Laboratory of Cell Signaling, Department of Internal Medicine, University of Campinas, Campinas, Brazil.
Department of Medicine, Division of General Internal Medicine, University of Washington, Seattle, WA, USA.
Int J Obes (Lond). 2020 Jan;44(1):178-185. doi: 10.1038/s41366-019-0399-8. Epub 2019 Jun 14.
BACKGROUND/OBJECTIVES: Hypothalamic neurons play a major role in the control of body mass. Obese subjects present radiologic signs of gliosis in the hypothalamus, which may reflect the damage or loss of neurons involved in whole-body energy homeostasis. It is currently unknown if hypothalamic gliosis (1) differs between obese nondiabetic (ND) and obese diabetic subjects (T2D) or (2) is modified by extensive body mass reduction via Roux-n-Y gastric bypass (RYGB).
SUBJECTS/METHODS: Fifty-five subjects (all female) including lean controls (CT; n = 13), ND (n = 28), and T2D (n = 14) completed at least one study visit. Subjects underwent anthropometrics and a multi-echo MRI sequence to measure mean bilateral T2 relaxation time in the mediobasal hypothalamus (MBH) and two reference regions (amygdala and putamen). The obese groups underwent RYGB and were re-evaluated 9 months later. Analyses were by linear mixed models.
Analyses of T2 relaxation time at baseline showed a group by region interaction only in the MBH (P < 0.0001). T2D had longer T2 relaxation times compared to either CT or ND groups. To examine the effects of RYGB on hypothalamic gliosis a three-way (group by region by time) mixed effects model adjusted for age was executed. Group by region (P < 0.0001) and region by time (P = 0.0005) interactions were significant. There was a reduction in MBH relaxation time by RYGB, and, although the T2D group still had higher T2 relaxation time overall compared to the ND group, the T2D group had significantly lower T2 relaxation time after surgery and the ND group showed a trend. The degree of reduction in MBH T2 relaxation time by RYGB was unrelated to clinical outcomes.
T2 relaxation times, a marker of hypothalamic gliosis, are higher in obese women with T2D and are reduced by RYGB-induced weight loss.
背景/目的：下丘脑神经元在控制体重方面起着重要作用。肥胖患者的下丘脑存在神经胶质增生的影像学迹象，这可能反映了全身能量平衡相关神经元的损伤或丢失。目前尚不清楚肥胖非糖尿病（ND）和肥胖 2 型糖尿病（T2D）患者之间的下丘脑神经胶质增生是否存在差异（1），或者（2）是否会因 Roux-n-Y 胃旁路手术（RYGB）导致的大量体重减轻而改变。
55 名受试者（均为女性），包括瘦对照组（CT；n=13）、ND（n=28）和 T2D（n=14），至少完成了一次研究访问。受试者接受了人体测量学和多回波 MRI 序列检查，以测量中基底下丘脑（MBH）双侧的平均 T2 弛豫时间和两个参考区域（杏仁核和壳核）。肥胖组接受了 RYGB 手术，并在 9 个月后重新评估。分析采用线性混合模型。
基线时 T2 弛豫时间的分析仅显示 MBH 存在组间-区域间的相互作用（P<0.0001）。与 CT 或 ND 组相比，T2D 的 T2 弛豫时间更长。为了研究 RYGB 对下丘脑神经胶质增生的影响，我们执行了一个调整年龄的三因素（组-区域-时间）混合效应模型。组间-区域（P<0.0001）和区域-时间（P=0.0005）的相互作用具有统计学意义。RYGB 可使 MBH 弛豫时间缩短，尽管 T2D 组的 T2 弛豫时间总体上仍高于 ND 组，但 T2D 组在手术后的 T2 弛豫时间显著降低，而 ND 组则呈下降趋势。RYGB 引起的 MBH T2 弛豫时间的降低程度与临床结果无关。
T2 弛豫时间是下丘脑神经胶质增生的标志物，在患有 T2D 的肥胖女性中更高，并且可以通过 RYGB 诱导的体重减轻而降低。
