Abstract:
Nonalcoholic steatohepatitis (NASH) is an inflammation of the liver, usually found in conjunction with Type II diabetes, and
results in fibrosis and a buildup of fatty acids. A current mouse model of this disease combines a knockout of the leptin
receptor (db/db) and a methionine and choline deficient (MCD) diet. Most fatty acids are synthesized in the liver and
transported to the brain, where they are essential for the structure and function of the nervous system. Due to the growing
prevalence of type II diabetes and NASH, a pilot study in the mouse model was conducted to see what effect this disease
had on fatty acid composition in the brain. Wild-type and db/db knockout mice were maintained on standard or MCD diets for
4 weeks. Whole brain total phospholipids were quantified using thin layer and gas chromatography. Compared to the wild
type without the MCD diet, the NASH model (db/db knockout with MCD diet) had significant differences in five of the 24
fatty acids measured (P<0.05) by ANOVA and Tukey’s test. Increases were observed in fatty acids 16:1 (+20%), 20:3n6 (+8%), and 22:5n3 (+51%), whereas decreases in fatty acids 20:1n9 (-10%) and 22:5n6 (-36%) were detected. These fatty acid alterations were the result of the combined effect of the knockout and the MCD diet. These observations suggest that alterations in brain phospholipid fatty acid composition may occur in NASH. The functional significance of these alterations must be determined in future studies.
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