Mechanistic and Metabolic Impacts of Non-Nutritive Sweeteners
非营养性甜味剂的机制和代谢影响
基本信息
- 批准号:RGPIN-2018-04238
- 负责人:
- 金额:$ 3.42万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2022
- 资助国家:加拿大
- 起止时间:2022-01-01 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
OVERVIEW. Novel work from my laboratory shows that the regular use of low-dose, non-caloric artificial sweeteners compounds ubiquitous in the Canadian marketplace and widely believed to reduce daily caloric intake, promote satiety, encourage weight loss and facilitate glucoregulation, unintentionally disrupt the balance of the gut microbiota resulting in distorted glucose metabolism.OBJECTIVES. This grant tests the central hypothesis that aspartame consumption either directly or indirectly (via changes in the gut microbiome and its metabolite production) alters glucose management thus contributing to insulin resistance. It will determine the sites of glucose regulation affected and probe the mechanism(s) or metabolites that are communicating this response. Primary aims are as follows:1. Determine the impact of chronic aspartame consumption on the gut microbiota and the means by which aspartame heightens the response to a glucose challenge by examining the intrinsic ability of the liver to both consume and produce glucose. 2. Examine the effects of aspartame-induced glucose-intolerance on whole body and tissue specific glucose disposal and insulin action. 3. Establish the contribution of the gut microbiota to aspartame induced alterations in glucose metabolism and its specific impacts on circulating factors.METHODOLOGY. As aspartame is one of the most commonly consumed artificial sweeteners in Canada, predominantly in the form of diet soda, it will be the primary focus. Fundamental studies will elucidate the mechanistic basis of how a commonly consumed sweetener alters host metabolism. The experimental model that will be used is the well-characterized, chronically catheterized, conscious rat. Rats will be fed a chow or high fat diet in combination with either water or low-dose aspartame. Glucose fluxes will be carefully monitored in vivo employing sophisticated isotopic tracers and euglycemic-hyperinsulinemic clamps. These techniques will provide an indication of whether aspartame either directly or indirectly (via alterations in the gut microbiota, altered production of metabolites) contributes to aberrant hepatic glucose production (gluconeogenesis) or declines in peripheral insulin sensitivity. Sequencing will assess the microbiome at both functional and taxonomical levels while extensive serum and fecal metabolomic profiling will uncover gut-host mediators influencing glucose metabolism. IMPACT. This grant will explore the mechanistic basis of artificial sweetener induced metabolic disturbances. Results have the potential to alter current perceptions that aspartame is a harmless food additive and may have far reaching implications for food industry, agriculture (artificial sweeteners are commonly added to animal starter feeds to encourage food consumption and weight gain), medical professionals and legislators alike.
概况.我实验室的新工作表明,经常使用低剂量,无热量的人工甜味剂化合物在加拿大市场上无处不在,并被广泛认为可以减少每日热量摄入,促进饱腹感,鼓励减肥和促进血糖调节,无意中破坏了肠道微生物群的平衡,导致扭曲的葡萄糖代谢。这项资助测试了一个核心假设,即食用甜菜碱直接或间接(通过肠道微生物组及其代谢产物的变化)改变了葡萄糖管理,从而导致胰岛素抵抗。它将确定受影响的葡萄糖调节位点,并探测传递这种反应的机制或代谢物。主要目标如下:1.通过检查肝脏消耗和产生葡萄糖的内在能力,确定长期摄入西莫来西莫来西2.检查西司他滨诱导的葡萄糖不耐受对全身和组织特异性葡萄糖处置和胰岛素作用的影响。3.确定肠道微生物群对葡萄糖代谢的影响及其对循环因子的具体影响。由于甜菜碱是加拿大最常见的人工甜味剂之一,主要以无糖汽水的形式存在,因此它将是主要的焦点。基础研究将阐明一种常用甜味剂如何改变宿主代谢的机理基础。将使用的实验模型是良好表征的、长期插管的、清醒的大鼠。大鼠将喂食普通饲料或高脂肪饲料,并同时喂食水或低剂量阿糖胞苷。将采用复杂的同位素示踪剂和正常血糖-高胰岛素钳夹在体内仔细监测葡萄糖通量。这些技术将提供一个指标,表明是否直接或间接地(通过改变肠道微生物群,改变代谢产物的产生),导致异常的肝葡萄糖产生(肝异生)或外周胰岛素敏感性下降。测序将在功能和分类学水平上评估微生物组,而广泛的血清和粪便代谢组学分析将揭示影响葡萄糖代谢的肠道-宿主介质。冲击该基金将用于研究人工甜味剂引起代谢紊乱的机制基础。结果有可能改变目前的看法,即甜素是一种无害的食品添加剂,并可能对食品工业,农业(人工甜味剂通常添加到动物起始饲料中,以鼓励食物消费和体重增加),医疗专业人员和立法者等产生深远的影响。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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专利数量(0)
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Shearer, Jane其他文献
STIMULANT-CONTAINING ENERGY DRINKS What You Need to Know
- DOI:
10.1249/fit.0000000000000379 - 发表时间:
2018-05-01 - 期刊:
- 影响因子:1.5
- 作者:
Higgins, John P.;Babu, Kavita M.;Shearer, Jane - 通讯作者:
Shearer, Jane
Long chain fatty acid uptake in vivo:: Comparison of [125I]-BMIPP and [3H]-bromopalmitate
- DOI:
10.1007/s11745-008-3183-4 - 发表时间:
2008-08-01 - 期刊:
- 影响因子:1.9
- 作者:
Shearer, Jane;Coenen, Kimberly R.;Rottman, Jeffrey N. - 通讯作者:
Rottman, Jeffrey N.
Metabolomic Modeling To Monitor Host Responsiveness to Gut Microbiota Manipulation in the BTBRT+tf/j Mouse
- DOI:
10.1021/acs.jproteome.5b01025 - 发表时间:
2016-04-01 - 期刊:
- 影响因子:4.4
- 作者:
Klein, Matthias S.;Newell, Christopher;Shearer, Jane - 通讯作者:
Shearer, Jane
Butyrate reduces adherent-invasive E. coli-evoked disruption of epithelial mitochondrial morphology and barrier function: involvement of free fatty acid receptor 3.
- DOI:
10.1080/19490976.2023.2281011 - 发表时间:
2023-12 - 期刊:
- 影响因子:12.2
- 作者:
Hamed, Samira A.;Mohan, Armaan;Navaneetha Krishnan, Saranya;Wang, Arthur;Drikic, Marija;Prince, Nicole L.;Lewis, Ian A.;Shearer, Jane;Keita, Asa V.;Soderholm, Johan D.;Shutt, Timothy E.;McKay, Derek M. - 通讯作者:
McKay, Derek M.
Intermittent vs continuous ketogenic diet: Impact on seizures, gut microbiota, and mitochondrial metabolism
- DOI:
10.1111/epi.17688 - 发表时间:
2023-06-29 - 期刊:
- 影响因子:5.6
- 作者:
Shearer, Jane;Scantlebury, Morris H.;Mu, Chunlong - 通讯作者:
Mu, Chunlong
Shearer, Jane的其他文献
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{{ truncateString('Shearer, Jane', 18)}}的其他基金
Mechanistic and Metabolic Impacts of Non-Nutritive Sweeteners
非营养性甜味剂的机制和代谢影响
- 批准号:
RGPIN-2018-04238 - 财政年份:2021
- 资助金额:
$ 3.42万 - 项目类别:
Discovery Grants Program - Individual
Mechanistic and Metabolic Impacts of Non-Nutritive Sweeteners
非营养性甜味剂的机制和代谢影响
- 批准号:
RGPIN-2018-04238 - 财政年份:2020
- 资助金额:
$ 3.42万 - 项目类别:
Discovery Grants Program - Individual
Mechanistic and Metabolic Impacts of Non-Nutritive Sweeteners
非营养性甜味剂的机制和代谢影响
- 批准号:
RGPIN-2018-04238 - 财政年份:2019
- 资助金额:
$ 3.42万 - 项目类别:
Discovery Grants Program - Individual
Gut Based Modulators of Metabolism
基于肠道的代谢调节剂
- 批准号:
RGPIN-2017-04139 - 财政年份:2017
- 资助金额:
$ 3.42万 - 项目类别:
Discovery Grants Program - Individual
Nutraceutical properties of chlorogenic acid
绿原酸的营养特性
- 批准号:
327129-2011 - 财政年份:2016
- 资助金额:
$ 3.42万 - 项目类别:
Discovery Grants Program - Individual
Nutraceutical properties of chlorogenic acid
绿原酸的营养特性
- 批准号:
327129-2011 - 财政年份:2015
- 资助金额:
$ 3.42万 - 项目类别:
Discovery Grants Program - Individual
Nutraceutical properties of chlorogenic acid
绿原酸的营养特性
- 批准号:
327129-2011 - 财政年份:2014
- 资助金额:
$ 3.42万 - 项目类别:
Discovery Grants Program - Individual
Nutraceutical properties of chlorogenic acid
绿原酸的营养特性
- 批准号:
327129-2011 - 财政年份:2013
- 资助金额:
$ 3.42万 - 项目类别:
Discovery Grants Program - Individual
Nutraceutical properties of chlorogenic acid
绿原酸的营养特性
- 批准号:
327129-2011 - 财政年份:2011
- 资助金额:
$ 3.42万 - 项目类别:
Discovery Grants Program - Individual
Coordinated regulation of muscle glucose and lipid uptake in vivo
体内肌肉葡萄糖和脂质摄取的协调调节
- 批准号:
267196-2003 - 财政年份:2004
- 资助金额:
$ 3.42万 - 项目类别:
Postdoctoral Fellowships
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非营养性甜味剂的机制和代谢影响
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非营养性甜味剂的机制和代谢影响
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