Activation of survival and apoptotic signaling pathways in lymphocytes exposed to palmitic acid

Abstract

Lymphocytes use both glucose and glutamine as metabolic fuels at high rates even when they are immunological quiescent. T‐Lymphocytes in their basal state express low levels of Insulin Receptor (IR) and Glucose Transporter‐4 (GLUT‐4), and cellular glucose uptake is mediated by GLUT‐1. Fatty acids are known to play diverse roles for immune cell function acting as a source of carbon for oxidation and as structural components of cell membrane phospholipids. However, there is increasing evidence that free fatty acids can cause cell death through activation of apoptosis. Palmitic Acid (PA) induced apoptosis of Jurkat cells in a dose‐dependent manner as indicated by DNA fragmentation, mitochondrial membrane depolarization, cytochrome c release and activation of caspases 3/9 and JNK, p38 and ERK proteins. Concomitantly, PA treated‐Jurkat cells exhibited an increase of IR and GLUT‐4 content in their plasma membrane in the absence of insulin. PA treatment increased glucose uptake but diminished its conversion to CO2, and raised the content of the major lipid classes: triglyceride, cholesterol ester, free fatty acid and phospholipids. We suggest that, in an attempt to survive, lymphocytes activate insulin signaling pathways and glucose utilization in response to PA so stimulating the synthesis of lipid macromolecules therefore removing PA from mediating intracellular cytotoxic effects.