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Its development has been intimately associated with a neuroinflammatory process mainly orchestrated by activated microglial cells. In this regard, our study aimed to investigate a target that is highly expressed in the hypothalamus and involved in the regulation of the inflammatory process, but still poorly investigated within the context of neuronal insulin resistance: the \u03b17 nicotinic acetylcholine receptor (\u03b17nAchR). Herein, we show that mHypoA-2\/29 neurons exposed to pro-inflammatory microglial conditioned medium (MCM) showed higher expression of the pro-inflammatory cytokines IL-6, IL-1\u03b2, and TNF-\u03b1, in addition to developing insulin resistance. Activation of \u03b17nAchR with the selective agonist PNU-282987 prevented microglial-induced inflammation by inhibiting NF-\u03baB nuclear translocation and increasing IL-10 and tristetraprolin (TTP) gene expression. The anti-inflammatory role of \u03b17nAchR was also accompanied by an improvement in insulin sensitivity and lower activation of neurodegeneration-related markers, such as GSK3 and tau. In conclusion, we show that activation of \u03b17nAchR anti-inflammatory signaling in hypothalamic neurons exerts neuroprotective effects and prevents the development of insulin resistance induced by pro-inflammatory mediators secreted by microglial cells.<\/jats:p>","DOI":"10.3390\/cells11142195","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T00:17:10Z","timestamp":1657844230000},"page":"2195","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Activation of the \u03b17 Nicotinic Acetylcholine Receptor Prevents against Microglial-Induced Inflammation and Insulin Resistance in Hypothalamic Neuronal Cells"],"prefix":"10.3390","volume":"11","author":[{"given":"Camila Libardi do","family":"Amaral","sequence":"first","affiliation":[{"name":"Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas, Limeira 13484-350, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00cdsis de C\u00e1ssia Alves","family":"Martins","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas, Limeira 13484-350, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alana Carolina Costa","family":"Veras","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas, Limeira 13484-350, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1672-9686","authenticated-orcid":false,"given":"Fernando Moreira","family":"Simabuco","sequence":"additional","affiliation":[{"name":"Multidisciplinary Laboratory of Food and Health, School of Applied Sciences, University of Campinas, Limeira 13484-350, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5500-404X","authenticated-orcid":false,"given":"Michael Glenn","family":"Ross","sequence":"additional","affiliation":[{"name":"The Lundquist Institute, David Geffen School of Medicine, Harbor-UCLA Medical Center, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina","family":"Desai","sequence":"additional","affiliation":[{"name":"The Lundquist Institute, David Geffen School of Medicine, Harbor-UCLA Medical Center, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia Martins","family":"Ign\u00e1cio-Souza","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas, Limeira 13484-350, Brazil"},{"name":"Obesity and Comorbidities Research Center, University of Campinas, Campinas 13083-864, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marciane","family":"Milanski","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas, Limeira 13484-350, Brazil"},{"name":"Obesity and Comorbidities Research Center, University of Campinas, Campinas 13083-864, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana Souza","family":"Torsoni","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas, Limeira 13484-350, Brazil"},{"name":"Obesity and Comorbidities Research Center, University of Campinas, Campinas 13083-864, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9663-5291","authenticated-orcid":false,"given":"Marcio Alberto","family":"Torsoni","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas, Limeira 13484-350, Brazil"},{"name":"Obesity and Comorbidities Research Center, University of Campinas, Campinas 13083-864, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/jnc.13607","article-title":"Neuroinflammation: The Devil is in the Details","volume":"139","author":"DiSabato","year":"2016","journal-title":"J. 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