Adipocyte Oxygen Sensing Machinery: A regulator of metabolic disease and beyond

Adipocyte Oxygen Sensing Machinery: A regulator of metabolic disease and beyond

Obesity poses a major global healthcare challenge because it increases the risk of co-morbidities such as type 2 diabetes, fatty liver, heart disease and certain cancers.  Excessive adipose accumulation in obesity leads to local relative hypoxia, collagen deposition that leads to uncontrolled scarring and dysfunctional adipose (Michailidou et al. , 2012 JBC; left panel). Tissue oxygen levels are sensed by the hypoxia-inducible factor (HIF-alpha)-pathway and its key regulatory proteins HIF-prolyl hydroxylases (PHDs; degrade HIF in normoxia; middle panel), both of which I have shown are dys-regulated in obesity. We have demonstrated that pharmacological inhibition & genetic PHD2 (dominant oxygen sensor) deletion in adipocytes leads to pseudohypoxia and a beneficial metabolic profile (Michailidou et al, 2015 Diabetes; right panel). My research focuses on mechanisms to harness the adipocyte oxygen sensing to combat obesity-related metabolic complications such as diabetes, fatty liver and certain cancers. 

Group:

Dr Z Michailidou (PI)

Miss Ahlam Darasi (PhD student)

Dr Diana Said (PhD student)

Collaborators:

Prof Sir Peter Ratcliffe (Oxford)

Prof Chris Schofeild (Oxford)

Prof Jeff Pollard (Edinburgh)

Prof Nik Morton (Edinburgh)

Prof Sarah Walmsley (Edinburgh)

Prof Kamil Kranc (Edinburgh)

Dr Roland Stimson (Edinburgh)

Dr Cecile Benezech (Edinburgh)

Dr Andy Finch (Edinburgh)

Prof Phil Scherer (Touchstone Diabetes Centre, Texas)