Cholesterol gallstones are a serious and expensive complication of the Western diet, commonly occurring in overweight women consuming too many calories and expressing a high plasma lipid, hyperinsulinemic profile. An elevated HDL2 pool seems conducive to gallstone induction for reasons that are unclear. The hamster also develops which the same metabolic profile, including an exaggerated HDL2 level. Thus, chronic feeding (postprandial condition) seems critical to biliary cholesterol saturation. Accordingly this research will investigate the nutritional aspects of this phenomenon by investigating diet-induced modulations in hamster biliary secretion.
The specific aims will be to identify the normal circadian flux (fed/fast cycle) of newly synthesized vs. performed cholesterol into biliary lipids in the hamster fed purified diets; to determine how this flux is altered by specific dietary components manipulated to enhance gallstone formation; and to examine specific lipoproteins contribution to that sterol flux in hamsters and compare these results to similar data to be generated in the human hepatoma cell line (HEP G2 cells) as a potential model for investigating mechanisms of lithogenesis. Methods will include mass measure of cholesterol synthesis with 3H2O, assay of biliary lipids collected by bile fistulas, in addition to the lithogenic index, and gallstones in gallbladder bile and in nascent biliary secretions. An index of hepatic cholesterol metabolism will be based on mRNA abundance for key apoliproteins, AI, E, B and LDL receptor. Collectively these data will provide new insights on the mechanisms of diet-induced gallstone formation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK035375-08
Application #
3233685
Study Section
Nutrition Study Section (NTN)
Project Start
1985-04-01
Project End
1994-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Brandeis University
Department
Type
Schools of Arts and Sciences
DUNS #
616845814
City
Waltham
State
MA
Country
United States
Zip Code
02454
Trautwein, E A; Liang, J; Hayes, K C (1993) Cholesterol gallstone induction in hamsters reflects strain differences in plasma lipoproteins and bile acid profiles. Lipids 28:305-12
Trautwein, E A; Liang, J; Hayes, K C (1993) Plasma lipoproteins, biliary lipids and bile acid profile differ in various strains of Syrian hamsters Mesocricetus auratus. Comp Biochem Physiol Comp Physiol 104:829-35
Hayes, K C; Khosla, P; Kaiser, A et al. (1992) Dietary fat and cholesterol modulate the plasma lipoprotein distribution and production of pigment or cholesterol gallstones in hamsters. J Nutr 122:374-84
Hayes, K C; Livingston, A; Trautwein, E A (1992) Dietary impact on biliary lipids and gallstones. Annu Rev Nutr 12:299-326
Hayes, K C; Khosla, P (1992) Dietary fatty acid thresholds and cholesterolemia. FASEB J 6:2600-7
Hayes, K C; Pronczuk, A; Lindsey, S et al. (1991) Dietary saturated fatty acids (12:0, 14:0, 16:0) differ in their impact on plasma cholesterol and lipoproteins in nonhuman primates. Am J Clin Nutr 53:491-8
Hayes, K C; Khosla, P; Pronczuk, A (1991) Diet-induced type IV-like hyperlipidemia and increased body weight are associated with cholesterol gallstones in hamsters. Lipids 26:729-35
Maclure, K M; Hayes, K C; Colditz, G A et al. (1990) Dietary predictors of symptom-associated gallstones in middle-aged women. Am J Clin Nutr 52:916-22
Lindsey, S; Benattar, J; Pronczuk, A et al. (1990) Dietary palmitic acid (16:0) enhances high density lipoprotein cholesterol and low density lipoprotein receptor mRNA abundance in hamsters. Proc Soc Exp Biol Med 195:261-9
Maclure, K M; Hayes, K C; Colditz, G A et al. (1989) Weight, diet, and the risk of symptomatic gallstones in middle-aged women. N Engl J Med 321:563-9

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