Obesity is the major risk factor for type 2 diabetes mellitus, atherosclerosis and nonalcoholic fatty liver disease.  Chronic low-grade inflammation of the adipose tissue (AT) as a consequence of adipocyte hypertrophy contributes to the development of insulin resistance. An imbalance between protease activity and protease inhibition is observed in obesity with detrimental consequences related to inflammation and insulin resistance.

This indicates proteases and specific inhibitors such as serpins as promising targets for the treatment of both obesity and associated metabolic diseases.

One part of this project focusses on the roles and interplay of the serine protease inhibitor vaspin (SERPINA12) and its target proteases in adipose tissue (AT) inflammation, insulin resistance and energy expenditure. Overexpression of endogenous serpin inhibitors such as vaspin in AT reduces weight gain, inflammation and preserves insulin sensitivity under high fat diet. Vice versa, global or conditional knock out of vaspin target protease KLK7 reduces weight gain, inflammation and preserves insulin sensitivity under HFD. We have identified the first two target proteases of vaspin (KLK7 and KLK14) as well as cofactors, binding molecules and adipocyte cell-surface receptors.