Epidemiological studies have indicated that branched-chain amino acids(BCAAs)increased and gut microbiota disordered in type 2 diabetes mellitus(T2DM).This study aimed to investigate the mechanism of Lactiplantibacill...Epidemiological studies have indicated that branched-chain amino acids(BCAAs)increased and gut microbiota disordered in type 2 diabetes mellitus(T2DM).This study aimed to investigate the mechanism of Lactiplantibacillus plantarum strain 84-3(Lp84-3)combined with Staphylococcus aureus bacteriophage on ameliorating T2DM.Here we perform a case-control study and identify that Staphylococcus_phage was inversely correlated with fasting blood glucose(FBG).It revealed that Lp84-3 could inhibit the growth of S.aureus,and Lp84-3 contains BCAAs degradation enzymes in its genome.Furthermore,Lp84-3 alone or combined with S.aureus bacteriophage interventions can improve blood glucose,insulin resistance,triglycerides,interleukin-1β,tumor necrosis factor-α(TNF-α),BCAAs,and acetyllactate synthase(ALS)in db/db mice.Lp84-3 and S.aureus bacteriophage decreased S.aureus,Malacoplasma iowae,and Oscillibacter sp.,and increased some beneficial such as L.plantarum and Muribaculaceae bacterium.Transcriptomic analyses revealed that Lp84-3 and S.aureus bacteriophage activated the PI3K/AKT/GLUT4 signaling pathway and upregulated key genes of Il22,Hgf,Col6a1,Gh,Itga10,Fgf23,and Prl involved in glucose metabolism in hypothalamus.Collectively,Lp84-3 and S.aureus bacteriophage alleviate T2DM by modulating gut microbiota and enhancing glucose metabolism in hypothalamus,supporting its potential use as a promising functional compound microecological agent for alleviating T2DM.展开更多
目的:观察固本化瘀法通过GLUT4/AKt调节肥胖型多囊卵巢综合征(polycystic ovary syndrome,PCOS)大鼠胰岛素抵抗的作用机制。方法:60只SPF级雌性SD大鼠随机分为对照组、模型组、中药低剂量组、中药中剂量组、中药高剂量组。模型组采用高...目的:观察固本化瘀法通过GLUT4/AKt调节肥胖型多囊卵巢综合征(polycystic ovary syndrome,PCOS)大鼠胰岛素抵抗的作用机制。方法:60只SPF级雌性SD大鼠随机分为对照组、模型组、中药低剂量组、中药中剂量组、中药高剂量组。模型组采用高脂加来曲唑复合造模。放射免疫法检测血清性激素水平,ELISA法检测胰岛素抵抗状态,Western blotting检测卵巢GLUT4/AKt蛋白表达变化。结果:模型组血清性激素水平紊乱,胰岛素敏感性降低,各级卵泡出现囊性扩张,闭锁卵泡增多,卵巢局部GLUT4/AKt表达降低显著(P<0.05 or P<0.01)。中药高、中剂量组血清性激素水平有一定改善,胰岛素抵抗有所抑制,皮质内发育不同阶段的各级卵泡及黄体和闭锁卵泡有所恢复,卵巢局部GLUT4/AKt表达升高显著(P<0.05 or P<0.01),尤以中剂量组整体恢复效果最佳。结论:肥胖型PCOS大鼠可出现严重的性激素紊乱,伴有全身胰岛素抵抗,卵泡成熟障碍的现象,固本化瘀法可显著改善这些不良症状,GLUT4/AKt可能是临床治疗PCOS患者的有效靶蛋白。展开更多
基金supported by research grants from the Guangdong Province Basic and Applied Basic Research Fund Project(2022A1515110447)Open Fund Project of the State Key Laboratory of Applied Microbiology in South China(SKLAM006-2022)+1 种基金74th batch of general funding from the China Postdoctoral Science Foundation(2023M740774)Guangdong Provincial People’s Hospital,Postdoctoral Research Launch Fund(BY012022017)。
文摘Epidemiological studies have indicated that branched-chain amino acids(BCAAs)increased and gut microbiota disordered in type 2 diabetes mellitus(T2DM).This study aimed to investigate the mechanism of Lactiplantibacillus plantarum strain 84-3(Lp84-3)combined with Staphylococcus aureus bacteriophage on ameliorating T2DM.Here we perform a case-control study and identify that Staphylococcus_phage was inversely correlated with fasting blood glucose(FBG).It revealed that Lp84-3 could inhibit the growth of S.aureus,and Lp84-3 contains BCAAs degradation enzymes in its genome.Furthermore,Lp84-3 alone or combined with S.aureus bacteriophage interventions can improve blood glucose,insulin resistance,triglycerides,interleukin-1β,tumor necrosis factor-α(TNF-α),BCAAs,and acetyllactate synthase(ALS)in db/db mice.Lp84-3 and S.aureus bacteriophage decreased S.aureus,Malacoplasma iowae,and Oscillibacter sp.,and increased some beneficial such as L.plantarum and Muribaculaceae bacterium.Transcriptomic analyses revealed that Lp84-3 and S.aureus bacteriophage activated the PI3K/AKT/GLUT4 signaling pathway and upregulated key genes of Il22,Hgf,Col6a1,Gh,Itga10,Fgf23,and Prl involved in glucose metabolism in hypothalamus.Collectively,Lp84-3 and S.aureus bacteriophage alleviate T2DM by modulating gut microbiota and enhancing glucose metabolism in hypothalamus,supporting its potential use as a promising functional compound microecological agent for alleviating T2DM.
文摘目的:观察固本化瘀法通过GLUT4/AKt调节肥胖型多囊卵巢综合征(polycystic ovary syndrome,PCOS)大鼠胰岛素抵抗的作用机制。方法:60只SPF级雌性SD大鼠随机分为对照组、模型组、中药低剂量组、中药中剂量组、中药高剂量组。模型组采用高脂加来曲唑复合造模。放射免疫法检测血清性激素水平,ELISA法检测胰岛素抵抗状态,Western blotting检测卵巢GLUT4/AKt蛋白表达变化。结果:模型组血清性激素水平紊乱,胰岛素敏感性降低,各级卵泡出现囊性扩张,闭锁卵泡增多,卵巢局部GLUT4/AKt表达降低显著(P<0.05 or P<0.01)。中药高、中剂量组血清性激素水平有一定改善,胰岛素抵抗有所抑制,皮质内发育不同阶段的各级卵泡及黄体和闭锁卵泡有所恢复,卵巢局部GLUT4/AKt表达升高显著(P<0.05 or P<0.01),尤以中剂量组整体恢复效果最佳。结论:肥胖型PCOS大鼠可出现严重的性激素紊乱,伴有全身胰岛素抵抗,卵泡成熟障碍的现象,固本化瘀法可显著改善这些不良症状,GLUT4/AKt可能是临床治疗PCOS患者的有效靶蛋白。
