Abstract 1160: Increased Stearoyl-CoA Desaturase-1 Expression in Obese and Diabetic Heart Plays a Protective Role Against Fatty Acid-Induced Cardiac Dysfunction
Elevated serum levels of free fatty acid (FFA) in obesity and type 2 diabetes can promote FFA uptake in the heart in excess of tissue capacity for utilization, lead to elevation of oxidative stress, and induce cardiac myocyte apoptosis by non-oxidative metabolic pathway. As a consequence, these effects contribute to cardiac dysfunction. The lipogenic gene stearoyl-CoA desaturase-1 (SCD1), a catalytic enzyme which converts saturated fatty acids into monounsaturated fatty acids, has been postulated to be a promising target for the treatment of obesity. However, the role of SCD1 for the obesity-related cardiac dysfunction remains to be determined. Here we examined the expression of cardiac SCD1 in obese rats which were induced by sucrose-rich chow for 1 to 3 months. Compared with rats fed a standard chow, those given a sucrose-rich chow induced visceral fat accumulation, hyperglycemia, hyperinsulinemia and increased plasma FFA. Real-time PCR and immunohistochemistry showed that the expression of SCD1 mRNA and protein was significantly increased in rat heart after sucrose-rich chow (1 month: 1.5±0.7 fold, 3 month: 2.0±0.4 fold*. vs control. n=6, *p<0.05). Furthermore, human heart showed that expression of SCD1 was increased in diabetic or obese heart compared with non-diabetic and non-obese heart. We confirmed that SCD1 mRNA expression was increased in neonatal rat cardiac myocytes by exposure to high concentration of glucose (450 mg/dl) or insulin (1 mg/dl). To establish a relationship between SCD1 and lipid metabolism or apoptosis, we prepared SCD1-overexpressing cardiac myocytes using adenovirus. SCD1-overexpression markedly suppressed palmitic acid-induced fatty acid oxidation in rat cardiac myocytes (2.8 to 1.6 fold*, vs control. n=7, *p<0.05). Furthermore, SCD1 overexpression significantly suppressed palmitic acid-induced caspase-3 activity and the number of TUNEL-positive staining cells (2.3 to 0.9 fold**, 2.1 to 1.1 fold**, vs control, n=9, **p<0.01). These effects were blunted by knockdown of SCD1 expression by using siRNA. In conclusions, our results demonstrated that SCD1 expression was up-regulated in obese and diabetic heart, and SCD1-overexpression protected cardiac myocytes from FFA-induced excess of oxidation and apoptosis.