An Integrative Approach to Study Adipocyte Extracellular Signaling Events Linked to the Development of Metabolic Disorders

Obesity increases the risks for secondary disorders including type 2 diabetes, atherosclerosis and cardiovascular diseases and is considered one of the most serious health problems in the 21st century. Adipocyte dysfunction in obesity, like for example insulin resistance is known to contribute to the development of type 2 diabetes. Cell surface proteins play a key role in signal transduction and cellular communication. Therefore, changed cell surface protein profiles are likely to contribute to the dysfunctional phenotype of adipose tissue in obesity and could be useful as well, as predictive markers for adipocyte malfunction. We characterized cell surface protein expression profiles of primary adipocytes derived from different mouse models of metabolic disorders in a label-free mass spectrometric approach. We were able to quantify hundreds of plasma membrane proteins and observed obesity induced cell surface changes. For several of these cell surface proteins we could demonstrate a function in adiponectin secretion, or the regulation of the lipolytic activity of adipocytes. Thus we conclude that the cell surface proteins exhibiting obesity induced changes and impacting adipocyte function at the same time contribute to adipocyte malfunction in obesity and the regulation of their activity could improve or prevent adipocyte malfunction.

Mot-clé: Cell Surface Proteins, Proteomics, Mass Spectrometry, Adipocytes, Obesity, Metabolic Disease