Obesity is associated with increased brain glucose uptake and activity but not neuroinflammation (TSPO availability) in monozygotic twin pairs discordant for BMI—Exercise training reverses increased brain activity

Abstract

<h3>Aims</h3><p>Obesity is associated with increased insulin-stimulated brain glucose uptake (BGU) which is opposite to decreased GU observed in peripheral tissues. Increased BGU was shown to be reversed by weight loss and exercise training, but the mechanisms remain unknown. We investigated whether neuroinflammation (TSPO availability) and brain activity drive the obesity-associated increase in BGU and whether this increase is reversed by exercise training.</p><h3>Materials and Methods</h3><p>Twelve monozygotic twin pairs mean age 40.4 (SD) years discordant for BMI (leaner mean 29.1 (SD) 6.3, heavier 36.7 (SD) 7.0 kg·m⁻²) performed 6-month long exercise intervention. Insulin-stimulated BGU during euglycaemic-hyperinsulinaemic clamp, brain inflammation (translocator protein (TSPO) availability) and brain resting state activity were studied by [¹⁸F]FDG-PET, [¹¹C]PK11195-PET, and fMRI, respectively. Cognitive function was assessed by an online survey.</p><h3>Results</h3><p>Exercise training had no effect on insulin-stimulated BGU, brain neuroinflammation (TSPO availability), or BMI. Exercise improved VO_2peak, whole-body insulin sensitivity, and cognitive function similarly in both groups (all, <em>p</em> <0.05) as well as decreased resting state brain activity in heavier co-twins (<em>p</em> <0.05). At baseline, heavier co-twins had worse whole-body insulin sensitivity (<em>p</em> <0.01), increased BGU in the parietal cortex and caudatus, as well as increased resting state brain activity (both, <em>p</em> <0.05) and no difference in cognitive function. Leaner co-twins had higher TSPO availability in white matter and the hippocampus (<em>p</em> <0.05).</p><h3>Conclusions</h3><p>Exercise training had no effect on insulin-stimulated BGU or neuroinflammation (TSPO availability) but it reversed increased resting state brain activity in heavier co-twins. At baseline, obesity was associated with increased insulin-stimulated BGU and resting state brain activity, independent of genetics.</p>