Identification of SOCS-3 as a potential mediator of central leptin resistance

Christian Bjørbæk, Joel K. Elmquist, J. Daniel Frantz, Steven E. Shoelson, Jeffrey S. Flier

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Leptin affects food intake and body weight by actions on the hypothalamus. Although leptin resistance is common in obesity, mechanisms have not been identified. We examined the effect of leptin on expression of the suppressors-of-cytokine-signaling (SOCS) family of proteins. Peripheral leptin administration to ob/ob, but not db/db mice, rapidly induced SOCS-3 mRNA in hypothalamus, but had no effect on CIS, SOCS-1, or SOCS-2. A leptin-dependent increase of SOCS-3 mRNA was seen in areas of hypothalamus expressing high levels of the leptin receptor long form. In mammalian cell lines, SOCS-3, but not CIS or SOCS-2, blocked leptin-induced signal transduction. Expression of SOCS-3 mRNA in the arcuate and dorsomedial hypothalamic nuclei is increased in Ay/a mice, a model of leptin-resistant murine obesity. In conclusion, SOCS-3 is a leptin-inducible inhibitor of leptin signaling, and a potential mediator of leptin resistance in obesity.

Original languageEnglish (US)
Pages (from-to)619-625
Number of pages7
JournalMolecular Cell
Issue number4
Publication statusPublished - Mar 1998


ASJC Scopus subject areas

  • Molecular Biology

Cite this

Bjørbæk, C., Elmquist, J. K., Frantz, J. D., Shoelson, S. E., & Flier, J. S. (1998). Identification of SOCS-3 as a potential mediator of central leptin resistance. Molecular Cell, 1(4), 619-625.