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Increased plasma lipoprotein lipase activity in males with autism spectrum disorder / Takaharu HIRAI in Research in Autism Spectrum Disorders, 77 (September 2020)
[article]
Titre : Increased plasma lipoprotein lipase activity in males with autism spectrum disorder Type de document : Texte imprimé et/ou numérique 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
in Research in Autism Spectrum Disorders > 77 (September 2020) . - 101630[article] Increased plasma lipoprotein lipase activity in males with autism spectrum disorder [Texte imprimé et/ou numérique] / 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 Resveratrol ameliorates prenatal progestin exposure-induced autism-like behavior through ERbeta activation / W. XIE in Molecular Autism, 9 (2018)
[article]
Titre : Resveratrol ameliorates prenatal progestin exposure-induced autism-like behavior through ERbeta activation Type de document : Texte imprimé et/ou numérique Auteurs : W. XIE, Auteur ; X. GE, Auteur ; L. LI, Auteur ; A. YAO, Auteur ; X. WANG, Auteur ; M. LI, Auteur ; X. GONG, Auteur ; Z. CHU, Auteur ; Z. LU, Auteur ; X. HUANG, Auteur ; Y. JIAO, Auteur ; Y. WANG, Auteur ; M. XIAO, Auteur ; H. CHEN, Auteur ; W. XIANG, Auteur ; P. YAO, Auteur Article en page(s) : 43p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder Estrogen receptor beta Lipid metabolism Mitochondria Oxidative stress Progestin Resveratrol Index. décimale : PER Périodiques Résumé : Background: Recent literatures indicate that maternal hormone exposure is a risk factor for autism spectrum disorder (ASD). We hypothesize that prenatal progestin exposure may counteract the neuroprotective effect of estrogen and contribute to ASD development, and we aim to develop a method to ameliorate prenatal progestin exposure-induced autism-like behavior. Methods: Experiment 1: Prenatal progestin exposure-induced offspring are treated with resveratrol (RSV) through either prenatal or postnatal exposure and then used for autism-like behavior testing and other biomedical analyses. Experiment 2: Prenatal norethindrone (NET) exposure-induced offspring are treated with ERbeta knockdown lentivirus together with RSV for further testing. Experiment 3: Pregnant dams are treated with prenatal NET exposure together with RSV, and the offspring are used for further testing. Results: Eight kinds of clinically relevant progestins were used for prenatal exposure in pregnant dams, and the offspring showed decreased ERbeta expression in the amygdala with autism-like behavior. Oral administration of either postnatal or prenatal RSV treatment significantly reversed this effect with ERbeta activation and ameliorated autism-like behavior. Further investigation showed that RSV activates ERbeta and its target genes by demethylation of DNA and histone on the ERbeta promoter, and then minimizes progestin-induced oxidative stress as well as the dysfunction of mitochondria and lipid metabolism in the brain, subsequently ameliorating autism-like behavior. Conclusions: We conclude that resveratrol ameliorates prenatal progestin exposure-induced autism-like behavior through ERbeta activation. Our data suggest that prenatal progestin exposure is a strong risk factor for autism-like behavior. Many potential clinical progestin applications, including oral contraceptive pills, preterm birth drugs, and progestin-contaminated drinking water or seafood, may be risk factors for ASD. In addition, RSV may be a good candidate for clinically rescuing or preventing ASD symptoms in humans, while high doses of resveratrol used in the animals may be a potential limitation for human application. En ligne : https://dx.doi.org/10.1186/s13229-018-0225-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371
in Molecular Autism > 9 (2018) . - 43p.[article] Resveratrol ameliorates prenatal progestin exposure-induced autism-like behavior through ERbeta activation [Texte imprimé et/ou numérique] / W. XIE, Auteur ; X. GE, Auteur ; L. LI, Auteur ; A. YAO, Auteur ; X. WANG, Auteur ; M. LI, Auteur ; X. GONG, Auteur ; Z. CHU, Auteur ; Z. LU, Auteur ; X. HUANG, Auteur ; Y. JIAO, Auteur ; Y. WANG, Auteur ; M. XIAO, Auteur ; H. CHEN, Auteur ; W. XIANG, Auteur ; P. YAO, Auteur . - 43p.
Langues : Anglais (eng)
in Molecular Autism > 9 (2018) . - 43p.
Mots-clés : Autism spectrum disorder Estrogen receptor beta Lipid metabolism Mitochondria Oxidative stress Progestin Resveratrol Index. décimale : PER Périodiques Résumé : Background: Recent literatures indicate that maternal hormone exposure is a risk factor for autism spectrum disorder (ASD). We hypothesize that prenatal progestin exposure may counteract the neuroprotective effect of estrogen and contribute to ASD development, and we aim to develop a method to ameliorate prenatal progestin exposure-induced autism-like behavior. Methods: Experiment 1: Prenatal progestin exposure-induced offspring are treated with resveratrol (RSV) through either prenatal or postnatal exposure and then used for autism-like behavior testing and other biomedical analyses. Experiment 2: Prenatal norethindrone (NET) exposure-induced offspring are treated with ERbeta knockdown lentivirus together with RSV for further testing. Experiment 3: Pregnant dams are treated with prenatal NET exposure together with RSV, and the offspring are used for further testing. Results: Eight kinds of clinically relevant progestins were used for prenatal exposure in pregnant dams, and the offspring showed decreased ERbeta expression in the amygdala with autism-like behavior. Oral administration of either postnatal or prenatal RSV treatment significantly reversed this effect with ERbeta activation and ameliorated autism-like behavior. Further investigation showed that RSV activates ERbeta and its target genes by demethylation of DNA and histone on the ERbeta promoter, and then minimizes progestin-induced oxidative stress as well as the dysfunction of mitochondria and lipid metabolism in the brain, subsequently ameliorating autism-like behavior. Conclusions: We conclude that resveratrol ameliorates prenatal progestin exposure-induced autism-like behavior through ERbeta activation. Our data suggest that prenatal progestin exposure is a strong risk factor for autism-like behavior. Many potential clinical progestin applications, including oral contraceptive pills, preterm birth drugs, and progestin-contaminated drinking water or seafood, may be risk factors for ASD. In addition, RSV may be a good candidate for clinically rescuing or preventing ASD symptoms in humans, while high doses of resveratrol used in the animals may be a potential limitation for human application. En ligne : https://dx.doi.org/10.1186/s13229-018-0225-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371