Year of Publication

2012

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Medicine

Department

Physiology

First Advisor

Dr. David C. Randall

Second Advisor

Dr. Timothy S. McClintock

Abstract

Dietary saturated fat intake contributes to diabetes and cardiovascular disease, as shown in numerous animal and human studies. However, the hypothesis that stearic acid, a saturated fat, has beneficial effects on these conditions has not been adequately tested. Leptin receptor deficient mice (db/db) and wild-type mice were fed either chow or a high fat diet enriched in either stearic acid or oleic acid for ten weeks. The progression of diabetes was evaluated with blood glucose, insulin, and metabolic parameter measurements. At the conclusion of the study, pancreatic islet organization was examined, and blood, liver and feces were assayed for fatty acid content.

The stearic acid enriched diet prevented increases in blood glucose levels independently of weight loss in db/db mice compared to an oleic acid or chow diet. Diabetic mice fed stearic acid maintained insulin responsiveness and pancreatic islet organization compared to the db/db mice fed chow and oleic diets. The islet organization of the stearic acid fed mice did not change over the course of the study and was similar to that of wild-type mice fed the same diet. Conversely, diabetic mice fed oleic acid and chow diets had decreased insulin responsiveness and disorganized islets. Stearic acid fed db/db mice had high fecal fat content and caloric intake calculations indicated low absorption of this fat.

Switching to stearic acid after prolonged hyperglycemia had a rescue effect on blood glucose levels. After feeding diabetic and wild-type mice standard chow diets for 6, 8, and 10 weeks to establish hyperglycemia, mice switched to a high fat diet enriched in stearic acid, but not one enriched in oleic acid diet, had significant reductions in blood glucose levels.

The ability of a stearic acid enriched high fat diet to slow the progression of diabetes and reverse hyperglycemia in db/db mice argues that risks and benefits of fats in the diet depend on the chemical structure, rather than the chemical class, of fats ingested. The beneficial effect of stearic acid appears to be associated with a decreased absorption of dietary fat.

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