| First Author | Fauconnier J | Year | 2007 |
| Journal | Diabetes | Volume | 56 |
| Issue | 4 | Pages | 1136-42 |
| PubMed ID | 17229941 | Mgi Jnum | J:122121 |
| Mgi Id | MGI:3713190 | Doi | 10.2337/db06-0739 |
| Citation | Fauconnier J, et al. (2007) Effects of palmitate on Ca(2+) handling in adult control and ob/ob cardiomyocytes: impact of mitochondrial reactive oxygen species. Diabetes 56(4):1136-42 |
| abstractText | Obesity and insulin resistance are associated with enhanced fatty acid utilization, which may play a central role in diabetic cardiomyopathy. We now assess the effect of the saturated fatty acid palmitate (1.2 mmol/l) on Ca(2+) handling, cell shortening, and mitochondrial production of reactive oxygen species (ROS) in freshly isolated ventricular cardiomyocytes from normal (wild-type) and obese, insulin-resistant ob/ob mice. Cardiomyocytes were electrically stimulated at 1 Hz, and the signal of fluorescent indicators was measured with confocal microscopy. Palmitate decreased the amplitude of cytosolic Ca(2+) transients (measured with fluo-3), the sarcoplasmic reticulum Ca(2+) load, and cell shortening by approximately 20% in wild-type cardiomyocytes; these decreases were prevented by the general antioxidant N-acetylcysteine. In contrast, palmitate accelerated Ca(2+) transients and increased cell shortening in ob/ob cardiomyocytes. Application of palmitate rapidly dissipated the mitochondrial membrane potential (measured with tetra-methyl rhodamine-ethyl ester) and increased the mitochondrial ROS production (measured with MitoSOX Red) in wild-type but not in ob/ob cardiomyocytes. In conclusion, increased saturated fatty acid levels impair cellular Ca(2+) handling and contraction in a ROS-dependent manner in normal cardiomyocytes. Conversely, high fatty acid levels may be vital to sustain cardiac Ca(2+) handling and contraction in obesity and insulin-resistant conditions. |
