Hypothalamic Gliosis Associated With Obesity in Kids?

Mediobasal hypothalamic gliosis noted on MRI appeared to be associated with adiposity gain in younger kids at risk for obesity, a researcher reported.

In a two-part study of a large, population-based, pediatric observational cohort, a significant interaction between mediobasal hypothalamic/amygdala T2 signal ratio and change in body mass index (BMI) z score varied based on a child's baseline weight status, reported Leticia Sewaybricker, MD, PhD, of the University of Washington in Seattle, during the ObesityWeek virtual meeting.

In part 1, mediobasal hypothalamic/amygdala signal ratio was positively associated with BMI z score (β = 4.27, P<0.001). Part 2 showed that higher mediobasal hypothalamic/amygdala signal ratios were associated with an increase in BMI z score for children with overweight (β = 0.58, P=0.01), but not obesity (β = 0.02, P=0.91), Sewaybricker and team wrote in the journal Obesity, where the study was simultaneously published.

"In our work, we saw that in children at risk for obesity, greater evidence of hypothalamic gliosis at baseline was associated with gain in adiposity over 1 year," Sewaybricker told MedPage Today. "It suggests that hypothalamic gliosis may have an important role in the development of obesity and excessive weight gain in children."

"By having gliosis in the hypothalamus -- a key brain region for the regulation of appetite and body weight -- a tissue or structural abnormality occurs, which can also lead to abnormal function of the hypothalamus," she added.

In the study, the researchers attempted to determine whether hypothalamic gliosis is a cause, rather than a consequence, of obesity in children.

They used imaging data accrued in the Adolescent Brain Cognitive Development Study and conducted cross-sectional and prospective cohort analyses. In part 1, they analyzed T2-weighted MRIs of 169 children with anthropometrics from baseline and 1-year follow-up visits. Signal ratios compared T2 signal intensity in the mediobasal hypothalamus and two reference regions -- the amygdala and putamen -- as a measure of mediobasal hypothalamic gliosis. Part 2, which consisted of 238 children who were overweight or diagnosed with obesity, was used to confirm the initial findings in an independent sample. All children in the study were 9 to 12 years old.

"Our current findings build on previous studies conducted in humans by showing, in the largest pediatric population assessed to date, a positive cross-sectional association between T2 signal in the mediobasal hypothalamus and BMI z score in children, independent of sex, age, and study site," the authors explained. "Control ratios confirmed that the findings were absent in a control region in the putamen and were irrespective of the reference region selected as the comparator. Furthermore, we found significantly elevated mediobasal hypothalamus T2 signal ratios when comparing normal with overweight and obese groups."

Sewaybricker suggested that the use of MRI would remain a tool in trying to further understand the relationship between hypothalamic injury and the development of obesity. "We don't anticipate that in clinical practice, having MRI will be needed or recommended for everybody," she noted. "On the other hand, research studies with imaging techniques can help to better understand what causes hypothalamic gliosis, whether it is negatively impacting the treatment for obesity, and if it is reversible. By answering these questions, there could be a direct impact in clinical practice and on how we prevent and treat childhood obesity."

"In sum, in a large, population-based sample of children, we provide further evidence that hypothalamic gliosis is present in young children with overweight and obesity, as well as the first longitudinal evidence that a greater degree of mediobasal hypothalamic gliosis predicts a subsequent increase in body adiposity among susceptible individuals," the authors wrote.

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