Stearoyl‐CoA desaturase: A novel control point of lipid metabolism and insulin sensitivity

Abstract

Stearoyl-CoA desaturase (SCD) is a central enzyme responsible for the synthesis of monounsaturated fatty acids -mainly oleate. Recent studies have shown that SCD1 plays also a significant role in the regulation of lipid metabolism. SCD1-deficient mice have increased energy expenditure, reduced body adiposity, increased insulin sensitivity and are resistant to diet-induced obesity and liver steatosis. SCD1 was found to be specifically repressed during leptin-mediated weight loss, and leptin-deficient ob/ob mice lacking SCD1 showed markedly reduced adiposity. In addition, SCD1 deficiency completely corrects the hypometabolic phenotype and hepatic steatosis of ob/ob mice and attenuates fasting-induced liver steatosis in PPARa-deficient mice. Lack of SCD1 expression also improves insulin action in skeletal muscles and prevents diet-induced hepatic insulin resistance in mice. Much evidence indicates that the direct antisteatotic and anti-diabetic effects of SCD1 deficiency stem from the decreased tissue lipid content caused by enhanced fatty acid oxidation and reduced lipid synthesis. In this review, we discuss our current understanding of the role of SCD1 in insulin resistance and regulation of hepatic lipid partitioning, and test the hypothesis that pharmacological manipulation of SCD might be of benefit in the treatment of nonalcoholic fatty liver disease and in the prevention of diabetes.

Differential gene expression in adipose tissue from obese human subjects during weight loss and weight maintenance

“…Meanwhile, it is important to keep in mind that there may be species differences because cidea in mice is exclusively expressed in brown adipose tissue (12). The gene coding for stearoyl-coenzyme A desaturase, which is an enzyme involved in the lipogenesis of unsaturated fatty acids and associated with insulin resistance (40,41), constitutes another example. SCD was downregulated during weight loss but upregulated during the weight-maintenance phase.…”

“…Weight loss Maintenance of reduced weight Men/women (n) 3/6 3/6 2 3/6 Age (y) 40 second assessment) was excluded from the analysis because of improper sampling ( Figure 1). …”

Increased serum triglycerides and reduced HDL cholesterol in male rats after intake of ammonium chloride for 3 weeks

“…Studies in mice lacking stearoyl-CoA desaturase (SCD) seem to offer an explanation of the epidemiological findings [5,22-25]. Mice lacking the enzyme do not have the ability to form monounsaturated fatty acids which are significant constituents of tissue lipids and serum lipoproteins.…”

The Oslo Health Study: A Dietary Index estimating high intake of soft drinks and low intake of fruits and vegetables was positively associated with components of the metabolic syndrome

“…Previously, others have reported increased hepatic D9, D6, and D5 desaturase activities in sucrose-fed rats (Brenner et al 2003). In mice, lack of stearoyl CoA desaturase seems to increase insulin sensitivity, inhibit growth, reduce hepatic lipogenesis and steatosis, and reduce serum triglyceride levels (Dobrzyn et al 2008). These previous reports are interesting in connection with the finding from this study of an association between dietary acid load and MetS, but no data are available to substantiate the hypothesis that an acid load in humans stimulates hepatic desaturase activities, thereby reducing insulin sensitivity, formation of monounsaturated fatty acids, and the synthesis of VLDL cholesterol, and promoting the development of MetS.…”