Obesity resistance of the stearoyl-CoA desaturase-deficient (scd1-/-) mouse results from disruption of the epidermal lipid barrier and adaptive thermoregulation.
Targeted deletion of the stearoyl-CoA desaturase 1 gene (scd1) in mouse causes obesity resistance and a severe skin phenotype. Here, we demonstrate that SCD1 deficiency disrupts the epidermal lipid barrier and leads to uncontrolled transepidermal water loss, breakdown of adaptive thermoregulation and cold resistance, as well as a metabolic wasting syndrome. The loss of omega-hydroxylated very long-chain fatty acids (VLCFA) and ceramides substituted with omega-hydroxylated VLCFA covalently linked to corneocyte surface proteins leads to the disruption of the epidermal lipid barrier in scd1-/- mutants. Artificial occlusion of the skin by topical lipid application largely reconstituted the epidermal barrier and also reversed dysregulation of thermogenesis and cold resistance, as well as the metabolic disturbances. Interestingly, SCD1 deficiency abolished expression of the key transcription factor Lef1, which is essential for interfollicular epidermis, sebaceous glands, and hair follicle development. Finally, the occurrence of SCD1 and a newly described hSCD5 (ACOD4) gene in humans suggests that the scd1-/- mouse mutant might be a valuable animal model for the study of human skin diseases associated with epidermal barrier defects.
Binczek
Erika
E
Laboratory of Molecular Neurosciences, Center of Molecular Medicine (CMMC), Center of Biochemistry, Faculty of Medicine, University of Cologne, Joseph-Stelzmann-Str. 52, D-50931 Köln, Germany.
Jenke
Britta
B
Holz
Barbara
B
Günter
Robert Heinz
RH
Thevis
Mario
M
Stoffel
Wilhelm
W
D000287:Administration, Topical; D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology*; D002518:Ceramides / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003080:Cold Temperature / Q000009:adverse effects; D015536:Down-Regulation; D004734:Energy Metabolism; D004817:Epidermis / Q000737:chemistry / Q000502:physiology*; D008055:Lipids / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000517:prevention & control*; D010577:Petrolatum / Q000008:administration & dosage / Q000627:therapeutic use; D015398:Signal Transduction; D012869:Skin Absorption / Q000502:physiology; D012873:Skin Diseases, Genetic / Q000503:physiopathology; D013230:Stearoyl-CoA Desaturase / Q000172:deficiency*; D014157:Transcription Factors / Q000096:biosynthesis; D014280:Triglycerides / Q000097:blood; D019282:Wasting Syndrome / Q000209:etiology; D014870:Water Loss, Insensible
D002518:Ceramides; C497574:Lef1 protein, mouse; D008055:Lipids; D051821:Lymphoid Enhancer-Binding Factor 1; D014157:Transcription Factors; D014280:Triglycerides; D010577:Petrolatum; D002784:Cholesterol; D013230:Stearoyl-CoA Desaturase