title: Chemerin is a novel adipocyte-derived factor inducing insulin resistance in primary human skeletal muscle cells.
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.
  
  
  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 10(6) cells). This process is slightly but significantly increased by tumor necrosis factor-alpha and markedly inhibited by >80% by peroxisome proliferator-activated receptor-gamma activation. Adipose tissue explants from obese patients are characterized by significantly higher chemerin secretion compared with lean control subjects (21 and 8 ng from 10(7) 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-kappaB, 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.
authors.affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany. henrike.sell@ddz.uni-duesseldorf.de
authors.forename: Henrike
authors.initials: H
authors.lastname: Sell
authors.forename: Jurga
authors.initials: J
authors.lastname: Laurencikiene
authors.forename: Annika
authors.initials: A
authors.lastname: Taube
authors.forename: Kristin
authors.initials: K
authors.lastname: Eckardt
authors.forename: Andrea
authors.initials: A
authors.lastname: Cramer
authors.forename: Angelika
authors.initials: A
authors.lastname: Horrighs
authors.forename: Peter
authors.initials: P
authors.lastname: Arner
authors.forename: Jürgen
authors.initials: J
authors.lastname: Eckel
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D015992:Body Mass Index; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins; D032342:Muscle Cells / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D020239:Receptor Cross-Talk; D019707:Receptors, Chemokine / Q000378:metabolism; D049629:Waist-Hip Ratio
chemical_list: C102741:CMKLR1 protein, human; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; C478630:RARRES2 protein, human; D019707:Receptors, Chemokine; D005947:Glucose