Skip to main content
Article
CTRP9 Transgenic Mice are Protected from Diet-induced Obesity and Metabolic Dysfunction
American Journal of Physiology (2013)
  • Jonathan M. Peterson, Johns Hopkins University School of Medicine
  • Zhikui Wei, Johns Hopkins University School of Medicine
  • Marcus M. Seldin, Johns Hopkins University School of Medicine
  • Mardi S. Byerly, Johns Hopkins University School of Medicine
  • Susan Aja, Johns Hopkins University School of Medicine
  • G. William Wong, Johns Hopkins University School of Medicine
Abstract
CTRP9 is a secreted multimeric protein of the C1q family and the closest paralog of the insulin-sensitizing adipokine, adiponectin. The metabolic function of this adipose tissue-derived plasma protein remains largely unknown. Here, we show that the circulating levels of CTRP9 are downregulated in diet-induced obese mice and upregulated upon refeeding. Overexpressing CTRP9 resulted in lean mice that dramatically resisted weight gain induced by a high-fat diet, largely through decreased food intake and increased basal metabolism. Enhanced fat oxidation in CTRP9 transgenic mice resulted from increases in skeletal muscle mitochondrial content, expression of enzymes involved in fatty acid oxidation (LCAD and MCAD), and chronic AMPK activation. Hepatic and skeletal muscle triglyceride levels were substantially decreased in transgenic mice. Consequently, CTRP9 transgenic mice had a greatly improved metabolic profile with markedly reduced fasting insulin and glucose levels. The high-fat diet-induced obesity, insulin resistance, and hepatic steatosis observed in wild-type mice were prevented in transgenic mice. Consistent with the in vivo data, recombinant protein significantly enhanced fat oxidation in L6 myotubes via AMPK activation and reduced lipid accumulation in H4IIE hepatocytes. Collectively, these data establish CTRP9 as a novel metabolic regulator and a new component of the metabolic network that links adipose tissue to lipid metabolism in skeletal muscle and liver.
Keywords
  • obesity,
  • type 2 diabetes,
  • C1q family,
  • energy,
  • metabolism,
  • fatty acid oxidation,
  • ampk
Publication Date
September 1, 2013
DOI
10.1152/ajpregu.00110.2013
Citation Information
Jonathan M. Peterson, Zhikui Wei, Marcus M. Seldin, Mardi S. Byerly, et al.. "CTRP9 Transgenic Mice are Protected from Diet-induced Obesity and Metabolic Dysfunction" American Journal of Physiology Vol. 305 Iss. 5 (2013) p. R522 - R533 ISSN: 1522-1490
Available at: http://works.bepress.com/jonathan-peterson/4/