Increased innate immune responses in adolescents with obesity and its relation to subclinical cardiovascular measures: An exploratory study

Siroon Bekkering; Christoph Saner; Boris Novakovic; Toby Mansell; Danielle K Longmore; Zoe McCallum; Anne-Louise Ponsonby; Markus Juonala; Mihai G Netea; Matthew A Sabin; Richard Saffery; Niels P Riksen; David P Burgner

doi:10.1016/j.isci.2024.109762

Increased innate immune responses in adolescents with obesity and its relation to subclinical cardiovascular measures: An exploratory study

iScience. 2024 Apr 23;27(5):109762. doi: 10.1016/j.isci.2024.109762. eCollection 2024 May 17.

Authors

Siroon Bekkering^{1

2}, Christoph Saner^{2

3

4}, Boris Novakovic^{2

5}, Toby Mansell^{2

5}, Danielle K Longmore^{2

6}, Zoe McCallum^{5

7}, Anne-Louise Ponsonby^{2

8}, Markus Juonala^{9

10}, Mihai G Netea^{1

11}, Matthew A Sabin^{2

6

5}, Richard Saffery^{2

5}, Niels P Riksen¹, David P Burgner^{2

5

12}

Affiliations

¹ Department of Internal Medicine, Radboud University Medical Centre, Nijmegen 6525 GA, the Netherlands.
² Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, VIC 3052, Australia.
³ Division of Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, University Children`s Hospital Bern, Inselspital, Bern 3010, Switzerland.
⁴ Department of Biomedical Research, University of Bern, 3010 Bern, Switzerland.
⁵ Department of Paediatrics, The University of Melbourne, Parkville, VIC 3052, Australia.
⁶ Department of Endocrinology, The Royal Children`s Hospital, Parkville, VIC 3052, Australia.
⁷ Department of Neurodevelopment and Disability, Royal Children's Hospital, Parkville, VIC 3052, Australia.
⁸ Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3052, Australia.
⁹ Department of Medicine, University of Turku, 20500 Turku, Finland.
¹⁰ Division of Medicine, Turku University Hospital, 20500 Turku, Finland.
¹¹ Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany.
¹² Department of Pediatrics, Monash University, Clayton, VIC 3168, Australia.

Abstract

Cardiometabolic risk accrues across the life course and childhood and adolescence are key periods for effective prevention. Obesity is associated with inflammation in adults, but pediatric data are scarce. In a cross-sectional and longitudinal study, we investigated immune cell composition and activation in 31 adolescents with obesity (41.9% male, BMIz>2.5, 14.4 years) and 22 controls with healthy weight (45.1% male, -1.5<BMIz<1.5, 14 years). In those with obesity, we assessed the impact of weight change and correlations between immune profiles and subclinical cardiovascular phenotypes at a 5-year follow-up. Compared to controls, those with obesity had increased monocyte activation and cytokine production upon stimulation. Monocyte transcriptomics demonstrated upregulated inflammatory pathways and downregulated antiviral responses. Weight change was not associated with changes in inflammation. Baseline inflammation correlated with cardiovascular measures at follow-up. Children with obesity have increased inflammation, which associates with worse subsequent subclinical cardiovascular measures. Adjunctive anti-inflammatory interventions may be needed to reverse adverse subclinical cardiovascular phenotypes.

Keywords: Disease; Health sciences; Immunology; Pathophysiology; Risk factor.