Role of Skin Stearoyl‐CoA desaturase‐1 in Energy Metabolism

A critical regulator of lipogenesis is stearoyl‐CoA desaturase (SCD), which catalyzes the synthesis of monounsaturated fatty acids (MUFA), mainly oleoyl‐ (18:1n9) and palmitoleoyl‐CoA (16:1n7). SCD expression is elevated in human and rodent obese and insulin resistant states, suggesting that excess 18:1n9 or 16:1n7 synthesis may contribute to metabolic disease development. Mice with a global deletion of SCD1 isoform (GKO) are resistant to diet‐ and genetically‐induced obesity, insulin resistance and liver steatosis. We have found that deletion of skin SCD1 (SKO mice) recapitulated the skin abnormalities observed in GKO mice and protected SKO mice from high‐fat diet‐induced obesity, hepatic triglyceride accumulation and glucose intolerance regardless of changes in ambient temperature. Microarray analysis of skin gene expression in mice fed a standard rodent diet revealed a robust elevation of skin retinol, retinoic acid and retinoic acid‐induced genes including that of lipocalin‐2 in SKO mice. Furthermore, cultured human SEB‐1 sebocytes treated with retinol and an SCD inhibitor also display an elevation in retinoic acid‐induced genes and secretion of lipocalin‐2 protein in the media. These results highlight the importance MUFA synthesis for maintaining retinol homeostasis and suggest that the skin is part of a metabolic network that controls energy intake, storage and expenditure. This work is supported by NIH DK‐62388.