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Identification of carboxypeptidase X (CPX)-1 as a positive regulator of adipogenesis

Title
Identification of carboxypeptidase X (CPX)-1 as a positive regulator of adipogenesis
Authors
Kim, Yu-HeeBarclay, Johanna L.He, JingjingLuo, XiaoO'Neill, Hayley M.Keshvari, SaharWebster, Julie A.Ng, ChoapingHutley, Louise J.Prins, Johannes B.Whitehead, Jonathan P.
Ewha Authors
김유희
SCOPUS Author ID
김유희scopus
Issue Date
2016
Journal Title
FASEB JOURNAL
ISSN
0892-6638JCR Link1530-6860JCR Link
Citation
vol. 30, no. 7, pp. 2528 - 2540
Keywords
obesityadipocytedifferentiationextracellular matrixcollagen
Publisher
FEDERATION AMER SOC EXP BIOL
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Adipose tissue expansion occurs through a combination of hypertrophy of existing adipocytes and generation of new adipocytes via the process of hyperplasia, which involves the proliferation and subsequent differentiation of preadipocytes. Deficiencies in hyperplasia contribute to adipose tissue dysfunction and the association of obesity with chronic cardiometabolic diseases. Thus, increased understanding of hyperplastic pathways may be expected to afford novel therapeutic strategies. We have reported that fibroblast growth factor (FGF)-1 promotes proliferation and differentiation of human preadipocytes and recently demonstrated that bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) is a central, proximal effector. Herein, we describe the identification and characterization of carboxypeptidase X (CPX)-1, a secreted collagen-binding glycoprotein, as a novel downstream effector in human primary and Simpson-Golabi-Behmel syndrome preadipocytes. CPX-1 expression increased after treatment of preadipocytes with FGF-1, BAMBI knockdown, or induction of differentiation. CPX-1 knockdown compromised preadipocyte differentiation coincident with reduced collagen expression. Furthermore, preadipocytes differentiated on matrix derived from CPX-1 knockdown cells exhibited reduced Glut4 expression and insulin-stimulated glucose uptake. Finally, CPX-1 expression was increased in adipose tissue from obese mice and humans. Collectively, these findings establish CPX-1 as a positive regulator of adipogenesis situated downstream of FGF-1/ BAMBI that may contribute to hyperplastic adipose tissue expansion via affecting extracellular matrix remodeling.
DOI
10.1096/fj.201500107R
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연구기관 > 의과학연구소 > Journal papers
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