title: Hypertriglyceridemia aggravates ER stress and pathogenesis of acute pancreatitis.
abstract: OBJECTIVE
  Endoplasmic reticulum (ER) stress and hypertriglyceridemia (HTG) have been implicated in acute pancreatitis (AP).
  
  
  METHODS
  For cellular model, rat exocrine acinar cells were preincubated with palmitic acid (0.05 or 0.1 mmol/L, 3 h) and stimulated with a cholecystokinin analog, CCK-8 (100 pmol/L, 30 min). For animal model, rats fed a high-fat diet to cause HTG and AP was induced by injection of caerulein (20 μg/kg). Injury to pancreatic cells was estimated by measuring amylase secretion, intracellular calcium concentration, apoptosis and histological changes. Expression of genes involved in ER stress-induced unfolded protein response (UPR) was monitored by RT-PCR and immunohistology.
  
  
  RESULTS
  In CCK-8 stimulated rat acinar cells, preincubation with PA caused an increased secretion of amylase, a higher and prolonged accumulation of intracellular calcium and increased apoptosis. Rats on high-fat diet had significantly elevated serum triglyceride levels. Induction of AP led to increased apoptosis in pancreatic tissue on high-fat diet than controls. For favoring HTG, expression of UPR components, GRP78/Bip, XBP-1, GADD153/CHOP and caspase-12 was upregulated.
  
  
  CONCLUSIONS
  Levels of markers of AP pathogenesis and components of UPR were elevated in the presence of excess fatty acids in pancreatic acinar cells. HTG appears to aggravate ER-stress and pathogenesis of AP.
authors.affiliation: Institute for the Study of Pancreatic Diseases, Department of Gastroenterology, Shanghai First People's Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zeng
authors.forename: Xingpeng
authors.initials: X
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Kai
authors.initials: K
authors.lastname: Wu
authors.forename: Jingjing
authors.initials: J
authors.lastname: Ma
mesh_terms: D000208:Acute Disease; D000681:Amylases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002108:Ceruletide; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D005786:Gene Expression Regulation; D015228:Hypertriglyceridemia / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D019308:Palmitic Acid / Q000378:metabolism; D046790:Pancreas, Exocrine / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012844:Sincalide / Q000378:metabolism; D013997:Time Factors; D046509:Tissue Culture Techniques; D056811:Unfolded Protein Response / Q000235:genetics
chemical_list: D019308:Palmitic Acid; D002108:Ceruletide; D000681:Amylases; D012844:Sincalide; D002118:Calcium