Recent evidence indicates that such fatty acids are partly, responsible for inducing steatosis and fueling hepatocyte insulin resistance . GLP-1 is an incretin that is released from the L-cells of the small intestine which targets pancreatic ?-cells to release insulin and reduce glucagon production in response to food intake . Insulin resistance also results in defective glucagon like peptide-1 release . Recently we demonstrated that GLP-1 receptors are present on human Tofacitinib hepatocytes and that exposure of hepatocytes to GLP-1 receptor agonists led to a reduction of fat load in hepatocyte cell lines, HepG2 and Huh7. Little work, however, has been performed in primary human hepatocytes in vitro to elucidate the lethal potential of such fatty acids discussed previously . Fatty acids are known to induce the unfolded protein response , a compensatory cellular mechanism to handle cell stress . This process, including protein degradation and inhibition of translation allows cells to survive stress caused by defective proteins. In addition to the UPR an additional component to maintain a healthy proteome in the cell – lysosomal degradation or autophagy, has been shown to be critical in removing potentially toxic fatty acids from cells. In addition to defective protein degradation, lysosomes have also been shown to degrade other intracellular components, including whole organelles, lipid deposits, proteinaceous inclusions and aggregates . Singh et al. recently demonstrated that a fatty acid load in mouse hepatocytes is reduced by macroautophagy . Another type of autophagy, chaperone mediated autophagy has also been demonstrated to reduce cell stress by removing proteins that have a signal sequence . While the molecular details regarding chaperone mediated autophagy are less well-developed regulators of CMA have recently been identified in murine hepatocytes .