Microstructure changes of the brain preceded glymphatic function changes in young obesity with and without food addiction

Obesity in young adults has become a public health issue that cannot be ignored. Previous studies have shown that obesity, emotional stress and food addiction can interact with each other. However, the underlying pathophysiological and neurobehavioral mechanisms of them are still unclear. We aimed to assess the concordance between the microstructural alterations of white matter (WM) and the functional alterations in the glymphatic system in the context of obesity, and to investigate the impact of body mass index (BMI), emotional stress on the integrity of WM and the functionality of the brain's lymphatic system among the participants. We applied neurite orientation dispersion and density imaging (NODDI) to monitor the modifications in the architecture of WM structure, and utilized diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) to evaluate the alterations in the functionality of the brain's glymphatic system. Imaging data were collected from 18 young individuals with obesity and food addiction (OFD), 28 young individuals with obesity but no food addiction and 32 young healthy controls (HC). We also explored the relationships among the WM structural alterations, cerebral lymphatic functional changes, BMI, emotional status, sleep quality and cognitive decline in the participants. Compared with HC, the changes in NODDI metrics mainly focused on increased ODIp, ODIs and ODItot in ONFD ( P ​< ​0.05). Compared with HC, the alterations in NODDI metrics mainly reflected in decreased Vic and Viso in OFD ( P ​< ​0.05). In addition, our results showed decreased Vic and Viso in OFD compared with ONFD ( P ​< ​0.05). We also found that the ODIp, ODIs and ODItot were significantly positively correlated with the BMI in the whole participants ( P ​< ​0.05). The partial correlation analysis disclosed a significant negative association between Vic and HAMD ( P ​< ​0.05), and between the Viso and HAMD for all obese patients ( P ​< ​0.05). Finally, our study found no difference among HC, OFD and ONFD in the DTI-ALPS index ( P ​≥ ​0.05). Widespread WM microstructural abnormalities were detected by NODDI in young obese patients, which might precede changes in brain glymphatic system function. Our study offers valuable insights into the degenerative trends observed in young individuals suffering from obesity and enhances our comprehension of the underlying biological mechanisms of WM microstructure alterations in depressed state in young individuals with obesity and food addiction. • Microstructure changes of the white matter precede cerebral glymphatic function changes in young obesity. • Microstructural changes precede cerebral glymphatic function changes in young obese individuals with or without food addiction. • Microstructure abnormalities mainly reflect in neurite loss and neurite disorganization in young obesity with and without food addiction respectively.