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
Affiliations
Siroon Bekkering
Department of Internal Medicine, Radboud University Medical Centre, Nijmegen 6525 GA, the Netherlands; Murdoch Children’s Research Institute, The Royal Children’s Hospital, Parkville, VIC 3052, Australia; Corresponding author
Christoph Saner
Murdoch Children’s Research Institute, The Royal Children’s Hospital, Parkville, VIC 3052, Australia; Division of Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, University Children`s Hospital Bern, Inselspital, Bern 3010, Switzerland; Department of Biomedical Research, University of Bern, 3010 Bern, Switzerland
Boris Novakovic
Murdoch Children’s Research Institute, The Royal Children’s Hospital, Parkville, VIC 3052, Australia; Department of Paediatrics, The University of Melbourne, Parkville, VIC 3052, Australia
Toby Mansell
Murdoch Children’s Research Institute, The Royal Children’s Hospital, Parkville, VIC 3052, Australia; Department of Paediatrics, The University of Melbourne, Parkville, VIC 3052, Australia
Danielle K. Longmore
Murdoch Children’s Research Institute, The Royal Children’s Hospital, Parkville, VIC 3052, Australia; Department of Endocrinology, The Royal Children`s Hospital, Parkville, VIC 3052, Australia
Zoe McCallum
Department of Paediatrics, The University of Melbourne, Parkville, VIC 3052, Australia; Department of Neurodevelopment and Disability, Royal Children’s Hospital, Parkville, VIC 3052, Australia
Anne-Louise Ponsonby
Murdoch Children’s Research Institute, The Royal Children’s Hospital, Parkville, VIC 3052, Australia; Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC 3052, Australia
Markus Juonala
Department of Medicine, University of Turku, 20500 Turku, Finland; Division of Medicine, Turku University Hospital, 20500 Turku, Finland
Mihai G. Netea
Department of Internal Medicine, Radboud University Medical Centre, Nijmegen 6525 GA, the Netherlands; Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany
Matthew A. Sabin
Murdoch Children’s Research Institute, The Royal Children’s Hospital, Parkville, VIC 3052, Australia; Department of Endocrinology, The Royal Children`s Hospital, Parkville, VIC 3052, Australia; Department of Paediatrics, The University of Melbourne, Parkville, VIC 3052, Australia
Richard Saffery
Murdoch Children’s Research Institute, The Royal Children’s Hospital, Parkville, VIC 3052, Australia; Department of Paediatrics, The University of Melbourne, Parkville, VIC 3052, Australia
Niels P. Riksen
Department of Internal Medicine, Radboud University Medical Centre, Nijmegen 6525 GA, the Netherlands
David P. Burgner
Murdoch Children’s Research Institute, The Royal Children’s Hospital, Parkville, VIC 3052, Australia; Department of Paediatrics, The University of Melbourne, Parkville, VIC 3052, Australia; Department of Pediatrics, Monash University, Clayton, VIC 3168, Australia; Corresponding author
Summary: 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.
