Two human brain systems micro-structurally associated with obesity

Kitzbichler, Manfred G., Martins, Daniel, Bethlehem, Richard Al, Dear, Richard, Romero-Garcia, Rafael, Warrier, Varun, Seidlitz, Jakob, Dipasquale, Ottavia, Turkheimer, Frederico, Cercignani, Mara ORCID: https://orcid.org/0000-0002-4550-2456, Bullmore, Edward T. and Harrison, Neil A. ORCID: https://orcid.org/0000-0002-9584-3769 2023. Two human brain systems micro-structurally associated with obesity. eLife 12 , e85175. 10.7554/eLife.85175

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Abstract

The relationship between obesity and brain structure is incompletely understood. Using diffusion-weighted MRI from ∼30,000 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-temporal-striatal 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 × 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Psychology Cardiff University Brain Research Imaging Centre (CUBRIC)
Publisher:	eLife Sciences Publications
ISSN:	2050-084X
Funders:	Wellcome Trust
Date of First Compliant Deposit:	18 October 2023
Date of Acceptance:	10 October 2023
Last Modified:	19 Dec 2023 15:36
URI:	https://orca.cardiff.ac.uk/id/eprint/163101

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