The present study aimed to explore the role of sterol regulatory element binding protein (SREBP)‑2 and 3‑hydroxy‑3‑methylglutaryl CoA reductase (HMGCR) in hypercholesterolemia susceptibility in gerbils.
Hypercholesterolemia in hypothyroidism is mainly due to a reduction in low-density lipoprotein (LDL) receptor activity, this accompanied by concomitant diminishing control by triiodothyronine (T3) of sterol regulatory element-binding protein 2 (SREBP-2), which modulates cholesterol biosynthesis by regulating rate-limit degrading enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA) activity.
The levels of Fatty acid synthase (FAS) and SREBP-2 expressions in placenta are significantly increased in the HC group while expression of both sterol regulatory element-binding proteins-1 (SREBP-1) and HMG-CoA reductase (HMGR) are not modified.
In summary, this is the first report of mutations in the human SREBP-2 gene to suggest that these and/or other mutations in this key regulator of cholesterol metabolism are associated with hypercholesterolaemia.