JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Minghan Li,Jialin Guo,Jinxin Meng,Xueting Wang,Tianxu Pan,Dongyu Zhao,Hongye Li,Ruyi Gao,Ya Wang,Hechun Li,Songyang Li,Jiagan Wang,Haibin Huang,Nan Wang,Shuyuan Yu,Jiayao Guan,Mingxiao Liu,Chunfeng Wang,Guilian Yang
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by inflammation and immune dysregulation, with the gut–liver axis playing a crucial role in immunometabolic balance. While dietary fibers show therapeutic potential, their mechanisms in T2DM remain unclear. This study investigates the effects of synbiotic intervention combining inulin and Lactiplantibacillus plantarum LPm77 on T2DM, focusing on the gut–liver axis. After 7 weeks of synbiotic treatment, significant improvements in hyperglycemia, insulin resistance, and hepatic steatosis were observed in T2DM mice. Inulin promoted L. plantarum LPm77 colonization, enhancing the gut microbiota balance and restoring the intestinal barrier function. It also regulated bile acid levels in the enterohepatic circulation. The synbiotic promoted tauro-ursodeoxycholic acid (TUDCA) biosynthesis, improving hepatic lipid metabolism and activating TGR5. TGR5 activation suppressed M1 macrophage polarization via the TGR5-TLR4-NF-κB pathway, reducing pro-inflammatory cytokines and increasing IL-10, thus alleviating systemic inflammation. This study highlights a novel therapeutic approach targeting immune-metabolic dysregulation in T2DM.
研究领域:
微生物学
·
内分泌学
·
免疫学
·
代谢紊乱
·
营养学
·
胃肠病学
·
肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2024
·
IF 12.2
Anfei Liu,Yunting Li,Lifan Li,Kaiju Chen,Meitao Tan,Fei Zou,Xingmei Zhang,Xiaojing Meng
Lead is a neurotoxic contaminant that exists widely in the environment. Although lead neurotoxicity has been found to be tightly linked to gut microbiota disturbance, the effect of host metabolic disorders caused by gut microbiota disturbance on lead neurotoxicity has not been investigated. In this work, the results of new object recognition tests and Morris water maze tests showed that chronic low-dose lead exposure caused learning and memory dysfunction in mice. The results of 16 S rRNA sequencing of cecal contents and fecal microbiota transplantation showed that the neurotoxicity of lead could be transmitted through gut microbiota. The results of untargeted metabolomics and bile acid targeted metabolism analysis showed that the serum bile acid metabolism profile of lead-exposed mice was significantly changed. In addition, supplementation with TUDCA or INT-777 significantly alleviated chronic lead exposure-induced learning and memory impairment, primarily through inhibition of the NLRP3 inflammasome in the hippocampus to relieve neuroinflammation. In conclusion, our findings suggested that dysregulation of host bile acid metabolism may be one of the mechanisms of lead-induced neurotoxicity, and supplementation of specific bile acids may be a possible therapeutic strategy for lead-induced neurotoxicity.
研究领域:
神经科学
·
毒理学
·
微生物学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
·
2022
·
IF 3.511
Wentao Sun,Yang Zhou,Hongmei Xue,Haitao Hou,Guowei He,Qin Yang
Although the association of elevated homocysteine level with cardiac hypertrophy has been reported, the molecular mechanisms by which homocysteine induces cardiac hypertrophy remain inadequately understood. In this study we aim to uncover the roles of cyclic nucleotide phosphodiesterase 1 (PDE1) and endoplasmic reticulum (ER) stress and their relationship to advance the mechanistic understanding of homocysteine-induced cardiac cell hypertrophy. H9c2 cells and primary neonatal rat cardiomyocytes are exposed to homocysteine with or without ER stress inhibitor TUDCA or PDE1-specific inhibitor Lu AF58027, or transfected with siRNAs targeting PDE1 isoforms prior to homocysteine-exposure. Cell surface area is measured and ultrastructure is examined by transmission electron microscopy. Hypertrophic markers, PDE1 isoforms, and ER stress molecules are detected by q-PCR and western blot analysis. Intracellular cGMP and cAMP are measured by ELISA. The results show that homocysteine causes the enlargement of H9c2 cells, increases the expressions of hypertrophic markers β-MHC and ANP, upregulates PDE1A and PDE1C, promotes the expressions of ER stress molecules, and causes ER dilatation and degranulation. TUDCA and Lu AF58027 downregulate β-MHC and ANP, and alleviate cell enlargement. TUDCA decreases PDE1A and PDE1C levels. Silencing of PDE1C inhibits homocysteine-induced hypertrophy, whereas PDE1A knockdown has minor effect. Both cAMP and cGMP are decreased after homocysteine-exposure, while only cAMP is restored by Lu AF58027 and TUDCA. TUDCA and Lu AF58027 also inhibit cell enlargement, downregulate ANP, β-MHC and PDE1C, and enhance cAMP level in homocysteine-exposed primary cardiomyocytes. ER stress mediates homocysteine-induced hypertrophy of cardiac cells via upregulating PDE1C expression Cyclic nucleotide, especially cAMP, is the downstream mediator of the ER stress-PDE1C signaling axis in homocysteine-induced cell hypertrophy.
研究领域:
心脏病学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）