Adipose Tissue Palmitoylation Cycling Mediates Insulin Resistance and Preservation of β-Cell Function in Mice

Palmitoylation, the reversible modification of proteins by palmitate, is altered in diabetes. We inactivated acyl protein thioesterase-1 (APT1), a key palmitoylation cycling enzyme, in adipose tissue to study how fat affects systemic metabolism. Given adiposity effects on β-cell failure, we asked if palmitoylation of proteins in fat affects insulin secretion. Adipose APT1-deficient mice had improved glucose metabolism and increased cell-autonomous insulin secretion in two models of insulin resistance, high-fat diet, and aging. Extracellular vesicles from APT1-deficient adipocytes promoted insulin secretion in insulinoma cells. Altering palmitoylation in fat may preserve β-cell function in insulin resistance.