review Dermato-endocrinology 3:2, 62-64; April/May/June 2011; © 2011 Landes Bioscience The role of fatty acid desaturases in epidermal metabolism Harini Sampath1 and James M. Ntambi2,* 1Center for r esearch on Occupational and environmental Toxicology; Oregon Health & Science University; Portland, Or USA; 2Departments of Biochemistry and Nutritional Sciences; University of w isconsin, Madison; Madison, w i USA Key words: sebaceous lipids, skin barrier, sebocyte hypoplasia, skin lipids, energy balance Abbreviations: SCD, stearoyl-CoA desaturase; FADS, fatty acid desaturase The lipid composition of skin is important to a variety of functions served by this organ. Therefore, skin expresses multiple enzymes that synthesize and metabolize lipids. An important class of lipid metabolism enzymes expressed in skin is the lipid desaturases. various isoforms of stearoyl- CoA desaturase, a delta-9 desaturase, as well as a delta-6 desaturase alter the lipid composition of the skin, thereby affecting skin barrier homeostasis and consequently, whole body energy balance. This review will focus on the role of fatty acid desaturases in maintaining epidermal metabolism. Introduction As the largest organ in the body, the skin serves a whole host of functions, the most important of which is to act as a protec- tive barrier between the organism and the external environment. This barrier function has two separate components: the perme- ability barrier and the antimicrobial barrier.1-4 The permeability barrier function of skin prevents loss of heat and water across the skin’s surface, thereby preventing dehydration, as well as helping to maintain body temperature and body weight in homeotherms. The skin permeability barrier consists of the outer layer of the epidermis, the stratum corneum, made up of differentiated kera- tinocytes and corneocytes. Another important component of the stratum corneum is the extracellular matrix which is enriched in neutral lipids such as cholesterol, ceramides and free fatty acids.1-4 The array of functions served by skin require the synthesis of large amounts of lipids, including cholesterol, phospholipids, tri- glycerides, ceramides, cholesterol esters and wax esters. These lip- ids are used as cell membrane components, signaling molecules, and as a source of energy and are constantly turned over due to the continuous shedding of dead keratinocytes from the epider- mis.1-7 Therefore, the different layers of skin express a multitude of enzymes involved in lipid metabolism, including lipid hydro- lases, sphingomyelinases, lipases and desaturases. *Correspondence to: James M. Ntambi; Email: ntambi@biochem.wisc.edu Submitted: 01/12/11; Accepted: 01/13/11 DOI: 10.4161/derm.3.2.14832 Much of what we know regarding the role of desaturases in the skin comes from studies using mouse models with sponta- neous or targeted deletions of specific desaturases, especially delta-9 desaturases. With the exception of stearoyl-CoA desatu- rase-4, which is solely expressed in the heart,8 all other isoforms of murine delta-9 desaturase have been shown to be expressed in various layers of skin. Stearoyl-CoA desaturase-1 is expressed in the dermal layer mainly in the sebaceous gland but has profound effects on skin metabolism, including the epidermal layer.9-11 Scd2 is primarily expressed in the epidermis and is integral to maintaining an intact skin barrier.12 Scd3 is expressed pre- dominantly in the sebaceous gland in the dermis, but its role in affecting epidermal metabolism is as yet unclear.13 Additionally, the delta-6 desaturase, FADS2, has been recently shown to be expressed in the skin, where it plays a role in maintaining skin homeostasis.14,15 Stearoyl-CoA Desaturase-1 SCD1 is primarily expressed within undifferentiated sebo- cytes at the base of the sebaceous gland in the dermal layer, but expression in the epidermis has also been reported, especially under conditions where SCD2, the main epidermal isoform, has been deleted.12 First identified as the mutation resulting in sebocyte atrophy and alopecia in asebia mice, SCD1 is regu- lated throughout the hair cycle.16 Subsequent studies in both asebia mice and mice with a targeted deletion of SCD1 (Scd1-/- mice) have established that this enzyme plays a critical role in the maintenance of skin integrity, as well as whole body energy metabolism.9-11,16-23 Scd1-/- mice are lean and resistant to diet- induced obesity and insulin resistance, and they also present with skin abnormalities including sebocyte hypoplasia and severe alopecia. However, the role of the cutaneous phenotype in Scd1- /- mice in regulating body weight was not clear until the recent development of a skin-specific Scd1-/- animal. Interestingly, dele- tion of SCD1 from the skin alone recapitulates the lean phe- notype of mice lacking SCD1 globally.11 These skin-specific Scd1-/- mice also have increased metabolic rates, stemming from an inability to maintain core body temperature due to loss of sebaceous lipids in the skin coupled with severe alopecia. While sebaceous lipids such as triglycerides and cholesterol esters were drastically reduced in mice lacking skin SCD1, free cholesterol 62 Dermato-endocrinology volume 3 issue 2