Disruption of tryptophan metabolism by high-fat diet-triggered maternal immune activation promotes social behavioral deficits in male mice
Abstract 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 imm...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-57414-4 |
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| author | Penghao Sun Mengli Wang Xuejun Chai Yong-Xin Liu Luqi Li Wei Zheng Shulin Chen Xiaoyan Zhu Shanting Zhao |
| author_facet | Penghao Sun Mengli Wang Xuejun Chai Yong-Xin Liu Luqi Li Wei Zheng Shulin Chen Xiaoyan Zhu Shanting Zhao |
| author_sort | Penghao Sun |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-29e427dd1d684a75a1ace33ad25fbb38 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-29e427dd1d684a75a1ace33ad25fbb382025-08-20T02:01:30ZengNature PortfolioNature Communications2041-17232025-03-0116111810.1038/s41467-025-57414-4Disruption of tryptophan metabolism by high-fat diet-triggered maternal immune activation promotes social behavioral deficits in male micePenghao Sun0Mengli Wang1Xuejun Chai2Yong-Xin Liu3Luqi Li4Wei Zheng5Shulin Chen6Xiaoyan Zhu7Shanting Zhao8College of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Basic Medicine, Xi’an Medical UniversityShenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural SciencesLife Science Research Core Services, Northwest A&F UniversityCollege of Resources and Environment Sciences, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityCollege of Veterinary Medicine, Northwest A&F UniversityAbstract 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.https://doi.org/10.1038/s41467-025-57414-4 |
| spellingShingle | Penghao Sun Mengli Wang Xuejun Chai Yong-Xin Liu Luqi Li Wei Zheng Shulin Chen Xiaoyan Zhu Shanting Zhao Disruption of tryptophan metabolism by high-fat diet-triggered maternal immune activation promotes social behavioral deficits in male mice Nature Communications |
| title | Disruption of tryptophan metabolism by high-fat diet-triggered maternal immune activation promotes social behavioral deficits in male mice |
| title_full | Disruption of tryptophan metabolism by high-fat diet-triggered maternal immune activation promotes social behavioral deficits in male mice |
| title_fullStr | Disruption of tryptophan metabolism by high-fat diet-triggered maternal immune activation promotes social behavioral deficits in male mice |
| title_full_unstemmed | Disruption of tryptophan metabolism by high-fat diet-triggered maternal immune activation promotes social behavioral deficits in male mice |
| title_short | Disruption of tryptophan metabolism by high-fat diet-triggered maternal immune activation promotes social behavioral deficits in male mice |
| title_sort | disruption of tryptophan metabolism by high fat diet triggered maternal immune activation promotes social behavioral deficits in male mice |
| url | https://doi.org/10.1038/s41467-025-57414-4 |
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