PRDM16, the PRD1-BF1-RIZ1 homologous domain containing 16, is a transcriptional regulator. It plays a crucial role in controlling cell fate switches, especially between skeletal myoblasts and brown fat cells. It is also involved in adipose tissue metabolism, such as adipocyte browning, thermogenesis, and beige adipocyte differentiation. Additionally, it is associated with pathways like PPAR-γ activation. Genetic models, including KO/CKO mouse models, are valuable for studying its functions [1,3,4,7].

In KO mouse models, Prdm16 deficiency in brown fat precursors leads to a loss of brown fat characteristics and promotes muscle differentiation [1]. In cardiac-specific Prdm16 knockout mice, it accelerates cardiomyopathy and worsens cardiac dysfunction in type 2 diabetes, aggravating mitochondrial dysfunction and apoptosis, and causing cardiac lipid accumulation [2]. Genetic loss of Prdm16 in mice mimics the effect of aging in promoting adipose fibrosis, while increasing PRDM16 in aged mice decreases fibrosis and restores beige adipose development [3]. Cardiomyocyte-specific ablation of Prdm16 in mice causes left-ventricular-specific dilation and dysfunction, as well as biventricular non-compaction, recapitulating left ventricular noncompaction cardiomyopathy (LVNC) [5]. Ablation of Prdm16 from kidney proximal tubules in mice inhibits NRF2 and GPX4 expression, leading to increased ferroptosis and AKI progression [6].

In conclusion, Prdm16 is essential in regulating cell fate, adipose tissue metabolism, and mitochondrial function. Prdm16 KO/CKO mouse models have revealed its significance in diseases such as cardiomyopathy, adipose fibrosis, LVNC, and sepsis-associated acute kidney injury, providing insights into disease mechanisms and potential therapeutic targets.