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Environment and Obesity: Preventing Stress Hormone-Induced Obesity With Genistein
Principal Investigator
Lu, Zhidong
Institute Receiving Award
Northwestern University
Location
Chicago, IL
Grant Number
K22ES014723
Funding Organization
National Institute of Environmental Health Sciences
Award Funding Period
22 Aug 2007to30 Apr 2010
DESCRIPTION (provided by applicant)
Physiological responses to environmental stressors elevate plasma stress hormones including glucocorticoids, which are well known to cause obesity. Our long-term goal is to prevent obesity caused by environmental exposures. Genistein, an environmental estrogen-like compound found in food sources, has been demonstrated to have anti-obesity properties. However, whether genistein counteracts the deleterious effects of glucocorticoids on metabolic genes, food intake behavior, and fat deposition is not known. The candidate hypothesizes that genistein may prevent glucocorticoid-induced obesity in a rodent model. To test this hypothesis, genes involved in glucocorticoid-induced obesity will be identified in two key metabolic organs: adipose tissue and brain. Similarly, the gene regulatory effects of genistein in these two metabolic control centers will also be determined. In addition, the candidate will investigate whether genistein counteracts the adverse actions of glucocorticoids in metabolic gene networks, food intake, and body fat accretion. To achieve these goals, mice will be treated with vehicle, corticosterone (an endogenous glucocorticoid), genistein, or corticosterone plus genistein. Microarray analysis will be performed to define the regulatory effects of each treatment on gene networks in the hypothalamus and in adipose tissue. In addition, regulation of food intake, blood lipid profiles, body weight, and body fat by each treatment will also be determined. Specific Aim 1 will define glucocorticoid-induced changes in metabolic gene networks and adiposity. Specific Aim 2 will define genistein-induced changes in metabolic gene networks and adiposity. Specific Aim 3 will determine the role of genistein in counteracting glucocorticoid-induced obesity. The candidate anticipates that genistein will counteract glucocorticoid-induced changes in metabolic gene networks, which in turn will result in positive physiological outcomes. Genistein plus corticosterone, compared to corticosterone alone treatment, is expected to yield improved metabolic gene expression patterns and favorable metabolic parameters including body weight. The regulation of representative genes will also be individually verified using real time PCR, radioimmunohistochemistry, or quantitative autoradiographical analysis. The findings of this proposal will improve the understanding of two environmental-related agents, i.e., stress hormones and genistein, and their actions in the multi-level systems regulating energy homeostasis and body weight. These studies will provide a framework to uncover the molecular basis underlying stress hormone-induced obesity and its potential treatment.
Crisp Terms/Key Words:
Science Code(s)/Area of Science(s)
Primary: 86 - Career Development Secondary: 51 - Obesity
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