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Biochimie Dec 2019The research literature on atherosclerosis includes findings investigating the atherosclerotic effect of oxysterols, which are the oxidation products of cholesterol; and... (Review)
Review
The research literature on atherosclerosis includes findings investigating the atherosclerotic effect of oxysterols, which are the oxidation products of cholesterol; and the literature on oxysterols refers to mechanisms by which oxysterols cause phospholipid packing defects in cell membranes. This review synthesizes these two bodies of research findings to describe how oxysterols cause phospholipid packing defects within the membranes of vascular endothelial cells, potentially increasing cell permeability of low-density lipoprotein cholesterol which may lead to atheroma formation. Exogenous sources of oxysterols are provided by dietary intake of animal-based foods that contain cholesterol oxidation products. This review proposes an explanation for the anti-atherosclerotic effect of plant-based dietary patterns, which is attributed to restriction or avoidance of dietary oxysterol intake from animal-based foods. Furthermore, raw-milk cheeses play an important role in the traditional French diet-low oxysterol content in these unheated foods may contribute to the French paradox, in which reduced coronary heart disease is associated with a diet high in saturated fat and cholesterol.
Topics: Atherosclerosis; Cholesterol, LDL; Diet; Endothelial Cells; Humans; Membranes; Oxidation-Reduction; Oxysterols; Phospholipids; Phytochemicals
PubMed: 31586653
DOI: 10.1016/j.biochi.2019.09.020 -
FASEB Journal : Official Publication of... Nov 2023Previous studies have revealed that membrane phospholipid composition controlled by lysophosphatidylcholine acyltransferase 3 (LPCAT3) is involved in the development of...
Previous studies have revealed that membrane phospholipid composition controlled by lysophosphatidylcholine acyltransferase 3 (LPCAT3) is involved in the development of insulin resistance in type 2 diabetes. In this study, we aimed to investigate the therapeutic potential of targeting Lpcat3 in the treatment of insulin resistance in diabetic mouse models. Lpcat3 expression was suppressed in the whole body by antisense oligonucleotides (ASO) injection or in the liver by adeno-associated virus (AAV)-encoded Cre in high-fat diet (HFD)-induced and genetic ob/ob type 2 diabetic mouse models. Glucose tolerance test (GTT), insulin tolerance test (ITT), fasting blood glucose, and insulin levels were used to assess insulin sensitivity. Lipid levels in the liver and serum were measured. The expression of genes involved in de novo lipogenesis was analyzed by real-time RT-PCR. Metabolic rates were measured by indirect calorimetry using the Comprehensive Lab Animal Monitoring System (CLAMS). Our data demonstrate that acute knockout of hepatic Lpcat3 by AAV-Cre improves both hyperglycemia and hypertriglyceridemia in HFD-fed mice. Similarly, whole-body ablation of Lpcat3 by ASO administration improves obesity and insulin resistance in both HFD-fed and ob/ob mice. These findings demonstrate that targeting LPCAT3 could be a novel therapy for insulin resistance.
Topics: Mice; Animals; Insulin Resistance; Phospholipids; Diabetes Mellitus, Type 2; Liver; Disease Models, Animal; Diet, High-Fat; Insulins; Mice, Inbred C57BL; Insulin; 1-Acylglycerophosphocholine O-Acyltransferase
PubMed: 37823674
DOI: 10.1096/fj.202301122RR -
The British Journal of Nutrition Jul 2022The results of epidemiological studies involving -3 PUFA and polycystic ovary syndrome (PCOS) are scarce. This matched case-control study assessed the associations...
The results of epidemiological studies involving -3 PUFA and polycystic ovary syndrome (PCOS) are scarce. This matched case-control study assessed the associations between -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 -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 -3 PUFA, 0·60 (0·38, 0·92) for long-chain -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 -3 PUFA, significant inverse associations were found only for long-chain -3 PUFA ( = 0·001), EPA ( = 0·047) and DHA ( = 0·030). Both dietary and serum -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 -3 PUFA, especially long-chain -3 PUFA, and PCOS prevalence. Higher intakes of -3 PUFA might be considered a protective factor for PCOS among Chinese females.
Topics: Female; Humans; Polycystic Ovary Syndrome; Case-Control Studies; Fatty Acids, Omega-3; Diet; Phospholipids
PubMed: 34372961
DOI: 10.1017/S0007114521003007 -
Advances in Experimental Medicine and... 2020Lipids constitute almost 60% of the brain's dry weight, and they are thought to be involved in inflammation, neurotransmission and synaptic plasticity. The brain mostly... (Review)
Review
Lipids constitute almost 60% of the brain's dry weight, and they are thought to be involved in inflammation, neurotransmission and synaptic plasticity. The brain mostly contains sphingolipids, glycerophospholipids and cholesterol which are abundant in myelin and neuronal membranes. The recent rise of the promising area of lipidomic data can be used as a diagnosing tool at the early stages of Alzheimer's disease allowing novel therapeutic targets. In this review, altered lipid metabolites as well as the impact of diet in the progress of Alzheimer's disease (AD) are analyzed.
Topics: Alzheimer Disease; Diet; Glycerophospholipids; Humans; Lipidomics; Lipids; Sphingolipids
PubMed: 32468464
DOI: 10.1007/978-3-030-32633-3_14 -
Nutrients May 2021Dietary intakes of polyunsaturated, monounsaturated and saturated fatty acids (FAs) have been inconsistently associated with puberty timing. We examined longitudinal...
Dietary intakes of polyunsaturated, monounsaturated and saturated fatty acids (FAs) have been inconsistently associated with puberty timing. We examined longitudinal associations of prepubertal dietary and plasma phospholipid FAs with several puberty timing traits in boys and girls. In the Avon Longitudinal Study of Parents and Children, prepubertal fat intakes at 3-7.5 years and plasma phospholipid FAs at 7.5 years were measured. Timings of Tanner stage 2 genital or breast development and voice breaking or menarche from repeated reports at 8-17 years, and age at peak height velocity (PHV) from repeated height measurements at 5-20 years were estimated. In linear regression models with adjustment for maternal and infant characteristics, dietary substitution of polyunsaturated FAs for saturated FAs, and higher concentrations of dihomo-γ-linolenic acid (20:3n6) and palmitoleic acid (16:1n7) were associated with earlier timing of puberty traits in girls ( = 3872) but not boys ( = 3654). In Mendelian Randomization models, higher genetically predicted circulating dihomo-γ-linolenic acid was associated with earlier menarche in girls. Based on repeated dietary intake data, objectively measured FAs and genetic causal inference, these findings suggest that dietary and endogenous metabolic pathways that increase plasma dihomo-γ-linolenic acid, an intermediate metabolite of n-6 polyunsaturated FAs, may promote earlier puberty timing in girls.
Topics: Adolescent; Adult; Age Factors; Child; Child, Preschool; Cohort Studies; Diet; Fatty Acids; Female; Humans; Longitudinal Studies; Male; Mendelian Randomization Analysis; Phospholipids; Puberty; Time; Young Adult
PubMed: 34070864
DOI: 10.3390/nu13061868 -
Journal of Lipid Research Aug 2023Acute kidney injury (AKI) is a global public health concern with high mortality and morbidity. In ischemic-reperfusion injury (IRI), a main cause of AKI, the brush...
Acute kidney injury (AKI) is a global public health concern with high mortality and morbidity. In ischemic-reperfusion injury (IRI), a main cause of AKI, the brush border membrane of S3 proximal tubules (PT) is lost to the tubular lumen. How injured tubules reconstitute lost membrane lipids during renal recovery is not known. Here, we identified Mfsd2a, a sodium-dependent lysophosphatidylcholine (LPC) transporter, to be expressed specifically in the basolateral membrane of S3 PT. Using an in vivo activity probe for Mfsd2a, transport activity was found to be specific to the S3 PT. Mice with haploinsufficiency of Mfsd2a exhibited delayed recovery of renal function after acute IRI, with depressed urine osmolality and elevated levels of histological markers of damage, fibrosis, and inflammation, findings corroborated by transcriptomic analysis. Lipidomics revealed a deficiency in docosahexaenoic acid (DHA) containing phospholipids in Mfsd2a haploinsufficiency. Treatment of Mfsd2a haploinsufficient mice with LPC-DHA improved renal function and reduced markers of injury, fibrosis, and inflammation. Additionally, LPC-DHA treatment restored S3 brush border membrane architecture and normalized DHA-containing phospholipid content. These findings indicate that Mfsd2a-mediated transport of LPC-DHA is limiting for renal recovery after AKI and suggest that LPC-DHA could be a promising dietary supplement for improving recovery following AKI.
Topics: Mice; Animals; Symporters; Membrane Transport Proteins; Docosahexaenoic Acids; Acute Kidney Injury; Phospholipids; Kidney
PubMed: 37467896
DOI: 10.1016/j.jlr.2023.100416 -
Journal of Animal Physiology and Animal... Jul 2023Milk fat globules (MFGs) surround the triacylglycerol core that composes milk fat. The aim of this study is to induce milk fat depression via dietary conjugated...
Milk fat globules (MFGs) surround the triacylglycerol core that composes milk fat. The aim of this study is to induce milk fat depression via dietary conjugated linoleic acid (CLA) supplementation to study MFG size parameters, number and glycerophospholipid composition. Eighteen Holstein dairy cows (136 ± 28 days in milk, 571 ± 37.9 kg body weight, 27.6 ± 2.1 kg milk/day) were selected and randomly assigned to a control or CLA group for a 14-day period. Cows were fed a basal diet (control, n = 8) or the control plus 400 g/day CLA (C18:2 cis-9, trans-11 38.1% and C18:2 trans-10, cis-12 36.8%) (n = 10) for 7 days after which the CLA group was switched to the basal diet for another 7 days along with the control group. Cow performance, milk composition, MFG size and numbers were measured daily. On the seventh day after the start of the experiment, milk samples were identified and the quantification of glycerophospholipid compounds, and RNA were isolated from milk fat samples for a real-time polymerase chain reaction. Compared with control, at Day 7 from the start of feeding, supplemental CLA did not affect milk production (28.09 vs. 28.50 kg/day), dry matter intake (14.9 vs. 15.4 kg/day), or milk protein (3.55/100 vs. 3.70 g/100 ml) and lactose contents (5.11/100 vs. 5.17 g/100 ml). However, although the specific surface area of MFG (2138 vs. 1815 m²/kg) was greater, CLA reduced milk fat content (1.95/100 vs 3.64 g/100 ml on Day 7) and particle size parameters of MFG. The number of MFG gradually decreased until Day 7 of feeding, and then increased by Day 14 (2.96 × 10 on Day 1, 1.63 × 10 on Day 7 and 2.28 × 10 on Day 14) in the CLA group. Compared with control, glycerophospholipid analysis revealed that concentrations of phosphatidylcholine (PC) (e.g., PC [16:0/18:1] 20322 vs. 29793 nmol/L), lysophosphatidylethanolamine (LPE) (e.g., LPE [18:1] 956 vs. 4610 nmol/L) and phosphatidylethanolamine (PE) (e.g., PE [16:0/18:1] 7000 vs. 9769 nmol/L) in milk lipids decreased during CLA feeding. In contrast, concentrations of phosphatidylinositol (PI) (e.g., PI [18:0/18:1] 4052 vs. 1799 nmol/L) and phosphatidylserine (PS) (e.g., PS [18:1/18:2] 9500 vs. 6843 nmol/L) increased. The messenger RNA abundance of fatty acid synthase, diacylglycerol O-acyltransferase 1, glycerol-3-phosphate acyltransferase 4 and phosphate cytidylyltransferase 1, choline, alpha (PCYT1A) were downregulated in the CLA group, confirming published data demonstrating a negative effect of CLA on lipogenesis in the mammary gland. Overall, these results provided evidence for the important role of lipogenic gene expression in the regulation of MFG size, number and glycerophospholipid composition.
Topics: Female; Animals; Cattle; Linoleic Acids, Conjugated; Lactation; Fatty Acids; Phospholipids; Diet; Glycerophospholipids; Dietary Supplements
PubMed: 36353940
DOI: 10.1111/jpn.13788 -
Clinical Nutrition (Edinburgh, Scotland) Jul 2023Diet and weight loss affect circulating metabolome. However, metabolite profiles induced by different weight loss maintenance diets and underlying longer term weight...
BACKGROUND & AIMS
Diet and weight loss affect circulating metabolome. However, metabolite profiles induced by different weight loss maintenance diets and underlying longer term weight loss maintenance remain unknown. Herein, we investigated after-weight-loss metabolic signatures of two isocaloric 24-wk weight maintenance diets differing in satiety value due to dietary fibre, protein and fat contents and identified metabolite features that associated with successful weight loss maintenance.
METHODS
Non-targeted LC-MS metabolomics approach was used to analyse plasma metabolites of 79 women and men (mean age ± SD 49.7 ± 9.0 years; BMI 34.2 ± 2.5 kg/m) participating in a weight management study. Participants underwent a 7-week very-low-energy diet (VLED) and were thereafter randomised into two groups for a 24-week weight maintenance phase. Higher satiety food (HSF) group consumed high-fibre, high-protein, and low-fat products, while lower satiety food (LSF) group consumed isocaloric low-fibre products with average protein and fat content as a part of their weight maintenance diets. Plasma metabolites were analysed before the VLED and before and after the weight maintenance phase. Metabolite features discriminating HSF and LSF groups were annotated. We also analysed metabolite features that discriminated participants who maintained ≥10% weight loss (HWM) and participants who maintained <10% weight loss (LWM) at the end of the study, irrespective of the diet. Finally, we assessed robust linear regression between metabolite features and anthropometric and food group variables.
RESULTS
We annotated 126 metabolites that discriminated the HSF and LSF groups and HWM and LWM groups (p < 0.05). Compared to LSF, the HSF group had lower levels of several amino acids, e.g. glutamine, arginine, and glycine, short-, medium- and long-chain acylcarnitines (CARs), odd- and even-chain lysoglycerophospholipids, and higher levels of fatty amides. Compared to LWM, the HWM group in general showed higher levels of glycerophospholipids with a saturated long-chain and a C20:4 fatty acid tail, and unsaturated free fatty acids (FFAs). Changes in several saturated odd- and even-chain LPCs and LPEs and fatty amides were associated with the intake of many food groups, particularly grain and dairy products. Increase in several (lyso)glycerophospholipids was associated with decrease in body weight and adiposity. Increased short- and medium-chain CARs were related to decreased body fat-free mass.
CONCLUSIONS
Our results show that isocaloric weight maintenance diets differing in dietary fibre, protein, and fat content affected amino acid and lipid metabolism. Increased abundances of several phospholipid species and FFAs were related with greater weight loss maintenance. Our findings indicate common and distinct metabolites for weight and dietary related variables in the context of weight reduction and weight management. The study was registered in isrctn.org with identifier 67529475.
Topics: Male; Humans; Female; Dietary Fats; Diet; Diet, Reducing; Dietary Fiber; Metabolome; Weight Loss
PubMed: 37268538
DOI: 10.1016/j.clnu.2023.05.011 -
Prostaglandins, Leukotrienes, and... Jul 2020Information regarding circulating fatty acids (FA) in association with metabolic health in black Africans is scarce, while the usefulness of circulating FAs as... (Comparative Study)
Comparative Study
BACKGROUND
Information regarding circulating fatty acids (FA) in association with metabolic health in black Africans is scarce, while the usefulness of circulating FAs as biomarkers of dietary fat intake and predictors for medical conditions is increasing.
OBJECTIVE
We compared eleven dietary and the levels of 26 plasma phospholipid FAs in metabolically healthy and unhealthy phenotypes in black South African adults.
METHODS
Adults from the South African arm of the Prospective Urban and Rural Epidemiology study baseline (n = 711) were categorised into four groups, namely normal weight without metabolic syndrome (MetS) (MHNW), normal weight with MetS (MUNW), metabolically healthy overweight/obese (MHO) and metabolically unhealthy overweight/obese (MUO). Dietary and plasma phospholipid FAs were measured by a quantitative food frequency questionnaire and gas chromatography-tandem mass spectrometry, respectively. We compared dietary FAs, plasma phospholipid FAs, and estimated desaturase activity between the metabolic status groups using ANCOVA adjusted for age and energy intake.
RESULTS
MetS was diagnosed in 35% of the participants. After adjustment for age and total energy intake, in comparison to the MHNW reference group, saturated dietary FAs (C14:0 to C18:0) and alpha-linolenic acid intakes were higher in both overweight/obese groups (MHO and MUO), while linoleic acid intakes were higher in the MUO group only. Plasma levels of most saturated FAs (C18:0 to C22:0) and PUFAs were higher, whereas selected MUFAs, palmitic acid, and estimated desaturase activities were lower in the overweight/obese groups.
CONCLUSIONS
The overweight groups generally had higher fat intakes than normal-weight groups, but lower plasma levels of palmitic, palmitoleic, oleic, cis-vaccenic and estimated desaturase activities. Therefore, in this population, lower plasma levels of palmitic, palmitoleic, oleic, and cis-vaccenic acids and decreased estimated desaturase activities may be biomarkers of abnormal metabolic health in overweight/obese study participants.
Topics: Adult; Case-Control Studies; Cross-Sectional Studies; Dietary Fats; Fatty Acids; Female; Gas Chromatography-Mass Spectrometry; Humans; Male; Metabolic Syndrome; Middle Aged; Overweight; Phospholipids; Prospective Studies; South Africa
PubMed: 31780327
DOI: 10.1016/j.plefa.2019.102039 -
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