Increased plasma lipoprotein lipase activity in males with autism spectrum disorder / Takaharu HIRAI in Research in Autism Spectrum Disorders, 77 (September 2020)  

Public ISBD [article]  inResearch in Autism Spectrum Disorders > 77 (September 2020) . - 101630 Titre : Increased plasma lipoprotein lipase activity in males with autism spectrum disorder Type de document : texte imprimé Auteurs : Takaharu HIRAI, Auteur ; Noriyoshi USUI, Auteur ; Keiko IWATA, Auteur ; Taishi MIYACHI, Auteur ; Kenji J. TSUCHIYA, Auteur ; Min-Jue XIE, Auteur ; Kazuhiko NAKAMURA, Auteur ; Masatsugu TSUJII, Auteur ; Toshiro SUGIYAMA, Auteur ; Hideo MATSUZAKI, Auteur Article en page(s) : 101630 Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Lipoprotein lipase  GPIHBP1  Lipid metabolism  ADI-R Index. décimale : PER Périodiques Résumé : Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex genetics, characterized by impaired social communication and repetitive behaviors and interests. The involvement of lipid metabolism in ASD pathophysiology has been demonstrated in previous studies; however, the molecular mechanisms of abnormal lipid metabolism are not fully understood. A mutation in Lipoprotein lipase (LPL), which has central roles in lipid metabolism, has been identified in patients with ASD. We have reported that Lpl is downregulated in ASD model mice. Therefore, we explored the role of LPL in lipid metabolism in ASD patients. Methods We quantified LPL amount, LPL activity, and glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) amount in the plasma of ASD male subjects (n = 28) compared with typical development (TD) controls (n = 28), using enzyme-linked immunosorbent assay for LPL amount and fluorometric assays for LPL activity. We examined the correlations of plasma LPL with GPIHBP1 and clinical characteristic scores from the Autism Diagnostic Interview-Revised (ADI-R). Results There was higher LPL activity, but not LPL amount, in the plasma of ASD subjects compared with controls. Receiver operating characteristics analysis also demonstrated that pure LPL activity (LPL activity/LPL amount) is a useful indicator to distinguish ASD from TD controls. There were no correlations between plasma LPL and ADI-R scores; however, LPL activity was negatively correlated with GPIHBP1 levels in the plasma of ASD subjects. Conclusions Our results demonstrate increased activity of plasma LPL, regulated by GPIHBP1, in ASD, providing novel insights into the lipid metabolism associated with ASD pathophysiology. En ligne : https://doi.org/10.1016/j.rasd.2020.101630 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=432 [article] Increased plasma lipoprotein lipase activity in males with autism spectrum disorder [texte imprimé] / Takaharu HIRAI, Auteur ; Noriyoshi USUI, Auteur ; Keiko IWATA, Auteur ; Taishi MIYACHI, Auteur ; Kenji J. TSUCHIYA, Auteur ; Min-Jue XIE, Auteur ; Kazuhiko NAKAMURA, Auteur ; Masatsugu TSUJII, Auteur ; Toshiro SUGIYAMA, Auteur ; Hideo MATSUZAKI, Auteur . - 101630. Langues : Anglais (eng) in Research in Autism Spectrum Disorders > 77 (September 2020) . - 101630 Mots-clés : Autism spectrum disorder  Lipoprotein lipase  GPIHBP1  Lipid metabolism  ADI-R Index. décimale : PER Périodiques Résumé : Background Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex genetics, characterized by impaired social communication and repetitive behaviors and interests. The involvement of lipid metabolism in ASD pathophysiology has been demonstrated in previous studies; however, the molecular mechanisms of abnormal lipid metabolism are not fully understood. A mutation in Lipoprotein lipase (LPL), which has central roles in lipid metabolism, has been identified in patients with ASD. We have reported that Lpl is downregulated in ASD model mice. Therefore, we explored the role of LPL in lipid metabolism in ASD patients. Methods We quantified LPL amount, LPL activity, and glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) amount in the plasma of ASD male subjects (n = 28) compared with typical development (TD) controls (n = 28), using enzyme-linked immunosorbent assay for LPL amount and fluorometric assays for LPL activity. We examined the correlations of plasma LPL with GPIHBP1 and clinical characteristic scores from the Autism Diagnostic Interview-Revised (ADI-R). Results There was higher LPL activity, but not LPL amount, in the plasma of ASD subjects compared with controls. Receiver operating characteristics analysis also demonstrated that pure LPL activity (LPL activity/LPL amount) is a useful indicator to distinguish ASD from TD controls. There were no correlations between plasma LPL and ADI-R scores; however, LPL activity was negatively correlated with GPIHBP1 levels in the plasma of ASD subjects. Conclusions Our results demonstrate increased activity of plasma LPL, regulated by GPIHBP1, in ASD, providing novel insights into the lipid metabolism associated with ASD pathophysiology. En ligne : https://doi.org/10.1016/j.rasd.2020.101630 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=432

Specific Association Patterns Between Brain Glutathione Levels, Myelination, and Functional Connectivity in Adults With Autism Spectrum Disorder / Toshiki IWABUCHI in Autism Research, 18-12 (December 2025)  

Public ISBD [article]  inAutism Research > 18-12 (December 2025) . - p.2451-2462 Titre : Specific Association Patterns Between Brain Glutathione Levels, Myelination, and Functional Connectivity in Adults With Autism Spectrum Disorder Type de document : texte imprimé Auteurs : Toshiki IWABUCHI, Auteur ; Takaharu HIRAI, Auteur ; Naoko UMEDA, Auteur ; Hideto YOGO, Auteur ; Yuuta NISHIMIYA, Auteur ; Yuuki NISHIGAKI, Auteur ; Masaru WATANABE, Auteur ; Hidenori YAMASUE, Auteur ; Masatsugu TSUJII, Auteur ; Kenji J. TSUCHIYA, Auteur ; Hideo MATSUZAKI, Auteur Article en page(s) : p.2451-2462 Langues : Anglais (eng) Mots-clés : autism spectrum disorder  glutathione  magnetic resonance spectroscopy  myelin map  resting-state functional connectivity Index. décimale : PER Périodiques Résumé : ABSTRACT Recent studies have implicated oxidative stress in the pathophysiology of autism spectrum disorder (ASD). Postmortem brain studies have revealed decreased levels of the reduced form of glutathione (GSH), an important antioxidant, in some brain regions in individuals with ASD; however, in vivo evidence is lacking. Using proton magnetic resonance spectroscopy, T1-weighted/T2-weighted ratio-derived myelin maps, resting-state functional magnetic resonance imaging (MRI), and cognitive tasks, we examined whether brain GSH levels are lower in individuals with ASD than in those with typical development (TD) and explored ASD-specific association patterns between brain GSH levels, myelination, functional connectivity, and behavioral characteristics. Data from 30 adults with ASD and 27 adults with TD were analyzed. Contrary to our hypothesis, GSH levels in the left temporoparietal junction (TPJ) were higher in the ASD group than in the TD group. Using individual myelin maps, we found a significant group difference in the correlation between left middle frontal gyrus (MFG) myelination and left TPJ GSH levels. Multivariate pattern analysis of resting-state functional MRI revealed that whole-brain functional connectivity patterns from the left MFG differed between the groups in their association with left MFG myelination. Finally, we found a significant group difference in the correlation between emotion recognition ability and the functional connectivity of the left MFG with the bilateral occipitoparietal junction. In conclusion, our findings demonstrate an ASD-specific pattern of associations between left TPJ GSH levels, left MFG myelination, whole-brain functional connectivity patterns of the left MFG, and cognitive phenotype, which suggests compensatory neural mechanisms in ASD. En ligne : https://doi.org/10.1002/aur.70134 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=578 [article] Specific Association Patterns Between Brain Glutathione Levels, Myelination, and Functional Connectivity in Adults With Autism Spectrum Disorder [texte imprimé] / Toshiki IWABUCHI, Auteur ; Takaharu HIRAI, Auteur ; Naoko UMEDA, Auteur ; Hideto YOGO, Auteur ; Yuuta NISHIMIYA, Auteur ; Yuuki NISHIGAKI, Auteur ; Masaru WATANABE, Auteur ; Hidenori YAMASUE, Auteur ; Masatsugu TSUJII, Auteur ; Kenji J. TSUCHIYA, Auteur ; Hideo MATSUZAKI, Auteur . - p.2451-2462. Langues : Anglais (eng) in Autism Research > 18-12 (December 2025) . - p.2451-2462 Mots-clés : autism spectrum disorder  glutathione  magnetic resonance spectroscopy  myelin map  resting-state functional connectivity Index. décimale : PER Périodiques Résumé : ABSTRACT Recent studies have implicated oxidative stress in the pathophysiology of autism spectrum disorder (ASD). Postmortem brain studies have revealed decreased levels of the reduced form of glutathione (GSH), an important antioxidant, in some brain regions in individuals with ASD; however, in vivo evidence is lacking. Using proton magnetic resonance spectroscopy, T1-weighted/T2-weighted ratio-derived myelin maps, resting-state functional magnetic resonance imaging (MRI), and cognitive tasks, we examined whether brain GSH levels are lower in individuals with ASD than in those with typical development (TD) and explored ASD-specific association patterns between brain GSH levels, myelination, functional connectivity, and behavioral characteristics. Data from 30 adults with ASD and 27 adults with TD were analyzed. Contrary to our hypothesis, GSH levels in the left temporoparietal junction (TPJ) were higher in the ASD group than in the TD group. Using individual myelin maps, we found a significant group difference in the correlation between left middle frontal gyrus (MFG) myelination and left TPJ GSH levels. Multivariate pattern analysis of resting-state functional MRI revealed that whole-brain functional connectivity patterns from the left MFG differed between the groups in their association with left MFG myelination. Finally, we found a significant group difference in the correlation between emotion recognition ability and the functional connectivity of the left MFG with the bilateral occipitoparietal junction. In conclusion, our findings demonstrate an ASD-specific pattern of associations between left TPJ GSH levels, left MFG myelination, whole-brain functional connectivity patterns of the left MFG, and cognitive phenotype, which suggests compensatory neural mechanisms in ASD. En ligne : https://doi.org/10.1002/aur.70134 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=578

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