(P20-010-24) Role of Dietary Cholesterol and Methionine on the Hepatic Markers of Portal Hypertension

Objectives: Since the combined effects of Cho and Met have not been studied in the liver and as foods of animal origin like meat, dairy and poultry extensively consumed in the US which are rich in cholesterol (Cho) and methionine (Met), the precursor of homocysteine (Hcy), we investigated the combined effects of Cho and Met. Additionally, sitagliptin was investigated for its antifibrotic effects.

Methods: Studies on the hepatic effects of a combination of Met+Cho were conducted in adult male SD rats fed ad libitum a control (Con) diet, or enriched with 1.5% Met, or 2.0% Cho, or their combination (1.5% Met+ 2.0% Cho) for 35 days. Liver samples were analyzed by conventional methods for the marker genes of portal hypertension. Portal hypertension (PH) being a likely complication in hepatic fibrosis and cirrhosis, we analyzed for the marker genes of PH.

Results: Contrary to the anticipation of seeing an additive effect of hepatic inflammation and fibrosis in the combination diet-fed rats, we saw such responses only in high Cho-fed rats. Interestingly, Met (due to Hcy) did not show such changes and in fact its presence in the combination diet prevented the fibrotic and inflammatory changes that were seen due to Cho. Sitagliptin, surprisingly exacerbated inflammation and fibrosis in the livers of high Cho rats by multiple folds as previously reported. However, Met (met+Cho diet) countered even the exacerbated fibrotic and inflammatory responses due to sitagliptin in high Cho-fed rats. The marker genes of PH were induced again only in high Cho-fed rats. Met in the combination diet helped in opposing the induction of genes of PH.

Conclusions: Feeding of high cholesterol diet promotes the development of scar tissue in the liver, which may result in portal hypertension and these changes were countered due to the presence of methionine, implying a beneficial role for methionine.

Funding Sources: (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health
Louisiana Biomedical Research Network