A potential role of fatty acid binding protein 4 in the pathophysiology of autism spectrum disorder.
A potential role of fatty acid binding protein 4 in the pathophysiology of autism spectrum disorder.
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DOI：
10.1093/braincomms/fcaa145
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发表时间：
2020
影响因子：
4.8
通讯作者：
Yoshikawa T
中科院分区：
文献类型：
--
作者：
Maekawa M;Ohnishi T;Toyoshima M;Shimamoto-Mitsuyama C;Hamazaki K;Balan S;Wada Y;Esaki K;Takagai S;Tsuchiya KJ;Nakamura K;Iwata Y;Nara T;Iwayama Y;Toyota T;Nozaki Y;Ohba H;Watanabe A;Hisano Y;Matsuoka S;Tsujii M;Mori N;Matsuzaki H;Yoshikawa T
自闭症谱系障碍是一种神经发育障碍，其特征是社会沟通和互动困难，以及重复和特征性的行为模式。虽然自闭症谱系障碍的发病机制尚不清楚，但婴儿期超重或肥胖以及出生时体重过轻被认为是一种风险，这表明代谢方面。在这项研究中，我们研究了脂肪组织发育作为自闭症谱系障碍的病理生理因素，通过检查自闭症谱系障碍儿童（n = 123）和典型发育儿童（n = 92）在4-12岁时的脂肪因子和其他代谢标志物的血清水平。在表现出年龄依赖性轨迹的多项测量中，瘦素水平在自闭症谱系障碍和典型发育儿童之间表现出不同的轨迹模式，支持自闭症谱系障碍的脂肪组织依赖性机制。特别令人感兴趣的是，在学龄前，自闭症谱系障碍儿童中的脂肪酸结合蛋白4（FABP 4）水平显著低于典型发育受试者（4-6岁：自闭症谱系障碍n = 21，典型发育n = 26）。接受者工作特征曲线分析区分自闭症谱系障碍儿童和正常发育儿童的敏感性为94.4%，特异性为75.0%。我们重新测序了一个日本队列中FABP 4基因的外显子，该队列包括659个自闭症谱系障碍和1000个对照样本，并在自闭症谱系障碍组中鉴定了两种罕见的功能变体。Trp 98 Stop是两种变体之一，从有抑郁症病史的母亲那里遗传给先证者。小鼠中Fabp 4基因的破坏诱发了自闭症谱系障碍样行为表型和锥体神经元顶端树突上棘密度的增加，这在自闭症谱系障碍受试者的死后大脑中观察到。Fabp 4基因敲除小鼠大脑皮层的脂肪酸组成发生了改变。总的来说，这些结果表明，“脂肪-脑轴”可能是自闭症谱系障碍的病理生理学基础，FABP 4是一种潜在的分子，可用作生物标志物。我们在自闭症谱系障碍儿童中发现了主要由脂肪组织分泌的低循环脂肪酸结合蛋白4（FABP 4），并在自闭症谱系障碍组中鉴定了功能性FABP 4变体。此外，Fabp 4基因敲除小鼠表现出自闭症谱系障碍相关的表型。我们提出，“脂肪-脑轴”可能是自闭症谱系障碍的病理生理基础。
Autism spectrum disorder is a neurodevelopmental disorder characterized by difficulties in social communication and interaction, as well as repetitive and characteristic patterns of behaviour. Although the pathogenesis of autism spectrum disorder is unknown, being overweight or obesity during infancy and low weight at birth are known as risks, suggesting a metabolic aspect. In this study, we investigated adipose tissue development as a pathophysiological factor of autism spectrum disorder by examining the serum levels of adipokines and other metabolic markers in autism spectrum disorder children (n = 123) and typically developing children (n = 92) at 4–12 years of age. Among multiple measures exhibiting age-dependent trajectories, the leptin levels displayed different trajectory patterns between autism spectrum disorder and typically developing children, supporting an adipose tissue-dependent mechanism of autism spectrum disorder. Of particular interest, the levels of fatty acid binding protein 4 (FABP4) were significantly lower in autism spectrum disorder children than in typically developing subjects, at preschool age (4–6 years old: n = 21 for autism spectrum disorder and n = 26 for typically developing). The receiver operating characteristic curve analysis discriminated autism spectrum disorder children from typically developing children with a sensitivity of 94.4% and a specificity of 75.0%. We re-sequenced the exons of the FABP4 gene in a Japanese cohort comprising 659 autism spectrum disorder and 1000 control samples, and identified two rare functional variants in the autism spectrum disorder group. The Trp98Stop, one of the two variants, was transmitted to the proband from his mother with a history of depression. The disruption of the Fabp4 gene in mice evoked autism spectrum disorder-like behavioural phenotypes and increased spine density on apical dendrites of pyramidal neurons, which has been observed in the postmortem brains of autism spectrum disorder subjects. The Fabp4 knockout mice had an altered fatty acid composition in the cortex. Collectively, these results suggest that an ‘adipo-brain axis’ may underlie the pathophysiology of autism spectrum disorder, with FABP4 as a potential molecule for use as a biomarker. We discovered lower circulating fatty acid binding protein 4 (FABP4), mainly secreted by the adipose tissue, in children with autism spectrum disorder, and identified functional FABP4 variants in the autism spectrum disorder group. Furthermore, Fabp4 knock-out mice displayed autism spectrum disorder-relevant phenotypes. We propose that the ‘adipo-brain axis’ may underlie the pathophysiology of autism spectrum disorder.
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影响因子：
6.2
作者：
Bozdagi O;Sakurai T;Papapetrou D;Wang X;Dickstein DL;Takahashi N;Kajiwara Y;Yang M;Katz AM;Scattoni ML;Harris MJ;Saxena R;Silverman JL;Crawley JN;Zhou Q;Hof PR;Buxbaum JD
通讯作者：
Buxbaum JD
DOI：
10.1111/obr.12358
发表时间：
2016-03
期刊：
Obesity reviews : an official journal of the International Association for the Study of Obesity
影响因子：
--
作者：
Heymsfield SB;Peterson CM;Thomas DM;Heo M;Schuna JM Jr
通讯作者：
Schuna JM Jr
影响因子：
8.8
作者：
Bachmann-Gagescu, Ruxandra;Mefford, Heather C.;Tsuchiya, Karen D.
通讯作者：
Tsuchiya, Karen D.
影响因子：
2.5
作者：
Belichenko, Pavel V.;Wright, Elena E.;Francke, Uta
通讯作者：
Francke, Uta
影响因子：
5.6
作者：
Berman RF;Murray KD;Arque G;Hunsaker MR;Wenzel HJ
通讯作者：
Wenzel HJ