lysophosphatidylethanolamine and lysophosphatidic-acid

Topics: Animals; Cell Physiological Phenomena; Drug Design; Fingolimod Hydrochloride; Humans; Immunosuppressive Agents; Inflammation; Insulin; Insulin Secretion; Lysophospholipids; Neurotransmitter Agents; Propylene Glycols; Receptors, G-Protein-Coupled; Sphingosine

Plasma lysophospholipids have emerged as signaling molecules with important effects on inflammation, insulin resistance, and fatty liver disease, each of which is linked closely to obesity. Dietary n-3 (ω-3) polyunsaturated fatty acids (PUFAs) may be able to improve these conditions.. The objective of this study was to assess the response of plasma lysophospholipids to obesity, n-3 PUFA consumption, and a high-fat meal challenge to better understand the role of lysophospholipid metabolism in the progression of obesity-related disorders.. We determined the concentrations of 8 lysophosphatidylcholines, 11 lysophosphatidylethanolamines, and 7 lysophosphatidylinositols in the plasma of 34 normal-weight and 38 obese subjects randomly assigned to consume corn oil (control) or n-3 PUFA-rich fish oil (3 g/d; n = 15-19/group) for 90 d. Blood samples were collected on the last day of the study under fasting conditions and 6 h after a high-fat meal (1135 kcal, 86 g fat) challenge. The profile of secreted lysophospholipids was studied in HepG2 cells under palmitate-induced steatosis.. Obese and normal-weight subjects had different profiles of plasma lysophospholipids. A multivariate combination of the 26 lysophospholipids could discriminate between normal-weight and obese subjects with an accuracy of 98%. The high-fat meal challenge altered the concentration of plasma lysophosphatidylcholines in an oil treatment-dependent manner in normal-weight but not obese subjects, suggesting that obesity impairs the sensitivity of lysophospholipid metabolism to n-3 PUFAs. Noncytotoxic steatosis in HepG2 cells affected the secretion pattern of lysophospholipids, partially resembling the changes observed in the plasma of obese subjects.. Obesity has a substantial impact on lysophospholipid metabolism, altering the plasma lysophospholipid profile and abolishing its sensitivity to dietary n-3 PUFAs. These effects could contribute to the onset or progression of alterations associated with obesity, such as inflammation, insulin resistance, and fatty liver disease. This trial was registered at www.controlled-trials.com as ISRCTN96712688.

Topics: Adult; Diet, High-Fat; Dietary Fats; Fatty Acids, Omega-3; Fatty Liver; Female; Hep G2 Cells; Humans; Inflammation; Insulin Resistance; Lysophospholipids; Male; Middle Aged; Obesity

Tobacco smoke (TS) is a major causative agent to lead to chronic bronchitis (CB). However the mechanisms of CB induced by TS are unclear. In this report, rats were exposed to different concentrations of TS and the metabolic features of CB were characterized by using a nontargeted metabolic profiling method based on liquid chromatography-mass spectrometry (LC-MS) to detect the altered metabolic patterns in serum from CB rats and investigate the mechanisms of CB. 11 potential biomarkers were identified in serum of rats. Among them, the levels of lysophosphatidylethanolamine (18:1), lysophosphatidic acid (18:1), lysophosphatidylethanolamine (18:0), lysophosphatidylethanolamine (16:0), lysophosphatidylethanolamine (20:4), docosahexaenoic acid, 5-hydroxyindoleacetic acid and 5'-carboxy-γ-tocopherol were higher in TS group compared to control group. Conversely, the levels of 4-imidazolone-5-propionic acid, 12-hydroxyeicosatetraenoic acid and uridine were lower in TS group. The results indicated that the mechanism of CB was related to amino acid metabolism and lipid metabolism, particularly lipid metabolism. In addition, lysophosphatidylethanolamines were proved to be important mediators, which could be used as biomarkers to diagnose CB. These results also suggested that metabolomics was suitable for diagnosing CB and elucidating the possible metabolic pathways of TS-induced CB.

Topics: Animals; Biomarkers; Bronchitis, Chronic; Chromatography, High Pressure Liquid; Female; Humans; Lysophospholipids; Male; Mass Spectrometry; Metabolomics; Nicotiana; Rats; Rats, Sprague-Dawley; Smoke

Lysophosphatidylethanolamine (LPE) is a lyso-type metabolite of phosphatidylethanolamine (a plasma membrane component), and its intracellular Ca(2+) ([Ca(2+)]i) increasing actions may be mediated through G-protein-coupled receptor (GPCR). However, GPCRs for lysophosphatidic acid (LPA), a structurally similar representative lipid mediator, have not been implicated in LPE-mediated activities in SK-OV3 or OVCAR-3 ovarian cancer cells or in receptor over-expression systems. In the present study, LPE-induced [Ca(2+)]i increase was observed in MDA-MB-231 cells but not in other breast cancer cell lines. In addition, LPE- and LPA-induced responses showed homologous and heterologous desensitization. Furthermore, VPC32183 and Ki16425 (antagonists of LPA1 and LPA3) inhibited LPE-induced [Ca(2+)]i increases, and knockdown of LPA1 by transfection with LPA1 siRNA completely inhibited LPE-induced [Ca(2+)]i increases. Furthermore, the involvement of CD97 (an adhesion GPCR) in the action of LPA1 in MDA-MB-231 cells was demonstrated by siRNA transfection. Pertussis toxin (a specific inhibitor of Gi/o proteins), edelfosine (an inhibitor of phospholipase C), or 2-APB (an inhibitor of IP3 receptor) completely inhibited LPE-induced [Ca(2+)]i increases, whereas HA130, an inhibitor of autotaxin/lysophospholipase D, did not. Therefore, LPE is supposed to act on LPA1-CD97/Gi/o proteins/phospholipase C/IP3/Ca(2+) rise in MDA-MB-231 breast cancer cells.

Topics: Antigens, CD; Boron Compounds; Calcium; Cell Line, Tumor; Female; Gene Expression Regulation, Neoplastic; GTP-Binding Protein alpha Subunits, Gi-Go; Humans; Inositol 1,4,5-Trisphosphate Receptors; Isoxazoles; Lysophospholipids; Organ Specificity; Organophosphates; Pertussis Toxin; Propionates; Pyridines; Receptors, G-Protein-Coupled; Receptors, Lysophosphatidic Acid; RNA, Small Interfering; Signal Transduction; Type C Phospholipases

In the yeast, mobilization of triacylglycerols (TAGs) is facilitated by the three TAG lipases Tgl3p, Tgl4p, and Tgl5p. Motif search analysis, however, indicated that Tgl3p and Tgl5p do not only contain the TAG lipase motif GXSXG but also an H-(X)(4)-D acyltransferase motif. Interestingly, lipid analysis revealed that deletion of TGL3 resulted in a decrease and overexpression of TGL3 in an increase of glycerophospholipids. Similar results were obtained with TGL5. Therefore, we tested purified Tgl3p and Tgl5p for acyltransferase activity. Indeed, both enzymes not only exhibited lipase activity but also catalyzed acylation of lysophosphatidylethanolamine and lysophosphatidic acid, respectively. Experiments using variants of Tgl3p created by site-directed mutagenesis clearly demonstrated that the two enzymatic activities act independently of each other. We also showed that Tgl3p is important for efficient sporulation of yeast cells, but rather through its acyltransferase than lipase activity. In summary, our results demonstrate that yeast Tgl3p and Tgl5p play a dual role in lipid metabolism contributing to both anabolic and catabolic processes.

Topics: Acyltransferases; Catalysis; Histidine; Lipase; Lipid Metabolism; Lysophospholipids; Mutagenesis, Site-Directed; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Spores, Fungal; Triglycerides