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Exploring the Temporal Relation between Body Mass Index and Corticosteroid Metabolite Excretion in Childhood

Emma Children’s Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Endocrinology, Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
Netherlands Twin Register, Department of Biological Psychology, Vrije Universiteit Amsterdam, Van der Boechorststraat 7-9, 1081 BT, Amsterdam, The Netherlands
Centre for Cardiovascular Science, University of Edinburgh, Queen’s Medical Research Institute, 47, Little France Crescent, Edinburgh EH16 4TJ, UK
Institute of Genetic Medicine, Newcastle University, Central Pkwy, Newcastle upon Tyne NE1 3BZ, UK
Department of Psychiatry, University Medical Center Utrecht, Brain Center, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands
Author to whom correspondence should be addressed.
Nutrients 2020, 12(5), 1525;
Received: 3 April 2020 / Revised: 10 May 2020 / Accepted: 20 May 2020 / Published: 23 May 2020
(This article belongs to the Section Nutrition and Metabolism)
Childhood obesity is associated with alterations in hypothalamus–pituitary–adrenal (HPA) axis activity. However, it is unknown whether these alterations are a cause or a consequence of obesity. This study aimed to explore the temporal relationship between cortisol production and metabolism, and body mass index (BMI). This prospective follow-up study included 218 children (of whom 50% were male), born between 1995 and 1996, who were assessed at the ages of 9, 12 and 17 years. Morning urine samples were collected for assessment of cortisol metabolites by gas chromatography-tandem mass spectrometry, enabling the calculation of cortisol metabolite excretion rate and cortisol metabolic pathways. A cross-lagged regression model was used to determine whether BMI at various ages during childhood predicted later cortisol production and metabolism parameters, or vice versa. The cross-lagged regression coefficients showed that BMI positively predicted cortisol metabolite excretion (p = 0.03), and not vice versa (p = 0.33). In addition, BMI predicted the later balance of 11β-hydroxysteroid dehydrogenase (HSD) activities (p = 0.07), and not vice versa (p = 0.55). Finally, cytochrome P450 3A4 activity positively predicted later BMI (p = 0.01). Our study suggests that changes in BMI across the normal range predict alterations in HPA axis activity. Therefore, the alterations in HPA axis activity as observed in earlier studies among children with obesity may be a consequence rather than a cause of increased BMI. View Full-Text
Keywords: obesity; glucocorticoids; BMI; HPA axis obesity; glucocorticoids; BMI; HPA axis
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Van Keulen, B.J.; Dolan, C.V.; Andrew, R.; Walker, B.R.; Hulshoff Pol, H.E.; Boomsma, D.I.; Rotteveel, J.; Finken, M.J. Exploring the Temporal Relation between Body Mass Index and Corticosteroid Metabolite Excretion in Childhood. Nutrients 2020, 12, 1525.

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