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

Research output: Contribution to journalArticle

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Abstract

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
Volume1
Issue number4
StatePublished - Mar 1998

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Leptin
Cytokines
Hypothalamus
Obesity
Messenger RNA
Dorsomedial Hypothalamic Nucleus
Suppressor of Cytokine Signaling Proteins
Leptin Receptors
Signal Transduction
Eating
Body Weight
Cell Line

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.

Identification of SOCS-3 as a potential mediator of central leptin resistance. / Bjørbæk, Christian; Elmquist, Joel K.; Frantz, J. Daniel; Shoelson, Steven E.; Flier, Jeffrey S.

In: Molecular Cell, Vol. 1, No. 4, 03.1998, p. 619-625.

Research output: Contribution to journalArticle

Bjørbæk, C, Elmquist, JK, Frantz, JD, Shoelson, SE & Flier, JS 1998, 'Identification of SOCS-3 as a potential mediator of central leptin resistance', Molecular Cell, vol. 1, no. 4, pp. 619-625.
Bjørbæk C, Elmquist JK, Frantz JD, Shoelson SE, Flier JS. Identification of SOCS-3 as a potential mediator of central leptin resistance. Molecular Cell. 1998 Mar;1(4):619-625.
Bjørbæk, Christian ; Elmquist, Joel K. ; Frantz, J. Daniel ; Shoelson, Steven E. ; Flier, Jeffrey S. / Identification of SOCS-3 as a potential mediator of central leptin resistance. In: Molecular Cell. 1998 ; Vol. 1, No. 4. pp. 619-625.
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