PTP1B regulates leptin signal transduction in vivo

Janice M. Zabolotny, Kendra K. Bence-Hanulec, Alain Stricker-Krongrad, Fawaz Haj, Yongping Wang, Yasuhiko Minokoshi, Young Bum Kim, Joel K. Elmquist, Louis A. Tartaglia, Barbara B. Kahn, Benjamin G. Neel

Research output: Contribution to journalArticle

622 Scopus citations


Mice lacking the protein-tyrosine phosphatase PTP1B are hypersensitive to insulin and resistant to obesity. However, the molecular basis for resistance to obesity has been unclear. Here we show that PTP1B regulates leptin signaling. In transfection studies, PTP1B dephosphorylates the leptin receptor-associated kinase, Jak2. PTP1B is expressed in hypothalamic regions harboring leptin-responsive neurons. Compared to wild-type littermates, PTP1B-/- mice have decreased leptin/body fat ratios, leptin hypersensitivity, and enhanced leptin-induced hypothalamic Stat3 tyrosyl phosphorylation. Gold thioglucose treatment, which ablates leptin-responsive hypothalamic neurons, partially overcomes resistance to obesity in PTP1B-/- mice. Our data indicate that PTP1B regulates leptin signaling in vivo, likely by targeting Jak2. PTP1B may be a novel target to treat leptin resistance in obesity.

Original languageEnglish (US)
Pages (from-to)489-495
Number of pages7
JournalDevelopmental cell
Issue number4
StatePublished - Jan 1 2002


ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Cite this

Zabolotny, J. M., Bence-Hanulec, K. K., Stricker-Krongrad, A., Haj, F., Wang, Y., Minokoshi, Y., Kim, Y. B., Elmquist, J. K., Tartaglia, L. A., Kahn, B. B., & Neel, B. G. (2002). PTP1B regulates leptin signal transduction in vivo. Developmental cell, 2(4), 489-495.