Hif3a, the hypoxia-inducible factor 3 alpha subunit, is a key regulator in the transcriptional response to changes in oxygen concentration, being part of the hypoxia-inducible transcription factors (HIFs) family. It is involved in multiple biological processes such as lung development and the metabolic process of fat tissue, and has potential connections to energy metabolism-related pathways [1,2]. Gene-knockout (KO) mouse models are valuable tools in studying Hif3a's function.

In Hif3a gene-disrupted mice, abnormal alveoli structure was observed, including a reduced number of alveoli and thickened alveolar walls, leading to early neonatal death. This indicates Hif3a's crucial role in maintaining the structure and function of alveoli [1]. In adipocyte studies, inhibiting Hif3a in murine pre-adipocyte 3T3-L1 cell line promoted "browning" of white adipocytes, activating thermogenesis, which reveals its role in energy metabolism regulation [2].

In conclusion, Hif3a is essential for lung development, especially in alveoli structure and function, and also plays a significant role in energy metabolism, particularly in the regulation of adipocyte browning. The use of Hif3a KO mouse models has provided important insights into its functions in these biological processes and related disease conditions such as neonatal lung-related disorders and metabolic disorders [1,2].