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Short-Term High-Fat Diet Consumption Reduces Hypothalamic Expression of the Nicotinic Acetylcholine Receptor α7 Subunit (α7nAChR) and Affects the Anti-inflammatory Response in a Mouse Model of Sepsis.
Front Immunol. 2019; 10:565.FI

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 α7 subunit (α7nAChR)- 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 α7nAChR 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 α7nAChR mRNA and protein levels in the hypothalamus and liver (p < 0.05). Immunofluorescence microscopy demonstrated lower cholinergic receptor nicotinic α7 subunit (α7nAChR)+ cells in the arcuate nucleus (ARC) (α7nAChR+ 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-α (Spleen and liver), IL-1β 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 α7nAChR expression in central and peripheral tissues, contributing to a higher probability of death in sepsis.

Authors+Show Affiliations

School of Applied Sciences, University of Campinas, Limeira, Brazil. Obesity and Comorbidities Research Center, State University of Campinas, Limeira, Brazil.School of Applied Sciences, University of Campinas, Limeira, Brazil. Obesity and Comorbidities Research Center, State University of Campinas, Limeira, Brazil.School of Applied Sciences, University of Campinas, Limeira, Brazil. Obesity and Comorbidities Research Center, State University of Campinas, Limeira, Brazil.School of Applied Sciences, University of Campinas, Limeira, Brazil. Obesity and Comorbidities Research Center, State University of Campinas, Limeira, Brazil.School of Applied Sciences, University of Campinas, Limeira, Brazil. Obesity and Comorbidities Research Center, State University of Campinas, Limeira, Brazil.School of Applied Sciences, University of Campinas, Limeira, Brazil. Obesity and Comorbidities Research Center, State University of Campinas, Limeira, Brazil.School of Applied Sciences, University of Campinas, Limeira, Brazil. Obesity and Comorbidities Research Center, State University of Campinas, Limeira, Brazil.School of Applied Sciences, University of Campinas, Limeira, Brazil. Obesity and Comorbidities Research Center, State University of Campinas, Limeira, Brazil.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30967878

Citation

Souza, Anelise Cristina Parras, et al. "Short-Term High-Fat Diet Consumption Reduces Hypothalamic Expression of the Nicotinic Acetylcholine Receptor Α7 Subunit (α7nAChR) and Affects the Anti-inflammatory Response in a Mouse Model of Sepsis." Frontiers in Immunology, vol. 10, 2019, p. 565.
Souza ACP, Souza CM, Amaral CL, et al. Short-Term High-Fat Diet Consumption Reduces Hypothalamic Expression of the Nicotinic Acetylcholine Receptor α7 Subunit (α7nAChR) and Affects the Anti-inflammatory Response in a Mouse Model of Sepsis. Front Immunol. 2019;10:565.
Souza, A. C. P., Souza, C. M., Amaral, C. L., Lemes, S. F., Santucci, L. F., Milanski, M., Torsoni, A. S., & Torsoni, M. A. (2019). Short-Term High-Fat Diet Consumption Reduces Hypothalamic Expression of the Nicotinic Acetylcholine Receptor α7 Subunit (α7nAChR) and Affects the Anti-inflammatory Response in a Mouse Model of Sepsis. Frontiers in Immunology, 10, 565. https://doi.org/10.3389/fimmu.2019.00565
Souza ACP, et al. Short-Term High-Fat Diet Consumption Reduces Hypothalamic Expression of the Nicotinic Acetylcholine Receptor Α7 Subunit (α7nAChR) and Affects the Anti-inflammatory Response in a Mouse Model of Sepsis. Front Immunol. 2019;10:565. PubMed PMID: 30967878.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Short-Term High-Fat Diet Consumption Reduces Hypothalamic Expression of the Nicotinic Acetylcholine Receptor α7 Subunit (α7nAChR) and Affects the Anti-inflammatory Response in a Mouse Model of Sepsis. AU - Souza,Anelise Cristina Parras, AU - Souza,Camilla Mendes, AU - Amaral,Camila Libardi, AU - Lemes,Simone Ferreira, AU - Santucci,Leticia Foglia, AU - Milanski,Marciane, AU - Torsoni,Adriana Souza, AU - Torsoni,Marcio Alberto, Y1 - 2019/03/22/ PY - 2018/05/19/received PY - 2019/03/04/accepted PY - 2019/4/11/entrez PY - 2019/4/11/pubmed PY - 2019/4/11/medline KW - LPS KW - high-fat diet KW - inflammation KW - sepsis KW - short-term KW - α7nAChR SP - 565 EP - 565 JF - Frontiers in immunology JO - Front Immunol VL - 10 N2 - 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 α7 subunit (α7nAChR)- 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 α7nAChR 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 α7nAChR mRNA and protein levels in the hypothalamus and liver (p < 0.05). Immunofluorescence microscopy demonstrated lower cholinergic receptor nicotinic α7 subunit (α7nAChR)+ cells in the arcuate nucleus (ARC) (α7nAChR+ 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-α (Spleen and liver), IL-1β 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 α7nAChR expression in central and peripheral tissues, contributing to a higher probability of death in sepsis. SN - 1664-3224 UR - https://www.unboundmedicine.com/medline/citation/30967878/Short_Term_High_Fat_Diet_Consumption_Reduces_Hypothalamic_Expression_of_the_Nicotinic_Acetylcholine_Receptor_α7_Subunit__α7nAChR__and_Affects_the_Anti_inflammatory_Response_in_a_Mouse_Model_of_Sepsis_ L2 - https://doi.org/10.3389/fimmu.2019.00565 DB - PRIME DP - Unbound Medicine ER -
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