Galanin-Like Peptide (GALP) Facilitates Thermogenesis via Synthesis of Prostaglandin E2 by Astrocytes in the Periventricular Zone of the Third Ventricle

Abstract

Administration of galanin-like peptide (GALP) leads to a decrease in both total food intake and body weight 24 h after injection, compared to controls. Moreover, GALP induces an increase in core body temperature. To elucidate the mechanism by which GALP exerts its effect on energy homeostasis, urethane-anesthetized rats were intracerebroventricularly injected with GALP or saline, after which oxygen consumption, heart rate, and body temperature were monitored for 4 h. In some cases, animals were also pretreated with the cyclooxygenase (COX) inhibitor, diclofenac, via intracerebroventricular (i.c.v.) or intravenous (i.v.) injection. c-Fos expression in the brain was also examined after injection of GALP, and the levels of COX and prostaglandin E(2) synthetase (PGES) mRNA in primary cultured astrocytes treated with GALP were analyzed by using qPCR. The i.c.v. injection of GALP caused biphasic thermogenesis, an effect which could be blocked by pretreatment with centrally (i.c.v.), but not peripherally (i.v.) administered diclofenac. c-Fos immunoreactivity was observed in astrocytes in the periventricular zone of the third ventricle. GALP treatment also increased COX-2 and cytosolic PGES, but not COX-1, microsomal PGES-1, or microsomal PGES-2 mRNA levels in cultured astrocytes. We, therefore, suggest that GALP elicits thermogenesis via a prostaglandin E(2)-mediated pathway in astrocytes of the central nervous system.

Galanin-like Peptide Ameliorates Obesity by Control of Food Intake and Energy Metabolism

“…We found increases in heart rate, oxygen consumption and core body temperature but not skin temperature. GALP-induced thermogenesis is perfectly inhibited by administration of the cyclooxygenase (COX) inhibitor in both our and Lawrence's experiments [38,44]. These studies suggesting that this effect could be dependent on the action of prostaglandin [38,44].…”

“…GALP-induced thermogenesis is perfectly inhibited by administration of the cyclooxygenase (COX) inhibitor in both our and Lawrence's experiments [38,44]. These studies suggesting that this effect could be dependent on the action of prostaglandin [38,44]. Intracerebroventriclar injection of GALP induced c-Fos expression in astrocytes in the periventricular zone of the third ventricle.…”

“…In addition, we examined COX1, COX2 and prostaglandin E 2 synthetases (PGESs) mRNA expression after the in primary cultured astrocytes treated with GALP. Both COX2 and cytosolic PGES expression was found to be significantly increased by this treatment, which suggests that GALP evokes thermogenesis via a prostaglandin E(2)-mediated pathway in astrocytes of the central nervous system [44]. The hyperthermia response due to GALP administration is similar to that achieved by the i.c.v.…”

Anti-obesity effect of intranasal administration of galanin-like peptide (GALP) in obese mice

“…Intracerebroventricular GALP also causes a dose-related increase in core body temperature in rats and mice, suggesting an increase in sympathetic nervous system activation810. These results indicate that GALP replacement therapy could represent an effective treatment for obesity.…”

The regulative effect of galanin family members on link of energy metabolism and reproduction

“…The i.c.v. injection of GALP in rats caused biphasic thermogenesis via a prostaglandin E(2)-mediated pathway, which could be blocked by pretreatment with diclofenac [75]. The GALP KO mice gained less weight as feed with the high-fat diet than wild-type mice, despite both genotypes consumed equal amounts of food [34].…”