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

Anne Nicolaysen¹^,*, Runhild Gammelsaeter¹^,, Jon Storm-Mathisen, Vidar Gundersen^, and Per Ole Iversen²^,**

^* Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
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 thiswork.

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

The adipocyte does not only serve as fuel storage but producesand secretes compounds with modulating effects on food intakeand energy homeostasis. Although there is firm evidence fora centrally mediated regulation of adipocyte function via theautonomous nervous system, little is known about signaling betweenadipocytes. Amino acid neurotransmitters are candidates forsuch paracrine signaling. Here, we applied immunohistochemistryto detect components required for amino acid transmitter signalingin rat fat depots. In interscapular brown adipose tissue aswell as in interscapular, mesenteric, perirenal, and epididymalwhite adipose tissues, we demonstrate robust immunosignals forthe excitatory neurotransmitter glutamate, the inhibitory neurotransmitter ${gamma}$ -aminobutyric acid (GABA), and the GABA-synthesizing enzymeglutamate decarboxylase (GAD) isoforms GAD65 and GAD67. Moreover,all adipose tissues stained for the vesicular glutamate transporterVGLUT1 and the vesicular GABA transporter VGAT in addition tothe vesicle marker synaptophysin. Electron microscopic immunocytochemistryshowed that VGLUT1 and VGAT, but not VGLUT2 or VGLUT3, are localizedin vesicular organelles in adipocytes. The receptors for glutamate(subunits GluR2/3 and NR1 but not mGluR2) and for GABA (GABA_AR ${alpha}$ 2)were present in the adipocytes. The presence of glutamate, GABA,their vesicular transporters, and their receptors indicatesa 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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