EFFECT OF DELTA(22)-5-BETA-TAUROCHOLENIC ACID AND DIETARY-FAT ON HEPATIC CHOLESTEROL AND FATTY-ACID IN HYPERGLYCEMIC-OBESE MICE

Previous work demonstrated that hyperglycemic obese mice (obob) fed a 1% corn oil diet accumulated cholesterol and fat in the liver when com pared with nonobese littermates. The present experiment was carried ou t to test the hypothesis that feeding the bile acid analog Delta(22)-5 beta-taurocholenic acid would correct this metabolic defect. Liver to tal fatty acid was greatly elevated in obob mice fed 1% corn oil compa red with nonobese controls (21.04+/-1.23% versus 4.41+/-0.27%). Incorp oration of [U-C-14]glucose into liver fatty acid was inhibited by taur ocholenic acid in both obese and nonobese mice fed 1% corn oil. Tauroc holenic acid reduced liver fatty acid in obob mice fed 1% corn oil to the level seen in nonobese mice(3.07+/-0.22% versus 4.41+/-0.27%). Cho lesterol greatly accumulated in the livers of obob mice fed 1% corn oi l compared with nonobese mice (0.97+/-0.08% versus 0.28+/-0.02%) and w as reduced to normal by feeding taurocholenic acid (0.27+/-0.05% versu s 0.28+/-0.01%) despite greatly elevating rates of incorporation of [U -C-14]glucose into liver cholesterol. Taurocholenic acid significantly reduced liver fat in obese mice fed 40% lard (11.62+/-1.41% versus 5. 87+/-1.03%) but had no significant effect on the percentage of liver c holesterol (0.68+/-0.05% versus 0.56+/-0.04%). It is suggested that th e elevation of liver cholesterol in obob mice fed 1% corn oil comes ab out through a defect in cholesterol removal from the liver, a defect c orrected by taurocholenic acid via increasing the excretion of cholest erol and bile acids in the bile by an as yet unknown mechanism. The ch olesterol accumulating in obob mice fed 40% lard occurs by a different mechanism than when these mice are red 1% corn oil since it is unaffe cted by taurocholenic acid.