ESPE Abstracts

Early puberty is associated with obesity in young girls and has physical, psychosocial, and reproductive implications. In adults and children, MRI evidence of cellular inflammation in the mediobasal hypothalamus (MBH gliosis) is seen in obesity, and its anatomic location overlaps with key neuronal populations controlling reproduction, fertility, and feeding. We sought to assess whether MRI evidence of MBH gliosis associates with pubertal development in girls and if that differs based on weight status. This retrospective cohort study included a subsample of 156 female participants from the NIH Adolescent Brain Cognitive Development (ABCD) study, a longitudinal, observational study. Self-reported pubertal developmental scale (PDS) at baseline and at 1y was used to classify subjects into one of 4 groups of change in puberty: Using a validated technique, baseline T2-weighted MRI scans were analyzed for evidence of MBH gliosis based on a signal ratio comparing the T2 signal intensity of the mean bilateral MBH to the Amygdala (MBH/AMY). Putamen (PUT)/AMY and MBH/PUT were used as negative and positive control ratios, respectively. Linear mixed models were adjusted for study site and tested for the interaction between T2 signal ratios, change in puberty stages and weight group.At baseline, mean age was 10±0.6y, and participants were well distributed across the 3 weight groups [healthy weight (HW) n = 51, overweight n = 52, and with obesity n = 53]. Subjects with obesity had a significant interaction between T2 signal ratios and change in puberty stages (chi²(6,53)=19.4; P = 0.004). This association was not seen among girls of HW (P = 0.37) and overweight (P = 0.25). Participants with obesity in the earlier stages of puberty presented greater MBH/AMY signal ratio than girls at mid and late stages of puberty (group 1 vs. group 3 and group 4 P < 0.05). Results were confirmed with the positive control ratio and absent with PUT/AMY signal ratio. Our data suggests that girls with obesity present greater MRI evidence of MBH gliosis at early vs. later stages of puberty. MBH gliosis may contribute to the link between childhood obesity and disturbances in initial stages of pubertal development. Due to its long-term ramifications for reproductive health, further studies are needed to understand the neurobiological mechanisms that regulate puberty onset and progression in girls with obesity.