Galanin-like peptide (GALP) is a hypothalamic regulator of energy homeostasis and reproduction

Abstract

Galanin-like peptide (GALP) was discovered in 1999 in the porcine hypothalamus and was found to be a 60 amino acid neuropeptide. GALP shares sequence homology to galanin (1-13) in position 9-21 and can bind to, as well as activate, the three galanin receptor subtypes (GalR1-3). GALP-expressing cells are limited, and are mainly found in the arcuate nucleus of the hypothalamus (ARC) and the posterior pituitary. GALP-positive neurons in the ARC project to several brain regions where they appear to make contact with multiple neuromodulators. These neuromodulators are involved in the regulation of energy homeostasis and reproduction, anatomical evidence that suggests a role for GALP in these physiological functions. In support of this idea, GALP gene expression is regulated by several factors that reflect metabolic state including the metabolic hormones leptin and insulin, thyroid hormones, and blood glucose. Considerable evidence now exists to support the hypothesis that GALP has a role in the regulation of energy homeostasis and reproduction; and, that GALP's role may be independent of the known galanin receptors. In this review, we (1) provide an overview of the distribution of GALP, and discuss the potential relationship between GALP and other neuromodulators of energy homeostasis and reproduction, (2) discuss the metabolic factors that regulate GALP expression, (3) review the evidence for the role of GALP in energy homeostasis and reproduction, (4) discuss the potential downstream mediators and mechanisms underlying GALP's effects, and (5) discuss the possibility that GALP may mediate its effects via an as yet unidentified GALP-specific receptor.

Fig. 1

A comparison of evolutionary relatedness between GALP and galanin. A) an example of the sequence alignment among galanin (top) and GALP (bottom) that demonstrates the higher degree of nucleotide substitution in GALP compared to galanin. Different colors in a column indicate nucleotide changes. B) Phylogenetic trees for galanin (black) and GALP (blue) from PAUP analyses of mean pairwise distances among aligned nucleotides. The numbers next to each arm indicate total number of changes to produce that clade. C). Non-parametric analyses revealed that GALP had a significantly (p < 0.05) higher PAUP value, indicating a greater rate of nucleotide substitutions compared to galanin.

Fig. 2

Distribution of GALP in the brain. A) schematic diagram of the distribution of GALP mRNA-containing cells in the rat and mouse, B) in situ hybridization for GALP mRNA in the rat, C) in situ hybridization for GALP mRNA in the mouse, D) schematic diagram of the distribution of GALP mRNA-containing cells in the monkey, E) in situ hybridization for GALP mRNA in the monkey.

Fig. 3

Factors that may influence hypothalamic GALP neurons. A schematic diagram that illustrates known and putative (question marks) regulators of GALP neuronal gene expression and/or neuronal activity. CA = catecholamine, 5HT = serotonin.

Fig. 4

GALP innervates other diencephalic systems that regulate reproduction and energy homeostasis. A schematic diagram that illustrates the targets of hypothalamic GALP neurons and the targets’ phenotypes.