Title

Phytochemical Induced Polarization of Macrophages: Implications on Obesity

Date of Award

2016

Degree Type

Thesis

Degree Name

Master of Science (MS)

First Advisor

Srujana Rayalam, PhD

Second Advisor

Rangaiah Shashidharamurthy, PhD

Third Advisor

Vishakha Bhave, PhD

Fourth Advisor

Bonnie Buxton, PhD

Fifth Advisor

Richard White, PhD, FAHA

Abstract

The epidemic of obesity is a major global problem because of the plethora of health and economic issues it induces. Obesity is associated with a state of chronic low-grade inflammation, which is reflected by an increased production of cytokines and pro-inflammatory adipokines by the obese adipose tissue. While energy storing white adipose tissue (WAT) primarily contributes to the inflammation associated with obesity, the role of energy dissipating brown adipose tissue (BAT) in inflammatory changes is not known. Recently, a third type of adipose tissue was discovered called beige adipose tissue which is functionally similar to BAT and has gained a lot on interest as a therapeutic target for obesity. Sympathetic activation of white adipocytes resulting from exposure to cold or beta adrenergic agonists results in the transdifferentiation of white adipocytes into beige adipocytes. Adipose tissue is composed of several cell types including macrophages and activation of anti-inflammatory M2 macrophages was shown to induce beiging of WAT in rodent models. Activated M2 macrophages secrete catecholamines which in turn induces beiging of WAT. In the current study, we propose to investigate novel strategies for beiging of WAT using plant chemicals. Phytochemicals like guggulsterone (GS) and resveratrol (RES) are studied for their anti-inflammatory and anti-obesity effects. In this study, we used a monocytic cell line RAW 264.7 cells to study the effects of RES and GS on M2 polarization and catecholamine production. We further confirmed the effects of iii phytochemical-induced catecholamines on beiging using 3T3-L1 murine adipocytes. We have employed ELISA, RT-PCR and Western blotting experiments to demonstrate polarization of macrophages, catecholamine biosynthesis and beiging of adipocytes.

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