Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD, USA.
Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, Baltimore, MD, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Trends Neurosci. 2019 Oct;42(10):709-726. doi: 10.1016/j.tins.2019.08.006. Epub 2019 Sep 5.
We review evidence that suggests a role for excessive consumption of energy-dense foods, particularly fructose, and consequent obesity and insulin resistance (metabolic syndrome) in the recent increase in prevalence of autism spectrum disorders (ASD). Maternal insulin resistance, obesity, and diabetes may predispose offspring to ASD by mechanisms involving chronic activation of anabolic cellular pathways and a lack of metabolic switching to ketosis resulting in a deficit in GABAergic signaling and neuronal network hyperexcitability. Metabolic reprogramming by epigenetic DNA and chromatin modifications may contribute to alterations in gene expression that result in ASD. These mechanistic insights suggest that interventions that improve metabolic health such as intermittent fasting and exercise may ameliorate developmental neuronal network abnormalities and consequent behavioral manifestations in ASD.
我们回顾了一些证据，这些证据表明，能量密集型食物（尤其是果糖）的过度消耗以及由此导致的肥胖和胰岛素抵抗（代谢综合征）在自闭症谱系障碍（ASD）患病率的近期增加中可能起到一定作用。母体的胰岛素抵抗、肥胖和糖尿病可能通过涉及细胞合成代谢途径的慢性激活和缺乏向酮症代谢转换的机制，使后代易患 ASD，从而导致 GABA 能信号传递和神经元网络过度兴奋的缺失。表观遗传 DNA 和染色质修饰的代谢重编程可能导致 ASD 中基因表达的改变。这些机制上的见解表明，改善代谢健康的干预措施，如间歇性禁食和运动，可能改善 ASD 中发育中的神经元网络异常和随后的行为表现。
