We have investigated the morphology of dimyristoyl phosphatidyl choline (DMPC)—cholesterol mixed monolayer formed on the water surface by dropping method using surface tension measurement (STm), Brewster angle micros...We have investigated the morphology of dimyristoyl phosphatidyl choline (DMPC)—cholesterol mixed monolayer formed on the water surface by dropping method using surface tension measurement (STm), Brewster angle microscopy (BAM), and infrared external reflection spectroscopy (IERS). STm results showed negative deviation of the limiting molecular area (A0) of cholesterol occurred when cholesterol was added to the DMPC monolayer. BAM images showed the expandable DMPC monolayer changed to the condensed rigid monolayer at more than cholesterol mole fraction (xChol) 0.4. IERS recordings showed that the addition of cholesterol at xChol = 0.4 occurred structural change from gauche- to trans- conformation of two DMPC molecule alkyl chains. From these results, it is found that cholesterol molecule has specific properties that cause structural transition of DMPC molecule alkyl chains.展开更多
Nonalcoholic steatohepatitis(NASH)is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder.Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NA...Nonalcoholic steatohepatitis(NASH)is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder.Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH,while the other lipids associated with the NASH pathogenesis remained unexplored.The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH via profiling the metabolic characteristics of lipids.Herein,multi-omics techniques based on LC—Q-TOF/MS,LC—MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment.A methionine and choline deficient(MCD)diet-induced mouse model of NASH was then constructed,and Schisandra lignans extract(SLE)was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14.Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines(PEs),and SLE could significantly reduce the accumulation of intrahepatic PEs.Notably,exogenous PE(18:0/18:1)was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis.Supplementing PE(18:0/18:1)also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors,while PE synthase inhibitor exerted a prominent hepatoprotective role.The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.展开更多
Emerging evidence suggests that dietary D-mannose,enriched naturally in many plants and fruits,show benefits in patients with bacterial urinary tract infection,diabetes,and obesity.However,it is noteworthy that the ph...Emerging evidence suggests that dietary D-mannose,enriched naturally in many plants and fruits,show benefits in patients with bacterial urinary tract infection,diabetes,and obesity.However,it is noteworthy that the physiological level of D-mannose in the blood is relatively low.Based on the study that D-mannose could be a safe and beneficial dietary supplement to obese,here phosphatidylation of mannose was proposed as a way to increase the physiological level of D-mannose and enhance the modulatory effect of mannose on obesity.In this study,phosphatidylmannoside(PtdMan)was synthesized via the approach of phospholipase D mediated transphosphatidylation.In vivo,we show that phosphatidylation of mannose enhanced the physiological level of mannose in blood.The benefits of PtdMan and D-mannose in high-fat diet-induced obesity were then investigated.Compared with D-mannose supplementary,increased physiological level of PtdMan enhanced the expression of fatty acid oxidation-related genes in liver and PPARγtargeted genes in adipose tissue,thus protecting from high-fat diet induced obesity,glucose tolerance,and insulin sensitivity.Together,our findings reveal the possibility that phosphatidylation of mannose could be used as a dietary approach to prevent obesity-associated diseases via its enhanced mannose bioavailability.展开更多
Phosphatidylinositol polyphosphate (PIPx) are related with tyrosine kinase activation and cell proliferation and carcinogenesis. PIPx is an important target compound for synthetic organic chemist. PIPx having saturate...Phosphatidylinositol polyphosphate (PIPx) are related with tyrosine kinase activation and cell proliferation and carcinogenesis. PIPx is an important target compound for synthetic organic chemist. PIPx having saturated fatty acid components have been reported. Recently we have succeeded in the synthesis of phosphatydylinositol-3,4,5-trisphosphate with unsaturated fatty acid component by the reaction of diethyl chlorophosphite with 1,2-di-O-cyclohexylidene-3,4-0-(tetraisopropyldisiloxane 1,3-diyl)-6-O-(4-oxopentanoyl)-myo-inositol.展开更多
文摘We have investigated the morphology of dimyristoyl phosphatidyl choline (DMPC)—cholesterol mixed monolayer formed on the water surface by dropping method using surface tension measurement (STm), Brewster angle microscopy (BAM), and infrared external reflection spectroscopy (IERS). STm results showed negative deviation of the limiting molecular area (A0) of cholesterol occurred when cholesterol was added to the DMPC monolayer. BAM images showed the expandable DMPC monolayer changed to the condensed rigid monolayer at more than cholesterol mole fraction (xChol) 0.4. IERS recordings showed that the addition of cholesterol at xChol = 0.4 occurred structural change from gauche- to trans- conformation of two DMPC molecule alkyl chains. From these results, it is found that cholesterol molecule has specific properties that cause structural transition of DMPC molecule alkyl chains.
基金supported by the National Natural Science Foundation of China(Grant Number:82274194)Jiangsu Natural Science Funds(Grant Number:BK20211224,China)the Project of State Key Laboratory of Natural Medicines(Grant Number:SKLNMZZ202001,China)。
文摘Nonalcoholic steatohepatitis(NASH)is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder.Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH,while the other lipids associated with the NASH pathogenesis remained unexplored.The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH via profiling the metabolic characteristics of lipids.Herein,multi-omics techniques based on LC—Q-TOF/MS,LC—MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment.A methionine and choline deficient(MCD)diet-induced mouse model of NASH was then constructed,and Schisandra lignans extract(SLE)was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14.Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines(PEs),and SLE could significantly reduce the accumulation of intrahepatic PEs.Notably,exogenous PE(18:0/18:1)was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis.Supplementing PE(18:0/18:1)also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors,while PE synthase inhibitor exerted a prominent hepatoprotective role.The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.
基金We greatly appreciate the financial support for this study provided from Ocean University of China and Jiangnan University.This work was supported by the National Natural Science Foundation of China and National Science Foundation for Post-doctoral Scientists of China[2021M701465]National Key R&D Program of China under Grant[2018YFC0311201].
文摘Emerging evidence suggests that dietary D-mannose,enriched naturally in many plants and fruits,show benefits in patients with bacterial urinary tract infection,diabetes,and obesity.However,it is noteworthy that the physiological level of D-mannose in the blood is relatively low.Based on the study that D-mannose could be a safe and beneficial dietary supplement to obese,here phosphatidylation of mannose was proposed as a way to increase the physiological level of D-mannose and enhance the modulatory effect of mannose on obesity.In this study,phosphatidylmannoside(PtdMan)was synthesized via the approach of phospholipase D mediated transphosphatidylation.In vivo,we show that phosphatidylation of mannose enhanced the physiological level of mannose in blood.The benefits of PtdMan and D-mannose in high-fat diet-induced obesity were then investigated.Compared with D-mannose supplementary,increased physiological level of PtdMan enhanced the expression of fatty acid oxidation-related genes in liver and PPARγtargeted genes in adipose tissue,thus protecting from high-fat diet induced obesity,glucose tolerance,and insulin sensitivity.Together,our findings reveal the possibility that phosphatidylation of mannose could be used as a dietary approach to prevent obesity-associated diseases via its enhanced mannose bioavailability.
文摘Phosphatidylinositol polyphosphate (PIPx) are related with tyrosine kinase activation and cell proliferation and carcinogenesis. PIPx is an important target compound for synthetic organic chemist. PIPx having saturated fatty acid components have been reported. Recently we have succeeded in the synthesis of phosphatydylinositol-3,4,5-trisphosphate with unsaturated fatty acid component by the reaction of diethyl chlorophosphite with 1,2-di-O-cyclohexylidene-3,4-0-(tetraisopropyldisiloxane 1,3-diyl)-6-O-(4-oxopentanoyl)-myo-inositol.
