Quantitative lipidomics reveals age-dependent perturbations of whole-body lipid metabolism in ACBP deficient mice.
The acyl-CoA binding protein (ACBP) plays a key role in chaperoning long-chain acyl-CoAs into lipid metabolic processes and acts as an important regulatory hub in mammalian physiology. This is highlighted by the recent finding that mice devoid of ACBP suffer from a compromised epidermal barrier and delayed weaning, the physiological process where newborns transit from a fat-based milk diet to a carbohydrate-rich diet. To gain insights into how ACBP impinges on weaning and the concomitant remodeling of whole-body lipid metabolism we performed a comparative lipidomics analysis charting the absolute abundance of 613 lipid molecules in liver, muscle and plasma from weaning and adult Acbp knockout and wild type mice. Our results reveal that ACBP deficiency affects primarily lipid metabolism of liver and plasma during weaning. Specifically, we show that ACBP deficient mice have elevated levels of hepatic cholesteryl esters, and that lipids featuring an 18:1 fatty acid moiety are increased in Acbp depleted mice across all tissues investigated. Our results also show that the perturbation of systemic lipid metabolism in Acbp knockout mice is transient and becomes normalized and similar to that of wild type as mice grow older. These findings demonstrate that ACBP serves crucial functions in maintaining lipid metabolic homeostasis in mice during weaning.
Department of Biochemistry and Molecular Biology, Villum Center for Bioanalytical Sciences, University of Southern Denmark, DK-5230 Odense, Denmark.
Sandra F
SF
Gallego
Department of Biochemistry and Molecular Biology, Villum Center for Bioanalytical Sciences, University of Southern Denmark, DK-5230 Odense, Denmark.
Richard R
RR
Sprenger
Department of Biochemistry and Molecular Biology, Villum Center for Bioanalytical Sciences, University of Southern Denmark, DK-5230 Odense, Denmark.
Ditte
D
Neess
Department of Biochemistry and Molecular Biology, Villum Center for Bioanalytical Sciences, University of Southern Denmark, DK-5230 Odense, Denmark.
Josch K
JK
Pauling
Department of Biochemistry and Molecular Biology, Villum Center for Bioanalytical Sciences, University of Southern Denmark, DK-5230 Odense, Denmark. Electronic address: nils.f@bmb.sdu.dk.
Nils J
NJ
Færgeman
Department of Biochemistry and Molecular Biology, Villum Center for Bioanalytical Sciences, University of Southern Denmark, DK-5230 Odense, Denmark. Electronic address: cse@bmb.sdu.dk.
Christer S
CS
Ejsing
D000818:Animals; D002788:Cholesterol Esters / Q000378:metabolism; D026261:Diazepam Binding Inhibitor / Q000172:deficiency*; D005227:Fatty Acids / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology*; D008055:Lipids / Q000502:physiology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout
D002788:Cholesterol Esters; D026261:Diazepam Binding Inhibitor; D005227:Fatty Acids; D008055:Lipids
Acyl-CoA binding protein; Lipid metabolism; Lipidomics; Weaning