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The impact of growth hormone on adipose tissue

$118,414K01FY2004DKNIH

Ohio University Athens, Athens OH

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): My long term goal is to establish an independent research career investigating the hormonal regulation of adipose tissue metabolism. During my graduate and postdoctoral training periods, I gained extensive research experience in the field of lipid metabolism. More recently, I acquired a broader perspective into mechanisms of obesity, diabetes, and cardiovascular biology while teaching undergraduate and graduate courses, delivering continuing education seminars to a variety of health professionals, and obtaining a Registered Dietitian credential. In pursuing the proposed research, I will develop new technical skills in studying adipose metabolism in animal models, in microarray technology, and in statistical analysis, while gaining additional knowledge in molecular endocrinology and adipose biology that will allow me to build an independent research program. Four prominent scholars with complementary expertise in growth hormone (GH) function and regulation of triacylglycerol (TAG) metabolism in adipocytes will serve as sponsors and cosponsors; a scientist with expertise in characterizing knockout mouse models of obesity and diabetes at Yale Mouse Metabolic Phenotyping Center will serve as a collaborator; and a statistican will serve as a consultant. The majority of the proposed research will be conducted in the laboratory of Dr. Kopchick, a molecular endocrinologist, at Ohio University. Visits to the laboratories of the cosponsors will occur as needed. As a model system, I will study a GH receptor/binding protein gene-disrupted (GHR -/-) mouse line previously generated in the Kopchick laboratory. Despite a dwarf appearance, GHR -/- mice have a higher percentage of body fat relative to body mass as compared to wild-type mice. The mechanism underlying this accumulation of excess adipose tissue has not been established. In this proposal, we will test the hypothesis that GH impacts adipose tissue in a depot-specific manner and will explore potential mechanisms for the increased fat mass in the GHR -/- mice. The specific goals of the proposed research are to 1) determine if GH influences TAG deposition or adipocyte differentiation in a depot-specific manner; 2) determine the mechanism for the increased fat mass in the absence of GH signaling; and 3) evaluate the role of perilipins, proteins surrounding the fat droplet, in GH-stimulated lipolysis. Accomplishment of this research will provide me with exceptional training in a new research area with untapped potential, as well as open multiple avenues of inquiry for the writing of competitive research proposals.

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