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Metabolic Regulation by C1q/TNF-related Protein-13 (CTRP13): Activation of AMP-activated Protein Kinase and Suppression of Fatty Acid-induced JNK Signaling
The Journal of Biological Chemistry (2011)
  • Zhikui Wei, 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
Members of the C1q/TNF family play important and diverse roles in the immune, endocrine, skeletal, vascular, and sensory systems. Here, we identify and characterize CTRP13, a new and extremely conserved member of the C1q/TNF family. CTRP13 is preferentially expressed by adipose tissue and the brain in mice and predominantly by adipose tissue in humans. Within mouse adipose tissue, CTRP13 is largely expressed by cells of the stromal vascular compartment. Due to sexually dimorphic expression patterns, female mice have higher transcript and circulating CTRP13 levels than males. CTRP13 transcript and circulating levels are elevated in obese male mice, suggesting a potential role in energy metabolism. The insulin-sensitizing drug rosiglitazone also increases the expression of CTRP13 in adipocytes, which correlates with the insulin-sensitizing action of CTRP13. In a heterologous expression system, CTRP13 is secreted as a disulfide-linked oligomeric protein. When co-expressed, CTRP13 forms heteromeric complexes with a closely related family member, CTRP10. This heteromeric association does not involve conserved N-terminal Cys residues. Functional studies using purified recombinant protein demonstrated that CTRP13 is an adipokine that promotes glucose uptake in adipocytes, myotubes, and hepatocytes via activation of the AMPK signaling pathway. CTRP13 also ameliorates lipid-induced insulin resistance in hepatocytes through suppression of the SAPK/JNK stress signaling that impairs the insulin signaling pathway. Further, CTRP13 reduces glucose output in hepatocytes by inhibiting the mRNA expression of gluconeogenic enzymes, glucose-6-phosphatase and the cytosolic form of phosphoenolpyruvate carboxykinase. These results provide the first functional characterization of CTRP13 and establish its importance in glucose homeostasis.
Keywords
  • adipose tissue,
  • amp-activated kinase,
  • ampk,
  • diabetes,
  • metabolic diseases,
  • metabolism,
  • metabolic regulation,
  • obesity
Publication Date
May 6, 2011
DOI
10.1074/jbc.M110.201087
Publisher Statement
© 2011 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 Journal of Biological Chemistry.
Citation Information
Zhikui Wei, Jonathan M. Peterson and G. William Wong. "Metabolic Regulation by C1q/TNF-related Protein-13 (CTRP13): Activation of AMP-activated Protein Kinase and Suppression of Fatty Acid-induced JNK Signaling" The Journal of Biological Chemistry Vol. 286 Iss. 18 (2011) p. 15652 - 15665 ISSN: 1083-351X
Available at: http://works.bepress.com/jonathan-peterson/11/