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 | |
| State | Published - 2002 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Developmental Biology
Cite this
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
}
TY - JOUR
T1 - PTP1B regulates leptin signal transduction in vivo
AU - Zabolotny, Janice M.
AU - Bence-Hanulec, Kendra K.
AU - Stricker-Krongrad, Alain
AU - Haj, Fawaz
AU - Wang, Yongping
AU - Minokoshi, Yasuhiko
AU - Kim, Young Bum
AU - Elmquist, Joel K.
AU - Tartaglia, Louis A.
AU - Kahn, Barbara B.
AU - Neel, Benjamin G.
PY - 2002
Y1 - 2002
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=18344379861&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=18344379861&partnerID=8YFLogxK
U2 - 10.1016/S1534-5807(02)00148-X
DO - 10.1016/S1534-5807(02)00148-X
M3 - Article
C2 - 11970898
AN - SCOPUS:18344379861
VL - 2
SP - 489
EP - 495
JO - Developmental Cell
JF - Developmental Cell
SN - 1534-5807
IS - 4
ER -