Serpins and Proteases in Obesity
Serpins and Proteases in Obesity
Proteolytic Enzymes and Their Regulators in Adipose Tissue, Obesity and Inflammation
A major focus of our research has been on serine protease inhibitors (serpins), their protease targets, and their interplay in adipose tissue function or dysfunction in obesity. Proteases play crucial roles in regulating the localization, activity, and interactions of their target proteins. Due to this broad functional repertoire, they are involved in many important cellular processes such as cell proliferation and differentiation, angiogenesis, and inflammation. Proper control of proteolytic activity is essential for healthy cell and tissue function while dysregulation is a contributing factor to many pathological conditions. In obesity, an imbalance between proteolytic activity and protease inhibition is observed and related to increased inflammation, insulin resistance, and reduced energy expenditure. Adipocyte hypertrophy, together with increased adipose tissue stresses such as hypoxia and fibrosis, contribute to local inflammation and the development of insulin resistance. Extracellular as well as intracellular proteases have been found to be dysregulated in the obese adipose tissue. Pharmacological targeting of key proteolytic enzymes may counteract adipose tissue dysfunction and prevent progress of metabolic diseases.
Publications
2023 FEBS J, doi: 10.1111/febs.16991
LRP1 is the cell-surface endocytosis receptor for vaspin in adipocytes
2023 Front Endocrinol, 14:1146454.
2023 Obesity, 31, 2862-2874.
Genetic dissection of serum vaspin highlights its causal role in lipid metabolism
2021 Adipocyte, 10(1):216-31
2021 Biomedicines, 9(2): 131
2020 Molecules, 25(8): 1992
Membrane Phospholipids and Polyphosphates as Cofactors and Binding Molecules of SERPINA12 (Vaspin)
2020 J Med Chem, 63: 5723-5733.
2019 Protein Reviews. Advances in Experimental Medicine and Biology, 1111:159-188.
2018 Biol Chem, 399(9): 1079-1084
Kallikrein-Related Peptidase 14 is the Second KLK Protease Targeted by the Serpin Vaspin
2018 Cell Mol Life Sci, 75(4): 727-42
2018 Mol Cell Endocrinol, 460: 181-88
2017 Biochim Biophys Acta Proteins Proteom, 1865(9): 1188-1194
2017 J Biol Chem, 292(3): 994-1004
Basic Residues of beta-Sheet A Contribute to Heparin Binding and Activation of Vaspin (Serpin A12)
2016 Biol Chem, 397(2): 111-23.
2015 Biochem J, 470(3): 357-67
2013 Cell Mol Life Sci, 70(14): 2569-83