Faculty Collaboration Database

Structural and functional characterization of the mouse fatty acid translocase promoter: activation during adipose differentiation. Biochem J 2001 Dec 01;360(Pt 2):305-12

Date

11/22/2001

Pubmed ID

11716758

Pubmed Central ID

PMC1222230

DOI

10.1042/0264-6021:3600305

Scopus ID

2-s2.0-0035625679 (requires institutional sign-in at Scopus site)   71 Citations

Abstract

Fatty acid translocase (FAT/CD36) is a cell-surface glycoprotein that functions as a receptor/transporter for long-chain fatty acids (LCFAs), and interacts with other protein and lipid ligands. FAT/CD36 is expressed by various cell types, including platelets, monocytes/macrophages and endothelial cells, and tissues with an active LCFA metabolism, such as adipose, small intestine and heart. FAT/CD36 expression is induced during adipose cell differentiation and is transcriptionally up-regulated by LCFAs and thiazolidinediones in pre-adipocytes via a peroxisome-proliferator-activated receptor (PPAR)-mediated process. We isolated and analysed the murine FAT/CD36 promoter employing C(2)C(12)N cells directed to differentiate to either adipose or muscle. Transient transfection studies revealed that the 309 bp upstream from the start of exon 1 confer adipose specific activity. Sequence analysis of this DNA fragment revealed the presence of two imperfect direct repeat-1 elements. Electrophoretic mobility-shift assay demonstrated that these elements were peroxisome-proliferator-responsive elements (PPREs). Mutagenesis and transfection experiments indicated that both PPREs co-operate to drive strong promoter activity in adipose cells. We conclude that murine FAT/CD36 expression in adipose tissue is dependent upon transcriptional activation via PPARs through binding to two PPREs located at -245 to -233 bp and -120 to -108 bp from the transcription start site.

Author List

Teboul L, Febbraio M, Gaillard D, Amri EZ, Silverstein R, Grimaldi PA

Author

Roy L. Silverstein MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adipocytes
Animals
Base Sequence
CD36 Antigens
Cell Differentiation
Cell Line
Clone Cells
Cloning, Molecular
Enzyme Activation
Gene Expression Regulation, Enzymologic
Humans
Membrane Glycoproteins
Mice
Molecular Sequence Data
Organic Anion Transporters
Promoter Regions, Genetic
Receptors, Cytoplasmic and Nuclear
Repetitive Sequences, Nucleic Acid
Response Elements
Stem Cells
Structure-Activity Relationship
Transcription Factors