Effect of green coffee bean extract and chlorogenic acid consumption on 11_HSD activity in humans and mice

Abstract

Increased 11_ hydroxysteroid dehydrogenase type 1 (11_HSD1) activity is implicated in the development of the metabolic syndrome. Identifying natural compounds that influence 11_HSD1 activity could lead to novel methods of treating obesity, cardiovascular disease and diabetes. In the present study, we tested the effect of green coffee bean extract (GCBE), rich in chlorogenic acid (CGA), in human volunteers and of CGA in mice on blood pressure (BP), lipid and glucose metabolism. Our hypothesis was that CGA would improve these parameters, by blocking the uptake of microsomal glucose-6-phosphate which in turn would limit the production of co-factor for 11_HSD1 reductase activity. With local Ethics Committee approval, 13 healthy overweight subjects were given GCBE containing 90 mg CGA twice daily for 2 weeks. Urinary 24 h free cortisol was reduced from 1.05230.45 to 0.7630.40 nmol/kg (P=0.07). Free cortisone excretion was reduced from 0.7120.38 to 0.4320.24 nmol/kg (P=0.007). Systolic BP decreased from 119.410.5 to 113.89.1 mmHg (P=0.05). Fasting plasma glucose (P=0.101), diastolic BP (P=0.114), free cortisol:cortisone ratio (P=0.216) and anthropometrical measurement were not affected. In vitro, 11_HSD1 activity (conversion of added cortisone to cortisol) in isolated mouse microsomes was inhibited dose-dependently by CGA. The effects of feeding diet containing 0.15% CGA for 17 days was tested in male C57BL6 mice. Adiposity was unaffected but liver (27.74.9 vs 15.52.2 mg/g, P<0.04) and plasma (1.240.18 vs 0.860.08 mg/ml, P<0.08) triglycerides tended to be reduced. Urinary 24 h cortisol excretion following IP injection of 20 mg/kg cortisone was 30.14.1 vs 24.25.3 nmol/kg (P<0.4) for control and CGA-treated mice. Peak plasma glucose levels in tolerance tests were earlier with CGA treatment although, over a 2 h period, glucose clearance was not affected.