Regulation of glucose metabolism by the skeleton: From individual pathways to systems biology

Skeletal research has focused on the pathogenicity of obesity and diabetes mellitus (DM) on the skeleton.

DM is associated with increased risk of osteoporotic fracture, whereas obesity increases bone mineral density (BMD) but impairs bone quality.

However, cellular, molecular and mouse models have recently revealed that the skeleton is not merely an endocrine target but also a secretory organ, modulating systemic energy homeostasis.

My previous research has identified that (1) the skeleton is a significant site of glucose uptake (using 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography and computerised tomography; PET/CT) (2) different bones have a unique glucose metabolism and form complex metabolic networks, identified using our newly developed PET fingerprinting technique.

My research aims to determine if compromised skeletal structure contributes to whole body metabolism.

A rat model of post-menopausal osteoporosis and healthy control will undergo dynamic 18F-FDG PET/CT to determine 18F-FDG uptake into the bone, cartilage, white and brown adipose tissue (WAT; BAT), heart, muscle, and liver.

Whole-body PET fingerprinting technology will be used to identify skeletal / metabolic networks and determine if these networks are altered by bone dysregulation.

Such knowledge might lead to the identification of novel pathways through which bone disease causes insulin resistance and metabolic disease.