-
Advances in Experimental Medicine and... 2020Plasmalogens (Pls) are one kind of phospholipids enriched in the brain and other organs. These lipids were thought to be involved in the membrane bilayer formation and... (Review)
Review
Plasmalogens (Pls) are one kind of phospholipids enriched in the brain and other organs. These lipids were thought to be involved in the membrane bilayer formation and anti-oxidant function. However, extensive studies revealed that Pls exhibit various beneficial biological activities including prevention of neuroinflammation, improvement of cognitive function, and inhibition of neuronal cell death. The biological activities of Pls were associated with the changes in cellular signaling and gene expression. Membrane-bound GPCRs were identified as possible receptors of Pls, suggesting that Pls might function as ligands or hormones. Aging, stress, and inflammatory stimuli reduced the Pls contents in cells, and addition of Pls inhibited inflammatory processes, which could suggest that reduction of Pls might be one of the risk factors for the diseases associated with inflammation. Oral ingestion of Pls showed promising health benefits among Alzheimer's disease (AD) patients, suggesting that Pls might have therapeutic potential in other neurodegenerative diseases.
Topics: Alzheimer Disease; Brain; Cell Death; Humans; Inflammation; Plasmalogens
PubMed: 33417215
DOI: 10.1007/978-3-030-60204-8_13 -
Metabolites Feb 2021Thermogenesis is an energy demanding process by which endotherms produce heat to maintain their body temperature in response to cold exposure. Mitochondria in the brown... (Review)
Review
Thermogenesis is an energy demanding process by which endotherms produce heat to maintain their body temperature in response to cold exposure. Mitochondria in the brown and beige adipocytes play a key role in thermogenesis, as the site for uncoupling protein 1 (UCP1), which allows for the diffusion of protons through the mitochondrial inner membrane to produce heat. To support this energy demanding process, the mitochondria in brown and beige adipocytes increase oxidation of glucose, amino acids, and lipids. This review article explores the various mitochondria-produced and processed lipids that regulate thermogenesis including cardiolipins, free fatty acids, and acylcarnitines. These lipids play a number of roles in thermogenic adipose tissue including structural support of UCP1, transcriptional regulation, fuel source, and activation of cell signaling cascades.
PubMed: 33671745
DOI: 10.3390/metabo11020124 -
Nature Communications Jul 2022Dysregulation of adipose tissue plasmalogen metabolism is associated with obesity-related metabolic diseases. We report that feeding mice a high-fat diet reduces adipose...
Dysregulation of adipose tissue plasmalogen metabolism is associated with obesity-related metabolic diseases. We report that feeding mice a high-fat diet reduces adipose tissue lysoplasmalogen levels and increases transmembrane protein 86 A (TMEM86A), a putative lysoplasmalogenase. Untargeted lipidomic analysis demonstrates that adipocyte-specific TMEM86A-knockout (AKO) increases lysoplasmalogen content in adipose tissue, including plasmenyl lysophosphatidylethanolamine 18:0 (LPE P-18:0). Surprisingly, TMEM86A AKO increases protein kinase A signalling pathways owing to inhibition of phosphodiesterase 3B and elevation of cyclic adenosine monophosphate. TMEM86A AKO upregulates mitochondrial oxidative metabolism, elevates energy expenditure, and protects mice from metabolic dysfunction induced by high-fat feeding. Importantly, the effects of TMEM86A AKO are largely reproduced in vitro and in vivo by LPE P-18:0 supplementation. LPE P-18:0 levels are significantly lower in adipose tissue of human patients with obesity, suggesting that TMEM86A inhibition or lysoplasmalogen supplementation might be therapeutic approaches for preventing or treating obesity-related metabolic diseases.
Topics: Adipocytes; Animals; Cyclic AMP-Dependent Protein Kinases; Diet, High-Fat; Energy Metabolism; Homeostasis; Humans; Hydrolases; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Plasmalogens; Thermogenesis
PubMed: 35835749
DOI: 10.1038/s41467-022-31805-3 -
Brain Research Bulletin Mar 2023Plasmalogens are a unique family of cellular glycerophospholipids that contain a vinyl-ether bond. Synthesis of plasmalogens is initiated in peroxisomes and completed in... (Review)
Review
Plasmalogens are a unique family of cellular glycerophospholipids that contain a vinyl-ether bond. Synthesis of plasmalogens is initiated in peroxisomes and completed in the endoplasmic reticulum. The absence of plasmalogens in several organs of patients with deficiency in peroxisome biogenesis suggests that de novo synthesis of plasmalogens contributes significantly to plasmalogen homeostasis in humans. Plasmalogen biosynthesis is spatiotemporally regulated by a feedback mechanism that senses the amount of plasmalogens in the inner leaflet of the plasma membrane and regulates the stability of fatty acyl-CoA reductase 1 (FAR1), the rate-limiting enzyme for plasmalogen biosynthesis. Dysregulation of plasmalogen synthesis impairs cholesterol synthesis in cells and brain, resulting in the reduced expression of genes such as mRNA encoding myelin basic protein, a phenotype found in the cerebellum of plasmalogen-deficient mice. In this review, we summarize the current knowledge of molecular mechanisms underlying the regulation of plasmalogen biosynthesis and the link between plasmalogen homeostasis and cholesterol biosynthesis, and address the pathogenesis of impaired plasmalogen homeostasis in rodent and humans.
Topics: Humans; Animals; Mice; Plasmalogens; Homeostasis; Cholesterol; Mammals
PubMed: 36720320
DOI: 10.1016/j.brainresbull.2023.01.011 -
Biochimica Et Biophysica Acta.... Sep 2021Studies of the lipidomes of twenty-one species of clostridia have revealed considerable diversity. Even among those species now defined as Clostridium sensu stricto,... (Review)
Review
Studies of the lipidomes of twenty-one species of clostridia have revealed considerable diversity. Even among those species now defined as Clostridium sensu stricto, which are related to Clostridium butyricum, the type species, lipid analysis has shown that a number of distinct clades have characteristic polar lipids. All species of Clostridium sensu stricto have phosphatidylethanolamine, phosphatidylglycerol and cardiolipin which are present as all acyl or alk-1'-enyl acyl (plasmalogen) species. In addition, almost every clade has specialized polar lipids. For example, the group closely related to Clostridium beijerinckii and several other solventogenic species has glycerol acetals of plasmenylethanolamine, which protects the membrane bilayer arrangement when the lipids are highly unsaturated or in the presence of solvents. The group related to Clostridium novyi has aminoacyl-phosphatidylglycerol, which protects these pathogens from cationic antimicrobial peptides (CAMPs) of innate immunity. Clostridium botulinum species, which fall into several groups, align with these clades, and have the same specific lipids. This review will present the current state of knowledge on clostridial lipids.
Topics: Clostridium; Lipidomics
PubMed: 33974975
DOI: 10.1016/j.bbalip.2021.158966 -
Frontiers in Physiology 2021It is becoming widely acknowledged that lipids play key roles in cellular function, regulating a variety of biological processes. Lately, a subclass of... (Review)
Review
It is becoming widely acknowledged that lipids play key roles in cellular function, regulating a variety of biological processes. Lately, a subclass of glycerophospholipids, namely plasmalogens, has received increased attention due to their association with several degenerative and metabolic disorders as well as aging. All these pathophysiological conditions involve chronic inflammatory processes, which have been linked with decreased levels of plasmalogens. Currently, there is a lack of full understanding of the molecular mechanisms governing the association of plasmalogens with inflammation. However, it has been shown that in inflammatory processes, plasmalogens could trigger either an anti- or pro-inflammation response. While the anti-inflammatory response seems to be linked to the entire plasmalogen molecule, its pro-inflammatory response seems to be associated with plasmalogen hydrolysis, ., the release of arachidonic acid, which, in turn, serves as a precursor to produce pro-inflammatory lipid mediators. Moreover, as plasmalogens comprise a large fraction of the total lipids in humans, changes in their levels have been shown to change membrane properties and, therefore, signaling pathways involved in the inflammatory cascade. Restoring plasmalogen levels by use of plasmalogen replacement therapy has been shown to be a successful anti-inflammatory strategy as well as ameliorating several pathological hallmarks of these diseases. The purpose of this review is to highlight the emerging role of plasmalogens in chronic inflammatory disorders as well as the promising role of plasmalogen replacement therapy in the treatment of these pathologies.
PubMed: 34744771
DOI: 10.3389/fphys.2021.730829 -
Molecular Metabolism Nov 2022Peroxisomes are single membrane-bound organelles named for their role in hydrogen peroxide production and catabolism. However, their cellular functions extend well... (Review)
Review
BACKGROUND
Peroxisomes are single membrane-bound organelles named for their role in hydrogen peroxide production and catabolism. However, their cellular functions extend well beyond reactive oxygen species (ROS) metabolism and include fatty acid oxidation of unique substrates that cannot be catabolized in mitochondria, and synthesis of ether lipids and bile acids. Metabolic functions of peroxisomes involve crosstalk with other organelles, including mitochondria, endoplasmic reticulum, lipid droplets and lysosomes. Emerging studies suggest that peroxisomes are important regulators of energy homeostasis and that disruption of peroxisomal functions influences the risk for obesity and the associated metabolic disorders, including type 2 diabetes and hepatic steatosis.
SCOPE OF REVIEW
Here, we focus on the role of peroxisomes in ether lipid synthesis, β-oxidation and ROS metabolism, given that these functions have been most widely studied and have physiologically relevant implications in systemic metabolism and obesity. Efforts are made to mechanistically link these cellular and systemic processes.
MAJOR CONCLUSIONS
Circulating plasmalogens, a form of ether lipids, have been identified as inversely correlated biomarkers of obesity. Ether lipids influence metabolic homeostasis through multiple mechanisms, including regulation of mitochondrial morphology and respiration affecting brown fat-mediated thermogenesis, and through regulation of adipose tissue development. Peroxisomal β-oxidation also affects metabolic homeostasis through generation of signaling molecules, such as acetyl-CoA and ROS that inhibit hydrolysis of stored lipids, contributing to development of hepatic steatosis. Oxidative stress resulting from increased peroxisomal β-oxidation-generated ROS in the context of obesity mediates β-cell lipotoxicity. A better understanding of the roles peroxisomes play in regulating and responding to obesity and its complications will provide new opportunities for their treatment.
Topics: Acetyl Coenzyme A; Bile Acids and Salts; Diabetes Mellitus, Type 2; Ethers; Fatty Acids; Homeostasis; Humans; Hydrogen Peroxide; Obesity; Plasmalogens; Reactive Oxygen Species
PubMed: 35988716
DOI: 10.1016/j.molmet.2022.101577 -
Molecules (Basel, Switzerland) Aug 2023Aging increases oxidative and inflammatory stress caused by a reduction in metabolism and clearance, thus leading to the development of age-associated diseases. The... (Review)
Review
Aging increases oxidative and inflammatory stress caused by a reduction in metabolism and clearance, thus leading to the development of age-associated diseases. The quality of our daily diet and exercise is important for the prevention of these diseases. Marine resources contain various valuable nutrients, and unique glycerophospholipid plasmalogens are found abundantly in some marine invertebrates, including ascidians. One of the major classes, the ethanolamine class (PlsEtn), exists in a high ratio to phospholipids in the brain and blood, while decreased levels have been reported in patients with age-associated diseases, including Alzheimer's disease. Animal studies have shown that the administration of marine PlsEtn prepared from marine invertebrates improved PlsEtn levels in the body and alleviated inflammation. Animal and human studies have reported that marine PlsEtn ameliorates cognitive impairment. In this review, we highlight the biological significance, relationships with age-associated diseases, food functions, and healthcare materials of plasmalogens based on recent knowledge and discuss the contribution of marine plasmalogens to health maintenance in aging.
Topics: Animals; Humans; Plasmalogens; Brain; Cognitive Dysfunction; Aging; Alzheimer Disease
PubMed: 37687157
DOI: 10.3390/molecules28176328 -
Trends in Endocrinology and Metabolism:... Oct 2019The global prevalence of obesity continues to increase, suggesting a need for alternative treatment approaches. Targeting brown fat function to promote energy... (Review)
Review
The global prevalence of obesity continues to increase, suggesting a need for alternative treatment approaches. Targeting brown fat function to promote energy expenditure represents one such approach. Brown adipocytes and the related beige adipocytes oxidize fatty acids and glucose to generate heat and are activated by cold exposure or consumption of high-calorie diets. Alternative, more practical means to activate thermogenic fat are needed. Here, we review emerging data suggesting new roles for lipids in activating thermogenesis that extend beyond their serving as a fuel source for heat generation. Lipids have also been implicated in mediating interorgan communication, crosstalk between organelles, and cellular signaling regulating thermogenesis. Understanding how lipids regulate thermogenesis could identify innovative therapeutic interventions for obesity.
Topics: Adipose Tissue, Beige; Animals; Humans; Mitochondria; Obesity; Plasmalogens; Thermogenesis
PubMed: 31422871
DOI: 10.1016/j.tem.2019.07.020 -
Biochimica Et Biophysica Acta May 2016Peroxisomes are dynamic organelles that play an essential role in a variety of cellular catabolic and anabolic metabolic pathways, including fatty acid alpha- and... (Review)
Review
Peroxisomes are dynamic organelles that play an essential role in a variety of cellular catabolic and anabolic metabolic pathways, including fatty acid alpha- and beta-oxidation, and plasmalogen and bile acid synthesis. Defects in genes encoding peroxisomal proteins can result in a large variety of peroxisomal disorders either affecting specific metabolic pathways, i.e., the single peroxisomal enzyme deficiencies, or causing a generalized defect in function and assembly of peroxisomes, i.e., peroxisome biogenesis disorders. In this review, we discuss the clinical, biochemical, and genetic aspects of all human peroxisomal disorders currently known.
Topics: ATPases Associated with Diverse Cellular Activities; Fatty Acids; Gene Expression Regulation; Humans; Membrane Proteins; Metabolic Networks and Pathways; Mutation; Organelle Biogenesis; Oxidation-Reduction; Peroxisomal Disorders; Peroxisomes; Plasmalogens; Protein Isoforms; Protein Sorting Signals; Protein Transport; Signal Transduction
PubMed: 26611709
DOI: 10.1016/j.bbamcr.2015.11.015