RESUMEN
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.
Asunto(s)
Adipocitos/enzimología , Grasa Intraabdominal/enzimología , Lipasa/metabolismo , Pancreatitis/enzimología , Transducción de Señal , Enfermedad Aguda , Adipocitos/patología , Animales , Ácidos Grasos no Esterificados/genética , Ácidos Grasos no Esterificados/metabolismo , Femenino , Humanos , Inflamación/enzimología , Inflamación/genética , Inflamación/patología , Grasa Intraabdominal/patología , Lipasa/genética , Masculino , Ratones , Ratones Noqueados , Pancreatitis/genética , Pancreatitis/patologíaRESUMEN
Parenteral nutrition (PN) has been associated with a higher rate of adverse outcomes compared with enteral feeding in patients with acute pancreatitis (AP). However, PN may be necessary when feeding via the enteral route is poorly tolerated or impossible, and PN is recommended as a second-line nutrition therapy in AP. Intravenous (IV) lipids are commonly used as a part of PN in patients with AP. While the adverse outcomes related to the use of PN in AP have commonly been attributed to infectious complications, data suggest that the unsaturated fatty acids in the triglycerides used in IV lipids may contribute to the development of organ failure. We discuss the clinical and experimental data on this issue and the alternative lipid emulsions that are being studied.