Functions of galanin, spexin and kisspeptin in metabolism, mood and behaviour

• Published in: Nature reviews. Endocrinology Vol. 17; no. 2; pp. 97 - 113
• Main Authors: Mills, Edouard G., Izzi-Engbeaya, Chioma, Abbara, Ali, Comninos, Alexander N., Dhillo, Waljit S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2021; Nature Publishing Group
• Subjects: 631/443/319/367; 692/163/2743/2037; 692/163/2743/2730; Affect - physiology; Animal models; Animals; Antidepressants; Anxiety; Behavior - physiology; Behavior, Animal - physiology; Beta cells; Depression; Eating - physiology; Emotion regulation; Endocrinology; Energy balance; Energy expenditure; Energy metabolism; Energy Metabolism - physiology; Food intake; Galanin; Galanin - physiology; Galanin-like peptide; Health aspects; Homeostasis; Human acts; Human behavior; Humans; Insulin; Insulin secretion; Insulin Secretion - physiology; Insulin-Secreting Cells - metabolism; Kiss1 protein; Kisspeptins - physiology; Medicine; Medicine & Public Health; Metabolic regulation; Metabolism; Mice; Mood; Mood (Psychology); Neuropeptides; Pancreas; Peptide Hormones - physiology; Peptides; Physiological aspects; Physiological research; Rats; Reproductive behavior; Reproductive Behavior - physiology; Review Article; Roles; Secretion; Sexual Behavior, Animal - physiology; Signal transduction; Therapeutic applications; Zebrafish; United Kingdom
• ISSN: 1759-5029; 1759-5037; 1759-5037
• DOI: 10.1038/s41574-020-00438-1

The bioactive peptides galanin, spexin and kisspeptin have a common ancestral origin and their pathophysiological roles are increasingly the subject of investigation. Evidence suggests that these bioactive peptides play a role in the regulation of metabolism, pancreatic β-cell function, energy homeostasis, mood and behaviour in several species, including zebrafish, rodents and humans. Galanin signalling suppresses insulin secretion in animal models (but not in humans), is potently obesogenic and plays putative roles governing certain evolutionary behaviours and mood modulation. Spexin decreases insulin secretion and has potent anorectic, analgesic, anxiolytic and antidepressive-like effects in animal models. Kisspeptin modulates glucose-stimulated insulin secretion, food intake and/or energy expenditure in animal models and humans. Furthermore, kisspeptin is implicated in the control of reproductive behaviour in animals, modulation of human sexual and emotional brain processing, and has antidepressive and fear-suppressing effects. In addition, galanin-like peptide is a further member of the galaninergic family that plays emerging key roles in metabolism and behaviour. Therapeutic interventions targeting galanin, spexin and/or kisspeptin signalling pathways could therefore contribute to the treatment of conditions ranging from obesity to mood disorders. However, many gaps and controversies exist, which must be addressed before the therapeutic potential of these bioactive peptides can be established. The bioactive peptides galanin, spexin and kisspeptin have a common ancestral origin. This Review summarizes the available evidence on the role of these peptides in the regulation of metabolism, pancreatic β-cell function, energy homeostasis, mood and behaviour. Key points The bioactive peptides galanin, spexin and kisspeptin have a common ancestral genetic origin and similar peptide sequences and have wide central and peripheral tissue distribution. Galanin and spexin act through galanin receptors 1–3, whereas kisspeptin acts through the kisspeptin receptor. These bioactive peptides control key metabolic, emotional and behavioural processes in species ranging from zebrafish to humans. Although some actions are well described in animal models, controversies remain about their roles in several aspects of human physiology. Further study of therapeutic agents targeting the signalling pathways of these bioactive peptides could identify a possible role for these in the management of type 2 diabetes mellitus, obesity, and behavioural and mood disorders.