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

192 Citations (SciVal)

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
Pages (from-to)183-194
Number of pages12
JournalCell Metabolism
Volume13
Issue number2
DOIs
StatePublished - Feb 2 2011

Bibliographical note

Funding Information:
We would like to thank Rui Chang, Martin Fasshauer, Sameer Halani, Harsha Madulla, Mark Real, and Ashlie Sewdass for excellent technical assistance; Abott for providing Freestyle glucometers and strips; Andrew Greenberg for the perilipin antibody; and Lauge Schaeffer from Novo Nordisk for the insulin antagonist. We would also like to thank Ronald Kahn and Jens Brüning for making available the NIRKO mice; Case Western University MMPC, which is supported by U24 DK76169, for the mass spectrometry analyses; and the Yale Center of Clinical Investigations, which is supported by CTSA Grant UL1 RR024139 from the National Center for Research Resources, for the NE measurements. We further thank Nir Barzilai and Radhika Muzumdar for WAT from calorically restricted, aged rats and Gary Schwartz for his advice and helpful discussions. This work was supported by NIH grants DK074873, DK083568, and DK082724 to C.B. and DK073683 to S.J.F. and by a European Foundation for the Study of Diabetes grant to T.S. C.B. is the recipient of a Junior Faculty Award from the American Diabetes Association.

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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