PRDM16, the PRD1-BF1-RIZ1 homologous domain containing 16, is a transcription factor highly expressed in adipocytes. It plays a crucial role in adipose tissue metabolism, such as adipocyte browning, thermogenesis, and myoblast adipogenic differentiation. PRDM16 also participates in regulating mitochondrial function through interacting with PPAR-α and PGC-1α, and is involved in epigenetic regulation via H3K4me3 [1,2,5]. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions.

In T2DM-induced cardiomyopathy, Prdm16 cardiac-specific deficiency in mice accelerated cardiomyopathy and worsened cardiac dysfunction, aggravating mitochondrial dysfunction and apoptosis, while overexpression alleviated these effects. Prdm16 deficiency also led to cardiac lipid accumulation and metabolic and molecular alterations. It regulated PPAR-α and PGC-1α mainly through epigenetic regulation of H3K4me3 [1]. In addition, Prdm16 deletion in mice was associated with sex-dependent cardiomyopathy and increased cardiac mortality, with female Prdm16 conditional knockout mice showing more severe contractile dysfunction, fibrosis, and higher mortality [3]. In left ventricular non-compaction cardiomyopathy, cardiomyocyte-specific ablation of Prdm16 in mice recapitulated the human disease phenotype, as PRDM16 functioned as a compact myocardium-enriched transcription factor regulating chamber-specific gene expression [4].

In summary, PRDM16 is essential for adipose tissue metabolism and mitochondrial function. Prdm16 KO/CKO mouse models have revealed its critical roles in cardiomyopathies, highlighting its potential as a therapeutic target for related heart diseases.

References:

1. Hu, Tongtong, Wu, Qingqing, Yao, Qi, Wan, Ying, Tang, Qizhu. 2023. PRDM16 exerts critical role in myocardial metabolism and energetics in type 2 diabetes induced cardiomyopathy. In Metabolism: clinical and experimental, 146, 155658. doi:10.1016/j.metabol.2023.155658. https://pubmed.ncbi.nlm.nih.gov/37433344/

2. Seale, Patrick, Bjork, Bryan, Yang, Wenli, Beier, David R, Spiegelman, Bruce M. . PRDM16 controls a brown fat/skeletal muscle switch. In Nature, 454, 961-7. doi:10.1038/nature07182. https://pubmed.ncbi.nlm.nih.gov/18719582/

3. Kramer, Ryan J, Fatahian, Amir Nima, Chan, Alice, Boudina, Sihem, Landstrom, Andrew P. 2023. PRDM16 Deletion Is Associated With Sex-dependent Cardiomyopathy and Cardiac Mortality: A Translational, Multi-Institutional Cohort Study. In Circulation. Genomic and precision medicine, 16, 390-400. doi:10.1161/CIRCGEN.122.003912. https://pubmed.ncbi.nlm.nih.gov/37395136/

4. Wu, Tongbin, Liang, Zhengyu, Zhang, Zengming, Fu, Xiang-Dong, Chen, Ju. 2021. PRDM16 Is a Compact Myocardium-Enriched Transcription Factor Required to Maintain Compact Myocardial Cardiomyocyte Identity in Left Ventricle. In Circulation, 145, 586-602. doi:10.1161/CIRCULATIONAHA.121.056666. https://pubmed.ncbi.nlm.nih.gov/34915728/

5. Jiang, Na, Yang, Ming, Han, Yachun, Zhao, Hao, Sun, Lin. 2022. PRDM16 Regulating Adipocyte Transformation and Thermogenesis: A Promising Therapeutic Target for Obesity and Diabetes. In Frontiers in pharmacology, 13, 870250. doi:10.3389/fphar.2022.870250. https://pubmed.ncbi.nlm.nih.gov/35462933/