Metabolic health specific functional connectivity signatures in the human brain

Obesity and metabolic dysfunction are among the strongest risk factors for poor brain and mental health, yet the neural mechanisms linking metabolism, brain, and behaviour remains poorly understood. Here, we provide the first evidence for two distinct large-scale brain network configurations--one associated with metabolic health and another with obesity-- identified using resting-state fMRI data and metabolic phenotypes from a large community cohort (N = 564). While obesity was linked to enhanced coupling between subcortical reward and higher-order cortical networks, metabolic health was characterized by functional integration among default mode, salience, and frontoparietal control regions (metabolic health functional connectivity; MHFC). The MHFC network mediated the relationship between eating restraint and metabolic health, independent on individuals body weight and metabolic status, and it was replicated with data from a different time point. Longitudinal analysis showed that change of MHFC strength predicted metabolic indicators over time, suggesting a role for this network as a potential marker of metabolic resilience. These findings reveal a neurobiological pathway through which executive and interoceptive regulatory systems contribute to metabolic health, offering new insights into the brain mechanisms linking eating behaviour, metabolism, and brain function.