Rachel K Crowley1,2, Conor P Woods3,4, Beverly A Hughes5, Joanna Gray6, Theresa McCarthy6, Angela E Taylor5, Laura L Gathercole7, Cedric H L Shackleton5, Nicola Crabtree6, Wiebke Arlt5, Paul M Stewart8, Jeremy W Tomlinson9. 1. Department of Endocrinology, St Vincent's University Hospital, Dublin, Ireland. 2. School of Medicine & Medical Sciences, University College Dublin, Dublin, Ireland. 3. Department of Endocrinology, Naas General Hospital, Kildare, Ireland. 4. Tallaght Hospital, Dublin, Ireland. 5. School of Clinical and Experimental Medicine, Institute of Biomedical Research, Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham, UK. 6. NIHR/Wellcome Trust Clinical Research Facility, Queen Elizabeth Hospital, Birmingham, UK. 7. Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, UK. 8. Medical School, University of Leeds, Leeds, UK. 9. Oxford Centre for Diabetes Endocrinology & Metabolism (OCDEM), NIHR Oxford Biomedical Research Centre, Churchill Hospital, University of Oxford, Oxford, UK.
Abstract
OBJECTIVE AND CONTEXT: Increasing adiposity, ageing and tissue-specific regeneration of cortisol through the activity of 11β-hydroxysteroid dehydrogenase type 1 have been associated with deterioration in glucose tolerance. We undertook a longitudinal, prospective clinical study to determine if alterations in local glucocorticoid metabolism track with changes in glucose tolerance. DESIGN, PATIENTS, AND MEASUREMENTS: Sixty-five overweight/obese individuals (mean age 50.3 ± 7.3 years) underwent oral glucose tolerance testing, body composition assessment, subcutaneous adipose tissue biopsy and urinary steroid metabolite analysis annually for up to 5 years. Participants were categorized into those in whom glucose tolerance deteriorated ("deteriorators") or improved ("improvers"). RESULTS: Deteriorating glucose tolerance was associated with increasing total and trunk fat mass and increased subcutaneous adipose tissue expression of lipogenic genes. Subcutaneous adipose tissue 11β-HSD1 gene expression decreased in deteriorators, and at study completion, it was highest in the improvers. There was a significant negative correlation between change in area under the curve glucose and 11β-HSD1 expression. Global 11β-HSD1 activity did not change and was not different between deteriorators and improvers at baseline or follow-up. CONCLUSION: Longitudinal deterioration in metabolic phenotype is not associated with increased 11β-HSD1 activity, but decreased subcutaneous adipose tissue gene expression. These changes may represent a compensatory mechanism to decrease local glucocorticoid exposure in the face of an adverse metabolic phenotype.
OBJECTIVE AND CONTEXT: Increasing adiposity, ageing and tissue-specific regeneration of cortisol through the activity of 11β-hydroxysteroid dehydrogenase type 1 have been associated with deterioration in glucose tolerance. We undertook a longitudinal, prospective clinical study to determine if alterations in local glucocorticoid metabolism track with changes in glucose tolerance. DESIGN, PATIENTS, AND MEASUREMENTS: Sixty-five overweight/obese individuals (mean age 50.3 ± 7.3 years) underwent oral glucose tolerance testing, body composition assessment, subcutaneous adipose tissue biopsy and urinary steroid metabolite analysis annually for up to 5 years. Participants were categorized into those in whom glucose tolerance deteriorated ("deteriorators") or improved ("improvers"). RESULTS: Deteriorating glucose tolerance was associated with increasing total and trunk fat mass and increased subcutaneous adipose tissue expression of lipogenic genes. Subcutaneous adipose tissue 11β-HSD1 gene expression decreased in deteriorators, and at study completion, it was highest in the improvers. There was a significant negative correlation between change in area under the curve glucose and 11β-HSD1 expression. Global 11β-HSD1 activity did not change and was not different between deteriorators and improvers at baseline or follow-up. CONCLUSION:Longitudinal deterioration in metabolic phenotype is not associated with increased 11β-HSD1 activity, but decreased subcutaneous adipose tissue gene expression. These changes may represent a compensatory mechanism to decrease local glucocorticoid exposure in the face of an adverse metabolic phenotype.
Authors: Martijn J J Finken; Aleid J G Wirix; Ines A von Rosenstiel-Jadoul; Bibian van der Voorn; Mai J M Chinapaw; Michaela F Hartmann; Joana E Kist-van Holthe; Stefan A Wudy; Joost Rotteveel Journal: Endocr Connect Date: 2022-07-14 Impact factor: 3.221
Authors: Elena Barengolts; Stefan J Green; George E Chlipala; Brian T Layden; Yuval Eisenberg; Medha Priyadarshini; Lara R Dugas Journal: Microorganisms Date: 2019-09-05
Authors: Conor Bentley; Claire Potter; Kamal Makram Yakoub; Kristian Brock; Victoria Homer; Emma Toman; Angela E Taylor; Fozia Shaheen; Lorna C Gilligan; Amrita Athwal; Darren Barton; Ronald Carrera; Katie Young; Amisha Desai; Kirsty McGee; Christos Ermogenous; Gurneet Sur; Carolyn A Greig; Jon Hazeldine; Wiebke Arlt; Janet M Lord; Mark A Foster Journal: BMJ Open Date: 2021-07-26 Impact factor: 2.692