1269-P: A Prospective, Population-Based Study of Hypothalamic Gliosis, Obesity, and Weight Gain in Children

• Published in: Diabetes (New York, N.Y.) Vol. 69; no. Supplement_1
• Main Authors: SEWAYBRICKER, LETICIA E., MELHORN, SUSAN J., SCHUR, ELLEN
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 01-06-2020
• Subjects: Adipose tissue; Amygdala; Body weight; Children; Cognitive ability; Diabetes; Gliosis; Hypothalamus; Inflammation; Magnetic resonance imaging; Metabolism; Obesity; Overweight; Pediatrics; Population studies; Putamen; Teenagers
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db20-1269-P

Hypothalamic gliosis is a cellular response that, in rodents, is necessary for weight gain and diet-induced obesity. Whether this inflammatory process in the mediobasal hypothalamus (MBH) plays a role in common obesity or change in weight status during growth and development in children is uncertain. Using T2-weighted MRI scans from a longitudinal population-based sample of young children, we measured signal ratios to evaluate evidence of MBH gliosis in relation to obesity and adiposity change over time. We included 169 children from 6 sites recruited as part of the NIH Adolescent Brain Cognitive Development (ABCD) study. Baseline T2-weighted MRI scans were analyzed for evidence of MBH gliosis based on the T2 intensity of the mean bilateral MBH/Amygdala signal ratio. Putamen/Amygdala was used as the control ratio. Models were adjusted for site, age, and sex. At baseline, mean age was 9.9 ± 0.6 y, 50% were female, and 64% were pre-pubertal. Mean BMI z-score was 0.77 ± 1.02 [23% with overweight (OV) and 21% with obesity (OB)]. At 1y assessments (10.8 mo. on average), mean ΔBMI z-score was 0.02 ± 0.36. MBH/Amygdala ratio was positively associated with BMI z-score (r=0.32, P<0.001) and waist/height ratio (r=0.26, P<0.001), a marker of metabolic risk, whereas the control ratio was not (r=-0.02, P=0.52 and r=-0.05, P=0.76). Overall, MBH/Amygdala ratio was not associated with ΔBMI z-score (r=-0.02, P=0.49), but a significant interaction [F(5,158)=5.16; P<0.001] indicated the relationship varied by group. Among children with OV, baseline MBH/Amygdala ratio positively correlated with ΔBMI z-score (r=0.43, P=0.01); this relationship was attenuated in children with OB (r=0.19, P=0.18) and absent among participants of normal weight (r=-0.07, P=0.36).
In conclusion, we found evidence that MBH gliosis is associated with excess adiposity in a large pediatric population. In children at risk for obesity, MBH gliosis may be an important predictor of increasing adiposity and metabolic risk.
Disclosure
L.E. Sewaybricker: None. S.J. Melhorn: None. E. Schur: None.
Funding
National Institutes of Health (R01DK117623, U01DA041022, U01DA041028, U01DA041048, U01DA041089, U01DA041106, U01DA041117, U01DA041120, U01DA041134, U01DA041148, U01DA041156, U01DA041174, U24DA041123, U24DA041147, U01DA041093, U01DA041025)