Appetite enhancement and weight gain by peripheral administration of TrkB agonists in non-human primates

John C. Lin, David Tsao, Paul Barras, Raul A. Bastarrachea, Bob Boyd, Joyce Chou, Rodnie Rosete, Hua Long, Alison Forgie, Yasmina Abdiche, Jeanette Dilley, Jennifer Stratton, Carlos Garcia, David L. Sloane, Anthony G. Comuzzie, Arnon Rosenthal

    Research output: Contribution to journalArticlepeer-review

    30 Scopus citations

    Abstract

    Loss of function mutations in the receptor tyrosine kinase TrkB pathway resulted in hyperphagia and morbid obesity in human and rodents. Conversely, peripheral or central stimulation of TrkB by its natural ligands BDNF or NT4 reduced body weight and food intake in mice, supporting the idea that TrkB is a key anorexigenic signal downstream of the melanocortin-4 receptor (Mc4r) system. Here we show that in non-human primates TrkB agonists were anorexigenic when applied centrally, but surprisingly orexigenic, leading to gain in appetite, body weight, fat deposits and serum leptin levels, when given peripherally. The orexigenic and pro-obesity effects of peripherally administered TrkB agonists appear to be dose dependent, not associated with-fluid retention nor with evidence of receptor down regulation. Our findings revealed that TrkB signaling exerts dual control on energy homeostasis in the primates that could be targeted for the treatment of either wasting disorders or obesity.

    Original languageEnglish (US)
    Article numbere1900
    JournalPloS one
    Volume3
    Issue number4
    DOIs
    StatePublished - Apr 2 2008

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Agricultural and Biological Sciences(all)
    • General

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