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Lookup NU author(s): Eileen Gibney
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Objectives: Obesity is associated with increased inactivation of cortisol by hepatic A-ring 5α- and 5β-reductases, impaired hepatic regeneration of cortisol from cortisone by 11β-hydroxysteroid dehydrogenase type 1 (11HSD1), but increased subcutaneous adipose 11HSD1 activity enhancing local cortisol levels in fat. Cause and effect between obesity and abnormal cortisol metabolism is untested. Design: Acute weight loss was induced by very low calorie diet (VLCD) or starvation in obese men. Methods: Otherwise healthy males (aged 20-55 years; body mass index (BMI) 30-40kg/m2) were studied after 6 days on a weight maintenance diet; then after either 6 days of starvation (n = 6) or 3 weeks of VLCD (2.55 MJ: n = 6): then after 1 week of weight maintenance; and finally after 2 weeks of being allowed to feed ad libitum. Plasma samples were obtained from indwelling cannulae at 0930 h and 1815 h and a 24 h urine collection was completed for analysis of cortisol metabolites by gas chromatography/mass spectrometry. Results: Data are mean±S.E.M. BMI fell (kg/m3) from 34.8±0.8 at baseline to 31.8±1.4 on VLCD and 32.7±1.1 on starvation. Starvation caused a rise in plasma cortisol (at 0930 h from 143±17 to 216±11 nM, P < 0.001 but no change in total urinary cortisol metabolites. VLCD did not alter plasma cortisol and markedly reduced cortisol metabolite excretion (from 15.8±1.1 mg/day at baseline to 7.0±1.1 mg/day, P < 0.001). Relative excretion of 5α-reduced cortisol metabolites fell on both diets, but there were no changes in cortisol/cortisone metabolite ratios reflecting 11HSD activities. Conclusions: Weight loss with VLCD in obesity reverses up-regulation of hepatic A-ring reductases and normalises cortisol production rate; in contrast, starvation produces acute stress and further activation of cortisol secretion. We suggest that activation of cortisol secretion is not an irreversible intrinsic abnormality in obese patients, and speculate that dietary content has an important influence on the neuroendocrine response to weight loss. © 2004 Society of the European Journal of Endocrinology.
Author(s): Johnstone AM, Faber P, Andrew R, Gibney ER, Elia M, Lobley G, Stubbs RJ, Walker BR
Publication type: Article
Publication status: Published
Journal: European Journal of Endocrinology
ISSN (print): 0804-4643
ISSN (electronic): 1479-683X
Publisher: BioScientifica Ltd
PubMed id: 14763916
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