Association of estradiol and visceral fat with structural brain networks and memory performance in adults

Importance Changes in estradiol during aging are associated with increased dementia risk. It remains unclear how estradiol supports cognitive health and whether risk factors, such as midlife obesity, are exacerbated by estrogen loss. Objectives To assess whether visceral adipose tissue (VAT) moderates the association between age and brain network structure and to investigate whether estradiol moderates the association between VAT and brain network structure. Design, Setting, and Participants Cross-sectional study of data from 974 cognitively healthy adults in Germany who participated in the Health Study of the Leipzig Research Centre for Civilization Diseases, a previously described population-based cohort study. Two moderation analyses were performed, including VAT as the moderator variable between age and brain network structure and estradiol as the moderator variable between VAT and brain network structure. The study was conducted from August 1, 2011, to November 23, 2014. Analyses were conducted from August 2017 to September 201

Optical and Geometric Properties of Free Silica Nanoparticles Studied by Small Angle X Ray Scattering

Abstract Elastic small-angle X-ray scattering (SAXS) of free silica (SiO2) nanoparticles is reported (d = 100–180 nm). The particles were prepared by a modified Stöber synthesis in narrow size distributions with controlled surface roughness and functionalization. Angle-resolved small-angle X-ray scattering patterns are shown to be sensitive to these changes in particle properties. It is reported that there is an exponential decrease in scattered X-ray intensity towards larger scattering angles as well as distinct oscillations, which is fully explained by Mie theory. Small-angle X-ray scattering of mesoporous nanoparticles with rough surfaces is compared to that of microporous nanoparticles with smooth surfaces, revealing distinct differences that are rationalized by diffuse scattering from nanoparticle pores in addition to the dominating contribution of Mie scattering. Furthermore, results from small-angle X-ray scattering experiments on functionalized silica nanoparticles are presented, where the incorporation of the dye fluorescein isothiocyanate is found to cause changes in the optical properties of the nanoparticles, as compared to non-functionalized samples. Small, but distinct deviations in particle size derived from electron microscopy and from small-angle X-ray scattering are observed. These are rationalized by particle shrinking occurring in electron microscopy as well as slight changes in optical properties of the nanoparticle samples.</jats:p

Sex differences in the relationship between abdominal fat distribution and structural brain network

Background: Accumulating evidence from neuroimaging studies in obesity suggests an inverse relationship between gray matter volume and abdominal fat accumulation. Abdominal visceral adiposity correlates negatively with verbal memory and attention, and represents a risk factor for dementia. Women seem to be more vulnerable to risk of developing cognitive impairment and dementia in association with abdominal visceral adiposity than with overall adiposity, as measured by BMI. Early patterns of grey matter loss can already be detected during mid-life, a time of substantial changes in body fat distribution, increased visceral fat accumulation, and ovarian-hormone fluctuations in women. So far, we do not know whether sex hormones affect the relationship between visceral abdominal fat accumulation and grey matter structure, in part because large cohort studies simultaneously including brain, abdominal and hormonal data are lacking. To address this issue, therefore, we examined whether sex hormones modulate the relationship between visceral adipose tissue volume (VAT) and structural grey matter (GM) networks. Methods: All analyses were performed in the comprehensively phenotyped adult cohort of the population-based Leipzig Research Center for Civilization Diseases (LIFE) study (N= 975, 474 females, 19-79 years of age). Participants with previous stroke, cancer, major neuropsychiatric pathologies and any current medication affecting the central nervous system were excluded. High-resolution T1-weighted images were assessed at a Siemens Verio 3 Tesla Scanner with a 32-channel head coil with an MPRAGE (ADNI) sequence with 1 mm isotropic voxels, 176 slices, TR=2300 ms, TE=2.98 ms, and inversion time (TI)=900 ms. Gray matter (GM) was preprocessed using FreeSurfer (www.freesurfer.net) and FSL-VBM (fsl.fmrib.ox.ac.uk). For the neuroimaging data-analysis, we applied a linked independent component analysis (FLICA: FMRIB’s Linked Independent Component Analysis) of (a) grey matter volume, (b) cortical thickness and (3) pial surface to identify structural neural networks. For the abdominal MR imaging data analysis, we segmented visceral and subcutaneous adipose tissue using a semi automatic macro in ImageJ. Serum levels for estrogen, progesterone and testosterone were analyzed by liquid chromatography tandem-mass spectrometry (LC-MS/MS) techniques. Results: Inter-rater variability for abdominal adipose tissue segmentation was excellent for both visceral (VAT, ICC= 0.98) and subcutaneous adipose tissue (SCAT, ICC=0.97). VAT was significantly higher in men than women (t(918.71)=12.22, p<0.001, alpha=0.05). The best model predicting VAT from age was a quadratic fit for men (adjusted R2=0.931, p<0.001) a polynomial fit of third degree (adjusted R2=0.851, p<0.001), with an inflection-point at 47 years of age, for women. VAT was significantly negatively associated with a large-scale, age-sensitive grey matter network, previously associated with heightened risk for dementia. Men showed a significantly steeper negative association between VAT and structural grey matter network than women (p<0.0024). Furthermore, estradiol (adjusted R2= 0.05, p<0.002) and progesterone (adjusted R2= 0.12, p<0.001) levels show a positive association with this structural network in women, even when correcting for age. Conclusions: The present data indicate a sex-specific interaction between visceral adipose fat and a structural grey matter network previously linked to cognitive impairment and dementia: While in men this inverse relationship can be consistently displayed throughout all age groups, premenopausal women do not show a significant negative association between visceral abdominal fat and structural grey matter load. Furthermore, our findings provide first evidence for a protective role of ovarian hormones estrogen and progesterone in maintaining the structural grey matter network organization, that, when compromised, has been associated with increased dementia-risk. This evidence supports a perimenopausal vulnerability model for the female brain during midlife, when women, possibly due to the loss of ovarian hormone production, start to experience increased visceral fat accumulation, which represents a risk factor for structural grey matter loss

Associations of <em>GHR, IGF-1</em> and <em>IGFBP-3 </em>expression in adipose tissue cells with obesity-related alterations in corresponding circulating levels and adipose tissue function in children.

Components of the growth hormone (GH) axis, such as insulin-like growth factor-1 (IGF-1), IGF-1 binding protein-3 (IGFBP-3), GH receptor (GHR) and GH-binding protein (GHBP), regulate growth and metabolic pathways. Here, we asked if serum levels of these factors are altered with overweight/obesity and if this is related to adipose tissue (AT) expression and/or increased fat mass. Furthermore, we hypothesized that expression of GHR, IGF-1 and IGFBP-3 is associated with AT function. Serum GHBP levels were increased in children with overweight/obesity throughout childhood, while for IGF-1 levels and the IGF-1/IGFBP-3 molar ratio obesity-related elevations were detectable until early puberty. Circulating levels did not correlate with AT expression of these factors, which was decreased with overweight/obesity. Independent from obesity, expression of GHR, IGF-1 and IGFBP-3 was related to AT dysfunction,and increased insulin levels. Serum GHBP was associated with liver fat percentage and transaminase levels. We conclude that obesity-related elevations in serum GHBP and IGF-1 are unlikely to be caused by increased AT mass and elevations in GHBP are more closely related to liver status in children. The diminished AT expression of these factors with childhood obesity may contribute to early AT dysfunction and a deterioration of the metabolic state

Sex differences in the relationship between abdominal fat distribution and structural brain networks

Background: Accumulating evidence from neuroimaging studies in obesity suggests an inverse relationship between gray matter volume and abdominal fat accumulation. Abdominal visceral adiposity correlates negatively with verbal memory and attention, and represents a risk factor for dementia. Women seem to be more vulnerable to risk of developing cognitive impairment and dementia in association with abdominal visceral adiposity than with overall adiposity, as measured by BMI. Early patterns of grey matter loss can already be detected during mid-life, a time of substantial changes in body fat distribution, increased visceral fat accumulation, and ovarian-hormone fluctuations in women. So far, we do not know whether sex hormones affect the relationship between visceral abdominal fat accumulation and grey matter structure, in part because large cohort studies simultaneously including brain, abdominal and hormonal data are lacking. To address this issue, therefore, we examined whether sex hormones modulate the relationship between visceral adipose tissue volume (VAT) and structural grey matter (GM) networks. Methods: All analyses were performed in the comprehensively phenotyped adult cohort of the population-based Leipzig Research Center for Civilization Diseases (LIFE) study (N= 975, 474 females, 19-79 years of age). Participants with previous stroke, cancer, major neuropsychiatric pathologies and any current medication affecting the central nervous system were excluded. High-resolution T1-weighted images were assessed at a Siemens Verio 3 Tesla Scanner with a 32-channel head coil with an MPRAGE (ADNI) sequence with 1 mm isotropic voxels, 176 slices, TR=2300 ms, TE=2.98 ms, and inversion time (TI)=900 ms. Gray matter (GM) was preprocessed using FreeSurfer (www.freesurfer.net) and FSL-VBM (fsl.fmrib.ox.ac.uk). For the neuroimaging data-analysis, we applied a linked independent component analysis (FLICA: FMRIB’s Linked Independent Component Analysis) of (a) grey matter volume, (b) cortical thickness and (3) pial surface to identify structural neural networks. For the abdominal MR imaging data analysis, we segmented visceral and subcutaneous adipose tissue using a semi automatic macro in ImageJ. Serum levels for estrogen, progesterone and testosterone were analyzed by liquid chromatography tandem-mass spectrometry (LC-MS/MS) techniques. Results: Inter-rater variability for abdominal adipose tissue segmentation was excellent for both visceral (VAT, ICC= 0.98) and subcutaneous adipose tissue (SCAT, ICC=0.97). VAT was significantly higher in men than women (t(918.71)=12.22, p<0.001, alpha=0.05). The best model predicting VAT from age was a quadratic fit for men (adjusted R2=0.931, p<0.001) a polynomial fit of third degree (adjusted R2=0.851, p<0.001), with an inflection-point at 47 years of age, for women. VAT was significantly negatively associated with a large-scale, age-sensitive grey matter network, previously associated with heightened risk for dementia. Men showed a significantly steeper negative association between VAT and structural grey matter network than women (p<0.0024). Furthermore, estradiol (adjusted R2= 0.05, p<0.002) and progesterone (adjusted R2= 0.12, p<0.001) levels show a positive association with this structural network in women, even when correcting for age. Conclusions: The present data indicate a sex-specific interaction between visceral adipose fat and a structural grey matter network previously linked to cognitive impairment and dementia: While in men this inverse relationship can be consistently displayed throughout all age groups, premenopausal women do not show a significant negative association between visceral abdominal fat and structural grey matter load. Furthermore, our findings provide first evidence for a protective role of ovarian hormones estrogen and progesterone in maintaining the structural grey matter network organization, that, when compromised, has been associated with increased dementia-risk. This evidence supports a perimenopausal vulnerability model for the female brain during midlife, when women, possibly due to the loss of ovarian hormone production, start to experience increased visceral fat accumulation, which represents a risk factor for structural grey matter loss

Abdominal fat distribution and its relationship to brain changes: the differential effects of age on cerebellar structure and function: a cross-sectional, exploratory study.

Objectives: To investigate whether the metabolically important visceral adipose tissue (VAT) relates differently to structural and functional brain changes in comparison with body weight measured as body mass index (BMI). Moreover, we aimed to investigate whether these effects change with age. Design: Cross-sectional, exploratory. Setting: University Clinic, Integrative Research and Treatment Centre. Participants: We included 100 (mean BMI=26.0 kg/m², 42 women) out of 202 volunteers randomly invited by the city's registration office, subdivided into two age groups: young-to-mid-age (n=51, 20–45 years of age, mean BMI=24.9, 24 women) versus old (n=49, 65–70 years of age, mean BMI=27.0, 18 women). Main outcome measures: VAT, BMI, subcutaneous abdominal adipose tissue, brain structure (grey matter density), functional brain architecture (eigenvector centrality, EC). Results: We discovered a loss of cerebellar structure with increasing VAT in the younger participants, most significantly in regions involved in motor processing. This negative correlation disappeared in the elderly. Investigating functional brain architecture showed again inverse VAT–cerebellum correlations, whereas now regions involved in cognitive and emotional processing were significant. Although we detected similar results for EC using BMI, significant age interaction for both brain structure and functional architecture was only found using VAT. Conclusions: Visceral adiposity is associated with cerebellar changes of both structure and function, whereas the regions involved contribute to motor, cognitive and emotional processes. Furthermore, these associations seem to be age dependent, with younger adults’ brains being adversely affected