Peripheral administration of nesfatin-1 reduces food intake in mice: the leptin-independent mechanism.

Abstract

Nesfatin-1 is a novel satiety molecule in the hypothalamus and is also present in peripheral tissues. Here we sought to identify the active segment of nesfatin-1 and to determine the mechanisms of its action after peripheral administration in mice. Intraperitoneal injection of nesfatin-1 suppressed food intake in a dose-dependent manner. Nesfatin-1 has three distinct segments; we tested the effect of each segment on food intake. Injection of the midsegment decreased food intake under leptin-resistant conditions such as db/db mice and mice fed a high-fat diet. After injection of the midsegment, expression of c-Fos was significantly activated in the brainstem nucleus tractus solitarius (NTS) but not in the hypothalamic arcuate nucleus; the nicotinic cholinergic pathway to the NTS contributed to midsegment-induced anorexia. Midsegment injection significantly increased expression of proopiomelanocortin and cocaine- and amphetamine-regulated transcript genes in the NTS but not in the arcuate nucleus. Investigation of mutant midsegments demonstrated that a region with amino acid sequence similarity to the active site of agouti-related peptide was indispensable for anorexigenic induction. Our findings indicate that the midsegment of nesfatin-1 causes anorexia, possibly by activating POMC and CART neurons in the NTS via a leptin-independent mechanism after peripheral stimulation.

• Authors: H Shimizu, S Oh-I, K Hashimoto, M Nakata, S Yamamoto, N Yoshida, H Eguchi, I Kato, K Inoue, T Satoh, S Okada, M Yamada, T Yada, M Mori
• Journal: Endocrinology (Endocrinology) Vol. 150 Issue 2 Pg. 662-71 (Feb 2009) ISSN: 1945-7170 [Electronic] United States
• PMID: 19176321 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calcium-Binding Proteins
• DNA-Binding Proteins
• Leptin
• Nerve Tissue Proteins
• Nucb1 protein, mouse
• Nucleobindins
• Proto-Oncogene Proteins c-fos
• cocaine- and amphetamine-regulated transcript protein
• Pro-Opiomelanocortin

Topics

• Animals
• Anorexia (chemically induced)
• Arcuate Nucleus of Hypothalamus (drug effects, metabolism)
• Calcium-Binding Proteins
• Conditioning, Psychological (drug effects)
• DNA-Binding Proteins
• Diabetes Mellitus, Experimental (pathology, physiopathology)
• Down-Regulation (drug effects)
• Eating (drug effects, physiology)
• Injections, Intraperitoneal
• Leptin (physiology)
• Male
• Mice
• Mice, Inbred ICR
• Nerve Tissue Proteins (administration & dosage, chemistry, genetics, metabolism)
• Nucleobindins
• Pro-Opiomelanocortin (genetics, metabolism)
• Protein Structure, Tertiary (physiology)
• Proto-Oncogene Proteins c-fos (metabolism)
• Signal Transduction (drug effects, genetics, physiology)
• Solitary Nucleus (drug effects, metabolism)
• Taste (drug effects)