Saturated free fatty acid toxicity: II. Lipid accumulation, ultrastructural alterations, and toxicity in mammalian cells in culture

Abstract

The addition of 3 × 10 −4 M long-chain saturated free fatty acids (FFA) to suspension tissue cultures of strain L mouse fibroblasts resulted in the inhibition of cell proliferation and eventual cell death. The earliest morphologic alterations associated with this toxicity were characteristic elongated dilatations of the endoplasmic reticulum (ER). These appeared as angular, slit-like, electron-translucent spaces which displaced the normal granular contents of the ER. Lipid analyses demonstrated the early accumulation of triglyceride and FFA in these cells. Longer incubations produced other morphologic changes associated with cell injury, and elevations of all lipid fractions were found. Unsaturated FFA at the same concentration did not inhibit culture growth. Cells incubated with unsaturated FFA contained numerous cytoplasmic lipid droplets, but no other ultrastructural abnormalities were noted. Intracellular triglyceride was markedly increased, without accumulation of any other major lipid fraction. These findings indicate that saturated FFA toxicity may be due to the deposition of saturated fats within the ER with subsequent interference with cellular metabolism.