Eicosapentaenoic acid and protein modulation to induce anabolism in COPD
二十碳五烯酸和蛋白质调节诱导慢性阻塞性肺病的合成代谢
基本信息
- 批准号:8104012
- 负责人:
- 金额:$ 36.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-08-06 至 2012-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcidsAcuteAddressAmino AcidsAnabolic AgentsAnabolismAnti-Inflammatory AgentsAnti-inflammatoryBloodBody CompositionBody Weight decreasedCachexiaCaseinsChronicChronic Obstructive Airway DiseaseClinicalDiseaseDrug FormulationsEicosapentaenoic AcidFatty AcidsHealthHourInflammationInflammatory ResponseIngestionIntakeLeucineLungMalignant NeoplasmsMethodologyMuscleMuscle ProteinsMuscular AtrophyNutritionalNutritional SupportOutcomePathologyPatientsPatternPeripheralPlasmaPlayProductionProtein BiosynthesisProteinsQuality of lifeRegulationRoleSeriesStagingSupplementationSystemic diseaseTestingTissue SampleTissuesWeightWeight GainWhey Proteinbaseclinically relevantcytokinedosagefeedingfunctional outcomesfunctional statusimprovedmortalitymuscle formmuscle metabolismnutritionprotein metabolismresearch studyresponsestable isotope
项目摘要
DESCRIPTION (provided by applicant): Chronic Obstructive Pulmonary Disease (COPD) is considered a systemic disease that involves pathology in several extra pulmonary tissues. Systemic features in COPD include chronic low-grade systemic inflammation and altered regulation of protein metabolism, which result initially in muscle atrophy only but in later stages in cachexia. Despite the well-recognized importance of treating cachexia in COPD with appropriate nutrition, current nutritional approaches are only partially successful. We recently observed that in order to enhance protein anabolism, manipulation of the composition of proteins and amino acids in nutrition is required in normal-weight COPD. Cachectic COPD patients are characterized by a decreased muscle protein synthesis and an elevated myofibrillar protein breakdown. A substantial number of these patients, characterized by an enhanced systemic inflammatory response, failed to respond to nutritional therapy, which is of clinical relevance as weight gain to nutritional therapy is a significant, independent predictor of mortality in COPD. Eicosapentaenoic acid (EPA) and docosahexanoic acid (DHA) are I-3 fatty acids, known to play an anti- inflammatory role through inhibition of cytokine production. EPA+DHA supplementation has been shown to effectively inhibit weight loss, however, weight and muscle mass gain was not achieved both in cancer and COPD. Factors like the low daily dosage of EPA+DHA, the delayed plasma EPA peak after intake, as well as the absence of anabolic agents like proteins and specific amino acids (ie leucine) might explain that EPA+DHA treatment was unsuccessful. Our hypothesis is that there is a unique combination of EPA+DHA, protein and leucine that maximally will stimulate meal-induced net muscle protein synthesis in cachectic COPD patients. In the first experiment, we will examine whether sip feeding of casein protein is preferable above whey protein in the stimulation of whole body net protein synthesis in cachectic COPD patients and whether adding leucine will be of additional benefit. In the second experiment, it will be examined whether daily ingestion of 4000 mg EPA+DHA as compared to 2000 mg EPA+DHA during 4 weeks in cachectic COPD patients will increase the acute response in muscle net protein synthesis to the optimal nutritional mixture as determined in Aim 1. In the third experiment, it will be examined whether daily ingestion of this combination of optimal nutritional mixture and EPA+DHA, as determined in aim 1 and 2, during 8 weeks in cachectic COPD patients will improve nutritional, functional and global clinical outcome as compared to an isocaloric control meal. The combination of plasma and muscle tissue sampling, stable isotope methodology, and assessment of body composition, functional status and quality of life will enable quantification of all endpoints. The results of this study should provide the basis for a new nutritional formulation to support protein anabolism and improve overall outcome in cachectic patients with Chronic Obstructive Pulmonary Disease. PUBLIC HEALTH RELEVANCE: The results of this study should provide the basis for a new nutritional formulation to support protein anabolism and improve overall outcome in cachectic patients with Chronic Obstructive Pulmonary Disease.
描述(由申请人提供):慢性阻塞性肺疾病(COPD)被认为是一种全身性疾病,涉及几种额外肺组织的病理学。COPD的全身性特征包括慢性低度全身性炎症和蛋白质代谢调节改变,其最初仅导致肌肉萎缩,但在晚期阶段导致恶病质。尽管通过适当的营养治疗COPD恶病质的重要性已得到公认,但目前的营养方法仅部分成功。我们最近观察到,为了增强蛋白质的抗氧化性,在正常体重的COPD中需要操纵营养中的蛋白质和氨基酸的组成。恶病质COPD患者的特征在于肌肉蛋白质合成减少和肌原纤维蛋白质分解升高。这些患者中有相当数量的患者,其特征是全身炎症反应增强,对营养治疗无反应,这具有临床意义,因为营养治疗后体重增加是COPD死亡率的重要独立预测因素。二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)是1 -3脂肪酸,已知其通过抑制细胞因子产生而发挥抗炎作用。EPA+DHA补充剂已被证明可有效抑制体重减轻,但在癌症和COPD中均未实现体重和肌肉质量增加。EPA+DHA的每日剂量低,摄入后延迟的血浆EPA峰值以及缺乏蛋白质和特定氨基酸(即亮氨酸)等合成代谢剂等因素可能解释EPA+DHA治疗不成功。我们的假设是,EPA+DHA、蛋白质和亮氨酸的独特组合将最大限度地刺激恶病质COPD患者的膳食诱导的净肌肉蛋白质合成。在第一个实验中,我们将检查在恶病质COPD患者中,在刺激全身净蛋白质合成方面,酪蛋白的啜喂是否优于乳清蛋白,以及添加亮氨酸是否会有额外的益处。在第二个实验中,将检查恶病质COPD患者在4周期间每天摄入4000 mg EPA + DHA与2000 mg EPA+DHA相比是否会增加肌肉网蛋白质合成对目标1中确定的最佳营养混合物的急性反应。在第三个实验中,将检查与等热量对照餐相比,恶病质COPD患者在8周期间每日摄入如目标1和2中确定的最佳营养混合物和EPA+DHA的这种组合是否会改善营养、功能和总体临床结果。血浆和肌肉组织采样、稳定同位素方法学以及身体成分、功能状态和生活质量评估的结合将能够量化所有终点。这项研究的结果应该为一种新的营养配方提供基础,以支持蛋白质的摄入,并改善慢性阻塞性肺疾病恶病质患者的总体预后。公共卫生相关性:这项研究的结果应该为一种新的营养配方提供基础,以支持蛋白质的摄入,并改善慢性阻塞性肺疾病恶病质患者的总体预后。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Nicolaas E Deutz其他文献
Nicolaas E Deutz的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Nicolaas E Deutz', 18)}}的其他基金
Minimally-invasive technology for personalized nutritional monitoring
用于个性化营养监测的微创技术
- 批准号:
10693521 - 财政年份:2023
- 资助金额:
$ 36.25万 - 项目类别:
Nutritional modulation to minimize resistance exercise induced metabolic deregulations and improve training responsiveness in Chronic Obstructive Pulmonary Disease
营养调节可最大程度地减少阻力运动引起的代谢失调并提高慢性阻塞性肺疾病的训练反应能力
- 批准号:
10009819 - 财政年份:2019
- 资助金额:
$ 36.25万 - 项目类别:
TSQ Vantage Bundle with Acquity UltraPerformance LC
TSQ Vantage 套装与 Acquity UltraPerformance LC
- 批准号:
7794275 - 财政年份:2010
- 资助金额:
$ 36.25万 - 项目类别:
Eicosapentaenoic acid and protein modulation to induce anabolism in COPD
二十碳五烯酸和蛋白质调节诱导慢性阻塞性肺病的合成代谢
- 批准号:
8298610 - 财政年份:2009
- 资助金额:
$ 36.25万 - 项目类别:
Eicosapentaenoic acid and protein modulation to induce anabolism in COPD
二十碳五烯酸和蛋白质调节诱导慢性阻塞性肺病的合成代谢
- 批准号:
7740483 - 财政年份:2009
- 资助金额:
$ 36.25万 - 项目类别:
Eicosapentaenoic acid and protein modulation to induce anabolism in COPD
二十碳五烯酸和蛋白质调节诱导慢性阻塞性肺病的合成代谢
- 批准号:
7908902 - 财政年份:2009
- 资助金额:
$ 36.25万 - 项目类别:
相似海外基金
Acute senescence: a novel host defence counteracting typhoidal Salmonella
急性衰老:对抗伤寒沙门氏菌的新型宿主防御
- 批准号:
MR/X02329X/1 - 财政年份:2024
- 资助金额:
$ 36.25万 - 项目类别:
Fellowship
Transcriptional assessment of haematopoietic differentiation to risk-stratify acute lymphoblastic leukaemia
造血分化的转录评估对急性淋巴细胞白血病的风险分层
- 批准号:
MR/Y009568/1 - 财政年份:2024
- 资助金额:
$ 36.25万 - 项目类别:
Fellowship
Combining two unique AI platforms for the discovery of novel genetic therapeutic targets & preclinical validation of synthetic biomolecules to treat Acute myeloid leukaemia (AML).
结合两个独特的人工智能平台来发现新的基因治疗靶点
- 批准号:
10090332 - 财政年份:2024
- 资助金额:
$ 36.25万 - 项目类别:
Collaborative R&D
Cellular Neuroinflammation in Acute Brain Injury
急性脑损伤中的细胞神经炎症
- 批准号:
MR/X021882/1 - 财政年份:2024
- 资助金额:
$ 36.25万 - 项目类别:
Research Grant
STTR Phase I: Non-invasive focused ultrasound treatment to modulate the immune system for acute and chronic kidney rejection
STTR 第一期:非侵入性聚焦超声治疗调节免疫系统以治疗急性和慢性肾排斥
- 批准号:
2312694 - 财政年份:2024
- 资助金额:
$ 36.25万 - 项目类别:
Standard Grant
Combining Mechanistic Modelling with Machine Learning for Diagnosis of Acute Respiratory Distress Syndrome
机械建模与机器学习相结合诊断急性呼吸窘迫综合征
- 批准号:
EP/Y003527/1 - 财政年份:2024
- 资助金额:
$ 36.25万 - 项目类别:
Research Grant
FITEAML: Functional Interrogation of Transposable Elements in Acute Myeloid Leukaemia
FITEAML:急性髓系白血病转座元件的功能研究
- 批准号:
EP/Y030338/1 - 财政年份:2024
- 资助金额:
$ 36.25万 - 项目类别:
Research Grant
KAT2A PROTACs targetting the differentiation of blasts and leukemic stem cells for the treatment of Acute Myeloid Leukaemia
KAT2A PROTAC 靶向原始细胞和白血病干细胞的分化,用于治疗急性髓系白血病
- 批准号:
MR/X029557/1 - 财政年份:2024
- 资助金额:
$ 36.25万 - 项目类别:
Research Grant
ロボット支援肝切除術は真に低侵襲なのか?acute phaseに着目して
机器人辅助肝切除术真的是微创吗?
- 批准号:
24K19395 - 财政年份:2024
- 资助金额:
$ 36.25万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Collaborative Research: Changes and Impact of Right Ventricle Viscoelasticity Under Acute Stress and Chronic Pulmonary Hypertension
合作研究:急性应激和慢性肺动脉高压下右心室粘弹性的变化和影响
- 批准号:
2244994 - 财政年份:2023
- 资助金额:
$ 36.25万 - 项目类别:
Standard Grant