title: Pancreatitis associated with hyperlipoproteinaemia type I in mink (Mustela vison): earliest detectable changes occur in mitochondria of exocrine cells.
abstract: Pancreatic tissue from young mink homozygous for a mutation in the lipoprotein lipase gene was studied by light and electron microscopy, with the aim of describing the earliest detectable changes in a process which rapidly progresses into overt pancreatitis. The mutation leads to hyperlipoproteinaemia, corresponding to hyperlipoproteinaemia type I in man. Assessment of relevant hepatic and pancreatic enzymes were included in the investigation. The earliest detectable changes consisted of widespread swelling and vacuolation of exocrine cells, arising mainly from swollen mitochondria. To a lesser extent, vesiculation of endoplasmic reticulum occurred. Mitochondria exhibited various changes, including cavitation and dilution of the matrix, with shortened and disorganized cristae displaced towards the periphery. Lamellar figures that developed within mitochondria were numerous. Acinar lumina were somewhat dilated, while plasma membranes were relatively well preserved and secretory granules seemed unchanged. Exfoliative processes progressively occurred, resulting in total necrosis of groups of parenchymal cells, while intercalated ducts were spared. The necrosis was rapidly followed by inflammatory reactions. The activity of the mitochondrial enzyme carnitine O-palmitoyltransferase, essential for the transport of fatty acids into the mitochondria, was lower in the pancreas than in the liver. The activity of the peroxisomal fatty acid beta-oxidation was high in the liver and low in the pancreas of both lipoprotein lipase-deficient and control mink. It is concluded that pancreatic lesions associated with hyperlipoproteinaemia start in exocrine cells, and are most probably the result of a metabolic disturbance, possibly a toxic effect of an excess of free fatty acids.
authors.affiliation: Norwegian School of Veterinary Science, Oslo, Norway.
authors.forename: K
authors.initials: K
authors.lastname: Nordstoga
authors.forename: B
authors.initials: B
authors.lastname: Christophersen
authors.forename: B
authors.initials: B
authors.lastname: Ytrehus
authors.forename: A
authors.initials: A
authors.lastname: Espenes
authors.forename: H
authors.initials: H
authors.lastname: Osmundsen
authors.forename: T
authors.initials: T
authors.lastname: Landsverk
authors.forename: T
authors.initials: T
authors.lastname: Olivecrona
authors.forename: G
authors.initials: G
authors.lastname: Olivecrona
mesh_terms: D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000648:ultrastructure; D006720:Homozygote; D008072:Hyperlipoproteinemia Type I / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D008907:Mink; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure*; D008933:Mitochondrial Swelling / Q000235:genetics; D009336:Necrosis; D010088:Oxidoreductases / Q000378:metabolism; D010170:Palmitoyl-CoA Hydrolase / Q000378:metabolism; D046790:Pancreas, Exocrine / Q000201:enzymology / Q000473:pathology*; D010195:Pancreatitis / Q000201:enzymology / Q000235:genetics / Q000473:pathology*
chemical_list: D010088:Oxidoreductases; D002374:Catalase; C028427:palmitoyl CoA oxidase; D002334:Carnitine O-Palmitoyltransferase; D010170:Palmitoyl-CoA Hydrolase