title: Delayed hepatic adaptation to weaning in ACBP-/- mice is caused by disruption of the epidermal barrier.
abstract: We previously reported that mice deficient in acyl-CoA-binding protein (ACBP) display a delayed metabolic adaptation to weaning. This includes a delayed activation of the hepatic lipogenic gene program, which may result from hepatic accumulation of triacylglycerol and/or cholesteryl esters in the late suckling period. To further investigate the basis for this phenotype, we generated mice deficient in ACBP in hepatocytes (Alb-ACBP(-/-)) and keratinocytes (K14-ACBP(-/-)). Surprisingly, the delayed adaptation to weaning, including hepatic lipid accumulation, is caused by ACBP deficiency in the skin rather than in the liver. Similarly to ACBP(-/-) mice, K14-ACBP(-/-) mice exhibit an increased transepidermal water loss, and we show that the hepatic phenotype is caused specifically by the epidermal barrier defect, which leads to increased lipolysis in white adipose tissue. Our data demonstrate that an imperfect epidermal barrier leads to profound suppression of the hepatic SREBP gene program and lipid accumulation in the liver.
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark.
authors: Ditte
authors: D
authors: Neess
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark.
authors: Signe
authors: S
authors: Bek
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark.
authors: Maria
authors: M
authors: Bloksgaard
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark.
authors: Ann-Britt
authors: AB
authors: Marcher
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark.
authors: Nils J
authors: NJ
authors: Færgeman
authors: Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark. Electronic address: s.mandrup@bmb.sdu.dk.
authors: Susanne
authors: S
authors: Mandrup
mesh_terms: D000222:Adaptation, Physiological; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D001834:Body Water / Q000378:metabolism; D026261:Diazepam Binding Inhibitor / Q000235:genetics / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism*; D008066:Lipolysis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051779:Sterol Regulatory Element Binding Proteins / Q000235:genetics / Q000378:metabolism; D014886:Weaning
chemical_list: D026261:Diazepam Binding Inhibitor; D051779:Sterol Regulatory Element Binding Proteins