FTO promotes weight gain via altering Kif1a splicing and axonal vesicle trafficking in AgRP neurons

ABSTRACT: N6-methyladenosine (m6A) is an abundant chemical RNA modification involved in the regulation of many biological processes. The m6A demethylase FTO (fat mass and obesity-associated protein) is known to affect body weight, but its systemic context and underlying mechanistsm remain unclear. Here, we found that mice lacking or overexpressing Fto in agouti-related peptide-expressing (AgRP) neurons in the hypothalamus exhibited decreased and increased body weight, respectively. FTO demethylated m6A on mRNAs for proteins associated with membrane trafficking and alternative splicing in AgRP neurons. Downstream, FTO- modulated alternative splicing of the axonal motor protein Kif1a affected its hinge region, which is relevant to the structure and function of KIF1A. Notably, Kif1a knockdown in AgRP n

SUBMITTER: Daisuke Kohno 

PROVIDER: S-SCDT-10_1038-S44318-025-00503-3 | biostudies-other |

REPOSITORIES: biostudies-other