Brain insulin controls adipose tissue lipolysis and lipogenesis |
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Authors: | Scherer Thomas O'Hare James Diggs-Andrews Kelly Schweiger Martina Cheng Bob Lindtner Claudia Zielinski Elizabeth Vempati Prashant Su Kai Dighe Shveta Milsom Thomas Puchowicz Michelle Scheja Ludger Zechner Rudolf Fisher Simon J Previs Stephen F Buettner Christoph |
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Institution: | Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1055, New York, NY 10029-6574, USA. |
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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. |
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