Lo Justin, Melhorn Susan J, Kee Sarah, Olerich Kelsey L W, Huang Alyssa, Yeum Dabin, Beiser Alexa, Seshadri Sudha, DeCarli Charles, Schur Ellen A
School of Medicine University of Washington Seattle WA USA.
Department of Medicine University of Washington Seattle WA USA.
J Am Heart Assoc. 2025 May 20;14(10):e039463. doi: 10.1161/JAHA.124.039463. Epub 2025 Apr 16.
Hypothalamic gliosis is mechanistically linked to obesity and insulin resistance in rodent models. We tested cross-sectional associations between radiologic measures of hypothalamic gliosis in humans and clinically relevant cardiovascular disease risk factors, as well as prevalent coronary heart disease.
Using brain magnetic resonance imaging from FHS (Framingham Heart Study) participants (N=867; mean age, 55 years; 55% women), T2-signal intensities were extracted bilaterally from the region of interest in the mediobasal hypothalamus (MBH) and reference regions in the amygdala and putamen. T2-signal ratios were created in which greater relative T2-signal intensity suggests gliosis. The primary measure compared MBH with amygdala (MBH/amygdala). Outcomes were body mass index, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting triglycerides, and the presence of hypertension (n=449), diabetes (n=66), metabolic syndrome (n=254), or coronary heart disease (n=25). Statistical testing was performed using linear or logistic regression. Greater MBH/amygdala T2-signal ratios were associated with higher body mass index (<0.001), higher fasting triglycerides (<0.001), lower high-density lipoprotein cholesterol (=0.034), and presence of hypertension (=0.0088), and the latter 2 were independent of body mass index. Findings for diabetes were mixed, whereas metabolic syndrome was strongly associated with greater MBH/amygdala T2-signal ratios (<0.001). T2-signal ratios were not associated with prevalent coronary heart disease (all >0.05), but CIs were wide.
Using a well-established study of cardiovascular disease development, we found evidence linking hypothalamic gliosis to multiple cardiovascular disease risk factors, independent of adiposity. Our results highlight the need to consider central nervous system mechanisms to understand and improve cardiometabolic health.
在啮齿动物模型中，下丘脑胶质增生在机制上与肥胖和胰岛素抵抗相关。我们测试了人类下丘脑胶质增生的放射学测量值与临床相关心血管疾病危险因素以及冠心病患病率之间的横断面关联。
利用弗雷明汉心脏研究（FHS）参与者的脑磁共振成像（N = 867；平均年龄55岁；55%为女性），从内侧基底下丘脑（MBH）的感兴趣区域以及杏仁核和壳核的参考区域双侧提取T2信号强度。创建T2信号比值，其中相对T2信号强度越高表明胶质增生越严重。主要测量指标是将MBH与杏仁核进行比较（MBH/杏仁核）。观察指标包括体重指数、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、空腹甘油三酯，以及高血压（n = 449）、糖尿病（n = 66）、代谢综合征（n = 254）或冠心病（n = 25）的存在情况。使用线性或逻辑回归进行统计检验。较高的MBH/杏仁核T2信号比值与较高的体重指数（<0.001）、较高的空腹甘油三酯（<0.001）、较低的高密度脂蛋白胆固醇（=0.034）以及高血压的存在（=0.0088）相关，后两者独立于体重指数。糖尿病的结果存在混杂情况，而代谢综合征与较高的MBH/杏仁核T2信号比值密切相关（<0.001）。T2信号比值与冠心病患病率无关（均>0.05），但置信区间较宽。
通过一项关于心血管疾病发展的成熟研究，我们发现了下丘脑胶质增生与多种心血管疾病危险因素相关的证据，且独立于肥胖。我们的结果强调了考虑中枢神经系统机制以理解和改善心脏代谢健康的必要性。
