Degree Type

Dissertation

Date of Award

1988

Degree Name

Doctor of Philosophy

Department

Food and Nutrition

First Advisor

Jacqueline Dupont

Abstract

Hepatic microsomal hydroxymethylglutaryl coenzyme A reductase (HMGR) activity was studied in obese and nonobese C57BL/6J, obese and nonobese DW db[superscript] Pas, and CBA/J mice. Mice exhibited differences due to age, sex, genotype, strain, and diets with variations in pectin and fat compositions and responded to light cycle and feeding schedule;CBA/J (hyporesponders to diet-induced hypercholesterolemia) and C57BR/cdJ (hyperresponders) mice showed metabolic differences in the response to small changes in dietary fats. Neither the US74 diet (40 en% fat, 347 mg cholesterol/1000 Kcal, P/S = 0.24) nor the modified fat diet (30 en% fat, 46 mg cholesterol/1000 Kcal, P/S = 0.91) induced hypercholesterolemia in either strain. The CBA/J mouse maintained constant serum cholesterol level mainly by adjusting the hepatic HMGR activity while the C57BR/cdJ mouse by changing the fecal excretion of cholesterol. Compared to the modified fat diet, the US74 diet decreased hepatic HMGR activity and fecal ergosterol and [beta]-sitosterol, and increased fecal cholesterol in both strains, and increased serum total to HDL cholesterol ratio, liver microsomal cholesterol and hepatic microsomal cholesterol 7[alpha]-hydroxylase activity in the CBA/J strain;Effects of dietary fats on whole body cholesterol kinetics were studied in CBA/J and C57BR/cdJ mice. Mice fed the US74 diet accumulated more cholesterol in livers than did those fed the modified fat diet, and the C57BR/cdJ strain had less cholesterol in serum, liver and carcass, but more in heart compared to the CBA/J strain. The kinetic data were consistent with the cholesterol mass data. Computer analysis using a three-compartment model (serum, heart and liver) showed that liver and serum were in rapid balance except in CBA/J mice fed the US74 diet. The heart showed an initial buildup of radioactivity which started to die away after 4 days;We conclude that the metabolic responses to small differences in dietary fat are different in CBA/J and C57BR/cdJ mice. A defect in the hepatic chylomicron remnant receptor in the C57BR/cdJ mouse was proposed to explain its metabolic responses to diets and susceptibility to atherogenic diet-induced hypercholesterolemia.

DOI

https://doi.org/10.31274/rtd-180813-11353

Publisher

Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/

Copyright Owner

Son-iu Kuan

Language

en

Proquest ID

AAI8825409

File Format

application/pdf

File Size

175 pages

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