Deletion of α7 Nicotinic Acetylcholine Receptor in POMC Neurons Impairs Energy Balance and Leptin-Induced Anorexigenic Response in Male Mice.
- 1Laboratory of Metabolic Disorders, School of Applied Sciences, Universidade Estadual de Campinas (UNICAMP), Limeira 13484-350, Brazil.
- 2Obesity and Comorbidities Research Center, Institute of Biology, Universidade Estadual de Campinas (UNICAMP), Campinas 13083-864, Brazil.
- 3Graduate Program in Nutrition, Federal University of Pernambuco (UFPE), Recife 50670-901, Brazil.
Abstract
Recent studies demonstrate that α7 nicotinic acetylcholine receptors (α7nAChR) in hypothalamic neurons, including pro-opiomelanocortin (POMC) neurons, modulate energy homeostasis. This study aimed to explore how the α7nAChR subunit in hypothalamic POMC neurons affects food intake and energy balance in mice. This study used site-specific knockout mice for α7nAChR in POMC neurons (Control: α7nAChRfl/fl; Knockout: α7nAChRfl/flPOMCCre) generated via the Cre-LoxP system. Body weight (BW) and body weight gain (BWG) were measured. We measured energy expenditure by respirometry and assessed glycemic homeostasis using an intraperitoneal glucose tolerance test (ipGTT) and an insulin tolerance test (ipITT). Food intake was measured after intraperitoneal injection of saline (0.9%), leptin (5 μg/g BW), or the selective α7nAChR agonist PNU-282987 (1 mg/kg BW). Afterward, fasted mice were injected intraperitoneally with saline (0.9%), leptin (2.5 μg/g BW), or PNU-282987 (1 mg/kg BW), and subsequently euthanized. RT-qPCR and Western blotting analyses were performed. The α7nAChRfl/flPOMCCre males were initially lighter but had higher BWG. The opposite was observed in females. α7nAChRfl/flPOMCCre male mice showed increased epididymal fat, serum leptin levels, and food intake. Knockout male mice showed no major impairment in glucose homeostasis and signaling. Furthermore, the leptin-induced anorectic response was delayed, with reduced hypothalamic anorectic proteins and a trend toward reduced pCREBSer133 after an acute leptin stimulus. PNU-282987 treatment increased pCREBSer133 content and Pcsk1 gene expression in vitro. The α7nAChR expressed in POMC neurons seems to contribute to energy and glycemic homeostasis and to the hypothalamic leptin-induced anorectic response mediated by CREB phosphorylation.
Related
- Receptor Binding Drives Toxicokinetic Processes: Insights from Two Amphipod Species Exposed to Insecticides Targeting the Nicotinic Acetylcholine Receptor
- Ingrilimine, a novel marine cytotoxic and apoptotic cyclic imine toxin with a high affinity and dual activity on human α7 nicotinic acetylcholine receptor
- Nicotinic Acetylcholine Receptors Modulate T-Tubule Architecture Under Sympathetic Overstimulation
- A systemic circadian nicotinic acid riboside (NaR) signal engages the unfolded protein response and adipogenesis via the prefoldin complex
- Title Mapping the brain signature of dyslexia risk onto histamine, acetylcholine and glutamate receptor systems
BibTeX
@article{chaves2026deletion,
title = {{Deletion of α7 Nicotinic Acetylcholine Receptor in POMC Neurons Impairs Energy Balance and Leptin-Induced Anorexigenic Response in Male Mice.}},
author = {Wenicios Ferreira Chaves and Suleyma de Oliveira Costa and Caroline Lobo Costa and Priscilla Karla Fernandes Lopes and Iracema Monteiro da Silva and Ísis de Cássia Alves Martins and Marciane Milanski and Letícia Martins Ignácio de Souza and Adriana Souza Torsoni and Raquel da Silva Aragão and Marcio Alberto Torsoni},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198697},
url = {https://europepmc.org/article/MED/42883940},
note = {CC BY},
}
RIS
TY - JOUR
TI - Deletion of α7 Nicotinic Acetylcholine Receptor in POMC Neurons Impairs Energy Balance and Leptin-Induced Anorexigenic Response in Male Mice.
AU - Wenicios Ferreira Chaves
AU - Suleyma de Oliveira Costa
AU - Caroline Lobo Costa
AU - Priscilla Karla Fernandes Lopes
AU - Iracema Monteiro da Silva
AU - Ísis de Cássia Alves Martins
AU - Marciane Milanski
AU - Letícia Martins Ignácio de Souza
AU - Adriana Souza Torsoni
AU - Raquel da Silva Aragão
AU - Marcio Alberto Torsoni
PY - 2026
DA - 2026/09/29
JO - International journal of molecular sciences
DO - 10.3390/ijms27198697
UR - https://europepmc.org/article/MED/42883940
AB - Recent studies demonstrate that α7 nicotinic acetylcholine receptors (α7nAChR) in hypothalamic neurons, including pro-opiomelanocortin (POMC) neurons, modulate energy homeostasis. This study aimed to explore how the α7nAChR subunit in hypothalamic POMC neurons affects food intake and energy balance in mice. This study used site-specific knockout mice for α7nAChR in POMC neurons (Control: α7nAChRfl/fl; Knockout: α7nAChRfl/flPOMCCre) generated via the Cre-LoxP system. Body weight (BW) and body weight gain (BWG) were measured. We measured energy expenditure by respirometry and assessed glycemic homeostasis using an intraperitoneal glucose tolerance test (ipGTT) and an insulin tolerance test (ipITT). Food intake was measured after intraperitoneal injection of saline (0.9%), leptin (5 μg/g BW), or the selective α7nAChR agonist PNU-282987 (1 mg/kg BW). Afterward, fasted mice were injected intraperitoneally with saline (0.9%), leptin (2.5 μg/g BW), or PNU-282987 (1 mg/kg BW), and subsequently euthanized. RT-qPCR and Western blotting analyses were performed. The α7nAChRfl/flPOMCCre males were initially lighter but had higher BWG. The opposite was observed in females. α7nAChRfl/flPOMCCre male mice showed increased epididymal fat, serum leptin levels, and food intake. Knockout male mice showed no major impairment in glucose homeostasis and signaling. Furthermore, the leptin-induced anorectic response was delayed, with reduced hypothalamic anorectic proteins and a trend toward reduced pCREBSer133 after an acute leptin stimulus. PNU-282987 treatment increased pCREBSer133 content and Pcsk1 gene expression in vitro. The α7nAChR expressed in POMC neurons seems to contribute to energy and glycemic homeostasis and to the hypothalamic leptin-induced anorectic response mediated by CREB phosphorylation.
SN - 1422-0067
ER -