Beta-Arrestin 1 Mediates Liver Thyrotropin Regulation of Cholesterol Conversion Metabolism via the Akt-Dependent Pathway.

Beta-Arrestin 1 Mediates Liver Thyrotropin Regulation of Cholesterol Conversion Metabolism via the Akt-Dependent Pathway. Int J Endocrinol. 2018;2018:4371396 Authors: Niu S, Li H, Chen W, Zhao J, Gao L, Bo T Abstract After activation, G protein-coupled receptors (GPCRs) are desensitized by β-arrestins (ARRBs). Moreover, ARRBs can initiate a second wave of signaling independent of G proteins. Thyroid-stimulating hormone receptor (TSHR) is one of the GPCR members. In our previous study, TSHR was identified in the liver; the major role of TSHR in cholesterol metabolism was illustrated, as TSH could regulate hepatic cholesterol metabolism via cAMP/PKA/CREB/HMGCR and SREBP2/HNF4α/CYP7A1 pathways. It has been reported that ARRB2 predominates over ARRB1 in TSHR internalization. However, the significance of ARRBs in TSH-initiated cholesterol metabolism has not been illustrated. In our study, the effects of ARRBs on TSH-regulated cholesterol metabolism are investigated. ARRB1/2 was genetically inactivated in C57BL/6 mice and HepG2 cell line, respectively. Cholesterol levels in arrestin-knockout mice and arrestin-knockdown cells were measured. Molecules participating in cholesterol metabolism were analyzed. It turned out that deficiencies in ARRB1 led to decreased cholesterol levels and decreased TSH-stimulated AKT phosphorylation. Subsequently, the inhibitory effect on CYP7A1 by SREBP2 was reduced due to lowered mature SREBP2 level. Other t...
Source: International Journal of Endocrinology - Category: Endocrinology Tags: Int J Endocrinol Source Type: research