Adipose tissue coregulates cognitive function

Oliveras Cañellas, Núria; Castells-Nobau, Anna; Vega-Correa, Lisset de la; Latorre-Luque, Jessica; Motger-Albertí, Anna; Arnoriaga Rodríguez, María; Garre-Olmo, Josep; Zapata-Tona, Cristina; Coll Martínez, Clàudia; Ramió-Torrentà, Lluís; Moreno-Navarrete, José Maria; Puig, Josep; Villarroya, Francesc; Ramos, Rafel; Casadó-Anguera, Verònica; Martín García, Elena, 1975-; Maldonado, Rafael, 1961-; Mayneris Perxachs, Jordi; Fernández Real, Jose M.

doi:http://dx.doi.org/10.1126/sciadv.adg4017

Adipose tissue coregulates cognitive function

Citation

Oliveras-Cañellas N, Castells-Nobau A, de la Vega-Correa L, Latorre-Luque J, Motger-Albertí A, Arnoriaga-Rodriguez M, Garre-Olmo J, Zapata-Tona C, Coll-Martínez C, Ramió-Torrentà L, Moreno-Navarrete JM, Puig J, Villarroya F, Ramos R, Casadó-Anguera V, Martín-García E, Maldonado R, Mayneris-Perxachs J, Fernández-Real JM. Adipose tissue coregulates cognitive function. Sci Adv. 2023 Aug 11;9(32):eadg4017. DOI: 10.1126/sciadv.adg4017

Abstract

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.