Elsevier

Neuropeptides

Volume 44, Issue 4, August 2010, Pages 333-340
Neuropeptides

Alarin stimulates food intake in male rats and LH secretion in castrated male rats

https://doi.org/10.1016/j.npep.2010.04.001Get rights and content

Abstract

Alarin is a newly identified member of the galanin family of neuropeptides that includes galanin-like peptide (GALP) and galanin. Alarin was discovered as an alternate transcript of the GALP gene in neuroblastoma cells, and subsequently alarin mRNA was detected in the brain of rodents. GALP and galanin are important central regulators of both feeding and reproductive behavior. We hypothesized, that, as a member of the galanin family of peptides, alarin would also have central effects on feeding and reproduction. To test this hypothesis, we treated male rats with alarin intracerebroventricularly (i.c.v.) and measured its effects on food intake and energy homeostasis as well as sexual behavior and luteinizing hormone (LH) secretion. We observed that i.c.v. injection of 1.0 nmol alarin significantly increased food intake (p < 0.01) and body weight (p < 0.05). Alarin did not affect sexual behavior in male rats; however, alarin did significantly (p < 0.01) increase LH levels in castrated, but not intact, male rats. Alarin immunoreactive cell bodies were detected within the locus coeruleus and locus subcoeruleus of the midbrain, which is a brainstem nucleus involved in coordinating many physiological activities, including food intake and reproduction. Lastly, alarin stimulated Fos induction in hypothalamic nuclei, such as the paraventricular nucleus and the nucleus of the tractus solitarious. Our studies demonstrate that alarin, like other members of the galanin family, is a neuromediator of food intake and body weight.

Introduction

The galanin family of peptides has an array of pleiotropic functions (Lang et al., 2007). Galanin and its receptors have been isolated from numerous tissues and are found throughout the central nervous system where they are known to regulate multiple physiologic processes, including the hypothalamic–pituitary–gonadal (HPG) axis, reproductive behaviors, food intake, and energy metabolism (for review see (Gundlach et al., 2001)). Galanin-like peptide (GALP) has also been identified in brain tissue of numerous species and, like galanin, has central actions on energy metabolism and reproduction. Galanin-producing neurons are distributed throughout the central nervous system; however, GALP mRNA is found mainly within the arcuate nucleus (ARC) of the hypothalamus (Ohtaki et al., 1999, Juréus et al., 2000, Juréus et al., 2001, Larm and Gundlach, 2000, Cunningham et al., 2002). Like galanin, GALP is also implicated in regulation of the HPG axis (Matsumoto et al., 2001, Seth et al., 2004, Kauffman et al., 2005, Uenoyama et al., 2008), male sexual behavior (Fraley et al., 2004b, Stoyanovitch et al., 2005), food intake (Lawrence et al., 2002a, Matsumoto et al., 2002, Seth et al., 2002, Krasnow et al., 2003b, Fraley, 2006) and energy metabolism (Rich et al., 2007).

Recently a third member of the galanin peptide family was identified. The new peptide, alarin, was discovered as an alternate transcript of the GALP gene (Santic et al., 2006, Santic et al., 2007, Lang et al., 2007). The alarin transcript excludes exon 3 of the GALP gene, resulting in a frame shift of the GALP mRNA sequence that produces a 25 amino acid alarin peptide. Alarin was first identified in neuroblastoma gangliocytes (Santic et al., 2006). Like galanin, alarin mRNA and alarin-like immunoreactivity have been found in the skin. In accordance with its vascular localization, alarin, in analogy to galanin and GALP (Bauer et al., 2008), inhibits plasma extravasation via a potent vasoconstrictor activity (Santic et al., 2007). In contrast to galanin and GALP in general, the physiological effects of alarin do not appear to be mediated via the known galanin receptors (Santic et al., 2007).

Alarin mRNA has also been identified in rodent brain (Santic et al., 2007); however, its site of expression and the function of alarin within the central nervous system are unknown. The purpose of this study was to determine if alarin has effects on energy homeostasis and reproduction in the male rat and to demonstrate the expression of alarin peptide within the rat brain. We report that alarin peptide is expressed in the hindbrain of the rat and that, like galanin and GALP, alarin alters feeding; but, unlike galanin and GALP, alarin has limited effects on the reproductive system.

Section snippets

Animals

Adult male Long Evans rats (280–300 g) were purchased from Harlan (Indianapolis, IN). Animals were individually housed in microenvironment chambers to prevent cross-hormonal influence. They were given a standard rodent diet and water ad libitum. They were kept on a 12:12 light–dark cycle with lights on at 07.00 h. All procedures were approved by the Hope College Animal Care and Use Committee in accordance with the National Institutes of Health Guide for Care and Use of Laboratory animals. All

Effect of alarin on food intake, body weight and metabolism

At the time of ICV injections, there was no significant difference in body weight among treatment groups. A consistent observation of both galanin and GALP is their stimulatory effect on food intake (Kyrkouli et al., 1990, Lawrence et al., 2002b, Matsumoto et al., 2002); thus, we utilized feeding behavior to determine effective doses of alarin. Because galanin peptides have the potential to act at several sites throughout the brain, our studies utilized cannulas placed into the lateral

Discussion

The objectives of this study were, first, to determine if central administration of alarin has similar actions in the rat as other members of the galanin family, and, second, to detect expression of alarin peptide within the rat brain. Our results indicate that, like GALP and galanin, central i.c.v. injection of alarin has effects on both feeding behavior and LH secretion, though alarin’s effects appear to be unique and focused primarily on energy homeostasis, rather than on reproduction.

Alarin

Acknowledgements

These studies were supported by NSF REU and Howard Hughes Medical Institute grants to the Biology Department at Hope College, and a grant of the Paracelsus Medical University Salzburg.

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