hart_vol

Zhixiong Ying, MSc

Development and validation of a new gold standard to quantify brown fat activity

Brown adipose tissue (BAT) is considered as a novel therapeutic target for obesity, type 2 diabetes, and relevant cardiovascular diseases, and therefore many BAT activating strategies are currently being pursued. The current gold standard to quantify BAT activity is [18F]fluorodeoxyglucose PET-CT, which assesses the uptake of a radioactive glucose analogue by BAT. However, this method may cause underestimation of BAT activity in insulin resistant individuals since BAT oxidizes fatty acids rather than lipids. Based on our previous studies (Berbée, Nat Commun 2015; Hoeke, Circ Res 2016; Van den Berg, Cell Rep 2018), we suggest that uptake of fatty acids (FAs) derived from triglyceride (TG)-rich lipoproteins (TRLs) may be a more accurate and relevant tracer for BAT activity.

Therefore, in my research project, glycerol tri[18F]oleate-labeled TRL-like particles will be generated to investigate their utility in the non-invasive assessment of BAT activity in preclinical studies using micro PET-CT. If successful, this new method will allow to identify novel BAT-activating agents, and monitor BAT activation in pharmacological strategies aimed at improving lipid metabolism and reducing atherosclerosis development.