Cellular Signaling Induced by Lipids
Dr. Singh's Pancreatitis and Acute Outcomes Research Lab is investigating how obesity-related pancreatic fat worsens local injury via unsaturated fatty acids. Recent studies suggest that lipids such as nonesterified fatty acids (NEFA) may further worsen pancreatic and distant organ injury. Understanding the pathological signaling induced by lipids is crucial to understanding systemic injury and organ failure resulting in severe pancreatitis.
Visceral fat may be hydrolyzed during pancreatitis. This series of images shows the process of pancreatitis increasing over time and causing organ failure.
Process of increasing pancreatitis causing organ failure
Fluid leaks from the injured pancreas (P) into the abdominal fat (black) during pancreatitis, which increases over time, causing an increase in the gray-colored collection (outlined in yellow). This fluid contains hydrolyzed lipid, as evidenced by a high concentration of lipid products, including NEFA, within such collections.
Using novel fluorescent lipid tracers unique to each class of interest, we can study the cellular uptake and localization, and effects on cell behavior, such as cytosolic ion fluxes, mitochondrial function, protein phosphorylation and metabolic status, in real time.
Live imaging of pancreatic exocrine cells showing the increase in cytosolic calcium, (green) with uptake of fluorescent linoleic acid (red). Note the reversal by changes in the extracellular medium (blue).