Effects of severe obesity and sleeve gastrectomy on cortical thickness in adolescents

Abstract

Objective: Neurocognitive differences in pediatric obesity may be underpinned by cortical structural alterations. Differences in cortical thickness associated with severe obesity were examined, and preliminary evidence was sought for changes following vertical sleeve gastrectomy (VSG).Methods: A total of 18 adolescents with severe obesity (OB) and 17 without obesity (nOB), aged 14 to 21, underwent T1-weighted structural magnetic resonance imaging.A subset was scanned twice 5 months apart to compare cortical thickness following VSG (n = 6) with two control groups: wait-listed (n = 9) and nOB (n = 12).Results: At baseline, OB had a thinner cortex than nOB in motor and superior parietal cortices. At follow-up, VSG adolescents lost weight, the wait-listed group gained weight, and nOB did not change. Group × Time interactions indicated that VSG had cortical thinning in orbitofrontal, primary sensorimotor, superior, and middle temporal cortices and thickening in lingual, fusiform, and lateral occipital cortices. Wait-listed and nOB groups largely did not change. Conclusions:Severe obesity is associated with a thinner cortex in motor and attentional function-associated regions. VSG resulted in cortical thinning in reward valuation, sensory, and perceptual regions and thickening in visual regions. Surgery-related changes in regions distinct from those associated with obesity suggest compensation, rather than normalization. These results provide preliminary evidence supporting structural neural alterations following sleeve gastrectomy.

A Brain-Penetrant Stearoyl-CoA Desaturase Inhibitor Reverses α-Synuclein Toxicity

“…While the culturing of primary rodent and iPSC-derived neurons in two-dimensional monolayers is a common approach to study neuronal biology in vitro, the use of three-dimensional (3D) neurosphere models to more accurately reflect the microenvironment of the brain has gained traction as a discovery model [ 32 ]. We have recently developed a protocol for generating high-quality, reproducible 3D cortical neurosphere cultures [ 33 ]. Two PD patient-derived iPSC lines harboring either the A53T mutation or gene triplication (S3) in the SNCA gene were used to evaluate the effect of SCD inhibition by YTX-7739 on multiple disease-relevant phenotypes (Fig.…”

“…In addition to aberrant fatty acid desaturation, A53T and S3 neurospheres accumulated total αSyn and pS129 αSyn levels as compared to their respective isogenic control neurospheres [ 33 ]. The abnormal accumulation of total and pS129 αSyn is a pathological hallmark observed in PD patient cells and several in vitro and in vivo model systems of PD [ 20 ].…”

“…The disease-causing A53T mutation or SNCA triplication was corrected in house using the CRISPR-Cas9 system to generate isogenic control pairs. Details of the mutation correction for these lines is described [ 33 ]. Multiple clones were evaluated and confirmed to have a normal karyotype.…”

Triangulating Causality Between Childhood Obesity and Neurobehavior: Twin and Longitudinal Evidence

“…Regarding brain morphology, associations between childhood obesity and cortical thickness have been found in diverse brain regions. Many studies have reported association to areas within the frontal lobe [9][10][11][12][13][14] . Yet, other brain regions may also play a role 15 .…”

“…Cortical surface area predicted subsequent BMI changes during adolescence (41). An experimental study observing brain morphology changes following bariatric surgery found an effect of childhood obesity on cortical thickness (12). Genetically informed analyses revealed directional effects from polygenic scores for BMI to ADHD, heavy smoking (42), and overeating (43), as well as cortical volume (44).…”