ANGPTL8 blockade with a monoclonal antibody promotes triglyceride clearance, energy expenditure, and weight loss in mice

Viktoria Gusarova, Serena Banfi, Corey A. Alexa-Braun, Lisa M. Shihanian, Ivory J. Mintah, Joseph S. Lee, Yurong Xin, Qi Su, Vishal Kamat, Jonathan C. Cohen, Helen H. Hobbs, Brian Zambrowicz, George D. Yancopoulos, Andrew J. Murphy, Jesper Gromada

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Angiopoietin-like protein (ANGPTL)8 is a negative regulator of lipoprotein lipase-mediated plasma triglyceride (TG) clearance. In this study, we describe a fully human monoclonal antibody (REGN3776) that binds monkey and human ANGPTL8 with high affinity. Inhibition of ANGPTL8 with REGN3776 in humanized ANGPTL8 mice decreased plasma TGs and increased lipoprotein lipase activity. Additionally, REGN3776 reduced body weight and fat content. The reduction in body weight was secondary to increased energy expenditure. Finally, single administration of REGN3776 normalized plasma TGs in dyslipidemic cynomolgus monkeys. In conclusion, we show that blockade of ANGPTL8 with monoclonal antibody strongly reduced plasma TGs in mice and monkeys. These data suggest that inhibition of ANGPTL8 may provide a new therapeutic avenue for the treatment of dyslipidemia with beneficial effects on body weight.

Original languageEnglish (US)
Pages (from-to)1252-1259
Number of pages8
JournalEndocrinology
Volume158
Issue number5
DOIs
StatePublished - May 1 2017

ASJC Scopus subject areas

  • Endocrinology

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    Gusarova, V., Banfi, S., Alexa-Braun, C. A., Shihanian, L. M., Mintah, I. J., Lee, J. S., Xin, Y., Su, Q., Kamat, V., Cohen, J. C., Hobbs, H. H., Zambrowicz, B., Yancopoulos, G. D., Murphy, A. J., & Gromada, J. (2017). ANGPTL8 blockade with a monoclonal antibody promotes triglyceride clearance, energy expenditure, and weight loss in mice. Endocrinology, 158(5), 1252-1259. https://doi.org/10.1210/en.2016-1894