Disruption of the acyl-coa binding protein gene delays hepatic adaptation to metabolic changes at weaning

Ditte Neess, Maria Bloksgaard, Signe Bek Sørensen, Ann-Britt Marcher, Ida C Elle, Torben Helledie, Marianne Due, Vasileios Pagmantidis, Bente Finsen, Johannes Wilbertz, Mogens Kruhoeffer, Nils Faergeman, Susanne Mandrup

Research output: Contribution to journalJournal articleResearchpeer-review


The acyl-CoA binding protein/diazepam binding inhibitor (ACBP/DBI) is an intracellular protein that binds C14-C22 acyl-CoA esters and is thought to act as an acyl-CoA transporter. In vitro analyses have indicated that ACBP can transport acyl-CoA esters between different enzymatic systems; however, little is known about the in vivo function in mammalian cells. We have generated mice with targeted disruption of ACBP (ACBP-/-). These mice are viable and fertile and develop normally. However, around weaning the ACBP-/- mice go through a crisis with overall weakness, and a slightly decreased growth rate. Using microarray analysis we show that the liver of ACBP-/- mice display a significantly delayed adaptation to weaning with late induction of target genes of the sterol regulatory element binding protein (SREBP) family. As a result, hepatic de novo cholesterogenesis is decreased at weaning. The delayed induction of SREBP target genes around weaning is caused by a compromised processing and decreased expression of SREBP precursors leading to reduced binding of SREBP to target sites in chromatin. In conclusion, lack of ACBP interferes with the normal metabolic adaptation to weaning and leads to delayed induction of the lipogenic gene program in the liver.
Original languageEnglish
JournalJournal of Biological Chemistry
Pages (from-to)3460-3472
Publication statusPublished - 2011


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