Dietary fructose and low-grade inflammation

描述（由申请人提供）：本提案的目的是研究果糖甜味饮料是否会引发健康男性和女性的低度全身性炎症。低度全身性炎症，特别是C反应蛋白（CRP）血浆浓度升高，是心血管疾病（CVD）的危险因素。虽然已知肥胖与炎症有关，但人类低度炎症的原因尚不清楚。在一项初步研究中，食用大量的果糖-而不是葡萄糖-或甜饮料-在健康，瘦，年轻的男性和女性中，在短短8天内强烈诱导轻度炎症。我们建议通过（a）招募更多的受试者，（B）招募肥胖和非肥胖受试者，以及（c）包括用高果糖玉米糖浆（HFCS）增甜的饮料来扩展这些发现。HFCS是美国消费的主要糖之一，也是膳食果糖的主要来源。我们的主要具体目标是评估果糖或HFCS甜味饮料的消费是否会促进系统性低度炎症，如通过CRP和IL-6的血浆浓度所测量的。我们假设，血浆CRP和IL-6浓度将升高后，消费含果糖的饮料（果糖和HFCS）相比，葡萄糖和甜菜碱甜饮料。我们的第二个具体目标是评估是否消费果糖或HFCS甜饮料降低血浆脂联素浓度。具体而言，我们假设，与葡萄糖或糖精饮料相比，受试者饮用果糖或HFCs甜味饮料后空腹血浆中的总脂联素和高分子量（HMW）脂联素浓度将降低。我们将招募12名肥胖（BMI > 30 kg/m2）和12名非肥胖（BMI < 30 kg/m2）男性和女性，他们没有慢性炎症或代谢性疾病。在双盲、随机交叉设计中，每名受试者将完成4个8天的标准化饮食期，仅在所给予的甜味饮料类型上有所不同。具体而言，将要求受试者每天喝四份饮料，该饮料是用果糖、葡萄糖、果糖或HFCS（55%果糖，45%葡萄糖）增甜的。在4个8天饮食阶段中，将提供所有固体食物，并可自由进食。在每个饮食阶段后，我们将收集空腹血液以测量全身炎症标志物和总脂联素和HMW-脂联素的血浆浓度。这项研究有可能确定低级炎症的饮食触发因素，这可能是CVD和代谢疾病的原因。该项目的公共卫生影响可能是相当大的，因为果糖在人群中的消费是普遍的，并且在个人和人群水平上是可以改变的。 公共卫生相关性：患有慢性低度炎症的人患某些疾病的风险更高，如心血管疾病或2型糖尿病。虽然众所周知，肥胖的人比瘦的人更容易表现出低度炎症的迹象，但目前还不清楚是什么导致了这种炎症。在这项拟议的研究中，我们将调查果糖在甜味饮料中食用时，与其他热量和无热量甜味剂相比，是否会引发健康男性和女性的轻度炎症。

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. PUBLIC HEALTH RELEVANCE: People with chronic low-grade inflammation have a higher risk for certain diseases such as cardiovascular disease or type 2 diabetes. While it is known that obese people are more likely to show signs of low-grade inflammation than lean individuals, it is unclear what causes this inflammation. In the proposed study, we will investigate whether the sugar fructose, when consumed in a sweetened beverage, triggers low-grade inflammation in healthy men and women compared with other caloric and non-caloric sweeteners.