Fibroblast growth factor-1 (FGF-1) promotes adipogenesis by downregulation of carboxypeptidase A4 (CPA4) – a negative regulator of adipogenesis implicated in the modulation of local and systemic insulin sensitivity

He, Jingjing, Chen, Daniel L., Samocha-Bonet, Dorit, Gillinder, Kevin R., Barclay, Johanna L., Magor, Graham W., Perkins, Andrew C., Greenfield, Jerry R., Yang, Gongshe and Whitehead, Jon (2016) Fibroblast growth factor-1 (FGF-1) promotes adipogenesis by downregulation of carboxypeptidase A4 (CPA4) – a negative regulator of adipogenesis implicated in the modulation of local and systemic insulin sensitivity. Growth Factors, 34 (5-6). pp. 210-216. ISSN 0897-7194

Documents
CPA4 - adipogenesis - Growth factors - accepted.pdf
[img]
[Download]
[img]
Preview
PDF
CPA4 - adipogenesis - Growth factors - accepted.pdf - Whole Document

1MB
Item Type:Article
Item Status:Live Archive

Abstract

Fibroblast growth factor-1 (FGF-1) promotes differentiation of human preadipocytes into mature adipocytes via modulation of a BMP and Activin Membrane-Bound Inhibitor (BAMBI)/Peroxisome proliferator-activated receptor (PPAR?)-dependent network. Here, we combined transcriptomic and functional investigations to identify novel downstream effectors aligned with complementary analyses of gene expression in human adipose tissue to explore relationships with insulin sensitivity. RNA-Seq and qRT-PCR analysis revealed significant down-regulation of carboxypeptidase A4 (CPA4) following FGF-1 treatment or induction of differentiation of human preadipocytes in a BAMBI/PPAR?-independent manner. siRNA-mediated knockdown of CPA4 resulted in enhanced differentiation of human preadipocytes. Furthermore, expression of CPA4 in subcutaneous adipose tissue correlated negatively with indices of local and systemic (liver and muscle) insulin sensitivity. These results identify CPA4 as a negative regulator of adipogenesis that is down-regulated by FGF-1 and a putative deleterious modulator of local and systemic insulin sensitivity. Further investigations are required to define the molecular mechanism(s) involved and potential therapeutic opportunities.

Keywords:Obesity, Adipogenesis, Growth Factor, Insulin sensitivity, JCNotOpen
Subjects:C Biological Sciences > C130 Cell Biology
C Biological Sciences > C741 Medical Biochemistry
Divisions:College of Science > School of Life Sciences
Related URLs:
ID Code:26591
Deposited On:03 Mar 2017 09:52

Repository Staff Only: item control page