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

Neuropharmacology. 2016 Nov;110(Pt A):165-174. doi: 10.1016/j.neuropharm.2016.07.020. Epub 2016 Jul 18.

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.

Keywords: Body weight; Food intake; Melanocortin; Nicotine; Sazetidine-A.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

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

Substances

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