Pediatrics

Visceral fat-related systemic inflammation and the adolescent brain: a mediating role of circulating glycerophosphocholines

Abstract

Objective

Life-long maintenance of brain health is important for the prevention of cognitive impairment in older age. Low-grade peripheral inflammation associated with excess visceral fat (VF) may influence brain structure and function. Here we examined (i) if this type of inflammation is associated with altered white-matter (WM) microstructure and lower cognitive functioning in adolescents, and (ii) if recently identified circulating glycerophosphocholines (GPCs) can index this type of inflammation and associated variations in WM microstructure and cognitive functioning.

Subjects

We studied a community-based sample of 872 adolescents (12–18 years, 48% males) in whom we assessed VF and WM microstructure with magnetic resonance imaging, processing speed with cognitive testing, serum C-reactive protein (CRP, a common marker of peripheral inflammation) with a high-sensitivity assay, and serum levels of a panel of 64 GPCs with advanced mass spectrometry.

Results

VF was associated with CRP, and CRP in turn was associated with “altered” WM microstructure and lower processing speed (all p < 0.003). Further, “altered” WM microstructure was associated with lower processing speed (p < 0.0001). Of all 64 tested GPCs, 4 were associated with both VF and CRP (at Bonferroni corrected p < 0.0004). One of them, PC16:0/2:0, was also associated with WM microstructure (p < 0.0001) and processing speed (p = 0.0003), and mediated the directed associations between VF and both WM microstructure (p < 0.0001) and processing speed (p = 0.02). As a mediator, PC16:0/2:0 explained 21% of shared variance between VF and WM microstructure, and 22% of shared variance between VF and processing speed. Similar associations were observed in an auxiliary study of 80 middle-aged adults.

Conclusions

Our results show that VF-related peripheral inflammation is associated with "altered" WM microstructure and lower cognitive functioning already in adolescents, and a specific circulating GPC may be a new molecule indexing this VF-related peripheral inflammation and its influences on brain structure and function.

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Acknowledgements

We thank the following individuals for their contributions in acquiring data in the SYS: Manon Bernard (database architect, The Hospital for Sick Children), Hélène Simard and her team of research assistants (Cégep de Jonquière), and Jacynthe Tremblay and her team of research nurses (Chicoutimi Hospital). We thank all participants who took part in the Saguenay Youth Study.

Funding

The Saguenay Youth Study has been funded by the Canadian Institutes of Health Research (TP and ZP), Heart and Stroke Foundation of Canada (ZP), and the Canadian Foundation for Innovation (ZP). Dr. Syme is a post-doctoral research fellow funded by the SickKids Research Institute. Dr. Abrahamowicz is a James McGill Professor at McGill University.

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Correspondence to Zdenka Pausova.

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Syme, C., Pelletier, S., Shin, J. et al. Visceral fat-related systemic inflammation and the adolescent brain: a mediating role of circulating glycerophosphocholines. Int J Obes 43, 1223–1230 (2019). https://doi.org/10.1038/s41366-018-0202-2

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