The pandemic rise in obesity has ultimately increased the incidence of metabolic complications too. Non-alcoholic fatty liver disease is the widely encountered hepatic manifestation of metabolic syndrome. These disorders feature adipose tissue expansion and hepatic fat accumulation further compromising local oxygen homeostasis. This tissue hypoxia accelerates adaptive responses to restore oxygenation and tissue metabolism and cell survival. Hypoxia-inducible factors (HIFs) act as key regulators of this hypoxia adaptive reaction and thus are hydroxylated by prolyl hydroxylases (PHDs). 

PHDs are the chief cellular oxygen sensors, which regulate HIF proteasomal degradation in an oxygen-dependent manner. HIFs and PHDs see their role in numerous physiological and pathological conditions. 

Researches on genetic models have demonstrated hypoxia signaling to be a key mechanism in adipose tissue dysfunction, causing adipose tissue fibrosis, inflammation and insulin resistance. Furthermore, hypoxia also impacts liver lipid metabolism and disturbs hepatic lipid accumulation. 

Source- Lefere S, Van Steenkiste C, Verhelst X. et al. Hypoxia-regulated mechanisms in the pathogenesis of obesity and non-alcoholic fatty liver disease. Cell. Mol. Life Sci. 2016;73:3419–3431. https://doi.org/10.1007/s00018-016-2222-1