Doctoral Dissertations

Date of Award

12-2001

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Human Ecology

Major Professor

Michael B. Zemel

Committee Members

Naima Moustaid-Moussa, Jay Whelan, John Koontz

Abstract

Intracellular Ca2+ ([Ca2+]i) plays a key role in metabolic disorders associated with obesity and insulin resistance. Previous data from this laboratory demonstrated that increasing [Ca2+]i via stimulation of either receptor or voltage-mediated calcium channels stimulates the expression and activity of fatty acid synthase (FAS), a key enzyme in de nova lipogenesis, and inhibits basal and agonist-stimulated lipolysis in both human and murine adipocytes. Therefore, increasing [Ca2+]i appears to promote adipocyte triglyceride accumulation by exerting a coordinated control over stimulation of lipogenesis and inhibition of lipolysis. These data suggest that adipocyte [Ca2+]i is a logical target for pharmacological/nutritional regulation of adiposity. However, the role of [Ca2+]i in human adipocyte differentiation, an important contributor to adiposity, is unknown. Moreover, specific adipocyte [Ca2+]i targets need to be further explored. Accordingly, our studies were designed to (1) determine the role of [Ca2+]i in human adipocyte differentiation, and (2) identify adipocyte targets which regulate [Ca2+]i and determine strategies for modulating these targets.

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