Two human brain systems micro-structurally associated with obesity.

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dc.creatorKitzbichler, Manfred G
dc.creatorMartins, Daniel
dc.creatorBethlehem, Richard AI
dc.creatorDear, Richard
dc.creatorRomero-Garcia, Rafael
dc.creatorWarrier, Varun
dc.creatorSeidlitz, Jakob
dc.creatorDipasquale, Ottavia
dc.creatorTurkheimer, Federico
dc.creatorCercignani, Mara
dc.creatorBullmore, Edward T
dc.creatorHarrison, Neil A
dc.date2023-12-04T16:50:30Z
dc.date2023-10-20
dc.date2022-11-26
dc.date2023-12-04T16:50:29Z
dc.date.accessioned2026-08-03T01:46:08Z
dc.descriptionPeer reviewed: True
dc.descriptionThe relationship between obesity and human 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.
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dc.identifier2050-084X
dc.identifier85175
dc.identifierhttps://www.repository.cam.ac.uk/handle/1810/361824
dc.identifier2050-084X
dc.identifier.urihttps://repo.dare.co.zw/handle/123456789/159187
dc.languageen
dc.languageeng
dc.publishereLife
dc.publisherhttps://doi.org/10.7554/elife.85175
dc.subjectBMI
dc.subjectGWAS
dc.subjectNODDI
dc.subjectUK Biobank
dc.subjectWHR
dc.subjecthuman
dc.subjectneuroscience
dc.subjectHumans
dc.subjectBrain
dc.subjectObesity
dc.subjectMagnetic Resonance Imaging
dc.subjectDiffusion Magnetic Resonance Imaging
dc.subjectWater
dc.titleTwo human brain systems micro-structurally associated with obesity.
dc.typeArticle

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