Evidence for the role of β2* nAChR desensitization in regulating body weight in obese mice.

Abstract

Nicotine's effect on food intake and body weight has been well documented; however, the relevant receptors underlying these effects have not been firmly established. The purpose of the present study was to: (1) identify the nicotinic acetylcholine receptor (nAChR) subtype involved in food intake and body weight; (2) establish whether food intake and body weight reduction produced by nicotinic drugs are due to activation or desensitization of nAChRs; and, (3) assess the role of the melanocortin system in nicotinic drug effects on food intake and body weight. To identify the nAChR, we tested the effect of sazetidine-A (SAZ-A), a relatively selective ligand of β2-containing nAChRs, on food intake and body weight in obese mice. SAZ-A (3 mg/kg; SC) administered twice-daily significantly decreased food intake and body weight. To assess whether these effects involved desensitization, SAZ-A was administered to non-obese mice via osmotic pump, which, due to its slow sustained drug delivery method, causes prolonged desensitization. SAZ-A via osmotic pump delivery significantly decreased the gain in body weight and reduced food intake. In contrast, body weight was unaffected by SAZ-A in β2(-/-) mice or in mice lacking the melanocortin 4 receptor (MC4R). These results indicate that β2 containing nAChRs are essential to SAZ-A's inhibitory effect on body weight and food intake and engage the melanocortin system.

• Authors: Ghazaul Dezfuli, Kenneth J Kellar, Kenneth L Dretchen, Yousef Tizabi, Niaz Sahibzada, Richard A Gillis
• Journal: Neuropharmacology (Neuropharmacology) Vol. 110 Issue Pt A Pg. 165-174 (11 2016) ISSN: 1873-7064 [Electronic] England
• PMID: 27444741 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemical References

• Azetidines
• Pyridines
• Receptors, Nicotinic
• nicotinic receptor beta2
• sazetidine-A
• Nicotine

Topics

• Animals
• Azetidines (administration & dosage)
• Body Weight (drug effects, physiology)
• Eating (drug effects, physiology)
• Infusion Pumps
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Obese
• Mice, Transgenic
• Nicotine (administration & dosage)
• Pyridines (administration & dosage)
• Receptors, Nicotinic (physiology)