Department of Psychiatry, Vanderbilt University, Nashville, TN, USA.
Genomics. 2012 Mar;99(3):144-51. doi: 10.1016/j.ygeno.2011.12.006. Epub 2011 Dec 29.
Obesity affects over 500 million people worldwide, and has far reaching negative health effects. Given that high body mass index (BMI) and insulin resistance are associated with alterations in many regions of brain and that physical activity can decrease obesity, we hypothesized that in Rhesus monkeys (Macaca mulatta) fed a high fat diet and who subsequently received reduced calories BMI would be associated with a unique gene expression signature in motor regions of the brain implicated in neurodegenerative disorders. In the motor cortex with increased BMI we saw the upregulation of genes involved in apoptosis, altered gene expression in metabolic pathways, and the downregulation of pERK1/2 (MAPK1), a protein involved in cellular survival. In the caudate nucleus with increased BMI we saw the upregulation of known obesity related genes (the insulin receptor (INSR) and the glucagon-like peptide-2 receptor (GLP2R)), apoptosis related genes, and altered expression of genes involved in various metabolic processes. These studies suggest that the effects of high BMI on the brain transcriptome persist regardless of two months of calorie restriction. We hypothesize that active lifestyles with low BMIs together create a brain homeostasis more conducive to brain resiliency and neuronal survival.
肥胖影响全球超过 5 亿人，对健康有深远的负面影响。鉴于高身体质量指数（BMI）和胰岛素抵抗与大脑许多区域的改变有关，而身体活动可以减少肥胖，我们假设在给予高脂肪饮食的恒河猴（Macaca mulatta）中，随后接受减少卡路里的饮食，BMI 与涉及神经退行性疾病的运动区域的独特基因表达特征相关。在与 BMI 增加相关的运动皮层中，我们看到了涉及细胞凋亡的基因上调、代谢途径中基因表达的改变以及参与细胞存活的 pERK1/2（MAPK1）蛋白的下调。在 BMI 增加的尾状核中，我们看到了已知与肥胖相关的基因（胰岛素受体（INSR）和胰高血糖素样肽-2 受体（GLP2R））、凋亡相关基因的上调以及涉及各种代谢过程的基因表达的改变。这些研究表明，高 BMI 对大脑转录组的影响持续存在，无论两个月的热量限制如何。我们假设低 BMI 的积极生活方式共同创造了更有利于大脑弹性和神经元存活的大脑内稳态。
