Feeding

Studies in rodents and goldfish have demonstrated that nesfatin-1 injected into the brain elicits an anorexigenic response. Centrally injected nesfatin-1 reduces the nocturnal food intake in mice by reducing meal size and increasing intervals between meals (1). The application of nesfatin-2 or -3 does not produce this same effect on feeding. The action of nesfatin-1 was found to occur through a leptin-independent mechanism since nesfatin-1 had an anorexigenic action in Zucker rats (4), which do not have functional leptin (4). Central nesfatin-1 is thought to mediate its anorexigenic effect via activation of melanocortin 3/4 and corticotropin releasing factor (CRF)-2 signaling and also by hyperpolarizing neurons containing neuropeptide Y (5). In addition, intracerebroventricular (icv) injection of nesfatin-1 in mice and rats inhibits gastric emptying and reduces gastroduodenal motility in mice. Nesfatin-1 also inhibits gastric acid secretion via a central vagal mechanism in rats. Also, there is evidence for a role of nesfatin-1 in the control of body fluid regulation (6).

Blood Glucose Homeostasis

In rodents, dogs, pigs and humans, nesfatin-1 has been found in the pancreatic islets co-localized with insulin. In a study to characterize the effects of nesfatin-1 on insulin secretion, nesfatin-1 stimulated glucose-induced insulin release from cultured MIN6 cells. In contrast, no significant difference in insulin release was found in the presence of low glucose. In addition, nesfatin-1 stimulated glucose-induced insulin release from mouse islets (7).

Depression and Anxiety

Nesfatin-1 may be involved in depression and mediating anxiety and fear related responses. It has been demonstrated that nesfatin-1 and two energy regulatory hormones, acylated and des-acylated ghrelin, are significantly higher in patients with moderate and severe major depression disorders and are associated with the severity of the depression (8). In rats, nesfatin-1 was shown to increase anxiety and fear-related behaviors such as a decreased percentage of time spent on open arms in an elevated maze and increased fear-potentiated startle response following icv injection of nesfatin-1 (9).

Sleep

Sleep disorders affect millions of people and are often a main symptom of depression. Patients with major depressive disorder possess high plasma levels of nesfatin-1. Investigators have examined the potential connection between nesfatin (mRNA and protein) expression and sleep. In rat studies, REM sleep deprivation resulted in reduced expression of nesfatin mRNA and protein expression while REM sleep rebound reversed this. In addition, central administration of nesfatin-1 decreased the time spent in REM sleep and intermediate stage of sleep (IS) (10).

Cardiovascular

Several of the peptides that influence feeding such as orexin, adrenomedullin and α-melanocyte-stimulating hormone (α-MSH), also have an impact on cardiovascular function. Researchers have been interested in exploring the potential influence of nesfatin-1 on cardiovascular actions. In rat studies, researchers tested the ability of nesfatin-1 to affect mean arterial pressure (MAP) and found that icv administration of nesfatin-1, in doses that inhibit feeding, resulted in significant increases in MAP in conscious freely moving rats (11).

Reproduction

Research in female rats has demonstrated that nesfatin-1 may play a key role in the control of female puberty. During female puberty transition, Nucb2 mRNA and protein expression were significantly increased in the hypothalamus. Conditions of negative energy balance such as fasting or subnutrition, decreased Nucb2 mRNA and protein expression in the hypothalamus. In addition, central nervous system administration of nesfatin-1 induced luteinizing hormone secretion in freely feeding and short-term fasted pubertal female rats. Conversely, administration of nesfatin-1 did not cause any detectable changes in the circulating levels of gonadotropins in adult female rats (12).

Conclusion

Nesfatin-1 plays roles in several areas such as feeding, depression and anxiety, cardiovascular system, sleep and reproduction. To support life scientists and researchers studying the roles of nesfatin-1 in these systems and processes, Bachem offers a selection of nesfatin peptides in addition to a comprehensive custom synthesis service.

References

1) A.Stengel and Y.Tache. Minireview: Nesfatin-1—an emerging new player in the brain-gut, endocrine, and metabolic axis. Endocrinology 152(11), 4033-4038 (2011)

2) R.Dore et al. Nesfatin-1: functions and physiology of a novel regulatory peptide. Journal of Endocrinology 32(1), R45-R65 (2017)

3) M.A.Schalla and A.Stengel. Current understanding of the role of nesfatin-1. Journal of the Endocrine Society 2, 1188-1206 (2018)

4) S.Oh-I et al. Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature 443, 709-712 (2006)

5) A.Stengel, M.Goebel and Y.Taché. Nesfatin-1: a novel inhibitory regulator of food intake and body weight. Obesity Reviews 12(4), 261-271 (2011)

6) A.Stengel, M.Mori and Y.Taché. The role of nesfatin-1 in the regulation of food intake and body weight – recent developments and future endeavors. Obesity Reviews 14(11), 859-870 (2013)

7) R.Gonzalez et al. Nesfatin-1 exerts a direct, glucose-dependent insulinotropic action on mouse islet β- and MIN6 cells. Journal of Endocrinology 208(3), R9-R16 (2011)

8) S.Algul and O.Ozcelik. Major depressive disorders. Psychiatry Investigation 15(2), 214-218 (2018)

9) Z.Merali et al. Nesfatin-1 increases anxiety- and fear-related behaviors in the rat. Psychopharmacology (Berl). 201(1), 115-123 (2008)

10) S.Vas. Nesfatin-1/NUCB2 as a potential new element of sleep regulation in rats. PLoS One 8(4), p. e59809 (2013)

11) G.L.C.Yosten and W.K.Samson. Nesfatin-1 exerts cardiovascular actions in brain: possible interaction with the central melanocortin system. American Journal of Physiology 297(2), R330-R336 (2009)

12) D.Garcia-Galiano et al. The anorexigenic neuropeptide, nesfatin-1, is indispensable for normal puberty onset in the female rat. Journal of Neuroscience 30(23), 7783-7792 (2010)