alkylglycerols

Adipose tissue mass is maintained by a balance between lipolysis and lipid storage. The contribution of adipose lipogenesis to fat mass, especially in the setting of high-fat feeding, is considered minor. Here, we report that adipose-specific knockout of the peroxisomal lipid synthetic protein PexRAP promotes diet-induced obesity and insulin resistance through activation of de novo lipogenesis. PexRAP inactivation inhibits the flux of carbons to ethanolamine plasmalogens. This increases nuclear PC/PE ratio and promotes cholesterol mislocalization, resulting in the activation of liver X receptor (LXR), a nuclear receptor known to be activated by increased intracellular cholesterol...

1- O -alkylglycerols are a class of natural existing lipids with broad biological activities. However, their use in food or agricultural fields remains to be investigated, especially for their antimicrobial activity. In this work, three 1- O -alkylglycerols, 1- O -octanylglycerol (C8 Gly1 ), 1- O -dodecylglycerol (C12 Gly1 ), and 1- O -hexadecylglycerol (C16 Gly1 ), were synthesized in the isolated yields of 71.3-89.8 % and characterized by 1 H NMR, 13 C NMR, FITR, mass spectra, and HPLC-ESLD. The critical micelle concentration (CMC) of 1- O -alkylglycerols was determined to be 1...

Alkylglycerols (1-O-alkyl-sn-glycerols) are microscale but critical lipids in foods. Conventional lipidomics analysis often loses sight of alkylglycerol analysis. In this study, we developed a high coverage pseudotargeted lipidomics method for analyzing alkylglycerols. The developed method integrated the advantages of GC-MS and LC-MS to profile alkylglycerol-type ether lipids comprehensively, with the help of a data processing Dart package termed FFIMA (Feature Fragments Information Matching Algorithm). The developed method exhibited competitive superiority to conventional lipidomics, such as wider coverage and higher accuracy...

BACKGROUND: Breastfed infants have lower disease risk compared to formula-fed infants, however, the mechanisms behind this protection are unknown. Human milk has a complex lipidome which may have many critical roles in health and disease risk. However, human milk lipidomics is challenging, and research is still required to fully understand the lipidome and to interpret and translate findings. This study aimed to address key human milk lipidome knowledge gaps and discuss possible implications for early life health...

The development of novel analgesics for chronic pain in the last 2 decades has proven virtually intractable, typically failing due to lack of efficacy and dose-limiting side effects. Identified through unbiased gene expression profiling experiments in rats and confirmed by human genome-wide association studies, the role of excessive tetrahydrobiopterin (BH4) in chronic pain has been validated by numerous clinical and preclinical studies. BH4 is an essential cofactor for aromatic amino acid hydroxylases, nitric oxide synthases, and alkylglycerol monooxygenase so a lack of BH4 leads to a range of symptoms in the periphery and central nervous system (CNS)...

Long-term results following solid organ transplantation do not mirror the excellent short-term results achieved in recent decades. It is therefore clear that current immunosuppressive maintenance protocols primarily addressing the adaptive immune system no longer meet the required clinical need. Identification of novel targets addressing this shortcoming is urgently needed. There is a growing interest in better understanding the role of the innate immune system in this context. In this review, we focus on macrophages, which are known to prominently infiltrate allografts and, during allograft rejection, to be involved in the surge of the adaptive immune response by expression of pro-inflammatory cytokines and direct cytotoxicity...

Alkylglycerol monooxygenase (AGMO) and plasmanylethanolamine desaturase (PEDS1) are enzymes involved in ether lipid metabolism. While AGMO degrades plasmanyl lipids by oxidative cleavage of the ether bond, PEDS1 exclusively synthesizes a specific subclass of ether lipids, the plasmalogens, by introducing a vinyl ether double bond into plasmanylethanolamine phospholipids. Ether lipids are characterized by an ether linkage at the sn-1 position of the glycerol backbone and they are found in membranes of different cell types...

We have previously described the remarkable capacity of radioiodinated alkyl phospholipids to be sequestered and retained by a variety of tumors in vivo. We have already established the influence of certain structural parameters of iodinated alkyl phospholipids on tumor avidity, such as stereochemistry at the sn -2 carbon of alkylglycerol phosphocholines, meta -or para -position of iodine in the aromatic ring of phenylalkyl phosphocholines, and the length of the alkyl chain in alkyl phospholipids. In order to determine the additional structural requirements for tumor uptake and retention, three new radioiodinated alkylphospholipid analogs, 2-4 , were synthesized as potential tumor imaging agents...

Pterins are an inseparable part of living organisms. Pterins participate in metabolic reactions mostly as tetrahydropterins. Dihydropterins are usually intermediates of these reactions, whereas oxidized pterins can be biomarkers of diseases. In this review, we analyze the available data on the quantum chemistry of unconjugated pterins as well as their photonics. This gives a comprehensive overview about the electronic structure of pterins and offers some benefits for biomedicine applications: (1) one can affect the enzymatic reactions of aromatic amino acid hydroxylases, NO synthases, and alkylglycerol monooxygenase through UV irradiation of H4 pterins since UV provokes electron donor reactions of H4 pterins; (2) the emission properties of H2 pterins and oxidized pterins can be used in fluorescence diagnostics; (3) two-photon absorption (TPA) should be used in such pterin-related infrared therapy because single-photon absorption in the UV range is inefficient and scatters in vivo; (4) one can affect pathogen organisms through TPA excitation of H4 pterin cofactors, such as the molybdenum cofactor, leading to its detachment from proteins and subsequent oxidation; (5) metal nanostructures can be used for the UV-vis, fluorescence, and Raman spectroscopy detection of pterin biomarkers...

Omega-3 polyunsaturated fatty acids (ω-3 PUFA) are substances that play an important role in human metabolism. They are essential nutritional factors and can improve the functioning of individual systems and the body as a whole. The main source of ω-3 PUFA has long been fish fat, which contains PUFA in the triglyceride form. A fairly new and promising alternative to fish fat is the liver fat of the Commander squid (Berryteuthis magister), which additionally contains alkylglycerols, contains PUFA in the phospholipid form and can be obtained from squid fishery waste...

Phospholipid transport from the periphery to the brain is an understudied topic. When certain lipid species are deficient due to impaired synthesis, though, transfer across the blood-brain barrier is essential for replenishing lipids in the brain. For example, the deficiency in plasmalogens, the most abundant ether lipids in mammals, has detrimental effects on the brain, which is a major issue in inherited peroxisomal disorders but also contributes to more common disorders like Alzheimer's disease. Oral administration of alkylglycerols like batyl alcohol, which carry a pre-formed ether bond, enables replenishment of ether lipids in various peripheral tissues...

The cytotoxicity-bioassay-guided fractionation of the ethanol extract from the marine sponge Guitarra abbotti , whose 1- O -alkyl- sn -glycerol ethers (AGEs) have not been investigated so far, led to the isolation of a complex lipid fraction containing, along with previously known compounds, six new lipids of the AGE type. The composition of the AGE fraction as well as the structures of 6 new and 22 previously known compounds were established using 1 H and 13 C NMR, GC/MS, and chemical conversion methods. The new AGEs were identified as: 1- O -(Z-docos-15-enyl)- sn -glycerol ( 1 ), 1- O -(Z-docos-17-enyl)- sn -glycerol ( 2 ), 1- O -(Z-tricos-15-enyl)- sn -glycerol ( 3 ), 1- O -(Z-tricos-16-enyl)- sn -glycerol ( 4 ), 1- O -(Z-tricos-17-enyl)- sn -glycerol ( 5 ), and 1- O -(Z-tetracos-15-enyl)- sn -glycerol ( 6 )...

Plasmalogens are a specific type of glycerophospholipid found in especially high levels in neuronal membranes. Decreased blood and brain levels of docosahexaenoic acid (DHA) containing plasmalogens are associated with decreased cognition and neuromuscular function in humans. Administration of 1-O-alkyl-2-acylglycerol (AAG) plasmalogen precursors containing DHA at the sn-2 position dose-dependently increase blood DHA plasmalogens and are neuroprotective in animal models of neurodegeneration at doses between 10 and 50 mg/kg...

Little is known about the physiological role of alkylglycerol monooxygenase (AGMO), the only enzyme capable of cleaving the 1-O-alkyl ether bond of ether lipids. Expression and enzymatic activity of this enzyme can be detected in a variety of tissues including adipose tissue. This labile lipolytic membrane-bound protein uses tetrahydrobiopterin as a cofactor, and mice with reduced tetrahydrobiopterin levels have alterations in body fat distribution and blood lipid concentrations. In addition, manipulation of AGMO in macrophages led to significant changes in the cellular lipidome, and alkylglycerolipids, the preferred substrates of AGMO, were shown to accumulate in mature adipocytes...

The biological screening of 44 marine sponge extracts for the research of bioactive molecules, with potential application in the treatment of age-related diseases (cancer and Alzheimer's disease) and skin aging, resulted in the selection of Scopalina hapalia extract for chemical study. As no reports of secondary metabolites of S. hapalia were found in the literature, we undertook this research to further extend current knowledge of Scopalina chemistry. The investigation of this species led to the discovery of four new compounds: two butenolides sinularone J ( 1 ) and sinularone K ( 2 ), one phospholipid 1- O -octadecyl-2-pentanoyl- sn -glycero-3-phosphocholine ( 3 ) and one lysophospholipid 1- O -(3-methoxy-tetradecanoyl)- sn -glycero-3-phosphocholine ( 4 ) alongside with known lysophospholipids ( 5 and 6 ), alkylglycerols ( 7 - 10 ), epidioxysterols ( 11 and 12 ) and diketopiperazines ( 13 and 14 )...

Ether lipids are a unique class of glycero- and glycerophospho-lipid that carry an ether or vinyl ether linked fatty alcohol at the sn -1 position of the glycerol backbone. These specialised lipids are important endogenous anti-oxidants with additional roles in regulating membrane fluidity and dynamics, intracellular signalling, immunomodulation and cholesterol metabolism. Lipidomic profiling of human population cohorts has identified new associations between reduced circulatory plasmalogen levels, an abundant and biologically active sub-class of ether lipids, with obesity and body-mass index...

The blood-brain barrier (BBB) is usually impermeable to several drugs, which hampers treatment of various brain-related diseases/disorders. There have been several approaches to open the BBB, including intracarotid infusion of hyperosmotic concentrations of arabinose, mannitol, oleic or linoleic acids, or alkylglycerols, intravenous infusion of bradykinin B2, administration of a fragment of the ZO toxin from vibrio cholera , targeting specific components of the tight junctions (e.g. claudin-5) with siRNA or novel peptidomimetic drugs, or the use of ultrasound with microbubbles...

BACKGROUND: The active ingredients in the shark liver oil (SLO) mixture were found to be a group of etherlinked glycerol known as alkylglycerols (AKGs). During the last century, initial clinical use of the SLO mixture was for treating leukemias and later preventing radiation sickness from cancer x-ray therapy. Selachyl alcohol is one of the most abundant AKGs in the SLO mixture and it displayed strong activity in reducing lung metastasis number on a model of grafted tumor in mice (Lewis lung carcinoma cells)...

Plasmalogens are membrane glycerophospholipids with diverse biological functions. Reduced plasmalogen levels have been observed in metabolic diseases; hence, increasing their levels might be beneficial in ameliorating these conditions. Shark liver oil (SLO) is a rich source of alkylglycerols that can be metabolized into plasmalogens. This study was designed to evaluate the impact of SLO supplementation on endogenous plasmalogen levels in individuals with features of metabolic disease. In this randomized, double-blind, placebo-controlled cross-over study, the participants (10 overweight or obese males) received 4-g Alkyrol® (purified SLO) or placebo (methylcellulose) per day for 3 weeks followed by a 3-week washout phase and were then crossed over to 3 weeks of the alternate placebo/Alkyrol® treatment...

Plasmalogens or alkenylphospholipids are a sub-class of glycerophospholipids with numerous biological functions and are thought to have protective effects against metabolic disease. Dietary supplementation with alkylglycerols (AKGs) has been shown to increase endogenous plasmalogen levels, however effective modulation of different molecular plasmalogen species has not yet been demonstrated. In this study, the effects of an orally-administered AKG mix (a mixture of chimyl, batyl and selachyl alcohol at a 1:1:1 ratio) on plasma and tissue lipids, including plasmalogens, was evaluated...