ArticleJournal of cachexia, sarcopenia and muscle2025
Therapeutic Targeting of Decr1 Ameliorates Cardiomyopathy by Suppressing Mitochondrial Fatty Acid Oxidation in Diabetic Mice.
Article in Journal of cachexia, sarcopenia and muscle, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Hepatocyte SLC31A1-dependent copper accumulation contributes to hepatic glucose and lipid metabolic disturbances through AMPKα1 inactivation.Biochemistry and biophysics reports · 2026Article
- GIPC1 governed ferroptosis by regulating DECR1-modulating lipid homeostasis during dilated cardiomyopathy (DCM).Cell death and differentiation · 2026Article
- Article
- Mitochondrial Transplantation as a New Therapeutic Approach Against Cardiac and Renal Consequences in Male Rats With Myocardial Infarction.Acta physiologica (Oxford, England) · 2026Article
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- HDAC3-driven immunometabolic reprogramming in type 2 diabetes and its complications: from enzymatic deacetylation to non-enzymatic scaffolding.Frontiers in immunology · 2026Review
- Research progress on metabolic abnormalities in myocardial hypertrophy.Frontiers in cardiovascular medicine · 2026Review
- Metabolic reprogramming in diabetic complications: mechanisms, pathologies, and molecular evidence from multi-organ studies.Frontiers in immunology · 2026Review
- HSF1 modulates lipid metabolism and ferroptosis in sarcopenia: a novel diagnostic biomarker and therapeutic target.Frontiers in molecular biosciences · 2026Article
- Loganic acid ameliorates diabetic cardiomyopathy via suppressing TLR4/p38 MAPK signaling-mediated oxidative stress and inflammation.Journal of clinical biochemistry and nutrition · 2025Article
- Identification of Mitochondria- and Macrophage Activation-Related Hub Genes in Sarcopenia.IET systems biologyArticle
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18 authors.
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Abstract
backgroundA significant increase in mitochondrial fatty acid oxidation (FAO) is now increasingly recognized as one of the metabolic alterations in diabetic cardiomyopathy (DCM). However, the molecular mechanisms underlying mitochondrial FAO impairment in DCM remain to be fully elucidated.
methodsA type 2 diabetes (T2D) mouse model was established by a combination of high-fat diet (HFD) and streptozotocin (STZ) injection. Neonatal rat cardiomyocytes were treated with high glucose (HG) and palmitic acid (HP) to simulate diabetic cardiac injury. Gain- and loss-of-function approaches and RNA sequencing were utilized to investigate the role and mechanism of 2,4-dienoyl-CoA reductase 1 (Decr1) in DCM.
resultsBy integrating the genomic data available in the Gene Expression Omnibus (GEO) with DCM rodents, we found that the transcriptional level of Decr1 was consistently upregulated in DCM (+255% for diabetic heart, p < 0.0001; +281% for diabetic cells, p < 0.0001). Cardiomyocytes-specific knockdown of Decr1 preserved cardiac function (+41% for EF, p < 0.0001; +24% for FS, p = 0.0052), inhibited cardiac hypertrophy (-34%, p < 0.0001), fibrosis (-69%, p < 0.0001), apoptosis (-56%, p < 0.0001) and oxidative damage (-59%, p < 0.0001) in DCM mice, while cardiomyocytes-specific overexpression of Decr1 aggravated DCM (-28% for EF, p = 0.0347; -17% for FS, p = 0.0014). Deletion of Decr1 prevented high glucose/palmitate (HG/HP)-induced hypertrophy (-22%, p = 0.0006), mitochondrial dysfunction and apoptosis (-74%, p < 0.0001) in cultured cardiomyocytes. Furthermore, RNA sequencing and functional analysis showed that Decr1 interacted with and upregulated pyruvate dehydrogenase kinase 4 (PDK4) in injured cardiomyocytes, and overexpression of PDK4 eliminated the benefits of Decr1 downregulation in DCM (-20% for EF, p = 0.0071; -28% for FS, p = 0.0022). Mechanistically, PDK4 acted as a kinase that induced phosphorylation and mitochondrial translocation of HDAC3. In the mitochondria, HDAC3 mediated the deacetylation of dehydrogenase trifunctional multienzyme complex α subunit (HADHA), contributing to excessive mitochondrial FAO and subsequent cardiac injury. From a screening of 256 natural products, we identified Atranorin and Kurarinone as potential inhibitors of Decr1, both demonstrating protective effects against DCM (Atranorin, +21% for EF, p = 0.0134; +24% for FS, p = 0.0006; Kurarinone, +20% for EF, p = 0.0183; +27% for FS, p = 0.0001).
conclusionsOur study delineates a molecular mechanism by which Decr1 potentiated higher mitochondrial lipid oxidation and cardiac damage by enhancing HADHA deacetylation through the PDK4/HDAC3 signalling pathway.
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