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Lookup NU author(s): Professor Brian WalkerORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. Background and aims: The effects of glucocorticoids on fuel metabolism are complex. Acute glucocorticoid excess promotes lipolysis but chronic glucocorticoid excess causes visceral fat accumulation. We hypothesized that interactions between cortisol and insulin and adrenaline account for these conflicting results. We tested the effect of cortisol on lipolysis and glucose production with and without insulin and adrenaline in humans both in vivo and in vitro. Materials and methods: A total of 20 healthy men were randomized to low and high insulin groups (both n = 10). Subjects attended on 3 occasions and received low (c. 150 nM), medium (c. 400 nM) or high (c. 1400 nM) cortisol infusion in a randomized crossover design. Deuterated glucose and glycerol were infused intravenously along with a pancreatic clamp (somatostatin with replacement of glucagon, insulin and growth hormone) and adrenaline. Subcutaneous adipose tissue was obtained for analysis. In parallel, the effect of cortisol on lipolysis was tested in paired primary cultures of human subcutaneous and visceral adipocytes. Results: In vivo, high cortisol increased lipolysis only in the presence of high insulin and/or adrenaline but did not alter glucose kinetics. High cortisol increased adipose mRNA levels of ATGL, HSL and CGI-58 and suppressed G0S2. In vitro, high cortisol increased lipolysis in the presence of insulin in subcutaneous, but not visceral, adipocytes. Conclusions: The acute lipolytic effects of cortisol require supraphysiological concentrations, are dependent on insulin and adrenaline and are observed only in subcutaneous adipose tissue. The resistance of visceral adipose tissue to cortisol's lipolytic effects may contribute to the central fat accumulation observed with chronic glucocorticoid excess.
Author(s): Stimson RH, Anderson AJ, Ramage LE, Macfarlane DP, de Beaux AC, Mole DJ, Andrew R, Walker BR
Publication type: Article
Publication status: Published
Journal: Diabetes, Obesity and Metabolism
Year: 2017
Volume: 19
Issue: 6
Pages: 883-891
Online publication date: 08/02/2017
Acceptance date: 03/02/2017
Date deposited: 20/12/2017
ISSN (print): 1462-8902
ISSN (electronic): 1463-1326
Publisher: Blackwell Publishing Ltd
URL: https://doi.org/10.1111/dom.12899
DOI: 10.1111/dom.12899
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