Date of Award:

5-2013

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Biology

Committee Chair(s)

David A. York

Committee

David A. York

Committee

Daryll B. DeWald

Committee

Timothy Gilbertson

Committee

Ilka Nemere

Committee

MieJung Park-York

Abstract

The prevalence of obesity is rapidly increasing; it is now one of the most serious public health problems worldwide. Obesity is thought to reflect the interaction between genetics and modern life style. In particular, high fat diets (HFD) are considered as a major contributing factor to the development of obesity and type 2 diabetes as well as other metabolic disorders such as cardiovascular disease, Alzheimer’s disease and some types of cancer. Recently, it has been suggested that insulin actions in the brain are important in the regulation of energy homeostasis and peripheral metabolism.

With the support of USTAR (The Utah Science Technology and Research program), Hyoungil Oh, a Ph.D student in Dr. York’s research group in the Department of Biology at Utah State University, studied the effect of HFD and elevated saturated fatty acids on brain insulin signaling pathways. The hypothesis investigated was that HFD induce insulin resistance in specific regions of the brain to impair energy homeostasis. The experimental model used was Sprague-Dawley rats fed on either High or Low fat diets in their cages for 3 days. In addition, cultures of brain neuronal cells were used to study the mechanism through which fatty acids inhibited insulin signaling.

The results of these studies confirmed the hypothesis that dietary fat, specifically increased levels of saturated fatty acids inhibited brain insulin signaling in neuronal cells in two parts of the brain, the hypothalamus and amygdala, of rats. It further suggested that a specific enzyme, protein kinase Cθ mediated this fatty acid inhibition of insulin signaling. This work contributes to our understanding of why dietary fat can lead to increased body weight and altered peripheral metabolism by inhibiting insulin actions in specific regions of the brain and may be helpful in the development of new treatment approaches for metabolic disorders such as obesity and Type 2 Diabetes.

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Comments

This work made publicly available electronically on December 21, 2012.

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