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
Tongluojiunao （TLJN） is an herbal medicine consisting of two main components, geniposide and ginsenoside Rg1. TLJN has been shown to protect primary cultured hippocampal neurons. How-ever, its mechanism of action re...Tongluojiunao （TLJN） is an herbal medicine consisting of two main components, geniposide and ginsenoside Rg1. TLJN has been shown to protect primary cultured hippocampal neurons. How-ever, its mechanism of action remains unclear. In the present study, primary cultured hippocampal neurons treated with Aβ1-42 （10 μmol/L） signiifcantly increased the release of lactate dehydroge-nase, which was markedly reduced by TLJN （2 μL/mL）, speciifcally by the component geniposide （26 μmol/L）, but not ginsenoside Rg1 （2.5 μmol/L）. hTe estrogen receptor inhibitor, ICI182780 （1 μmol/L）, did not block TLJN-or geniposide-mediated decrease of lactate dehydrogenase under Aβ1-42-exposed conditions. However, the phosphatidyl inositol 3-kinase or mitogen-activated protein kinase pathway inhibitor, LY294002 （50 μmol/L） or U0126 （10 μmol/L）, respectively blo cked the decrease of lactate dehydrogenase mediated by TLJN or geniposide. hTerefore, these results suggest that the non-classical estrogen pathway （i.e., phosphatidyl inositol 3-kinase or mitogen-activated protein kinase） is involved in the neuroprotective effect of TLJN, speciifcally its component, geniposide, against Aβ1-42-mediated cell death in primary cultured hippocampal neurons.展开更多
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
Biomembranes mainly consist of lipids and proteins. Their various physiological functions can be affected by the phase transition behavior of membrane lipids. Many techniques have been used to study the phase transiti...Biomembranes mainly consist of lipids and proteins. Their various physiological functions can be affected by the phase transition behavior of membrane lipids. Many techniques have been used to study the phase transition of the membrane lipids, namely, the differential scanning calorimetry, the electron spin resonance, the nuclear magnetic resonance, etc. Recently, the phase transition and phase separation of the lipo-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
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supported by the National Natural Science Foundation of China No.81072901the New Teacher Fund for Doctor Station,Ministry of Education,No.20120013110013+1 种基金grants from the Nautical Traditional Chinese Medicine Discipline,No.522/0100604054grants from the Nautical Traditional Chinese Medicine Collaborative Innovation Center,No.522/0100604299
文摘Tongluojiunao （TLJN） is an herbal medicine consisting of two main components, geniposide and ginsenoside Rg1. TLJN has been shown to protect primary cultured hippocampal neurons. How-ever, its mechanism of action remains unclear. In the present study, primary cultured hippocampal neurons treated with Aβ1-42 （10 μmol/L） signiifcantly increased the release of lactate dehydroge-nase, which was markedly reduced by TLJN （2 μL/mL）, speciifcally by the component geniposide （26 μmol/L）, but not ginsenoside Rg1 （2.5 μmol/L）. hTe estrogen receptor inhibitor, ICI182780 （1 μmol/L）, did not block TLJN-or geniposide-mediated decrease of lactate dehydrogenase under Aβ1-42-exposed conditions. However, the phosphatidyl inositol 3-kinase or mitogen-activated protein kinase pathway inhibitor, LY294002 （50 μmol/L） or U0126 （10 μmol/L）, respectively blo cked the decrease of lactate dehydrogenase mediated by TLJN or geniposide. hTerefore, these results suggest that the non-classical estrogen pathway （i.e., phosphatidyl inositol 3-kinase or mitogen-activated protein kinase） is involved in the neuroprotective effect of TLJN, speciifcally its component, geniposide, against Aβ1-42-mediated cell death in primary cultured hippocampal neurons.
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.
文摘Biomembranes mainly consist of lipids and proteins. Their various physiological functions can be affected by the phase transition behavior of membrane lipids. Many techniques have been used to study the phase transition of the membrane lipids, namely, the differential scanning calorimetry, the electron spin resonance, the nuclear magnetic resonance, etc. Recently, the phase transition and phase separation of the lipo-
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.
