Current Projects

Genetic determinants of obesity

Within the framework of the CRC Obesity Mechanisms of the University of Leipzig we explore the influence of genetic factors on obesity-related behaviours, such as unhealthy and compulsive eating traits, and their neuronal correlates using high-resolution magnetic resonance imaging (MRI) in a population-based sample - the Health Study of the Leipzig Research Center for Civilization Diseases (LIFE)-cohort. To further increase statistical power, we initiated meta-analyses in the international NeuroCHARGE-consortium. Preliminary results indicate that hypothalamus microstructure predicted variance in body mass index (BMI), and genetic underpinnings of this phenotype would now allow us to characterize possible mechanistic pathways.

Correlation of genetic risk for obesity with body mass index (BMI, black line) in the LIFE-cohort.
Semi-automated segmentation of the human hypothalamus (red) on anatomical 3T-magnetic resonance imaging (MRI).

Eating behaviour

Besides genetic factors, our "obesogenic environment", i.e., abundance of cheap high-caloric food together with low physical activity demands at work and in leisure times, promotes weight gain. Here, the inability to control hedonic eating and avoid unhealthy food refrains from maintaining a normal weight, and intriguingly, recent studies propose that the food that we consume could also change subsequent decision-making. We thus aim to explore the complex interplay between homeostasis-regulating brain centers, cognitive control of impulsivity and reward tendencies, as well as nutrient signalling in determining every-day eating behaviour and obesity.

Dietary impact

Studies in patients undergoing bariatric surgery indicated that food reward evaluation normalized after surgery. Yet, how dietary changes induce plasticity in the human brain that leads to healthier food choices and better cognition remains to be fully understood. In a study evaluating alternative eating habits such as vegetarian and vegan diets, we study the possibility that a plant-based diet, possibly via changes in the metabolism and microbiota composition, changes the neuronal processing of food preference and further psychological measures such as mood and well-being. While clarifying if a potentially both environmentally and economically friendly eating pattern impacts cognitive processes, our study might help to get a better mechanistic understanding of gut-body-brain interactions.

Detrimental consequences of obesity

On the long run, overeating and obesity affect brain structure and function via co-morbidities such as hypertension and type 2 diabetes. Also, excess of inflammatory cytokines and adipokines by adipose tissue is detrimental for the brain. It has been shown that even in the absence of manifest obesity, better metabolic profiles exert protective effects on Alzheimer’s disease (AD) risk and might protect AD-related brain areas. In the LIFE-study, our group revealed that a higher BMI and more so visceral fat is linked with white matter lesions and gray matter reductions in the aging population even after controlling for confounders, and lower grey matter volume for example in prefrontal areas also mediated the negative effect of higher age and higher BMI on memory. We were further able to show that higher BMI is associated with reduced connectivity in the default mode network, a finding that may reflect a predisposition to AD.

Higher BMI is associated with decreased posterior default mode network connectivity. A: Decreased functional connectivity in default mode network component 29 is found in clusters in the posterior cingulate cortex (PCC) and precuneus. Blue color map represents log(P)-values of significant voxels (P < 0.05, FDR corrected, using model 1: main BMI effect correcting for sex). MNI coordinates of peak voxel in component 29 in the PCC is (23, 233, 27). Red color map represents the spatial map of the component. B: Decreased functional connectivity in default mode network component 42 is found in clusters in the precuneus and parietal cortex. Blue color map represents log(p)-val-ues of significant voxels (P < 0.05, FDR corrected, using model 1: main BMI effect correcting for sex). MNI coordinates of peak voxel in the precuneus: (23, 254, 26). Red color map represents the spatial map of the component.

Association of higher waist-to-hip ratio and lower white matter fractional anisotropy adjusted for age, sex, and volume of white matter hyperintensities (p < 0.05, family-wise-error-corrected, n 1⁄4 1251). This figure is layered on a T1-weighted image (coordinates according to MNI152 template). Color bar represents t-value. Abbreviations: L, left; R, right.

Preventive options for healthy aging

In first interventional studies, we and other showed the potential of dietary factors, including caloric restriction, polyphenols and omega-3 fatty acids, for improving cognitive functions and AD-related brain structures in older humans, possibly via improvements in metabolic and inflammatory markers. However, a recent study of our group could not confirm results for supplementary resveratrol, challenging the hypothesis that a single nutrient exerts influence when not tightly controlling further lifestyle-related behaviours. To address this issue more comprehensively, we are now testing if a multi-component lifestyle intervention, compared to clinical routine, exerts synergistic effects on brain structure and cognition in an ongoing long-term multi-center trial.

Study design and outcome measures for testing the effects of supplementary resveratrol on brain structure and function. Healthy elderly subjects were screened for eligibility based on inclusion and exclusion criteria, and 60 participants were randomly assigned to either resveratrol or placebo group. Baseline and follow-up measurements included neuropsychological testing, fasting blood draw (glucose- and lipid-metabolism, inflammatory markers, neurotrophic factors), anthropometric measures (weight, height, waist- and hip-circumference, body fat), as well as multimodal neuroimaging. 27 participants receiving resveratrol and 26 participants receiving placebo completed 26 weeks of pill intake and were included in primary analyses of verbal memory performance. In addition, pattern recognition performance was tested using the ModBent task. Volume and mean diffusivity of hippocampus subfield was assessed using high-resolution MRI at 7 T. Abbreviations: BMI: body mass index, CA: cornu ammonis, CNS: central nervous system, DG: dentate gyrus, DWI: diffusion weighted imaging, MMSE: Mini Mental Status Examination, MP2RAGE: Magnetization-Prepared 2 RApid Gradient Echoes MRI: magnetic resonance imaging, T: Tesla, TSE: turbo spin echo.
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