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Dietary pyruvate targets cytosolic phospholipase A2 to mitigate inflammation and obesity in mice
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作者 Sadaf Hasan Nabil Ghani +5 位作者 xiangli zhao Julia Good Amanda Huang Hailey Lynn Wrona Jody Liu Chuan-ju Liu 《Protein & Cell》 SCIE CSCD 2024年第9期661-685,共25页
Obesity has a multifactorial etiology and is known to be a state of chronic low-grade inflammation,known as meta-inflammation.This state is associated with the development of metabolic disorders such as glucose intole... Obesity has a multifactorial etiology and is known to be a state of chronic low-grade inflammation,known as meta-inflammation.This state is associated with the development of metabolic disorders such as glucose intolerance and nonalcoholic fatty liver disease.Pyruvate is a glycolytic metabolite and a crucial node in various metabolic pathways.However,its role and molecular mechanism in obesity and associated complications are obscure.In this study,we reported that pyruvate substantially inhibited adipogenic differentiation in vitro and its administration significantly prevented HFD-induced weight gain,white adipose tissue inflammation,and metabolic dysregulation.To identify the target proteins of pyruvate,drug affinity responsive target stability was employed with proteomics,cellular thermal shift assay,and isothermal drug response to detect the interactions between pyruvate and its molecular targets.Consequently,we identified cytosolic phospholipase A2(cPLA2)as a novel molecular target of pyruvate and demonstrated that pyruvate restrained diet-induced obesity,white adipose tissue inflammation,and hepatic steatosis in a cPLA2-dependent manner.Studies with global ablation of cPLA2 in mice showed that the protective effects of pyruvate were largely abrogated,confirming the importance of pyruvate/cPLA2 interaction in pyruvate attenuation of inflammation and obesity.Overall,our study not only establishes pyruvate as an antagonist of cPLA2 signaling and a potential therapeutic option for obesity but it also sheds light on the mechanism of its action.Pyruvate’s prior clinical use indicates that it can be considered a safe and viable alternative for obesity,whether consumed as a dietary supplement or as part of a regular diet. 展开更多
关键词 metabolic disease PYRUVATE cytosolic phospholipase OBESITY
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Delayed allogeneic skin graft rejection in CD26-deficient mice 被引量:5
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作者 xiangli zhao Kai Zhang +3 位作者 Peter Daniel Natali Wisbrun Hendrik Fuchs Hua Fan 《Cellular & Molecular Immunology》 SCIE CAS CSCD 2019年第6期557-567,共11页
Organ transplantation is an effective therapeutic tool for treating many terminal diseases.However,one of the biggest challenges of transplantation is determining how to achieve the long-term survival of the allogenei... Organ transplantation is an effective therapeutic tool for treating many terminal diseases.However,one of the biggest challenges of transplantation is determining how to achieve the long-term survival of the allogeneic or xenogeneic transplant by,for example,preventing transplant rejection.In the current study,CD26 gene-knockout mice were used to investigate the potential role of CD26/dipeptidyl peptidase-4(DPPIV)in allogeneic skin graft rejection by tail-skin transplantation.Compared with wild-type(CD26^(+/+))counterparts,CD26^(-/-)mice showed reduced necrosis of grafts and delayed graft rejection after skin transplantation.Concentrations of serum IgG,including its subclasses IgG1 and IgG2a,were significantly reduced in CD26^(-/-)mice during graft rejection.Moreover,after allogeneic skin transplantation,the secretion levels of the cytokines IFN-γ,IL-2,IL-6,IL-4,and IL-13 were significantly reduced,whereas the level of the cytokine IL-10 was increased in the serum of CD26^(-/-)mice compared with that in the serum of CD26^(+/+)mice.Additionally,the concentration of IL-17 in serum and the percentage of cells secreting IL-17 in mouse peripheral blood lymphocytes(MPBLs)were both significantly lower,while the percentage of regulatory T cells(Tregs)was significantly higher in MPBLs of CD26^(-/-)mice than in those of CD26^(+/+)mice.Furthermore,a lower percentage of CD8^(+)T cells in MPBLs and fewer infiltrated macrophages and T cells in graft tissues of CD26^(-/-)mice were detected during graft rejection.These results indicate that CD26 is involved in allogeneic skin graft rejection and provides another hint that CD26 deficiency leads to less rejection due to lower activation and proliferation of host immune cells. 展开更多
关键词 Allogeneic graft rejection CD26/DPPIV CYTOKINE IGG T lymphocytes
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