Abstract
Background and aimsThe 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 methodsA 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.ConclusionsThe 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.
Highlights
Background and aimsThe effects of glucocorticoids on fuel metabolism are complex
This work shows that glucocorticoids are dependent on insulin and/or adrenaline in order to increase whole body lipolysis in vivo
In slightly higher insulin concentrations (c. 22 mU/L) designed to suppress lipolysis by 50%, high cortisol concentrations increased rate of appearance (Ra) glycerol by 20% to 25%, showing that cortisol antagonizes the effect of insulin
Summary
Two studies have examined the effect of physiological cortisol concentrations on in vivo lipolysis and had conflicting results in the fasted state;[1,10] neither study used a pancreatic clamp to control counter-regulatory hormones. It is unclear whether changes in cortisol concentrations within the physiological range alter whole body lipolysis. Over and above prevailing glucocorticoid concentrations, a further critical confounder is the effect of other hormones regulating lipolysis, notably insulin and adrenaline.[5,6] In vivo, the effect of interactions between cortisol and either adrenaline[11] or insulin[12] has been examined only once in humans, systemic rates of lipolysis were not measured as the appropriate tracers were not infused. We collected adipose tissue biopsies in vivo to determine how glucocorticoids alter lipolysis and tested in vitro whether glucocorticoids have differential effects on lipolysis in subcutaneous and visceral adipocytes
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