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

doi:10.1016/S1534-5807(02)00148-X

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 journal › Article

628 Scopus citations

Abstract

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 language	English (US)
Pages (from-to)	489-495
Number of pages	7
Journal	Developmental Cell
Volume	2
Issue number	4
DOIs	https://doi.org/10.1016/S1534-5807(02)00148-X
State	Published - 2002
Externally published	Yes

ASJC Scopus subject areas

Developmental Biology

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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. https://doi.org/10.1016/S1534-5807(02)00148-X

PTP1B regulates leptin signal transduction in vivo. / Zabolotny, Janice M.; Bence-Hanulec, Kendra K.; Stricker-Krongrad, Alain; Haj, Fawaz; Wang, Yongping; Minokoshi, Yasuhiko; Kim, Young Bum; Elmquist, Joel K.; Tartaglia, Louis A.; Kahn, Barbara B.; Neel, Benjamin G.

In: Developmental Cell, Vol. 2, No. 4, 2002, p. 489-495.

Research output: Contribution to journal › Article

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abstract = "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.",

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AU - Wang, Yongping

AU - Minokoshi, Yasuhiko

AU - Kim, Young Bum

AU - Elmquist, Joel K.

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AB - 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.

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