David Burgner1,2,3, Christoph Saner4,5,6, Toby Mansell1,2, Costan G Magnussen7,8,9, Joel Nuotio1,7,8,10, Tomi T Laitinen1,7,8,11, Brooke E Harcourt1,2, Siroon Bekkering1,12, Zoe McCallum1,2, Kung-Ting Kao1,2,13, Matthew A Sabin1,2,13, Markus Juonala1,14, Richard Saffery1,2. 1. Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, VIC, Australia. 2. Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia. 3. Department of Paediatrics, Monash University, Clayton, VIC, Australia. 4. Murdoch Children's Research Institute, The Royal Children's Hospital, Parkville, VIC, Australia. christoph.saner@insel.ch. 5. Division of Pediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. christoph.saner@insel.ch. 6. Department of Biomedical Research, University of Bern, Bern, Switzerland. christoph.saner@insel.ch. 7. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland. 8. Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland. 9. Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia. 10. Heart Centre, Turku University Hospital and University of Turku, Turku, Finland. 11. Paavo Nurmi Centre, Sports & Exercise Medicine Unit, Department of Physical Activity and Health, University of Turku, Turku, Finland. 12. Department of Internal Medicine and Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands. 13. Department of Endocrinology, The Royal Children's Hospital, Parkville, VIC, Australia. 14. Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland.
Abstract
BACKGROUND: Obesity in childhood is associated with metabolic dysfunction, adverse subclinical cardiovascular phenotypes and adult cardiovascular disease. Longitudinal studies of youth with obesity investigating changes in severity of obesity with metabolomic profiles are sparse. We investigated associations between (i) baseline body mass index (BMI) and follow-up metabolomic profiles; (ii) change in BMI with follow-up metabolomic profiles; and (iii) change in BMI with change in metabolomic profiles (mean interval 5.5 years). METHODS: Participants (n = 98, 52% males) were recruited from the Childhood Overweight Biorepository of Australia study. At baseline and follow-up, BMI and the % >95th BMI-centile (percentage above the age-, and sex-specific 95th BMI-centile) indicate severity of obesity, and nuclear magnetic resonance spectroscopy profiling of 72 metabolites/ratios, log-transformed and scaled to standard deviations (SD), was performed in fasting serum. Fully adjusted linear regression analyses were performed. RESULTS: Mean (SD) age and % >95th BMI-centile were 10.3 (SD 3.5) years and 134.6% (19.0) at baseline, 15.8 (3.7) years and 130.7% (26.2) at follow-up. Change in BMI over time, but not baseline BMI, was associated with metabolites at follow-up. Each unit (kg/m2) decrease in sex- and age-adjusted BMI was associated with change (SD; 95% CI; p value) in metabolites of: alanine (-0.07; -0.11 to -0.04; p < 0.001), phenylalanine (-0.07; -0.10 to -0.04; p < 0.001), tyrosine (-0.07; -0.10 to -0.04; p < 0.001), glycoprotein acetyls (-0.06; -0.09 to -0.04; p < 0.001), degree of fatty acid unsaturation (0.06; 0.02 to 0.10; p = 0.003), monounsaturated fatty acids (-0.04; -0.07 to -0.01; p = 0.004), ratio of ApoB/ApoA1 (-0.05; -0.07 to -0.02; p = 0.001), VLDL-cholesterol (-0.04; -0.06 to -0.01; p = 0.01), HDL cholesterol (0.05; 0.08 to 0.1; p = 0.01), pyruvate (-0.08; -0.11 to -0.04; p < 0.001), acetoacetate (0.07; 0.02 to 0.11; p = 0.005) and 3-hydroxybuturate (0.07; 0.02 to 0.11; p = 0.01). Results using the % >95th BMI-centile were largely consistent with age- and sex-adjusted BMI measures. CONCLUSIONS: In children and young adults with obesity, decreasing the severity of obesity was associated with changes in metabolomic profiles consistent with lower cardiovascular and metabolic disease risk in adults.
BACKGROUND: Obesity in childhood is associated with metabolic dysfunction, adverse subclinical cardiovascular phenotypes and adult cardiovascular disease. Longitudinal studies of youth with obesity investigating changes in severity of obesity with metabolomic profiles are sparse. We investigated associations between (i) baseline body mass index (BMI) and follow-up metabolomic profiles; (ii) change in BMI with follow-up metabolomic profiles; and (iii) change in BMI with change in metabolomic profiles (mean interval 5.5 years). METHODS: Participants (n = 98, 52% males) were recruited from the Childhood Overweight Biorepository of Australia study. At baseline and follow-up, BMI and the % >95th BMI-centile (percentage above the age-, and sex-specific 95th BMI-centile) indicate severity of obesity, and nuclear magnetic resonance spectroscopy profiling of 72 metabolites/ratios, log-transformed and scaled to standard deviations (SD), was performed in fasting serum. Fully adjusted linear regression analyses were performed. RESULTS: Mean (SD) age and % >95th BMI-centile were 10.3 (SD 3.5) years and 134.6% (19.0) at baseline, 15.8 (3.7) years and 130.7% (26.2) at follow-up. Change in BMI over time, but not baseline BMI, was associated with metabolites at follow-up. Each unit (kg/m2) decrease in sex- and age-adjusted BMI was associated with change (SD; 95% CI; p value) in metabolites of: alanine (-0.07; -0.11 to -0.04; p < 0.001), phenylalanine (-0.07; -0.10 to -0.04; p < 0.001), tyrosine (-0.07; -0.10 to -0.04; p < 0.001), glycoprotein acetyls (-0.06; -0.09 to -0.04; p < 0.001), degree of fatty acid unsaturation (0.06; 0.02 to 0.10; p = 0.003), monounsaturated fatty acids (-0.04; -0.07 to -0.01; p = 0.004), ratio of ApoB/ApoA1 (-0.05; -0.07 to -0.02; p = 0.001), VLDL-cholesterol (-0.04; -0.06 to -0.01; p = 0.01), HDL cholesterol (0.05; 0.08 to 0.1; p = 0.01), pyruvate (-0.08; -0.11 to -0.04; p < 0.001), acetoacetate (0.07; 0.02 to 0.11; p = 0.005) and 3-hydroxybuturate (0.07; 0.02 to 0.11; p = 0.01). Results using the % >95th BMI-centile were largely consistent with age- and sex-adjusted BMI measures. CONCLUSIONS: In children and young adults with obesity, decreasing the severity of obesity was associated with changes in metabolomic profiles consistent with lower cardiovascular and metabolic disease risk in adults.
Authors: William S Weintraub; Stephen R Daniels; Lora E Burke; Barry A Franklin; David C Goff; Laura L Hayman; Donald Lloyd-Jones; Dilip K Pandey; Eduardo J Sanchez; Andrea Parsons Schram; Laurie P Whitsel Journal: Circulation Date: 2011-07-25 Impact factor: 29.690
Authors: Asheley Cockrell Skinner; Sophie N Ravanbakht; Joseph A Skelton; Eliana M Perrin; Sarah C Armstrong Journal: Pediatrics Date: 2018-03 Impact factor: 7.124
Authors: Christian Delles; Naomi J Rankin; Charles Boachie; Alex McConnachie; Ian Ford; Antti Kangas; Pasi Soininen; Stella Trompet; Simon P Mooijaart; J Wouter Jukema; Faiez Zannad; Mika Ala-Korpela; Veikko Salomaa; Aki S Havulinna; Paul Welsh; Peter Würtz; Naveed Sattar Journal: Eur J Heart Fail Date: 2017-12-11 Impact factor: 15.534
Authors: Elizabeth T Cirulli; Lining Guo; Christine Leon Swisher; Naisha Shah; Lei Huang; Lori A Napier; Ewen F Kirkness; Tim D Spector; C Thomas Caskey; Bernard Thorens; J Craig Venter; Amalio Telenti Journal: Cell Metab Date: 2018-10-11 Impact factor: 27.287