Circulating progenitor cells are positively associated with cognitive function among overweight/obese children

Abstract

Recent evidence has indicated that overweight/obese children may experience cognitive and immune dysfunction, but the underlying mechanisms responsible for the association between overweight/obesity, immune dysfunction, and cognition have yet to be established. The present study aimed to identify a novel link between obesity-induced immune system dysregulation and cognition in preadolescent children. A total of 27 male children (age: 8-10years) were recruited and separated by body mass index (BMI) into healthy weight (HW: 5th-84.9th percentile, n=16) and overweight/obese (OW: ⩾85th percentile, n=11) groups. Adiposity was assessed using dual energy X-ray absorptiometry (DXA), and aspects of executive function were assessed using the Woodcock-Johnson III Tests of Cognitive Abilities. Monocyte populations (CD14(+)CD16(-), CD14(+)CD16(+)) with and without expression of chemokine receptor type 2 (CCR2), and circulating progenitor cells (CPCs: CD34(+)CD45(dim)), in peripheral blood were quantified by flow cytometry. CPCs were isolated by flow sorting and cultured for 24h for collection of conditioned media (CM) that was applied to SH-SY5Y neuroblastomas to examine the paracrine effects of CPCs on neurogenesis. OW had significantly higher quantities of both populations of monocytes (CD14(+)CD16(-): 57% increase; CD14(+)CD16(+): 95% increase, both p<0.01), monocytes expressing CCR2 (CD14(+)CD16(-)CCR2(+): 66% increase; CD14(+)CD16(+)CCR2(+): 168% increase, both p<0.01), and CPCs (47% increase, p<0.05) than HW. CPCs were positively correlated with abdominal adiposity in OW, and negatively correlated in HW with a significant difference between correlations (p<0.05). CPC content was positively correlated with executive processes in OW, and negatively correlated in HW with a significant difference in the strength of the correlations between groups (p<0.05 for correlation between OW and HW). Finally, CPC-CM from OW trended to increase neuroblast viability in vitro relative to HW (1.79 fold, p=0.07). These novel findings indicate that increased content of CPCs among OW children may play a role in preventing decrements in cognitive function via paracrine mechanisms.

Keywords: Executive function; Hematopoietic stem/progenitor cells; Inflammation; Neurogenesis; Paracrine factor.