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Activation of the α7 Nicotinic Acetylcholine Receptor Prevents against Microglial-Induced Inflammation and Insulin Resistance in Hypothalamic Neuronal Cells.
Amaral, Camila Libardi do; Martins, Ísis de Cássia Alves; Veras, Alana Carolina Costa; Simabuco, Fernando Moreira; Ross, Michael Glenn; Desai, Mina; Ignácio-Souza, Leticia Martins; Milanski, Marciane; Torsoni, Adriana Souza; Torsoni, Marcio Alberto.
Afiliação
  • Amaral CLD; Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas, Limeira 13484-350, Brazil.
  • Martins ÍCA; Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas, Limeira 13484-350, Brazil.
  • Veras ACC; Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas, Limeira 13484-350, Brazil.
  • Simabuco FM; Multidisciplinary Laboratory of Food and Health, School of Applied Sciences, University of Campinas, Limeira 13484-350, Brazil.
  • Ross MG; The Lundquist Institute, David Geffen School of Medicine, Harbor-UCLA Medical Center, University of California, Los Angeles, CA 90095, USA.
  • Desai M; The Lundquist Institute, David Geffen School of Medicine, Harbor-UCLA Medical Center, University of California, Los Angeles, CA 90095, USA.
  • Ignácio-Souza LM; Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas, Limeira 13484-350, Brazil.
  • Milanski M; Obesity and Comorbidities Research Center, University of Campinas, Campinas 13083-864, Brazil.
  • Torsoni AS; Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas, Limeira 13484-350, Brazil.
  • Torsoni MA; Obesity and Comorbidities Research Center, University of Campinas, Campinas 13083-864, Brazil.
Cells ; 11(14)2022 07 14.
Article em En | MEDLINE | ID: mdl-35883638
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-1ß, 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Resistência à Insulina / Receptor Nicotínico de Acetilcolina alfa7 Limite: Animals Idioma: En Revista: Cells Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Resistência à Insulina / Receptor Nicotínico de Acetilcolina alfa7 Limite: Animals Idioma: En Revista: Cells Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça