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Clinical Studies and Practice

Diet-induced weight loss has chronic tissue-specific effects on glucocorticoid metabolism in overweight postmenopausal women



Tissue-specific glucocorticoid metabolism is altered in obesity, and may increase cardiovascular risk. This dysregulation is normalized by short-term calorie restriction and weight loss, an effect that varies with dietary macronutrient composition. However, tissue-specific glucocorticoid metabolism has not been studied during long-term (>6 months) dietary interventions. Therefore our aim was to test whether long-term dietary interventions, either a paleolithic-type diet (PD) or a diet according to Nordic nutrition recommendations (NNR) could normalize tissue-specific glucocorticoid metabolism in overweight and obese women.


Forty-nine overweight/obese postmenopausal women were randomized to a paleolithic diet or a diet according to NNR for 24 months. At baseline, 6 and 24 months anthropometric measurements, insulin sensitivity, excretion of urinary glucocorticoid metabolites in 24-hour collections, conversion of orally administered cortisone to plasma cortisol and transcript levels of 11β hydroxysteroid dehydrogenase type 1 (11βHSD1) in subcutaneous adipose tissue were studied.


Both diet groups achieved significant and sustained weight loss. Weight loss with the PD was greater than on NNR diet after 6 months (P<0.001) but similar at 24 months. Urinary measurement of 5α-reductase activity was increased after 24 months in both groups compared with baseline (P<0.001). Subcutaneous adipose tissue 11βHSD1 gene expression decreased at 6 and 24 months in both diet groups (P=0.036). Consistent with increased liver 11βHSD1, conversion of oral cortisone to cortisol increased at 6 months (P=0.023) but was unchanged compared with baseline by 24 months.


Long-term weight loss in postmenopausal women has tissue-specific and time-dependent effects on glucocorticoid metabolism. This may alter local-tissue cortisol exposure contributing to improved metabolic function during weight loss.

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We thank all of the participants for taking part in this study. We also thank Susanne Sandberg, Inger Arnesjö and Marie Eriksson, Umeå University and the staff of the Wellcome Trust Clinical Research Facility Mass Spectrometry Core, University of Edinburgh. This study was supported by grants from The Swedish Council for Working Life and Social Research (2006-0699 and 2010-0398), the Swedish Research Council (K2011-12237-15-6), the Swedish Heart and Lung Foundation, the County Council of Västerbotten, and Umeå University, Sweden, the British Heart Foundation and the Wellcome Trust.

Clinical trials number: NCT00692536.

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Correspondence to A Stomby.

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BRW is an inventor on relevant patents owned by the University of Edinburgh. AS, KS, CM, MR, RHS, CL, BL, RA and TO have nothing to disclose.

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Stomby, A., Simonyte, K., Mellberg, C. et al. Diet-induced weight loss has chronic tissue-specific effects on glucocorticoid metabolism in overweight postmenopausal women. Int J Obes 39, 814–819 (2015).

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