Naturally occurring HCA1 missense mutations result in loss of function: potential impact on lipid deposition.

ABSTRACT: The hydroxy-carboxylic acid receptor (HCA1) is a G protein-coupled receptor that is highly expressed on adipocytes and considered a potential target for the treatment of dyslipidemia. In the current study, we investigated the pharmacological properties of naturally occurring variants in this receptor (H43Q, A110V, S172L, and D253H). After transient expression of these receptors into human embryonic kidney 293 cells, basal and ligand-induced signaling were assessed using luciferase reporter gene assays. The A110V, S172L, and D253 variants showed reduced basal activity; the S172L mutant displayed a decrease in potency to the endogenous ligand L-lactate. Both the S172L and D253H variants also showed impaired cell surface expression, which may in part explain the reduced activity of these rece

SUBMITTER: Doyle JR 

PROVIDER: S-EPMC3617956 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature