Thomas Chloe, Njoku Dolores B
Laboratory Njoku, Department of Anesthesiology and Pain Medicine, Washington University in St. Louis, St. Louis, MO, United States.
Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO, United States.
Front Med (Lausanne). 2024 Aug 20;11:1425528. doi: 10.3389/fmed.2024.1425528. eCollection 2024.
Males are at higher risk for developing metabolic dysfunction-associated steatohepatitis (MASH) than females; however, mechanisms mediating sexual dimorphism in MASH development are not completely understood. Nutrition-based mouse models suggest that dysregulated fatty acid biosynthesis promotes MASH. Drugs recapitulate MASH without diet variabilities. This brief report investigates associations of sexual dimorphism with male susceptibility to MASH utilizing a drug-induced MASH model and focuses on very-long-chain fatty acid biosynthesis pathways. We assessed male and female mouse livers at 5 and 15 weeks following MASH induction by immunizations and age-matched un-immunized controls utilizing Western blot. Our results suggest that PPAR alpha and CYP4a12a protect females, while CYP4v2 does not protect males from MASH development. Our results have important implications for understanding sexual dimorphism in the pathogenesis of MASH.
男性患代谢功能障碍相关脂肪性肝炎（MASH）的风险高于女性；然而，介导MASH发生过程中性别差异的机制尚未完全明确。基于营养的小鼠模型表明，脂肪酸生物合成失调会促进MASH的发生。药物可在无饮食差异的情况下重现MASH。本简短报告利用药物诱导的MASH模型研究性别差异与男性对MASH易感性之间的关联，并聚焦于极长链脂肪酸生物合成途径。我们通过免疫诱导MASH，并利用蛋白质印迹法评估了5周和15周龄的雄性和雌性小鼠肝脏以及年龄匹配的未免疫对照。我们的结果表明，过氧化物酶体增殖物激活受体α（PPAR alpha）和细胞色素P450 4A12A（CYP4a12a）可保护雌性，而细胞色素P450 4V2（CYP4v2）不能保护雄性免受MASH的发生。我们的结果对于理解MASH发病机制中的性别差异具有重要意义。
