11β-Hydroxysteroid Dehydrogenase Type 1 in Adipose Tissue and Prospective Changes in Body Weight and Insulin Resistance*

Abstract

Increased mRNA and activity levels of 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) in human adipose tissue (AT) are associated with obesity and insulin resistance. The aim of our study was to investigate whether 11betaHSD1 expression or activity in abdominal subcutaneous AT of non-diabetic subjects are associated with subsequent changes in body weight and insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)]. Prospective analyses were performed in 20 subjects (two whites and 18 Pima Indians) who had baseline measurements of 11betaHSD1 mRNA and activity in whole AT (follow-up, 0.3 to 4.9 years) and in 47 Pima Indians who had baseline assessments of 11betaHSD1 mRNA in isolated adipocytes (follow-up, 0.8 to 5.3 years). In whole AT, although 11betaHSD1 mRNA levels showed positive associations with changes in weight and HOMA-IR, 11betaHSD1 activity was associated with changes in HOMA-IR but not in body weight. 11betaHSD1 mRNA levels in isolated adipocytes were not associated with follow-up changes in any of the anthropometric or metabolic variables. Our results indicate that increased expression of 11betaHSD1 in subcutaneous abdominal AT may contribute to risk of worsening obesity and insulin resistance. This prospective relationship does not seem to be mediated by increased 11betaHSD1 expression in adipocytes.