IMPACT OF GINGER-RELATED COMPOUNDS, ZINGERONE AND CURCUMIN, ON PPARγ ACTIVATION, LIPID ACCUMULATION, AND CELL VIABILITY IN 3T3-L1 FIBROBLASTS

Author

Nicole Louise Lence, Southern Illinois University CarbondaleFollow

Date of Award

8-1-2013

Degree Name

Master of Science

Department

Food and Nutrition

First Advisor

Davis, Jeremy

Abstract

The prevalence over overweight and obesity has risen dramatically during the past few decades corresponding with a clustering of metabolic pathologies including cardiovascular disease, type 2 diabetes, endometrial, breast, and colon cancers. Obesity is not only implicated as one of the primary causes of these degenerative diseases but also represents a major component of the metabolic syndrome. In obesity, the primary defect leading to these metabolic pathologies appears to be an impairment of adipogenesis resulting in adipocyte hypertrophy and dysfunction. Current pharmacological therapies prescribed for T2DM, such as thiazolidinones (TZDs), improve insulin sensitivity through regulation of adipogenesis. However, utilization of these drugs is often associated with several side effects, including weight gain, liver disease, and bone loss. Thus, there is an important need to identify alternative therapies that can modify these adipogenic regulators without adverse complications. Ginger (Zingiber officinale Roscoe), a member of the Zingiberaceae family, has a long history of use in traditional medicine and as been used for a wide array of ailments such as arthritis, diabetes, nausea, and stroke. Several studies have demonstrated anti-emetic, anti-inflammatory, and anti-carcinogenic properties of ginger. When used at high concentrations (μM), two phytochemcials derived from ginger root curcumin and zingerone, have been shown to promote weight loss and modify adipogenic signaling. However, due to the low bioavailability of curcumin the physiological relevance of these findings remains to be determined. The purpose of this study was to determine the extent to which curcumin and zingerone modify adipogenesis in 3T3-L1 fibroblasts. To determine the effects of the bioactive components in varying concentrations, 3T3-L1 preadipocytes were exposed to either 100pM, 100nM, or 100μM of curcumin or zingerone and tested for cell viability, lipid accumulation, and PPARγ activation. The results of this study suggest that high concentrations of curcumin (100 μM) may be toxic to 3T3-L1 fibroblasts in vitro and significantly inhibit both cell viability and lipid accumulation. The resultant low PPARγ activity may be attributable to cell necrosis rather than dose-dependent inhibition, suggesting need for further research into extreme curcumin supplementation. While results for zingerone did not differ significantly from vehicle, the results of this study provide evidence that further research is needed to ascertain to what extent curcumin and zingerone dose-dependently modify PPARγ and TCF/LEF in 3T3-L1 fibroblasts using lower physiologically relevant doses.