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

• 批准号: 10742432
• 负责人: Suchitra Chandrasekaran
• 金额: $ 44.84万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10742432
• 关键词: Abdomen; Adipose tissue; Affect; Amniotic Fluid; Automobile Driving; Blood Volume; Body Weight decreased; Body mass index; Brain; Brain region; Cardiovascular Diseases; Clinical; Clinical Markers; Clinical Trials; Complex; Conceptions; Data; Deposition; Development; Diet; Disabled Persons; Drug or chemical Tissue Distribution; Endocrine; Exposure to; Fatty acid glycerol esters; Fetus; First Pregnancy Trimester; Future; Future Generations; Gestational Diabetes; Gliosis; Glucose; Guidelines; Health; Health Care Costs; High Fat Diet; Hip region structure; Human; Hypertension; Hypothalamic structure; Inflammation; Inflammatory; Inflammatory Response; Institute of Medicine (U.S.); Insulin Resistance; Intervention; Intervention Trial; Intra-abdominal; Knowledge; Literature; Magnetic Resonance Imaging; Measures; Metabolic; Metabolic Diseases; Metabolic Marker; Metabolic dysfunction; Metabolic syndrome; Metformin; Modification; Neurobiology; Neuronal Injury; Neurons; Neurosecretory Systems; Obesity; Organ; Overweight; Pathologic; Pathway interactions; Persons; Pharmaceutical Preparations; Physical activity; Physiological; Physiology; Placenta; Populations at Risk; Pregnancy; Pregnant Women; Process; Provider; Publishing; Radiology Specialty; Regulation; Research; Research Personnel; Risk; Rodent; Role; Scientific Advances and Accomplishments; Severities; Signal Pathway; Signal Transduction; Solid; Structure of nucleus infundibularis hypothalami; Techniques; Testing; Third Pregnancy Trimester; Tissues; Uterus; Variant; Visceral; Visceral fat; Weight; Weight Gain; adult obesity; biological adaptation to stress; brain magnetic resonance imaging; cytokine; energy balance; experience; gestational weight gain; high reward; high risk; innovation; insight; maternal stress; maternal weight; millisecond; neuroimaging; neuromechanism; novel; overweight child; post pregnancy; pregnant; prepregnancy; prevent; recruit; response; subcutaneous; success

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.

项目摘要 妊娠是一种独特的状态，在这种状态下，母体妊娠期体重增加（GWG）是生理适应性的 也是必要的过度妊娠体重增加（EGWG）是体重增加超过指南，并有助于 长期的母体代谢功能障碍。虽然许多基于饮食和活动的干预试验已经 虽然进行了限制EGWG的研究，但关于成功预防妊娠期EGWG的数据不一致。 潜在地，成功缓解EGWG所面临的障碍来自于我们对以下方面缺乏明确性： 生理性GWG的潜在机制。因此，饮食和体力活动完全可以解释 妊娠期GWG的定量变化过于简单化。体重调节是一个复杂的过程， 多种神经生物学和内分泌途径之间的相互作用，但中央控制占主导地位 发生在下丘脑内侧基底核（MBH），特别是弓状核。非妊娠患者的近期研究 人类证实MBH中的神经胶质增生（一种细胞炎症反应）与肥胖有关。 对暴露于高脂饮食的啮齿动物的研究表明，MBH神经胶质增生先于体重增加，这些神经胶质增生可能与体重增加有关。 炎症反应是体重增加的必要条件和充分条件。在人类中，T2信号增加， T2加权脑MRI是神经胶质增生的放射学标记。MBH中T2信号的增加与肥胖有关， 胰岛素抵抗和内脏脂肪组织（VAT）增加，与体重指数（BMI）无关。增值税，脂肪 周围的腹腔内实体器官，产生更多的促炎细胞因子比皮下脂肪， 与代谢性疾病的风险增加有关。我们和其他人已经表明， 增值税增加和妊娠代谢疾病。因此，根据啮齿动物文献和非啮齿动物中的发现， 怀孕的人，似乎合理的MBH胶质细胞增生可能与病理性GWG或影响 怀孕期间优先缴纳增值税。R21提案的基础数据将提供第一个 关于神经机制的信息潜在的失调或病理性体重增加在怀孕。