Disruption of the Acyl-CoA binding protein gene delays hepatic adaptation to metabolic changes at weaning

Research output: Contribution to conference without publisher/journalPosterResearch


The acyl-CoA binding protein/diazepam binding inhibitor (ACBP/DBI) is an evolutionary conserved intracellular protein that binds C14-C22 acyl-CoA esters with very high affinity. ACBP is thought to act as an acyl-CoA transporter, and 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 show decreased growth rate and increased levels of plasma cholesterol combined with hepatic accumulation of triglycerides and cholesteryl esters. We show by microarray analysis that the liver of ACBP-/- mice displays a significantly delayed induction of target genes of the sterol regulatory element binding protein (SREBP) family, around the weaning period. As a result, the hepatic de novo cholesterogenesis is significantly 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 causes elevated levels of plasma and hepatic lipids during weaning, which interferes with the normal metabolic adaptation to weaning by delaying induction of the lipogenic gene programs in the liver.
Original languageDanish
Publication date12. Jan 2011
Number of pages1
Publication statusPublished - 12. Jan 2011
EventKeystone Symposia: Type 2 Diabetes, Insulin Resistance and Metabolic Dysfunction - Keystone, Keystone, Colorado, United States
Duration: 12. Jan 201117. Jan 2011


ConferenceKeystone Symposia: Type 2 Diabetes, Insulin Resistance and Metabolic Dysfunction
Country/TerritoryUnited States
CityKeystone, Colorado

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