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Article
CTRP3 Attenuates Diet-induced Hepatic Steatosis by Regulating Triglyceride Metabolism
American Journal of Physiology - Gastrointestinal and Liver Physiology
  • Jonathan M. Peterson, Johns Hopkins University School of Medicine; East Tennessee State University
  • Marcus M. Seldin, Johns Hopkins University School of Medicine
  • Zhikui Wei, Johns Hopkins University School of Medicine
  • Susan Aja, Johns Hopkins University School of Medicine
  • G. William Wong, John Hopkins University School of Medicine
Document Type
Article
Publication Date
8-1-2013
Description

CTRP3 is a secreted plasma protein of the C1q family that helps regulate hepatic gluconeogenesis and is downregulated in a diet-induced obese state. However, the role of CTRP3 in regulating lipid metabolism has not been established. Here, we used a transgenic mouse model to address the potential function of CTRP3 in ameliorating high-fat diet-induced metabolic stress. Both transgenic and wild-type mice fed a high-fat diet showed similar body weight gain, food intake, and energy expenditure. Despite similar adiposity to wild-type mice upon diet-induced obesity (DIO), CTRP3 transgenic mice were strikingly resistant to the development of hepatic steatosis, had reduced serum TNF-α levels, and demonstrated a modest improvement in systemic insulin sensitivity. Additionally, reduced hepatic triglyceride levels were due to decreased expression of enzymes (GPAT, AGPAT, and DGAT) involved in triglyceride synthesis. Importantly, short-term daily administration of recombinant CTRP3 to DIO mice for 5 days was sufficient to improve the fatty liver phenotype, evident as reduced hepatic triglyceride content and expression of triglyceride synthesis genes. Consistent with a direct effect on liver cells, recombinant CTRP3 treatment reduced fatty acid synthesis and neutral lipid accumulation in cultured rat H4IIE hepatocytes. Together, these results establish a novel role for CTRP3 hormone in regulating hepatic lipid metabolism and highlight its protective function and therapeutic potential in attenuating hepatic steatosis.

Citation Information
Jonathan M. Peterson, Marcus M. Seldin, Zhikui Wei, Susan Aja, et al.. "CTRP3 Attenuates Diet-induced Hepatic Steatosis by Regulating Triglyceride Metabolism" American Journal of Physiology - Gastrointestinal and Liver Physiology Vol. 305 Iss. 3 (2013) p. G214 - G224 ISSN: 1522-1547
Available at: http://works.bepress.com/jonathan-peterson/21/