Disruption of tryptophan metabolism by high-fat diet-triggered maternal immune activation promotes social behavioral deficits in male mice
文献类型： 外文期刊
作者： Sun, Penghao 1 ; Wang, Mengli 1 ; Chai, Xuejun 2 ; Liu, Yong-Xin 3 ; Li, Luqi 4 ; Zheng, Wei 5 ; Chen, Shulin 1 ; Zhu, Xiaoyan 1 ; Zhao, Shanting 1 ;
作者机构： 1.Northwest A&F Univ, Coll Vet Med, Xianyang, Shaanxi, Peoples R China
2.Xian Med Univ, Coll Basic Med, Xian, Shaanxi, Peoples R China
3.Chinese Acad Agr Sci, Agr Genom Inst Shenzhen, Shenzhen Branch,Genome Anal Lab Minist Agr & Rural, Guangdong Lab Lingnan Modern Agr, Shenzhen, Guangdong, Peoples R China
4.Northwest A&F Univ, Life Sci Res Core Serv, Xianyang, Shaanxi, Peoples R China
5.Northwest A&F Univ, Coll Resources & Environm Sci, Xianyang, Shaanxi, Peoples R China
期刊名称：NATURE COMMUNICATIONS （ 影响因子：15.7； 五年影响因子：17.2 ）
ISSN：
年卷期： 2025 年 16 卷 1 期
页码：
收录情况： SCI
摘要： Diet-related maternal obesity has been implicated in neurodevelopmental disorders in progeny. Although the precise mechanisms and effective interventions remain uncertain, our research elucidates some of these complexities. We established that a prenatal high-fat diet triggered maternal immune activation (MIA), marked by elevated serum lipopolysaccharide levels and inflammatory-cytokine overproduction, which dysregulated the maternal tryptophan metabolism promoting the accumulation of neurotoxic kynurenine metabolites in the embryonic brain. Interventions aimed at mitigating MIA or blocking the kynurenine pathway effectively rescued the male mice social performance. Furthermore, excessive kynurenine metabolites initiated oxidative stress response causing neuronal migration deficits in the fetal neocortex, an effect that was mitigated by administering the glutathione synthesis precursor N-Acetylcysteine, underscoring the central role of maternal immune-metabolic homeostasis in male mice behavioral outcomes. Collectively, our study accentuated the profound influence of maternal diet-induced immuno-metabolic dysregulation on fetal brain development and provided the preventive strategies for addressing neurodevelopmental disorders.
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