MC3R inhibition as a strategy to maintain weight loss in obesity
MC3R 抑制作为肥胖患者维持体重减轻的策略
基本信息
- 批准号:10593110
- 负责人:
- 金额:$ 24.9万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-03-16 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:AmericanAnorexiaBehaviorBehavioralBindingBiologyBody WeightBody Weight decreasedBrainBrain imagingCalciumCaloric RestrictionConeDataDietEatingEating DisordersElectrophysiology (science)EvaluationExerciseFastingFeeding behaviorsGeneticGrantHungerHypothalamic structureImageImpairmentIn Situ HybridizationIndividualKineticsKnockout MiceMapsMediatingMelanocortin 3 ReceptorMelanocortin 4 ReceptorMentorsMentorshipMetabolicMetabolic syndromeModalityMolecularMusNeuroendocrinologyNeuronsNeurosciencesNeurosecretory SystemsObesityOperative Surgical ProceduresPathway interactionsPatientsPeptidesPharmacologyPhysiologyPublic HealthPublishingReportingResearchResearch PersonnelRoleSiteSliceStructure of nucleus infundibularis hypothalamiTestingTherapeuticTrainingUnited StatesViralWeightWeight GainWeight-Loss Drugsantagonistdiet and exercisedietary restrictiondietingdruggable targetefficacy testingexperienceexperimental studyfeedinggamma-Aminobutyric Acidin vivoknock-downliraglutidemicroendoscopymouse modelneural circuitneuroregulationnovelnovel strategiesnovel therapeutic interventionnovel therapeuticsobesity treatmentpharmacologicpresynapticpreventprogramsresponsetherapeutic targetweight maintenance
项目摘要
Proposal Summary:
The increasing rates of obesity and associated metabolic syndrome pose a major public health concern.
Although behavioral (diet and/or exercise), surgical, and pharmacological modalities exist for weight loss, many
individuals are unable to maintain this weight loss due to behavioral and neuroendocrine adaptions in the brain
promoting weight re-gain. Therefore, pathways preventing compensatory adaptations to weight loss would
provide a wholly novel approach to the conundrum of obesity treatment. Hypothalamic agouti-related peptide
(AgRP) neurons are activated by hunger and dieting and potently engage behavioral and neuroendocrine
neural circuits to drive behaviors promoting increased food intake and rebound weight gain. Here, we show
that the melanocortin 3 receptor is densely expressed in AgRP neurons, with 97% of AgRP neurons containing
MC3R. Furthermore, pharmacological manipulation of MC3R bi-directionally regulates feeding in an AgRP
neuron dependent manner, with agonism of MC3R stimulating feeding and antagonism of MC3R suppressing
feeding. Consistently, mice with impaired MC3R function do not re-feed normally following both fasting and
caloric restriction and fail to adequately activate neuroendocrine responses to weight loss. In this proposal, we
will evaluate the utility of MC3R specific antagonists as a therapeutic strategy for preventing compensatory
responses to weight loss. We will also determine the cellular and molecular mechanism(s) mediating the
anorexigenic effects of MC3R antagonism. The principle investigator in this training grant, Dr. Patrick
Sweeney, has extensive experience in behavioral neuroscience and mouse feeding behavior. In this training
grant, Dr. Sweeney will receive additional training in metabolic physiology, neuroendocrinology, obesity
biology, and pharmacology from the primary research mentor, Dr. Roger Cone. Furthermore, under the
guidance of an expert team of collaborators, Dr. Sweeney will receive hands on training in brain slice
electrophysiology and in vivo endomicroscopic brain imaging. Together, the mentorship and training in this
K99/R00 application will provide the necessary technical and conceptual background for Dr. Sweeney to
initiate an independent research program focusing on MC3R neural circuits as therapeutic targets for obesity
and eating disorders.
方案简介:
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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Patrick Sweeney其他文献
Patrick Sweeney的其他文献
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{{ truncateString('Patrick Sweeney', 18)}}的其他基金
MC3R inhibition as a strategy to maintain weight loss in obesity
MC3R 抑制作为肥胖患者维持体重减轻的策略
- 批准号:
10542486 - 财政年份:2022
- 资助金额:
$ 24.9万 - 项目类别:
MC3R inhibition as a strategy to maintain weight loss in obesity
MC3R 抑制作为肥胖患者维持体重减轻的策略
- 批准号:
10248564 - 财政年份:2020
- 资助金额:
$ 24.9万 - 项目类别:
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