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 ⌬ 9 -desaturases, which catalyze the synthesis in ⌬ 9 -monounsaturated lipids, primarily oleoyl-CoA (18:1n-9) and palmitoylCoA (16:1n-7), the major monounsaturated fatty acids in cutaneous lipids. Mice with a deletion of the ⌬ 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.

Elucidating the roles of stearoyl-CoA desaturase 1 in adipocyte fatty acid metabolism and cellular function

“…Prior research has indicated that the two human SCD transcripts originate from one structural SCD gene via alternative polyadenylation sites [40]. The human SCD1 isoform, which is located on chromosome 10, is highly homologous (~85%) with murine Scd1 and is predominantly expressed in AT and liver [28]; however SCD1 expression has also been noted in skeletal muscle, heart, brain, lungs and pancreas [38,39,41]. In contrast to SCD1 expression, SCD5 is mostly confined to the pancreas and brain [37,42], yet low SCD5 expression has also been detected in the lungs, kidneys, heart and placenta [37,39,43].…”

“…The human SCD1 isoform, which is located on chromosome 10, is highly homologous (~85%) with murine Scd1 and is predominantly expressed in AT and liver [28]; however SCD1 expression has also been noted in skeletal muscle, heart, brain, lungs and pancreas [38,39,41]. In contrast to SCD1 expression, SCD5 is mostly confined to the pancreas and brain [37,42], yet low SCD5 expression has also been detected in the lungs, kidneys, heart and placenta [37,39,43]. SCD5, which is unique to primate species, is located on chromosome 4 and its amino acid sequence is fairly dissimilar to any of the murine Scd isoforms [37,42].…”

“…Humans express only two SCD enzyme isoforms throughout the body: SCD1 and SCD5 [37][38][39]. Prior research has indicated that the two human SCD transcripts originate from one structural SCD gene via alternative polyadenylation sites [40].…”

“…An examination of rat liver demonstrated that the half-life of SCD1 protein is only 2-4 hours [28,97]. Therefore, any factors that influence the stability or degradation of the SCD1 protein have the potential to alter the level of SCD1 activity [33,39]. For example, ATPase p97 is involved in the regulation of proteasome-dependent degradation of SCD1 in several cultured cell lines (e.g., 3T3-L1 cells,…”

“…Taken together, these results may suggest that adipocytes require SCD1 activity to promote the storage of excess FAs into TAGs (e.g., TAG-MUFAs) to prevent cellular inflammation. [10,39,251]. By causing an accumulation of SFAs and a reduction of MUFAs, a decrease in SCD1 activity would be expected to increase the rigidity of the cell membrane, which in turn could influence cell signaling cascades (e.g., insulin signaling) [125].…”