Visceral adipose tissue is associated with microstructural brain tissue damage

Widya, Ralph L.; Kroft, Lucia J.M.; Altmann-Schneider, Irmhild; Berg-Huysmans, Annette A. van den; Bijl, Noortje van der; Roos, Albert de; Lamb, Hildo J.; Buchem, Mark A. van; Slagboom, P. Eline; Heemst, Diana van

doi:10.1002/oby.21048

Cited by 29 publications

(31 citation statements)

References 39 publications

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“…42 These latter mechanisms could have contributed to our results, given that visceral obesity is linked to higher circulating IL6 and high-sensitivity CRP, indicating lowgrade systemic inflammation. 9,44 Our study supports these findings and indicates, by means of mediation path analyses, that visceral obesity increases the development of dWMHs through increases in inflammatory activity, indexed by circulating IL6. 9,44 Our study supports these findings and indicates, by means of mediation path analyses, that visceral obesity increases the development of dWMHs through increases in inflammatory activity, indexed by circulating IL6.…”

Section: Underlying Mechanismssupporting

confidence: 82%

“…20,43 Interestingly, studies comparing subcutaneous with visceral adipose tissue not only revealed a higher association with inflammatory markers for visceral adipose tissue, but also correlated specifically central obesity (ie, a higher amount of visceral fat) with microstructural brain damage. 9,44 Our study supports these findings and indicates, by means of mediation path analyses, that visceral obesity increases the development of dWMHs through increases in inflammatory activity, indexed by circulating IL6. For CRP, we observed a similar tendency, which did not reach statistical significance.…”

Section: Underlying Mechanismssupporting

confidence: 82%

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Visceral obesity relates to deep white matter hyperintensities via inflammation

Lampe

Zhang

Beyer

et al. 2019

Annals of Neurology

130

100

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Objective White matter hyperintensities (WMHs) are linked to vascular risk factors and increase the risk of cognitive decline, dementia, and stroke. We here aimed to determine whether obesity contributes to regional WMHs using a whole‐brain approach in a well‐characterized population‐based cohort. Methods Waist‐to‐hip ratio (WHR), body mass index (BMI), systolic/diastolic blood pressure, hypertension, diabetes and smoking status, blood glucose and inflammatory markers, as well as distribution of WMH were assessed in 1,825 participants of the LIFE‐adult study (age, 20–82 years; BMI, 18.4–55.4 kg/m 2 ) using high‐resolution 3‐Tesla magnetic resonance imaging. Voxel‐wise analyses tested if obesity predicts regional probability of WMH. Additionally, mediation effects of high‐sensitive C‐reactive protein and interleukin‐6 (IL6) measured in blood were related to obesity and WMH using linear regression and structural equation models. Results WHR related to higher WMH probability predominantly in the deep white matter, even after adjusting for effects of age, sex, and systolic blood pressure (mean ß = 0.0043 [0.0008 SE], 95% confidence interval, [0.00427, 0.0043]; threshold‐free cluster enhancement, family‐wise error‐corrected p < 0.05). Conversely, higher systolic blood pressure was associated with WMH in periventricular white matter regions. Mediation analyses indicated that both higher WHR and higher BMI contributed to increased deep‐to‐periventricular WMH ratio through elevated IL6. Interpretation Our results indicate an increased WMH burden selectively in the deep white matter in obese subjects with high visceral fat accumulation, independent of common obesity comorbidities such as hypertension. Mediation analyses proposed that visceral obesity contributes to deep white matter lesions through increases in proinflammatory cytokines, suggesting a pathomechanistic link. Longitudinal studies need to confirm this hypothesis. ANN NEUROL 2019;85:194–203.

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Section: Underlying Mechanismssupporting

confidence: 82%

Section: Underlying Mechanismssupporting

confidence: 82%

Visceral obesity relates to deep white matter hyperintensities via inflammation

Lampe

Zhang

Beyer

et al. 2019

Annals of Neurology

130

100

View full text Add to dashboard Cite

show abstract

“…Much of the focus has been on visceral adiposity (Debette et al, 2010; Widya et al, 2015) due to the accompanying metabolic derangements of insulin resistance, hypertension, and pro-inflammatory and pro-thrombotic states. These likely relate to the release of adipokines and inflammatory cytokines, including interleukin-6 and TNFα, and by altered free fatty acid metabolism in the portal circulation.…”

Section: Discussionmentioning

confidence: 99%

Adiposity is inversely associated with hippocampal volume in African Americans and European Americans with diabetes

Hsu

Yuan

Bowden

et al. 2016

Journal of Diabetes and its Complications

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Aims To assess associations between body mass index (BMI), waist circumference (WC), and computed tomography-determined volumes of pericardial, visceral, and subcutaneous adipose tissue with magnetic resonance imaging-(MRI) based cerebral structure and cognitive performance in individuals with type 2 diabetes (T2D). Methods This study was performed in 348 African Americans (AAs) and 256 European Americans (EAs) with T2D. Associations between adiposity measures with cerebral volumes of white matter (WMV), gray matter (GMV), white matter lesions, hippocampal GMV, and hippocampal WMV, cognitive performance and depression were examined using marginal models incorporating generalized estimating equations. All models were adjusted for age, sex, education, smoking, HbA1c, hypertension, statins, cardiovascular disease, MRI scanner (MRI outcomes only), and time between scans; some neuroimaging measures were additionally adjusted for intracranial volume. Results Participants were 59.9% female with mean (SD) age 57.7(9.3) years, diabetes duration 9.6(6.8) years, and HbA1c 7.8(1.9) %. In AAs, inverse associations were detected between hippocampal GMV and both BMI (β [95% CI] −0.18 [−0.30, −0.07], p=0.0018) and WC (−0.23 [−0.35, −0.12], p=0.0001). In the full bi-ethnic sample, inverse associations were detected between hippocampal WMV and WC (p<0.0001). Positive relationships were observed between BMI (p=0.0007) and WC (p<0.0001) with depression in EAs. Conclusions In patients with T2D, adiposity is inversely associated with hippocampal gray and white matter volumes.

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“…A meta-analysis on the role of blood pressure implicates loss of brain tissue in the frontal and temporal lobes (Beauchet et al, 2013;Schneider et al, 2017). Another study reported that it is visceral adipose tissue that appears to be tied to microstructural changes in the brain (Widya et al, 2015). Another study reported that it is visceral adipose tissue that appears to be tied to microstructural changes in the brain (Widya et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…A casecontrol comparison of people with and without metabolic syndrome reported reduced white matter, in addition to gray matter (Sala et al, 2014). Another study reported that it is visceral adipose tissue that appears to be tied to microstructural changes in the brain (Widya et al, 2015). Typically, these MVRFs co-occur in people, requiring precise physiological endpoints and large samples to disentangle their effects.…”

Section: Introductionmentioning

confidence: 99%

Metabolic and vascular risk factors are associated with reduced cerebral blood flow and poorer midlife memory performance

MacIntosh

Shirzadi

Atwi

et al. 2019

Human Brain Mapping

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Midlife metabolic and vascular risk factors (MVRFs) predict cognitive decline and dementia; however, these risk factors tend to overlap, and the mechanisms underlying their effects on cognitive performance are not well understood. This crosssectional study investigates the contributions of MVRFs to regional cerebral blood flow (CBF) and verbal learning & memory among middle-aged adults. We used partial least squares (PLS) analysis to create latent risk factor profiles and examine their associations to CBF in 93 regions of interest among 451 participants (age 50.3 ± 3.5 years) of the Coronary Artery Risk Development in Young Adults. This multivariate analysis revealed regional CBF was lower in relation to obesity (higher body mass index and waist circumference), dysregulated glucose homeostasis (higher fasting glucose, oral glucose tolerance, and higher fasting insulin), and adverse fasting lipid profile (lower high-density lipoprotein cholesterol and higher triglycerides). In a sensitivity analysis, we found that significant associations between MVRFs and CBF were prominent in the hypertension-medicated subgroup. In a mediation model, the PLSbased MVRFs profile was associated with memory performance (rey auditory verbal learning test); however, CBF was not a significant mediator of this association. The Bradley J. MacIntosh and Zahra Shirzadi contributed equally to this work.

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Visceral adipose tissue is associated with microstructural brain tissue damage

Abstract: Our data indicate that increased abdominal VAT rather than SAT is associated with microstructural brain tissue damage in elderly individuals.

Cited by 29 publications

References 39 publications

Visceral obesity relates to deep white matter hyperintensities via inflammation

Visceral obesity relates to deep white matter hyperintensities via inflammation

Adiposity is inversely associated with hippocampal volume in African Americans and European Americans with diabetes

Metabolic and vascular risk factors are associated with reduced cerebral blood flow and poorer midlife memory performance

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