Biomedical Sciences ETDs

Author

Nicholas Card

Publication Date

7-1-2013

Abstract

Obesity is an increasing trend within the United States and the importance of addressing both causation and effects of obesity are becoming more important. It has been shown that environment, genetics, and social behavior factors can lead to an increased risk of obesity. Obesity has also been associated with several negative health concerns including increased risk for heart disease, cancer, poor nutrition, and diabetes, among others. Beyond identifying individual factors that may lead to obesity, and be associated with it, it is important to take into account complex obese biological systems which may have multiple factors compounding any health problems. Evidence has shown that obese adipose tissue can develop a state of chronic low grade inflammation with the presence of pro-inflammatory cytokines. Normal physiological agents, such as β-adrenergic agonists (for example epinephrine), can induce lipolytic function, though it has now also been shown that these pro-inflammatory cytokines can also stimulate lipolysis. To begin addressing the more complex issue of multiple obesity-related factors that contribute to health problems, we looked at a direct multi-factor based compounding system. This system assessed the impact of multiple pro-inflammatory cytokines (Tumor Necrosis Factor-alpha and Interleukin-6) in combination with a β-adrenergic agonist (isoproterenol) to determine any combinatory effects on lipolytic function. Another biological system we used to assess lipolytic regulation was that of a disease based mouse model (Niemann-Pick Disease Type C1 Carrier — NPC1 +/-) which has been shown to affect cholesterol transport and cause weight gain and even obesity. We assessed the lipolytic impact that both of these systems may have. In the first system, assessments showed that pro-inflammatory cytokines, in combination with a β-adrenergic response, can induce an additive lipolytic stimulation. In the second system, decreased NPC1 gene dosage appeared to have an impact on Hormone Sensitive Lipase (HSL) mRNA levels and trends toward a decrease in glycerol release, an effective measure of lipolytic function. In all, these findings demonstrate that complex obese biological systems present multiple factors (either direct stimulating agents or indirect disease mechanisms) that can have substantial effects on lipolytic function.

Keywords

lipolysis, inflammation, adipocytes, adipose tissue, glycerol release

Document Type

Thesis

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Masters

Department Name

Biomedical Sciences Graduate Program

First Advisor

Orlando, Dr. Robert

First Committee Member (Chair)

Sun, Dr. Yijuan

Second Committee Member

Garver, Dr. William

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