Intracerebroventricular and intranasal application of alarin reduces body weight in male rats.

OBJECTIVE: Obesity represents a major public health burden, necessitating novel therapeutic targets. Alarin, one of the most recently discovered members of the galanin neuropeptide family, may be a potential candidate for anti-obesity therapy. Alarin has been shown to reduce food intake and increase energy expenditure when administered centrally, but its long-term effects on body weight remain unclear. Here, we examined the impact of a 7-day intracerebroventricular alarin infusion on energy homeostasis. Because intranasal delivery is a clinically feasible route for delivery of centrally acting anorexigenic peptides, we also assessed the acute effects of intranasal alarin on food intake and body weight.

METHODS: Male Wistar rats received chronic central alarin infusion, while food intake, body weight, heart rate (indicating metabolic rate), locomotor activity, and body temperature were continuously monitored via biotelemetry. FOSB immunohistochemistry was performed in the central amygdala and median and medial preoptic nuclei. Acute effects of intranasal alarin and the potential antagonistic action of its truncated analogue, 6-25Cys-alarin were tested in ad libitum-fed and 24-h-fasted rats using an automated FeedScale system.

RESULTS: Central alarin infusion significantly reduced food intake and increased heat production resulting in weight loss. Alarin increased FOSB-immunoreactive cell numbers in the amygdala and the medial preoptic nuclei, indicating neuronal activation. Intranasal alarin also decreased body weight. Its anorexigenic effect was antagonized by 6-25Cys-alarin.

CONCLUSION: Prolonged central administration of alarin shifts energy balance toward body weight loss. Intranasal delivery of alarin represents a promising, clinically relevant therapeutic option for obesity treatment.