Dietary fructose and low-grade inflammation

描述(申请人提供)：这项提案的目的是调查含果糖饮料是否会在健康的男性和女性中引发轻度全身炎症。低度全身炎症，特别是血浆C反应蛋白(CRP)浓度升高，是心血管疾病(CVD)的危险因素。虽然众所周知，肥胖与炎症有关，但人类低度炎症的原因尚不清楚。在一项试点研究中，在短短8天内，摄入大量果糖--而不是葡萄糖--或阿斯巴甜甜味饮料，可以有效地在健康、苗条的年轻男性和女性中诱导低度炎症。我们建议通过(A)招募更多的受试者，(B)纳入肥胖者和非肥胖者，以及(C)包括一种用高果糖玉米糖浆(HFCS)加糖的饮料来扩展这些发现。HFC是美国人消费的主要糖之一，也是饮食中果糖的主要来源。我们的主要目标是评估饮用果糖或HFCS甜味饮料是否会促进全身低度炎症，这是通过血浆中CRP和IL-6的浓度来衡量的。我们假设，与含葡萄糖和阿斯巴甜的饮料相比，饮用含有果糖的饮料(果糖和HFCS)后，血浆中的CRP和IL-6浓度会升高。我们的第二个特定目标是评估饮用果糖或HFCS甜味饮料是否会降低血浆脂联素浓度。具体地说，我们假设，与葡萄糖或阿斯巴甜饮料相比，受试者饮用果糖或HFCS含糖饮料后，空腹血浆中总和高分子(HMW)-脂联素浓度将较低。我们将招募12名肥胖(BMI&>30 kg/m2)和12名非肥胖(BMI&lt；30 kg/m2)没有慢性炎症性或代谢性疾病的男性和女性。在双盲随机交叉设计中，每个受试者将完成四个为期8天的标准化饮食期，只是提供的含糖饮料的类型不同。具体地说，受试者被要求每天喝四份含有阿斯巴甜、葡萄糖、果糖或HFCS(55%果糖，45%葡萄糖)甜味的饮料。所有固体食物将在四个8天的饮食期间提供，并将自由食用。在每个饮食周期之后，我们将收集空腹血液来测量全身炎症的标志物以及血浆总脂联素和HMW-脂联素的浓度。这项研究有可能确定低级别炎症的饮食触发因素，可能是心血管疾病和代谢性疾病的贡献者。鉴于果糖在人群中的消费无处不在，并且可以在个人和人群水平上改变，该项目对公共卫生的影响可能是相当大的。

DESCRIPTION (provided by applicant): The objective of this proposal is to investigate whether fructose-sweetened beverages trigger low-grade systemic inflammation in healthy men and women. Low-grade systemic inflammation, specifically elevated plasma concentrations of C-reactive protein (CRP), is a risk factor for cardiovascular disease (CVD). While it is known that obesity is associated with inflammation, the causes of low-grade inflammation in humans are not well understood. In a pilot study, the consumption of large amounts of fructose-, but not glucose- or aspartame- sweetened beverages potently induced low-grade inflammation in healthy, lean, young men and women in as little as 8 days. We propose to extend these findings by (a) enrolling a greater number of subjects, (b) enroll obese as well as non-obese subjects, and (c) include a beverage that is sweetened with high fructose corn syrup (HFCS). HFCS is one of the primary sugars consumed in the United States, and a major source of dietary fructose. Our primary specific aim is to assess whether the consumption of fructose- or HFCS- sweetened beverages promotes systemic low-grade inflammation, as measured by plasma concentrations of CRP and IL-6. We hypothesize that plasma CRP and IL-6 concentrations will be elevated after consumption of fructose-containing beverages (fructose and HFCS) when compared to the glucose- and aspartame-sweetened beverages. Our secondary specific aim is to assess whether the consumption of fructose- or HFCS-sweetened beverages lowers plasma adiponectin concentrations. Specifically, we hypothesize that total and high molecular weight (HMW)-adiponectin concentrations in fasting plasma will be lower after subjects have consumed the fructose- or HFCS-sweetened beverages, compared to the glucose- or aspartame-sweetened beverages. We will recruit 12 obese (BMI > 30 kg/m2) and 12 non-obese (BMI < 30 kg/m2) men and women who are free of chronic inflammatory or metabolic disease. In a double-blind, randomized cross-over design, each subject will complete four 8-day standardized dietary periods that will differ only in the type of sweetened beverage administered. Specifically, subjects will be asked to drink four servings of a beverage each day that is sweetened with aspartame, glucose, fructose, or HFCS (55% fructose, 45% glucose). All solid food will be provided for each of the four 8-day diet periods, and will be consumed ad libitum. Following each dietary period, we will collect fasting blood to measure markers of systemic inflammation and plasma concentrations of total and HMW-adiponectin. This study has the potential to identify a dietary trigger of low-grade inflammation, a likely contributor to CVD and metabolic diseases. The public health impact of this project might be considerable given that the consumption of fructose in the population is pervasive, and is modifiable on an individual as well as a population level.