title: Metabolic changes in skin caused by Scd1 deficiency: a focus on retinol metabolism.
abstract: We previously reported that mice with skin-specific deletion of stearoyl-CoA desaturase-1 (Scd1) recapitulated the skin phenotype and hypermetabolism observed in mice with a whole-body deletion of Scd1. In this study, we first performed a diet-induced obesity experiment at thermoneutral temperature (33°C) and found that skin-specific Scd1 knockout (SKO) mice still remain resistant to obesity. To elucidate the metabolic changes in the skin that contribute to the obesity resistance and skin phenotype, we performed microarray analysis of skin gene expression in male SKO and control mice fed a standard rodent diet. We identified an extraordinary number of differentially expressed genes that support the previously documented histological observations of sebaceous gland hypoplasia, inflammation and epidermal hyperplasia in SKO mice. Additionally, transcript levels were reduced in skin of SKO mice for genes involved in fatty acid synthesis, elongation and desaturation, which may be attributed to decreased abundance of key transcription factors including SREBP1c, ChREBP and LXRα. Conversely, genes involved in cholesterol synthesis were increased, suggesting an imbalance between skin fatty acid and cholesterol synthesis. Unexpectedly, we observed a robust elevation in skin retinol, retinoic acid and retinoic acid-induced genes in SKO mice. Furthermore, SEB-1 sebocytes treated with retinol and SCD inhibitor also display an elevation in retinoic acid-induced genes. These results highlight the importance of monounsaturated fatty acid synthesis for maintaining retinol homeostasis and point to disturbed retinol metabolism as a novel contributor to the Scd1 deficiency-induced skin phenotype.
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, United States of America. mflowers@biochem.wisc.edu
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Flowers
authors.forename: Chad M
authors.initials: CM
authors.lastname: Paton
authors.forename: Sheila M
authors.initials: SM
authors.lastname: O'Byrne
authors.forename: Kevin
authors.initials: K
authors.lastname: Schiesser
authors.forename: John A
authors.initials: JA
authors.lastname: Dawson
authors.forename: William S
authors.initials: WS
authors.lastname: Blaner
authors.forename: Christina
authors.initials: C
authors.lastname: Kendziorski
authors.forename: James M
authors.initials: JM
authors.lastname: Ntambi
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004817:Epidermis / Q000187:drug effects / Q000473:pathology; D005227:Fatty Acids / Q000096:biosynthesis; D020869:Gene Expression Profiling; D006197:Hair / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006965:Hyperplasia; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000473:pathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D047494:PPAR delta / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D012627:Sebaceous Glands / Q000002:abnormalities / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000378:metabolism*; D013230:Stearoyl-CoA Desaturase / Q000172:deficiency* / Q000378:metabolism; D013261:Sterols / Q000378:metabolism; D013696:Temperature; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology; D014801:Vitamin A / Q000378:metabolism*
chemical_list: D000209:Acute-Phase Proteins; D005227:Fatty Acids; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D047494:PPAR delta; D018168:Receptors, Retinoic Acid; D013261:Sterols; D014157:Transcription Factors; D014801:Vitamin A; C071332:Lcn2 protein, mouse; D014212:Tretinoin; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase