Our goal is to identify the potential role of the novel adipose tissue-derived factor, C1q TNF Related Protein 3 (CTRP3), as a therapeutic target to treat/prevent alcoholic fatty liver disease (AFLD). Background: Alcoholic fatty liver disease (AFLD) is a significant public health concern. Cirrhosis is the 12th leading cause of death in the United States with approximately half of its cases attributed to AFLD. Currently, there are no known pharmacological treatments available to treat AFLD. Rationale: We identified a novel adipose tissue-derived factor, CTRP3, which significantly inhibits high fat diet-induced hepatic steatosis. The CTRP3 levels, however, may be reduced with alcohol consumption. The inhibitory effect of CTRP3 on alcoholic-induced hepatic steatosis and reduction in CTRP3 levels in ALFD has not been established. Hypothesis: CTRP3 attenuates alcoholic-induced hepatic lipid accumulation.
Specific Aims : 1) to determine whether increased circulating CTRP3 levels can reduce alcohol-induced hepatic lipid accumulation and 2) to confirm that alcohol exposure reduces circulating CTRP3 levels.
These aims are designed to establish not only the beneficial effect of CTRP3 towards preventing AFLD, but also show that normal CTRP3 levels are suppressed by alcohol consumption. These data will identify the potential pharmaceutical impact of CTRP3 treatment. Research Design: To test our hypothesis we will determine the ability of transgenic overexpression of CTRP3 (CTRP3 Tg) to prevent alcohol-induced hepatic lipid accumulation in mice. Further, we will examine the effects of alcohol-feeding on circulating CTRP3 levels in wild type mice. Relevance: The proposed research is highly innovative since it examines a completely novel mechanism that leads to AFLD. Additionally, the proposed research has the potential for high impact since CTRP3 may be used clinically as a treatment for AFLD.
Alcoholic fatty liver disease (AFLD) is a significant public health concern in the United States and the first step in pathogenesis of AFLD is the development of a fatty liver. Health complications and mortality risk is much worse for patients with alcoholic fatty liver. We identified CTRP3 as a potent inhibitor of high fat diet-induced fatt liver. Therefore we propose to determine if CTRP3 can prevent alcohol-induced liver lipid accumulation.
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|Kwon, Megan R; Cress, Eileen; Clark, W Andrew et al. (2018) The adipokine C1q TNF related protein 3 (CTRP3) is elevated in the breast milk of obese mothers. PeerJ 6:e4472|
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|Li, Ying; Ozment, Tammy; Wright, Gary L et al. (2016) Identification of Putative Receptors for the Novel Adipokine CTRP3 Using Ligand-Receptor Capture Technology. PLoS One 11:e0164593|
|Wagner, Roy Marshal; Sivagnanam, Kamesh; Clark, William Andrew et al. (2016) Divergent relationship of circulating CTRP3 levels between obesity and gender: a cross-sectional study. PeerJ 4:e2573|