Metabolic Implications of Circadian–HIF Crosstalk

Research over the past few decades has shed light on the mechanisms underlying the link between circadian disruption and the development of metabolic diseases such as obesity, type 2 diabetes, and cancer. However, how the clock network interacts with tissue-specific nutrient-sensing pathways during conditions of nutrient stress or pathological states remains incompletely understood. Recent work has demonstrated that the circadian clock can ‘reprogram’ the transcriptome to control distinct sets of genes during altered nutrient conditions, such as high fat diet, aging, and exercise. In this review, I discuss connections between circadian clock transcription factors and the oxygen- and nutrient-responsive hypoxia-inducible factor (HIF) pathway. I highlight recently uncovered mechanistic insights underlying these pathway interactions and address potential implications for the role of circadian disruption in metabolic diseases.