La 11β-hydroxystéroïde déshydrogénase de type 1 - 1re partie

Abdominal obesity plays a key role in the development of metabolic syndrome. Similarities between metabolic syndrome and Cushing disease suggest that excessive local tissue exposition to glucocorticoids, despite normal circulating plasma levels, might contribute to the pathophysiology of metabolic syndrome. To this respect, 11β-hydroxysteroid dehydrogenase type 1 (11HSD1), the enzyme which converts cortisone (inactive) to cortisol (active) in target tissues, raises much interest. Indeed, several studies showed both increased expression and activity of this enzyme in adipose tissues in presence of obesity. Even more striking, experimental data in rodents showed a direct link between increased 11HSD1 activity and the development of metabolic abnormalities. Furthermore, studies in mice KO for 11HSD1 confirmed the potential of inhibiting this enzyme to attenuate metabolic abnormalities related to visceral adiposity. Selective inhibitors of 11HSD1 are currently in development, and preliminary results obtained in rodents appear promising, with significant improvements in glucose and lipid profiles. The development of potent and selective 11HSD1 inhibitors may open new prospects in the treatment of metabolic syndrome or type 2 diabetes associated with abdominal obesity in humans.