Increased circulating branched-chain amino acids(BCAAs)have been involved in the pathogenesis of obesity and insulin resistance.However,evidence relating berberine(BBR),gut microbiota,BCAAs,and insulin resis⁃tance is ...Increased circulating branched-chain amino acids(BCAAs)have been involved in the pathogenesis of obesity and insulin resistance.However,evidence relating berberine(BBR),gut microbiota,BCAAs,and insulin resis⁃tance is limited.Here,we showed that BBR could effectively rectify steatohepatitis and glucose intolerance in high-fat diet(HFD)-fed mice.BBR reorganized gut microbiota populations under both the normal chow diet(NCD)and HFD.Particu⁃larly,BBR noticeably decreased the relative abundance of BCAA-producing bacteria,including order Clostridiales;fami⁃lies Streptococcaceae,Clostridiaceae,and Prevotellaceae;and genera Streptococcus and Prevotella.Compared with the HFD group,predictive metagenomics indicated a reduction in the proportion of gut microbiota genes involved in BCAA biosynthesis but the enrichment genes for BCAA degradation and transport by BBR treatment.Accordingly,the elevated serum BCAAs of HFD group were significantly decreased by BBR.Furthermore,the Western blotting results implied that BBR could promote the BCAA catabolism in the liver and epididymal white adipose tissues of HFD-fed mice by acti⁃vation of the multienzyme branched-chain α-ketoacid dehydrogenase complex,whereas by inhibition of the phosphoryla⁃tion state of BCKDHA(E1α subunit)and branched-chain α-ketoacid dehydrogenase kinase.The ex vivo assay further confirmed that BBR could increase BCAA catabolism in both AML12 hepatocytes and 3T3-L1 adipocytes.Finally,data from healthy subjects and diabetics confirmed that BBR could improve glycemic control and modulate circulating BCAAs.Besides,functional microbiomics integrated high-throughput microbial genomics,metabolomics and molecular biotechnology has also been successfully applied to reveal the anti-obesity mechanism of hydroxysafflor yellow A.展开更多
选取了ALS位点突变和未突变的不同水稻品种(系),筛选出对甲氧咪草烟具有抗性差异的水稻品种(系)及其相应的作用浓度,并进一步以缬氨酸(Val)、亮氨酸(Leu)和异亮氨酸(Ile)这3种支链氨基酸复配作为安全剂,在此基础上复配了对植物生长和抗...选取了ALS位点突变和未突变的不同水稻品种(系),筛选出对甲氧咪草烟具有抗性差异的水稻品种(系)及其相应的作用浓度,并进一步以缬氨酸(Val)、亮氨酸(Leu)和异亮氨酸(Ile)这3种支链氨基酸复配作为安全剂,在此基础上复配了对植物生长和抗性有广谱效果的碧护和芸苔素内酯,分析了甲氧咪草烟对水稻造成的药害及防护剂的修复效果,以及支链氨基酸安全剂对不同水稻材料经甲氧咪草烟处理后的生长发育、ALS酶活性、内源抗氧化酶和解毒酶活性的变化。结果表明:敏感品种南粳9108耐受甲氧咪草烟浓度不超过28.8 g a.i./hm^(2),具有ALS突变位点的抗性水稻品种(金粳818、73119、K37)均对浓度不超过144.0g a.i./hm^(2)的甲氧咪草烟具有抗性;3种支链氨基酸安全剂组分和配比均对植株鲜重具有显著的缓解作用,其中以Leu∶Ile∶Val=3∶1∶1的缓解效果最好,即联合喷施1125 g/hm^(2)支链氨基酸(675 g/hm^(2)L-Leu∶225 g/hm^(2)L-Ile∶225 g/hm^(2)L-Val=3∶1∶1)可以显著地缓解100.0 g a.i./hm^(2)甲氧咪草烟对K37的生长抑制作用;与常用安全剂碧护或芸苔素内酯复配的安全剂相比,复配支链氨基酸安全剂的效果更好,5叶期比4叶期喷施的解毒效果则更好,不影响除杀杂草稻的效果。复配的支链氨基酸安全剂对缓解水稻甲氧咪草烟的药害机制并不是提高了靶标ALS酶活性,而是它可以诱导水稻内源解毒关键酶和抗氧化酶活性的增加。因此,通过混用或药害产生后在水稻5叶期追施上述复配的支链氨基酸安全剂,能够有效缓解甲氧咪草烟对不同抗性类型水稻的药害,使其恢复正常或接近正常的生长水平,且不影响对杂草稻的毒杀。展开更多
文摘Increased circulating branched-chain amino acids(BCAAs)have been involved in the pathogenesis of obesity and insulin resistance.However,evidence relating berberine(BBR),gut microbiota,BCAAs,and insulin resis⁃tance is limited.Here,we showed that BBR could effectively rectify steatohepatitis and glucose intolerance in high-fat diet(HFD)-fed mice.BBR reorganized gut microbiota populations under both the normal chow diet(NCD)and HFD.Particu⁃larly,BBR noticeably decreased the relative abundance of BCAA-producing bacteria,including order Clostridiales;fami⁃lies Streptococcaceae,Clostridiaceae,and Prevotellaceae;and genera Streptococcus and Prevotella.Compared with the HFD group,predictive metagenomics indicated a reduction in the proportion of gut microbiota genes involved in BCAA biosynthesis but the enrichment genes for BCAA degradation and transport by BBR treatment.Accordingly,the elevated serum BCAAs of HFD group were significantly decreased by BBR.Furthermore,the Western blotting results implied that BBR could promote the BCAA catabolism in the liver and epididymal white adipose tissues of HFD-fed mice by acti⁃vation of the multienzyme branched-chain α-ketoacid dehydrogenase complex,whereas by inhibition of the phosphoryla⁃tion state of BCKDHA(E1α subunit)and branched-chain α-ketoacid dehydrogenase kinase.The ex vivo assay further confirmed that BBR could increase BCAA catabolism in both AML12 hepatocytes and 3T3-L1 adipocytes.Finally,data from healthy subjects and diabetics confirmed that BBR could improve glycemic control and modulate circulating BCAAs.Besides,functional microbiomics integrated high-throughput microbial genomics,metabolomics and molecular biotechnology has also been successfully applied to reveal the anti-obesity mechanism of hydroxysafflor yellow A.
文摘选取了ALS位点突变和未突变的不同水稻品种(系),筛选出对甲氧咪草烟具有抗性差异的水稻品种(系)及其相应的作用浓度,并进一步以缬氨酸(Val)、亮氨酸(Leu)和异亮氨酸(Ile)这3种支链氨基酸复配作为安全剂,在此基础上复配了对植物生长和抗性有广谱效果的碧护和芸苔素内酯,分析了甲氧咪草烟对水稻造成的药害及防护剂的修复效果,以及支链氨基酸安全剂对不同水稻材料经甲氧咪草烟处理后的生长发育、ALS酶活性、内源抗氧化酶和解毒酶活性的变化。结果表明:敏感品种南粳9108耐受甲氧咪草烟浓度不超过28.8 g a.i./hm^(2),具有ALS突变位点的抗性水稻品种(金粳818、73119、K37)均对浓度不超过144.0g a.i./hm^(2)的甲氧咪草烟具有抗性;3种支链氨基酸安全剂组分和配比均对植株鲜重具有显著的缓解作用,其中以Leu∶Ile∶Val=3∶1∶1的缓解效果最好,即联合喷施1125 g/hm^(2)支链氨基酸(675 g/hm^(2)L-Leu∶225 g/hm^(2)L-Ile∶225 g/hm^(2)L-Val=3∶1∶1)可以显著地缓解100.0 g a.i./hm^(2)甲氧咪草烟对K37的生长抑制作用;与常用安全剂碧护或芸苔素内酯复配的安全剂相比,复配支链氨基酸安全剂的效果更好,5叶期比4叶期喷施的解毒效果则更好,不影响除杀杂草稻的效果。复配的支链氨基酸安全剂对缓解水稻甲氧咪草烟的药害机制并不是提高了靶标ALS酶活性,而是它可以诱导水稻内源解毒关键酶和抗氧化酶活性的增加。因此,通过混用或药害产生后在水稻5叶期追施上述复配的支链氨基酸安全剂,能够有效缓解甲氧咪草烟对不同抗性类型水稻的药害,使其恢复正常或接近正常的生长水平,且不影响对杂草稻的毒杀。