Acute physiological effects of glucocorticoids on fuel metabolism in humans are permissive but not direct.
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.



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.



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.



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.
Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
Roland H
0000-0002-9002-6188
RH
Stimson
Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
Anna J
AJ
Anderson
Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
Lynne E
LE
Ramage
Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
David P
DP
Macfarlane
Department of Upper GI Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK.
Andrew C
AC
de Beaux
Department of Upper GI Surgery, Royal Infirmary of Edinburgh, Edinburgh, UK.|MRC Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
Damian J
DJ
Mole
Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
Ruth
R
Andrew
Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
Brian R
BR
Walker
D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004837:Epinephrine / Q000378:metabolism; D005938:Glucocorticoids / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage*; D005990:Glycerol / Q000008:administration & dosage*; D064368:Healthy Volunteers; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D007328:Insulin / Q000378:metabolism; D008066:Lipolysis / Q000502:physiology; D008297:Male; D008875:Middle Aged; D050151:Subcutaneous Fat / Q000378:metabolism*; D055815:Young Adult
D005938:Glucocorticoids; D007328:Insulin; D005947:Glucose; D005990:Glycerol; D006854:Hydrocortisone; D004837:Epinephrine
adipose tissue; adrenaline; body composition; drug mechanism; glucocorticoid; glucose; insulin resistance; metabolism