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Identification of carboxypeptidase X (CPX)‐1 as a positive regulator of adipogenesis
Author(s) -
Kim YuHee,
Barclay Johanna L.,
He Jingjing,
Luo Xiao,
O'Neill Hayley M.,
Keshvari Sahar,
Webster Julie A.,
Ng Choaping,
Hutley Louise J.,
Prins Johannes B.,
Whitehead Jonathan P.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201500107r
Subject(s) - adipogenesis , adipose tissue , endocrinology , medicine , fgf21 , gene knockdown , chemistry , biology , microbiology and biotechnology , fibroblast growth factor , biochemistry , apoptosis , receptor
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.— Kim, Y.‐H., Barclay, J. L., He, J., Luo, X., O'Neill, H. M., Keshvari, S., Webster, J. A., Ng, C., Hutley, L. J., Prins, J. B., Whitehead, J. P. Identification of carboxypeptidase X (CPX)‐1 as a positive regulator of adipogenesis. FASEB J. 30, 2528‐2540 (2016). www.fasebj.org