Impact of chronic and acute high-fat feeding on acute experimental pancreatitis complicated by endotoxinaemia.
BACKGROUND
Obesity is associated with increased severity in patients with acute pancreatitis (AP). The underlying mechanisms are unknown. Genetically obese rats exhibit decreased survival rate in experimental AP, but the clinical relevance of this model of obesity may be questioned. It is proposed that development of organ failure in AP occurs in two stages: initial priming of leucocytes followed by a second inflammatory attack. The aim was to evaluate the impact of diet-induced obesity on outcome in a 'two-hit' model of AP.


METHODS
Lipopolysaccharide (LPS) was injected i.p. 3 h after retrograde bile duct infusion of sodium taurocholate in rats. Three experiments were done: 1) an LPS dose-response experiment, 2) chronic high-fat feeding (HF) for 16 weeks, and 3) acute HF for 10 days. Control rats received normal chow. Obesity, morphology and survival rate were assessed.


RESULTS
LPS dose-dependently decreased survival rate and increased morphological severity. HF increased weight, intra-abdominal and liver fat. Only acute HF induced hyperlipidaemia. In AP, acute obese rats exhibited less pancreatic inflammation, but total histological severity between groups was not different. In the chronic experiment only obese animals succumbed before 24 h of pancreatitis, but 72-h survival rate was not statistically different in either high-fat experiment.


CONCLUSIONS
An addition of LPS to AP decreases survival rate and intensifies the peri-pancreatic processes. Despite significant obesity, neither hyperlipidaemia nor increased intra-abdominal or hepatic fat influenced local pancreatic injury or survival negatively. The amount of fat per se seems not to be responsible for the deleterious influence of obesity on acute pancreatitis.
Segersvärd
R
R
Center for Surgical Sciences, Huddinge University Hospital, Karolinska Institutet, Stockholm, Sweden. ralf.segersvard@cfss.ki.se
Sylván
M
M
Lempinen
M
M
Larsson
J
J
Permert
J
J
D000818:Animals; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D023421:Models, Animal; D009765:Obesity / Q000150:complications* / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000150:complications* / Q000473:pathology*; D051381:Rats; D011924:Rats, Zucker
D004041:Dietary Fats; D008070:Lipopolysaccharides