Role of obesity in the release of extracellular nucleosomes in acute pancreatitis: a clinical and experimental study
Por:
Perez, S, Finamor, I, Marti-Andres, P, Pereda, J, Campos, A, Domingues, R, Haj, F, Sabater, L, De madaria E and Sastre, J
Publicada:
1 ene 2019
Resumen:
Background/objectives A high body mass index increases the risk of severe pancreatitis and associated mortality. Our aims were: (1) To determine whether obesity affects the release of extracellular nucleosomes in patients with pancreatitis; (2) To determine whether pancreatic ascites confers lipotoxicity and triggers the release of extracellular nucleosomes in lean and obese rats.
Methods DNA and nucleosomes were determined in plasma from patients with mild or moderately severe acute pancreatitis either with normal or high body mass index (BMI). Lipids from pancreatic ascites from lean and obese rats were analyzed and the associated toxicity measured in vitro in RAW 264.7 macrophages. The inflammatory response, extracellular DNA and nucleosomes were determined in lean or obese rats with pancreatitis after peritoneal lavage.
Results Nucleosome levels in plasma from obese patients with mild pancreatitis were higher than in normal BMI patients; these levels markedly increased in obese patients with moderately severe pancreatitis vs. those with normal BMI. Ascites from obese rats exhibited high levels of palmitic, oleic, stearic, and arachidonic acids. Necrosis and histone 4 citrullination-marker of extracellular traps-increased in macrophages incubated with ascites from obese rats but not with ascites from lean rats. Peritoneal lavage abrogated the increase in DNA and nucleosomes in plasma from lean or obese rats with pancreatitis. It prevented fat necrosis and induction of HIF-related genes in lung.
Conclusions Extracellular nucleosomes are intensely released in obese patients with acute pancreatitis. Pancreatitis-associated ascitic fluid triggers the release of extracellular nucleosomes in rats with severe pancreatitis.
Filiaciones:
Perez, S:
Department of Physiology, School of Pharmacy, University of Valencia, Av. Vicente Andrés Estellés s/n, 46100, Burjasot, Valencia, Spain
Finamor, I:
Department of Physiology, School of Pharmacy, University of Valencia, Av. Vicente Andrés Estellés s/n, 46100, Burjasot, Valencia, Spain
Department of Physiology and Pharmacology, Federal University of Santa Maria (UFSM), 1000, Santa Maria, Brazil
Marti-Andres, P:
Department of Physiology, School of Pharmacy, University of Valencia, Av. Vicente Andrés Estellés s/n, 46100, Burjasot, Valencia, Spain
Pereda, J:
Department of Physiology, School of Pharmacy, University of Valencia, Av. Vicente Andrés Estellés s/n, 46100, Burjasot, Valencia, Spain
Campos, A:
Department of Chemistry, University of Aveiro, 3810-193, Aveiro, Portugal
Domingues, R:
Department of Chemistry, University of Aveiro, 3810-193, Aveiro, Portugal
Haj, F:
Department of Nutrition, University of California Davis, One Shields Ave, Davis, CA, 95616, USA
Sabater, L:
Department of Surgery, University of Valencia, University Clinic Hospital, Av. Blasco Ibañez 15, 46010, Valencia, Spain
De madaria E:
Department of Gastroenterology, University General Hospital of Alicante, Institute of Sanitary and Biomedical Research of Alicante (ISABIAL), Alicante, Spain
Sastre, J:
Department of Physiology, School of Pharmacy, University of Valencia, Av. Vicente Andrés Estellés s/n, 46100, Burjasot, Valencia, Spain.
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