Metabolic regulation by C1q/TNF-related protein-13 (CTRP13): activation OF AMP-activated protein kinase and suppression of fatty acid-induced JNK signaling

J Biol Chem. 2011 May 6;286(18):15652-65. doi: 10.1074/jbc.M110.201087. Epub 2011 Mar 4.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism*
  • Adipocytes / metabolism
  • Adipokines / physiology*
  • Animals
  • Complement C1q / physiology*
  • Energy Metabolism / physiology*
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • Fatty Acids / metabolism*
  • Fatty Acids / pharmacology
  • Female
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Developmental / physiology
  • Glucose / metabolism
  • Glucose-6-Phosphatase / biosynthesis
  • Glucose-6-Phosphatase / genetics
  • Hepatocytes / metabolism
  • Humans
  • MAP Kinase Kinase 4 / genetics
  • MAP Kinase Kinase 4 / metabolism*
  • Male
  • Mice
  • Mice, Obese
  • Phosphoenolpyruvate Carboxylase / biosynthesis
  • Phosphoenolpyruvate Carboxylase / genetics
  • Protein Multimerization / drug effects
  • Protein Multimerization / physiology
  • Sex Characteristics
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Tumor Necrosis Factors / biosynthesis*
  • Tumor Necrosis Factors / genetics


  • Adipokines
  • C1QL3 protein, human
  • Fatty Acids
  • Tumor Necrosis Factors
  • Complement C1q
  • AMP-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Glucose-6-Phosphatase
  • Phosphoenolpyruvate Carboxylase
  • Glucose