Volume 142, Issue 6, Pages 1288-1292 (May 2012) HCV Infection and Metabolic Syndrome: Which Is the Chicken and Which Is the Egg?  Francesco Negro  Gastroenterology  Volume 142, Issue 6, Pages 1288-1292 (May 2012) DOI: 10.1053/j.gastro.2011.12.063 Copyright © 2012 AGA Institute Terms and Conditions

Figure 1 Simplified depiction of some proposed interactions between HCV and lipid metabolism that might lead to steatosis of hepatocytes. HCV has been shown (in vitro and in human liver) to inhibit transcription (and thereby expression and nuclear translocation) of the nuclear transcription factor peroxisome proliferator-activated receptor α (PPARα). In this case, PPARα would not heterodimerize with the retinoid X receptor (RXR) and bind to the peroxisome proliferator responsive element (PPRE); lack of binding would reduce transcription of enzymes involved in fatty acid α-oxidation, such as the carnitine palmitoyltransferase I. HCV might also activate the transcription factors steroid responsive element binding protein (SREBP)-1c and -2, which control expression of enzymes involved in the synthesis of fatty acids and cholesterol, respectively. Finally, HCV interferes with the expression and/or activity of MTTP, a protein that associates with the endoplasmic reticulum and is involved in assembly of VLDL. Although the HCV core protein seems to be sufficient for most of the molecular alterations that lead to steatosis, other viral and host proteins are likely to participate in this process (see Bugianesi et al8). Gastroenterology 2012 142, 1288-1292DOI: (10.1053/j.gastro.2011.12.063) Copyright © 2012 AGA Institute Terms and Conditions

Figure 2 Ways in which HCV might affect insulin signaling in hepatocytes and contribute to hepatic insulin resistance. ER, endoplasmic reticulum; IRS, insulin receptor substrate; JNK, c-Jun-N-terminal kinase; mTORC, mammalian target of rapamycin complex; P, phosphate residue; PDK1, phosphoinositide-dependent protein kinase 1; PIP, phosphatidylinositol phosphate; PKB, protein kinase B; PP2A, protein phosphatase 2A; SOCS, suppressor of cytokine signaling. For further details, please refer to Kaddai and Negro,7 from which the figure was adapted, with permission, and reproduced using images available at www.servier.fr. Gastroenterology 2012 142, 1288-1292DOI: (10.1053/j.gastro.2011.12.063) Copyright © 2012 AGA Institute Terms and Conditions

Gastroenterology 2012 142, 1288-1292DOI: (10. 1053/j. gastro. 2011. 12 Copyright © 2012 AGA Institute Terms and Conditions