| Part 1 Different influences of MC4R rs12970134 polymorphism on resting-state networks and gray matter volume within obese and normal weight groupsObjective:This study explored the different influences of obesity-related MC4R rs 12970134 polymorphism on the resting-state networks (RSNs) and gray matter volume (GMV) within obese and normal weight groups.Materials and Methods:A total of 70 healthy obese (n=36) and normal weight (n=34) Chinese Han individuals were recruited. Genomic DNA of all the participants was extracted from the whole blood. Genotyping of MC4R rs 12970134 was performed using the PCR (polymerase chain reaction) method. Data of resting-state fMRI and high-resolution structural imaging were acquired using a Philips Achieva TX 3.0T magnetic resonance scanner. Group ICA (independent component analysis) was performed using GIFT running on Matlab R2011b. Five networks including default-mode network (DMN; anterior, posterior), salience network (SN), basal ganglia network (BGN) and executive control network (ECN) were chosen. The processing steps of high-resolution structural imaging including segmentation, spatial normalization and smooth were performed using VBM within SPM8. The differences of functional connectivity (FC) and GMV within 5 RSNs between the obese and normal weight groups were investigated. Furthermore, we explored the differences of FC and GMV within 5 RSNs between the MC4R rs 12970134 A-allele carriers and the GG genotypes separately in the obese and normal weight groups, using the statistical analysis within SPM8.Results:The significantly different distribution of frequencies of MC4R rs12970134 A and G alleles in obese and normal weight groups demonstrated that MC4R rs12970134 was associated with obesity. A total of 62 obese (n=32) and normal weight (n=30) participants were with qualified resting-state fMRI data. ① In comparison with normal weight group, the obese group showed significantly decreased FCs in local regions of pDMN, ECN and BGN, while significantly increased FCs in the left insula of SN. Moreover, compared to the MC4R rs 12970134 GG genotype, the A-allele carriers in the obese group showed significantly increased FCs in the right PCC of the pDMN. However, the A-allele carriers in the normal weight group showed significantly increased FCs in the left medial prefrontal cortex (PFC) of the aDMN and the lateral PFC of the ECN, but decreased FCs in the right caudate head of the BGN. The FCs of those regions were significantly associated with waist circumference. ② The obese group showed increased GMV in the bilateral putamen, but decreased GMV in the left PFC in comparison with the normal weight group. The ROI (region of interest) method based on five RSNs showed significantly increased GMV in the bilateral putamen of the BGN. Compared to the MC4R rs 12970134 GG genotype, the A-allele carriers showed decreased GMV in the left medial PFC (within the obese group) and right ventromedial PFC (within the normal weight group) of the ECN.Conclusion:The obese individuals had alterations of FCs in the RSNs and global GMV in comparison with normal weight individuals. The obesity-related MC4R rs 12970134 A-allele affected the aDMN, BGN and ECN within the normal weight group and pDMN within the obese group to play a part in the development of central obesity. MC4R rs12970134 risk A-allele might affect the GMV in the PFC of the ECN. pDMN, ECN and BGN, while significantly increased FCs in the left insula of SN. Moreover, compared to the MC4R rs 12970134 GG genotype, the A-allele carriers in the obese group showed significantly increased FCs in the right PCC of the pDMN. However, the A-allele carriers in the normal weight group showed significantly increased FCs in the left medial prefrontal cortex (PFC) of the aDMN and the lateral PFC of the ECN, but decreased FCs in the right caudate head of the BGN. The FCs of those regions were significantly associated with waist circumference. ② The obese group showed increased GMV in the bilateral putamen, but decreased GMV in the left PFC in comparison with the normal weight group. The ROI (region of interest) method based on five RSNs showed significantly increased GMV in the bilateral putamen of the BGN. Compared to the MC4R rs 12970134 GG genotype, the A-allele carriers showed decreased GMV in the left medial PFC (within the obese group) and right ventromedial PFC (within the normal weight group) of the ECN.Conclusion:The obese individuals had alterations of FCs in the RSNs and global GMV in comparison with normal weight individuals. The obesity-related MC4R rs 12970134 A-allele affected the aDMN, BGN and ECN within the normal weight group and pDMN within the obese group to play a part in the development of central obesity. MC4R rs12970134 risk A-allele might affect the GMV in the PFC of the ECN.Part 2 BMI-related structural alterations of brain white matterObjective:This study explored the underlying physiological mechanisms of the structural differences in white matter (WM) associated with obesity in Chinese Han adults.Materials and Methods:A total of 49 healthy obese or overweight (OO, n=22) and normal weight (NW, n=27) Chinese Han individuals were recruited. After a 12-h overnight fast, the participants underwent blood tests to measure their glucose, triglyceride, HDL, LDL, and total cholesterol levels. Demographic and physiological data were analyzed using the Statistical Package for the Social Sciences (SPSS) version 13.0 for Windows. P<0.05 was considered statistically significant. Data of high-resolution structural imaging and diffusion tensor imaging (DTI) were acquired using a Philips Achieva TX 3.0T magnetic resonance scanner. The processing steps of high-resolution structural imaging were performed using VBM within SPM8 based on Matlab R2011b. The difference of the WM volume of whole brain was investigated between the two groups. The data of DTI were analyzed by the method of TBSS (tract-based spatial statistics analysis). The analysis of skeletonized FA (fractional anisotropy) data was performed using a permutation-based inference tool for nonparametric statistics. Partial correlation analysis was performed between the physiological data obtained and the abnormal microstructural alterations.Results:No significant differences were observed between the NW and 00 groups in terms of age, gender. Participants from the 00 group had significantly higher triglyceride levels, total cholesterol levels, and LDL levels than those from the NW group. Male and female participants did not differ in terms of BMI, waist circumference, fasting glucose, total cholesterol levels, or plasma HDL levels. However, male participants exhibited significantly higher triglyceride and LDL levels. The 00 group exhibited significantly smaller volume of WM in the bilateral basal ganglia, the right amygdala, and the left insula (P<0.05, FDR corrected). The 00 group exhibited lower FA in bilateral frontal corticospinal tracts and the right brainstem. FA values of those three clusters were observed significantly negative correlated with waist circumference as well as BMI. High plasma LDL levels were correlated with low FA values in the right frontal corticospinal tract. Interestingly, the negative correlation was limited to male participants.Conclusion:Obesity-related atrophy of WM volume was observed predominantly in food reward circuit, while BMI-related microstructural alterations of WM were observed predominantly in bilateral frontal corticospinal tracts and the right brainstem. Further, early elevated plasma LDL might contribute to low right frontal FA values of male adults. |
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