A blood-based lipid profile associated with hippocampal volume and brain resting state activation observed in obese adults from the UK Biobank

Abstract

Abstract Background/Objectives Obesity is associated with functional and structural brain alterations. Less is known about the mechanisms behind such associations. This study investigates whether hippocampus volume and resting state function are associated with a dyslipidemia profile based on high-density lipoprotein, low-density lipoprotein, and triglyceride levels within obese and non-obese adults. A whole-brain analysis was also conducted to examine the effect of dyslipidemia on resting state function across the brain. Subjects/Methods A total of 554 UK Biobank participants comprised three groups based on body mass index (BMI) rankings: adults with obesity with a higher ranked BMI (OHigh, n=185, ), a second obese group with a lower ranked BMI (OLow, n=182, ), and non-obese controls (n=187). T1-weighted magnetic resonance imaging (MRI) and functional MRI (fMRI) data were accessed. The fMRI data were reconstructed as the fractional amplitude of low-frequency fluctuations (fALFF) maps to reflect resting-state brain activity. A lipid health score was created using principal component analysis. Linear models tested for associations between the lipid health score and hippocampal volume/fALFF, accounting for age, sex, hemoglobin A1c, total grey matter, and white matter volume. Results With a higher lipid health factor corresponding to a lower dyslipidemia risk, we observed a positive correlation between hippocampal volume with the lipid health factor exclusively in group OLow (P=0.01). Meanwhile, we found a positive association between the lipid health factor and hippocampal fALFF in group OHigh (P=0.02). Additional whole brain voxel-wise analysis to group OHigh also implicated the premotor cortex, amygdala, thalamus, subcallosal cortex, temporal fusiform cortex, and middle temporal gyrus brain regions. Conclusion This study examined three distinct and well-matched groups and highlighted associations between lipids and regional brain volume/resting state function with a primary focus on the hippocampus. These findings support the obesity and brain literature with novel findings regarding the sub-group anthropomorphic differences.