Endocrine Abstracts

Background: Excess glucocorticoid (GC) exposure is associated with an adverse body composition and metabolic profile characterised by increasing fat mass, muscle atrophy, insulin resistance, fatty liver, and dyslipidaemia culminating in increased cardiovascular risk. GCs are widely prescribed with increasing age where their effects can have deleterious effects.

Objectives: To investigate the impact of GC exposure on subcutaneous adipose lipid metabolism across healthy human ageing and to investigate associations with phenotypic and hormonal markers of ageing.

Setting: NIHR–Wellcome Trust Clinical Research Facility.

Participants: Human volunteers aged 20–81 years (n=134; 77 women and 57 men). A sub-section (n=72) had adipose microdialysis analysis performed.

Methods: Day attendance for baseline observations, DEXA, 24-h urine collection for GC/MS analysis, measurement of prednisolone generation from prednisone by LC/MS and subcutaneous adipose tissue microdialysis for 4 h following 10 mg oral prednisone.

Results: Subcutaneous adipose microdialysis glucose (1.9-fold, IQR 1.4–2.7), lactate (4.6-fold, IQR 3.2–8.2), pyruvate (4.0-fold, IQR 2.2–9.1), and glycerol (2.8-fold, IQR 1.9–4.4) were increased in response to prednisone. There was a positive correlation between glycerol (AUC; a lipolysis marker) and age (ρ=0.31, P=0.04), with no associations with other measured adipose metabolites. Glycerol also correlated positively with total fat (ρ=0.29, P=0.04). These correlations were more marked in men (total fat ρ=0.64, P=0.01 and % body fat ρ=0.78, P=0.0009). There were significant correlations between glycerol and urine (DHEA/THE+THF+5aTHF) (ρ=−0.29, P=0.04) and PT/(THE+THF+5aTHF) (ρ=-0.40, P=0.005). In women, correlations were also seen with (DHEA/THE+THF+5aTHF) (ρ=−0.38, P=0.02) and PT/(THE+THF+5aTHF) (ρ=−0.43, P=0.01), along with 16a-OH DHEA (ρ=−0.35, P=0.04). Glycerol also correlated negatively with serum DHEAS (ρ=-0.38, P=0.03).

Conclusion: GC-induced adipose tissue lipolysis is increased with age, which is likely a function of increased fat mass. The metabolite ratio associations raise the possibility that DHEA exerts an anti-GC effect in adipose tissue. Further interventional studies are required to determine the impact of androgens on lipid metabolism.