Liver Is the Site of Splanchnic Cortisol Production in Obese Nondiabetic Humans

  1. Rita Basu1,
  2. Ananda Basu1,
  3. Meagan Grudzien2,
  4. Paul Jung2,
  5. Peer Jacobson2,
  6. Michael Johnson3,
  7. Ravinder Singh4,
  8. Michael Sarr5 and
  9. Robert A. Rizza1
  1. 1Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic College of Medicine, Rochester, Minnesota
  2. 2Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, Illinois
  3. 3Department of Radiology, Mayo Clinic College of Medicine, Rochester, Minnesota
  4. 4Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota
  5. 5Department of Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota
  1. Corresponding author: Robert A. Rizza, rizza.robert{at}mayo.edu

Abstract

OBJECTIVE—To determine the contribution of liver and viscera to splanchnic cortisol production in humans.

RESEARCH DESIGN AND METHODS—D4 cortisol was infused intravenously; arterial, portal venous, and hepatic venous blood was sampled; and liver and visceral fat were biopsied in subjects undergoing bariatric surgery.

RESULTS—Ratios of arterial and portal vein D4 cortisol/cortisoltotal (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-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) occurred. Conversely, ratios of both D4 cortisol to cortisoltotal (0.05 ± 0.01; P < 0.05) and D4 cortisol to D3 cortisol (1.33 ± 0.11; P < 0.001) were lower in the hepatic vein than in the 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 approximately ninefold higher (P < 0.01) in liver than in visceral fat. Although 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 nondiabetic humans. In contrast, the viscera releases cortisone into the portal vein, thereby providing substrate for intrahepatic cortisol production.

Footnotes

  • Published ahead of print at http://diabetes.diabetesjournals.org on 13 October 2008.

    Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    See accompanying commentary, p. 14

    • Accepted September 20, 2008.
    • Received August 6, 2008.
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  1. Published online before print October 13, 2008, doi: 10.2337/db08-1079 Diabetes January 2009 vol. 58 no. 1 39-45
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