Portal and peripheral cortisol levels in obese humans

Excess total body and visceral fat has been associated with insulin resistance, diabetes and the metabolic syndrome. Excess glucocorticoids produce both central obesity and diabetes. However, systemic glucocorticoid levels are normal in typical Type 2 diabetes and persons with idiopathic obesity. Glucocorticoids can be produced locally through the enzyme 11 beta hydroxysteroid dehydrogenase type 1 (11 beta HSD-1). Transgenic mice with selective overexpression in adipose tissue of 11 beta HSD-1 to levels seen in humans develop visceral obesity, hyperlipidaemia and insulin-resistant diabetes associated with a 2.7-fold increase in corticosterone levels in portal compared to peripheral circulation. To examine whether the liver is exposed to higher levels of glucocorticoids, which may undergo metabolic degradation prior to measurement in the systemic circulation, we assessed concentrations of cortisol in the portal and peripheral circulation in morbidly obese humans.

Portal and peripheral blood samples were obtained simultaneously from six morbidly obese humans with and without diabetes during bariatric abdominal surgery. The samples were assessed for serum cortisol to determine whether an increase in the portal to peripheral circulation is found in obese humans. Insulin, which undergoes metabolic clearance in the liver, and thyroxin (free T(4)), which does not, were also assessed.

Levels of serum cortisol (698.8+/-200.4 vs 696.3+/-232.4 nmol/l, portal vs peripheral, p=0.9) and free T(4) (22.0+/-7.8 vs 20.6+/-8.1 pmol/l, portal vs peripheral, p=0.3) were not significantly different in portal compared to peripheral circulation. Portal insulins were significantly higher than peripheral levels (466.7+/-302.9 vs 78.5+/-50.9 pmol/l, portal vs peripheral, p=0.03).

These observations suggest that in morbidly obese humans the liver is not exposed to excess glucocorticoids.