The major green tea polyphenol, epigallocatechin gallate, inhibits 11β‐hydroxysteroid dehydrogenase type 1 activity in rodent adipocytes

Abstract

Epigallocatechin gallate (EGCG) in green tea is thought to be useful as an anti‐obesity compound since it has been shown to reduce diet‐induced obesity in mice, rats and humans. On the other hand, 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) converts inactive glucocorticoid (GC) to active GC in the liver and adipose tissue. Activated GC plays an important role in the pathogenesis of central obesity. This study investigated the effect of EGCG on 11β‐HSD1 activity in rodent adipose tissue. Microsome (Mc) containing 11β‐HSD1 was prepared from rat mesenteric adipose depots. Then 11β‐HSD1 activity in Mc was determined in MOPS buffer containing 1 μM 11‐dehydrocorticosterone and varying concentrations of EGCG (NADPH‐regenerating system). After the addition of Mc, the reactants were incubated at 37°C for 60 min. Corticosterone produced in the medium was measured by HPLC. Significant inhibition of 11β‐HSD1 by EGCG (1–40 μM) was observed. Kinetic study demonstrated that EGCG acted as a non‐competitive inhibitor of 11β‐HSD1 with an IC50 of 2.5 μM. The inhibition of 11β‐HSD1 appeared within 60 min in a cell‐free system. These findings suggest that the most likely mechanism of 11β‐HSD1 inhibition by EGCG is via direct interaction between EGCG and 11β‐HSD1 enzyme, rather than via transcriptional pathway. The anti‐obesity effects of EGCG are attributed, at least in part, to the inhibition of 11β‐HSD1 activity in adipocytes.