{"doi":"10.3390/cells11142195","title":"Activation of the α7 Nicotinic Acetylcholine Receptor Prevents against Microglial-Induced Inflammation and Insulin Resistance in Hypothalamic Neuronal Cells","abstract":"Neuronal hypothalamic insulin resistance is implicated in energy balance dysregulation and contributes to the pathogenesis of several neurodegenerative diseases. 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 α7 nicotinic acetylcholine receptor (α7nAchR). 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-1β, and TNF-α, in addition to developing insulin resistance. Activation of α7nAchR with the selective agonist PNU-282987 prevented microglial-induced inflammation by inhibiting NF-κB nuclear translocation and increasing IL-10 and tristetraprolin (TTP) gene expression. The anti-inflammatory role of α7nAchR 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 α7nAchR 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.","journal":"Cells","year":2022,"id":262184,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":917494,"name":"Ísis de Cássia Alves Martins","orcid":"0000-0002-7446-3521","position":1,"is_corresponding":false},{"id":917495,"name":"Alana Carolina Costa Verás","orcid":"0000-0002-7093-5165","position":2,"is_corresponding":false},{"id":716678,"name":"Fernando Moreira Simabuco","orcid":"0000-0002-1672-9686","position":3,"is_corresponding":false},{"id":468937,"name":"Michael G. Ross","orcid":"0000-0001-5500-404X","position":4,"is_corresponding":false},{"id":468936,"name":"Mina Desai","orcid":"0000-0002-0192-0189","position":5,"is_corresponding":false},{"id":695691,"name":"Letícia Martins Ignácio-Souza","orcid":"0000-0002-2040-1851","position":6,"is_corresponding":false},{"id":695692,"name":"Marciane Milanski","orcid":"0000-0002-6322-5368","position":7,"is_corresponding":false},{"id":695694,"name":"Adriana Souza Torsoni","orcid":"0000-0003-2287-7180","position":8,"is_corresponding":false},{"id":695693,"name":"Márcio Alberto Torsoni","orcid":"0000-0002-9663-5291","position":9,"is_corresponding":false},{"id":917989,"name":"Camila Libardi do Amaral","orcid":null,"position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T00:26:20.717229Z","pmid":"35883638","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}