PDK4 and neoplasm: 17 While the transcription of PDHK1 and 3 genes is activated by low oxygen levels in response to HIF-1α in tumour cells,18, 19 PDHK4 expression is upregulated in tissues with high rates of fatty acid synthesis, suggesting a critical role in lipid metabolism.20 The roles of PDHK2 and PDHK4 have been reported to be more relevant in starvation and diabetes, as their expression levels can be controlled by nutritional factors, hormones, steroids and fatty acids.21