Role of GPER in Obesity and Lipid Metabolism.
GPER 在肥胖和脂质代谢中的作用。
基本信息
- 批准号:10680278
- 负责人:
- 金额:$ 4.43万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-05-01 至 2026-06-30
- 项目状态:未结题
- 来源:
- 关键词:AdipocytesAdultAgonistAnti-Inflammatory AgentsAtherosclerosisBiological AssayBiological ModelsBody WeightCRISPR/Cas technologyCardiovascular DiseasesCaringCell LineCell SurvivalCellsChronicComplexDesire for foodDiabetes MellitusDiseaseDisease ProgressionEstradiolEstrogen Nuclear ReceptorEstrogen Receptor alphaEstrogen Receptor betaEstrogen ReceptorsEstrogensExhibitsFatty acid glycerol estersFemaleGPER geneGene ExpressionGenerationsGenesGenus HippocampusGoalsHomeostasisHormonesHydrogen PeroxideHyperlipidemiaHypertensionInflammationInflammatoryInterleukin-1 betaInterleukin-6InterventionKnock-outKnockout MiceKnowledgeLaboratoriesLigandsLipaseLipidsLipolysisLiver diseasesMediatingMedicalMembraneMetabolicMetabolic DiseasesMetabolic dysfunctionMetabolismMitochondriaMusNational Health and Nutrition Examination SurveyObese MiceObesityOutcomeOverweightOxidative StressPathway interactionsPhysiologicalPhysiological ProcessesPlayPublic HealthReceptor ActivationReceptor SignalingRegulationRespirationRiskRoleSignal TransductionSmokingStress TestsSupplementationSystems DevelopmentTNF geneTestingTherapeuticTimeTissuesUnited StatesWeight GainWestern BlottingWild Type Mouseadipokinesagedantagonistantioxidant enzymebody systemcomorbiditycostcytokinedrug developmentimprovedin vivoinflammatory markerinhibitorlipid biosynthesislipid metabolismmalenon-genomicnovel therapeuticsobesity treatmentpreventable deathprotein expressionreceptor expressionreproductive developmenttherapeutic developmenttreatment strategy
项目摘要
PROJECT SUMMARY/ABSTRACT
Obesity poses as a serious and worsening public health issue in the United States and is the second
most common cause of preventable death behind smoking. Obesity is associated with the risk of developing
additional comorbidities, such as hypertension, atherosclerosis, and diabetes.
Estrogens (primarily 17β-estradiol, referred to as E2) can ameliorate weight gain and multiple aspects
of metabolic dysfunction. The effects of estrogens are mediated through multiple estrogen receptors (ERs),
including the classical nuclear ERs (ERα and ERβ), which traditionally regulate gene expression, and the 7-
transmembrane G protein-coupled estrogen receptor (GPER), which predominantly mediates rapid “non-
genomic” signaling. Our preliminary results suggest a potential intervention employing a highly selective GPER
agonist, with promising outcomes against multiple negative effects of obesity. With the opportunity to employ
the GPER-selective agonist G-1 as a novel therapeutic for obesity, understanding the direct effects of GPER in
adipocytes is critical. The long-term goal is to determine whether selective activators of GPER, such as G-1,
can improve lipid homeostasis, oxidative stress, and inflammation in adipocytes. The overall objective of this
proposal is to understand the mechanisms of E2-mediated effects via GPER in metabolic regulation,
specifically in adipocytes. The central hypothesis to be tested is whether GPER signaling directly improves lipid
homeostasis, oxidative stress, inflammation, and mitochondrial function in adipocytes. These findings will
inform drug development by making significant advancements in our knowledge regarding the role of GPER in
obesity and lipid metabolism, ultimately advancing the current insufficient therapeutic treatment options
available for obesity. The specific aims of this proposal are: Aim 1: Evaluate the roles of GPER in lipid
metabolism of adipocytes. The working hypothesis for this aim is that GPER’s effects on obesity are in part
mediated by direct actions on lipid metabolism on adipocytes. Aim 2: Determine the role of GPER in
oxidative stress, inflammation, and mitochondrial function in adipocytes. The working hypothesis for this
aim is that GPER plays a direct protective role against oxidative stress, inflammation, and improves
mitochondrial function in adipocytes.
This proposal will investigate the direct effects of GPER in adipocytes pertaining to lipid homeostasis,
oxidative stress, inflammation, and mitochondrial function, with the potential to significantly advance the study
of novel therapeutics protecting against obesity.
项目总结/摘要
肥胖在美国是一个严重且日益恶化的公共健康问题,
仅次于吸烟的最常见的可预防死亡原因。肥胖与发展为
其他合并症,如高血压、动脉粥样硬化和糖尿病。
雌激素(主要是17β-雌二醇,称为E2)可以改善体重增加和多个方面
代谢紊乱的症状雌激素的作用是通过多种雌激素受体(ER)介导的,
包括传统上调节基因表达的经典核ER(ERα和ERβ),以及7-
跨膜G蛋白偶联雌激素受体(GPER),主要介导快速的“非-
基因组”信号。我们的初步结果表明,一个潜在的干预采用高度选择性GPER
激动剂,具有对抗肥胖的多种负面影响的有希望的结果。有机会雇用
GPER选择性激动剂G-1作为一种新型的肥胖治疗药物,了解GPER在肥胖中的直接作用,
脂肪细胞至关重要。长期目标是确定GPER的选择性激活剂,如G-1,
可以改善脂肪细胞中的脂质稳态、氧化应激和炎症。本报告的总体目标
建议是了解E2通过GPER介导的代谢调节作用的机制,
特别是脂肪细胞。有待检验的中心假设是GPER信号是否直接改善脂质代谢。
体内平衡、氧化应激、炎症和脂肪细胞中的线粒体功能。这些发现将
通过在我们对GPER在以下方面的作用的认识方面取得重大进展,为药物开发提供信息:
肥胖和脂质代谢,最终推进目前不足的治疗选择
用于治疗肥胖症。本提案的具体目标是:目标1:评估GPER在脂质中的作用
脂肪细胞的代谢。这一目标的工作假设是,GPER对肥胖的影响部分是
通过对脂肪细胞的脂质代谢的直接作用介导。目标2:确定GPER在以下方面的作用
脂肪细胞中的氧化应激、炎症和线粒体功能。对此的工作假设是
目的是GPER对氧化应激、炎症起直接保护作用,并改善
脂肪细胞中的线粒体功能。
该提案将研究GPER在脂肪细胞中对脂质稳态的直接影响,
氧化应激,炎症和线粒体功能,有可能显着推进研究
新的治疗方法来预防肥胖。
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 }}
Randy Ko其他文献
Randy Ko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 }}
相似海外基金
Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
- 批准号:
MR/Z503605/1 - 财政年份:2024
- 资助金额:
$ 4.43万 - 项目类别:
Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
- 批准号:
2336167 - 财政年份:2024
- 资助金额:
$ 4.43万 - 项目类别:
Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
- 批准号:
2402691 - 财政年份:2024
- 资助金额:
$ 4.43万 - 项目类别:
Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
- 批准号:
24K12150 - 财政年份:2024
- 资助金额:
$ 4.43万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
- 批准号:
2341428 - 财政年份:2024
- 资助金额:
$ 4.43万 - 项目类别:
Standard Grant
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
- 批准号:
DE240100561 - 财政年份:2024
- 资助金额:
$ 4.43万 - 项目类别:
Discovery Early Career Researcher Award
RUI: Evaluation of Neurotrophic-Like properties of Spaetzle-Toll Signaling in the Developing and Adult Cricket CNS
RUI:评估发育中和成年蟋蟀中枢神经系统中 Spaetzle-Toll 信号传导的神经营养样特性
- 批准号:
2230829 - 财政年份:2023
- 资助金额:
$ 4.43万 - 项目类别:
Standard Grant
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
- 批准号:
23K09542 - 财政年份:2023
- 资助金额:
$ 4.43万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
- 批准号:
23K07552 - 财政年份:2023
- 资助金额:
$ 4.43万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
- 批准号:
23K07559 - 财政年份:2023
- 资助金额:
$ 4.43万 - 项目类别:
Grant-in-Aid for Scientific Research (C)