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.
Highlights
The epidermis has a large capacity for synthesizing both fatty acids and cholesterol, which are utilized to form a variety of complex lipids including phospholipids, triglycerides, sphingolipids, esterified cholesterol, wax esters and retinyl esters [1,2,3]
We previously reported that Scd1 knockout (SKO) mice recapitulate the hypermetabolic phenotype observed in mice with a whole-body deletion of SCD1, resulting in resistance to high-fat diet-induced obesity when housed at ambient temperature (21uC) [7]
Microarray analysis of skin of SKO mice To explore mechanisms other than heat loss that may be responsible for the skin-derived alteration in whole-body energy metabolism in SKO mice, we analyzed skin gene expression in 8–9 week old male SKO mice (n = 3) and Scd1flox/flox (Lox) control mice (n = 3) using Affymetrix 430 2.0 microarrays
Summary
The epidermis has a large capacity for synthesizing both fatty acids and cholesterol, which are utilized to form a variety of complex lipids including phospholipids, triglycerides, sphingolipids, esterified cholesterol, wax esters and retinyl esters [1,2,3]. These epidermal lipids are essential for maintaining a permeability barrier that protects against transepidermal loss of water and electrolytes, as well as providing an anti-microbial barrier that prevents microorganism colonization and infection [1,3,4]. Whereas overproduction of sebum by the sebaceous gland contributes to the development of acne and seborrhea, inadequate sebum production due to sebocyte dysfunction impairs the function of the hair follicle [2]
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