Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity

Hiroyuki Mori, Reiko Hanada, Toshikatsu Hanada, Daisuke Aki, Ryuichi Mashima, Hitomi Nishinakamura, takehiro torisu, Kenneth R. Chien, Hideo Yasukawa, Akihiko Yoshimura

Research output: Contribution to journalArticle

449 Citations (Scopus)

Abstract

Leptin is an adipocyte-derived hormone that plays a key role in energy homeostasis, yet resistance to leptin is a feature of most cases of obesity in humans and rodents. In vitro analysis suggested that the suppressor of cytokine signaling-3 (Socs3) is a negative-feedback regulator of leptin signaling involved in leptin resistance. To determine the functional significance of Socs3 in vivo, we generated neural cell-specific SOCS3 conditional knockout mice using the Cre-IoxP system. Compared to their wild-type littermates, Socs3-deficient mice showed enhanced leptin-induced hypothalamic Stat3 tyrosine phosphorylation as well as pro-opiomelanocortin (POMC) induction, and this resulted in a greater body weight loss and suppression of food intake. Moreover, the Socs3-deficient mice were resistant to high fat diet-induced weight gain and hyperleptinemia, and insulin-sensitivity was retained. These data indicate that Socs3 is a key regulator of diet-induced leptin as well as insulin resistance. Our study demonstrates the negative regulatory role of Socs3 in leptin signaling in vivo, and thus suppression of Socs3 in the brain is a potential therapy for leptin-resistance in obesity.

Original languageEnglish
Pages (from-to)739-743
Number of pages5
JournalNature medicine
Volume10
Issue number7
DOIs
Publication statusPublished - Jul 1 2004

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Nutrition
Leptin
Brain
Obesity
Cytokines
Diet
Insulin Resistance
Pro-Opiomelanocortin
Insulin
Phosphorylation
High Fat Diet
Adipocytes
Knockout Mice
Weight Gain
Tyrosine
Weight Loss
Rodentia
Homeostasis
Eating
Body Weight

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Mori, H., Hanada, R., Hanada, T., Aki, D., Mashima, R., Nishinakamura, H., ... Yoshimura, A. (2004). Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. Nature medicine, 10(7), 739-743. https://doi.org/10.1038/nm1071

Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. / Mori, Hiroyuki; Hanada, Reiko; Hanada, Toshikatsu; Aki, Daisuke; Mashima, Ryuichi; Nishinakamura, Hitomi; torisu, takehiro; Chien, Kenneth R.; Yasukawa, Hideo; Yoshimura, Akihiko.

In: Nature medicine, Vol. 10, No. 7, 01.07.2004, p. 739-743.

Research output: Contribution to journalArticle

Mori, H, Hanada, R, Hanada, T, Aki, D, Mashima, R, Nishinakamura, H, torisu, T, Chien, KR, Yasukawa, H & Yoshimura, A 2004, 'Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity', Nature medicine, vol. 10, no. 7, pp. 739-743. https://doi.org/10.1038/nm1071
Mori, Hiroyuki ; Hanada, Reiko ; Hanada, Toshikatsu ; Aki, Daisuke ; Mashima, Ryuichi ; Nishinakamura, Hitomi ; torisu, takehiro ; Chien, Kenneth R. ; Yasukawa, Hideo ; Yoshimura, Akihiko. / Socs3 deficiency in the brain elevates leptin sensitivity and confers resistance to diet-induced obesity. In: Nature medicine. 2004 ; Vol. 10, No. 7. pp. 739-743.
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