Role of obesity in the release of extracellular nucleosomes in acute pancreatitis: a clinical and experimental study

Salvador Pérez, Isabela Finamor, Pablo Martí-Andrés, Javier Pereda, Ana Campos, Rosário Domingues, Fawaz Haj, Luis Sabater, Enrique de-Madaria, Juan Sastre

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalInternational Journal of Obesity
DOIs
StateAccepted/In press - May 1 2018

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

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    Pérez, S., Finamor, I., Martí-Andrés, P., Pereda, J., Campos, A., Domingues, R., Haj, F., Sabater, L., de-Madaria, E., & Sastre, J. (Accepted/In press). Role of obesity in the release of extracellular nucleosomes in acute pancreatitis: a clinical and experimental study. International Journal of Obesity, 1-11. https://doi.org/10.1038/s41366-018-0073-6