The Gene Encoding the Acyl-CoA-binding Protein Is Activated by Peroxisome Proliferator-activated Receptor γ through an Intronic Response Element Functionally Conserved between Humans and Rodents

Abstract

The acyl-CoA-binding protein (ACBP) is a 10-kDa intracellular protein that specifically binds acyl-CoA esters with high affinity and is structurally and functionally conserved from yeast to mammals. In vitro studies indicate that ACBP may regulate the availability of acylCoA esters for various metabolic and regulatory purposes. The protein is particularly abundant in cells with a high level of lipogenesis and de novo fatty acid synthesis and is significantly induced during adipocyte differentiation. However, the molecular mechanisms underlying the regulation of ACBP expression in mammalian cells have remained largely unknown. Here we report that ACBP is a novel peroxisome proliferator-activated receptor (PPAR)␥ target gene. The rat ACBP gene is directly activated by PPAR␥/retinoid X receptor ␣ (RXR␣) and PPAR␣/RXR␣, but not by PPAR␦/RXR␣, through a PPAR-response element in intron 1, which is functionally conserved in the human ACBP gene. The intronic PPAR-response element (PPRE) mediates induction by endogenous PPAR␥ in murine adipocytes and confers responsiveness to the PPAR␥-selective ligand BRL49653. Finally, we have used chromatin immunoprecipitation to demonstrate that the intronic PPRE efficiently binds PPAR␥/RXR in its natural chromatin context in adipocytes. Thus, the PPRE in intron 1 of the ACBP gene is a bona fide PPAR␥-response element.

Farnesoid X Receptor Regulates Bile Acid-Amino Acid Conjugation

“…However, analysis of the rat genomic sequence for BAT showed a similar location (intron 1) of an IR-1 as for the human gene (data not shown), further supporting the conclusion that FXR regulates the BAT gene via an intronic FXRE. Functional intronic nuclear receptor binding sites have recently been found in the lipoprotein lipase gene and the gene encoding acyl-CoA-binding protein (26,27). The current study demonstrates that BACS and BAT mRNAs are induced in rat liver in response to natural and synthetic FXR ligands.…”

Proteomic Analysis of Rat Liver Peroxisome

“…It has an acyl-CoA-binding protein (ACBP) domain in the Nterminal. ACBP, a 10-kDa lipid-binding protein that may regulate the availability of acyl-CoA esters, is formed from the precursor protein and directly regulated by peroxisome proliferator-activated receptor-␥ and -␣ through the intronic peroxisome proliferator response element (35). It is intriguing to assume a physiological role of this C-terminal domain produced from a larger precursor in the transport/metabolism of lipid metabolites.…”

Regulation of Lipogenic Genes in Obesity

“…Another recently identified direct target gene of PPAR in adipocytes is Acyl-CoA Binding Protein (ACBP) (11). It was proposed that ACBP would repress PPAR-mediated transactivation induced by exogenous fatty acids, thereby inhibiting 3T3-L1 adipogenesis.…”