The Liver is the Site of Splanchnic Cortisol Production in Obese Non-diabetic Humans

Abstract

Objective: To determine the contribution of liver and viscera to splanchnic cortisol production in humans.

Research Design: D4 cortisol was infused intravenously; arterial, portal venous and hepatic venous blood sampled; liver and visceral fat biopsied in subjects undergoing bariatric surgery.

Results: Ratios of arterial and portal vein D4 cortisol/cortisol_total (0.06 ± 0.01 vs. 0.06 ± 0.01) and D4 cortisol/D3 cortisol (1.80 ± 0.14 vs. 1.84 ± 0.14) did not differ, indicating that no visceral cortisol production or conversion of D4 cortisol to D3 cortisol via 11β-HSD-1 occurred. Conversely, ratios of both D4 cortisol/cortisol_total (0.05 ± 0.01; p<0.05) and D4 cortisol/D3 cortisol (1.33 ± 0.11; p<0.001) were lower in the hepatic vein than portal vein, indicating production of both cortisol and D3 cortisol by the liver. The viscera did not produce either cortisol (-8.1 ± 2.6 μg/min) or D3 cortisol (-0.2 ± 0.1 μg/min). In contrast, the liver produced both cortisol (22.7 ± 3.90 μg/min) and D3 cortisol (1.9 ± 0.4 μg/min) and accounted for all splanchnic cortisol and D3 cortisol production. Additionally, 11β-HSD-1 mRNA was ∼9 fold higher (p<0.01) in liver than visceral fat. While 11β-HSD-2 gene expression was very low in visceral fat, the viscera released cortisone (p<0.001) and D3 cortisone (p<0.01) into the portal vein.

Conclusions: The liver accounts for all splanchnic cortisol production in obese non-diabetic humans. In contrast, the viscera releases cortisone into the portal vein thereby providing substrate for intra-hepatic cortisol production.