Hypothalamic nesfatin-1 mediates feeding behavior via MC3/4R-ERK signaling pathway after weight loss in obese Sprague-Dawley rats.

Abstract

Nesfatin-1 is an anorexic peptide derived from nucleobindin 2 (NUCB2). An increase in hypothalamic nesfatin-1 inhibits feeding behavior and promotes weight loss. However, the effects of weight loss on hypothalamic nesfatin-1 levels are unclear. In this study, obese rats lost weight in three ways: Calorie Restriction diet (CRD), Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). We found an increase in nesfatin-1 serum and cerebrospinal fluid levels after weight loss in obese Sprague-Dawley (SD) rats. Moreover, weight loss also increased hypothalamic melanocortin 3/4 receptor (MC3/4R) and extracellular regulated kinase phosphorylation (p-ERK) signaling. Third ventricle administration of antisense morpholino oligonucleotide (MON) against the gene encoding NUCB2 inhibited hypothalamic nesfatin-1 and p-ERK signaling, increased food intake and reduced body weight loss in SG and RYGB obese rats. Third ventricle administration of SHU9119 (MC3/4R blocker) blocked hypothalamic MC3/4R, inhibited p-ERK signaling, increased food intake and reduced body weight loss in SG and RYGB obese rats. These findings indicate that weight loss leads to an increase in hypothalamic nesfatin-1. The increase in hypothalamic nesfatin-1 participates in regulating feeding behavior through the MC3/4R-ERK signaling especially after SG and RYGB.

• Authors: Tianyi Zhang, Mofei Wang, Lei Liu, Bing He, Jingyao Hu, Yong Wang
• Journal: Peptides (Peptides) Vol. 119 Pg. 170080 (09 2019) ISSN: 1873-5169 [Electronic] United States
• PMID: 31260713 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019. Published by Elsevier Inc.

Chemical References

• Morpholinos
• Nucb2 protein, rat
• Nucleobindins
• Receptor, Melanocortin, Type 3
• Receptor, Melanocortin, Type 4

Topics

• Animals
• Feeding Behavior
• Hypothalamus (metabolism, pathology)
• MAP Kinase Signaling System
• Male
• Morpholinos (genetics, pharmacology)
• Nucleobindins (antagonists & inhibitors, genetics, metabolism)
• Obesity (genetics, metabolism, pathology)
• Rats
• Rats, Sprague-Dawley
• Receptor, Melanocortin, Type 3 (genetics, metabolism)
• Receptor, Melanocortin, Type 4 (genetics, metabolism)