title: Identification of carboxypeptidase X (CPX)-1 as a positive regulator of adipogenesis.
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.-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.
authors.affiliation: Metabolic Medicine Group, Mater Research Institute, University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Yu-Hee
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Metabolic Medicine Group, Mater Research Institute, University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Johanna L
authors.initials: JL
authors.lastname: Barclay
authors.affiliation: Metabolic Medicine Group, Mater Research Institute, University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Jingjing
authors.initials: J
authors.lastname: He
authors.affiliation: Metabolic Medicine Group, Mater Research Institute, University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Xiao
authors.initials: X
authors.lastname: Luo
authors.affiliation: Metabolic Medicine Group, Mater Research Institute, University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Hayley M
authors.initials: HM
authors.lastname: O'Neill
authors.affiliation: Metabolic Medicine Group, Mater Research Institute, University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Sahar
authors.initials: S
authors.lastname: Keshvari
authors.affiliation: Metabolic Medicine Group, Mater Research Institute, University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Webster
authors.affiliation: Metabolic Medicine Group, Mater Research Institute, University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Choaping
authors.initials: C
authors.lastname: Ng
authors.affiliation: Metabolic Medicine Group, Mater Research Institute, University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Louise J
authors.initials: LJ
authors.lastname: Hutley
authors.affiliation: Metabolic Medicine Group, Mater Research Institute, University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
authors.forename: Johannes B
authors.initials: JB
authors.lastname: Prins
authors.affiliation: Metabolic Medicine Group, Mater Research Institute, University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia jon.whitehead@mater.uq.edu.au.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Whitehead
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000502:physiology; D050156:Adipogenesis / Q000187:drug effects / Q000502:physiology*; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000818:Animals; D002454:Cell Differentiation; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D045727:Metalloexopeptidases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D009765:Obesity / Q000209:etiology / Q000378:metabolism
chemical_list: C485671:BAMBI protein, human; C485672:Bambi protein, mouse; C000621999:CPXM1 protein, human; D004041:Dietary Fats; D006023:Glycoproteins; D008565:Membrane Proteins; D016220:Fibroblast Growth Factor 1; D045727:Metalloexopeptidases; C117650:Cpxm1 protein, mouse
keywords: adipocyte; collagen; differentiation; extracellular matrix; obesity