转录组
生物
基因
代谢组
脂肪组织
认知
认知功能衰退
功能(生物学)
候选基因
神经科学
基因表达
生物信息学
遗传学
内分泌学
内科学
医学
代谢组学
痴呆
疾病
作者
Núria Oliveras-Cañellas,Anna Castells-Nobau,Lisset de la Vega-Correa,Jèssica Latorre,Anna Motger‐Albertí,María Arnoriaga‐Rodríguez,Josep Garré-Olmo,Cristina Zapata-Tona,Clàudia Coll,Ll Ramió-Torrentà,José María Moreno-Navarrete,Josep Puig,Francesc Villarroya,Rafael Ramos,Verònica Casadó-Anguera,Elena Martín‐García,Rafaël Maldonado,Jordi Mayneris‐Perxachs,José Manuel Fernández‐Real
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2023-08-11
卷期号:9 (32)
被引量:1
标识
DOI:10.1126/sciadv.adg4017
摘要
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 Drosophila fat body significantly altered flies memory and learning. Among them, down-regulation of the neurotransmitter release cycle-associated gene SLC18A2 improved cognitive abilities in Drosophila and in mice. Up-regulation of RIMS1 in Drosophila 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.
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