The accelerating accumulation of surplus lipids in the pancreas triggers structural and functional changes in type 2 diabetes-affected islets. Pancreatic β-cells exhibit a restricted capacity to store fat reservoirs in lipid droplets (LDs), which act as transient buffers to prevent lipotoxic stress. With the increasing incidence of obesity, growing interest has been seen in the intracellular regulation of LD metabolism for β-cell function. Stearoyl-CoA desaturase 1 (SCD1) is critical for producing unsaturated fatty acyl moieties for fluent storage into and out of LDs, likely affecting the overall rate of β-cell survival. We explored LD-associated composition and remodeling in SCD1-deprived INS-1E cells and in pancreatic islets in wildtype and SCD1-/- mice in the lipotoxic milieu. Deficiency in the enzymatic activity of SCD1 led to decrease in the size and number of LDs and the lower accumulation of neutral lipids. This occurred in parallel with a higher compactness and lipid order inside LDs, followed by changes in the saturation status and composition of fatty acids within core lipids and the phospholipid coat. The lipidome of LDs was enriched in 18:2n-6 and 20:4n-6 in β-cells and pancreatic islets. These rearrangements markedly contributed to differences in protein association with the LD surface. Our findings highlight an unexpected molecular mechanism by which SCD1 activity affects the morphology, composition and metabolism of LDs. We demonstrate that SCD1-dependent disturbances in LD enrichment can impact pancreatic β-cells and islet susceptibility to palmitate, which may have considerable diagnostic and methodological value for the characterization of LDs in human β-cells in type 2 diabetes patients.
Keywords: Lipid droplets; Lipotoxicity; Pancreatic islets; SCD1; Type 2 diabetes; β-Cells.
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