Adipose tissue may not be a major player in the inflammatory pathogenesis of Autism Spectrum Disorder
Purpose: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder increasingly recognized for its strong association with chronic inflammation. Adipose tissue functions as an endocrine organ and can secrete inflammatory cytokines to mediate inflammation. However, its involvement in AS...
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| Format: | Article |
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Elsevier
2025-02-01
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| Series: | Brain, Behavior, & Immunity - Health |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666354624002072 |
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| author | Baojiang Wang Yueyuan Qin Yong Chen Xiujie Zheng Yanjuan Chen Juan Zhao Feng Zhang Shan Duan |
| author_facet | Baojiang Wang Yueyuan Qin Yong Chen Xiujie Zheng Yanjuan Chen Juan Zhao Feng Zhang Shan Duan |
| author_sort | Baojiang Wang |
| collection | DOAJ |
| description | Purpose: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder increasingly recognized for its strong association with chronic inflammation. Adipose tissue functions as an endocrine organ and can secrete inflammatory cytokines to mediate inflammation. However, its involvement in ASD-related inflammation remains unclear. The present study aimed to clarify the role of adipose tissue in inducing inflammatory responses associated with ASD. Methods: A total of 36 children with ASD and 18 unrelated healthy controls, aged 2–14.5 years, were enrolled in the study. The up-regulated differentially expressed genes from the GSE18123 dataset were subjected to gene ontology (GO) enrichment analysis to explore ASD-associated pathways. Plasma cytokines and adipokines levels were quantified using Milliplex MAP immunoaffinity technology. The BTBR T + Itprtf/J (BTBR) mice that are known for their core ASD behavioral traits and inflammatory phenotypes were employed as an animal ASD model to verify the key clinical findings. Results: GO enrichment analyses revealed immune dysfunction in ASD. Symptom analysis showed that the recruited individuals had typical autistic symptoms. Plasma analysis showed no significant difference in adipokines levels, including adiponectin, leptin, resistin, adipsin, and lipocalin-2, between the ASD and control groups. However, markedly elevated levels of IL-6, IL-8, and tumor necrosis factor (TNF-α) were detected in children with ASD, suggesting that the inflammatory state is independent of adipokines. Similar results were also observed in BTBR autistic mice. Notably, levels of insulin, which are closely related to the exertion of adipokines function, also showed no significant changes. Conclusions: Our findings suggest that inflammation in ASD likely originates from non-adipocyte sources, implying that adipose tissue may not play a major role in inflammatory pathogenesis of ASD. Consequently, targeting adipose-related inflammation may not be an effective treatment approach, providing new directions for the development of targeted interventions. |
| format | Article |
| id | doaj-art-6a25f648a87643e1947863763cfa3b4f |
| institution | Kabale University |
| issn | 2666-3546 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain, Behavior, & Immunity - Health |
| spelling | doaj-art-6a25f648a87643e1947863763cfa3b4f2025-01-26T05:05:02ZengElsevierBrain, Behavior, & Immunity - Health2666-35462025-02-0143100929Adipose tissue may not be a major player in the inflammatory pathogenesis of Autism Spectrum DisorderBaojiang Wang0Yueyuan Qin1Yong Chen2Xiujie Zheng3Yanjuan Chen4Juan Zhao5Feng Zhang6Shan Duan7Institute of Maternal and Child Medicine, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, China; Shenzhen Key Laboratory of Maternal and Child Health and Diseases, Shenzhen, China; Corresponding author. Institute of Maternal and Child Medicine, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, 4009# Xinzhou Road, Futian District, Shenzhen City, 518040, China.Institute of Maternal and Child Medicine, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, ChinaDepartment of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, ChinaInstitute of Maternal and Child Medicine, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, ChinaDepartment of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, ChinaInstitute of Maternal and Child Medicine, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, ChinaStomatology Health Care Center, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, ChinaInstitute of Maternal and Child Medicine, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, China; Shenzhen Key Laboratory of Maternal and Child Health and Diseases, Shenzhen, China; Corresponding author. Institute of Maternal and Child Medicine, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, 4009# Xinzhou Road, Futian District, Shenzhen City, 518040, China.Purpose: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder increasingly recognized for its strong association with chronic inflammation. Adipose tissue functions as an endocrine organ and can secrete inflammatory cytokines to mediate inflammation. However, its involvement in ASD-related inflammation remains unclear. The present study aimed to clarify the role of adipose tissue in inducing inflammatory responses associated with ASD. Methods: A total of 36 children with ASD and 18 unrelated healthy controls, aged 2–14.5 years, were enrolled in the study. The up-regulated differentially expressed genes from the GSE18123 dataset were subjected to gene ontology (GO) enrichment analysis to explore ASD-associated pathways. Plasma cytokines and adipokines levels were quantified using Milliplex MAP immunoaffinity technology. The BTBR T + Itprtf/J (BTBR) mice that are known for their core ASD behavioral traits and inflammatory phenotypes were employed as an animal ASD model to verify the key clinical findings. Results: GO enrichment analyses revealed immune dysfunction in ASD. Symptom analysis showed that the recruited individuals had typical autistic symptoms. Plasma analysis showed no significant difference in adipokines levels, including adiponectin, leptin, resistin, adipsin, and lipocalin-2, between the ASD and control groups. However, markedly elevated levels of IL-6, IL-8, and tumor necrosis factor (TNF-α) were detected in children with ASD, suggesting that the inflammatory state is independent of adipokines. Similar results were also observed in BTBR autistic mice. Notably, levels of insulin, which are closely related to the exertion of adipokines function, also showed no significant changes. Conclusions: Our findings suggest that inflammation in ASD likely originates from non-adipocyte sources, implying that adipose tissue may not play a major role in inflammatory pathogenesis of ASD. Consequently, targeting adipose-related inflammation may not be an effective treatment approach, providing new directions for the development of targeted interventions.http://www.sciencedirect.com/science/article/pii/S2666354624002072InflammationAdipokinesAutism spectrum disorderInflammatory cytokinesInsulin |
| spellingShingle | Baojiang Wang Yueyuan Qin Yong Chen Xiujie Zheng Yanjuan Chen Juan Zhao Feng Zhang Shan Duan Adipose tissue may not be a major player in the inflammatory pathogenesis of Autism Spectrum Disorder Brain, Behavior, & Immunity - Health Inflammation Adipokines Autism spectrum disorder Inflammatory cytokines Insulin |
| title | Adipose tissue may not be a major player in the inflammatory pathogenesis of Autism Spectrum Disorder |
| title_full | Adipose tissue may not be a major player in the inflammatory pathogenesis of Autism Spectrum Disorder |
| title_fullStr | Adipose tissue may not be a major player in the inflammatory pathogenesis of Autism Spectrum Disorder |
| title_full_unstemmed | Adipose tissue may not be a major player in the inflammatory pathogenesis of Autism Spectrum Disorder |
| title_short | Adipose tissue may not be a major player in the inflammatory pathogenesis of Autism Spectrum Disorder |
| title_sort | adipose tissue may not be a major player in the inflammatory pathogenesis of autism spectrum disorder |
| topic | Inflammation Adipokines Autism spectrum disorder Inflammatory cytokines Insulin |
| url | http://www.sciencedirect.com/science/article/pii/S2666354624002072 |
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