Increased hepatic synthesis of cholesterol following jejunoileal bypass.

Fatty infiltration of liver and formation of cholesterol stones are significant problems following jejunoileal bypass for morbid obesity. This report evaluates hepatic lipid metabolism and fat absorption in genetically obese, bypassed, and lean Zucker rats. Ninety percent jejunoileal bypass was performed in 12 (500 grams) obese rats (BP). Similar numbers of unoperated "fat rats" (FR) and lean litter mates (LR) were controls. Food consumption, weight gain or loss, and fecal fat were evaluated. At 4 weeks serum triglycerides, hepatic cholesterol, total lipids, triglycerides, and hepatic synthesis of fatty acids and cholesterol were measured in vivo. Food intake was excessive in FR's (23.8 +/- 0.7 gm/day), decreased in BP (18.3 +/- 2.3 gm/day), and lowest in LRss ( less than 0.05) and excessive fecal fat excretion (p less than 0.05). Serum triglycerides were elevated in FR's (284 +/- 32 mg/dl), reduced in BP rats (148 +/- 20 mg/dl) (p less than 0.05), and low in LR's (86 +/- 16 mg/dl). Total hepatic lipids, triglycerides, and hepatic synthesis of fatty acids were elevated in FR's (p less than 0.05) and were unchanged by bypass. Hepatic cholesterol was similar in all groups. Hepatic synthesis of cholesterol, however, was increased significantly in bypassed rats (p less than 0.05), (BP--102 +/- 22 micronnmole/"C2"/minute/gm, FR--39 +/- 6.0, LR--30 +/- 4.0). Jejunolileal bypass in FR's results in weight loss, decreased food intake, increased fecal fat, decreased serum triglycerides, and increased hepatic synthesis of cholesterol. Bypass had little effect on reducing elevated hepatic lipids, triglycerides, or fatty acid synthesis in FR's. These data suggest that following bypass increased hepatic cholesterol synthesis (as a precursor for bile acids) is related to interruption of the enterohepatic circulation and bile salt pool depletion. This implies that excess synthesis of hepatic cholesterol results in supersaturation of bile which is choletithocenic and may explein in part the increased incidence of gall stones observed following jejunoileal bypass.