Date of Completion

Spring 5-2-2017

Project Advisor(s)

Christopher Blesso, Ji-Young Lee, Mary Bruno, Hedley Freake

University Scholar Major

Nutritional Sciences

Disciplines

Molecular, Genetic, and Biochemical Nutrition

Abstract

Obesity is associated with a number of complications that may increase the risk for chronic disease, including inflammation and dysfunctional high-density lipoprotein (HDL) particles. Scavenger receptor class B member 1 (SR-B1) is an HDL receptor found in the cell plasma membrane involved in cholesterol exchange and the initiation of intracellular signaling cascades. During the process of adipocyte (fat cell) formation (adipogenesis), there is a delicate balance of transcriptional programs that affect cholesterol transport and facilitate lipid accumulation. Mice fed a high fat diet have increased SR-B1 mRNA expression in adipose tissue depots. Furthermore, SR-B1 mRNA expression was significantly increased in mature adipocytes. In this study, 3T3-L1 pre-adipocytes were differentiated into mature adipocytes[BC1] and transfected with SR-B1 siRNA. There was a 70% suppression of SR-B1, indicating a successful knockdown. Mature adipocytes were stimulated through lipopolysaccharides (LPS) and macrophage-conditioned media (MCM) to determine SR-B1 function in inflammatory conditions. Inflammatory stimulations demonstrated that there is increased mRNA expression of the inflammatory marker monocyte chemoattractant protein 1 (MCP-1) when cells are treated with MCM or LPS, however no significant effects of SR-B1 silencing were observed. Future experiments will include performing additional trials for inflammatory experiments, conducting Western blot analysis to determine protein suppression, and using small molecules to inhibit SR-B1 lipid transfer activity, such as block-lipid transport 1.

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