Project A07

Metabolic regulation of adrenocortical function

Steroidogenesis is an energy-demanding process but its metabolic requirements are not entirely understood. We study how cell metabolism and particularly polyunsaturated fatty acid metabolism, cholesterol biosynthesis and the citrate cycle regulate steroidogenesis in adrenocortical cells. We explore the contribution of cholesterol biosynthesis in adrenocortical steroidogenesis and the metabolic mechanisms regulating acetyl-CoA availability in adrenocortical cells. Moreover, we found that FADS2 (fatty acid desaturase 2), the rate limiting enzyme for polyunsaturated fatty acid synthesis, regulates the lipidomic landscape of adrenocortical cells and promotes adrenocortical steroidogenesis by increasing cholesterol uptake in mitochondria. We demonstrated that an eicosapentaenoic acid analogue, icosapent ethyl, which is in clinical use for lowering the risk of cardiovascular disease, reduces FADS2 expression in adrenocortical cells and corticoid production in obese mice. As a continuation of these preclinical studies, we aim to delineate whether icosapent ethyl has cortisol-lowering effects in humans.

© SFB/TRR 205