J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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Originally published In Press as doi:10.1194/jlr.M700021-JLR200 on June 28, 2007

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Journal of Lipid Research, Vol. 48, 2123-2132, October 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

The components required for amino acid neurotransmitter signaling are present in adipose tissues

Anne Nicolaysen1,*, Runhild Gammelsaeter1,{dagger}, Jon Storm-Mathisen{dagger}, Vidar Gundersen{dagger},§ and Per Ole Iversen2,**

* Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
{dagger} Department of Anatomy and Center for Molecular Biology and Neuroscience, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
** Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
§ Department of Neurology, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway

Published, JLR Papers in Press, June 28, 2007.

1 A. Nicolaysen and R. Gammelsaeter contributed equally to this work.

2 To whom correspondence should be addressed. e-mail: poiversen{at}hotmail.com

The adipocyte does not only serve as fuel storage but produces and secretes compounds with modulating effects on food intake and energy homeostasis. Although there is firm evidence for a centrally mediated regulation of adipocyte function via the autonomous nervous system, little is known about signaling between adipocytes. Amino acid neurotransmitters are candidates for such paracrine signaling. Here, we applied immunohistochemistry to detect components required for amino acid transmitter signaling in rat fat depots. In interscapular brown adipose tissue as well as in interscapular, mesenteric, perirenal, and epididymal white adipose tissues, we demonstrate robust immunosignals for the excitatory neurotransmitter glutamate, the inhibitory neurotransmitter {gamma}-aminobutyric acid (GABA), and the GABA-synthesizing enzyme glutamate decarboxylase (GAD) isoforms GAD65 and GAD67. Moreover, all adipose tissues stained for the vesicular glutamate transporter VGLUT1 and the vesicular GABA transporter VGAT in addition to the vesicle marker synaptophysin. Electron microscopic immunocytochemistry showed that VGLUT1 and VGAT, but not VGLUT2 or VGLUT3, are localized in vesicular organelles in adipocytes. The receptors for glutamate (subunits GluR2/3 and NR1 but not mGluR2) and for GABA (GABAAR{alpha}2) were present in the adipocytes. The presence of glutamate, GABA, their vesicular transporters, and their receptors indicates a paracrine signaling role for amino acids in adipose tissues.

Supplementary key words adipocyte • {gamma}-aminobutyric acid • glutamate • synaptic vesicle • vesicular transporter

Abbreviations: AMPA, {alpha}-amino-hydroxy-5-methyl-4-isoxazolepropiorate; BAT, brown adipose tissue; CNS, central nervous system; GABA, {gamma}-aminobutyric acid; GAD, glutamate decarboxylase; GFAP, glial fibrillary acidic protein; MAP2, microtubule-associated protein 2; NMDA, N-methyl-D-aspartate; SV, synaptic vesicle; WAT, white adipose tissue


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Copyright © 2007 by the American Society for Biochemistry and Molecular Biology.