Effect of almond consumption on iron status in inflammatory states

项目摘要/摘要 炎症性贫血(AI)是第二种最常见的贫血形式。它是由慢性炎症引起的 与衰老和慢性病有关，如癌症和类风湿性关节炎。虽然有人工智能的人有 体内有足够的铁，由于蛋白海普西丁浓度升高而增加了封存，从而导致 红细胞合成所需的循环铁不足。人工智能也因红血的破坏而加剧 炎症引起的巨噬细胞(RBC)。不幸的是，目前的治疗方法，包括输血， 不要降低升高的海普西丁浓度；此外，输血会增加过量铁的风险， 这可能会造成不良影响。虽然针对海普西丁的实验药物正在开发中，但它们的长期- 术语不良反应是未知的，需要新的非药物方法。我们的长期目标是 确定减轻AI的饮食方法。食用杏仁可能通过不同的机制缓解AI； 这些措施包括(I)减少炎症，(Ii)改变肠道微生物群组成，以及(Iii)改善 通过增加红细胞的维生素E含量来保护红细胞免受氧化损伤，从而增强红细胞的稳定性。在这 建议的R15研究，我们将检验食用杏仁将改善体内铁状况的总体假设 炎症状态，使用肥胖和衰老的小鼠。我们之所以选择这些小鼠模型，是因为这两种情况 与炎症、海普西丁增加和铁状态标志物受损有关。我们的初选8周 利用小鼠肥胖模型进行的研究提供了有提示意义的证据，表明经常摄入杏仁可以减少肝素 和改善血浆中的铁浓度；然而，需要更长时间的研究才能获得确凿证据。 我们提议的研究将调查24周含杏仁的高脂肪饮食的影响(来自 杏仁)对C57BL/6小鼠循环铁浓度的影响。我们假设这种治疗方法将显著地 与高脂肪和低脂肪饮食相比，改善铁的状况。我们还将调查这些杏仁的摄入量是否 可以减轻C57BL/6小鼠衰老相关的AI，这是衰老研究中经常使用的模型。我们将进一步调查 可能影响这些效应的潜在机制，包括肠道微生物区系组成的变化， 红细胞中的抗氧化剂系统。如果我们的假设得到证实，我们将 证明杏仁作为一种饮食方法来缓解AI的潜力。此外，这项工作将是 首次阐明肠道微生物区系和红细胞抗氧化系统在减轻AI中的作用。

Project Summary/Abstract Anemia of inflammation (AI) is the second most prevalent form of anemia. It is caused by chronic inflammation associated with aging and chronic diseases such as cancer and rheumatoid arthritis. While people with AI have sufficient body iron, increased sequestration due to elevated concentration of the protein hepcidin leads to insufficient circulating iron for red blood cell synthesis. AI is also exacerbated by the destruction of red blood cells (RBCs) by macrophages due to inflammation. Unfortunately, current therapies, including blood transfusion, do not reduce the elevated concentrations of hepcidin; furthermore, transfusion increases risk of excess iron, which can cause adverse effects. While experimental drugs targeting hepcidin are being developed, their long- term adverse effects are not known, warranting new non-pharmaceutical approaches. Our long-term goal is to identify dietary approaches for mitigating AI. Consumption of almonds may mitigate AI by different mechanisms; these include (i) reducing inflammation, (ii) altering the gut microbiome composition, and (iii) improving robustness of RBCs by increasing their vitamin E content, which protects them from oxidative damage. In this proposed R15 study, we will test the overall hypothesis that almond consumption will improve iron status in inflammatory states, using obese and aging mice. We chose these mouse models because both conditions are associated with inflammation, increased hepcidin, and impaired iron status markers. Our preliminary 8-week study using a mouse model of obesity provided suggestive evidence that regular almond intake reduced hepcidin and improved iron concentrations in plasma; however, a longer-duration study is needed for conclusive evidence. Our proposed study will investigate the effects of a 24-week high-fat diet with almonds (15% calories from almonds) on circulating iron concentrations in C57BL/6 mice. We hypothesize this treatment will significantly improve iron status compared to high-fat and low-fat diets. We will also investigate whether this intake of almonds can mitigate aging-related AI in C57BL/6 mice, a frequently used model in aging research. We will further probe underlying mechanisms that may influence these effects, including changes in gut microbiota composition, hepcidin concentrations, and the antioxidant system in RBCs. If our hypotheses are borne out, we will demonstrate the potential of almonds as a dietary approach to mitigating AI. Furthermore, this work would be the first to elucidate the contributions of gut microbiota and RBC antioxidant system in mitigating AI.