Milk fat globules(MFG)are the primary source of energy and functional factor in dairy-based products.To evaluate the suitability of commercial MFG substitutes for infant and adult consumers,the lipolysis properties an...Milk fat globules(MFG)are the primary source of energy and functional factor in dairy-based products.To evaluate the suitability of commercial MFG substitutes for infant and adult consumers,the lipolysis properties and regulatory factors in digesting bovine,caprine,and human MFG were compared.The lipolysis kinetic models of bovine and caprine MFG are comparable,with bovine MFG displaying the highest degree of lipolysis(50.21%)during gastric digestion in infants,resulting in the production short-chain saturated fatty acids.Caprine MFG has a high rate of lipolysis due to its weak phospholipid-glycoprotein layer,which is prominent in both infants'and adults'digestion.The effects of consuming bovine and caprine MFG for adults are comparable in terms of lipolysis properties and nutritional value of fatty acid.After gastrointestinal digestion,human MFG has the highest digestibility(93.98%).The advantages of human MFG include its phospholipid structure,exogenous lipase,and lipolysis-regulating proteins.This study provides recommendation for the selection of milk fat substitutes and improvements in commercial dairy.展开更多
Autism spectrum disorder(ASD)is a neurodevelopmental disorder influenced by genes and the environment.This study investigated the protective effects of bovine milk fat globule membrane(BMFGM)and goat milk fat globule ...Autism spectrum disorder(ASD)is a neurodevelopmental disorder influenced by genes and the environment.This study investigated the protective effects of bovine milk fat globule membrane(BMFGM)and goat milk fat globule membrane(GMFGM)supplementation on ASD model mice.Analysis of phospholipid composition showed higher levels of phosphatidylcholine in BMFGM and phosphatidylethanolamine in GMFGM.Behavioral results indicated MFGMs ameliorated social deficits,with GMFGM being more effective.Milk fat globule membrane(MFGM)mitigated neuroinflammation by suppressing microglial overactivation and proinflammatory cytokines expression,meanwhile GMFGM increased the anti-inflammatory factor interleukin(IL)-10.MFGMs also altered gut microbiota composition and maintained gut barrier integrity.Uniquely,GMFGM increased butyrate production.Correlation analysis revealed positive associations between social behavior,levels of phosphatidylcholine,sphingomyelin,and the abundance of Allobaculum,Clostridium_sensu_stricto,and Turicibacter.Overall,these findings revealed the protective effects of MFGMs on neurodevelopment in ASD animal models and the underlying mechanism could be partly explained by their regulation of gut microbiota by the phospholipid components in MFGM.展开更多
BACKGROUND Liver injury is common in severe acute pancreatitis(SAP).Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes,which induces lipid peroxidation and mitochondrial iron deposition and ...BACKGROUND Liver injury is common in severe acute pancreatitis(SAP).Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes,which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis.Our previous study found that milk fat globule epidermal growth factor 8(MFG-E8)alleviates acinar cell damage during SAP via binding toαvβ3/5 integrins.MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy.AIM To speculate whether MFG-E8 could also alleviate SAP induced liver injury by restoring the abnormal autophagy flux.METHODS SAP was induced in mice by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine or 7 hly injections of 50μg/kg cerulein plus lipopolysaccharide.mfge8-knockout mice were used to study the effect of MFG-E8 deficiency on SAPinduced liver injury.Cilengitide,a specificαvβ3/5 integrin inhibitor,was used to investigate the possible mechanism of MFG-E8.RESULTS The results showed that MFG-E8 deficiency aggravated SAP-induced liver injury in mice,enhanced autophagy flux in hepatocyte,and worsened the degree of ferroptosis.Exogenous MFG-E8 reduced SAP-induced liver injury in a dose-dependent manner.Mechanistically,MFG-E8 mitigated excessive autophagy and inhibited ferroptosis in liver cells.Cilengitide abolished MFG-E8’s beneficial effects in SAP-induced liver injury.CONCLUSION MFG-E8 acts as an endogenous protective mediator in SAP-induced liver injury.MFG-E8 alleviates the excessive autophagy and inhibits ferroptosis in hepatocytes by binding to integrinαVβ3/5.展开更多
Milk fat globule epithelial growth factor VIII(MFG-E8) is a novel adhesion protein mainly produced by macrophages and dendritic cells; it is expressed in most of the human tissues and functions to prompt cancer progre...Milk fat globule epithelial growth factor VIII(MFG-E8) is a novel adhesion protein mainly produced by macrophages and dendritic cells; it is expressed in most of the human tissues and functions to prompt cancer progression and survival. MFG-E8 contains a signal sequence for secretion, two epidermal growth factor(EGF)-like domains at the NH2 terminus and two discoidin domains with blood-clotting factor V/factor Ⅷ(C1 and C2) at the COOH terminus. The second EGF domain contains an arginine-glycine-aspartic(RGD) integrin-binding motif that engages α_vβ_5 integrins to facilitate cell adhesion and induce integrinmediated signal transduction. Integrin α_vβ_3 associates with VEGF receptor 2, engagement of integrins can promote angiogenesis, which plays key roles in growth, proliferation, and survival of cancer cells. VEGF stimulates the expression of α_vβ_3 and α_vβ_5 integrins on angiogenic vasculature, thereby potentiating effects of VEGF receptor engagement. Mice expressing a mutant form of α_vβ_3 integrin are unable to undergo tyrosine phosphorylation, confirming the important role that this integrin plays in pathological angiogenesis and providing important mechanistic insights. The C-terminus discoidin-like domains promote binding to membrane phospholipids, functioning close to VEGF like angiogenesis. MFG-E8 is an opsonin for apoptotic cells, and it acts as a bridging protein between apoptotic cells and phagocytes. It also influences cell immunities by altering CD4^+ and/or CD8^+ cells. Antibody or small peptide works with MFG-E8 at different functional sites or interacts with EGF-like domains and/or discoidin-like domains may play an important role in anti-angiogenesis or immune restoration. Altering the structures and/or functions of MFG-E8 and/or its domains is promising for development of novel anti-cancer strategies.展开更多
Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects ...Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.展开更多
This study evaluated the expression of defense compounds from the secondary metabolism of Eucalyptus globulus plants, subjected to direct and indirect stimuli by the insect Ctenarytaina eucalypti (blue gum Psyllid). R...This study evaluated the expression of defense compounds from the secondary metabolism of Eucalyptus globulus plants, subjected to direct and indirect stimuli by the insect Ctenarytaina eucalypti (blue gum Psyllid). Results showed that defense responses were activated in plants in all tested cases. Were detected and identified thirty-two compounds in the leaves of treated plants, of which five compounds differed with the control, and all are part of the chemical defenses from the plants, three of them were oxygenated monoterpenes (borneol, exo-2-hydroxy cineole and thymol), a aromatic carboxylic acid (benzoic acid) and a quinone (6-acethyl-flaviolin). The plants induced by volatile compounds and by indirect entomological manner, showed its capability to synthesize defensive compounds without a wound that promotes these responses. Were also found some constitutive secondary metabolites over expressed in the different inductions compared with the control.展开更多
The milk fat globule membrane(MFGM)is a complex structure with numerous functions,and its composition is affected by many factors.There have been few systematic investigations on goat MFGM proteome profiling during la...The milk fat globule membrane(MFGM)is a complex structure with numerous functions,and its composition is affected by many factors.There have been few systematic investigations on goat MFGM proteome profiling during lactation.Individual milk samples from 15 healthy dairy goats were obtained at six lactation time points for investigation of the MFGM proteome using both data-independent acquisition(DIA)and data-dependent acquisition(DDA)proteomics techniques combined with multivariate statistical analysis.Using the DIA method,890 variably abundant MFGM proteins were discovered throughout the lactation cycle.From 1 to 240 d,butyrophilin subfamily 1 member A1,lipoprotein lipase,perilipin-2,and adipose triglyceride lipase were upregulated,while APOE,complement C3,clusterin,and IgG were downregulated.Furthermore,from 1 to 90 d,annexin A1,annexin A2,and antithrombin-ll were downregulated,then upregulated by d 240.Albumin had a high degree of connectedness,indicating that it was a key protein,according to protein-protein interaction research.Overall,our findings gave new insights into the biological features of MFGM protein in goat milk throughout lactation,which may aid in the creation of specialized MFGM products and infant formula.展开更多
基金supported by the Young Scientists Fund in National Natural Science Foundation of China(31901650)Ministry of Science and Technology of the People’s Republic of China(2016YFD0401404)Innovation Fund of Tianjin University of Science and Technology for Young Teachers(2017LG01)。
文摘Milk fat globules(MFG)are the primary source of energy and functional factor in dairy-based products.To evaluate the suitability of commercial MFG substitutes for infant and adult consumers,the lipolysis properties and regulatory factors in digesting bovine,caprine,and human MFG were compared.The lipolysis kinetic models of bovine and caprine MFG are comparable,with bovine MFG displaying the highest degree of lipolysis(50.21%)during gastric digestion in infants,resulting in the production short-chain saturated fatty acids.Caprine MFG has a high rate of lipolysis due to its weak phospholipid-glycoprotein layer,which is prominent in both infants'and adults'digestion.The effects of consuming bovine and caprine MFG for adults are comparable in terms of lipolysis properties and nutritional value of fatty acid.After gastrointestinal digestion,human MFG has the highest digestibility(93.98%).The advantages of human MFG include its phospholipid structure,exogenous lipase,and lipolysis-regulating proteins.This study provides recommendation for the selection of milk fat substitutes and improvements in commercial dairy.
基金supported by the Central Government Guidance Local Science and Technology Development Fund Project(2021Szvup119)the Key Research and Development Plan of Shaanxi Province(2023-YBNY-184)+3 种基金the Regional Consolidated Fund-Youth Fund Project in Guangdong Province(2022A1515110717)China Postdoctoral Science Foundation(2022M72261)Guangdong Basic and Applied Basic Research Foundation(2021A1515110813)the 2021-National Center of Technology Innovation for Dairy-5.
文摘Autism spectrum disorder(ASD)is a neurodevelopmental disorder influenced by genes and the environment.This study investigated the protective effects of bovine milk fat globule membrane(BMFGM)and goat milk fat globule membrane(GMFGM)supplementation on ASD model mice.Analysis of phospholipid composition showed higher levels of phosphatidylcholine in BMFGM and phosphatidylethanolamine in GMFGM.Behavioral results indicated MFGMs ameliorated social deficits,with GMFGM being more effective.Milk fat globule membrane(MFGM)mitigated neuroinflammation by suppressing microglial overactivation and proinflammatory cytokines expression,meanwhile GMFGM increased the anti-inflammatory factor interleukin(IL)-10.MFGMs also altered gut microbiota composition and maintained gut barrier integrity.Uniquely,GMFGM increased butyrate production.Correlation analysis revealed positive associations between social behavior,levels of phosphatidylcholine,sphingomyelin,and the abundance of Allobaculum,Clostridium_sensu_stricto,and Turicibacter.Overall,these findings revealed the protective effects of MFGMs on neurodevelopment in ASD animal models and the underlying mechanism could be partly explained by their regulation of gut microbiota by the phospholipid components in MFGM.
基金Supported by the National Natural Science Foundation of China,No.82100685the Scientific Research Fund of Xi’an Health Commission,No.2021yb08+1 种基金Scientific Research Fund of Xi’an Central Hospital,No.2022QN07Innovation Capability Support Plan of Xi’an Science and Technology Bureau,No.23YXYJ0097.
文摘BACKGROUND Liver injury is common in severe acute pancreatitis(SAP).Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes,which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis.Our previous study found that milk fat globule epidermal growth factor 8(MFG-E8)alleviates acinar cell damage during SAP via binding toαvβ3/5 integrins.MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy.AIM To speculate whether MFG-E8 could also alleviate SAP induced liver injury by restoring the abnormal autophagy flux.METHODS SAP was induced in mice by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine or 7 hly injections of 50μg/kg cerulein plus lipopolysaccharide.mfge8-knockout mice were used to study the effect of MFG-E8 deficiency on SAPinduced liver injury.Cilengitide,a specificαvβ3/5 integrin inhibitor,was used to investigate the possible mechanism of MFG-E8.RESULTS The results showed that MFG-E8 deficiency aggravated SAP-induced liver injury in mice,enhanced autophagy flux in hepatocyte,and worsened the degree of ferroptosis.Exogenous MFG-E8 reduced SAP-induced liver injury in a dose-dependent manner.Mechanistically,MFG-E8 mitigated excessive autophagy and inhibited ferroptosis in liver cells.Cilengitide abolished MFG-E8’s beneficial effects in SAP-induced liver injury.CONCLUSION MFG-E8 acts as an endogenous protective mediator in SAP-induced liver injury.MFG-E8 alleviates the excessive autophagy and inhibits ferroptosis in hepatocytes by binding to integrinαVβ3/5.
基金Supported by a grant from Medical Technology Research Center for Health Development of China National Health and Family Planning Commission(No.W2012FZ007)
文摘Milk fat globule epithelial growth factor VIII(MFG-E8) is a novel adhesion protein mainly produced by macrophages and dendritic cells; it is expressed in most of the human tissues and functions to prompt cancer progression and survival. MFG-E8 contains a signal sequence for secretion, two epidermal growth factor(EGF)-like domains at the NH2 terminus and two discoidin domains with blood-clotting factor V/factor Ⅷ(C1 and C2) at the COOH terminus. The second EGF domain contains an arginine-glycine-aspartic(RGD) integrin-binding motif that engages α_vβ_5 integrins to facilitate cell adhesion and induce integrinmediated signal transduction. Integrin α_vβ_3 associates with VEGF receptor 2, engagement of integrins can promote angiogenesis, which plays key roles in growth, proliferation, and survival of cancer cells. VEGF stimulates the expression of α_vβ_3 and α_vβ_5 integrins on angiogenic vasculature, thereby potentiating effects of VEGF receptor engagement. Mice expressing a mutant form of α_vβ_3 integrin are unable to undergo tyrosine phosphorylation, confirming the important role that this integrin plays in pathological angiogenesis and providing important mechanistic insights. The C-terminus discoidin-like domains promote binding to membrane phospholipids, functioning close to VEGF like angiogenesis. MFG-E8 is an opsonin for apoptotic cells, and it acts as a bridging protein between apoptotic cells and phagocytes. It also influences cell immunities by altering CD4^+ and/or CD8^+ cells. Antibody or small peptide works with MFG-E8 at different functional sites or interacts with EGF-like domains and/or discoidin-like domains may play an important role in anti-angiogenesis or immune restoration. Altering the structures and/or functions of MFG-E8 and/or its domains is promising for development of novel anti-cancer strategies.
基金supported by the National Key Research and Development Program of China(Grant No.2019YFC1605000)National Natural Science Foundation of China(Grant No.31871806)the Beijing Livestock Industry Innovation Team(BAIC05-2023)。
文摘Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.
文摘This study evaluated the expression of defense compounds from the secondary metabolism of Eucalyptus globulus plants, subjected to direct and indirect stimuli by the insect Ctenarytaina eucalypti (blue gum Psyllid). Results showed that defense responses were activated in plants in all tested cases. Were detected and identified thirty-two compounds in the leaves of treated plants, of which five compounds differed with the control, and all are part of the chemical defenses from the plants, three of them were oxygenated monoterpenes (borneol, exo-2-hydroxy cineole and thymol), a aromatic carboxylic acid (benzoic acid) and a quinone (6-acethyl-flaviolin). The plants induced by volatile compounds and by indirect entomological manner, showed its capability to synthesize defensive compounds without a wound that promotes these responses. Were also found some constitutive secondary metabolites over expressed in the different inductions compared with the control.
基金This work was supportedby theNational KeyR&D Program of China(2022YFD1301005)the Shandong Provincial Natural Science Foundation,China(ZR2022MC184)the High-level Talents Foundation of Qingdao Agricultural University,China(665/1120053,665/1120080).
文摘The milk fat globule membrane(MFGM)is a complex structure with numerous functions,and its composition is affected by many factors.There have been few systematic investigations on goat MFGM proteome profiling during lactation.Individual milk samples from 15 healthy dairy goats were obtained at six lactation time points for investigation of the MFGM proteome using both data-independent acquisition(DIA)and data-dependent acquisition(DDA)proteomics techniques combined with multivariate statistical analysis.Using the DIA method,890 variably abundant MFGM proteins were discovered throughout the lactation cycle.From 1 to 240 d,butyrophilin subfamily 1 member A1,lipoprotein lipase,perilipin-2,and adipose triglyceride lipase were upregulated,while APOE,complement C3,clusterin,and IgG were downregulated.Furthermore,from 1 to 90 d,annexin A1,annexin A2,and antithrombin-ll were downregulated,then upregulated by d 240.Albumin had a high degree of connectedness,indicating that it was a key protein,according to protein-protein interaction research.Overall,our findings gave new insights into the biological features of MFGM protein in goat milk throughout lactation,which may aid in the creation of specialized MFGM products and infant formula.
