Dataset Information

Radiologic evidence that hypothalamic gliosis is associated with obesity and insulin resistance in humans.

ABSTRACT:

Objective

To use quantitative magnetic resonance imaging (MRI) to test whether mediobasal hypothalamic (MBH) gliosis is associated with obesity and insulin resistance in humans.

Methods

Sixty-seven participants underwent a fasting blood draw and MRI. Cases with radiologic evidence of MBH gliosis (N = 22) were identified as the upper tertile of left MBH T2 relaxation time and were compared to controls (N = 23) from the lowest tertile. In a separate postmortem study, brain slices (N = 10) through the MBH were imaged by MRI and stained for glial fibrillary acidic protein (GFAP).

Results

In all participants, longer T2 relaxation time in the left MBH was associated with higher BMI (P = 0.01). Compared with controls, cases had longer T2 relaxation times in the right MBH (P < 0.05), as well as higher BMI (P < 0.05), fasting insulin concentrations (P < 0.01), and HOMA-IR values (P < 0.01), adjusted for sex and age. Elevations in insulin and HOMA-IR were also independent of BMI. In the postmortem study, GFAP staining intensity was positively associated with MBH T2 relaxation time (P < 0.05), validating an MRI-based method for the detection of MBH gliosis in humans.

Conclusions

These findings link hypothalamic gliosis to insulin resistance in humans and suggest that the link is independent of the level of adiposity.

SUBMITTER: Schur EA

PROVIDER: S-EPMC4634110 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Publications

Radiologic evidence that hypothalamic gliosis is associated with obesity and insulin resistance in humans.

Schur Ellen A EA Melhorn Susan J SJ Oh Seok-Kyun SK Lacy J Matthew JM Berkseth Kathryn E KE Guyenet Stephan J SJ Sonnen Joshua A JA Tyagi Vidhi V Rosalynn Mary M De Leon B B Webb Mary F MF Gonsalves Zenobia T ZT Fligner Corinne L CL Schwartz Michael W MW Maravilla Kenneth R KR

Obesity (Silver Spring, Md.) 20151101 11

<h4>Objective</h4>To use quantitative magnetic resonance imaging (MRI) to test whether mediobasal hypothalamic (MBH) gliosis is associated with obesity and insulin resistance in humans.<h4>Methods</h4>Sixty-seven participants underwent a fasting blood draw and MRI. Cases with radiologic evidence of MBH gliosis (N = 22) were identified as the upper tertile of left MBH T2 relaxation time and were compared to controls (N = 23) from the lowest tertile. In a separate postmortem study, brain slices (N ...[more]

PMID: 26530930

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Project description:BackgroundHypothalamic 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.MethodsUsing brain MRI images from Framingham Heart Study participants (N=867; mean age, 55 years; 55% females), T2 signal intensities were extracted bilaterally from the region of interest in the mediobasal hypothalamus (MBH) and reference regions in the amygdala (AMY) and putamen (PUT). T2 signal ratios were created in which greater relative T2 signal intensity suggests gliosis. The primary measure compared MBH to AMY (MBH/AMY); a positive control ratio (MBH/PUT) also assessed MBH whereas a negative control (PUT/AMY) did not. Outcomes were BMI, HDL-C, LDL-C, fasting triglycerides, and the presence of hypertension (n=449), diabetes mellitus (n=66), metabolic syndrome (n=254), or coronary heart disease (n=25). Dietary risk factors for gliosis were assessed in a prospective analysis. Statistical testing was performed using linear or logistic regression.ResultsGreater MBH/AMY T2 signal ratios were associated with higher BMI (β = 21.5 [95% CI, 15.4-27.6]; P<0.001), higher fasting triglycerides (β = 1.1 [95% CI, 0.6-1.7]; P<0.001), lower HDL-C (β = -20.8 [95% CI, -40.0 to -1.6]; P=0.034), and presence of hypertension (odds ratio, 1.2 [95% CI, 1.1-1.4]; P=0.0088), and the latter two were independent of BMI. Findings for diabetes mellitus were mixed and attenuated by adjusting for BMI. Metabolic syndrome was associated with MBH/AMY T2 signal ratios (odds ratio, 1.3 [95% CI, 1.1-1.6]; P<0.001). Model results were almost uniformly confirmed by the positive control ratios, whereas negative control ratios that did not test the MBH were unrelated to any outcomes (all P≥0.05). T2 signal ratios were not associated with prevalent coronary heart disease (all P>0.05), but confidence intervals were wide. Self-reported percentages of macronutrient intake were not consistently related to future T2 signal ratios.ConclusionsUsing a well-established study of cardiovascular disease development, we found evidence linking hypothalamic gliosis to multiple cardiovascular disease risk factors, even independent of adiposity. Our results highlight the need to consider neurologic mechanisms to understand and improve cardiometabolic health.

Dataset Information

Radiologic evidence that hypothalamic gliosis is associated with obesity and insulin resistance in humans.

Objective

Methods

Results

Conclusions

Publications

Radiologic evidence that hypothalamic gliosis is associated with obesity and insulin resistance in humans.

Similar Datasets

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