Rodent and human β-cells exhibit differential susceptibility to lipotoxicity from long-chain saturated fatty acids (LC-SFA). This study investigated the intracellular disposition of palmitate in human and rodent β-cells to understand the mechanisms behind this difference. Results show palmitate accumulates in the Golgi apparatus of rodent INS-1 cells, causing membrane distension but not ER stress. In contrast, palmitate in human EndoC-BH1 cells preferentially routes to lipid droplets, maintaining viability. Co-incubation with oleate in INS-1 cells attenuated palmitate's toxicity and redirected palmitate to lipid droplets. This suggests that palmitate routing to lipid droplets contributes to β-cell viability in both cell types.

Patricia Thomas, Catherine Arden, Jenna Corcoran, Christian Hacker, Hannah J. Welters, Noel G. Morgan