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Type: Artigo
Title: Short-term high-fat diet consumption reduces hypothalamic expression of the nicotinic acetylcholine receptor alpha 7 subunit (alpha 7nAChR) and affects the anti-inflammatory response in a mouse model of sepsis
Author: Parras Souza, Anelise Cristina
Souza, Camilla Mendes
Amara, Camila Libardi
Lemes, Simone Ferreira
Santucci, Leticia Foglia
Milanski, Marciane
Torsoni, Adriana Souza
Torsoni, Marcio Alberto
Abstract: Sepsis is one of the leading causes of death in hospitalized patients and the chronic and low-grade inflammation observed in obesity seems to worsen susceptibility and morbidity of infections. However, little is known with respect to a short-term high-fat diet (HFD) and its role in the development of sepsis. Here, we show for the first time, that short-term HFD consumption impairs early nicotinic acetylcholine receptor alpha 7 subunit (alpha 7nAChR)-mediated signaling, one of the major components of the cholinergic anti-inflammatory pathway, with a focus on hypothalamic inflammation and innate immune response. Mice were randomized to a HFD or standard chow (SC) for 3 days, and sepsis was subsequently induced by a lethal intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) or by cecal ligation and puncture (CLP) surgery. In a separate experiment, both groups received LPS (i.p.) or LPS (i.p.) in conjunction with the selective a alpha nAChR agonist, PNU-282987 (i.p. or intracerebroventricular; i.c.v.), and were sacrificed 2 h after the challenge. Short-term HFD consumption significantly reduced the alpha 7nAChR mRNA and protein levels in the hypothalamus and liver (p < 0.05). Immunofluorescence microscopy demonstrated lower cholinergic receptor nicotinic alpha 7 subunit (alpha 7nAChR)+ cells in the arcuate nucleus (ARC) (alpha 7nAChR+ cells in SC = 216 and HFD = 84) and increased F4/80+ cells in the ARC (2.6-fold) and median eminence (ME) (1.6-fold), which can contribute to neuronal damage. Glial fibrillary acidic protein (GFAP)+ cells and neuronal nuclear antigen (NeuN)+ cells were also increased following consumption of HFD. The HFD-fed mice died quickly after a lethal dose of LPS or following CLP surgery (2-fold compared with SC). The LPS challenge raised most cytokine levels in both groups; however, higher levels of TNF-alpha (Spleen and liver), IL-1 beta and IL-6 (in all tissues evaluated) were observed in HFD-fed mice. Moreover, PNU-282987 administration (i.p. or i.c.v.) reduced the levels of inflammatory markers in the hypothalamus following LPS injection. Nevertheless, when the i.c.v. injection of PNU-282987 was performed the anti-inflammatory effect was much smaller in HFD-fed mice than SC-fed mice. Here, we provide evidence that a short-term HFD impairs early alpha 7nAChR expression in central and peripheral tissues, contributing to a higher probability of death in sepsis
Subject: Sepse
Country: Suiça
Editor: Frontiers Research Foundation
Rights: Aberto
Identifier DOI: 10.3389/fimmu.2019.00565
Date Issue: 2019
Appears in Collections:IB - Artigos e Outros Documentos
FCM - Artigos e Outros Documentos
FCA - Artigos e Outros Documentos

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