权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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：
Suchitra Chandrasekaran
金额：
$ 44.84万
依托单位：
EMORY UNIVERSITY
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：
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

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