HIF-1 regulates energy metabolism of the Tibetan chicken brain during embryo development under hypoxia

The Tibetan chicken (Gallus gallus; TBC) is an indigenous breed found in the Qinghai-Tibet Plateau that are well adapted to a hypoxic environment. The energy metabolism of embryonic brains in TBCs under hypoxia has been little reported. This study investigated changes in energy metabolism of the TBC brain during embryo development under hypoxia. We found that TBCs exhibited a change of glycolysis and the tricarboxylic acid cycle during embryo development under hypoxia. Hypoxia-inducible factor (HIF)-1 was potentially involved in this by directly inducing overexpression of pyruvate dehydrogenase kinase 1 (PDK1) and the glycolytic genes hexokinase 1 (HK1) and lactate dehydrogenase A (LDHA) to increase glycolysis of TBCs to adapt to hypoxia. Although these may not be unique to TBCs, as we had also found similar results in Dwarf Laying Chickens, a lowland chicken breed, TBCs had a stronger regulating ability. In summary, our study revealed that HIF-1 induced energy metabolism changes in the TBC brain via upregulating expressions of PDK1 and other HIF-1 target genes like HK1 and LDHA to increase glycolysis for TBC hypoxic adaptations during embryo development. It indicates the potential application of TBC energy metabolism research for other animals living on the Qinghai-Tibet Plateau.