Desensitization of the nicotinic acetylcholine receptor (nAChR) containing the β2 subunit is a potentially critical mechanism underlying the body weight (BW) reducing effects of nicotine. The purpose of this study was a) to determine the α subunit(s) that partners with the β2 subunit to form the nAChR subtype that endogenously regulates energy balance and b) to probe the extent to which nAChR desensitization could be involved in the regulation of BW. We demonstrate that deletion of either the α4 or the β2, but not the α5, subunit of the nAChR suppresses weight gain in a sex-dependent manner. Furthermore, chronic treatment with the β2-selective nAChR competitive antagonist dihydro-β-erythroidine (DHβE) in mice fed a high-fat diet suppresses weight gain. These results indicate that heteromeric α4β2 nAChRs play a role as intrinsic regulators of energy balance and that desensitizing or inhibiting this nAChR is likely a relevant mechanism and thus could be a strategy for weight loss.

中文翻译：

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α4β2烟碱乙酰胆碱受体从本质上影响小鼠的体重。

含有β2亚基的烟碱型乙酰胆碱受体（nAChR）的脱敏是降低烟碱体重（BW）的潜在关键机制。这项研究的目的是：a）确定与β2亚基结合形成内源性调节能量平衡的nAChR亚型的α亚基，以及b）探讨nAChR脱敏作用可能参与调控nAChR的程度。 BW。我们证明，删除nAChR的α4或β2，但不删除α5亚基，会以性别依赖性的方式抑制体重增加。此外，在高脂饮食喂养的小鼠中，使用β2选择性nAChR竞争性拮抗剂二氢-β-类胡萝卜素（DHβE）进行长期治疗可抑制体重增加。