Doctoral Dissertations

Date of Award

8-2003

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Human Ecology

Major Professor

Michael R. Zemel

Committee Members

Naima Moustaid-Moussa, Jay Whelan, Michael Karlstad

Abstract

Dietary macronutrient composition plays a critical role in health and disease. The contribution of dietary carbohydrate source in the development of obesity and related diseases is often given minimal attention. The present studies demonstrate that both quantitative and qualitative changes in dietary carbohydrate influence body composition and adiposity in a rodent model of diet-induced obesity. In heterozygous (fa/+) Zuker rats, consumption of a high-fat, carbohydrate free ad libitum, attenuated weight gain and adiposity by increasing energy efficiency and blunting expression of fatty acid synthase, a key enzyme in de novo lipogenesis. These effects were independent of significant changes in plasma insulin levels. Moreover, the addition of a modest level of sucrose to the high-fat diet completely reversed the effects of carbohydrate restriction, resulting in significant increases in body weight and adiposity, mediated in part by enhanced expression of fatty acid synthase.

In a separate series of experiments, we evaluated the effect of ad libitum or energy restricted (70% of ad libitum) high-fat diets, varying in carbohydrate source on adiposity in aP2-Agouti transgenic mice. In the context of an energy restricted diet, animals consuming diets shown to result in lower postprandial blood glucose levels (ROLL and MUNG) reduced adipose tissue accumulation in the perirenal and retroperitoneal and resulted in smaller adipocytes compared with diets evoking greater postprandial blood glucose excursions.

In ad libitum fed animals, the expression of lipogenic enzymes in the liver and selected adipose tissue depots was significantly enhanced by consumption of a high-fat, sucrose-rich diet. Expression of genes or fatty acid oxidation was enhanced in the muscle of animals consuming the low-glucose response diets. These data suggest that dietary carbohydrate source modulates adipose tissue accumulation and body weight by partitioning substrate utilization between lipid oxidation in skeletal muscle, and reducing lipogenesis in visceral adipose tissue.

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