The control of apolipoprotein C-I gene expression during adipocyte differentiation

Author(s)David, John M.
Date Accessioned2020-08-12T12:29:40Z
Date Available2020-08-12T12:29:40Z
Publication Date2006
AbstractSerial analysis of gene expression (SAGE) was used to generate global gene expression profiles of 3T3-L1 preadipocytes and adipocytes. Our primary interest was in late gene expression, specifically genes that encode secreted proteins, so that we may detect novel adipocyte genes that are related to energy balance and obesity. SAGE detected the expression of apolipoprotein C-I (apoC-I) mRNA in 3T3-L1 adipocytes, but not preadipocytes. ApoC-I, the product of the Apoc1 gene, is a 6.6 kDa protein which is found in plasma associated with chylomicrons, very low-density lipoproteins (VLDLs), and high-density lipoproteins (HDLs). The function of apoC-I and the regulation of its production is not well understood, though studies have suggested that it may interfere with triglyceride-rich lipoprotein clearance, free fatty acid transport into peripheral tissues, and cholesterol ester transfer protein (CETP) activity (Jong, et al., 1999). To elucidate the SAGE findings, the expression of apoC-I was determined by quantitative PCR and ELISA. Apoc1 mRNA expression was shown to increase during late-phase adipocyte differentiation and positively correlate with lipid accumulation, suggesting that it may be regulated by cellular triglyceride or cholesterol content. Quantitative PCR was used to monitor the expression of Apoc1 mRNA during 3T3-L1 differentiation under cholesterol-depleted conditions, and Apoc1 expression was suppressed by the cholesterol depletion. Lastly, to investigate the role of specific transcription factors in the regulation of the Apoc1 gene, 3T3-L1 cells were treated with synthetic agonists of the peroxisome proliferator-activated receptor gamma (PPAR_and liver X receptor (LXR) during differentiation. Apoc1 mRNA expression was suppressed by the PPAR_ agonists pioglitazone and rosiglitazone; however, Apoc1 expression was increased by the LXR agonist T0901317. These results suggest that Apoc1 expression in adipocytes is involved with cholesterol efflux and may be controlled by LXR.en_US
AdvisorUsher, David C.
DegreeM.S.
DepartmentUniversity of Delaware, Department of Biological Sciences
Unique Identifier76822990
URLhttps://udspace.udel.edu/handle/19716/27390
PublisherUniversity of Delawareen_US
URIhttps://search.proquest.com/docview/305322618?accountid=10457
dc.subject.lcshApolipoproteins
dc.subject.lcshGene expression
TitleThe control of apolipoprotein C-I gene expression during adipocyte differentiationen_US
TypeThesisen_US
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