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Review
. 2023 Jun 27:14:1202089.
doi: 10.3389/fendo.2023.1202089. eCollection 2023.

Histaminergic regulation of food intake

Axelle Khouma  1   2 , Moein Minbashi Moeini  1   2 , Julie Plamondon  1 , Denis Richard  1   3 , Alexandre Caron  1   2   4 , Natalie Jane Michael  1   2
Affiliations
Review

Histaminergic regulation of food intake

Axelle Khouma et al. Front Endocrinol (Lausanne). .

Abstract

Histamine is a biogenic amine that acts as a neuromodulator within the brain. In the hypothalamus, histaminergic signaling contributes to the regulation of numerous physiological and homeostatic processes, including the regulation of energy balance. Histaminergic neurons project extensively throughout the hypothalamus and two histamine receptors (H1R, H3R) are strongly expressed in key hypothalamic nuclei known to regulate energy homeostasis, including the paraventricular (PVH), ventromedial (VMH), dorsomedial (DMH), and arcuate (ARC) nuclei. The activation of different histamine receptors is associated with differential effects on neuronal activity, mediated by their different G protein-coupling. Consequently, activation of H1R has opposing effects on food intake to that of H3R: H1R activation suppresses food intake, while H3R activation mediates an orexigenic response. The central histaminergic system has been implicated in atypical antipsychotic-induced weight gain and has been proposed as a potential therapeutic target for the treatment of obesity. It has also been demonstrated to interact with other major regulators of energy homeostasis, including the central melanocortin system and the adipose-derived hormone leptin. However, the exact mechanisms by which the histaminergic system contributes to the modification of these satiety signals remain underexplored. The present review focuses on recent advances in our understanding of the central histaminergic system's role in regulating feeding and highlights unanswered questions remaining in our knowledge of the functionality of this system.

Keywords: GPCR; food intake; histamine; histamine receptors; hypothalamus; leptin; melanocortin; neurometabolism.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Histaminergic neuron distribution throughout the hypothalamus. RNAscope® in situ hybridization (ISH) targeting Hdc shows histaminergic neurons (red) densely packed in the core region of the tuberomammillary nucleus (marked TMN) along with diffusely scattered histaminergic neurons throughout the hypothalamus. The RNAscope® ISH was performed on hypothalamic brain slices (25µm) from male mice according to the manufacturer’s instructions (Advanced Cell Diagnostics, Inc., USA).
Figure 2
Figure 2
G protein–coupled receptor (GPCR) signaling from brain expressed histamine receptors. Histamine activation of H1R and H2R lead to neuronal excitation via Gαq and/or Gαs dependent mechanisms respectively. Activation of H3R leads to neuronal inhibition and suppression of neurotransmitter release. PLC, phospholipase C; PKC, protein kinase C; AC, adenylate cyclase; NHE, sodium–proton exchanger; GIRK, G protein-gated inwardly rectifying potassium channels; VGCCs, voltage-gated calcium channels; cAMP, cyclic adenosine monophosphate. Figure created with BioRender.com.
Figure 3
Figure 3
Histamine mediates its effects on feeding via activation of histamine receptors within the hypothalamus. Activation of the H1R is associated with an anorexigenic effect and is believed to be mediated via H1Rs expressed in the PVH and VMH. In contrast, activation of the H3R is orexigenic and occurs via autoinhibition of the histaminergic neurons. H3Rs in unidentified sites may also contribute to the orexigenic effects of H3R activation. Figure created with BioRender.com.
See this image and copyright information in PMC

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