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Provitamin A Carotenoid-Biofortified Maize Consumption Increases Pupillary Responsiveness among Zambian Children in a Randomized Controlled Trial. 在一项随机对照试验中,维生素原A类胡萝卜素生物强化玉米消费增加赞比亚儿童瞳孔反应性。
Pub Date : 2016-12-01 DOI: 10.3945/JN.116.239202
A. Palmer, Katherine Healy, Maxwell A. Barffour, W. Siamusantu, J. Chileshe, K. Schulze, K. West, A. Labrique
BACKGROUNDImpaired dark adaptation is an early functional indicator of vitamin A deficiency that may be prevented by regular dietary intake of foods containing provitamin A carotenoids.OBJECTIVEWe tested the impact of provitamin A carotenoid-biofortified maize consumption (∼15 μg β-carotene/g) on dark adaptation in Zambian children.METHODSWe used a cluster-randomized trial of children aged 4-8 y (n = 1024) in Mkushi District, Zambia, and compared the regular consumption (2 meals/d, 6 d/wk for 6 mo) of biofortified orange maize (OM) to white maize (WM). The primary outcome was the serum retinol response. In a random sample (n = 542), we used a digital pupillometer to test pre- and postintervention responses to graded light stimuli (-2.9 to 0.1 log cd/m2) in a dark-adapted state.RESULTSAt baseline, 11.7% of the children had serum retinol <0.7 μmol/L, 14.4% had impaired dark adaptation (pupillary threshold ≥ -1.11 log cd/m2), and 2.3% had night blindness. The mean ± SD pupillary responsiveness to light stimuli was poorer at baseline in the OM group (16.1% ± 6.6%) than the WM group (18.1% ± 6.4%) (P = 0.02) but did not differ at follow-up (OM: 17.6% ± 6.5%; WM: 18.3% ± 6.5%). Among children with serum retinol <1.05 μmol/L at baseline, there was greater improvement in pupillary responsiveness in the OM group (2.2%; 95% CI: 0.1%, 4.3%) than the WM group (0.2%; 95% CI: -1.1%, 1.5%; P = 0.01), but there were no differences in children with adequate baseline status. We found no effect of treatment on pupillary threshold or night blindness.CONCLUSIONSThe regular consumption of provitamin A carotenoid-biofortified maize increased pupillary responsiveness among children with marginal or deficient vitamin A status, providing evidence of a functional benefit to consuming this biofortified crop. This trial was registered at clinicaltrials.gov as NCT01695148.
黑暗适应能力受损是维生素A缺乏症的早期功能指标,可以通过定期摄入含有维生素A原类胡萝卜素的食物来预防。目的:我们测试了维生素A原类胡萝卜素生物强化玉米消费(~ 15 μg β-胡萝卜素/g)对赞比亚儿童黑暗适应的影响。方法对赞比亚Mkushi地区4-8岁儿童(n = 1024)进行整群随机试验,比较生物强化橙玉米(OM)和白玉米(WM)的常规食用量(2餐/d, 6天/周,6个月)。主要终点是血清视黄醇反应。在随机样本(n = 542)中,我们使用数字瞳孔计测试了在黑暗适应状态下对渐变光刺激(-2.9至0.1 log cd/m2)的干预前后反应。结果基线时,11.7%的儿童血清视黄醇<0.7 μmol/L, 14.4%的儿童黑暗适应受损(瞳孔阈值≥-1.11 log cd/m2), 2.3%的儿童患有夜盲症。OM组对光刺激的平均±SD反应性在基线时(16.1%±6.6%)低于WM组(18.1%±6.4%)(P = 0.02),但在随访时无差异(OM: 17.6%±6.5%;Wm: 18.3%±6.5%)。在基线时血清视黄醇<1.05 μmol/L的患儿中,OM组瞳孔反应性改善更大(2.2%;95% CI: 0.1%, 4.3%)高于WM组(0.2%;95% ci: -1.1%, 1.5%;P = 0.01),但基线状态良好的儿童无差异。我们发现治疗对瞳孔阈值或夜盲症没有影响。结论:经常食用维生素A原类胡萝卜素生物强化玉米可提高维生素A边缘或缺乏儿童的瞳孔反应性,为食用这种生物强化作物的功能益处提供了证据。该试验在clinicaltrials.gov注册为NCT01695148。
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引用次数: 45
The Use of Digital Images in 24-Hour Recalls May Lead to Less Misestimation of Portion Size Compared with Traditional Interviewer-Administered Recalls. 与传统的访谈者管理的回忆相比,在24小时回忆中使用数字图像可能导致对份量大小的错误估计更少。
Pub Date : 2016-12-01 DOI: 10.3945/JN.116.237271
S. Kirkpatrick, N. Potischman, K. Dodd, D. Douglass, T. Zimmerman, L. Kahle, F. Thompson, Stephanie M George, A. Subar
BACKGROUNDThe Automated Self-Administered 24-hour (ASA24) dietary recall system enhances the feasibility of collecting high-quality intake data in population-based studies.OBJECTIVEThe aim of this study was to assess the accuracy of portion size reporting in the ASA24 compared with interviewer-administered recalls.METHODSTrue intake for 3 meals was ascertained in 81 adults aged 20-70 y from the Washington, DC area. Participants were randomly assigned to complete an unannounced ASA24 or an interviewer-administered Automated Multiple-Pass Method (AMPM) recall the following day. An adapted Bland-Altman approach was used to assess agreement between true and reported portion sizes. Linear regression was used to assess log-scale differences between true and reported portion sizes by recall mode. The proportions of reported portion sizes within 10% and 25% of truth were estimated. Analyses were conducted for all foods and drinks and predetermined categories.RESULTSMean differences between true and reported portion sizes were 3.7 g for the ASA24 and 11.8 g for the AMPM. According to the Bland-Altman-type plots, between 92% and 100% (depending on food or drink category and recall mode) of observations fell within the limits of agreement. After adjustment for multiple testing, the mean ratio of reported to true portion sizes was significantly >1 for the categories of all foods and drinks, all foods excluding liquids, amorphous or soft foods, and small pieces among AMPM respondents. Misestimation in the AMPM was significantly different from that in the ASA24 for all foods and drinks and for all foods excluding liquids. Small proportions of reported portions fell within 10% (16.2% for the ASA24 and 14.9% for the AMPM) and 25% (37.5% for the ASA24 and 33.2% for the AMPM) of truth.CONCLUSIONSThe results raise the possibility that digital images tailored to different types and formats of foods may facilitate improved estimation of amounts eaten but highlight the need for continued work in this aspect of dietary assessment. This trial was registered at clinicaltrials.gov as NCT00978406.
背景:自动自我管理24小时(ASA24)膳食召回系统提高了在基于人群的研究中收集高质量摄入数据的可行性。目的:本研究的目的是评估ASA24中份量报告的准确性与访谈者管理的回忆。方法对来自华盛顿地区的81名年龄在20-70岁的成年人进行3餐的真实摄入量测定。参与者被随机分配在第二天完成未通知的ASA24或面试官管理的自动多次通过方法(AMPM)回忆。采用一种适应的Bland-Altman方法来评估真实和报告的份量大小之间的一致性。通过召回模式,线性回归用于评估真实和报告的分量大小之间的对数尺度差异。对报告的分量大小在10%和25%之间的比例进行了估计。对所有食品和饮料以及预定类别进行了分析。结果ASA24和AMPM的真实份量和报告份量的平均差异为3.7 g和11.8 g。根据bland - altman型图,92%到100%的观察结果(取决于食物或饮料类别和回忆模式)在一致的范围内。经过多次测试调整后,在AMPM受访者中,所有食品和饮料、所有食品(不包括液体、无定形或软食品)和小块食品的类别中,报告的真实份量的平均比率显著为bbbb1。对于所有食品和饮料以及除液体以外的所有食品,AMPM的错误估计与ASA24的错误估计有显著差异。一小部分报告的分量在10% (ASA24为16.2%,AMPM为14.9%)和25% (ASA24为37.5%,AMPM为33.2%)的真实性范围内。结论针对不同类型和格式的食物定制的数字图像可能有助于改进对食用量的估计,但也强调了在这方面的工作需要继续进行。该试验在clinicaltrials.gov注册为NCT00978406。
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引用次数: 60
Associations between Vitamin D and Cardiovascular Disease Risk Factors in African Americans Are Partly Explained by Circulating Adipokines and C-Reactive Protein: The Jackson Heart Study. 循环脂肪因子和 C 反应蛋白可部分解释非裔美国人维生素 D 与心血管疾病风险因素之间的关系:杰克逊心脏研究》。
Pub Date : 2016-12-01 Epub Date: 2016-10-26 DOI: 10.3945/jn.116.239509
Rumana J Khan, Samson Y Gebreab, Pia Riestra, Mario Sims, Amadou Gaye, Ruihua Xu, Sharon K Davis

Background: Although it is recognized that vitamin D deficiency is associated with cardiovascular disease (CVD) risk factors, and is more common in African Americans (AAs), the pathologic mechanisms by which vitamin D may influence these risk factors are poorly understood.

Objectives: We explored the association between vitamin D status, as reflected by serum 25-hydroxyvitamin D [25(OH)D] concentrations, and CVD risk factors including mean arterial pressure (MAP), fasting plasma glucose (FPG), plasma HDL cholesterol, and waist circumference (WC) in adult AAs. We also tested whether plasma C-reactive protein (CRP), adipokines (adiponectin and leptin), and aldosterone mediated the associations between 25(OH)D and these risk factors.

Methods: Data on 4010 (63.8% women; mean age: 54.0 y) individuals from the Jackson Heart Study were analyzed. Multivariable linear regression models were used to examine the associations of 25(OH)D with CVD risk factors. We used path analysis and bootstrapping methods to quantify and test the share of these associations that was statistically explained by each of the mediators by decomposing the associations into direct and indirect effects.

Results: Serum 25(OH)D concentrations were inversely associated with WC, FPG, and MAP and were positively associated with HDL cholesterol in multivariable analysis. A nearly 20% effect of 25(OH)D on MAP was masked by aldosterone (total indirect effect: β = 0.01, P < 0.05). Approximately 23% of the effect of 25(OH)D on WC (β = -0.03, P < 0.05) and ∼9% of the effect of 25(OH)D on FPG (β = -0.02, P < 0.05) were mediated through CRP, adiponectin, and leptin together. A 23% share of the association between 25(OH)D and HDL cholesterol was mediated by adiponectin alone (β = 0.03, P < 0.05).

Conclusions: Our findings suggest that the associations between vitamin D status and CVD risk factors in AAs are partially mediated through circulating adipokines and CRP. More evidence, however, is required from longitudinal and randomized controlled studies to validate our findings.

背景:尽管维生素 D 缺乏与心血管疾病(CVD)风险因素有关,而且在非裔美国人(AA)中更为常见,但人们对维生素 D 影响这些风险因素的病理机制却知之甚少:我们探讨了血清 25- 羟基维生素 D [25(OH)D] 浓度所反映的维生素 D 状态与心血管疾病风险因素(包括平均动脉压 (MAP)、空腹血浆葡萄糖 (FPG)、血浆高密度脂蛋白胆固醇和腰围 (WC))之间的关系。我们还检测了血浆 C 反应蛋白(CRP)、脂肪因子(脂肪连接蛋白和瘦素)和醛固酮是否介导 25(OH)D 与这些风险因素之间的关联:分析了杰克逊心脏研究中 4010 人(63.8% 为女性;平均年龄:54.0 岁)的数据。采用多变量线性回归模型来研究 25(OH)D 与心血管疾病风险因素之间的关系。我们采用路径分析和引导法,通过将关联分解为直接效应和间接效应,量化并检验了这些关联中由每个中介因素统计解释的份额:结果:在多变量分析中,血清 25(OH)D 浓度与体重、血脂和血压成反比,与高密度脂蛋白胆固醇成正比。醛固酮掩盖了 25(OH)D 对 MAP 近 20% 的影响(总间接影响:β = 0.01,P < 0.05)。25(OH)D 对 WC(β = -0.03,P<0.05)的影响中约有 23%,25(OH)D 对 FPG(β = -0.02,P<0.05)的影响中约有 9%是通过 CRP、脂肪连接蛋白和瘦素共同介导的。25(OH)D与高密度脂蛋白胆固醇之间的关系有23%是由脂肪连通素单独介导的(β = 0.03,P < 0.05):我们的研究结果表明,AA 族维生素 D 状态与心血管疾病风险因素之间的关联部分是通过循环脂肪因子和 CRP 介导的。然而,还需要更多的纵向和随机对照研究来验证我们的发现。
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引用次数: 0
Obese Mice Fed a Diet Supplemented with Enzyme-Treated Wheat Bran Display Marked Shifts in the Liver Metabolome Concurrent with Altered Gut Bacteria. 饲粮中添加酶处理麦麸的肥胖小鼠肝脏代谢组发生显著变化,同时肠道细菌发生改变。
Pub Date : 2016-12-01 DOI: 10.3945/JN.116.238923
D. Kieffer, B. Piccolo, M. Marco, E. Kim, M. Goodson, M. Keenan, T. Dunn, K. Knudsen, S. Adams, Roy J Martin
BACKGROUNDEnzyme-treated wheat bran (ETWB) contains a fermentable dietary fiber previously shown to decrease liver triglycerides (TGs) and modify the gut microbiome in mice. It is not clear which mechanisms explain how ETWB feeding affects hepatic metabolism, but factors (i.e., xenometabolites) associated with specific microbes may be involved.OBJECTIVEThe objective of this study was to characterize ETWB-driven shifts in the cecal microbiome and to identify correlates between microbial changes and diet-related differences in liver metabolism in diet-induced obese mice that typically display steatosis.METHODSFive-week-old male C57BL/6J mice fed a 45%-lard-based fat diet supplemented with ETWB (20% wt:wt) or rapidly digestible starch (control) (n = 15/group) for 10 wk were characterized by using a multi-omics approach. Multivariate statistical analysis was used to identify variables that were strong discriminators between the ETWB and control groups.RESULTSBody weight and liver TGs were decreased by ETWB feeding (by 10% and 25%, respectively; P < 0.001), and an index of liver reactive oxygen species was increased (by 29%; P < 0.01). The cecal microbiome showed an increase in Bacteroidetes (by 42%; P < 0.05) and a decrease in Firmicutes (by 16%; P < 0.05). Metabolites that were strong discriminators between the ETWB and control groups included decreased liver antioxidants (glutathione and α-tocopherol); decreased liver carbohydrate metabolites, including glucose; lower hepatic arachidonic acid; and increased liver and plasma β-hydroxybutyrate. Liver transcriptomics revealed key metabolic pathways affected by ETWB, especially those related to lipid metabolism and some fed- or fasting-regulated genes.CONCLUSIONSTogether, these changes indicate that dietary fibers such as ETWB regulate hepatic metabolism concurrently with specific gut bacteria community shifts in C57BL/6J mice. It is proposed that these changes may elicit gut-derived signals that reach the liver via enterohepatic circulation, ultimately affecting host liver metabolism in a manner that mimics, in part, the fasting state.
背景酶处理的麦麸(ETWB)含有一种可发酵的膳食纤维,先前的研究表明,它可以降低小鼠肝脏甘油三酯(tg)并改变肠道微生物群。目前尚不清楚哪种机制解释了ETWB喂养如何影响肝脏代谢,但与特定微生物相关的因素(即异种代谢物)可能参与其中。本研究的目的是表征etwb驱动的盲肠微生物组的变化,并确定饮食诱导的典型脂肪变性肥胖小鼠肝脏代谢中微生物变化与饮食相关差异之间的相关性。方法采用多组学方法对5周龄雄性C57BL/6J小鼠进行多组学分析,以45%猪油为基础的脂肪饲粮中添加ETWB (20% wt:wt)或快速消化淀粉(对照组)(n = 15/组),饲喂10周。多变量统计分析用于识别ETWB组与对照组之间的强判别变量。结果饲用乙酸乙酯可使大鼠体重和肝脏tg分别降低10%和25%;P < 0.001),肝脏活性氧指数增加了29%;P < 0.01)。盲肠微生物组显示拟杆菌门增加(增加42%;P < 0.05),厚壁菌门降低(16%;P < 0.05)。ETWB组与对照组之间的强鉴别代谢物包括肝脏抗氧化剂(谷胱甘肽和α-生育酚)降低;肝脏碳水化合物代谢物减少,包括葡萄糖;低肝花生四烯酸;肝脏和血浆β-羟基丁酸增加。肝脏转录组学揭示了ETWB影响的关键代谢途径,特别是与脂质代谢和一些摄食或禁食调节基因相关的代谢途径。综上所述,这些变化表明膳食纤维如ETWB在调节C57BL/6J小鼠肝脏代谢的同时,也调节了特定肠道菌群的变化。有人提出,这些变化可能引发肠道来源的信号,通过肠肝循环到达肝脏,最终以部分模仿禁食状态的方式影响宿主肝脏代谢。
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引用次数: 16
Dietary Fiber Intake Is Inversely Associated with Periodontal Disease among US Adults. 美国成年人的膳食纤维摄入量与牙周病成反比。
Pub Date : 2016-12-01 Epub Date: 2016-10-26 DOI: 10.3945/jn.116.237065
Samara Joy Nielsen, Maria Angelica Trak-Fellermeier, Kaumudi Joshipura, Bruce A Dye

Background: Approximately 47% of adults in the United States have periodontal disease. Dietary guidelines recommend a diet providing adequate fiber. Healthier dietary habits, particularly an increased fiber intake, may contribute to periodontal disease prevention.

Objective: Our objective was to evaluate the relation of dietary fiber intake and its sources with periodontal disease in the US adult population (≥30 y of age).

Methods: Data from 6052 adults participating in NHANES 2009-2012 were used. Periodontal disease was defined (according to the CDC/American Academy of Periodontology) as severe, moderate, mild, and none. Intake was assessed by 24-h dietary recalls. The relation between periodontal disease and dietary fiber, whole-grain, and fruit and vegetable intakes were evaluated by using multivariate models, adjusting for sociodemographic characteristics and dentition status.

Results: In the multivariate logistic model, the lowest quartile of dietary fiber was associated with moderate-severe periodontitis (compared with mild-none) compared with the highest dietary fiber intake quartile (OR: 1.30; 95% CI: 1.00, 1.69). In the multivariate multinomial logistic model, intake in the lowest quartile of dietary fiber was associated with higher severity of periodontitis than dietary fiber intake in the highest quartile (OR: 1.27; 95% CI: 1.00, 1.62). In the adjusted logistic model, whole-grain intake was not associated with moderate-severe periodontitis. However, in the adjusted multinomial logistic model, adults consuming whole grains in the lowest quartile were more likely to have more severe periodontal disease than were adults consuming whole grains in the highest quartile (OR: 1.32; 95% CI: 1.08, 1.62). In fully adjusted logistic and multinomial logistic models, fruit and vegetable intake was not significantly associated with periodontitis.

Conclusions: We found an inverse relation between dietary fiber intake and periodontal disease among US adults ≥30 y old. Periodontal disease was associated with low whole-grain intake but not with low fruit and vegetable intake.

背景:美国约有 47% 的成年人患有牙周病。膳食指南建议在饮食中提供足够的纤维。更健康的饮食习惯,尤其是增加纤维摄入量,可能有助于预防牙周病:我们的目的是评估美国成年人(≥30 岁)膳食纤维摄入量及其来源与牙周病的关系:方法:采用参加 2009-2012 年美国国家健康调查(NHANES)的 6052 名成年人的数据。根据美国疾病预防控制中心/美国牙周病学会的定义,牙周病分为重度、中度、轻度和无。摄入量通过 24 小时饮食回顾进行评估。使用多变量模型评估了牙周病与膳食纤维、全谷物、水果和蔬菜摄入量之间的关系,并对社会人口特征和牙齿状况进行了调整:在多变量逻辑模型中,与膳食纤维摄入量最高的四分位数相比,膳食纤维摄入量最低的四分位数与中度-重度牙周炎(与轻度-无牙周炎相比)相关(OR:1.30;95% CI:1.00,1.69)。在多变量多叉逻辑模型中,与膳食纤维摄入量最高的四分位数相比,膳食纤维摄入量最低的四分位数与牙周炎严重程度较高相关(OR:1.27;95% CI:1.00,1.62)。在调整后的逻辑模型中,全谷物摄入量与中度-重度牙周炎无关。然而,在调整后的多叉逻辑模型中,摄入全谷物最低四分位数的成年人比摄入全谷物最高四分位数的成年人更有可能患有更严重的牙周病(OR:1.32;95% CI:1.08,1.62)。在完全调整的逻辑模型和多叉逻辑模型中,水果和蔬菜的摄入量与牙周炎的关系并不明显:我们发现,在年龄≥30 岁的美国成年人中,膳食纤维摄入量与牙周疾病之间存在反向关系。牙周病与全谷物摄入量低有关,但与水果和蔬菜摄入量低无关。
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引用次数: 0
Sugar-Sweetened Beverage but Not Diet Soda Consumption Is Positively Associated with Progression of Insulin Resistance and Prediabetes. 饮用含糖饮料而非无糖汽水与胰岛素抵抗和前驱糖尿病的进展呈正相关。
Pub Date : 2016-11-09 DOI: 10.3945/JN.116.234047
Jiantao Ma, P. Jacques, J. Meigs, C. Fox, G. Rogers, Caren E. Smith, A. Hruby, E. Saltzman, N. McKeown
BACKGROUNDPrevious studies have shown an inconsistent relation between habitual beverage consumption and insulin resistance and prediabetes.OBJECTIVEThe objective of the present study was to test the hypothesis that the consumption of sugar-sweetened beverages (SSBs), rather than diet soda, is associated with long-term progression of insulin resistance and the development of prediabetes.METHODSWe analyzed the prospective association between cumulative mean consumption of SSBs or diet soda and incident prediabetes (n = 1685) identified across a median of 14 y of follow-up in participants [mean ± SD age: 51.9 ± 9.2 y; 59.6% women; mean ± SD body mass index (BMI; kg/m2): 26.3 ± 4.4] of the Framingham Offspring cohort. The prospective association between beverage consumption and change in homeostasis model assessment of insulin resistance (HOMA-IR; n = 2076) over ∼7 y was also analyzed. The cumulative mean consumption of SSBs and diet soda was estimated by using food-frequency questionnaires. Multivariable Cox proportional hazards models and linear regression models were implemented to estimate the HRs of incident prediabetes and change in HOMA-IR, respectively.RESULTSAfter adjustment for multiple potential confounders, including baseline BMI, we observed that SSB intake was positively associated with incident prediabetes (P-trend < 0.001); the highest SSB consumers (>3 servings/wk; median: 6 servings/wk) had a 46% higher risk of developing prediabetes than did the SSB nonconsumers (HR: 1.46; 95% CI: 1.16, 1.83). Higher SSB intake was also associated with a greater increase in HOMA-IR (P-trend = 0.006). No prospective associations were observed between diet soda intake and risk of prediabetes (P-trend = 0.24) or changes in HOMA-IR (P-trend = 0.25). These associations were similar after additional adjustment for change in BMI.CONCLUSIONRegular SSB intake, but not diet soda intake, is associated with a greater increase in insulin resistance and a higher risk of developing prediabetes in a group of middle-aged adults.
先前的研究表明,习惯性饮料消费与胰岛素抵抗和前驱糖尿病之间的关系并不一致。本研究的目的是验证一种假设,即摄入含糖饮料(SSBs),而不是无糖汽水,与胰岛素抵抗的长期进展和前驱糖尿病的发展有关。方法:我们分析了SSBs或无糖汽水的累积平均消费量与糖尿病前期事件(n = 1685)之间的前瞻性关联,这些参与者在随访的中位数为14年[平均±SD年龄:51.9±9.2岁;59.6%的女性;平均±SD体重指数(BMI;kg/m2): 26.3±4.4]。饮料消费与胰岛素抵抗(HOMA-IR)稳态模型评估变化的前瞻性关联N = 2076)超过~ 7y也进行了分析。使用食物频率问卷对SSBs和无糖汽水的累积平均消费量进行估算。采用多变量Cox比例风险模型和线性回归模型分别估计糖尿病前期事件的hr和HOMA-IR的变化。在校正了包括基线BMI在内的多个潜在混杂因素后,我们观察到SSB摄入量与前驱糖尿病的发生呈正相关(p趋势< 0.001);SSB最高消费人群(>3份/周);中位数:6份/周)患前驱糖尿病的风险比不食用SSB的人高46% (HR: 1.46;95% ci: 1.16, 1.83)。SSB摄入量的增加也与HOMA-IR的增加有关(P-trend = 0.006)。无糖汽水摄入与前驱糖尿病风险(P-trend = 0.24)或HOMA-IR变化(P-trend = 0.25)之间没有前瞻性关联。在对BMI变化进行额外调整后,这些关联相似。结论:在一组中年人中,定期摄入SSB,而非无糖汽水,与胰岛素抵抗的增加和患前驱糖尿病的风险增加有关。
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引用次数: 66
Metabolomic Changes in Serum of Children with Different Clinical Diagnoses of Malnutrition123 不同临床诊断营养不良患儿血清代谢组学变化[j]
Pub Date : 2016-11-02 DOI: 10.3945/jn.116.239145
Valeria E. Di Giovanni, C. Bourdon, Dominic Wang, Swapna Seshadri, E. Senga, Christian J Versloot, W. Voskuijl, R. Semba, Indi Trehan, R. Moaddel, M. I. Ordiz, Ling Zhang, J. Parkinson, M. Manary, R. Bandsma
Background: Mortality in children with severe acute malnutrition (SAM) remains high despite standardized rehabilitation protocols. Two forms of SAM are classically distinguished: kwashiorkor and marasmus. Children with kwashiorkor have nutritional edema and metabolic disturbances, including hypoalbuminemia and hepatic steatosis, whereas marasmus is characterized by severe wasting. The metabolic changes underlying these phenotypes have been poorly characterized, and whether homeostasis is achieved during hospital stay is unclear. Objectives: We aimed to characterize metabolic differences between children with marasmus and kwashiorkor at hospital admission and after clinical stabilization and to compare them with stunted and nonstunted community controls. Methods: We studied children aged 9–59 mo from Malawi who were hospitalized with SAM (n = 40; 21 with kwashiorkor and 19 with marasmus) or living in the community (n = 157; 78 stunted and 79 nonstunted). Serum from patients with SAM was obtained at hospital admission and 3 d after nutritional stabilization and from community controls. With the use of targeted metabolomics, 141 metabolites, including amino acids, biogenic amines, acylcarnitines, sphingomyelins, and phosphatidylcholines, were measured. Results: At admission, most metabolites (128 of 141; 91%) were lower in children with kwashiorkor than in those with marasmus, with significant differences in several amino acids and biogenic amines, including those of the kynurenine-tryptophan pathway. Several phosphatidylcholines and some acylcarnitines also differed. Patients with SAM had profiles that were profoundly different from those of stunted and nonstunted controls, even after clinical stabilization. Amino acids and biogenic amines generally improved with nutritional rehabilitation, but most sphingomyelins and phosphatidylcholines did not. Conclusions: Children with kwashiorkor were metabolically distinct from those with marasmus, and were more prone to severe metabolic disruptions. Children with SAM showed metabolic profiles that were profoundly different from stunted and nonstunted controls, even after clinical stabilization. Therefore, metabolic recovery in children with SAM likely extends beyond discharge, which may explain the poor long-term outcomes in these children. This trial was registered at isrctn.org as ISRCTN13916953.
背景:尽管有标准化的康复方案,严重急性营养不良(SAM)儿童的死亡率仍然很高。典型的SAM有两种形式:夸希奥尔病和消瘦症。患有营养不良的儿童有营养性水肿和代谢紊乱,包括低白蛋白血症和肝脂肪变性,而消瘦症的特征是严重消瘦。这些表型背后的代谢变化特征不明确,住院期间是否能实现体内平衡尚不清楚。目的:我们的目的是表征消瘦和夸希奥尔克尔儿童在入院时和临床稳定后的代谢差异,并将其与发育迟缓和非发育迟缓的社区对照进行比较。方法:我们研究了马拉维9-59个月住院的SAM儿童(n = 40;21例患有夸希奥尔克病,19例患有消瘦症)或居住在社区(n = 157;发育不良78例,非发育不良79例)。从SAM患者入院时和营养稳定后3 d以及社区对照中提取血清。利用靶向代谢组学,测定了141种代谢物,包括氨基酸、生物胺、酰基肉碱、鞘磷脂和磷脂酰胆碱。结果:入院时,大多数代谢物(141例中的128例;(91%),在营养不良儿童中比消瘦症儿童低,在几种氨基酸和生物胺,包括犬尿氨酸-色氨酸途径的氨基酸和生物胺方面存在显著差异。几种磷脂酰胆碱和一些酰基肉碱也不同。即使在临床稳定后,SAM患者的特征也与发育迟缓和非发育迟缓对照组有很大的不同。氨基酸和生物胺通常随着营养康复而改善,但大多数鞘磷脂和磷脂酰胆碱没有改善。结论:夸希奥尔科患儿在代谢方面与消瘦症患儿不同,更容易发生严重的代谢紊乱。即使在临床稳定后,患有SAM的儿童的代谢谱也与发育迟缓和非发育迟缓的对照组有很大的不同。因此,SAM患儿的代谢恢复可能延续到出院后,这可能解释了这些患儿较差的长期预后。该试验在isrctn.org上注册为ISRCTN13916953。
{"title":"Metabolomic Changes in Serum of Children with Different Clinical Diagnoses of Malnutrition123","authors":"Valeria E. Di Giovanni, C. Bourdon, Dominic Wang, Swapna Seshadri, E. Senga, Christian J Versloot, W. Voskuijl, R. Semba, Indi Trehan, R. Moaddel, M. I. Ordiz, Ling Zhang, J. Parkinson, M. Manary, R. Bandsma","doi":"10.3945/jn.116.239145","DOIUrl":"https://doi.org/10.3945/jn.116.239145","url":null,"abstract":"Background: Mortality in children with severe acute malnutrition (SAM) remains high despite standardized rehabilitation protocols. Two forms of SAM are classically distinguished: kwashiorkor and marasmus. Children with kwashiorkor have nutritional edema and metabolic disturbances, including hypoalbuminemia and hepatic steatosis, whereas marasmus is characterized by severe wasting. The metabolic changes underlying these phenotypes have been poorly characterized, and whether homeostasis is achieved during hospital stay is unclear. Objectives: We aimed to characterize metabolic differences between children with marasmus and kwashiorkor at hospital admission and after clinical stabilization and to compare them with stunted and nonstunted community controls. Methods: We studied children aged 9–59 mo from Malawi who were hospitalized with SAM (n = 40; 21 with kwashiorkor and 19 with marasmus) or living in the community (n = 157; 78 stunted and 79 nonstunted). Serum from patients with SAM was obtained at hospital admission and 3 d after nutritional stabilization and from community controls. With the use of targeted metabolomics, 141 metabolites, including amino acids, biogenic amines, acylcarnitines, sphingomyelins, and phosphatidylcholines, were measured. Results: At admission, most metabolites (128 of 141; 91%) were lower in children with kwashiorkor than in those with marasmus, with significant differences in several amino acids and biogenic amines, including those of the kynurenine-tryptophan pathway. Several phosphatidylcholines and some acylcarnitines also differed. Patients with SAM had profiles that were profoundly different from those of stunted and nonstunted controls, even after clinical stabilization. Amino acids and biogenic amines generally improved with nutritional rehabilitation, but most sphingomyelins and phosphatidylcholines did not. Conclusions: Children with kwashiorkor were metabolically distinct from those with marasmus, and were more prone to severe metabolic disruptions. Children with SAM showed metabolic profiles that were profoundly different from stunted and nonstunted controls, even after clinical stabilization. Therefore, metabolic recovery in children with SAM likely extends beyond discharge, which may explain the poor long-term outcomes in these children. This trial was registered at isrctn.org as ISRCTN13916953.","PeriodicalId":22788,"journal":{"name":"The Journal of Nutrition Health and Aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82709502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 54
Soy-Dairy Protein Blend or Whey Protein Isolate Ingestion Induces Similar Postexercise Muscle Mechanistic Target of Rapamycin Complex 1 Signaling and Protein Synthesis Responses in Older Men1234 摄入大豆-乳制品蛋白混合物或乳清蛋白分离物可诱导老年男性运动后雷帕霉素复合物1信号和蛋白质合成反应的相似肌肉机制靶点[34
Pub Date : 2016-10-26 DOI: 10.3945/jn.116.231159
Michael S. Borack, P. Reidy, Syed H Husaini, M. Markofski, R. Deer, Abigail B Richison, B. Lambert, M. Cope, R. Mukherjea, K. Jennings, E. Volpi, B. Rasmussen
Background: Previous work demonstrated that a soy-dairy protein blend (PB) prolongs hyperaminoacidemia and muscle protein synthesis in young adults after resistance exercise. Objective: We investigated the effect of PB in older adults. We hypothesized that PB would prolong hyperaminoacidemia, enhancing mechanistic target of rapamycin complex 1 (mTORC1) signaling and muscle protein anabolism compared with a whey protein isolate (WPI). Methods: This double-blind, randomized controlled trial studied men 55–75 y of age. Subjects consumed 30 g protein from WPI or PB (25% soy, 25% whey, and 50% casein) 1 h after leg extension exercise (8 sets of 10 repetitions at 70% one-repetition maximum). Blood and muscle amino acid concentrations and basal and postexercise muscle protein turnover were measured by using stable isotopic methods. Muscle mTORC1 signaling was assessed by immunoblotting. Results: Both groups increased amino acid concentrations (P < 0.05) and mTORC1 signaling after protein ingestion (P < 0.05). Postexercise fractional synthesis rate (FSR; P ≥ 0.05), fractional breakdown rate (FBR; P ≥ 0.05), and net balance (P = 0.08) did not differ between groups. WPI increased FSR by 67% (mean ± SEM: rest: 0.05% ± 0.01%; postexercise: 0.09% ± 0.01%; P < 0.05), decreased FBR by 46% (rest: 0.17% ± 0.01%; postexercise: 0.09% ± 0.03%; P < 0.05), and made net balance less negative (P < 0.05). PB ingestion did not increase FSR (rest: 0.07% ± 0.03%; postexercise: 0.09% ± 0.01%; P ≥ 0.05), tended to decrease FBR by 42% (rest: 0.25% ± 0.08%; postexercise: 0.15% ± 0.08%; P = 0.08), and made net balance less negative (P < 0.05). Within-group percentage of change differences were not different between groups for FSR, FBR, or net balance (P ≥ 0.05). Conclusions: WPI and PB ingestion after exercise in older men induced similar responses in hyperaminoacidemia, mTORC1 signaling, muscle protein synthesis, and breakdown. These data add new evidence for the use of whey or soy-dairy PBs as targeted nutritional interventions to counteract sarcopenia. This trial was registered at clinicaltrials.gov as NCT01847261.
背景:先前的研究表明,大豆-乳制品蛋白混合物(PB)可以延长年轻人在阻力运动后的高氨基酸血症和肌肉蛋白质合成。目的:探讨铅对老年人的影响。我们假设与乳清分离蛋白(WPI)相比,PB可以延长高氨基酸酸血症,增强雷帕霉素复合物1 (mTORC1)信号传导的机制靶点和肌肉蛋白合成代谢。方法:这项双盲、随机对照试验研究了55-75岁的男性。受试者在腿部伸展运动后1小时,从WPI或PB中摄取30 g蛋白质(25%大豆,25%乳清和50%酪蛋白)(8组,每组10次,每次最多重复70%)。采用稳定同位素法测定血液和肌肉氨基酸浓度以及基础和运动后肌肉蛋白质周转。通过免疫印迹法评估肌肉mTORC1信号。结果:两组摄入蛋白质后氨基酸浓度升高(P < 0.05), mTORC1信号通路升高(P < 0.05)。运动后分数合成率;P≥0.05),分数击穿率(FBR;P≥0.05),净平衡组间差异无统计学意义(P = 0.08)。WPI使FSR增加67%(平均值±SEM:其余0.05%±0.01%;运动后:0.09%±0.01%;P < 0.05), FBR降低46%(其余:0.17%±0.01%;运动后:0.09%±0.03%;P < 0.05),使净余额减少负(P < 0.05)。摄入铅不增加FSR(其余:0.07%±0.03%;运动后:0.09%±0.01%;P≥0.05),有使FBR降低42%的趋势(其余:0.25%±0.08%;运动后:0.15%±0.08%;P = 0.08),使净余额减少负(P < 0.05)。FSR、FBR、净平衡组内变化百分比差异无统计学意义(P≥0.05)。结论:老年男性运动后摄入WPI和PB在高氨基酸酸血症、mTORC1信号传导、肌肉蛋白合成和分解方面有相似的反应。这些数据为使用乳清或大豆-乳制品PBs作为有针对性的营养干预措施来对抗肌肉减少症提供了新的证据。该试验在clinicaltrials.gov注册为NCT01847261。
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引用次数: 51
Glycine Regulates Protein Turnover by Activating Protein Kinase B/Mammalian Target of Rapamycin and by Inhibiting MuRF1 and Atrogin-1 Gene Expression in C2C12 Myoblasts. 甘氨酸通过激活蛋白激酶B/哺乳动物雷帕霉素靶蛋白以及抑制C2C12成肌细胞MuRF1和Atrogin-1基因表达调控蛋白质周转。
Pub Date : 2016-10-26 DOI: 10.3945/JN.116.231266
Kaiji Sun, Zhenlong Wu, Yun Ji, Guoyao Wu
BACKGROUNDThe regulation of protein turnover in skeletal muscle is essential for the maintenance of integrity, growth, and function of this tissue. We recently reported that glycine enhances skeletal muscle growth in young pigs. However, the underlying mechanisms remain unknown.OBJECTIVEThis study was conducted with a mouse myoblast cell line, C2C12, to test the hypothesis that glycine activates protein kinase B/mammalian target of rapamycin (Akt/mTOR), as well as inhibits 5'-adenosine monophosphate-activated protein kinase (AMPK) and the expression of genes for proteolysis.METHODSC2C12 myoblasts were cultured with 0, 0.25 (physiologic concentration in mouse plasma), 0.5, or 1.0 mmol glycine/L. Cell proliferation, activation of mammalian target of rapamycin complex 1 (mTORC1), AMPK signaling, mRNA levels of atrogin-1 and muscle-specific ring finger protein 1 (MuRF1), and protein synthesis and degradation were measured in the absence or presence of an Akt inhibitor, LY294002, or an AMPK activator, 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR).RESULTSCompared with control cells, 0.25-1.0 mmol glycine/L enhanced cell growth (by 12-15%) after 24 h (P < 0.05). Glycine treatment led to increased DNA replication (by 70-80%) while enhancing mTORC1 activation by upregulating Akt and inhibiting AMPK signaling (P < 0.05). Accordingly, glycine exposure increased (P < 0.05) the rate of protein synthesis (by 20-80%) and inhibited (P < 0.05) the rate of protein degradation (by 15-30%) in a concentration-dependent manner in C2C12 cells. These observations were validated by the use of an Akt inhibitor, LY294002, or an AMPK activator, AICAR. Moreover, glycine addition resulted in decreased mRNA levels for atrogin-1 and MuRF1 (by 20-40% and 30-50%, respectively; P < 0.05). The repressing effect of glycine on the expression of MuRF1, instead of atrogin-1, was abolished by LY294002 (P < 0.05).CONCLUSIONSThese findings indicate that glycine plays a previously unrecognized role in enhancing protein synthesis and inhibiting protein degradation in C2C12 cells. Glycine regulates protein turnover by activating mTORC1 and by inhibiting the expression of genes for proteolysis. Our results indicate that glycine is a functional amino acid that improves muscle cell growth.
骨骼肌中蛋白质转换的调节对于维持该组织的完整性、生长和功能至关重要。我们最近报道了甘氨酸促进仔猪骨骼肌生长。然而,其潜在机制尚不清楚。目的以小鼠成肌细胞系C2C12为实验对象,验证甘氨酸激活雷帕霉素蛋白激酶B/哺乳动物靶蛋白Akt/mTOR,抑制5′-腺苷单磷酸活化蛋白激酶(AMPK)及蛋白水解基因表达的假说。方法用0、0.25(小鼠血浆生理浓度)、0.5、1.0 mmol甘氨酸/L培养sc2c12成肌细胞。在Akt抑制剂LY294002或AMPK激活剂5-氨基咪唑-4-羧基酰胺核糖核苷(AICAR)缺失或存在的情况下,研究人员测量了细胞增殖、哺乳动物雷帕霉素靶蛋白1 (mTORC1)的激活、AMPK信号传导、atroggin -1和肌肉特异性无名指蛋白1 (MuRF1)的mRNA水平,以及蛋白质的合成和降解。结果与对照细胞相比,0.25 ~ 1.0 mmol甘氨酸/L可促进24 h细胞生长(P < 0.05);甘氨酸处理导致DNA复制增加(70-80%),同时通过上调Akt和抑制AMPK信号传导增强mTORC1的激活(P < 0.05)。因此,甘氨酸暴露使C2C12细胞的蛋白质合成率提高(P < 0.05) 20 ~ 80%,蛋白质降解率降低(P < 0.05) 15 ~ 30%,且呈浓度依赖性。使用Akt抑制剂LY294002或AMPK激活剂AICAR验证了这些观察结果。此外,甘氨酸的添加导致atrogin-1和MuRF1 mRNA水平分别下降20-40%和30-50%;P < 0.05)。glycine对MuRF1表达的抑制作用被LY294002所消除(P < 0.05),而不是atrogin-1。结论甘氨酸在C2C12细胞中具有促进蛋白质合成和抑制蛋白质降解的作用。甘氨酸通过激活mTORC1和抑制蛋白水解基因的表达来调节蛋白质周转。我们的研究结果表明,甘氨酸是一种促进肌肉细胞生长的功能性氨基酸。
{"title":"Glycine Regulates Protein Turnover by Activating Protein Kinase B/Mammalian Target of Rapamycin and by Inhibiting MuRF1 and Atrogin-1 Gene Expression in C2C12 Myoblasts.","authors":"Kaiji Sun, Zhenlong Wu, Yun Ji, Guoyao Wu","doi":"10.3945/JN.116.231266","DOIUrl":"https://doi.org/10.3945/JN.116.231266","url":null,"abstract":"BACKGROUND\u0000The regulation of protein turnover in skeletal muscle is essential for the maintenance of integrity, growth, and function of this tissue. We recently reported that glycine enhances skeletal muscle growth in young pigs. However, the underlying mechanisms remain unknown.\u0000\u0000\u0000OBJECTIVE\u0000This study was conducted with a mouse myoblast cell line, C2C12, to test the hypothesis that glycine activates protein kinase B/mammalian target of rapamycin (Akt/mTOR), as well as inhibits 5'-adenosine monophosphate-activated protein kinase (AMPK) and the expression of genes for proteolysis.\u0000\u0000\u0000METHODS\u0000C2C12 myoblasts were cultured with 0, 0.25 (physiologic concentration in mouse plasma), 0.5, or 1.0 mmol glycine/L. Cell proliferation, activation of mammalian target of rapamycin complex 1 (mTORC1), AMPK signaling, mRNA levels of atrogin-1 and muscle-specific ring finger protein 1 (MuRF1), and protein synthesis and degradation were measured in the absence or presence of an Akt inhibitor, LY294002, or an AMPK activator, 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR).\u0000\u0000\u0000RESULTS\u0000Compared with control cells, 0.25-1.0 mmol glycine/L enhanced cell growth (by 12-15%) after 24 h (P < 0.05). Glycine treatment led to increased DNA replication (by 70-80%) while enhancing mTORC1 activation by upregulating Akt and inhibiting AMPK signaling (P < 0.05). Accordingly, glycine exposure increased (P < 0.05) the rate of protein synthesis (by 20-80%) and inhibited (P < 0.05) the rate of protein degradation (by 15-30%) in a concentration-dependent manner in C2C12 cells. These observations were validated by the use of an Akt inhibitor, LY294002, or an AMPK activator, AICAR. Moreover, glycine addition resulted in decreased mRNA levels for atrogin-1 and MuRF1 (by 20-40% and 30-50%, respectively; P < 0.05). The repressing effect of glycine on the expression of MuRF1, instead of atrogin-1, was abolished by LY294002 (P < 0.05).\u0000\u0000\u0000CONCLUSIONS\u0000These findings indicate that glycine plays a previously unrecognized role in enhancing protein synthesis and inhibiting protein degradation in C2C12 cells. Glycine regulates protein turnover by activating mTORC1 and by inhibiting the expression of genes for proteolysis. Our results indicate that glycine is a functional amino acid that improves muscle cell growth.","PeriodicalId":22788,"journal":{"name":"The Journal of Nutrition Health and Aging","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75985916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 39
The Noncaloric Sweetener Rebaudioside A Stimulates Glucagon-Like Peptide 1 Release and Increases Enteroendocrine Cell Numbers in 2-Dimensional Mouse Organoids Derived from Different Locations of the Intestine. 无热量甜味剂雷鲍迪甙A刺激胰高血糖素样肽1的释放并增加来自肠道不同位置的二维小鼠类器官的肠内分泌细胞数量。
Pub Date : 2016-10-26 DOI: 10.3945/JN.116.232678
Nikkie van der Wielen, J. T. ten Klooster, Susanne Muckenschnabl, R. Pieters, H. Hendriks, R. Witkamp, J. Meijerink
BACKGROUNDGlucagon-like peptide 1 (GLP-1) contributes to satiety and plays a pivotal role in insulin secretion and glucose homeostasis. Similar to GLP-1, peptide YY (PYY) and cholecystokinin also influence food intake. The secretion of these hormones by enteroendocrine cells along the intestine is modulated by nutrients. Preparations from the Stevia rebaudiana plant, including rebaudioside A, are increasingly being used as noncaloric sweeteners.OBJECTIVEWe investigated the effects of rebaudioside A on enteroendocrine cells by assessing both cell numbers as well as their secretory capacity in an organoid model.METHODSA 2-dimensional organoid model derived from duodenal, jejunal, and ileal crypts of a C57BL/6J mouse was developed and characterized with the use of gene expression and immunofluorescence. We stimulated these organoids with 10 mmol/L rebaudioside A for 1 h and measured their GLP-1, PYY, and cholecystokinin release. We also analyzed the effects of rebaudioside A on gene expression in enteroendocrine cells after an 18-h incubation.RESULTSThe 2-dimensional organoids contained crypt cells and differentiated villus cells, including enterocytes and goblet and enteroendocrine cells. These enteroendocrine cells stained positive for GLP-1, PYY, and serotonin. The cultured 2-dimensional organoids maintained their location-specific gene expression patterns. Compared with the control, rebaudioside A induced GLP-1 secretion 1.7-fold in the duodenum (P < 0.01), 2.2-fold in the jejunum (P < 0.01), and 4.3-fold in the ileum (P < 0.001). PYY release was increased by rebaudioside A 3-fold in the ileum compared with the control (P < 0.05). Long-term (18-h) stimulation with the sweetener induced the expression of the enteroendocrine-specific markers chromogranin A, glucagon, Pyy, and cholecystokinin 3.5- (P < 0.001), 3.5- (P < 0.001), 3.8- (P < 0.05), and 6.5-fold (P < 0.001), respectively.CONCLUSIONSThese results show novel ex vivo effects of rebaudioside A on enteroendocrine cells of the mouse small intestine and highlight potentially new applications for rebaudioside A in metabolic diseases.
胰高血糖素样肽1 (GLP-1)有助于饱腹感,并在胰岛素分泌和葡萄糖稳态中起关键作用。与GLP-1类似,肽YY (PYY)和胆囊收缩素也影响食物摄入。肠道内分泌细胞沿肠道分泌这些激素是受营养物质调节的。从甜菊糖苷植物中提取的制剂,包括甜菊糖苷A,越来越多地被用作无热量甜味剂。目的研究雷鲍迪苷A对类器官模型肠内分泌细胞数量和分泌能力的影响。方法建立C57BL/6J小鼠十二指肠、空肠和回肠隐窝的二维类器官模型,采用基因表达和免疫荧光技术对模型进行表征。我们用10 mmol/L雷鲍迪苷A刺激这些类器官1小时,并测量它们的GLP-1、PYY和胆囊收缩素的释放。我们还分析了雷鲍迪甙A在孵育18小时后对肠内分泌细胞基因表达的影响。结果二维类器官包含隐窝细胞和分化的绒毛细胞,包括肠细胞、杯状细胞和肠内分泌细胞。这些肠内分泌细胞GLP-1、PYY和血清素染色阳性。培养的二维类器官保持其位置特异性基因表达模式。与对照组相比,雷鲍迪苷A诱导十二指肠、空肠和回肠GLP-1分泌分别增加1.7倍(P < 0.01)、2.2倍(P < 0.01)和4.3倍(P < 0.001)。与对照组相比,雷鲍迪甙A可使回肠PYY释放量增加3倍(P < 0.05)。长期(18小时)刺激可诱导肠内分泌特异性标志物嗜铬粒蛋白A、胰高血糖素、Pyy和胆囊收缩素的表达分别为3.5倍(P < 0.001)、3.5倍(P < 0.001)、3.8倍(P < 0.05)和6.5倍(P < 0.001)。结论利鲍迪糖苷A对小鼠小肠肠内分泌细胞具有新的体外作用,在代谢性疾病治疗中具有潜在的新应用前景。
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引用次数: 28
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The Journal of Nutrition Health and Aging
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