The association between maternal lipid profile after birth and offspring risk of autism spectrum disorder

Park, Bo Y.; Yao, Ruofan; Tierney, Elaine; Brucato, Martha; Hong, Xiumei; Wang, Guoying; Ji, Yuelong; Pearson, Colleen; Fallin, M. Daniele; Wang, Xiaobin; Volk, Heather E.

doi:10.1016/j.annepidem.2020.08.009

Cited by 11 publications

(12 citation statements)

References 33 publications

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“…Recent studies have suggested that low levels of low-density lipoprotein-cholesterol in maternal plasma at birth increases the risk of the development of autism. 7 Previous studies in children have also demonstrated an association between hypocholesterolemia and autism. 3,5 Children born with inborn errors in cholesterol metabolism (e.g., Smith–Lemli–Opitz disorder) frequently have autistic-like behaviors.…”

Section: Discussionmentioning

confidence: 97%

Cholesterol deficiency as a mechanism for autism: A valproic acid model

Peltier,

Behbodikhah,

Renna

et al. 2023

Journal of Investigative Medicine

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Dysregulated cholesterol metabolism represents an increasingly recognized feature of Autism spectrum disorder (ASD). Children with fetal valproate syndrome caused by prenatal exposure to valproic acid (VPA), an anti-epileptic and mood-stabilizing drug, have a higher incidence of developing ASD. However, the role of VPA in cholesterol homeostasis in neurons and microglial cells remains unclear. Therefore, we examined the effect of VPA exposure on regulation of cholesterol homeostasis in the human microglial clone 3 (HMC3) cell line and the human neuroblastoma cell line SH-SY5Y. HMC3 and SH-SY5Y cells were each incubated in increasing concentrations of VPA, followed by quantification of mRNA and protein expression of cholesterol transporters and cholesterol metabolizing enzymes. Cholesterol efflux was evaluated using colorimetric assays. We found that VPA treatment in HMC3 cells significantly reduced ABCA1 mRNA, but increased ABCG1 and CD36 mRNA levels in a dose-dependent manner. However, ABCA1 and ABCG1 protein levels were reduced by VPA in HMC3. Further, similar experiments in SH-SY5Y cells showed increased mRNA levels for ABCA1, ABCG1, CD36 and 27-hydroxylase with VPA treatment. VPA exposure significantly reduced protein levels of ABCA1 in a dose-dependent manner, but increased the ABCG1 protein level at the highest dose in SH-SY5Y cells. In addition, VPA treatment significantly increased cholesterol efflux in SH-SY5Y, but had no impact on efflux in HMC3. VPA differentially controls the expression of ABCA1 and ABCG1, but regulation at the transcriptional and translational levels are not consistent and changes in the expression of these genes do not correlate with cholesterol efflux in vitro.

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Section: Discussionmentioning

confidence: 97%

Cholesterol deficiency as a mechanism for autism: A valproic acid model

Peltier,

Behbodikhah,

Renna

et al. 2023

Journal of Investigative Medicine

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“…Abnormal lipid metabolism has been implicated in both obesity and ASD. [ 39 , 40 ] Clinical evidence revealed that maternal obesity with altered lipid profiling was associated with increased prevalence of ASD in offspring, [ 41 ] suggesting the likelihood that some lipid molecules could lead to the development of ASD. Recently, we reported significant decline in sphingomyelin species and ceramide species (i.e., sphingolipids) in the striatum of the 7Slx1b‐Sept1 DF model of ASD, which was directly linked to abnormal myelin structure.…”

Section: Discussionmentioning

confidence: 99%

Microduplication of 16p11.2 locus Potentiates Hypertrophic Obesity in Association with Imbalanced Triglyceride Metabolism in White Adipose Tissue

Wang

Mai

Yang

et al. 2022

Molecular Nutrition Food Res

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Scope: Copy number variation (CNV) of 16p11.2 is a common genetic factor contributing to the etiology of abnormal weight status, while the underlying mechanism is not fully elucidated yet. Methods and Results: The 16p11.2 CNV mouse model with microduplication of the 7Slx1b-Sept1 region (dp/+) is evaluated under normal chow conditions. Compared to the wild type littermates (WT), the dp/+ mice exhibit obvious obese phenotype characterized by significant increase in body mass index, fat pad mass, and fat ratio, with visceral-dominant fat deposits at 12-week age. White adipose tissue (WAT), liver tissue, and plasma are sampled to assess the comorbid metabolic syndrome. In dp/+ mice, histopathologic analyses reveal hypertrophic adipocytes and hepatic steatosis; serological examinations show hyperlipemia and hyperinsulinemia. Further, by comparing lipidomic and transcriptomic profiling of epididymal WAT between dp/+ and WT mice, the study finds the triglyceride (TG) accumulation in dp/+ mice in association with the dysfunction of lipid droplets. Validation of TG-metabolism-associated genes in WAT and in primary cultured adipocytes show enhanced TG synthesis and declined TG hydrolysis in the dp/+ model. Conclusion: This study elucidates that the imbalanced TG synthesis/hydrolysis in adipocytic lipid droplets may contribute to the hypertrophic obesity and metabolic disorders in mice with 16p11.2 microduplication.

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“…Differently, they showed increased levels of TC and BMI for ASD individuals, one possible reason for this difference could be the different age range. Interestingly, a nested case-control study demonstrated that lower maternal postpartum plasma LDL concentration was associated with increased odds of ASD in offspring [27]. Moreover, a retrospective case-control study of a group of French-Canadian ASD individuals observed four times more hypocholesterolemia in ASD than in the general population [28].…”

Section: Discussionmentioning

confidence: 99%

Retinol-binding protein 4 in combination with lipids to predict the regression phenomenon of autism spectrum disorders

Chen

et al. 2021

Lipids Health Dis

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Background About 20–40 % of autistic people experience a phenomenon of regression. Retinol binding protein 4 (RBP4) plays an important role as an inflammatory neurotrophic adipokine and is a promising mediator of the fat-brain axis. Abnormal fatty acid metabolism and lipid mediators have been reported to be related to the etiological mechanism in autism, and amelioration of impaired lipid metabolism can be recognized as a treatment strategy for autism. The purpose of this study is to explore the relationship between RBP4, lipids, and the autistic regression phenomenon, and to discuss their potentials as biomarkers for the autistic regression phenomenon. Methods A total of 60 autistic individuals (18 with regression phenomenon, 42 without regression phenomenon) (ASD group) and 36 healthy controls were enrolled in this case-control study. The levels of RBP4, total cholesterol (TC), high-density lipoprotein (HDLC), low–density lipoprotein (LDLC), and triglyceride (TG) were measured. Childhood Autism Rating Scale (CARS) is used to assess the severity of autism. Ethical measures were performed in compliance with the current Declaration of Helsinki and written informed consent was obtained from the parents before enrollment of the children and adolescents. Results Compared with control subjects, autistic individuals had lower levels of TC (P = 0.007), RBP4 (P = 0.001), and HDLC (P = 0.027). The levels of RBP4 in ASD group were positively correlated with TG (r = 0.355, P = 0.005), HDLC (r = 0.257, P = 0.047), TG/TC (r = 0.376, P = 0.003) and TG/LDLC (r = 0.363, P = 0.004), and were negatively correlated with CARS (r=-0.296, P = 0.003). Further logistic regression demonstrated that decreased RBP4 concentration was associated with the presentation of the autistic regression phenomenon even after the adjustment of the potential confounding factors. Conclusions Serum RBP4 is associated with the autistic regression phenomenon and the severity of ASD. Further studies are needed to expound whether decreased RBP4 participates in the development of the autistic regression phenomenon.

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The association between maternal lipid profile after birth and offspring risk of autism spectrum disorder

Cited by 11 publications

References 33 publications

Cholesterol deficiency as a mechanism for autism: A valproic acid model

Cholesterol deficiency as a mechanism for autism: A valproic acid model

Microduplication of 16p11.2 locus Potentiates Hypertrophic Obesity in Association with Imbalanced Triglyceride Metabolism in White Adipose Tissue

Retinol-binding protein 4 in combination with lipids to predict the regression phenomenon of autism spectrum disorders

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