Xiaokun Ding, Neeraj K. Saxena, Songbai Lin, Narita Gupta, Frank A. Anania – 22 December 2005 – Nonalcoholic fatty liver disease (NAFLD) represents a burgeoning problem in hepatology, and is associated with insulin resistance. Exendin‐4 is a peptide agonist of the glucagon‐like peptide (GLP) receptor that promotes insulin secretion. The aim of this study was to determine whether administration of Exendin‐4 would reverse hepatic steatosis in ob/ob mice. Ob/ob mice, or their lean littermates, were treated with Exendin‐4 [10 μg/kg or 20 μg/kg] for 60 days.

Pengfei Gong, Arthur I. Cederbaum – 22 December 2005 – Induction of CYP2E1 by ethanol is one pathway through which ethanol generates oxidative stress. Nrf2 is a transcription factor that regulates important antioxidant and phase II detoxification genes. Nrf2 induction by CYP2E1 and its importance in the adaptive response to increased oxidative stress caused by CYP2E1 was studied. Increases in Nrf2 protein and mRNA were observed in livers or hepatocytes of chronic alcohol‐fed mice or rats and of pyrazole‐treated rats or mice, conditions known to elevate CYP2E1.

Steven M. Kerfoot, Charlotte D'Mello, Henry Nguyen, Maureen N. Ajuebor, Paul Kubes, Tai Le, Mark G. Swain – 22 December 2005 – Signaling occurs between the liver and brain in cholestatic liver disease, giving rise to sickness behaviors such as fatigue. However, the signaling pathways involved are poorly defined. Circulating inflammatory mediator levels are increased in cholestasis, leading to speculation that they may be capable of activating circulating immune cells that subsequently could gain access to the brain.

Jun Yu, Liang Qiao, Lars Zimmermann, Matthias P. A. Ebert, Hongxia Zhang, Wendy Lin, Christoph Röcken, Peter Malfertheiner, Geoffrey C. Farrell – 22 December 2005 – Peroxisome proliferator‐activated receptor γ (PPARγ) has been implicated in the differentiation and growth inhibition of cancer cells. We examined the effects of PPARγ activation by troglitazone on hepatocellular carcinoma (HCC) cell growth, proliferation, and apoptosis in vitro and in vivo. We also studied relationships between PPARγ activation and cyclooxygenase‐2 (COX‐2) expression.

Marco Arrese, Juan F. Miquel, Meenakshisundaram Ananthanarayanan – 22 December 2005 – We have generated a line of mutant mouse that lacks βKlotho, a protein that structurally resembles Klotho. The synthesis and excretion of bile acids were found to be dramatically elevated in these mutants, and the expression of 2 key bile acid synthase genes, cholesterol 7α‐hydroxylase (Cyp7a1) and sterol 12α‐hydroxylase (Cyp8b1), was strongly upregulated.

Snorri S. Thorgeirsson, Joe W. Grisham – 22 December 2005 – The authors reviewed 77 published reports available before August 1, 2005 that examined the ability of hematopoietic cells to generate hepatocytes in the liver. A list of these publications and a synopsis of each are available on‐line.

Jörn M. Schattenberg, Rajat Singh, Yongjun Wang, Jay H. Lefkowitch, Raina M. Rigoli, Philipp E. Scherer, Mark J. Czaja – 22 December 2005 – Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and varying degrees of necroinflammation. Although chronic oxidative stress, inflammatory cytokines, and insulin resistance have been implicated in the pathogenesis of NAFLD, the mechanisms that underlie the initiation and progression of this disease remain unknown.

Andrés Klein, Ludwig Amigo, María José Retamal, María Gabriela Morales, Juan Francisco Miquel, Attilio Rigotti, Silvana Zanlungo – 22 December 2005 – The liver plays a critical role in the metabolism of lipoprotein cholesterol and in controlling its elimination through the bile. Niemann‐Pick type C 2 (NPC2), a cholesterol‐binding protein, is key for normal intracellular trafficking of lipoprotein cholesterol, allowing its exit from the endolysosomal pathway into the metabolically active pool of the cell. In addition, NPC2 is a secretory protein from astrocytes and epididymal cells.

Roberto de Franchis – 22 December 2005

Oscar Quintana‐Bustamante, Alberto Alvarez‐Barrientos, Alexander V. Kofman, Isabel Fabregat, Juan A. Bueren, Neil D. Theise, José C. Segovia – 22 December 2005 – The mechanisms for in vivo production of bone marrow–derived hepatocytes (BMDHs) remain largely unclear. We investigated whether granulocyte colony–stimulating factor (G‐CSF)–mediated mobilization of hematopoietic cells increases the phenomenon. Recurrent liver injury in mice expressing green fluorescent protein (EGFP) in all hematopoietic‐derived cells was produced by 3 months of carbon tetrachloride (CCL4) injections.