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Myonectin (CTRP15), A Novel Myokine that Links Skeletal Muscle to Systemic Lipid Homeostasis
The Journal of Biological Chemistry (2012)
  • Marcus M. Seldin, Johns Hopkins University School of Medicine
  • Jonathan M. Peterson, Johns Hopkins University School of Medicine
  • Mardi S. Byerly, Johns Hopkins University School of Medicine
  • Zhikui Wei, Johns Hopkins University School of Medicine
  • G. William Wong, Johns Hopkins University School of Medicine
Abstract
Skeletal muscle plays important roles in whole-body glucose and fatty acid metabolism. However, muscle also secretes cytokines and growth factors (collectively termed myokines) that can potentially act in an autocrine, a paracrine, and/or an endocrine manner to modulate metabolic, inflammatory, and other processes. Here, we report the identification and characterization of myonectin, a novel myokine belonging to the C1q/TNF-related protein (CTRP) family. Myonectin transcript was highly induced in differentiated myotubes and predominantly expressed by skeletal muscle. Circulating levels of myonectin were tightly regulated by the metabolic state; fasting suppressed, but refeeding dramatically increased, its mRNA and serum levels. Although mRNA and circulating levels of myonectin were reduced in a diet-induced obese state, voluntary exercise increased its expression and circulating levels. Accordingly, myonectin transcript was up-regulated by compounds (forskolin, epinephrine, ionomycin) that raise cellular cAMP or calcium levels. In vitro, secreted myonectin forms disulfide-linked oligomers, and when co-expressed, forms heteromeric complexes with other members of the C1q/TNF-related protein family. In mice, recombinant myonectin administration reduced circulating levels of free fatty acids without altering adipose tissue lipolysis. Consistent with this, myonectin promoted fatty acid uptake in cultured adipocytes and hepatocytes, in part by up-regulating the expression of genes (CD36, FATP1, Fabp1, and Fabp4) that promote lipid uptake. Collectively, these results suggest that myonectin links skeletal muscle to lipid homeostasis in liver and adipose tissue in response to alterations in energy state, revealing a novel myonectin-mediated metabolic circuit.
Keywords
  • adipokines,
  • exercise,
  • fatty acid transport,
  • lipid metabolism,
  • skeletal muscles,
  • skeletal muscle metabolism,
  • myokine
Publication Date
April 6, 2012
DOI
10.1074/jbc.M111.336834
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 Journal of Biological Chemistry.
Citation Information
Marcus M. Seldin, Jonathan M. Peterson, Mardi S. Byerly, Zhikui Wei, et al.. "Myonectin (CTRP15), A Novel Myokine that Links Skeletal Muscle to Systemic Lipid Homeostasis" The Journal of Biological Chemistry Vol. 287 Iss. 15 (2012) p. 11968 - 11980 ISSN: 1083-351X
Available at: http://works.bepress.com/jonathan-peterson/8/