Journal Article

Pancreatic triglyceride lipase mediates lipotoxic systemic inflammation

Trivedi, Shubham, Faigel, Douglas O., Martinez, Melissa N., Patel, Krutika S., Kostenko, Sergiy, Pannala, Rahul, Papachristou, Georgios I., Singh, Vijay P., Bag, Arup, Balakrishnan, Bijinu, Lowe, Mark E., de Oliveira, Cristiane, Khatua, Biswajit, Noel, Pawan, Navina, Sarah, Guerra, Andre A., Fukami, Norio, Phillips, Anna Evans, Lam-Himlin, Dora M., Kershaw, Erin E., McCullough, Ann

2020

نظرة عامة

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.

• الناشر: American Society for Clinical Investigation
• موضوع: Abdominal diseases / Acute Disease / Adipocytes / Adipocytes - enzymology / Adipocytes - pathology / Adipose tissue / Animals / Biomedical research / Comparative analysis / Development and progression / Diseases / Diverticulitis / Fatty acids / Fatty Acids, Nonesterified - genetics / Fatty Acids, Nonesterified - metabolism / Female / Humans / Inflammation / Inflammation - enzymology / Inflammation - genetics / Inflammation - pathology / Intra-Abdominal Fat - enzymology / Intra-Abdominal Fat - pathology / Lipase / Lipase - genetics / Lipase - metabolism / Lipolysis / Male / Medical research / Mice / Mice, Knockout / Obesity / Pancreas / Pancreatitis / Pancreatitis - enzymology / Pancreatitis - genetics / Pancreatitis - pathology / Signal Transduction / Triglycerides