Fig. 7. Schematic of the proposed cellular metabolic processes for M381 cells under SCD1 inhibition.

SCD1 inhibition blocks de novo MUFA synthesis from SFA, which leads to an imbalance of intracellular SFA and UFA. This imbalance drives the release of UFAs stored in M381 lipid droplets, which act as reservoirs of unsaturated lipids, to restore the balance between SFA and UFA. Prolonged SCD1 inhibition eventually depletes the stored UFA. The resulting imbalance between SFA and UFA transforms fluid normal membrane domains into phase-separated solid membranes. The accompanied loss of membrane fluidity and exclusion of membrane-residing proteins are associated with an induced apoptosis—a cell fate that can be rescued by supplying excess UFA in the culture medium.