title: Hair Growth Cycle Is Arrested in SCD1 Deficiency by Impaired Wnt3a-Palmitoleoylation and Retrieved by the Artificial Lipid Barrier.
abstract: Stearoyl-CoA desaturase 1 (SCD1) is the dominant member of the SCD-isozyme family, regarded as a major regulator of lipid and energy metabolism in liver and adipose tissue. SCD1 deficiency impairs the desaturation of de novo-synthesized palmitoyl- and stearoyl-CoA to palmitoleoyl- and oleoyl-CoA. Scd1-/-mice develop metabolic waste syndrome and skin lesions: epidermal barrier disruption, alopecia, and degeneration of sebaceous glands. The unifying molecular link between the two divergent traits remains incompletely understood. Here we show the absence of palmitoleic acid (9Z-16:1) in the lipidome of the scd1-null mouse, which prohibits posttranslational O-palmitoleoylation of Wnt3a protein, essential for Wnt3a/ß-catenin signaling in stem cell lineage decision in development of the epidermal barrier, hair growth cycle, and sebaceous glands. Substitution of the disrupted epidermal lipid barrier by an inert hydrocarbon coat prevents excessive transepidermal water loss, normalizes thermogenesis and metabolic parameters, and surprisingly leads to the activation of hair bulge progenitor cells and reprograming of a regular hair growth cycle and development of a regular fur in scd1-/-mice. Progenitor sebocytes are not activated. Independent of age, application or removal of the artificial lipid barrier allows the reversible telogen-anagen reentry and exit of the hair growth cycle.
authors.affiliation: Laboratory of Molecular Neurosciences, Institute of Biochemistry, University of Cologne, Cologne, Germany; CMMC (Center of Molecular Medicine), University of Cologne, Cologne, Germany; CECAD (Cluster of Excellence: Cellular Stress Responses in Aging-Associated Diseases), University of Cologne, Cologne, Germany. Electronic address: wilhelm.stoffel@uni-koeln.de.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Stoffel
authors.affiliation: Laboratory of Molecular Neurosciences, Institute of Biochemistry, University of Cologne, Cologne, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Schmidt-Soltau
authors.affiliation: Laboratory of Molecular Neurosciences, Institute of Biochemistry, University of Cologne, Cologne, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Jenke
authors.affiliation: Laboratory of Molecular Neurosciences, Institute of Biochemistry, University of Cologne, Cologne, Germany.
authors.forename: Erika
authors.initials: E
authors.lastname: Binczek
authors.affiliation: Laboratory of Molecular Neurosciences, Institute of Biochemistry, University of Cologne, Cologne, Germany; CMMC (Center of Molecular Medicine), University of Cologne, Cologne, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Hammels
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation; D018859:Hair Follicle / Q000254:growth & development* / Q000378:metabolism; D007150:Immunohistochemistry; D050356:Lipid Metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012313:RNA / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012627:Sebaceous Glands / Q000378:metabolism*; D013230:Stearoyl-CoA Desaturase / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D060509:Wnt3A Protein / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; D012313:RNA; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase