Metabolomic analysis of a selective ABCA1 inducer in obesogenic challenge provides a rationale for therapeutic development.

ABSTRACT:

Background

Therapeutic agents with novel mechanisms of action are needed to combat the growing epidemic of type 2 diabetes (T2D) and related metabolic syndromes. Liver X receptor (LXR) agonists possess preclinical efficacy yet produce side effects due to excessive lipogenesis. Anticipating that many beneficial and detrimental effects of LXR agonists are mediated by ABCA1 and SREPB1c expression, respectively, we hypothesized that a phenotypic optimization strategy prioritizing selective ABCA1 induction would identify an efficacious lead compound with an improved side effect profile over existing LXRβ agonists.

Methods

We synthesized and characterized a novel small molecule for selective induction of ABCA1 vs. SREBP1c in vitro. This compound was evaluated in both wild-type mic

SUBMITTER: Lewandowski CT 

PROVIDER: S-EPMC8010624 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature