Investigation of nesfatin-1 as a peptide product of the gastric X/A-like cell on anxiety behavior in animals and humans.

• Applicant: Professor Dr. Andreas Stengel
• Subject Area: Endocrinology, Diabetology, Metabolism ; Nutritional Sciences ; Gastroenterology
• Term: from 2012 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 216245554

• Final Report Year: 2023

Final Report Abstract

The present studies give novel insight into the occurrence and function of two novel gastrointestinal peptide hormones, NUCB2/nesfatin-1 and phoenixin, in animal models and in human. Firstly, NUCB2/nesfatin-1 was shown to be increased in the blood of rats due to immobilization stress and able to affect (increase) anxiety in normal-weight rats. Moreover, also in human subjects nesfatin-1 in the blood was elevated due to acute stress in normal-weight females, while in obese women this was not the case. Additionally, in women with obesity that suffered from high anxiety NUCB2/nesfatin-1 in the blood was higher than in obese women with low anxiety. Furthermore, phoenixin-14 was demonstrated to increase food intake in rats by reducing satiety. It was also shown that this peptide activates various regions in the brain, among others brain areas where NUCB2/nesfatin-1 has been detected. Finally, brain regions where phoenixin-14 is detected are activated by different stressors and immobilization or inflammation stress increased phoenixin expression. NUCB2/nesfatin-1 and phoenixin both play a role in stress and anxiety regulation and thus might represent therapeutic targets in the treatment of stress-related diseases and anxiety disorders; this should be further followed up in a translational approach.

Publications

• Central and peripheral expression sites of phoenixin-14 immunoreactivity in rats. Biochemical and Biophysical Research Communications, 493(1), 195-201.
  Prinz, Philip; Scharner, Sophie; Friedrich, Tiemo; Schalla, Martha; Goebel-Stengel, Miriam; Rose, Matthias & Stengel, Andreas
  
• Phoenixin-14 injected intracerebroventricularly but not intraperitoneally stimulates food intake in rats. Peptides, 96, 53-60.
  Schalla, Martha; Prinz, Philip; Friedrich, Tiemo; Scharner, Sophie; Kobelt, Peter; Goebel-Stengel, Miriam; Rose, Matthias & Stengel, Andreas
  
• Nesfatin-130-59 Injected Intracerebroventricularly Increases Anxiety, Depression-Like Behavior, and Anhedonia in Normal Weight Rats. Nutrients, 10(12), 1889.
  Kühne, Stephanie; Schalla, Martha; Friedrich, Tiemo; Kobelt, Peter; Goebel-Stengel, Miriam; Long, Melissa; Rivalan, Marion; Winter, York; Rose, Matthias & Stengel, Andreas
  
• Intracerebroventricular injection of phoenixin alters feeding behavior and activates nesfatin-1 immunoreactive neurons in rats. Brain Research, 1715, 188-195.
  Friedrich, T.; Schalla, M.A.; Scharner, S.; Kühne, S.G.; Goebel-Stengel, M.; Kobelt, P.; Rose, M. & Stengel, A.
  
• Central blockage of nesfatin-1 has anxiolytic effects but does not prevent corticotropin-releasing factor-induced anxiety in male rats. Biochemical and Biophysical Research Communications, 529(3), 773-777.
  Schalla, MA.; Kühne, SG.; Friedrich, T.; Kobelt, P.; Goebel-Stengel, M.; Long, M.; Rivalan, M.; Winter, Y.; Mori, M.; Rose, M. & Stengel, A.
  
• Restraint stress affects circulating NUCB2/nesfatin-1 and phoenixin levels in male rats. Psychoneuroendocrinology, 122, 104906.
  Schalla, M.A.; Goebel-Stengel, M.; Friedrich, T.; Kühne, S.G.; Kobelt, P.; Rose, M. & Stengel, A.
  
• Restraint stress increases the expression of phoenixin immunoreactivity in rat brain nuclei. Brain Research, 1743, 146904.
  Friedrich, T.; Schalla, M.A.; Lommel, R.; Goebel-Stengel, M.; Kobelt, P.; Rose, M. & Stengel, A.
  
• Sucrose Preference and Novelty-Induced Hypophagia Tests in Rats using an Automated Food Intake Monitoring System. Journal of Visualized Experiments, 159.
  Schalla, Martha Anna; Kühne, Stephanie Gladys; Friedrich, Tiemo; Hanel, Vivien; Kobelt, Peter; Goebel-Stengel, Miriam; Rose, Matthias & Stengel, Andreas
  
• Inflammatory Stress Induced by Intraperitoneal Injection of LPS Increases Phoenixin Expression and Activity in Distinct Rat Brain Nuclei. Brain Sciences, 12(2), 135.
  Friedrich, Tiemo; Schalla, Martha Anna; Goebel-Stengel, Miriam; Kobelt, Peter; Rose, Matthias & Stengel, Andreas
  
• Abdominal surgery increases activity in several phoenixin immunoreactive nuclei. Neuroscience Letters, 792, 136938.
  Friedrich, Tiemo; Goebel-Stengel, Miriam; Schalla, Martha Anna; Kobelt, Peter; Rose, Matthias & Stengel, Andreas
  
• NUCB2/nesfatin-1 in the acute stress response of obese women with high and low anxiety. Psychoneuroendocrinology, 155, 106325.
  Schaper, Selina Johanna; Wölk, Ellen; Hofmann, Tobias; Friedrich, Tiemo; Römer, Marthe; de Punder, Karin; Rose, Matthias & Stengel, Andreas