TY - JOUR AU - de Oliveira, Cristiane AU - Khatua, Biswajit AU - Noel, Pawan AU - Kostenko, Sergiy AU - Bag, Arup AU - Balakrishnan, Bijinu AU - Patel, Krutika S. AU - Guerra, Andre A. AU - Martinez, Melissa N. AU - Trivedi, Shubham AU - McCullough, Ann AU - Lam-Himlin, Dora M. AU - Navina, Sarah AU - Faigel, Douglas O. AU - Fukami, Norio AU - Pannala, Rahul AU - Phillips, Anna Evans AU - Papachristou, Georgios I. AU - Kershaw, Erin E. AU - Lowe, Mark E. AU - Singh, Vijay P. T1 - Pancreatic triglyceride lipase mediates lipotoxic systemic inflammation PY - 2020/04/01/ AB - Visceral adipose tissue plays a critical role in numerous diseases. Although imaging studies often show adipose involvement in abdominal diseases, their outcomes may vary from being a mild self-limited illness to one with systemic inflammation and organ failure. We therefore compared the pattern of visceral adipose injury during acute pancreatitis and acute diverticulitis to determine its role in organ failure. Acute pancreatitis–associated adipose tissue had ongoing lipolysis in the absence of adipocyte triglyceride lipase (ATGL). Pancreatic lipase injected into mouse visceral adipose tissue hydrolyzed adipose triglyceride and generated excess nonesterified fatty acids (NEFAs), which caused organ failure in the absence of acute pancreatitis. Pancreatic triglyceride lipase (PNLIP) increased in adipose tissue during pancreatitis and entered adipocytes by multiple mechanisms, hydrolyzing adipose triglyceride and generating excess NEFAs. During pancreatitis, obese PNLIP-knockout mice, unlike obese adipocyte-specific ATGL knockouts, had lower visceral adipose tissue lipolysis, milder inflammation, less severe organ failure, and improved survival. PNLIP-knockout mice, unlike ATGL knockouts, were protected from adipocyte-induced pancreatic acinar injury without affecting NEFA signaling or acute pancreatitis induction. Therefore, during pancreatitis, unlike diverticulitis, PNLIP leaking into visceral adipose tissue can cause excessive visceral adipose tissue lipolysis independently of adipocyte-autonomous ATGL, and thereby worsen organ failure. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI132767 VL - 130 IS - 4 UR - https://doi.org/10.1172/JCI132767 SP - 1931 EP - 1947 PB - The American Society for Clinical Investigation ER -