Hif3a, or Hypoxia-inducible factor 3 alpha, is a key transcriptional regulator in the body's response to oxygen concentration changes. It is part of the hypoxia-inducible transcription factor (HIF) family, which controls the body's adaptation to hypoxia. Besides its role in regulating hypoxia-responsible gene expression, Hif3a is also involved in lung development and the metabolic process of fat tissue [1,2].

In gene-disrupted Hif3a mice, abnormal alveoli structure was observed, including a reduced number of alveoli and thickened alveolar walls, leading to early neonatal death. Transcriptome analysis revealed upregulation of stearoyl-Coenzyme A desaturase 1, and gas chromatography analysis indicated an imbalance in fatty acid distribution in the lung surfactant. However, glucocorticoid injection during pregnancy restored normal alveolar counts and decreased neonatal mortality [1]. In murine pre-adipocyte 3T3-L1 cell line, silencing of Hif3a promoted "browning" of white adipocytes, activating thermogenesis through upregulation of key genes. This was also validated in a thermogenesis-induced in vivo model [2].

In conclusion, Hif3a plays a crucial role in maintaining the structure and function of alveoli in the lung and in regulating energy metabolism in adipose tissue. The use of Hif3a gene-disrupted mouse models has provided valuable insights into its role in lung development and neonatal survival, as well as its potential in treating metabolic disorders such as obesity and diabetes.