Central obesity is associated with increased morbidity and mortality. Preadipocyte proliferation and differentiation contribute to increases in adipose tissue mass, yet the mechanisms that underlie these processes remain unclear. Patients with
glucocorticoid excess develop a reversible form of
central obesity, but circulating
cortisol levels in idiopathic
obesity are invariably normal. We have hypothesized that the
enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), by converting inactive
cortisone to active
cortisol in adipose tissue, might be an important autocrine regulator of fat mass. Paired omental and sc fat biopsies were obtained from 32 women (median age, 43 yr; range, 28-65; median body mass index, 27.5 kg/m(2); range, 19.7-39.2) undergoing elective abdominal surgery.
11beta-HSD1 activity and
mRNA levels were assessed in whole tissue and in isolated preadipocytes and adipocytes using specific
enzyme assays and real-time PCR. Preadipocyte proliferation was measured using tritiated
thymidine incorporation. Whole adipose tissue
11beta-HSD1 mRNA levels did not differ between omental and sc samples (P = 0.73). In addition,
mRNA levels did not correlate with body mass index (omental: r = 0.1; P = 0.6; sc: r = 0.15; P = 0.4). In keeping with earlier studies,
11beta-HSD1 mRNA levels were higher in omental compared with sc preadipocytes. However, in cultured omental preadipocytes,
11beta-HSD1 activity inversely correlated with body mass index (r = -0.47; P = 0.03). In omental preadipocytes, both
cortisol and
cortisone decreased proliferation (P < 0.05). Inhibition of
11beta-HSD1 with
glycyrrhetinic acid partially reversed the
cortisone-induced decrease in preadipocyte proliferation (P < 0.05). Enhanced preadipocyte proliferation within omental adipose tissue as a consequence of decreased
11beta-HSD1 mRNA levels and activity may contribute to increases in visceral adipose tissue mass in obese patients.