Role of stearoyl-CoA desaturase-1 in skin integrity and whole body energy balance

Abstract

The skin is the single largest organ in humans, serving as a major barrier to infection, water loss, and abrasion. The functional diversity of skin requires the synthesis of large amounts of lipids, such as triglycerides, wax esters, squalene, ceramides, free cholesterol, free fatty acids, and cholesterol and retinyl esters. Some of these lipids are used as cell membrane components, signaling molecules, and a source of energy. An important class of lipid metabolism enzymes expressed in skin is the Δ(9)-desaturases, which catalyze the synthesis in Δ(9)-monounsaturated lipids, primarily oleoyl-CoA (18:1n-9) and palmitoyl-CoA (16:1n-7), the major monounsaturated fatty acids in cutaneous lipids. Mice with a deletion of the Δ(9)-desaturase-1 isoform (SCD1) either globally (Scd1(-/-)) or specifically in the skin (skin-specific Scd1-knockout; SKO) present with marked changes in cutaneous lipids and skin integrity. Interestingly, these mice also exhibit increased whole body energy expenditure, protection against diet-induced adiposity, hepatic steatosis, and glucose intolerance. The increased energy expenditure in skin-specific Scd1-knockout (SKO) mice is a surprising phenotype, as it links cutaneous lipid homeostasis with whole body energy balance. This minireview summarizes the role of skin SCD1 in regulating skin integrity and whole body energy homeostasis and offers a discussion of potential pathways that may connect these seemingly disparate phenotypes.

Keywords: Energy Metabolism; Fatty Acid Metabolism; Lipids; Obesity; Skin.

FIGURE 1.

Cutaneous changes in SCD1-deficient mice and relationship to whole body energy expenditure: a model. The major cutaneous changes observed in SCD1-deficient animals are depicted. The inability to desaturate fatty acids, such as palmitate and stearate, results in hypoplastic sebaceous glands and a thickened stratum corneum (SC). A concurrent increase in free cholesterol (FC), ceramides, and retinol metabolites, along with a significant depletion of TG and wax diesters (WDE), in the skin of SCD1-deficient mice accompanies various cutaneous phenotypes, including increased inflammation and heat and water loss across the surface of the skin. These cutaneous phenotypes appear to be causally linked to the favorable metabolic phenotype of SCD1-deficient mice, potentially due to an increase in energetic demand for body temperature maintenance or due to the energy-intensive nature of cutaneous wound healing.