[3] Interestingly, Cbs−/− mice exhibit severe liver injury, steatosis, and fibrosis.[32] In a similar manner, we also investigated the role of PLIN2 on a background of high SAMe. For these studies we generated a novel, double Gnmt−/−/Plin2−/− knockout mouse model that is characterized by high hepatic SAMe and low PE content, much like Gnmt−/− mice, that in contrast did not develop fatty liver. Consistent with previous findings,[12, 13] knockout of Plin2 in GNMT-depleted livers decreased lipogenesis and increased TG secretion. Plin2 ablation increased Hydroxychloroquine cell line gluconeogenesis, indicating that crosstalk exists between lipid synthesis and sequestration

and glucose metabolism. Since PE methylation has been shown to promote LD formation,[26] these results Panobinostat chemical structure support a model where increased

PEMT activity induces both TG synthesis and its accumulation into newly formed LD. Collectively, these observations, taken in light of previous findings,[5, 6] demonstrate that SAMe regulates liver lipid homeostasis through a concerted series of homeostatic actions that include: activation of lipogenesis and inhibition of TG secretion at low SAMe, and activation of TG synthesis via PEMT at high SAMe. This cascade of events goes a long way towards explaining why a chronic imbalance in hepatic SAMe synthesis,[4] or catabolism,[8] is capable of inducing NAFLD. We thank Virginia Gutiérrez de Juan and Begoña Rodríguez-Iruretagoyena for technical Dichloromethane dehalogenase support and Azucena Castro for discussion; and human and technical support from Unidad de formación e investigación UFI11/20, University of Basque Country. Additional Supporting Information may be found in the online version of this article. “
“An 83-year-old man with hepatocellular carcinoma was found to have a low-echoic and low-density tumor measuring 7.2 cm × 5.6 cm. Caroli’s disease was absent. Clinical diagnosis was intrahepatic cholangiocarcinoma. Three cores of liver biopsy were obtained from the tumor. Histologically, it consisted of

liver cysts, ductal plate malformations, peribiliary glands, hepatocytes, portal tracts and mesenchymal tissue. Apparent features of cirrhosis were not found. The liver cysts were lined by a layer of cuboidal cells with multiple papillary protrusions. The ductal plate malformations resembled fetal ductal plates. The peribiliary glands were seromucous glands. Immunohistochemically, these abnormal ductal structures showed positive reaction to biliary type cytokeratins, namely, cytokeratin (CK)7, CK8, CK18 and CK19. Mucin gene expression showed that these biliary structures are positive for fetal antigen MUC1. MUC6 is also positive in them. Aberrant expression of CD10 was observed in these biliary structures. MUC2, MUC5AC and CDX2 were negative.