet are not fully elucidated. In this review, we summarise the preclinical and clinical studies available on phospholipid-based strategies for improved brain health across the lifespan. Moreover, we summarize the hypothesized direct and indirect mechanisms of action of these lipid-based interventions which may be used to promote resilience to stress and improve age-related cognitive decline in vulnerable populations.
Topics: Aging; Animals; Brain; Cognitive Dysfunction; Dietary Fats; Gastrointestinal Microbiome; Human Development; Humans; Hypothalamo-Hypophyseal System; Phospholipids; Stress, Psychological
PubMed: 31945391
DOI: 10.1016/j.neubiorev.2020.01.012 -
The British Journal of Nutrition Oct 2014Previous studies have suggested that long-chain n-3 fatty acids derived from seafood are associated with a lower risk of mortality, CHD and stroke. Whether α-linolenic...
Previous studies have suggested that long-chain n-3 fatty acids derived from seafood are associated with a lower risk of mortality, CHD and stroke. Whether α-linolenic acid (ALA, 18 : 3n-3), a plant-derived long-chain essential n-3 fatty acid, is associated with a lower risk of these outcomes is unclear. The aim of the present study was to examine the associations of plasma phospholipid and dietary ALA with the risk of mortality, CHD and stroke among older adults who participated in the Cardiovascular Health Study, a cohort study of adults aged ≥ 65 years. A total of 2709 participants were included in the plasma phospholipid ALA analysis and 2583 participants were included in the dietary ALA analysis. Cox regression was used to assess the associations of plasma phospholipid and dietary ALA with the risk of mortality, incident CHD and stroke. In minimally and multivariable-adjusted models, plasma phospholipid ALA was found to be not associated with the risk of mortality, incident CHD or stroke. After adjustment for age, sex, race, enrolment site, education, smoking status, diabetes, BMI, alcohol consumption, treated hypertension and total energy intake, higher dietary ALA intake was found to be associated with a lower risk of total and non-cardiovascular mortality; on comparing the highest quintiles of dietary ALA with the lowest quintiles, the HR for total mortality and non-cardiovascular mortality were found to be 0·73 (95 % CI 0·61, 0·88) and 0·64 (95 % CI 0·52, 0·80), respectively. Dietary ALA was found to be not associated with the risk of cardiovascular mortality, incident CHD or stroke. In conclusion, the results of the present suggest study that dietary ALA, but not plasma phospholipid ALA, is associated with a lower risk of total and non-cardiovascular mortality in older adults.
Topics: Aged; Cardiovascular Diseases; Cohort Studies; Coronary Disease; Diet; Female; Humans; Male; Mortality; Phospholipids; Proportional Hazards Models; Prospective Studies; Risk Factors; Stroke; United States; alpha-Linolenic Acid
PubMed: 25159901
DOI: 10.1017/S0007114514001925 -
Diabetes Care Feb 2021Islet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid n-3...
Interaction Between GAD65 Antibodies and Dietary Fish Intake or Plasma Phospholipid n-3 Polyunsaturated Fatty Acids on Incident Adult-Onset Diabetes: The EPIC-InterAct Study.
OBJECTIVE
Islet autoimmunity is associated with diabetes incidence. We investigated whether there was an interaction between dietary fish intake or plasma phospholipid n-3 polyunsaturated fatty acid (PUFA) concentration with the 65-kDa isoform of GAD (GAD65) antibody positivity on the risk of developing adult-onset diabetes.
RESEARCH DESIGN AND METHODS
We used prospective data on 11,247 incident cases of adult-onset diabetes and 14,288 noncases from the EPIC-InterAct case-cohort study conducted in eight European countries. Baseline plasma samples were analyzed for GAD65 antibodies and phospholipid n-3 PUFAs. Adjusted hazard ratios (HRs) for incident diabetes in relation to GAD65 antibody status and tertiles of plasma phospholipid n-3 PUFA or fish intake were estimated using Prentice-weighted Cox regression. Additive (proportion attributable to interaction [AP]) and multiplicative interactions between GAD65 antibody positivity (≥65 units/mL) and low fish/n-3 PUFA were assessed.
RESULTS
The hazard of diabetes in antibody-positive individuals with low intake of total and fatty fish, respectively, was significantly elevated (HR 2.52 [95% CI 1.76-3.63] and 2.48 [1.79-3.45]) compared with people who were GAD65 antibody negative and had high fish intake, with evidence of additive (AP 0.44 [95% CI 0.16-0.72] and 0.48 [0.24-0.72]) and multiplicative ( = 0.0465 and 0.0103) interactions. Individuals with high GAD65 antibody levels (≥167.5 units/mL) and low total plasma phospholipid n-3 PUFAs had a more than fourfold higher hazard of diabetes (HR 4.26 [2.70-6.72]) and an AP of 0.46 (0.12-0.80) compared with antibody-negative individuals with high n-3 PUFAs.
CONCLUSIONS
High fish intake or relative plasma phospholipid n-3 PUFA concentrations may partially counteract the increased diabetes risk conferred by GAD65 antibody positivity.
Topics: Adult; Animals; Cohort Studies; Diabetes Mellitus; Diet; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Humans; Phospholipids; Prospective Studies
PubMed: 33303636
DOI: 10.2337/dc20-1463 -
Nutrition Journal Oct 2017Previously, a "purchase" pattern (rich in vegetable oil, manufactured foods, red meat and poultry, fruits, and vegetables) was identified among adults in urban Ghana and...
BACKGROUND
Previously, a "purchase" pattern (rich in vegetable oil, manufactured foods, red meat and poultry, fruits, and vegetables) was identified among adults in urban Ghana and was inversely associated with T2D, while a "traditional" pattern (rich in fish, palm oil, plantain, green-leafy vegetables, beans, garden egg, fermented maize products,) increased the odds of T2D. To investigate, if specific fatty acids (FAs), partly reflecting the intakes of certain food groups and cooking methods, might explain the observed diet-disease relationships, serum phospholipid fatty acid profiles were characterized and their relationships with blood lipids that are common risk factors for T2D were analyzed.
METHODS
The relative proportions of 28 FAs (%) in 653 Ghanaians without T2D were measured by gas chromatography. In a cross-sectional analysis, the associations of FAs with dietary patterns and with serum lipids that are likely involved in T2D development were investigated. The FAs distributions across dietary pattern scores were examined. Standardized beta coefficients (β) were calculated for the associations of dietary pattern scores (per 1 standard deviation (SD) increase) with FAs. Across the tertiles of selected diet-related FAs, adjusted means of serum triglycerides, cholesterol, HDL-cholesterol and LDL-cholesterol were calculated.
RESULTS
In this mainly female (76%), middle-aged (mean age: 46.4, SD: 15.3 years) and predominately overweight study population (mean body mass index: 25.8, SD: 5.4 kg/m), saturated FAs (SFAs) contributed 52% to total serum FAs, n-6 polyunsaturated FAs (PUFAs) 27%, monounsaturated FAs 12%, n-3 PUFAs 9% and trans FAs (TFAs) <1%. The "purchase" pattern was related to lower proportions of n-3 PUFAs (β per 1 score SD: -0.25, p < 0.0001), but higher proportions of linoleic acid (LA) (β per 1 score SD: 0.24, p < 0.0001). The "traditional" pattern was characterized by lower proportions of arachidic acid (β per 1 score SD: -0.10, p = 0.001). LA was inversely associated with triglycerides, but positively with HDL-cholesterol and LDL-cholesterol.
CONCLUSIONS
In this Ghanaian population, serum FA profiles reflected the intake of key components of dietary patterns, such as fish and vegetable oil. FAs from manufactured foods (SFAs) and deep-fried meals (TFAs) did not contribute to the observed associations between dietary patterns and T2D. Still, LA might partly explain the health-beneficial effect of the "purchase" pattern.
Topics: Adult; Body Mass Index; Cholesterol; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diet; Fatty Acids; Fatty Acids, Monounsaturated; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Ghana; Humans; Male; Middle Aged; Phospholipids; Risk Factors; Trans Fatty Acids; Triglycerides
PubMed: 28969694
DOI: 10.1186/s12937-017-0286-x -
Diabetes Nov 2023Cell membrane phosphatidylcholine (PC) composition is regulated by lysophosphatidylcholine acyltransferase (LPCAT); changes in membrane PC saturation are implicated in...
Cell membrane phosphatidylcholine (PC) composition is regulated by lysophosphatidylcholine acyltransferase (LPCAT); changes in membrane PC saturation are implicated in metabolic disorders. Here, we identified LPCAT3 as the major isoform of LPCAT in adipose tissue and created adipocyte-specific Lpcat3-knockout mice to study adipose tissue lipid metabolism. Transcriptome sequencing and plasma adipokine profiling were used to investigate how LPCAT3 regulates adipose tissue insulin signaling. LPCAT3 deficiency reduced polyunsaturated PCs in adipocyte plasma membranes, increasing insulin sensitivity. LPCAT3 deficiency influenced membrane lipid rafts, which activated insulin receptors and AKT in adipose tissue, and attenuated diet-induced insulin resistance. Conversely, higher LPCAT3 activity in adipose tissue from ob/ob, db/db, and high-fat diet-fed mice reduced insulin signaling. Adding polyunsaturated PCs to mature human or mouse adipocytes in vitro worsened insulin signaling. We suggest that targeting LPCAT3 in adipose tissue to manipulate membrane phospholipid saturation is a new strategy to treat insulin resistance.
Topics: Humans; Animals; Mice; Phosphatidylcholines; Insulin Resistance; Adipose Tissue; Phospholipids; Insulin; Mice, Inbred C57BL; Diet, High-Fat; 1-Acylglycerophosphocholine O-Acyltransferase
PubMed: 37625119
DOI: 10.2337/db23-0317 -
Molecules (Basel, Switzerland) Nov 2017In this review paper, the latest literature on the functional properties of phospholipids in relation to inflammation and inflammation-related disorders has been... (Review)
Review
In this review paper, the latest literature on the functional properties of phospholipids in relation to inflammation and inflammation-related disorders has been critically appraised and evaluated. The paper is divided into three sections: presents an overview of the relationship between structures and biological activities (pro-inflammatory or anti-inflammatory) of several phospholipids with respect to inflammation. and are dedicated to the structures, functions, compositions and anti-inflammatory properties of dietary phospholipids from animal and marine sources. Most of the dietary phospholipids of animal origin come from meat, egg and dairy products. To date, there is very limited work published on meat phospholipids, undoubtedly due to the negative perception that meat consumption is an unhealthy option because of its putative associations with several chronic diseases. These assumptions are addressed with respect to the phospholipid composition of meat products. Recent research trends indicate that dairy phospholipids possess anti-inflammatory properties, which has led to an increased interest into their molecular structures and reputed health benefits. Finally, the structural composition of phospholipids of marine origin is discussed. Extensive research has been published in relation to ω-3 polyunsaturated fatty acids (PUFAs) and inflammation, however this research has recently come under scrutiny and has proved to be unreliable and controversial in terms of the therapeutic effects of ω-3 PUFA, which are generally in the form of triglycerides and esters. Therefore, this review focuses on recent publications concerning marine phospholipids and their structural composition and related health benefits. Finally, the strong nutritional value of dietary phospholipids are highlighted with respect to marine and animal origin and avenues for future research are discussed.
Topics: Animals; Anti-Inflammatory Agents; Aquatic Organisms; Dairy Products; Inflammation Mediators; Meat; Phospholipids; Structure-Activity Relationship
PubMed: 29135918
DOI: 10.3390/molecules22111964 -
World Journal of Gastroenterology Feb 2015Geographically the prevalence of duodenal ulceration is related to the staple foods in the diet in regions of developing countries where the diet is stable. It is higher... (Review)
Review
Geographically the prevalence of duodenal ulceration is related to the staple foods in the diet in regions of developing countries where the diet is stable. It is higher in regions where the diet is based on milled rice, refined wheat or maize, yams, cassava, sweet potato, or green bananas, and is lower in regions where the staple diet is based on unrefined wheat or maize, soya, certain millets or certain pulses. Experiments on rat gastric and duodenal ulcer models showed that it was the lipid fraction in staple foods from low prevalence areas that was protective against both gastric and duodenal ulceration, including ulceration due to non-steroidal anti-inflammatory drugs (NSAIDs). It also promoted ulcer healing. The lipid from the pulse, Dolichos biflorus, horse gram which was highly protective was used to identify the fractions with protective activity in the lipid. The protective activity lay in the phospholipid, sterol and sterol ester fractions. In the phospholipid fraction phosphatidyl choline (lethicin) and phosphatidyl ethanolamine (cephalin) were predominant. In the sterol fraction the sub-fractions showing protective activity contained β-sitosterol, stigmasterol, and an unidentified isomer of β-sitosterol. The evidence from animal models shows that certain dietary phospholipids and phytosterols have a protective action against gastroduodenal ulceration, both singly and in combination. This supports the protective role of staple diets in areas of low duodenal ulcer prevalence and may prove to be of importance in the prevention and treatment of duodenal ulceration and management of recurrent ulcers. A combination of phospholipids and phytosterols could also play an important role in protection against ulceration due to NSAIDs.
Topics: Animals; Cytoprotection; Diet; Dietary Fats; Dietary Fiber; Disease Models, Animal; Duodenal Ulcer; Duodenum; Gastric Mucosa; Phospholipids; Phytosterols; Plant Oils; Rats; Stomach; Stomach Ulcer
PubMed: 25663757
DOI: 10.3748/wjg.v21.i5.1377 -
Molecular Nutrition & Food Research Aug 2016Cardiolipin is a specialized phospholipid found primarily in the inner mitochondrial membrane. Because of its unique dimeric structure, cardiolipin plays an important... (Review)
Review
Cardiolipin is a specialized phospholipid found primarily in the inner mitochondrial membrane. Because of its unique dimeric structure, cardiolipin plays an important role in mitochondrial function, stability, and membrane fluidity. As such, cardiolipin is subject to a high degree of remodeling by phospholipases, acyltransferases, and transacylases that create a fatty acyl profile that tends to be highly tissue-specific. Despite this overarching regulation, the molecular species of cardiolipin produced are also influenced by dietary lipid composition. A number of studies have characterized the tissue-specific profile of cardiolipin species and have investigated the specific nature of cardiolipin remodeling, including the role of both enzymes and diet. The aim of this review is to highlight tissue specific differences in cardiolipin composition and, collectively, the enzymatic and dietary factors that contribute to these differences. Consequences of aberrant cardiolipin fatty acyl remodeling are also discussed.
Topics: Cardiolipins; Diet; Dietary Fats; Linoleic Acid; Membrane Fluidity; Mitochondria; Models, Biological; Oleic Acid; Phospholipids
PubMed: 27061349
DOI: 10.1002/mnfr.201500966 -
International Journal of Cancer Sep 2015The associations between intake of or circulating fatty acids and risk of colorectal cancer (CRC) are unclear. We examined prospectively the associations between dietary...
The associations between intake of or circulating fatty acids and risk of colorectal cancer (CRC) are unclear. We examined prospectively the associations between dietary or biomarker fatty acids and CRC. For 41,514 men and women, aged 40-69 years, baseline (1990-94) dietary intakes of fatty acids were estimated using a food frequency questionnaire and plasma phospholipid (PPL) fatty acids were measured for 4,205 participants including 395 CRC cases, according to a case-cohort design. Hazard ratios were computed using Cox regression adjusting for education, alcohol intake, smoking status, physical activity and total energy intake; and stratified for gender, ethnicity and family history of cancer, with age as the time scale. We assessed the heterogeneity of associations with colon and rectal cancers. PPL saturated fatty acids (SFAs) were positively associated with CRC risk, while total n-3 polyunsaturated fatty acids (PUFA) and long chain marine n-3 PUFAs showed inverse associations, significant only for 22:5 n-3. No significant associations were observed for dietary fatty acid intakes but positive associations with CRC of borderline significance were seen for both dietary and PPL linoleic acid. Positive associations with dietary palmitic acid (16:0), MUFAs and n-6 PUFAs were seen for rectal but not colon cancers. PPL 22:6 n-3 was inversely associated with rectal cancer. Limiting intakes of SFAs and MUFAs could be assisted by following existing guidelines to limit red and processed meats which are important sources in the Australian diet. Our observations regarding linoleic acid should be examined further.
Topics: Adult; Aged; Biomarkers; Case-Control Studies; Colorectal Neoplasms; Dietary Fats; Female; Humans; Male; Middle Aged; Nutrition Surveys; Phospholipids; Prospective Studies; Regression Analysis; Risk Factors
PubMed: 25683336
DOI: 10.1002/ijc.29479