Please use this identifier to cite or link to this item:
Title: Thyroid hormone regulates the hypotriglyceridemic gene APOA5*
Author: Prieur, X.
Huby, T.
Coste, H.
Schaap, F.G.
Chapman, M.J.
Rodríguez Rubio, Joan Carles
Keywords: Regulació genètica
Genetic regulation
Thyroid gland
Issue Date: 7-Jun-2005
Publisher: American Society for Biochemistry and Molecular Biology
Abstract: The apolipoprotein AV gene (APOA5) is a key determinant of plasma triglyceride levels, a major risk factor for coronary artery disease and a biomarker for the metabolic syndrome. Since thyroid hormones influence very low density lipoprotein triglyceride metabolism and clinical studies have demonstrated an inverse correlation between thyroid status and plasma triglyceride levels, we examined whether APOA5 is regulated by thyroid hormone. Here we report that 3,5,3 -triiodo-Lthyronine (T3) and a synthetic thyroid receptor (TR ) ligand increase APOA5 mRNA and protein levels in hepatocytes. Our data revealed that T3-activated TR directly regulates APOA5 promoter through a functional direct repeat separated by four nucleotides (DR4). Interestingly, we show that upstream stimulatory factor 1, a transcription factor associated with familial combined hyperlipidemia and elevated triglyceride levels in humans, and upstream stimulatory factor 2 cooperate with TR, resulting in a synergistic activation of APOA5 promoter in a ligand-dependent manner via an adjacent E-box motif. In rats, we observed that apoAV levels declines with thyroid hormone depletion but returned to normal levels upon T3 administration. In addition, treatments with a TR -selective agonist increased apoAV and diminished triglyceride levels. The identification of APOA5 as a T3 target gene provides a new potential mechanism whereby thyroid hormones can influence triglyceride homeostasis. Additionally, these data suggest that TR may be a potential pharmacological target for the treatment of hypertriglyceridemia.
Note: Reproducció del document publicat a:
It is part of: Journal of Biological Chemistry, 2005, vol. 280, num. 30, p. 27533-27543
Related resource:
ISSN: 0021-9258
Appears in Collections:Articles publicats en revistes (Bioquímica i Fisiologia)

Files in This Item:
File Description SizeFormat 
570939.pdf491.32 kBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.