Chemerin Is a Novel Adipocyte-Derived Factor Inducing Insulin Resistance in Primary Human Skeletal Muscle Cells

  1. Henrike Sell1,
  2. Jurga Laurencikiene2,
  3. Annika Taube1,
  4. Kristin Eckardt1,
  5. Andrea Cramer1,
  6. Angelika Horrighs1,
  7. Peter Arner2 and
  8. Jürgen Eckel1
  1. 1Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany;
  2. 2Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
  1. Corresponding author: Henrike Sell, henrike.sell{at}ddz.uni-duesseldorf.de.

Abstract

OBJECTIVE Chemerin is an adipokine that affects adipogenesis and glucose homeostasis in adipocytes and increases with BMI in humans. This study was aimed at investigating the regulation of chemerin release and its effects on glucose metabolism in skeletal muscle cells.

RESEARCH DESIGN AND METHODS Human skeletal muscle cells were treated with chemerin to study insulin signaling, glucose uptake, and activation of stress kinases. The release of chemerin was analyzed from in vitro differentiated human adipocytes and adipose tissue explants from 27 lean and 26 obese patients.

RESULTS Human adipocytes express chemerin and chemokine-like receptor 1 (CMKLR1) differentiation dependently and secrete chemerin (15 ng/ml from 106 cells). This process is slightly but significantly increased by tumor necrosis factor-α and markedly inhibited by >80% by peroxisome proliferator–activated receptor-γ activation. Adipose tissue explants from obese patients are characterized by significantly higher chemerin secretion compared with lean control subjects (21 and 8 ng from 107 cells, respectively). Chemerin release is correlated with BMI, waist-to-hip ratio, and adipocyte volume. Furthermore, higher chemerin release is associated with insulin resistance at the level of lipogenesis and insulin-induced antilipolysis in adipocytes. Chemerin induces insulin resistance in human skeletal muscle cells at the level of insulin receptor substrate 1, Akt and glycogen synthase kinase 3 phosphorylation, and glucose uptake. Furthermore, chemerin activates p38 mitogen-activated protein kinase, nuclear factor-κB, and extracellular signal–regulated kinase (ERK)-1/2. Inhibition of ERK prevents chemerin-induced insulin resistance, pointing to participation of this pathway in chemerin action.

CONCLUSIONS Adipocyte-derived secretion of chemerin may be involved in the negative cross talk between adipose tissue and skeletal muscle contributing to the negative relationship between obesity and insulin sensitivity.

Footnotes

  • The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Received February 24, 2009.
    • Accepted August 10, 2009.
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  1. Diabetes vol. 58 no. 12 2731-2740
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