Hypertriglyceridemia aggravates ER stress and pathogenesis of acute pancreatitis

Endoplasmic reticulum (ER) stress and hypertriglyceridemia (HTG) have been implicated in acute pancreatitis (AP).

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.

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.

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.