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Biochemical Pharmacology Nov 2022The endocannabinoids 2-arachidonoyl-glycerol (2-AG) and N-arachidonoyl-ethanolamine (AEA) are eicosanoids implicated in numerous physiological processes like appetite,... (Review)
Review
The endocannabinoids 2-arachidonoyl-glycerol (2-AG) and N-arachidonoyl-ethanolamine (AEA) are eicosanoids implicated in numerous physiological processes like appetite, adipogenesis, inflammatory pain and inflammation. They mediate most of their physiological effects by activating the cannabinoid (CB) receptors 1 and 2. Other than directly binding to the CB receptors, 2-AG and AEA are also metabolized by most eicosanoid biosynthetic enzymes, yielding many metabolites that are part of the oxyendocannabinoidome. Some of these metabolites have been found in vivo, have the ability to modulate specific receptors and thus potentially influence physiological processes. In this review, we discuss the biosynthesis and metabolism of 2-AG and AEA, as well as their congeners from the monoacyl-glycerol and N-acyl-ethanolamine families, with a special focus on the metabolism by oxygenases involved in arachidonic acid metabolism. We highlight the knowledge gaps in our understanding of the regulation and roles the oxyendocannabinoidome mediators.
Topics: Humans; Endocannabinoids; Glycerides; Monoglycerides; Arachidonic Acid; Glycerol; Polyunsaturated Alkamides; Ethanolamines; Cannabinoids; Oxygenases
PubMed: 36152677
DOI: 10.1016/j.bcp.2022.115261 -
Nutrients Sep 2019There is mounting evidence that the consumption of fermented dairy products such as cheese and yoghurt is associated with a reduced risk of type II diabetes. This effect... (Comparative Study)
Comparative Study
There is mounting evidence that the consumption of fermented dairy products such as cheese and yoghurt is associated with a reduced risk of type II diabetes. This effect is greater than in fresh milk and differs between cheese and yoghurt. However, the molecular components responsible for the effect are not known. We tested the hypothesis that the lipid and/or glyceride profiles of yoghurts and cheeses are distinct from one another and fresh milk. We developed a novel sample preparation technique for high-fat samples that can be used with Direct Infusion-Mass Spectrometry. We found that the lipid and glyceride profiles of cheddars from the UK, Ireland and France, and hard cheeses from Sweden and Italy were similar to one another but distinct from unfermented dairy products. The lipid and glyceride profile of yoghurts was varied and included types that may be similar to fresh milk. Several odd-chain-containing triglycerides were more abundant, while a variety of others were less abundant, in fermented milk samples. Phosphatidylcholines and phosphatidylethanolamines were more abundant in cheeses, with evidence that the phosphatidylethanomine profile is re-modelled in a way that reflects the bacterial cell envelope. We concluded that a combination of microorganismal metabolism, concentration of the lipid/glyceride fraction and oxidation during fermentation contribute to the observed lipid profile if fermented dairy foods. These differences in the lipid and glyceride profile provide a new avenue for understanding why different fermented dairy foods show a different association with reduced disease risk compared to unfermented dairy.
Topics: Animals; Cheese; Diabetes Mellitus, Type 2; Fermentation; Food Microbiology; Glycerides; Humans; Lipidomics; Lipids; Mass Spectrometry; Milk; Nutritive Value; Yogurt
PubMed: 31514309
DOI: 10.3390/nu11092178 -
Frontiers in Bioscience (Landmark... Mar 2020Glycerol-lactate esters are energy supplements for exercise, but effects of trilactic glyceride (TLG) on intestinal function and hepatic metabolism are unknown. We found...
Glycerol-lactate esters are energy supplements for exercise, but effects of trilactic glyceride (TLG) on intestinal function and hepatic metabolism are unknown. We found that dietary supplementation with 0.5% TLG to weanling piglets decreased plasma concentrations of low-density lipoprotein and gamma-glutamyl transferase but increased those of D-xylose and high-density lipoprotein. TLG supplementation enhanced mRNA levels for fatty acid synthase (FASN) and SLC27A2 in white adipose tissue; insulin receptor in duodenum; aquaporin-8 in ileum, jejunum and colon; aquaporin-10 in duodenum and ileum; nuclear factor like-2 in jejunum and colon; glutathione -transferase and phosphoenolpyruvate carboxykinase-1 in intestines; and abundances of claudin-1 and occludin proteins. TLG supplementation decreased mRNA levels for: hepatic hormone-sensitive lipase E, lipoprotein lipase, FASN, insulin-like growth factor-binding protein-3, and SLC27A2; and intestinal lipoprotein lipase, FASN and NADPH oxidase. Furthermore, TLG supplementation enhanced abundances of genus Bifidobacterium, while reducing abundances of family Enterobacteriaceae in ileum, colon and cecum; jejunal caspase-3 protein and diarrhea rate. In conclusion, dietary supplementation with TLG modulated lipid metabolism and alleviated diarrhea by improving intestinal function and regulating intestinal microflora in piglets.
Topics: Animals; Coenzyme A Ligases; Dietary Supplements; Fatty Acid Synthases; Gastrointestinal Microbiome; Gene Expression Regulation; Glycerides; Intestinal Mucosa; Lactic Acid; Lipid Metabolism; Lipoprotein Lipase; NADPH Oxidases; Receptor, Insulin; Swine; Weaning
PubMed: 32114435
DOI: 10.2741/4858 -
Biological & Pharmaceutical Bulletin Feb 2007Cubosomes are nanoparticles but instead of the solid particles, cubosomes are self-assembled liquid crystalline particles of certain surfactant with proper ratio of... (Review)
Review
Cubosomes are nanoparticles but instead of the solid particles, cubosomes are self-assembled liquid crystalline particles of certain surfactant with proper ratio of water with a microstructure that provides unique properties of practical interest. The discovery of cubosomes is a unique story and spans the field of food science, differential geometry, biological membranes and digestive processes. One of the most common surfactants used to make cubosomes is the monoglyceride glycerol monoolein. Bicontinuous cubic liquid crystalline phase is an optically clear, very viscous material that has a unique structure at the nanometer scale. The word bicontinuous refers to the division of the two continuous but non-intersecting aqueous regions by a lipid bilayer that is contorted into a space-filling structure. Hydrating a surfactant or polar lipid that forms cubic phase and then dispersing the solid-like phase into smaller particles usually form Cubosomes. There is a lot of excitement about the cubic phases because its unique microstructure is biologically compatible and capable of controlled release of solubilized active ingredients like drugs and proteins.
Topics: Drug Delivery Systems; Glycerides; Nanoparticles; Poloxamer; Surface-Active Agents
PubMed: 17268078
DOI: 10.1248/bpb.30.350 -
Nutrients May 2019We tested the hypothesis that the lipid composition of infant formula is consistent between manufacturers, countries and target demographic. We developed techniques to... (Comparative Study)
Comparative Study
We tested the hypothesis that the lipid composition of infant formula is consistent between manufacturers, countries and target demographic. We developed techniques to profile the lipid and glyceride fraction of milk and formula in a high throughput fashion. Formula from principal brands in the UK (2017-2019; bovine-, caprine-, soya-based), the Netherlands (2018; bovine-based) and South Africa (2018; bovine-based) were profiled along with fresh British animal and soya milk and skimmed milk powder. We found that the lipid and glyceride composition of infant formula differed by region, manufacturer and date of manufacture. The formulations within some brands, aimed at different target age ranges, differed considerably where others were similar across the range. Soya lecithin and milk lipids had characteristic phospholipid profiles. Particular sources of fat, such as coconut oil, were also easy to distinguish. Docosahexaenoic acid is typically found in triglycerides rather than phospholipids in formula. The variety by region, manufacturer, date of manufacture and sub-type for target demographics lead to an array of lipid profiles in formula. This makes it impossible to predict its molecular profile. Without detailed profile of the formula fed to infants, it is difficult to characterise the relationship between infant nutrition and their growth and development.
Topics: Age Factors; Child Development; Food Analysis; Glycerides; High-Throughput Screening Assays; Humans; Infant; Infant Formula; Infant Nutritional Physiological Phenomena; Infant, Newborn; Lipids; Nutritive Value; Quality Control
PubMed: 31137537
DOI: 10.3390/nu11051122 -
Trends in Biochemical Sciences Jun 2019In eukaryotes, organelles and vesicles modulate their contents and identities through highly regulated membrane fusion events. Membrane trafficking and fusion are... (Review)
Review
In eukaryotes, organelles and vesicles modulate their contents and identities through highly regulated membrane fusion events. Membrane trafficking and fusion are carried out through a series of stages that lead to the formation of SNARE complexes between cellular compartment membranes to trigger fusion. Although the protein catalysts of membrane fusion are well characterized, their response to their surrounding microenvironment, provided by the lipid composition of the membrane, remains to be fully understood. Membranes are composed of bulk lipids (e.g., phosphatidylcholine), as well as regulatory lipids that undergo constant modifications by kinases, phosphatases, and lipases. These lipids include phosphoinositides, diacylglycerol, phosphatidic acid, and cholesterol/ergosterol. Here we describe the roles of these lipids throughout the stages of yeast vacuole homotypic fusion.
Topics: Cholesterol; Ergosterol; Glycerides; Humans; Membrane Fusion; Phosphatidic Acids; Phosphatidylinositols; Vacuoles
PubMed: 30587414
DOI: 10.1016/j.tibs.2018.12.003 -
British Journal of Pharmacology Mar 2014The endogenous cannabinoid signalling system, composed of endogenous cannabinoids, cannabinoid receptors and the enzymes that synthesize and degrade the endogenous... (Review)
Review
UNLABELLED
The endogenous cannabinoid signalling system, composed of endogenous cannabinoids, cannabinoid receptors and the enzymes that synthesize and degrade the endogenous cannabinoids, is much more complex than initially conceptualized. 2-Arachidonoylglycerol (2-AG) is the most abundant endocannabinoid and plays a major role in CNS development and synaptic plasticity. Over the past decade, many key players in 2-AG synthesis and degradation have been identified and characterized. Most 2-AG is synthesized from membrane phospholipids via sequential activation of a phospholipase Cβ and a diacylglycerol lipase, although other pathways may contribute in specialized settings. 2-AG breakdown is more complicated with at least eight different enzymes participating. These enzymes can either degrade 2-AG into its components, arachidonic acid and glycerol, or transform 2-AG into highly bioactive signal molecules. The implications of the precise temporal and spatial control of the expression and function of these pleiotropic metabolizing enzymes have only recently come to be appreciated. In this review, we will focus on the primary organization of the synthetic and degradative pathways of 2-AG and then discuss more recent findings and their implications, with an eye towards the biological and therapeutic implications of manipulating 2-AG synthesis and metabolism.
LINKED ARTICLES
This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6.
Topics: Acylation; Animals; Arachidonic Acids; Central Nervous System; Endocannabinoids; Glycerides; Humans; Monoacylglycerol Lipases; Phosphorylation
PubMed: 24102242
DOI: 10.1111/bph.12411 -
Progress in Lipid Research Jul 20182-Arachidonoylglycerol (2-AG) is a signaling lipid in the central nervous system that is a key regulator of neurotransmitter release. 2-AG is an endocannabinoid that... (Review)
Review
2-Arachidonoylglycerol (2-AG) is a signaling lipid in the central nervous system that is a key regulator of neurotransmitter release. 2-AG is an endocannabinoid that activates the cannabinoid CB receptor. It is involved in a wide array of (patho)physiological functions, such as emotion, cognition, energy balance, pain sensation and neuroinflammation. In this review, we describe the biosynthetic and metabolic pathways of 2-AG and how chemical and genetic perturbation of these pathways has led to insight in the biological role of this signaling lipid. Finally, we discuss the potential therapeutic benefits of modulating 2-AG levels in the brain.
Topics: Animals; Arachidonic Acids; Biosynthetic Pathways; Brain; Endocannabinoids; Glycerides; Humans; Lipid Metabolism; Models, Chemical; Molecular Structure; Receptor, Cannabinoid, CB1; Signal Transduction
PubMed: 29751000
DOI: 10.1016/j.plipres.2018.05.002 -
Drug Delivery and Translational Research Aug 2022The present study describes a preliminary study on the use of monoolein aqueous dispersions (MADs) as delivery systems for antioxidant molecules, namely, ascorbyl...
The present study describes a preliminary study on the use of monoolein aqueous dispersions (MADs) as delivery systems for antioxidant molecules, namely, ascorbyl palmitate (AP) and alpha-tocopherol (AT). MAD, produced by emulsifying monoolein (4.5% w/w) in water and poloxamer 407 (0.5% w/w) as emulsifier, was characterized in terms of size, morphology, and antioxidant activity by mean of PCS, cryo-TEM, and (2,2-diphenyl-1-picrylhydrazyl) assay. MAD-AP or MAD-AT gave rise to a bimodal size distribution with mean size around 200 nm. All the preparations stored at 25 °C showed quite stable size at least up to 90 days. Cryo-TEM images confirmed MAD size distribution and indicated different MAD morphologies as a function of the loaded antioxidant molecule. Indeed, in the case of MAD-AP, vesicles and cubosomes with the typical inner cubic structure were observed, while vesicles and hexosomes were shown for MAD-AT. The encapsulation efficiency of both antioxidants reached more than 90% with respect to the total amount of drug used for MAD preparation. Moreover, AP and AT antioxidant activity was retained after encapsulation, and in vitro Franz cell experiments showed that the MAD enabled to better control the drug release. These preliminary results suggest that MAD formulations could be further investigated as a potential delivery system for antioxidant supplementation in dietary or cosmetic fields.
Topics: Antioxidants; Glycerides; Particle Size; Poloxamer; Water
PubMed: 35084708
DOI: 10.1007/s13346-022-01119-4 -
Journal of the American Chemical Society Oct 20192-Arachidonoylglycerol (2-AG) is acting as a full agonist of cannabinoid receptor 1 and 2. Direct manipulation of 2-AG levels is a challenging task. The amphiphilic...
2-Arachidonoylglycerol (2-AG) is acting as a full agonist of cannabinoid receptor 1 and 2. Direct manipulation of 2-AG levels is a challenging task. The amphiphilic properties and the instability of 2-AG in aqueous media complicate its use as a drug-like molecule. Additionally, inhibition of the protein machinery that regulates 2-AG levels may also affect other monoacylglycerols. Therefore, we developed a novel method to elevate 2-AG levels with a flash of light. The resulting tool is a photoactivatable "caged" 2-arachidonoylglycerol (cg2-AG) allowing for the rapid photorelease of the signaling lipid in live cells. We characterized the mechanism of uncaging and the effect of 2-AG on the regulation of the β-cell signaling network. After uncaging of 2-AG, we monitored calcium levels, CB1-GIRK channel coupling, and CB1-mediated inhibition of adenylate cyclase and protein kinase A activity.
Topics: Animals; Arachidonic Acids; Cell Line; Cell Survival; Endocannabinoids; Glycerides; Light; Mice
PubMed: 31560527
DOI: 10.1021/jacs.9b05978