Adrenal medullary dysfunction as a feature of obesity

Although there is strong evidence linking obesity with increased sympathoneural activity, involvement of the adrenal medulla is less clear. We therefore investigated adrenal medullary function under fasting and feeding conditions in normal weight (NW, n=33), overweight (OW, n=28) and obese (OB, n=36) adults (59% women).

Ninety-seven healthy adults participated in a cross-sectional study with recruitment stratified according to BMI. Plasma for catecholamines and metanephrines was sampled in the fasting state, at 30-min intervals during a 120-min glucose tolerance test and during an euglycaemic-hyperinsulinaemic clamp (40 mU m^-2 min^-1 insulin dose). Body composition was determined by leg-to-leg bioelectrical impedance analysis.

Obese subjects had the lowest fasting plasma concentrations of epinephrine (NW: 0.17, 95% confidence interval (CI): 0.14-0.20 nmol l^-1; OW: 0.16, 95% CI: 0.12-0.19 nmol l^-1; OB: 0.11, 95% CI: 0.08-0.13 nmol l^-1; P=0.018) and metanephrine (NW: 0.17, 95% CI: 0.15-0.19 nmol l^-1; OW: 0.15, 95% CI: 0.13-0.16 nmol l^-1; OB: 0.13, 95% CI: 0.12-0.15 nmol l^-1; P=0.022), the latter reflecting adrenal medullary store size. Fasting plasma epinephrine (r=-0.437; P<0.001) and metanephrine (r=-0.477; P<0.001) concentrations were additionally inversely correlated with whole-body fat percentage. Suppression of epinephrine secretion in response to carbohydrate ingestion was significantly blunted in overweight and obese subjects compared with the normal weight subjects (P_interaction=0.045). Most of the variance in basal epinephrine was related to whole-body fat percentage (β=-0.389, 95% CI: -0.09 to -0.69; P=0.012) that explained the lower concentrations of epinephrine and metanephrine in women than men.

We provide evidence that adrenomedullary dysfunction is a characteristic feature of obesity that involves both reduced adrenal secretion of epinephrine and size of adrenal medullary epinephrine stores.