Research ReportObesity-mediated inflammation may damage the brain circuit that regulates food intake

Adiposity is associated with chronic low-grade systemic inflammation and increased inflammation in the hypothalamus, a key structure in feeding behavior. It remains unknown whether inflammation impacts other brain structures that regulate feeding behavior. We studied 44 overweight/obese and 19 lean individuals with MRI and plasma fibrinogen levels (marker of inflammation). We performed MRI-based segmentations of the medial and lateral orbitofrontal cortex (OFC) and hippocampal volumes. Gray matter (GM) volumes were adjusted for head size variability. We conducted logistic and hierarchical regressions to assess the association between fibrinogen levels and brain volumetric data. Using diffusion tensor imaging (DTI), we created apparent diffusion coefficient (ADC) maps and conducted voxelwise correlational analyses. Fibrinogen concentrations were higher among the overweight/obese (t[61] =−2.33, P = 0.023). Lateral OFC associated together with fibrinogen correctly classified those with excess of weight (accuracy = 76.2%, sensitivity = 95.5%, and specificity = 31.6%). The lateral OFC volumes of overweight/obese were negatively associated with fibrinogen (r =−0.37, P = 0.016) and after accounting for age, hypertension, waist/hip ratio and lipid and sugar levels, fibrinogen significantly explained an additional 9% of the variance in the lateral OFC volume (β =−0.348, ΔR2 = 0.093, ΔF P = 0.046). Among overweight/obese the associations between GM ADC and fibrinogen were significantly positive (P < 0.001) in the left and right amygdala and the right parietal region. Among lean individuals these associations were negative and located in the left prefrontal, the right parietal and the left occipital lobes. This is the first study to report that adiposity-related inflammation may reduce the integrity of some of the brain structures involved in reward and feeding behaviors.

Research Highlights►Smaller orbitofrontal cortex and higher fibrinogen levels separate the obese from the lean. ►Increased fibrinogen is associated with decreased orbitofrontal cortex volumes. ►Increased fibrinogen is associated with increased water diffusion in the amygdala. ►Inflammation by affecting these two areas may impact feeding and reward systems.