G Noppe1,2,3, E L T van den Akker2,4, Y B de Rijke1,2,5, J W Koper1,2, V W Jaddoe3,4,6, E F C van Rossum1,2. 1. Department of Internal Medicine, Division of Endocrinology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. 2. Obesity Center CGG, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. 3. The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. 4. Department of Pediatrics, Sophia Children's Hospital, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. 5. Department of Clinical Chemistry, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. 6. Department of Epidemiology and Biostatistics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Abstract
BACKGROUND: Childhood obesity is an important risk factor for premature development of the metabolic syndrome (MetS) at adulthood. There is need for understanding of the mechanisms underlying the MetS and obesity. Patients with Cushing's disease suffer from similar metabolic complications, leading to the hypothesis that inter-individual cortisol variation may contribute to the onset of obesity. In addition, glucocorticoid receptor (GR)-gene polymorphisms resulting in differential glucocorticoid (GC) sensitivity, have been associated with an adverse metabolic profile. AIM: To study associations of GC levels in scalp hair, as a marker of long-term systemic GC concentrations, and genetically determined GC sensitivity with obesity and body-fat distribution in children. METHODS: We performed a cross-sectional study of cortisol and cortisone concentrations over a 3-month period, measured by LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry) in hair of 3019 6-year-old children participating in the Generation R study. Genotyping of GR-gene polymorphisms was performed. RESULTS: Of all children, 4.3% was obese and 13.4% overweight. Cortisol was significantly associated with risk of obesity (odd ratio (OR): 9.4 (3.3-26.9)) and overweight (OR: 1.4 (1.0-2.0)). Cortisone was associated with risk of obesity (OR: 1.9 (1.0-3.5)). Cortisol and cortisone were significantly positively associated with body mass index, fat mass (FM) index and android/gynecoid FM ratio. GR polymorphisms were not associated with adiposity parameters. CONCLUSION: Long-term cortisol concentrations are strongly associated with an increased risk of childhood obesity and adverse body-fat distribution. Future research may reveal whether these are causal relations and may be a target for therapy.
BACKGROUND: Childhood obesity is an important risk factor for premature development of the metabolic syndrome (MetS) at adulthood. There is need for understanding of the mechanisms underlying the MetS and obesity. Patients with Cushing's disease suffer from similar metabolic complications, leading to the hypothesis that inter-individual cortisol variation may contribute to the onset of obesity. In addition, glucocorticoid receptor (GR)-gene polymorphisms resulting in differential glucocorticoid (GC) sensitivity, have been associated with an adverse metabolic profile. AIM: To study associations of GC levels in scalp hair, as a marker of long-term systemic GC concentrations, and genetically determined GC sensitivity with obesity and body-fat distribution in children. METHODS: We performed a cross-sectional study of cortisol and cortisone concentrations over a 3-month period, measured by LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry) in hair of 3019 6-year-old children participating in the Generation R study. Genotyping of GR-gene polymorphisms was performed. RESULTS: Of all children, 4.3% was obese and 13.4% overweight. Cortisol was significantly associated with risk of obesity (odd ratio (OR): 9.4 (3.3-26.9)) and overweight (OR: 1.4 (1.0-2.0)). Cortisone was associated with risk of obesity (OR: 1.9 (1.0-3.5)). Cortisol and cortisone were significantly positively associated with body mass index, fat mass (FM) index and android/gynecoid FM ratio. GR polymorphisms were not associated with adiposity parameters. CONCLUSION: Long-term cortisol concentrations are strongly associated with an increased risk of childhood obesity and adverse body-fat distribution. Future research may reveal whether these are causal relations and may be a target for therapy.
Authors: Gerard Noppe; Elisabeth F C Van Rossum; Jan Willem Koper; Laura Manenschijn; G Jan Bruining; Yolanda B de Rijke; Erica L T van den Akker Journal: Horm Res Paediatr Date: 2014-08-09 Impact factor: 2.852
Authors: Miranda J J Geelhoed; Eric A P Steegers; Jan W Koper; Elisabeth F C van Rossum; Henriette A Moll; Hein Raat; Henning Tiemeier; Albert Hofman; Vincent W V Jaddoe Journal: BMC Med Genet Date: 2010-03-03 Impact factor: 2.103
Authors: R Pasquali; S Cantobelli; F Casimirri; M Capelli; L Bortoluzzi; R Flamia; A M Labate; L Barbara Journal: J Clin Endocrinol Metab Date: 1993-08 Impact factor: 5.958
Authors: Robin Lengton; Anand M Iyer; Eline S van der Valk; Ellen K Hoogeveen; Onno C Meijer; Bibian van der Voorn; Elisabeth F C van Rossum Journal: Obes Rev Date: 2021-11-27 Impact factor: 10.867
Authors: Vidhu V Thaker; Stavroula K Osganian; Sarah D deFerranti; Kendrin R Sonneville; Jennifer K Cheng; Henry A Feldman; Tracy K Richmond Journal: BMC Pediatr Date: 2020-06-10 Impact factor: 2.125
Authors: Hilal Ince-Askan; Erica L T van den Akker; Yolanda B de Rijke; Elisabeth F C van Rossum; Johanna M W Hazes; Radboud J E M Dolhain Journal: RMD Open Date: 2019-01-30
Authors: T Kowatsch; D l'Allemand; A Stasinaki; D Büchter; C-H I Shih; K Heldt; S Güsewell; B Brogle; N Farpour-Lambert Journal: BMC Pediatr Date: 2021-07-09 Impact factor: 2.125