Date of Award

Summer 2014

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Food Science

First Advisor

Kee-Hong Kim

Committee Chair

Kee-Hong Kim

Committee Member 1

Kimberly Buhman

Committee Member 2

Mario Ferruzzi

Abstract

The rise in obesity rate has drastically increased over the last few decades and has quickly grown into a worldwide epidemic. Large increases in visceral adipose tissue accumulation increase risk for metabolic disorders including insulin resistance, type 2 diabetes, and cardiovascular diseases. Currently, increased levels of circulating non-esterified fatty acids (NEFA) have been suggested to be the mediator linking obesity and type 2 diabetes. Studies identifying ways to alleviate mobilization of NEFA in adipose tissue via dietary phytochemicals may useful as a therapeutic approach. Despite the established benefits of resveratrol in health and in the development of obesity, the role of resveratrol metabolites in lipid metabolism remains unknown.^ The objectives of this study were to determine the role of resveratrol metabolites in adipose function with a focus on the effect in lipolysis and lipogenesis. Resveratrol metabolite, piceatannol, previously demonstrated its role as an antilipolytic agent through the suppression of lipolysis via protein degradation of adipose triglyceride lipase (ATGL) and comparative gene identification-58 (CGI-58). We hypothesized other resveratrol metabolites exhibit similar effects in modulating the lipolysis process. In our study, we examined several resveratrol metabolites and identified trans-3, 4', 5-trimethoxy resveratrol (TMR) having ability to suppress lipolysis in basal and stimulated conditions in mature murine adipocytes at non-cytotoxic levels. Upon further mechanistic studies, TMR at 50 µM reduces ATGL and CGI-58 protein expression with greatest efficacy in an acute, three hour treatment. mRNA expression analysis displayed that TMR may also play a role in transcriptionally regulating lipolytic genes. Additionally, we investigated the role of TMR in lipogenesis in maturing preadipocytes. Although TMR did not display significant reductions in lipid accumulation during lipogenesis, gene expression profiling indicates it may induce transcriptional remodeling of adipocyte function. Of interest, TMR upregulates expression of genes involved in mitochondria function suggesting increased catabolic processes, thermogenesis, and potential enhanced capacity for energy expenditure during development. Collectively, our study provides evidence that TMR, a resveratrol metabolite, might have a therapeutic potential in attenuating adiposity and its associated metabolic disorders.

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