Impaired creatine metabolism in white adipocytes of obese subjects promotes insulin resistance and type-2 diabetes

Besides their capacity to store lipids and secrete hormones, we recently identified white adipocytes to be a “sink” for excess energy storage in the form of phosphocreatine.

In obesity, creatine metabolism is perturbed leading to a hyperenergetic state with accumulation of phosphocreatine and ATP overproduction (1).

These changes initiate white adipose tissue (WAT) inflammation, a cornerstone in the development of insulin resistance and type 2 diabetes (T2D). However, the causal mechanisms leading to altered creatine metabolism in obesity and its link to T2D remain unknown.

My preliminary data identify creatine kinase B (CKB), an enzyme which interconverts creatine and phosphocreatine, as a central regulator of adipocyte function and insulin sensitivity.

By combining advanced molecular techniques, including omics analyses, with state-of-the-art clinical and preclinical approaches, I will identify creatine-driven determinants of insulin resistance.

The results generated in this project will uncover novel mechanisms controlling cellular glucose homeostasis and may provide new therapeutic avenues to treat T2D.