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Fibrosis reduces severity of acute-on-chronic pancreatitis in humans.
Gastroenterology. 2013 Aug; 145(2):466-75.G

Abstract

BACKGROUND & AIMS

Acute pancreatitis (AP) and chronic pancreatitis (CP) share etiologies, but AP can be more severe and is associated with a higher rate of mortality. We investigated features of CP that protect against severe disease. The amount of intrapancreatic fat (IPF) is increased in obese patients and fibrosis is increased in patients with CP, so we studied whether fibrosis or fat regulate severity of AP attacks in patients with CP.

METHODS

We reviewed records from the University of Pittsburgh Medical Center/Presbyterian Hospital Autopsy Database (1998-2008) for patients with a diagnosis of AP (n = 23), CP (n = 35), or both (AP-on-CP; n = 15). Pancreatic histology samples from these patients and 50 randomly selected controls (no pancreatic disease) were analyzed, and IPF data were correlated with computed tomography data. An adipocyte and acinar cell Transwell coculture system, with or without collagen type I, was used to study the effects of fibrosis on acinar-adipocyte interactions. We studied the effects of nonesterified fatty acids (NEFAs) and adipokines on acinar cells in culture.

RESULTS

Levels of IPF were significantly higher in nonobese patients with CP than in nonobese controls. In patients with CP or AP-on-CP, areas of IPF were surrounded by significantly more fibrosis than in controls or patients with AP. Fat necrosis-associated peri-fat acinar necrosis (PFAN, indicated by NEFA spillage) contributed to most of the necrosis observed in samples from patients with AP; however, findings of peri-fat acinar necrosis and total necrosis were significantly lower in samples from patients with CP or AP-on-CP. Fibrosis appeared to wall off the fat necrosis and limit peri-fat acinar necrosis, reducing acinar necrosis. In vitro, collagen I limited the lipolytic flux between acinar cells and adipocytes and prevented increases in adipokines in the acinar compartment. This was associated with reduced acinar cell necrosis. However, NEFAs, but not adipokines, caused acinar cell necrosis.

CONCLUSIONS

Based on analysis of pancreatic samples from patients with CP, AP, or AP-on-CP and in vitro studies, fibrosis reduces the severity of acute exacerbations of CP by reducing lipolytic flux between adipocytes and acinar cells.

Authors+Show Affiliations

Department of Medicine, University of Pittsburgh Medical Center Passavant, Pittsburgh, Pennsylvania, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

23684709

Citation

Acharya, Chathur, et al. "Fibrosis Reduces Severity of Acute-on-chronic Pancreatitis in Humans." Gastroenterology, vol. 145, no. 2, 2013, pp. 466-75.
Acharya C, Cline RA, Jaligama D, et al. Fibrosis reduces severity of acute-on-chronic pancreatitis in humans. Gastroenterology. 2013;145(2):466-75.
Acharya, C., Cline, R. A., Jaligama, D., Noel, P., Delany, J. P., Bae, K., Furlan, A., Baty, C. J., Karlsson, J. M., Rosario, B. L., Patel, K., Mishra, V., Dugampudi, C., Yadav, D., Navina, S., & Singh, V. P. (2013). Fibrosis reduces severity of acute-on-chronic pancreatitis in humans. Gastroenterology, 145(2), 466-75. https://doi.org/10.1053/j.gastro.2013.05.012
Acharya C, et al. Fibrosis Reduces Severity of Acute-on-chronic Pancreatitis in Humans. Gastroenterology. 2013;145(2):466-75. PubMed PMID: 23684709.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fibrosis reduces severity of acute-on-chronic pancreatitis in humans. AU - Acharya,Chathur, AU - Cline,Rachel A, AU - Jaligama,Deepthi, AU - Noel,Pawan, AU - Delany,James P, AU - Bae,Kyongtae, AU - Furlan,Alessandro, AU - Baty,Catherine J, AU - Karlsson,Jenny M, AU - Rosario,Bedda L, AU - Patel,Krutika, AU - Mishra,Vivek, AU - Dugampudi,Chandra, AU - Yadav,Dhiraj, AU - Navina,Sarah, AU - Singh,Vijay P, Y1 - 2013/05/15/ PY - 2012/08/12/received PY - 2013/04/15/revised PY - 2013/05/06/accepted PY - 2013/5/21/entrez PY - 2013/5/21/pubmed PY - 2013/9/28/medline KW - AP KW - ATP KW - BMI KW - CP KW - CT KW - FN KW - IPF KW - Inflammation KW - Mechanism KW - NEFA KW - Necrosis KW - PFAN KW - PI KW - Pancreas KW - SAP KW - UFA KW - acute pancreatitis KW - adenosine triphosphate KW - body mass index KW - chronic pancreatitis KW - computed tomography KW - fat necrosis KW - intrapancreatic fat KW - nonesterified fatty acid KW - peri-fat acinar necrosis KW - propidium iodide KW - severe acute pancreatitis KW - unsaturated fatty acid SP - 466 EP - 75 JF - Gastroenterology JO - Gastroenterology VL - 145 IS - 2 N2 - BACKGROUND & AIMS: Acute pancreatitis (AP) and chronic pancreatitis (CP) share etiologies, but AP can be more severe and is associated with a higher rate of mortality. We investigated features of CP that protect against severe disease. The amount of intrapancreatic fat (IPF) is increased in obese patients and fibrosis is increased in patients with CP, so we studied whether fibrosis or fat regulate severity of AP attacks in patients with CP. METHODS: We reviewed records from the University of Pittsburgh Medical Center/Presbyterian Hospital Autopsy Database (1998-2008) for patients with a diagnosis of AP (n = 23), CP (n = 35), or both (AP-on-CP; n = 15). Pancreatic histology samples from these patients and 50 randomly selected controls (no pancreatic disease) were analyzed, and IPF data were correlated with computed tomography data. An adipocyte and acinar cell Transwell coculture system, with or without collagen type I, was used to study the effects of fibrosis on acinar-adipocyte interactions. We studied the effects of nonesterified fatty acids (NEFAs) and adipokines on acinar cells in culture. RESULTS: Levels of IPF were significantly higher in nonobese patients with CP than in nonobese controls. In patients with CP or AP-on-CP, areas of IPF were surrounded by significantly more fibrosis than in controls or patients with AP. Fat necrosis-associated peri-fat acinar necrosis (PFAN, indicated by NEFA spillage) contributed to most of the necrosis observed in samples from patients with AP; however, findings of peri-fat acinar necrosis and total necrosis were significantly lower in samples from patients with CP or AP-on-CP. Fibrosis appeared to wall off the fat necrosis and limit peri-fat acinar necrosis, reducing acinar necrosis. In vitro, collagen I limited the lipolytic flux between acinar cells and adipocytes and prevented increases in adipokines in the acinar compartment. This was associated with reduced acinar cell necrosis. However, NEFAs, but not adipokines, caused acinar cell necrosis. CONCLUSIONS: Based on analysis of pancreatic samples from patients with CP, AP, or AP-on-CP and in vitro studies, fibrosis reduces the severity of acute exacerbations of CP by reducing lipolytic flux between adipocytes and acinar cells. SN - 1528-0012 UR - https://www.unboundmedicine.com/medline/citation/23684709/Fibrosis_reduces_severity_of_acute_on_chronic_pancreatitis_in_humans_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(13)00724-5 DB - PRIME DP - Unbound Medicine ER -