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American Liver Foundation
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New York, New York 10006
American Liver Foundation Liver Scholar Award
Washington University School of Medicine, St. Louis, MO
PGC-1β- mediated control of hepatic fatty acid metabolism through ChREBP
Obesity-related metabolic disease is an emerging public health crisis. The liver is an organ that is particularly affected by obesity-related metabolic disease. Obesity is associated with hepatic fat accumulation (hepatic steatosis) and abnormalities in circulating triglyceride and glucose levels that are under the control of the liver. In fact, intrahepatic triglyceride levels are highly predictive of systemic insulin resistance, obesity, and metabolic syndrome.
The peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) transcriptional coactivators regulate several components of the hepatic fatty acid and glucose metabolic pathways. Three members of the PGC-1 transcriptional coactivator family have been identified: PGC-1α, PGC-1β, and PRC-1. Previous work suggests that PGC-1α and PGC-1β functionally overlap in most tissues (BAT, heart, skeletal muscle). In contrast, it appears that the functions of PGC-1α and PGC-1β may diverge somewhat in liver. For example, PGC-1β is believed to drive de novo lipogenesis and triglyceride synthesis in hepatocytes through activation of SREBP-1, while PGC-1α does not elicit this effect. However, the molecular mechanisms by which PGC-1β activates these distinct pathways have yet to be comprehensively characterized.
Based on Dr. Chambers’ preliminary data, she hypothesizes that PGC-1β may also serve as a novel transcriptional coactivator for carbohydrate response element binding protein (ChREBP) to coordinate the hepatic lipogenic response by coactivating multiple transcription factors that control lipogenic gene expression.
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