Two human brain systems micro-structurally associated with obesity
- University of Cambridge, United Kingdom
- King's College London, United Kingdom
- University of Pennsylvania, United States
- Cardiff University, United Kingdom
Abstract
The relationship between obesity and human brain structure is incompletely understood. Using diffusion-weighted MRI from í30,000 UK Biobank participants we test the hypothesis that obesity (waist-to-hip ratio, WHR) is associated with regional differences in two micro-structural MRI metrics: isotropic volume fraction (ISOVF), an index of free water, and intra-cellular volume fraction (ICVF), an index of neurite density. We observed significant associations with obesity in two coupled but distinct brain systems: a prefrontal-temporalstriatal system associated with ISOVF and a medial temporal-occipital-striatal system associated with ICVF. The ISOVF~WHR system colocated with expression of genes enriched for innate immune functions, decreased glial density, and high mu opioid (MOR) and other neurotransmitter receptor density. Conversely, the ICVF~WHR system co-located with expression of genes enriched for G-protein coupled receptors and decreased density of MOR and other receptors. To test whether these distinct brain phenotypes might differ in terms of their underlying shared genetics or relationship to maps of the inflammatory marker C-reactive Protein (CRP), we estimated the genetic correlations between WHR and ISOVF (rg = 0:026, P = 0:36) and ICVF (rg = 0:112, P < 9 x 10*4) as well as comparing correlations between WHR maps and equivalent CRP maps for ISOVF and ICVF (p<0.05). These correlational results are consistent with a two-way mechanistic model whereby genetically determined differences in neurite density in the medial temporal system may contribute to obesity, whereas water content in the prefrontal system could reflect a consequence of obesity mediated by innate immune system activation.
Data availability
Data were provided by the UK Biobank (application IDs 20904 & 48943).Source code can be found on GitHub under https://github.com/ucam-department-of-psychiatry/UKB
Article and author information
Author details
Manfred G Kitzbichler
Richard AI Bethlehem
Funding
Wellcome Trust (104025/Z/14/Z)
- Manfred G Kitzbichler
- Federico Turkheimer
- Mara Cercignani
- Neil A Harrison
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Susie Y Huang, Massachusetts General Hospital, United States
Version history
- Received: November 26, 2022
- Preprint posted: November 27, 2022 (view preprint)
- Accepted: October 5, 2023
- Accepted Manuscript published: October 20, 2023 (version 1)
- Version of Record published: November 30, 2023 (version 2)
Copyright
© 2023, Kitzbichler et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Two human brain systems micro-structurally associated with obesity
eLife 12:e85175.
https://doi.org/10.7554/eLife.85175
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