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C1q/Tumor Necrosis Factor-related Protein 11 (CTRP11), A Novel Adipose Stroma-derived Regulator of Adipogenesis
The Journal of Biological Chemistry (2013)
  • Zhikui Wei, Johns Hopkins University School of Medicine
  • Marcus M. Seldin, Johns Hopkins University School of Medicine
  • Niranjana Natarajan, Johns Hopkins University School of Medicine
  • David C. Djemal, Johns Hopkins University School of Medicine
  • Jonathan M. Peterson, Johns Hopkins University School of Medicine
  • G. William Wong, Johns Hopkins University School of Medicine
Abstract
C1q/TNF-related proteins (CTRPs) are a family of secreted regulators of glucose and lipid metabolism. Here, we describe CTRP11, a novel and phylogenetically conserved member of the C1q family. Our studies revealed that white and brown adipose are major tissues that express CTRP11, and its expression is acutely regulated by changes in metabolic state. Within white adipose tissue, CTRP11 is primarily expressed by stromal vascular cells. As a secreted multimeric protein, CTRP11 forms disulfide-linked oligomers. Although the conserved N-terminal Cys-28 and Cys-32 are dispensable for the assembly of higher-order oligomeric structures, they are unexpectedly involved in modulating protein secretion. When co-expressed, CTRP11 forms heteromeric complexes with closely related CTRP10, CTRP13, and CRF (CTRP14) via the C-terminal globular domains, combinatorial associations that potentially generate functionally distinct complexes. Functional studies revealed a role for CTRP11 in regulating adipogenesis. Ectopic expression of CTRP11 or exposure to recombinant protein inhibited differentiation of 3T3-L1 adipocytes. The expression of peroxisome proliferator-activated receptor-γ and CAAT/enhancer binding protein-α, which drive the adipogenic gene program, was markedly suppressed by CTRP11. Impaired adipogenesis was caused by a CTRP11-mediated decrease in p42/44-MAPK signaling and inhibition of mitotic clonal expansion, a process essential for adipocyte differentiation in culture. These results implicate CTRP11 as a novel secreted regulator of adipogenesis and highlight the potential paracrine cross-talk between adipocytes and cells of the stromal vascular compartment in maintaining adipose tissue homeostasis.
Keywords
  • adipocyte,
  • adipogenesis,
  • adipokines,
  • adipose tissue,
  • map kinases,
  • mapks
Publication Date
April 12, 2013
DOI
10.1074/jbc.M113.458711
Publisher Statement
© 2012 by The American Society for Biochemistry and Molecular Biology, Inc. Author’s may post the final edited PDFs created by the publisher to their own Web sites 12 months after publication. This document was originally published in The Journal of Biological Chemistry.
 
Citation Information
Zhikui Wei, Marcus M. Seldin, Niranjana Natarajan, David C. Djemal, et al.. "C1q/Tumor Necrosis Factor-related Protein 11 (CTRP11), A Novel Adipose Stroma-derived Regulator of Adipogenesis" The Journal of Biological Chemistry Vol. 288 Iss. 15 (2013) p. 10214 - 10229 ISSN: 0021-9258
Available at: http://works.bepress.com/jonathan-peterson/3/
Creative Commons license
Creative Commons License
This work is licensed under a Creative Commons CC_BY International License.