RGD Reference Report - Protective effects of Acyl-coA thioesterase 1 on diabetic heart via PPARα/PGC1α signaling. - Rat Genome Database

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Protective effects of Acyl-coA thioesterase 1 on diabetic heart via PPARα/PGC1α signaling.

Authors: Yang, Shenglan  Chen, Chen  Wang, Hong  Rao, Xiaoquan  Wang, Feng  Duan, Quanlu  Chen, Fuqiong  Long, Guangwen  Gong, Wei  Zou, Ming-Hui  Wang, Dao Wen 
Citation: Yang S, etal., PLoS One. 2012;7(11):e50376. doi: 10.1371/journal.pone.0050376. Epub 2012 Nov 30.
RGD ID: 13831128
Pubmed: PMID:23226270   (View Abstract at PubMed)
PMCID: PMC3511550   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0050376   (Journal Full-text)


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/PPARγ coactivator 1α (PPARα/PGC1α) signaling, as shown by decreased expression of PGC1α and the downstream genes involved in FAs use.
CONCLUSION: Our results demonstrated that ACOT1 played a crucial protective role in diabetic heart via PPARα/PGC1α signaling.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Diabetic Cardiomyopathies  ISOAcot1 (Mus musculus)13831128; 13831128associated with type 2 diabetes mellitusRGD 
Diabetic Cardiomyopathies  IMP 13831128associated with type 2 diabetes mellitusRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of cardiac muscle cell apoptotic process  IMP 13831128 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Acot1  (acyl-CoA thioesterase 1)

Genes (Mus musculus)
Acot1  (acyl-CoA thioesterase 1)

Genes (Homo sapiens)
ACOT1  (acyl-CoA thioesterase 1)


Additional Information