Fat-free body mass but not fat mass is associated with reduced gray matter volume of cortical brain regions implicated in autonomic and homeostatic regulation.

Obesity has been associated with alterations of both functional and structural aspects of the human central nervous system. In obese individuals both fat mass (FM; primarily consisting of adipose tissue) and fat-free mass (FFM; all non-adipose tissues) are increased and it remains unknown whether these compartments have separate effects on human brain morphology. We used voxel-based morphometry to investigate the relationships between measures of body composition and regional gray matter volume (GMV) in 76 healthy adults with a wide range of adiposity (24 F/52 M; age 32.1 ± 8.8 years; percentage of body fat [PFAT%] 25.5 ± 10.9%; BMI 29.8 ± 8.9). Fat-free mass index (FFMI kg × m(-2)) showed negative associations in bilateral temporal regions, the bilateral medial and caudolateral OFC, and the left insula. Fat mass index (FMI kg × m(-2)) showed similar, but less extensive negative associations within temporal cortical regions and the left caudolateral orbitofrontal cortex (OFC). In addition, negative associations were seen for FMI with GMV of the cerebellum. Associations of FFMI with temporal and medial orbitofrontal GMV appeared to be independent of adiposity. No associations were seen between measures of adiposity (i.e. FM and PFAT) and GMV when adjusted for FFM. The majority of regions that we find associated with FFM have been implicated in the regulation of eating behavior and show extensive projections to central autonomic and homeostatic core structures. These data indicate that not adipose tissue or relative adiposity itself, but obesity related increases in absolute tissue mass and particularly FFM may have a more predominant effect on the human brain. This might be explained by the high metabolic demand of FFM and related increases in total energy needs.