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Quantitative Determination of De Novo Fatty Acid Synthesis in Brown Adipose Tissue Using Deuterium Oxide
Published on: May 12, 2023
ACBP--a PPAR and SREBP modulated housekeeping gene
Ditte Neess1, Pia Kiilerich, Maria B Sandberg
1Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230, Odense M, Denmark.
Acyl-CoA binding protein (ACBP) gene expression is regulated by transcription factors like PPAR and SREBP. These factors control ACBP levels in various cell types, influencing fatty acid metabolism.
Area of Science:
- Molecular Biology
- Biochemistry
- Cell Biology
Background:
- Acyl-CoA binding protein (ACBP) is a key intracellular lipid transporter.
- ACBP expression varies significantly across cell types, correlating with fatty acid turnover.
- Understanding ACBP gene regulation is crucial for metabolic research.
Purpose of the Study:
- To elucidate the regulatory mechanisms controlling the rat ACBP gene promoter.
- To identify transcription factors involved in ACBP expression in different cell types.
Main Methods:
- Analysis of rat ACBP gene promoter activity in fibroblasts and hepatoma cells.
- Investigating the roles of Sp1, NF-Y, PPAR, and SREBP transcription factor families.
- Studying ACBP regulation during adipocyte differentiation and in response to hormonal and environmental cues.
Main Results:
- Basal promoter activity in fibroblasts and hepatoma cells depends on sequences between -331 and -182, and Sp1/NF-Y sites.
- PPARgamma partly drives ACBP induction during adipocyte differentiation.
- SREBP-1c is the primary regulator in hepatocytes responding to insulin, while PPARalpha counteracts this during fasting and mediates peroxisome proliferator response.
- PPARalpha and PPARgamma require sequences upstream of -182, whereas SREBP-1c needs intron 1 sequences.
Conclusions:
- The rat ACBP gene promoter is differentially regulated by distinct transcription factors in various cell types.
- PPAR and SREBP family members play critical roles in modulating ACBP expression in response to metabolic states and differentiation.
- Specific promoter and intronic regions are essential for the transactivation activity of these transcription factors.
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