Tissue Specific Ablation of ACSL4 Results in Disturbed Steroidogenesis. Endocrinology Wang, W., Hao, X., Han, L., Yan, Z., Shen, W., Dong, D., Hasbargen, K., Bittner, S., Cortez, Y., Greenberg, A. S., Azhar, S., Kraemer, F. B. 2019


ACSL4 is a member of the ACSL family that catalyzes the conversion of long chain fatty acids to acyl CoAs, which are essential for fatty acid incorporation and utilization into diverse metabolic pathways including cholesteryl ester synthesis. Cholesteryl esters in steroidogenic tissues such as the adrenal gland are particularly enriched in cholesteryl esters of long chain polyunsaturated fatty acids and constitute an important pool supplying cholesterol for steroid synthesis. The current studies addressed whether ACSL4 is required for normal steroidogenesis. CYP11A1 promoter-mediated Cre was used to generate steroid-tissue specific ACSL4 KO mice. Results demonstrate that ACSL4 plays an important role in adrenal cholesteryl ester formation, as well as determining the fatty acyl composition of adrenal cholesteryl esters, with ACSL4 deficiency leading to reductions in cholesteryl ester storage and alterations in cholesteryl ester composition. Statistically significant reductions in corticosterone and testosterone, but not progesterone, production were observed in vivo, and these deficits were accentuated in ex vivo and in vitro studies of isolated steroid tissues and cells from ACSL4 deficient mice. However, these effects on steroid production appear due to reductions in cholesteryl ester stores rather than disturbances of signaling pathways. We conclude that ACSL4 is dispensable for normal steroidogenesis.

View details for DOI 10.1210/en.2019-00464

View details for PubMedID 31504388