Secretome profiling identifies T-Cadherin as a potential biomarker for adipose tissue plasticity

Research question:

Obesity represents the main risk factor for the development of type 2 diabetes mellitus, but does not implicate secondary characteristics per se. In this context, the secretome of primary murine adipocytes was analysed. Additionally, the role of the newly identified adipokine T-Cadherin should be investigated within the adipose tissue.

Methods:

Conditioned medium of primary adipocytes of mouse models for obesity (B6.Cg-Lep^ob; ob) and diabetes (B6.BKS(D)-Lepr^db; db) and respective controls were generated and analyzed via high resolution mass spectrometry. For analysis during adipogenesis T-Cadherin mRNA expression wasmonitored via qPCR in 3T3-L1 cells. Lipid accumulation and fatty acid uptake were analysed upon siRNA knockdown of T-Cadherin. Adipose tissue mRNA expression and plasma levels of T-Cadherin were determined in human cohorts by qPCR and ELISA respectively.

Results:

T-cadherin protein abundance as well as mRNA expression in the visceral white adipose tissue (vWAT) is consequently downregulated in the obese mouse models. In vitro, downregulation of T-cadherin expression lowered PPARγ and C/EBPα expression resulting in deceleration of adipogenesis and a decrease of lipid content of the adipocyte. Translational experiments confirmed the lower levels of T-cadherin expression in the vWAT as well as decreased circulating levels of T-cadherin in obese patients compared to lean controls. Interestingly, bariatric surgery induced weight-loss re-established circulating T-cadherin comparable to lean control levels.

Conclusion:

These results suggest that T-cadherin could be used as a biomarker to monitor the health status of the adipose tissue.