Nucleobindin-derived peptides and stress regulation in vertebrates

Stress response entails a complex array of interactions between the neuroendocrine and nervous systems. When a sensory stimulus is perceived as stressful, the brain triggers a response controlled by two key neuroendocrine systems: the sympathetic pathways for the "fight or flight" response, and the hypothalamus-pituitary-adrenal (HPA) axis, for a long-term stress response. Growing evidence suggests that nucleobindin (Nucb)-derived peptides nesfatin-1 and nesfatin-1-like peptide (NLP), two anorexigens and metabolic regulators, are also involved in stress regulation. Nesfatin-1 stimulates corticotropin-releasing hormone (CRH) in the hypothalamus to induce stress and satiety. Nesfatin-1 and NLP activate the stress axis, by stimulating adrenocorticotropic hormone (ACTH) synthesis and through the modulation of cortisol synthesis. Nesfatin-1 elicits stress behavior, such as anxiety and depression. Nesfatin-1 and NLP regulate both stress and metabolism, suggesting their role in interlinking these processes. This review discusses the involvement of nesfatin-1 and NLP in stress-related pathways in vertebrates, their mechanism of action, as well as existing knowledge gaps that warrant further research.