FALCON systematically interrogates free fatty acid biology and identifies a novel mediator of lipotoxicity.
Nicolas WiederJuliana Coraor FriedChoah KimEriene-Heidi SidhomMatthew R BrownJamie L MarshallCarlos ArevaloMoran Dvela-LevittMaria Kost-AlimovaJonas SieberKatlyn R GabrielJulian PachecoAndrew T ChanHamdah Shafqat AbbasiShantanu SinghJustine RutterMartine TherrienHaejin YoonZon Weng LaiAaron BaublisRenuka SubramanianRanjan DevkotaJonnell SmallVedagopuram SreekanthMyeonghoon HanDonghyun LimAnne E CarpenterJason FlannickHilary FinucaneMarcia C HaigisMelina ClaussnitzerEric SheuBeth StevensBridget K WagnerAmit ChoudharyJillian L ShawJuan Lorenzo PabloAnna GrekaPublished in: bioRxiv : the preprint server for biology (2023)
FALCON (Fatty Acid Library for Comprehensive ONtologies) enables multimodal profiling of 61 free fatty acids (FFAs) to reveal 5 FFA clusters with distinct biological effectsFALCON is applicable to many and diverse cell typesA subset of monounsaturated FAs (MUFAs) equally or more toxic than canonical lipotoxic saturated FAs (SFAs) leads to decreased membrane fluidityNew approach prioritizes genes that represent the combined effects of environmental (FFA) exposure and genetic risk for diseaseC-Maf inducing protein (CMIP) is identified as a suppressor of FFA-induced lipotoxicity via Akt-mediated signaling.