Patients with Cushing’s syndrome have similar characteristics as individuals with the metabolic syndrome, such as intra-abdominal (visceral) obesity, insulin resistance, and dyslipidemia. Long-term glucocorticoid therapy is also associated with the development of these complications. Studies in animals have demonstrated that AMP-activated protein kinase (AMPK) is a key regulatory enzyme for lipid and carbohydrate metabolism and is involved in the development of harmful effects in the presence of excess glucocorticoids. This study investigated AMPK activity of the intra-abdominal adipose tissue of 11 patients with Cushing’s syndrome, nine sex-, age-, and weight-matched patients with adrenal incidentalomas, and four patients with non-endocrine related abdominal surgery (controls). A 70% reduction in AMPK activity was observed in the adipose tissue of patients with Cushing’s syndrome compared to patients with adrenal incidentalomas and the control group. Fatty acid synthase and phosphoenol-pyruvate carbokinase, which are important rate-limiting enzymes in fatty acid synthesis and glyceroneogenesis, were also measured in the three groups of patients. Only fatty acid synthase mRNA was significantly upregulated in the intra-abdominal adipose tissue of patients with Cushing’s syndrome compared to control subjects. Results of this study suggest that glucocorticoids inhibit AMPK activity in adipose tissue and could be one mechanism to explain the deposition of adipose tissue in the intra-abdominal depot in patients with Cushing’s syndrome.
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