A twin study of obesity pathogenesis using fMRI

摘要 肥胖治疗的长期健康益处受到几乎普遍存在的体重恢复的限制。 在进行减肥干预后，患者和临床医生都感到沮丧。在外行术语中，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，能量动态平衡的过程，定向 通过下丘脑弓状核中的神经元，有力地捍卫较高水平的肥胖 多年来，在行为减肥后促进体重恢复。然而，减肥手术可以减轻体重。 随着时间的推移，这会更耐用。这些现象仍然没有完全被理解。目前的提案 致力于通过研究大脑在肥胖持续中的作用来解决这一关键的科学鸿沟 减肥后体重又会恢复。具体地说，对啮齿动物的研究表明，饮食诱导的体重增加需要 下丘脑弓状核内的一种炎症和细胞反应，称为胶质细胞增多症 这种神经胶质增生症在持续的饮食暴露中持续存在。重要的是，在老鼠和人类身上都可以检测到胶质细胞增多症。 通过磁共振成像(MRI)。使用核磁共振成像，研究人员发现了第一个证据 肥胖人群中的下丘脑胶质细胞增多症。研究人员还表明，下丘脑胶质细胞增多症 经Roux-en-Y胃分流术(RYGB)改善，表明体重的有效性和持久性 减肥手术造成的损失可以部分解释为其逆转胶质细胞增生的能力。新的发现表明， 下丘脑胶质细胞增多症对大脑的食欲调节有负面影响。根据这些调查结果，建议的 研究调查新问题，即下丘脑胶质细胞增多症可能对临床体重的影响 管理层。首先，它将确定当患有高血压的人是否存在下丘脑胶质细胞增多症的程度 肥胖症开始行为减肥计划关系到他们在治疗成功或体重恢复后 治疗。其次，目前的提案还涉及到胶质增多症是否会减少到更大程度的问题 通过RYGB减肥的程度比仅仅通过改变生活方式来减肥的程度要好。最后，该调查使用了 啮齿动物实验，测试2种不同类型的下丘脑神经胶质细胞在体重减轻后恢复体重中的作用。在……里面 综上所述，基础科学的进步已经确定了促进体重增加的下丘脑细胞反应 营养丰富的倍数，但这种生物过程也能够形成胶质疤痕 对神经功能有害。因此，目前的研究调查了 正在接受肥胖治疗的人类的下丘脑胶质细胞增生症。更好地理解 大脑在成功的肥胖治疗中可能为研究、干预和预防开辟新的途径 减轻肥胖带来的健康风险。

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.