INHIBITION OF CORTISONE FORMATION IN CENTRAL OBESITY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The active form of cortisone is cortisol, a substance made in the adrenal glands. Cortisol is inactivated by the kidney to form inactive cortisone, and cortisone is reactivated in liver and fat tissue to reform active cortisol. Recent evidence suggests that fat cells in obese individuals have increased activity of the enzyme that reactivates cortisone. Since overproduction of cortisol causes abdominal obesity, it is possible that the overactivity of this reactivation process is responsible for worsening obesity in some individuals. In order to determine the importance of this pathway, we plan to block the formation of cortisone in the kidney using a licorice extract. If reactivation of cortisone in fat cells is important in causing abdominal obesity, inhibition of cortisone formation should cause a decrease in abdominal fat. We will study six women with abdominal obesity. Each subject will be treated with licorice extract for six months. We will measure weight, abdominal and total body fat content, sugar, insulin, cholesterol and blood pressure before treatment and during treatment. Known side effects of licorice include salt retention, increased blood pressure and potassium loss. In order to prevent these side effects, we will administer spironolactone along with the licorice extract. Spironolactone is an effective inhibitor of the hypertensive, salt retaining effects and potassium wasting effects of licorice.