Mediobasal Hypothalamic p70 S6 Kinase 1 Modulates the Control of Energy Homeostasis

Clémence Blouet, Hiraku Ono, Gary J. Schwartz

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p70 S6 kinase 1 (S6K) is a major downstream effector of the mammalian target of rapamycin (mTOR), primarily implicated in the control of protein synthesis, cell growth, and proliferation. Here we demonstrate that specific bidirectional molecular targeting of mediobasal hypothalamic (MBH) S6K activity in rats is sufficient to significantly alter food intake, body weight, hypothalamic orexigenic neuropeptide expression, hypothalamic leptin sensitivity, and the metabolic and feeding responses to a fast. In addition, adenoviral-mediated constitutive activation of MBH S6K improved cold tolerance and protected against high-fat diet-induced overeating, fat deposition, and insulin resistance. Our results provide direct evidence that MBH S6K activity bidirectionally drives behavioral and metabolic determinants of energy balance and promote the assessment of MBH S6K activity as a therapeutic target in metabolic diseases.

Original languageEnglish (US)
Pages (from-to)459-467
Number of pages9
JournalCell metabolism
Issue number6
StatePublished - Dec 6 2008




ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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