L-Fucose alleviates inflammation, pyroptosis and mitochondrial injury in obesity-related cardiac injury via TLR4/MyD88/NF-κB pathway

作者：Jiaxin Gong, Feng Wei, Tianyu Wu, Ningzhi Zhang, Yongqiao Zhang, Zhaoqiang Cui, Junbo Ge · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-025-06834-3 · 被引用次数：4 · 研究领域：Inflammasome and immune disorders、Adipokines, Inflammation, and Metabolic Diseases、Peroxisome Proliferator-Activated Receptors

BACKGROUND: Obesity-related cardiac injury is a serious global condition associated with excessive fat intake, which is strongly linked to chronic low-degrade inflammation. Pyroptosis, a pro-inflammatory form of cell death, has been implicated in obesity recently. L-Fucose (Fuc), a sulfated polysaccharide with anti-inflammatory and antioxidant properties, remains unexplored in the area of pyroptosis and obesity-related cardiac injury. METHODS: Six-week-old wide type C57BL/6 mice were subjected to high-fat diet (HFD) feeding for 20 weeks to induce obesity with or without Fuc gavaging, followed by assessment of metabolic related indicators. Echocardiography, histopathological analysis and enzymatic assays were used to assess cardiac function. The level of pro-inflammatory cytokines was detected by ELISA, qRT-PCR and CD68 staining. Pyroptosis-related protein including NLRP3, GSDMD, pro-caspase-1, cleaved-caspase-1, IL-1β, and ASC were evaluated by western blot. Oxidative stress was detected by ROS level. Cardiac mitochondrial structure was assessed by electron microscopy and mitotracker staining. Mitochondrial function was measured by mitochondrial membrane potential (MMP) and oxygen consumption rate (OCR) assay. Molecular docking and molecular dynamics (MD) simulations were conducted to look for the potential target of Fuc. Cellular thermal shift assay (CETSA) and western blot were used to investigate the interaction between Fuc and its target. Palmitic acid (PA) induced lipoto...