1. ^*Endocrinology Unit, Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom;
2. ^†Division of Endocrinology and Metabolism, Department of Internal Medicine, the Mayo Clinic, Rochester, Minnesota.

Correspondence: Nicholas M. Morton Endocrinology Unit, Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. E-mail: Nik.Morton@ed.ac.uk

^*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.

Received 30 July 2006; Revised  0000; Accepted 15 November 2006.

Abstract

Objectives: In ideopathic obesity, there is evidence that enhanced cortisol regeneration within abdominal subcutaneous adipose tissue may contribute to adiposity and metabolic disease. Whether the cortisol regenerating enzyme, 11-hydroxysteroid dehydrogenase type 1 (11HSD1), or glucocorticoid receptor (GR) levels are altered in other adipose depots remains uncertain. Our objective was to determine the association between 11HSD1 and GR mRNA levels in four distinct adipose depots and measures of obesity and the metabolic syndrome.

Research Methods and Procedures: Adipose tissue biopsies were collected from subcutaneous (abdominal, thigh, gluteal) and intra-abdominal (omental) adipose depots from 21 women. 11HSD1 and GR mRNA levels were measured by real-time polymerase chain reaction. Body composition, fat distribution, fat cell size, and blood lipid, glucose, and insulin levels were measured.

Results: 11HSD1 mRNA was highest in abdominal subcutaneous (p < 0.001) and omental (p < 0.001) depots and was positively correlated with BMI and visceral adiposity in all depots. Omental 11HSD1 correlated with percent body fat (R = 0.462, p < 0.05), fat cell size (R = 0.72, p < 0.001), and plasma triglycerides (R = 0.46, p < 0.05). Conversely, GR mRNA was highest in omental fat (p < 0.001). GR mRNA was negatively correlated with BMI in the abdominal subcutaneous (R = -0.589, p < 0.05) and omental depots (R = -0.627, p < 0.05). Omental GR mRNA was inversely associated with visceral adiposity (R = -0.507, p < 0.05), fat cell size (R = -0.52, p < 0.01), and triglycerides (R = -0.50, p < 0.05).

Discussion: Obesity was associated with elevated 11HSD1 mRNA in all adipose compartments. GR mRNA is reduced in the omental depot with obesity. The novel correlation of 11HSD1 with omental fat cell size, independent of obesity, suggests that intracellular cortisol regeneration is a strong predictor of hypertrophy in the omentum.