Brain Insulin Controls Adipose Tissue Lipolysis and Lipogenesis

Thomas Scherer; James O'Hare; 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

doi:10.1016/j.cmet.2011.01.008

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Brain Insulin Controls Adipose Tissue Lipolysis and Lipogenesis

Journal article

Open access

Peer reviewed

Brain Insulin Controls Adipose Tissue Lipolysis and Lipogenesis

Thomas Scherer, James O'Hare, Kelly Diggs-Andrews, Martina Schweiger, Bob Cheng, Claudia Lindtner, Elizabeth Zielinski, Prashant Vempati, Kai Su, Shveta Dighe, …

Cell metabolism, Vol.13(2), pp.183-194

2011

DOI: https://doi.org/10.1016/j.cmet.2011.01.008

PMCID: PMC3061443

PMID: 21284985

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. ► Insulin signaling suppresses lipolysis by reducing sympathetic output to fat tissue ► Neuronal insulin signaling induces de novo lipogenesis in adipose tissue ► Impairment of hypothalamic insulin signaling unrestrains adipose tissue lipolysis

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Title: Brain Insulin Controls Adipose Tissue Lipolysis and Lipogenesis
Creators: Thomas Scherer - Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1055, New York, NY 10029-6574, USA
James O'Hare - Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1055, New York, NY 10029-6574, USA
Kelly Diggs-Andrews - Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110, USA
Martina Schweiger - Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/3, A-8010 Graz, Austria
Bob Cheng - Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1055, New York, NY 10029-6574, USA
Claudia Lindtner - Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1055, New York, NY 10029-6574, USA
Elizabeth Zielinski - Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1055, New York, NY 10029-6574, USA
Prashant Vempati - Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1055, New York, NY 10029-6574, USA
Kai Su - Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1055, New York, NY 10029-6574, USA
Shveta Dighe - Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1055, New York, NY 10029-6574, USA
Thomas Milsom - Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1055, New York, NY 10029-6574, USA
Michelle Puchowicz - Department of Nutrition, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA
Ludger Scheja - Department of Biochemistry and Molecular Biology II, University Medical Center, 20246 Hamburg, Germany
Rudolf Zechner - Institute of Molecular Biosciences, University of Graz, Humboldtstrasse 50/3, A-8010 Graz, Austria
Simon J Fisher - Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, 660 South Euclid, St. Louis, MO 63110, USA
Stephen F Previs - Department of Nutrition, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA
Christoph Buettner - Department of Medicine, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1055, New York, NY 10029-6574, USA
Publication Details: Cell metabolism, Vol.13(2), pp.183-194
Date published: 2011
Publisher: Elsevier Inc
Academic Unit: Medicine - Endocrinology, Metabolism and Nutrition (RWJMS)
Language: English
Resource Type: Journal article
Identifiers: 991031665231504646