Brain insulin controls adipose tissue lipolysis and lipogenesis

Thomas Scherer, James OHare, Kelly Diggs-Andrews, Martina Schweiger, Bob Cheng, Claudia Lindtner, Elizabeth Zielinski, Prashant Vempati, Kai Su, Shveta Dighe, Thomas Milsom, Michelle Puchowicz, Ludger Scheja, Rudolf Zechner, Simon J. Fisher, Stephen F. Previs, Christoph Buettner

Research output: Contribution to journalArticlepeer-review

162 Scopus citations

Abstract

White adipose tissue (WAT) dysfunction plays a key role in the pathogenesis of type 2 diabetes (DM2). Unrestrained WAT lipolysis results in increased fatty acid release, leading to insulin resistance and lipotoxicity, while impaired de novo lipogenesis in WAT decreases the synthesis of insulin-sensitizing fatty acid species like palmitoleate. Here, we show that insulin infused into the mediobasal hypothalamus (MBH) of Sprague-Dawley rats increases WAT lipogenic protein expression, inactivates hormone-sensitive lipase (Hsl), and suppresses lipolysis. Conversely, mice that lack the neuronal insulin receptor exhibit unrestrained lipolysis and decreased de novo lipogenesis in WAT. Thus, brain and, in particular, hypothalamic insulin action play a pivotal role in WAT functionality.

Original languageEnglish (US)
Pages (from-to)183-194
Number of pages12
JournalCell metabolism
Volume13
Issue number2
DOIs
StatePublished - Feb 2 2011
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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