Stearoyl-CoA desaturase-1 (SCD1) augments saturated fatty acid-induced lipid accumulation and inhibits apoptosis in cardiac myocytes

• Published in: PloS one 2012-03, Vol.7 (3), p.e33283
• Main Authors: Matsui, Hiroki, Yokoyama, Tomoyuki, Sekiguchi, Kenichi, Iijima, Daisuke, Sunaga, Hiroaki, Maniwa, Moeno, Ueno, Manabu, Iso, Tatsuya, Arai, Masashi, Kurabayashi, Masahiko
• Format: Article
• Language: English
• Subjects: Accumulation; Adenoviruses; Adipocytes; Animals; Apoptosis; Apoptosis - drug effects; Atherosclerosis; Biology; Blood Glucose - metabolism; Cardiomyocytes; Cardiomyopathy; Caspase; Caspase-3; Catabolism; Cell death; Cells, Cultured; Ceramide; Coenzyme A; Dehydrogenases; Desaturase; Diabetes; Diet; Diet - adverse effects; Diglycerides; Energy metabolism; Enzymes; Fatty acids; Fatty Acids - pharmacology; Fatty Acids, Nonesterified - metabolism; Gene expression; Gene Expression - drug effects; Genes; Glucose; Health sciences; Heart; Heart diseases; Humans; Hydrogen Peroxide - pharmacology; Hypertension; Insulin; Insulin - metabolism; Insulin resistance; Kinases; Laboratories; Ligands; Lipid Metabolism; Lipids; Male; Medicine; Metabolic disorders; Metabolic syndrome; Metabolism; Mitochondria; Monounsaturated fatty acids; Myocardium; Myocardium - metabolism; Myocytes; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Neonates; Obesity; Obesity, Abdominal - etiology; Oxidants - pharmacology; Oxidation; Oxidation-Reduction; Oxygen; Palmitic acid; Physiological aspects; Rats; Rats, Wistar; Reactive oxygen species; Reactive Oxygen Species - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Saturated fatty acids; siRNA; Stearoyl-CoA desaturase; Stearoyl-CoA Desaturase - genetics; Stearoyl-CoA Desaturase - metabolism; Studies; Sucrose; Sugar; Synthesis; Type 2 diabetes; University graduates
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0033283

Mismatch between the uptake and utilization of long-chain fatty acids in the myocardium leads to abnormally high intracellular fatty acid concentration, which ultimately induces myocardial dysfunction. Stearoyl-Coenzyme A desaturase-1 (SCD1) is a rate-limiting enzyme that converts saturated fatty acids (SFAs) to monounsaturated fatty acids. Previous studies have shown that SCD1-deficinent mice are protected from insulin resistance and diet-induced obesity; however, the role of SCD1 in the heart remains to be determined. We examined the expression of SCD1 in obese rat hearts induced by a sucrose-rich diet for 3 months. We also examined the effect of SCD1 on myocardial energy metabolism and apoptotic cell death in neonatal rat cardiac myocytes in the presence of SFAs. Here we showed that the expression of SCD1 increases 3.6-fold without measurable change in the expression of lipogenic genes in the heart of rats fed a high-sucrose diet. Forced SCD1 expression augmented palmitic acid-induced lipid accumulation, but attenuated excess fatty acid oxidation and restored reduced glucose oxidation. Of importance, SCD1 substantially inhibited SFA-induced caspase 3 activation, ceramide synthesis, diacylglycerol synthesis, apoptotic cell death, and mitochondrial reactive oxygen species (ROS) generation. Experiments using SCD1 siRNA confirmed these observations. Furthermore, we showed that exposure of cardiac myocytes to glucose and insulin induced SCD1 expression. Our results indicate that SCD1 is highly regulated by a metabolic syndrome component in the heart, and such induction of SCD1 serves to alleviate SFA-induced adverse fatty acid catabolism, and eventually to prevent SFAs-induced apoptosis.