Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, Girona, Spain.
Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IdibGi), Girona, Spain.
Sci Adv. 2023 Aug 11;9(32):eadg4017. doi: 10.1126/sciadv.adg4017.
Obesity is associated with cognitive decline. Recent observations in mice propose an adipose tissue (AT)-brain axis. We identified 188 genes from RNA sequencing of AT in three cohorts that were associated with performance in different cognitive domains. These genes were mostly involved in synaptic function, phosphatidylinositol metabolism, the complement cascade, anti-inflammatory signaling, and vitamin metabolism. These findings were translated into the plasma metabolome. The circulating blood expression levels of most of these genes were also associated with several cognitive domains in a cohort of 816 participants. Targeted misexpression of candidate gene ortholog in the fat body significantly altered flies memory and learning. Among them, down-regulation of the neurotransmitter release cycle-associated gene improved cognitive abilities in and in mice. Up-regulation of in fat body enhanced cognitive abilities. Current results show previously unidentified connections between AT transcriptome and brain function in humans, providing unprecedented diagnostic/therapeutic targets in AT.
肥胖与认知能力下降有关。最近在小鼠身上的观察结果提出了脂肪组织（AT）-大脑轴的概念。我们从三个队列的 AT 的 RNA 测序中鉴定了 188 个与不同认知领域表现相关的基因。这些基因主要涉及突触功能、磷脂酰肌醇代谢、补体级联、抗炎信号和维生素代谢。这些发现被转化为血浆代谢组学。在 816 名参与者的队列中，这些基因的大多数循环血液表达水平也与多个认知领域相关。候选基因直系同源物在 脂肪体中的靶向异常表达显著改变了果蝇的记忆和学习能力。其中，神经递质释放循环相关基因的下调改善了 和小鼠的认知能力。在 脂肪体中上调 增强了认知能力。目前的结果表明，人类脂肪组织转录组和大脑功能之间存在以前未识别的联系，为脂肪组织提供了前所未有的诊断/治疗靶点。
