Aguilar Edenil Costa, Fernandes-Braga Weslley, Leocádio Paola Caroline Lacerda, Campos Gianne Paul, Lemos Virginia Soares, de Oliveira Rafael Pires, Caetano de Faria Ana Maria, Dos Santos Aggum Capettini Luciano, Alvarez-Leite Jacqueline I
Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais/UFMG, Caixa Postal 486, 30161-970 Belo Horizonte, Brazil.
Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai, New York, USA.
Food Funct. 2023 Apr 3;14(7):3332-3347. doi: 10.1039/d3fo00149k.
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disorder in the world. We have seen that gluten intake exacerbated obesity and atherosclerosis in apolipoprotein E knockout (ApoE-/-) mice. In this study, we investigated the effect of gluten consumption on inflammation and oxidative stress in the liver of mice with NAFLD. Male ApoE-/- mice were fed a gluten-free (GF-HFD) or gluten-containing (G-HFD) high-fat diet for 10 weeks. Blood, liver, and spleen were collected to perform the analyses. The animals of the gluten group had increased hepatic steatosis, followed by increased serum AST and ALT. Gluten intake increased hepatic infiltration of neutrophils, macrophages, and eosinophils, as well as the levels of chemotaxis-related factors CCL2, , and . The production of the TNF, IL-1β, IFNγ, and IL-4 cytokines in the liver was also increased by gluten intake. Furthermore, gluten exacerbated the hepatic lipid peroxidation and nitrotyrosine deposition, which were associated with increased production of ROS and nitric oxide. These effects were related to increased expression of NADPH oxidase and iNOS, as well as decreased activity of superoxide dismutase and catalase enzymes. There was an increased hepatic expression of the NF-κB and AP1 transcription factors, corroborating the worsening effect of gluten on inflammation and oxidative stress. Finally, we found an increased frequency of CD4+FOXP3+ lymphocytes in the spleen and increased gene expression of Foxp3 in the livers of the G-HFD group. In conclusion, dietary gluten aggravates NAFLD, exacerbating hepatic inflammation and oxidative stress in obese ApoE-deficient mice.
非酒精性脂肪性肝病（NAFLD）是全球最常见的慢性肝脏疾病。我们已经观察到，摄入麸质会加重载脂蛋白E基因敲除（ApoE-/-）小鼠的肥胖和动脉粥样硬化。在本研究中，我们调查了摄入麸质对患有NAFLD的小鼠肝脏炎症和氧化应激的影响。将雄性ApoE-/-小鼠喂食无麸质（GF-HFD）或含麸质（G-HFD）的高脂饮食10周。采集血液、肝脏和脾脏进行分析。麸质组动物的肝脏脂肪变性增加，随后血清AST和ALT升高。摄入麸质会增加肝脏中中性粒细胞、巨噬细胞和嗜酸性粒细胞的浸润，以及趋化相关因子CCL2等的水平。摄入麸质还会增加肝脏中TNF、IL-1β、IFNγ和IL-4细胞因子的产生。此外，麸质会加剧肝脏脂质过氧化和硝基酪氨酸沉积，这与活性氧和一氧化氮产生增加有关。这些作用与NADPH氧化酶和诱导型一氧化氮合酶的表达增加以及超氧化物歧化酶和过氧化氢酶的活性降低有关。肝脏中NF-κB和AP1转录因子的表达增加，证实了麸质对炎症和氧化应激的恶化作用。最后，我们发现G-HFD组小鼠脾脏中CD4+FOXP3+淋巴细胞的频率增加，肝脏中Foxp3的基因表达增加。总之，饮食中的麸质会加重NAFLD，加剧肥胖的ApoE缺陷小鼠的肝脏炎症和氧化应激。
