Biliary lipids, cholesterol and bile synthesis: different adaptive mechanisms to dietary cholesterol in lean and obese subjects

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Abstract
Increased biliary cholesterol secretion together with elevated cholesterol synthesis may predispose obese subjects to cholesterol gallstone formation. To investigate whether processing of dietary cholesterol is altered in obesity, we enrolled eight lean and seven obese subjects in a double-blind crossover study. Cholesterol consumption was 300 mg/day on low and 1300 mg/day on high cholesterol diet. After 3 weeks on either diet, hepatic bile was collected to determine biliary lipid secretion, and bile salt composition by high-performance liquid chromatography and cholesterol saturation index was calculated. Cholesterol synthesis was measured employing mass isotopomer distribution analysis. Bile acid synthesis via neutral and acidic pathway was assessed by serum levels of 7alpha-hydroxy-4-cholesten-3-one and 27-hydroxycholesterol. Cholesterol synthesis was increased in obese compared with lean and feedback inhibited only in obese. On low cholesterol diet, cholesterol secretion was doubled in obese but bile acid composition and synthesis was similar between the two groups. After high cholesterol diet, cholesterol saturation index and bile secretion were unchanged. In contrast to obese, lean increased bile acid synthesis only via the acidic pathway. Dietary cholesterol appears to preferentially induce bile acid synthesis via the acidic pathway in lean, whereas cholesterol synthesis was inhibited in obese. Thus, stable cholesterol saturation index may be achieved by different mechanisms.

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