Fibroblast activation protein enzyme deficiency prevents liver steatosis, insulin resistance and glucose intolerance and increases fibroblast growth factor-21 in diet induced obese mice

@article{Chowdhury2018FibroblastAP,
  title={Fibroblast activation protein enzyme deficiency prevents liver steatosis, insulin resistance and glucose intolerance and increases fibroblast growth factor-21 in diet induced obese mice},
  author={Sumaiya Islam Chowdhury and Sunmi Song and Hui Emma Zhang and Xin Maggie Wang and Margaret G. Gall and Denise Ming Tse Yu and Angelina J. Lay and Michelle Sui Wen Xiang and Kathryn A Evans and S Wetzel and Yolanda Liu and Belinda Yau and Andrew L. Coppage and Lisa W-Y Lo and Rebecca A. Stokes and Wayne J. Hawthorne and Gregory J. Cooney and Susan V. Mclennan and Jenny E. Gunton and William W. Bachovchin and Nigel Turner and Melkam A. Kebede and Geoffrey W McCaughan and Stephen Morris Twigg and Mark D. Gorrell},
  journal={bioRxiv},
  year={2018}
}
Background & Aims Fibroblast activation protein-a (FAP) is a post-proline peptidase closely related to dipeptidyl peptidase-4. FAP degrades bioactive peptides including fibroblast growth factor-21 (FGF-21) and neuropeptide Y. We examined metabolic outcomes of specific genetic ablation of FAP and its enzyme activity in a mouse model of diet-induced obesity (DIO) causing fatty liver. Methods Wildtype (WT) and genetically modified FAP deficient mice that specifically lacked either the FAP protein… 
2 Citations
Discovery of a novel fibroblast activation protein (FAP) inhibitor, BR103354, with anti-diabetic and anti-steatotic effects
TLDR
Together, BR103354 acts as an effective FAP inhibitor in vitro and in vivo, thereby demonstrating its potential application as an anti-diabetic and anti-NASH agent.
Identification of Novel Natural Substrates of Fibroblast Activation Protein-alpha by Differential Degradomics and Proteomics*
TLDR
This study greatly expands the repertoire of FAP substrates and shows that FAP has a role in coagulation in the mouse and provides insight into the physiological and potential pathological roles of this enigmatic protease.

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