High Fat/Cholesterol Diet Leads to Accumulation of an Electron-Dense Lamellar Material in Pig Hepatocytes
Cristina D Cole, Lauren N Bell, William G Van Alstine, Mouhamad Alloosh, Michael Sturek, Naga Chalasani, Romil Saxena. Indiana University School of Medicine, Indianapolis, IN; Purdue University School of Veterinary Medicine, West Lafayette, IN
Background: Nonalcoholic fatty liver disease, one of the most common chronic liver diseases in humans, is clinically categorized into simple steatosis and nonalcoholic steatohepatitis (NASH). While simple steatosis is believed to be reversible, NASH progresses to cirrhosis over a variable period of time. Diagnosis of NASH is based on the presence of ballooned hepatocytes, which are thought to signify cellular damage by as yet undefined factors. We describe the ultrastructural changes in hepatocytes of Ossabaw swine, which represent a large animal model of metabolic syndrome and nutritionally-induced NASH.
Design: Ossabaw swine were fed a modified atherogenic diet (NASH diet group; n=5) consisting of 16.5% calories from protein, 20% calories from fructose, 46% calories from fat (admixture of hydrogenated soybean oil, coconut oil, and lard), and 2% cholesterol or standard chow (control group; n=6) for 24 weeks. Differences between the two groups were evaluated on H&E sections and electron microscopy (EM).
Results: Hepatocytes in pigs fed the NASH diet show accumulation of electron-dense material arranged as whorled lamellar structures (n=5) (fig 1). This material is present within membrane-bound vesicles, consistent with secondary lysosomes. Hepatocytes in the control group do not contain similar material (n=0) (fig 2). All but one pig fed the NASH diet show variable numbers of enlarged, pale staining hepatocytes on H&E stain (n=4). This change is not seen in the control group (n=0). Steatosis is not seen on H&E stain, but scattered lipid droplets are present on EM in both groups.
Conclusions: Pigs fed the NASH diet accumulate an abnormal material in their hepatocytes, which is reminiscent of membranous profiles observed in a variety of conditions such as phospholipidosis and the phospholipid storage disease, Niemann-Pick. This similarity raises the possibility that the accumulated material represents phospholipids, possibly arising from damaged cellular or subcellular membranes. This may in turn reflect the effects of increased hepatocyte lipid loading. The finding of similar material in human NASH may pave the way for more accurate identification of ballooned hepatocytes.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 232, Wednesday Morning