A twin study of obesity pathogenesis using fMRI

使用功能磁共振成像 (fMRI) 进行肥胖发病机制的双胞胎研究

• 批准号: 10436221
• 负责人: Ellen A Schur
• 金额: $ 71.05万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-20 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10436221
• 关键词: Address; Aftercare; Animal Model; Appetite Regulation; Area; Astrocytes; Basic Science; Behavioral; Biological Process; Biology; Body Weight; Body Weight decreased; Brain; Caloric Restriction; Cicatrix; Clinical; Cohort Studies; Cues; Data; Desire for food; Diet; Dietary Factors; Disease; Energy Metabolism; Food; Functional Magnetic Resonance Imaging; Gastric Bypass; Genetic; Gliosis; Grant; Health; Health Benefit; High Fat Diet; Homeostasis; Hormones; Human; Hypothalamic structure; Individual; Inflammation; Inflammatory; Inflammatory Response; Injury; Insulin Resistance; Intervention; Investigation; Life Style; MRI Scans; Magnetic Resonance Imaging; Measures; Mediating; Microglia; Modeling; Mus; Neuraxis; Neuroglia; Neuronal Injury; Neurons; Nutrient; Nutritional; Obese Mice; Obesity; Operative Surgical Procedures; Outcome; Participant; Pathogenesis; Pathogenicity; Patients; Persons; Phase; Play; Prevention; Process; Public Health; Reducing diet; Regulation; Research; Research Design; Research Personnel; Rest; Risk Factors; Rodent; Role; Science; Scientific Advances and Accomplishments; Severities; Signal Transduction; Specific qualifier value; Structure of nucleus infundibularis hypothalami; Sum; Testing; Time; Tissues; Treatment outcome; Twin Studies; Weight; Weight Gain; Weight maintenance regimen; Work; arm; bariatric surgery; base; cell type; cohort; diet-induced obesity; dietary; effective intervention; epidemiology study; feeding; imaging modality; improved; increased appetite; mouse model; novel; novel strategies; obese person; obesity development; obesity management; obesity risk; obesity treatment; prevent; relating to nervous system; research study; response; success; treatment comparison; weight loss intervention; weight loss program; weight maintenance

ABSTRACT The long-term health benefits of obesity treatment are limited by the weight regain that almost universally follows a weight loss intervention, frustrating patients and clinicians alike. In lay terms, a new, higher “set point” seems to occur after people gain weight, and research shows that processes of energy homeostasis, directed by neurons in the arcuate nucleus of the hypothalamus, vigorously defend the higher level of adiposity for years, promoting weight regain after behavioral weight loss. Bariatric surgery, however, results in weight loss that is more durable over time. These phenomena remain incompletely understood. The current proposal endeavors to address this crucial scientific gap by investigating the brain's role in the persistence of obesity and weight regain after weight loss. Specifically, studies in rodents show that diet-induced weight gain requires an inflammatory and cellular response, known as gliosis, within the arcuate nucleus of the hypothalamus and that this gliosis persists with continued dietary exposure. Importantly, gliosis is detectable in mice and humans by magnetic resonance imaging (MRI). Using MRI, the investigators discovered the first evidence of hypothalamic gliosis in obese humans. The investigators have also shown that hypothalamic gliosis is improved by Roux-en-Y gastric bypass (RYGB) surgery, suggesting that the efficacy and durability of weight loss via bariatric surgery could be partially explained by its ability to reverse gliosis. New findings show that hypothalamic gliosis negatively impacts brain regulation of appetite. Based on such findings, the proposed research investigates novel questions about the possible implications of hypothalamic gliosis for clinical weight management. First, it will determine whether the extent of hypothalamic gliosis present when people with obesity start a behavioral weight loss program is related to their success in treatment or weight regain after treatment. Second, the current proposal also addresses the question of whether gliosis is reduced to a greater extent when weight loss occurs by RYGB than by lifestyle change alone. Finally, this investigation uses a rodent study to test the role of 2 different hypothalamic glial cell types in weight regain after weight loss. In sum, basic science advances have identified hypothalamic cellular responses that facilitate weight gain during times of nutritional abundance, but this biological process is also capable of forming glial scars that are detrimental to neuronal functioning. The current research therefore investigates the implications of hypothalamic gliosis for humans undergoing obesity treatment. Achieving a better understanding of the role of the brain in successful obesity treatment could open new avenues for research, intervention, and prevention to alleviate the health risks of obesity.

摘要 肥胖治疗的长期健康益处受到几乎普遍存在的体重反弹的限制 减肥干预后，沮丧的病人和临床医生一样。通俗地说，一个新的，更高的“设定点” 似乎发生在人们体重增加之后，研究表明，能量稳态的过程， 下丘脑弓状核的神经元，大力捍卫更高水平的肥胖， 年，促进体重反弹后，行为减肥。然而减肥手术会导致体重减轻 随着时间的推移，它更耐用。这些现象仍然不完全清楚。现时的建议 通过研究大脑在肥胖持续性中的作用， 体重减轻后又恢复了。具体来说，对啮齿动物的研究表明，饮食诱导的体重增加需要 下丘脑弓状核内的炎症和细胞反应，称为神经胶质增生， 这种神经胶质增生会随着持续的饮食接触而持续。重要的是，在小鼠和人类中可以检测到神经胶质增生 磁共振成像（MRI）。利用核磁共振成像，研究人员发现了第一个证据， 肥胖人群的下丘脑神经胶质增生研究人员还表明，下丘脑神经胶质增生症是一种 通过Roux-en-Y胃旁路手术（RYGB）改善，表明体重的有效性和持久性 通过减肥手术的损失可以部分解释为它逆转神经胶质增生的能力。新的发现表明， 下丘脑神经胶质增生对食欲的大脑调节产生负面影响。根据这些调查结果， 一项研究调查了下丘脑神经胶质增生对临床体重的可能影响的新问题 管理首先，它将确定下丘脑胶质增生的程度是否存在时，人们与 肥胖者开始一项行为减肥计划与他们治疗成功或体重恢复后有关 治疗其次，目前的建议也解决了神经胶质增生是否减少到更大的问题。 RYGB比单独改变生活方式更能减轻体重。最后，本研究使用了 啮齿动物研究，以测试2种不同的下丘脑胶质细胞类型在体重减轻后体重恢复中的作用。在 总而言之，基础科学进展已经确定了下丘脑细胞反应，促进体重增加， 倍的营养丰富，但这一生物过程也能够形成胶质疤痕， 对神经功能有害。因此，目前的研究调查的影响， 下丘脑神经胶质增生症。更好地了解联合国的作用 成功的肥胖治疗中的大脑可以为研究、干预和预防开辟新的途径， 减轻肥胖的健康风险。