PhD students participating in August Krogh seminars receive 0,2 ECTS per seminar
AKC seminar: Regulation of sphingolipid synthesis by acyl-CoA channeling; role in systemic energy expenditure
August Krogh Seminar
Professor Nils J. Færgeman
Department of Biochemistry and Molecular Biology, University of Southern Denmark.
Long-chain fatty acyl-CoA esters are key intermediates in numerous lipid metabolic pathways and recognized as important cellular signalling molecules. The intracellular flux and regulatory properties of acyl-CoA esters have been proposed to be coordinated by acyl-CoA-binding protein (ACBP), which belongs to a family of highly evolutionary conserved and ubiquitously expressed lipid-binding proteins.
Acbp-/- mice are viable and fertile and born in a normal Mendelian ratio. Acbp-/- mice show reduced body weight during the weaning period and display a delayed hepatic upregulation of SREBP-regulated lipogenic gene programs at weaning compared to wild type mice. Tissue-specific loss of ACBP in the skin, but not in hepatocytes, phenocopies the SREBP-regulated gene expression in the liver of full body Acbp-/- mice, arguing that the biochemical changes in the liver are caused by loss of ACBP in the skin.
Accordingly, transepidermal water loss is significantly increased in both skin-specific and full-body Acbp-/- mice. By applying artificial barriers to the skin of Acbp-/- mice SREBP-regulated gene expression in the liver is rescued, emphasizing that loss of ACBP results in an impaired epidermal permeability barrier, which not only affects the metabolism in the skin but also has systemic effects in other tissues.
Post weaning and during aging Acbp-/- mice have increased energy expenditure, increased food intake and increased browning of the inguinal white adipose tissue, which all are reversed by housing the mice at 30 °C or by blocking beta-adrenergic receptor signalling with propranolol. Consistent with increased energy expenditure, both full-body and skin-specific Acbp-/- mice are completely resistant to diet-induced obesity and the diabetogenic effects of a high-fat diet.
Our observations therefore suggest that epidermal ACBP is indispensable for systemic energy homeostasis. Notably, ACBP potently facilitates very-long acyl chain ceramide synthesis via direct interaction with ceramide synthases, that are required for maintaining a normal epidermal barrier. Thus, ACBP is required for synthesis of very-long acyl chain ceramides to support a functional epidermal barrier, and thus plays a key role in maintaining systemic metabolic homeostasis.
25 February 2022
14:00-15:00: Seminar and discussion
15:00-16:00: Post seminar servings and socializing
Auditorium 1, August Krogh Building, Universitetsparken 13, DK-2100 Copenhagen
Participation is free, but please register here.
For PhD students
Jens Frey Halling, email@example.com
Jonas Møller Kristensen, firstname.lastname@example.org