Research led by The Hong Kong Polytechnic University finds that regional fat distribution exerts distinct effects on brain structure, connectivity and cognition, revealing patterns not explained by body mass index (BMI).
Obesity has been associated with structural and functional changes in the brain, including reductions in gray matter, disruptions in white matter and impaired connectivity, which have been associated with cognitive decline.
Previous studies frequently used BMI as the central measure of obesity, a highly generalized metric that cannot capture the biological differences in fat depots. Adipose tissue in different body regions is known to affect metabolic and inflammatory pathways differently, and earlier work has suggested that visceral (around organs in the abdominal cavity) and leg fat contribute unequally to disease risk.
This raises questions about whether fat distribution, rather than overall body size, may provide more precise insights into brain aging and cognitive health.
In the study “Regional adiposity shapes brain and cognition in adults,” published in Nature Mental Health, investigators designed a multimodal analysis to disentangle the influence of fat distribution from general obesity and to assess its associations with brain morphology, connectivity, microstructure and cognition.
Research drew on UK Biobank data, including 23,088 adults with arm, leg and trunk fat percentage data and 18,886 with visceral adiposity measurements. Participants with major physical, neurological or psychiatric diseases were excluded.
Adiposity was measured using dual-energy X-ray absorptiometry, and brain health was characterized with structural MRI, resting-state fMRI and diffusion imaging. Cognitive performance was evaluated with tasks assessing reasoning, executive function, processing speed and memory. Brain age prediction models were applied to estimate system-specific brain age gaps.
Findings showed that arm, leg, trunk and visceral fat were each associated with distinct patterns of cortical and subcortical atrophy, altered functional connectivity and changes in white-matter integrity. Associations clustered within four systems: sensorimotor, limbic, default mode and subcortical–cerebellar–brainstem.
Visceral fat showed the strongest negative associations, including reduced axon density and increased tissue disorganization. Cortical brain age gaps mediated links between visceral adiposity and poorer performance across reasoning, executive function, processing speed, and memory.
Researchers conclude that regional adiposity exerts heterogeneous effects on brain and cognitive aging, independent of BMI. Visceral fat, in particular, appears to play a disproportionate role in neurocognitive risk. Findings suggest that brain health assessments and interventions may need to consider fat distribution, not just overall obesity with BMI, when addressing risks of cognitive decline.
While the authors interpret patterns as evidence that regional adiposity relates to brain and cognitive aging, the reported effects are modest and derived from cross-sectional, residualization-based models. Results are associational and model-sensitive, not causal, making generalizability and mechanistic directionality uncertain.
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More information:
Die Zhang et al, Regional adiposity shapes brain and cognition in adults, Nature Mental Health (2025). DOI: 10.1038/s44220-025-00501-8
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