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Biochemical Society Transactions Oct 2015Bile is synthesized in the liver and is essential for the emulsification of dietary lipids and lipid-soluble vitamins. It is a complex mixture of amphiphilic bile acids... (Review)
Review
Bile is synthesized in the liver and is essential for the emulsification of dietary lipids and lipid-soluble vitamins. It is a complex mixture of amphiphilic bile acids (BAs; which act as detergent molecules), the membrane phospholipid phosphatidylcholine (PC), cholesterol and a variety of endogenous metabolites and waste products. Over the last 20 years, the combined effort of clinicians, geneticists, physiologists and biochemists has shown that each of these bile components is transported across the canalicular membrane of the hepatocyte by its own specific ATP-binding cassette (ABC) transporter. The bile salt export pump (BSEP) ABCB11 transports the BAs and drives bile flow from the liver, but it is now clear that two lipid transporters, ABCB4 (which flops PC into the bile) and the P-type ATPase ATP8B1/CDC50 (which flips a different phospholipid in the opposite direction) play equally critical roles that protect the biliary tree from the detergent activity of the bile acids. Understanding the interdependency of these lipid floppases and flippases has allowed the development of an assay to measure ABCB4 function. ABCB4 harbours numerous mis-sense mutations which probably reflects the spectrum of liver disease rooted in ABCB4 aetiology. Characterization of the effect of these mutations at the protein level opens the possibility for the development of personalized prognosis and treatment.
Topics: ATP-Binding Cassette Transporters; Animals; Bile Acids and Salts; Biological Transport; Humans; Lipid Bilayers; Liver; Liver Diseases; Models, Biological; Mutation; Phospholipids
PubMed: 26517915
DOI: 10.1042/BST20150132 -
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 -
Molecules (Basel, Switzerland) Sep 2018The worldwide demographical trend is changing towards a more elderly population. In particular, this phenomenon is increasing the number of neurodegenerative disease... (Review)
Review
The worldwide demographical trend is changing towards a more elderly population. In particular, this phenomenon is increasing the number of neurodegenerative disease cases (e.g., Alzheimer's disease) in advanced countries. Therefore, there is a fertile field for neuroprotective approaches to address this problem. A useful strategy to protect the membrane integrity of cells and reduce inflammatory processes. In this context, the neurons represent particularly vulnerable cells. Thus, a protection strategy should include their membrane preservation and improved anti-inflammatory processes. The contribution of phospholipid derivatives to this issue is crucial and many articles evidence their role in both health and disease. On the other hand, some lipids containing choline actively participate to increase the choline levels in the nervous system. It is acknowledged that the cholinergic system plays a pivotal role both in the central and in the peripheral nervous system. Neurons cannot synthesize choline, which is provided by the diet. The reuptake of ACh and its hydrolysis represent the principal source of choline. Therefore, to cover choline needs, choline-containing lipids may be used. There are different works which demonstrate their neuroprotective features This review article analyzes phospholipid and lipid derivatives that through different mechanisms are involved in these protective processes, although, sometimes the same molecules may behave as neurotoxic elements, therefore, their protective machinery should be detailed better.
Topics: Animals; Cholesterol; Choline; Humans; Lipids; Membrane Lipids; Neurons; Neuroprotection; Neuroprotective Agents; Phospholipids; Receptors, Lysosphingolipid; Sphingosine
PubMed: 30189584
DOI: 10.3390/molecules23092257 -
Nutrients Oct 2018Choline, an essential dietary nutrient for humans, is required for the synthesis of the neurotransmitter, acetylcholine, the methyl group donor, betaine, and... (Review)
Review
Choline, an essential dietary nutrient for humans, is required for the synthesis of the neurotransmitter, acetylcholine, the methyl group donor, betaine, and phospholipids; and therefore, choline is involved in a broad range of critical physiological functions across all stages of the life cycle. The current dietary recommendations for choline have been established as Adequate Intakes (AIs) for total choline; however, dietary choline is present in multiple different forms that are both water-soluble (e.g., free choline, phosphocholine, and glycerophosphocholine) and lipid-soluble (e.g., phosphatidylcholine and sphingomyelin). Interestingly, the different dietary choline forms consumed during infancy differ from those in adulthood. This can be explained by the primary food source, where the majority of choline present in human milk is in the water-soluble form, versus lipid-soluble forms for foods consumed later on. This review summarizes the current knowledge on dietary recommendations and assessment methods, and dietary choline intake from food sources across the life cycle.
Topics: Acetylcholine; Adult; Betaine; Choline; Diet; Eating; Human Development; Humans; Infant; Milk, Human; Nutritional Requirements; Phospholipids
PubMed: 30332744
DOI: 10.3390/nu10101513 -
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 -
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 -
Nutrients Jul 2022Over the last few years, the vegan diet has become increasingly popular in Germany. It has been proposed that this diet is generally lower in fat, but less is known...
Over the last few years, the vegan diet has become increasingly popular in Germany. It has been proposed that this diet is generally lower in fat, but less is known about the impact on fatty acid (FA) profiles. Therefore, the cross-sectional “Risks and Benefits of a Vegan Diet” (RBVD) study (n = 72) was used to investigate dietary FA intake as well as plasma phospholipid FA in vegans (n = 36) compared to omnivores (n = 36). Vegans had a significantly lower dietary intake of total fat (median 86 g/day, IQR 64−111) in comparison to omnivores (median 104 g/day, IQR 88−143, p = 0.004). Further, vegans had a lower intake of saturated fatty acids (SFA) (p < 0.0001) and monounsaturated fatty acids (MUFA) (p = 0.001) compared to omnivores. Vegans had a higher intake in total polyunsaturated fatty acids (PUFA), omega-3 and omega-6 PUFA compared to omnivores, but without statistical significance after Bonferroni correction. According to plasma phospholipid profiles, relatively lower proportions of SFA (p < 0.0001), total trans fatty acids (TFA) (p = 0.0004) and omega-3-FA (p < 0.0001), but higher proportions of omega-6-FA (p < 0.0001) were observed in vegans. With the exception of omega-3 PUFA, a vegan diet is associated with a more favorable dietary fat intake and more favorable plasma FA profiles and therefore may reduce cardiovascular risk.
Topics: Cross-Sectional Studies; Diet; Diet, Vegan; Dietary Fats; Fatty Acids; Fatty Acids, Omega-3; Humans; Phospholipids; Risk Assessment; Vegans
PubMed: 35889855
DOI: 10.3390/nu14142900 -
Nutrients Apr 2015Eggs are a major source of phospholipids (PL) in the Western diet. Dietary PL have emerged as a potential source of bioactive lipids that may have widespread effects on... (Review)
Review
Eggs are a major source of phospholipids (PL) in the Western diet. Dietary PL have emerged as a potential source of bioactive lipids that may have widespread effects on pathways related to inflammation, cholesterol metabolism, and high-density lipoprotein (HDL) function. Based on pre-clinical studies, egg phosphatidylcholine (PC) and sphingomyelin appear to regulate cholesterol absorption and inflammation. In clinical studies, egg PL intake is associated with beneficial changes in biomarkers related to HDL reverse cholesterol transport. Recently, egg PC was shown to be a substrate for the generation of trimethylamine N-oxide (TMAO), a gut microbe-dependent metabolite associated with increased cardiovascular disease (CVD) risk. More research is warranted to examine potential serum TMAO responses with chronic egg ingestion and in different populations, such as diabetics. In this review, the recent basic science, clinical, and epidemiological findings examining egg PL intake and risk of CVD are summarized.
Topics: Animals; Biomarkers; Cardiovascular Diseases; Cardiovascular System; Cholesterol, HDL; Diet; Eggs; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Lipid Metabolism; Methylamines; Models, Animal; Phospholipids; Randomized Controlled Trials as Topic
PubMed: 25871489
DOI: 10.3390/nu7042731 -
Nutrients May 2018Since the Seven Countries Study, dietary cholesterol and the levels of serum cholesterol in relation to the development of chronic diseases have been somewhat demonised.... (Review)
Review
Since the Seven Countries Study, dietary cholesterol and the levels of serum cholesterol in relation to the development of chronic diseases have been somewhat demonised. However, the principles of the Mediterranean diet and relevant data linked to the examples of people living in the five blue zones demonstrate that the key to longevity and the prevention of chronic disease development is not the reduction of dietary or serum cholesterol but the control of systemic inflammation. In this review, we present all the relevant data that supports the view that it is inflammation induced by several factors, such as platelet-activating factor (PAF), that leads to the onset of cardiovascular diseases (CVD) rather than serum cholesterol. The key to reducing the incidence of CVD is to control the activities of PAF and other inflammatory mediators via diet, exercise, and healthy lifestyle choices. The relevant studies and data supporting these views are discussed in this review.
Topics: Cholesterol; Chronic Disease; Diet, Healthy; Diet, Mediterranean; Exercise; Health Behavior; Humans; Incidence; Inflammation; Life Style; Observational Studies as Topic; Platelet Activating Factor; Risk Factors
PubMed: 29757226
DOI: 10.3390/nu10050604