Coordinated transcriptional control of adipocyte triglyceride lipase (Atgl) by transcription factors Sp1 and peroxisome proliferator–activated receptor γ (PPARγ) during adipocyte differentiation

Content Provider	Scilit
Author	Roy, Debasish Farabaugh, Kenneth T. Wu, Jing Charrier, Alyssa Smas, Cynthia Hatzoglou, Maria Thirumurugan, Kavitha Buchner, David A.
Copyright Year	2017
Description	Journal: Journal of Biological Chemistry The breakdown of stored fat deposits into its components is a highly regulated process that maintains plasma levels of free fatty acids to supply energy to cells. Insulin-mediated transcription of Atgl, the enzyme that mediates the rate-limiting step in lipolysis, is a key point of this regulation. Under conditions such as obesity or insulin resistance, Atgl transcription is often misregulated, which can contribute to overall disease progression. The mechanisms by which Atgl is induced during adipogenesis are not fully understood. We utilized computational approaches to identify putative transcriptional regulatory elements in Atgl and then tested the effect of these elements and the transcription factors that bind to them in cultured preadipocytes and mature adipocytes. Here we report that Atgl is down-regulated by the basal transcription factor Sp1 in preadipocytes and that the magnitude of down-regulation depends on interactions between Sp1 and peroxisome proliferator–activated receptor γ (PPARγ). In mature adipocytes, when PPARγ is abundant, PPARγ abrogated transcriptional repression by Sp1 at the Atgl promoter and up-regulated Atgl mRNA expression. Targeting the PPARγ–Sp1 interaction could be a potential therapeutic strategy to restore insulin sensitivity by modulating Atgl levels in adipocytes.
Related Links	http://www.jbc.org/content/292/36/14827.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5592664/pdf http://www.jbc.org/article/S0021925820343088/pdf
Ending Page	14835
Page Count	9
Starting Page	14827
ISSN	00219258
e-ISSN	1083351X
DOI	10.1074/jbc.m117.783043
Journal	Journal of Biological Chemistry
Issue Number	36
Volume Number	292
Language	English
Publisher	Elsevier BV
Publisher Date	2017-09-01
Access Restriction	Open
Subject Keyword	Journal: Journal of Biological Chemistry Biochemistry and Molecular Biology Adipose Triglyceride Lipase (atgl) Peroxisome Proliferator–activated Receptor (ppar) Specificity Protein 1 (sp1)
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology