| First Author | Yang S | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 11 | Pages | e50376 |
| PubMed ID | 23226270 | Mgi Jnum | J:195446 |
| Mgi Id | MGI:5484486 | Doi | 10.1371/journal.pone.0050376 |
| Citation | Yang S, et al. (2012) Protective effects of Acyl-coA thioesterase 1 on diabetic heart via PPARalpha/PGC1alpha signaling. PLoS One 7(11):e50376 |
| abstractText | BACKGROUND: Using fatty acids (FAs) exclusively for ATP generation was reported to contribute to the development of diabetic cardiomyopathy. We studied the role of substrate metabolism related genes in the heart of the diabetes to find out a novel therapeutic target for diabetic cardiomyopathy. METHODS AND RESULTS: By microarray analysis of metabolic gene expression, acyl-CoA thioesterase 1 (acot1) was clearly upregulated in the myocardia of db/db mice, compared with normal control C57BL/Ks. Therefore, gain-of-function and loss-of-function approaches were employed in db/db mice to investigate the functions of ACOT1 in oxidative stress, mitochondrial dysfunction and heart function. We found that in the hearts of db/db mice which overexpressed ACOT1, H(2)O(2) and malondialdehyde (MDA) were reduced, the activities of ATPases in mitochondria associated with mitochondrial function were promoted, the expression of uncoupling protein 3 (UCP3) contributing to oxygen wastage for noncontractile purposes was decreased, and cardiac dysfunction was attenuated, as determined by both hemodynamic and echocardiographic detections. Consistently, ACOT1 deficiency had opposite effects, which accelerated the cardiac damage induced by diabetes. Notably, by real-time PCR, we found that overexpression of ACOT1 in diabetic heart repressed the peroxisome proliferator-activated receptor alpha/PPARgamma coactivator 1alpha (PPARalpha/PGC1alpha) signaling, as shown by decreased expression of PGC1alpha and the downstream genes involved in FAs use. CONCLUSION: Our results demonstrated that ACOT1 played a crucial protective role in diabetic heart via PPARalpha/PGC1alpha signaling. |
