Fibroblast activation protein (FAP) as a novel metabolic target.

ABSTRACT:

Objective

Fibroblast activation protein (FAP) is a serine protease belonging to a S9B prolyl oligopeptidase subfamily. This enzyme has been implicated in cancer development and recently reported to regulate degradation of FGF21, a potent metabolic hormone. Using a known FAP inhibitor, talabostat (TB), we explored the impact of FAP inhibition on metabolic regulation in mice.

Methods

To address this question we evaluated the pharmacology of TB in various mouse models including those deficient in FGF21, GLP1 and GIP signaling. We also studied the ability of FAP to process FGF21 in vitro and TB to block FAP enzymatic activity.

Results

TB administration to diet-induced obese (DIO) animals led to profound decreases in body weight, reduced food consumption and adiposity, inc

SUBMITTER: Sanchez-Garrido MA 

PROVIDER: S-EPMC5034526 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature