Investigation of an ALDH1A1-specific inhibitor for suppression of weight gain in a diet-induced mouse model of obesity.

ABSTRACT:

Background

Retinoic acid (RA) controls diverse physiological functions including weight regulation and energy metabolism. It has been reported that mice lacking ALDH1A1, one of the aldehyde dehydrogenases (ALDH) that synthesize RA, are healthy and resistant to weight gain, raising the possibility that inhibiting this enzyme might treat obesity. We previously demonstrated that treatment with a pan-ALDH1A enzyme inhibitor, WIN18446, suppressed weight gain in mice fed a high-fat diet (HFD), but caused increased hepatic lipidosis and reversible male infertility.

Methods

A series of piperazine compounds that inhibited ALDH1A1 were identified and their inhibitory activity was characterized in vitro using purified recombinant enzymes and cell-based assay systems. One potent compoun

SUBMITTER: Haenisch M 

PROVIDER: S-EPMC8238815 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature