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

Abstract

Alarin is a newly identified member of the galanin family of neuropeptides that includes galaninlike 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.

Central alarin ameliorated insulin resistance of adipocytes in type 2 diabetic rats

“…The data shown are the meansGS.E.M. *P!0.05, **P!0.01 vs NCs; C P!0.05, CC P!0.01 vs DCs; # P!0.05 vs alarin group; body weight of animals (Boughton et al 2010, Van Der Kolk et al 2010, Fraley et al 2012. The alarin-induced gain of body weight in mice could be due to not only an increase in food and water intake, but also a decrease in excretion of feces and urine, and metabolic rate (Fraley et al 2012).…”

“…A study with the anti-alarin antibody revealed alarin-like immunoreactivity in the locus coeruleus and subcoeruleus (Eberhard et al 2012). Using anterograde tracing, the projections from the hypothalamus to the locus coeruleus have been found (Van Der Kolk et al 2010). These areas of the brain are implicated in the regulation of appetite and food intake (Boughton et al 2010).…”

“…This peptide is a member of the galanin peptide family that includes galanin and galanin-like peptide (GALP), etc. (Santic et al 2007, Van Der Kolk et al 2010. Alarin shares the same first five amino acids as GALP in the N-terminal end, encoding a splice variant of the Galp gene in exclusion of exon 3, but the following 20 amino acids show no sequence identity to galanin or GALP (Santic et al 2006, Wada et al 2013.…”

“…Similar to galanin and GALP, alarin stimulates an orexigenic behavior as well as increasing body weight and secretion of luteinizing hormone and gonadotropinreleasing hormone in murine models (Boughton et al 2010, Van Der Kolk et al 2010, Fraley et al 2013. Recently, we and others have found that central galanin may facilitate GLUT4 translocation and insulin sensitivity in healthy and type 2 diabetic rats (T2DR) , Liang et al 2012, Bu et al 2013.…”

Physiology, Signaling, and Pharmacology of Galanin Peptides and Receptors: Three Decades of Emerging Diversity

“…Synthetic alarin inhibits neurogenic inflammation of the skin and has actions typical of a neuropeptide in that it regulates food intake, metabolism, reproductive behavior, and hormone secretion (Boughton et al, 2010;Van Der Kolk et al, 2010;Fraley et al, 2012Fraley et al, , 2013. Furthermore, alarin has antidepressant-like effects that are Galanin Family Peptides and Receptors associated with reduced serum levels of corticotrophinreleasing hormone, adrenocorticotropic hormone, and corticosterone .…”