A precision medicine approach to understand the complexity of insulin resistance

Insulin resistance is a critical factor in the pathogenesis of type 2 diabetes and cardiovascular diseases, yet the underlying cellular mechanisms remain inadequately understood.

We have recently identified a distinct subtype of human adipocytes, termed AdipoPLIN, which in healthy human subjects constitutes a unique subpopulation displaying high sensitivity to insulin.

Thus, contrary to traditional views of adipocyte homogeneity, our findings suggest cellular heterogeneity as a key determinant of insulin sensitivity. However, the pathophysiological significance of AdipoPLIN remains unclear.

Our hypothesis is that this subtype is an important determinant of systemic insulin sensitivity and the response to therapies targeting insulin resistance.

Through three independent aims, we will mechanistically investigate insulin action in AdipoPLIN, evaluate its function in vivo through transplantation models, and assess its role in intervention studies.

By leveraging advanced techniques including spatial transcriptomics, proteomics, and clinical intervention trials, we seek to define the pathophysiological role of AdipoPLIN and its relevance to metabolic diseases. Ultimately, this research may pave the way for personalized interventions in insulin resistance and type 2 diabetes.