Role of Stearoyl-CoA Desaturase-1 in Metabolism: Implication in Human Diseases

The rapid adaptation to a modernized lifestyle, characterized by reduced physical activity and increased consumption of processed foods rich in carbohydrate and fat, has resulted in a dramatic rise in the incidence of adult and child obesity in many nations of the World. Obesity increases the risk for numerous conditions that shorten life, including diabetes, coronary artery disease, hypertension, inflammation and fatty liver disease and other symptoms of the metabolic syndrome. The precise etiology of the numerous obesity-related risk factors is still unknown; however an increasing body of evidence indicates that genetics and environmental factors play a major role. Studies of the complex interactions among genes and nutrients are beginning to uncover the role of diets in human health and disease. Diets cause alterations in the expression of genes of lipid and carbohydrate metabolism. A critical regulator gene of energy metabolism is stearoyl-CoA desaturase 1 (SCD1), that encodes an enzyme (SCD) which catalyzes the synthesis of monounsaturated fatty acids mainly oleate. SCD1 expression is elevated in human and rodent obese and insulin resistant states, suggesting that excess oleate synthesis may contribute to the development of these disease states. Animal models with a global deficiency in SCD-1 exhibit a decrease in cellular oleate levels, a decrease in de novo hepatic lipogenesis and are protected from genetic and high-fat-induced obesity, insulin resistance, liver steatosis and other symptoms of the metabolic syndrome. However, in these mice Scd1 is deleted from all tissues presenting a complex phenotype due to metabolic changes occurring in many organs. Therefore, the tissue-specific contribution of SCD1 expression to metabolic outcomes remains to be explored. NIH supports this work.

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