Abstract
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 (GABA(A)Ralpha2) 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.
Highlights
The adipocyte does serve as fuel storage but produces and secretes compounds with modulating effects on food intake and energy homeostasis
We further assessed whether the presence of g-aminobutyric acid (GABA) in the adipose tissues could be attributable to intracellular synthesis using immunofluorescence labeling with antibodies raised against the GABA-synthesizing enzyme GAD65
We found that GAD65 was present in brown adipose tissue (BAT) and mesenteric white adipose tissue (WAT) (Fig. 2) as well as in the other studied WAT depots; similar data were obtained with antibodies recognizing the GAD67 isoform
Summary
The adipocyte does serve as fuel storage but produces and secretes compounds with modulating effects on food intake and energy homeostasis. In addition to its function as a heat-producing organ, alterations in BAT metabolism may affect nutritional homeostasis [5] These data underlie the hypothesis that a dysregulated sympathetic tone might modify adipose tissues and contribute to obesity-related disorders [3]. Because of the lack of innervation of the surgically removed adipose tissue, these latter findings indicate important endocrine signaling between adipocytes originating from various, distant organ regions. The nature of this intercellular signaling remains unknown, but the discovery that the excitatory neurotransmitter glutamate and the inhibitory neurotransmitter g-aminobutyric acid (GABA) can have signaling functions outside of the central nervous system (CNS), With the increasing prevalence of overweight and obesity worldwide, a growing interest in the functions of adipocytes has been stirred. This article is available online at http://www.jlr.org
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