Cysteine cathepsin S processes leptin, inactivating its biological activity

Author(s)

Oliveira, Marcela ^[1] ; Assis, Diego M. ^[1] ; Paschoalin, Thaysa ^[2] ; Miranda, Antonio ^[1] ; Ribeiro, Eliane B. ^[3] ; Juliano, Maria A. ^[1] ; Broemme, Dieter ^[4] ; Christoffolete, Marcelo Augusto ^[5] ; Barros, Nilana M. T. ^{[1, 6]} ; Carmona, Adriana K. ^[1]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Biofis, BR-04039032 Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Dept Microbiol Imunol & Parasitol, BR-04023062 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Fisiol, BR-04023062 Sao Paulo - Brazil

^[4] Univ British Columbia, Dept Oral Biol & Med Sci, Vancouver, BC V6T 1Z3 - Canada

^[5] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210170 Sao Paulo - Brazil

^[6] Univ Fed Sao Paulo, Dept Ciencias Exatas & Terra, BR-09972270 Sao Paulo - Brazil

• Document type: Journal article
• Source: Journal of Endocrinology; v. 214, n. 2, p. 217-224, AUG 2012.
• Web of Science Citations: 5

Abstract

Leptin is a 16 kDa hormone mainly produced by adipocytes that plays an important role in many biological events including the regulation of appetite and energy balance, atherosclerosis, osteogenesis, angiogenesis, the immune response, and inflammation. The search for proteolytic enzymes capable of processing leptin prompted us to investigate the action of cysteine cathepsins on human leptin degradation. In this study, we observed high cysteine peptidase expression and hydrolytic activity in white adipose tissue (WAT), which was capable of degrading leptin. Considering these results, we investigated whether recombinant human cysteine cathepsins B, K, L, and S were able to degrade human leptin. Mass spectrometry analysis revealed that among the tested enzymes, cathepsin S exhibited the highest catalytic activity on leptin. Furthermore, using a Matrigel assay, we observed that the leptin fragments generated by cathepsin S digestion did not exhibit angiogenic action on endothelial cells and were unable to inhibit food intake in Wistar rats after intracerebroventricular administration. Taken together, these results suggest that cysteine cathepsins may be putative leptin activity regulators in WAT. Journal of Endocrinology (2012) 214, 217-224 (AU)

• FAPESP's process: 11/50495-0 - Study of the metallo-peptidase PHEX involvement in physiological and pathophysiological processes
• Grantee: Nilana Meza Tenório de Barros Jaggi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 08/10700-1 - Energy homeostasis in different mouse lineages: influence of food, physical activity mimetics and genetics
• Grantee: Marcelo Augusto Christoffolete
• Support Opportunities: Research Grants - Young Investigators Grants