Metabolic effects of non-nutritive sweeteners

非营养性甜味剂的代谢影响

基本信息

批准号：
10457779
负责人：
Kristina Rother
金额：
$ 13.19万
依托单位：
EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10457779
关键词：
ABCB1 gene Acute Adult African American Amniotic Fluid Animals Artificial Sweeteners Body Composition CYP3A4 gene Calories Cardiovascular Diseases Chicago Child Collaborations Consumption Cytochrome P450 Cytochrome a Data Desire for food Diabetes Mellitus Diet Double-Blind Method Drug Interactions Drug Kinetics Drug Prescriptions Eating Enzymes Exposure to Fatty Liver Fatty acid glycerol esters Food Additives GLUT-2 protein Gastric Emptying Glucose Gut Mucosa Hispanics Hormonal Hormones Hour Human Human Milk Individual Infant Inflammatory Insulin Insulin Resistance Intake Intervention Studies Intestines L Cells Lactation Link Liver Liver diseases Lung Mediating Mediator of activation protein Membrane Transport Proteins Metabolic Metabolic syndrome Metabolism Mothers OGTT Obesity Oklahoma Oral Organ Oropharyngeal Overweight Palate Pancreas Participant Perception Pharmaceutical Preparations Pharmacology Pilot Projects Plasma Play Potassium Pregnant Women Randomized Receptor Activation Research Design Research Personnel Rodent Role Saliva Sampling Structure of beta Cell of islet Sucrose Sweetening Agents Taste Buds Taste Perception Taste preferences Testing Time Tissues Universities Up-Regulation Water Weight Gain Woman absorption bariatric surgery base clinically relevant cytokine design epidemiology study glucagon-like peptide 1 glucose metabolism gut microbiome healthy volunteer impaired glucose tolerance inhibitor/antagonist insulin secretion lipid metabolism microbiome obesity development prenatal exposure prospective response soft drink stem subcutaneous sugar sweet taste perception trend

项目摘要

Artificial sweeteners (non-nutritive sweeteners, NNS) are 100-20,000 times sweeter than sucrose and provide sweet taste with no or few calories. Consumption of NNS has steadily increased in both children and adults (including pregnant women) in the US. This trend will likely continue, since sugar intake has been linked to the development of obesity, and NNS offer a palatable alternative. However, several epidemiologic studies have suggested adverse metabolic effects of NNS resulting in similar consequences as high sugar intake, including weight gain, insulin resistance, fatty liver disease, diabetes and cardiovascular disease. In a previous pilot study, we observed that diet soda (Diet Rite Cola) augmented glucose-stimulated GLP-1 secretion in young, healthy volunteers. We then showed that the combination of 2 NNS (sucralose and acesulfame-potassium) in diet soda was partially responsible for the observed increase in GLP-1, but that the taste of diet soda or other ingredients also played a role. Furthermore, we found that insulin secretion was slightly higher when study participants received NNS (either in water or in diet soda) immediately before an OGTT compared to water as a pretreatment. We speculate that this may be due to pancreatic beta cell sweet taste receptor activation. In collaboration with the University of Oklahoma, we quantified NNS concentrations in breast milk after a known exposure (diet soda) of mothers and repeated breast milk sampling for 6 hours. In another collaboration with the University of Chicago, we are investigating whether NNS plasma concentrations can explain the varying insulin secretory responses observed in the study participants. Since NNS are frequently consumed in combination with prescription medications, it is important to find out whether there are possible NNS-drug interactions. This hypothesis is based on a rodent study, in which sucralose increased the activity of P-glycoprotein (P-gp), a membrane transporter involved in absorption and distribution of a wide range of pharmacologic compounds, and CYP3A, a cytochrome P-450 enzyme important to the first-pass metabolism of many drugs. So far, experimental NNS effects in humans were mostly observed after acute (one time) or short-term exposure. In the above mentioned pharmacokinetic study, we administer sucralose orally for 4 weeks to overweight and obese African American and Hispanic women (in a parallel design, randomized, double blind study). By obtaining subcutaneous fat tissue (pre- and post-sucralose exposure), we will have the opportunity to investigate whether this sweetener upregulates inflammatory cytokines. We will also determine whether the described hormonal responses persist after prolonged compared to acute exposure.

人工甜味剂（非营养性甜味剂，NNS）的甜度是蔗糖的 100-20,000 倍，并且在没有或很少热量的情况下提供甜味。在美国，儿童和成人（包括孕妇）的 NNS 消费量稳步增长。这种趋势可能会持续下去，因为糖的摄入量与肥胖的发生有关，而 NNS 提供了一种美味的替代品。然而，一些流行病学研究表明，NNS 的不良代谢作用会导致与高糖摄入类似的后果，包括体重增加、胰岛素抵抗、脂肪肝、糖尿病和心血管疾病。在之前的一项试点研究中，我们观察到无糖汽水 (Diet Rite Cola) 增强了年轻健康志愿者中葡萄糖刺激的 GLP-1 分泌。然后我们表明，无糖汽水中 2 种 NNS（三氯蔗糖和乙酰磺胺酸钾）的组合是观察到的 GLP-1 增加的部分原因，但无糖汽水或其他成分的味道也发挥了作用。此外，我们发现，当研究参与者在 OGTT 前立即接受 NNS（水或无糖汽水中）时，与水作为预处理相比，胰岛素分泌略高。我们推测这可能是由于胰腺β细胞甜味受体激活所致。我们与俄克拉荷马大学合作，在母亲已知接触无糖汽水并重复母乳取样 6 小时后，量化了母乳中的 NNS 浓度。在与芝加哥大学的另一项合作中，我们正在研究 NNS 血浆浓度是否可以解释研究参与者中观察到的不同胰岛素分泌反应。由于 NNS 经常与处方药结合使用，因此了解 NNS 与药物之间是否可能存在相互作用非常重要。这一假设基于一项啮齿动物研究，其中三氯蔗糖增加了 P-糖蛋白 (P-gp) 和 CYP3A（一种细胞色素 P-450 酶）的活性，P-糖蛋白是一种膜转运蛋白，参与多种药理化合物的吸收和分布对许多药物的首过代谢很重要。迄今为止，人类实验性 NNS 效应大多是在急性（一次性）或短期暴露后观察到的。在上述药代动力学研究中，我们对超重和肥胖的非洲裔美国和西班牙裔女性口服三氯蔗糖 4 周（平行设计、随机、双盲研究）。通过获得皮下脂肪组织（三氯蔗糖暴露前后），我们将有机会研究这种甜味剂是否上调炎症细胞因子。我们还将确定与急性暴露相比，长时间暴露后所描述的激素反应是否持续存在。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Maternal Exposure to Non-nutritive Sweeteners Impacts Progeny's Metabolism and Microbiome.

母亲接触非营养性甜味剂会影响后代的新陈代谢和微生物组。

DOI：
发表时间：
2019
期刊：
影响因子：
0
作者：
Olivier;Rother, Kristina I;Hanover, John A
通讯作者：
Hanover, John A

Safety and efficacy of low-dose sirolimus in the PIK3CA-related overgrowth spectrum.

低剂量西罗莫司在 PIK3CA 相关过度生长谱中的安全性和有效性。

DOI：
发表时间：
2019
期刊：
影响因子：
0
作者：
Parker, Victoria E R;Keppler;Faivre, Laurence;Luu, Maxime;Oden, Neal L;De Silva, Leena;Sapp, Julie C;Andrews, Katrina;Bardou, Marc;Chen, Kong Y;Darling, Thomas N;Gautier, Elodie;Goldspiel, Barry R;Hadj;Harris, Jul
通讯作者：
Harris, Jul

Trends in Low-Calorie Sweetener Consumption Among Pregnant Women in the United States.

美国孕妇低热量甜味剂消费趋势。