The Role of Mediobasal Hypothalamic Gliosis in Gestational Weight Gain and Gestational Visceral Fat Accretion
下丘脑内侧胶质细胞增生在妊娠期体重增加和妊娠期内脏脂肪堆积中的作用
基本信息
- 批准号:10742432
- 负责人:
- 金额:$ 44.84万
- 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:2023-08-18 至 2025-08-17
- 项目状态:未结题
- 来源:
- 关键词:AbdomenAdipose tissueAffectAmniotic FluidAutomobile DrivingBlood VolumeBody Weight decreasedBody mass indexBrainBrain regionCardiovascular DiseasesClinicalClinical MarkersClinical TrialsComplexConceptionsDataDepositionDevelopmentDietDisabled PersonsDrug or chemical Tissue DistributionEndocrineExposure toFatty acid glycerol estersFetusFirst Pregnancy TrimesterFutureFuture GenerationsGestational DiabetesGliosisGlucoseGuidelinesHealthHealth Care CostsHigh Fat DietHip region structureHumanHypertensionHypothalamic structureInflammationInflammatoryInflammatory ResponseInstitute of Medicine (U.S.)Insulin ResistanceInterventionIntervention TrialIntra-abdominalKnowledgeLiteratureMagnetic Resonance ImagingMeasuresMetabolicMetabolic DiseasesMetabolic MarkerMetabolic dysfunctionMetabolic syndromeMetforminModificationNeurobiologyNeuronal InjuryNeuronsNeurosecretory SystemsObesityOrganOverweightPathologicPathway interactionsPersonsPharmaceutical PreparationsPhysical activityPhysiologicalPhysiologyPlacentaPopulations at RiskPregnancyPregnant WomenProcessProviderPublishingRadiology SpecialtyRegulationResearchResearch PersonnelRiskRodentRoleScientific Advances and AccomplishmentsSeveritiesSignal PathwaySignal TransductionSolidStructure of nucleus infundibularis hypothalamiTechniquesTestingThird Pregnancy TrimesterTissuesUterusVariantVisceralVisceral fatWeightWeight Gainadult obesitybiological adaptation to stressbrain magnetic resonance imagingcytokineenergy balanceexperiencegestational weight gainhigh rewardhigh riskinnovationinsightmaternal stressmaternal weightmillisecondneuroimagingneuromechanismnoveloverweight childpost pregnancypregnantprepregnancypreventrecruitresponsesubcutaneoussuccess
项目摘要
PROJECT SUMMARY
Pregnancy is a unique state in which maternal gestational weight gain (GWG) is physiologically adaptive
and necessary. Excessive gestational weight gain (EGWG) is weight gain exceeding guidelines and contributes
to long term maternal metabolic dysfunction. While many diet- and activity-based intervention trials have been
performed to limit EGWG, the data are inconsistent regarding successfully preventing EGWG in pregnancy.
Potentially, the impediments faced in successfully mitigating EGWG arise from our lack of clarity about
mechanisms underlying physiologic GWG. Therefore, the concept that diet and physical activity fully account for
quantitative GWG variation in pregnancy is far too simplistic. Weight regulation is a complex process involving
interactions among multiple neurobiological and endocrine pathways, but the central control predominantly
occurs in the mediobasal hypothalamus (MBH), specifically the arcuate nucleus. Recent studies in nonpregnant
humans demonstrate that gliosis (a cellular inflammatory response) in the MBH is associated with obesity.
Studies in rodents exposed to a high-fat diet show that MBH gliosis precedes weight gain and that these glial
inflammatory responses are both necessary and sufficient for weight gain. In humans, increased T2 signal on
T2-weighted brain MRI is a radiologic marker of gliosis. Increased T2 signal in the MBH associates with obesity,
insulin resistance and increased visceral adipose tissue (VAT), independent of body mass index (BMI). VAT, fat
surrounding intra-abdominal solid organs, produces more pro-inflammatory cytokines than subcutaneous fat and
is associated with increased risk for metabolic disease. We, and others, have shown associations between
increased VAT and gestational metabolic disease. Therefore, based on rodent literature and findings in non-
pregnant humans, it seems plausible that MBH gliosis could associate with pathological GWG or affect
preferential deposition of VAT during pregnancy. Foundational data from this R21 proposal will provide the first
information regarding a neural mechanism underlying dysregulated or pathological weight gain in pregnancy.
项目总结
项目成果
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