BACKGROUND: 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. METHODS AND RESULTS: 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 ( CONCLUSIONS: 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.