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Regulation by Cholesterol of the Gene Expression of Spot 14 in Adipocytes
Author(s) -
Kelleher James David,
Usher David C,
David John
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a91-c
Subject(s) - lipogenesis , fatty acid synthase , liver x receptor , medicine , endocrinology , phosphoenolpyruvate carboxykinase , gene expression , adipocyte , atp citrate lyase , peroxisome proliferator activated receptor , malic enzyme , biology , transcription factor , chemistry , receptor , adipose tissue , lipid metabolism , gene , enzyme , biochemistry , nuclear receptor , citrate synthase , dehydrogenase
Thyroid hormone responsive Spot 14 (THRSP) is a transcription cofactor that is expressed in the liver and adipocytes. Spot 14’s expression in the liver is controlled by various factors which suggest that it acts as a control point in the lipogenesis pathway. However, its synthesis has also been shown to be under the control of the liver X receptor (LXR), a transcription factor that is sensitive to cholesterol levels. Spot 14’s regulation in adipocytes has yet to be investigated. In this study we used cholesterol depletion (β‐cyclodextrin treatment) and peroxisome proliferator‐activated receptor (PPARγ ) and LXR agonists, rosiglitizone and T0901317, respectively, to examine Spot 14’s regulation in 3T3‐L1 adipocytes. Gene expression of these treated cells was examined through quantitative PCR for Spot 14 and its hypothesized target genes, fatty acid synthase (FAS), ATP‐citrate lyase (ACLY), malic enzyme (ME), and phosphoenolpyruvate carboxykinase (PCK1). Spot 14’s expression in 3T3‐L1 cells decreased with the cyclodextrin treatment and increased with the T0901317 treatment, indicating direct control by LXR. T0901317 also induced upregulation in Spot 14 target genes FAS, ME, and ACLY, but the cyclodextrin treatment had little to no effect on these genes. Rosiglitizone treatment also had very little effect on Spot 14 or its target genes. These results indicate that adipocyte cholesterol levels are important for controlling Spot 14 synthesis. This research was funded in part by the Howard Hughes Medical Institute Undergraduate Science Education program.