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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Recent studies demonstrate that \u03b17 nicotinic acetylcholine receptors (\u03b17nAChR) in hypothalamic neurons, including pro-opiomelanocortin (POMC) neurons, modulate energy homeostasis. This study aimed to explore how the \u03b17nAChR subunit in hypothalamic POMC neurons affects food intake and energy balance in mice. This study used site-specific knockout mice for \u03b17nAChR in POMC neurons (Control: \u03b17nAChRfl\/fl; Knockout: \u03b17nAChRfl\/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 \u03bcg\/g BW), or the selective \u03b17nAChR agonist PNU-282987 (1 mg\/kg BW). Afterward, fasted mice were injected intraperitoneally with saline (0.9%), leptin (2.5 \u03bcg\/g BW), or PNU-282987 (1 mg\/kg BW), and subsequently euthanized. RT-qPCR and Western blotting analyses were performed. The \u03b17nAChRfl\/flPOMCCre males were initially lighter but had higher BWG. The opposite was observed in females. \u03b17nAChRfl\/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 \u03b17nAChR expressed in POMC neurons seems to contribute to energy and glycemic homeostasis and to the hypothalamic leptin-induced anorectic response mediated by CREB phosphorylation.<\/jats:p>","DOI":"10.3390\/ijms27198697","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:10:54Z","timestamp":1790673054000},"page":"8697","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deletion of \u03b17 Nicotinic Acetylcholine Receptor in POMC Neurons Impairs Energy Balance and Leptin-Induced Anorexigenic Response in Male Mice"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6582-417X","authenticated-orcid":false,"given":"Wenicios Ferreira","family":"Chaves","sequence":"first","affiliation":[{"name":"Laboratory of Metabolic Disorders, School of Applied Sciences, Universidade Estadual de Campinas (UNICAMP), Limeira 13484-350, 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Behav."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.tins.2012.12.005","article-title":"Hypothalamic Control of Energy Balance: Insights into the Role of Synaptic Plasticity","volume":"36","author":"Dietrich","year":"2013","journal-title":"Trends Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1007\/s12020-015-0658-y","article-title":"Hypothalamic-Autonomic Control of Energy Homeostasis","volume":"50","author":"Gonzalez","year":"2015","journal-title":"Endocrine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1242\/dmm.026609","article-title":"Hypothalamic Circuits Regulating Appetite and Energy Homeostasis: Pathways to Obesity","volume":"10","author":"Timper","year":"2017","journal-title":"Dis. Models Mech."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6604","DOI":"10.1038\/s41467-024-50913-w","article-title":"Fasting Induces Metabolic Switches and Spatial Redistributions of Lipid Processing and Neuronal Interactions in Tanycytes","volume":"15","author":"Brunner","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nrn.2018.8","article-title":"Signalling from the Periphery to the Brain That Regulates Energy Homeostasis","volume":"19","author":"Kim","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/embor.2012.174","article-title":"Leptin and Insulin Pathways in POMC and AgRP Neurons That Modulate Energy Balance and Glucose Homeostasis","volume":"13","author":"Varela","year":"2012","journal-title":"EMBO Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1038\/nature05026","article-title":"Central Nervous System Control of Food Intake and Body Weight","volume":"443","author":"Morton","year":"2006","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/35007534","article-title":"Central Nervous System Control of Food Intake","volume":"404","author":"Schwartz","year":"2000","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"R209","DOI":"10.1016\/j.cub.2024.01.055","article-title":"Seasonal Biology: Tanycytes Give the Hypothalamus a Spring Makeover","volume":"34","author":"Rivagorda","year":"2024","journal-title":"Curr. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"11582","DOI":"10.1523\/JNEUROSCI.5712-08.2009","article-title":"Enhanced Stat3 Activation in POMC Neurons Provokes Negative Feedback Inhibition of Leptin and Insulin Signaling in Obesity","volume":"29","author":"Ernst","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1159\/000326785","article-title":"Intracellular Leptin-Signaling Pathways in Hypothalamic Neurons: The Emerging Role of Phosphatidylinositol-3 Kinase-Phosphodiesterase-3B-cAMP Pathway","volume":"93","author":"Sahu","year":"2011","journal-title":"Neuroendocrinology"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"McFadden, K.L., Cornier, M.-A., and Tregellas, J.R. (2014). The Role of Alpha-7 Nicotinic Receptors in Food Intake Behaviors. Front. Psychol., 5.","DOI":"10.3389\/fpsyg.2014.00553"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"227","DOI":"10.2337\/diabetes.52.2.227","article-title":"Insulin Activation of Phosphatidylinositol 3-Kinase in the Hypothalamic Arcuate Nucleus: A Key Mediator of Insulin-Induced Anorexia","volume":"52","author":"Niswender","year":"2003","journal-title":"Diabetes"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zanesco, A.M., Mendes, N.F., Engel, D.F., Gaspar, R.S., Sidarta-Oliveira, D., Donato, J., and Velloso, L.A. (2022). Hypothalamic CREB Regulates the Expression of Pomc-Processing Enzyme Pcsk2. Cells, 11.","DOI":"10.3390\/cells11131996"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1152\/physrev.00024.2017","article-title":"POMC: The Physiological Power of Hormone Processing","volume":"98","author":"Harno","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Sch\u00f6ne, C., and Burdakov, D. (2012). Glutamate and GABA as Rapid Effectors of Hypothalamic \u201cPeptidergic\u201d Neurons. Front. Behav. Neurosci., 6.","DOI":"10.3389\/fnbeh.2012.00081"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"229","DOI":"10.5483\/BMBRep.2015.48.4.272","article-title":"Network of Hypothalamic Neurons That Control Appetite","volume":"48","author":"Sohn","year":"2015","journal-title":"BMB Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1172\/JCI30555","article-title":"Physiology and Immunology of the Cholinergic Antiinflammatory Pathway","volume":"117","author":"Tracey","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.bbi.2008.06.011","article-title":"Brain Acetylcholinesterase Activity Controls Systemic Cytokine Levels through the Cholinergic Anti-Inflammatory Pathway","volume":"23","author":"Pavlov","year":"2009","journal-title":"Brain Behav. Immun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.tips.2014.12.002","article-title":"Nicotinic ACh Receptors as Therapeutic Targets in CNS Disorders","volume":"36","author":"Dineley","year":"2015","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1111\/ejn.13966","article-title":"Molecular and Cellular Characterization of Nicotinic Acetylcholine Receptor Subtypes in the Arcuate Nucleus of the Mouse Hypothalamus","volume":"48","author":"Calarco","year":"2018","journal-title":"Eur. J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Souza, A.C.P., Souza, C.M., Amaral, C.L., Lemes, S.F., Santucci, L.F., Milanski, M., Torsoni, A.S., and Torsoni, M.A. (2019). Short-Term High-Fat Diet Consumption Reduces Hypothalamic Expression of the Nicotinic Acetylcholine Receptor A7 Subunit (\u03b17nAChR) and Affects the Anti-Inflammatory Response in a Mouse Model of Sepsis. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00565"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Benfante, R. (2022). Special Issue: Cholinergic Control of Inflammation. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147758"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"701","DOI":"10.33594\/000000166","article-title":"JAK2\/STAT3 Pathway Is Required for \u03b17NAChR-Dependent Expression of POMC and AgRP Neuropeptides in Male Mice","volume":"53","author":"Souza","year":"2019","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1038\/nri2566","article-title":"Reflex Control of Immunity","volume":"9","author":"Tracey","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1124\/jpet.109.154633","article-title":"An A7 Nicotinic Acetylcholine Receptor-Selective Agonist Reduces Weight Gain and Metabolic Changes in a Mouse Model of Diabetes","volume":"332","author":"Marrero","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Gausser\u00e8s, B., Liu, J., Foppen, E., Tourrel-Cuzin, C., Sanchez-Archidona, A.R., Delangre, E., Cruciani-Guglielmacci, C., Pons, S., Maskos, U., and Thorens, B. (2020). The Constitutive Lack of A7 Nicotinic Receptor Leads to Metabolic Disorders in Mouse. Biomolecules, 10.","DOI":"10.3390\/biom10071057"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"113808","DOI":"10.1016\/j.foodres.2023.113808","article-title":"Hypothalamic Inflammation and the Development of an Obese Phenotype Induced by High-Fat Diet Consumption Is Exacerbated in Alpha7 Nicotinic Cholinergic Receptor Knockout Mice","volume":"176","author":"Lopes","year":"2024","journal-title":"Food Res. Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"173444","DOI":"10.1016\/j.pbb.2022.173444","article-title":"The Alpha-7 Nicotinic Acetylcholine Receptor Agonist GTS-21 Does Not Affect Food Intake in Rats","volume":"219","author":"DiBrog","year":"2022","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1038\/s41366-021-00843-0","article-title":"Sexual Dimorphism in Adipose Tissue Mitochondrial Function and Metabolic Flexibility in Obesity","volume":"45","author":"MacCannell","year":"2021","journal-title":"Int. J. Obes."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zhu, Q., Qi, N., Shen, L., Lo, C.C., Xu, M., Duan, Q., Ollberding, N.J., Wu, Z., Hui, D.Y., and Tso, P. (2023). Sexual Dimorphism in Lipid Metabolism and Gut Microbiota in Mice Fed a High-Fat Diet. Nutrients, 15.","DOI":"10.3390\/nu15092175"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.metabol.2017.11.002","article-title":"Nicotinic Acetylcholine Receptor A7 Subunit Improves Energy Homeostasis and Inhibits Inflammation in Nonalcoholic Fatty Liver Disease","volume":"79","author":"Li","year":"2018","journal-title":"Metab. Clin. Exp."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2787","DOI":"10.1007\/s00018-013-1550-7","article-title":"Neuronal Calcium Signaling: Function and Dysfunction","volume":"71","author":"Brini","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1016\/j.cmet.2021.07.008","article-title":"Mitochondrial Cristae-Remodeling Protein OPA1 in POMC Neurons Couples Ca2+ Homeostasis with Adipose Tissue Lipolysis","volume":"33","author":"Pozo","year":"2021","journal-title":"Cell Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.1021\/acschemneuro.8b00173","article-title":"Food-Induced Increase of Acetylcholine in Mouse Hypothalamus","volume":"10","author":"Thinnes","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s12986-021-00569-w","article-title":"STAT3 Phosphorylation in Central Leptin Resistance","volume":"18","author":"Liu","year":"2021","journal-title":"Nutr. Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/bcpt.13311","article-title":"Muscarinic Receptors in Energy Homeostasis: Physiology and Pharmacology","volume":"126","author":"Falk","year":"2020","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"100012","DOI":"10.1016\/j.crneur.2021.100012","article-title":"Regulation of Neuronal Excitability by Reactive Oxygen Species and Calcium Signaling: Insights into Brain Aging","volume":"2","author":"Doser","year":"2021","journal-title":"Curr. Res. Neurobiol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kawamoto, E.M., Vivar, C., and Camandola, S. (2012). Physiology and Pathology of Calcium Signaling in the Brain. Front. Pharmacol., 3.","DOI":"10.3389\/fphar.2012.00061"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e25641","DOI":"10.7554\/eLife.25641","article-title":"Energy Imbalance Alters Ca2+ Handling and Excitability of POMC Neurons","volume":"6","author":"Paeger","year":"2017","journal-title":"eLife"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s44385-025-00036-8","article-title":"Central and Peripheral Neural Circuits Regulating Glucose Homeostasis","volume":"2","author":"Espinoza","year":"2025","journal-title":"npj Biomed. Innov."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.cmet.2011.01.010","article-title":"Melanocortin-4 Receptors Expressed by Cholinergic Neurons Regulate Energy Balance and Glucose Homeostasis","volume":"13","author":"Rossi","year":"2011","journal-title":"Cell Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1038\/nn.3737","article-title":"Melanocortin 4 Receptors in Autonomic Neurons Regulate Thermogenesis and Glycemia","volume":"17","author":"Berglund","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1016\/j.celrep.2016.02.032","article-title":"Central Insulin Action Activates Kupffer Cells by Suppressing Hepatic Vagal Activation via the Nicotinic Alpha 7 Acetylcholine Receptor","volume":"14","author":"Kimura","year":"2016","journal-title":"Cell Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1007\/s12031-018-1185-0","article-title":"Leptin Signaling in the Control of Metabolism and Appetite: Lessons from Animal Models","volume":"66","author":"Estrada","year":"2018","journal-title":"J. Mol. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.2337\/db14-1206","article-title":"Enhancement of Hypothalamic Stat3 Acetylation by Nuclear Receptor Nur77 Dictates Leptin Sensitivity","volume":"64","author":"Chen","year":"2015","journal-title":"Diabetes"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"11067","DOI":"10.1074\/jbc.RA117.001387","article-title":"JAK1-Mediated Sirt1 Phosphorylation Functions as a Negative Feedback of the JAK1-STAT3 Pathway","volume":"293","author":"Wang","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Song, Z., Wang, Y., Zhang, F., Yao, F., and Sun, C. (2019). Calcium Signaling Pathways: Key Pathways in the Regulation of Obesity. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112768"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.mcn.2007.05.008","article-title":"CaMKII and CaMKIV Mediate Distinct Prosurvival Signaling Pathways in Response to Depolarization in Neurons","volume":"36","author":"Bok","year":"2007","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Yan, X., Liu, J., Ye, Z., Huang, J., He, F., Xiao, W., Hu, X., and Luo, Z. (2016). CaMKII-Mediated CREB Phosphorylation Is Involved in Ca2+-Induced BDNF mRNA Transcription and Neurite Outgrowth Promoted by Electrical Stimulation. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162784"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/nm.1866","article-title":"The Creb1 Coactivator Crtc1 Is Required for Energy Balance and Fertility","volume":"14","author":"Altarejos","year":"2008","journal-title":"Nat. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1016\/j.neuroscience.2008.07.063","article-title":"Differential Regulation of Prohormone Convertase 1\/3, Prohormone Convertase 2 and Phosphorylated Cyclic-AMP-Response Element Binding Protein by Short-Term and Long-Term Morphine Treatment: Implications for Understanding the \u201cSwitch\u201d to Opiate Addiction","volume":"156","author":"Espinosa","year":"2008","journal-title":"Neuroscience"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.stemcr.2016.12.021","article-title":"PC1\/3 Deficiency Impacts Pro-Opiomelanocortin Processing in Human Embryonic Stem Cell-Derived Hypothalamic Neurons","volume":"8","author":"Wang","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1152\/ajpregu.2000.279.2.R695","article-title":"Effect of Intracerebroventricular \u03b1-MSH on Food Intake, Adiposity, c-Fos Induction, and Neuropeptide Expression","volume":"279","author":"McMinn","year":"2000","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.mce.2015.12.004","article-title":"High-Fat Diet during Pregnancy and Lactation Impairs the Cholinergic Anti-Inflammatory Pathway in the Liver and White Adipose Tissue of Mouse Offspring","volume":"422","author":"Payolla","year":"2016","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"De Fante, T., Simino, L.A., Reginato, A., Payolla, T.B., Vitor\u00e9li, D.C.G., De Souza, M., Torsoni, M.A., Milanski, M., and Torsoni, A.S. (2016). Diet-Induced Maternal Obesity Alters Insulin Signalling in Male Mice Offspring Rechallenged with a High-Fat Diet in Adulthood. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0160184"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e96728","DOI":"10.1172\/jci.insight.96728","article-title":"PI3K\u03b1 Inactivation in Leptin Receptor Cells Increases Leptin Sensitivity but Disrupts Growth and Reproduction","volume":"2","author":"Borges","year":"2017","journal-title":"JCI Insight"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1152\/ajpendo.1997.273.5.E903","article-title":"Role of the Kidney in Human Leptin Metabolism","volume":"273","author":"Meyer","year":"1997","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"R1258","DOI":"10.1152\/ajpregu.00529.2015","article-title":"Leptin Receptor Null Mice with Reexpression of LepR in GnRHR Expressing Cells Display Elevated FSH Levels but Remain in a Prepubertal State","volume":"310","author":"Allen","year":"2016","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"13669","DOI":"10.1074\/jbc.M115.646885","article-title":"Negative Regulation of Leptin-Induced Reactive Oxygen Species (ROS) Formation by Cannabinoid CB1 Receptor Activation in Hypothalamic Neurons","volume":"290","author":"Palomba","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"543","DOI":"10.18632\/aging.102640","article-title":"Activation of A7 nAChR by PNU-282987 Improves Synaptic and Cognitive Functions through Restoring the Expression of Synaptic-Associated Proteins and the CaM-CaMKII-CREB Signaling Pathway","volume":"12","author":"Wang","year":"2020","journal-title":"Aging"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Amaral, C.L.d., Martins, \u00cd.d.C.A., Veras, A.C.C., Simabuco, F.M., Ross, M.G., Desai, M., Ign\u00e1cio-Souza, L.M., Milanski, M., Torsoni, A.S., and Torsoni, M.A. (2022). Activation of the A7 Nicotinic Acetylcholine Receptor Prevents against Microglial-Induced Inflammation and Insulin Resistance in Hypothalamic Neuronal Cells. Cells, 11.","DOI":"10.3390\/cells11142195"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8697\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:14:19Z","timestamp":1790673259000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8697"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":63,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["ijms27198697"],"URL":"https:\/\/doi.org\/10.3390\/ijms27198697","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]}}}