Decr1, encoding 2,4-dienoyl-CoA [coenzyme A] reductase 1, is a rate-limiting enzyme involved in β-oxidation, a key process in fatty acid metabolism. It is associated with multiple biological pathways related to lipid homeostasis, energy production, and cell survival [1,2,3]. Genetic models, such as knockout (KO) mouse models, have been crucial in uncovering its functions in various disease-related processes.

In mouse models, DECR1 deficiency exacerbates myocardial infarction (MI)-induced cardiac damage, while BMP9-mediated increase in DECR1 expression promotes cardiac mitochondrial bioenergetics and mitigates cardiomyocyte injury, suggesting its importance in MI protection [1]. In diabetic cardiomyopathy (DCM) mouse models, cardiomyocytes-specific knockdown of Decr1 preserves cardiac function, inhibits hypertrophy, fibrosis, apoptosis, and oxidative damage, while overexpression aggravates DCM. Decr1 interacts with PDK4 in injured cardiomyocytes, which is involved in excessive mitochondrial fatty acid oxidation (FAO) and cardiac injury [4].

In summary, Decr1 plays essential roles in maintaining cardiac function during MI and DCM through its impact on mitochondrial bioenergetics and fatty acid oxidation. The use of KO and cell-specific knockdown mouse models has provided valuable insights into its functions in these disease conditions, highlighting its potential as a therapeutic target for related cardiovascular diseases.

References:

1. Duan, Zikun, Huang, Zhouqing, Lei, Wei, Li, Yulin, Lin, Zhuofeng. 2024. Bone Morphogenetic Protein 9 Protects Against Myocardial Infarction by Improving Lymphatic Drainage Function and Triggering DECR1-Mediated Mitochondrial Bioenergetics. In Circulation, 150, 1684-1701. doi:10.1161/CIRCULATIONAHA.123.065935. https://pubmed.ncbi.nlm.nih.gov/39315433/

2. Nassar, Zeyad D, Mah, Chui Yan, Dehairs, Jonas, Swinnen, Johannes V, Butler, Lisa M. 2020. Human DECR1 is an androgen-repressed survival factor that regulates PUFA oxidation to protect prostate tumor cells from ferroptosis. In eLife, 9, . doi:10.7554/eLife.54166. https://pubmed.ncbi.nlm.nih.gov/32686647/

3. Blomme, Arnaud, Ford, Catriona A, Mui, Ernest, Zanivan, Sara, Leung, Hing Y. 2020. 2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer. In Nature communications, 11, 2508. doi:10.1038/s41467-020-16126-7. https://pubmed.ncbi.nlm.nih.gov/32427840/

4. Lu, Qing-Bo, Sun, He-Ting, Zhou, Kuo, Zhu, Xue-Xue, Sun, Hai-Jian. . Therapeutic Targeting of Decr1 Ameliorates Cardiomyopathy by Suppressing Mitochondrial Fatty Acid Oxidation in Diabetic Mice. In Journal of cachexia, sarcopenia and muscle, 16, e13761. doi:10.1002/jcsm.13761. https://pubmed.ncbi.nlm.nih.gov/40052435/