Enteric dysbiosis associated with a mouse model of alcoholic liver disease.

Unlabelled: The translocation of bacteria and bacterial products into the circulation contributes to alcoholic liver disease. Intestinal bacterial overgrowth is common in patients with alcoholic liver disease. The aims of our study were to investigate bacterial translocation, changes in the enteric microbiome, and its regulation by mucosal antimicrobial proteins in alcoholic liver disease.

Liver X receptor signaling is a determinant of stellate cell activation and susceptibility to fibrotic liver disease.

Background & Aims: Liver X receptors (LXRs) are lipid-activated nuclear receptors with important roles in cholesterol transport, lipogenesis, and anti-inflammatory signaling. Hepatic stellate cells activate during chronic liver injury and mediate the fibrotic response. These cells are also major repositories for lipids, but the role of lipid metabolism during stellate cell activation remains unclear.

Alcohol induces RNA polymerase III-dependent transcription through c-Jun by co-regulating TATA-binding protein (TBP) and Brf1 expression.

Chronic alcohol consumption is associated with steatohepatitis and cirrhosis, enhancing the risk for hepatocellular carcinoma. RNA polymerase (pol) III transcribes a variety of small, untranslated RNAs, including tRNAs and 5S rRNAs, which determine the biosynthetic capacity of cells. Increased RNA pol III-dependent transcription, observed in transformed cells and human tumors, is required for oncogenic transformation.

Intragastric ethanol infusion model in rodents.

Alcohol-associated life-style disease, as exemplified by alcoholic liver disease (ALD), is multifactorial with intricate interactions among genetic and environmental factors predicating individual predisposition. To experimentally dissect the interfaces of these interactions for better understanding of the pathogenesis, it is essential to have an animal model that provides maximal control over ethanol and dietary intake and that enables a precise addition or deletion analysis for a risk or protective factor of interest. Rodent intragastric ethanol infusion (IEI) model was developed two decades ago to meet this requirement.

Fibroblast growth factor 10 is critical for liver growth during embryogenesis and controls hepatoblast survival via beta-catenin activation.

Unlabelled: Fibroblast growth factor (FGF) signaling and beta-catenin activation have been shown to be crucial for early embryonic liver development. This study determined the significance of FGF10-mediated signaling in a murine embryonic liver progenitor cell population as well as its relation to beta-catenin activation. We observed that Fgf10(-/-) and Fgfr2b(-/-) mouse embryonic livers are smaller than wild-type livers; Fgf10(-/-) livers exhibit diminished proliferation of hepatoblasts.

Fat paradox in liver disease.

Alcoholic liver disease (ALD) is characterized by accumulation of neutral lipids in hepatocytes leading to micro and macro-vesicular steatosis and balloon cell degeneration. Hypercaloric alimentation and resultant obesity also cause similar changes as evident in non-alcoholic fatty liver disease (NAFLD). Thus, accumulation of lipids in hepatocytes is a pathologic hallmark of ALD and NAFLD.

Adipogenic phenotype of hepatic stellate cells.

Transdifferentiation of hepatic stellate cells (HSC) constitutes a major cellular event in the genesis of alcoholic liver fibrosis and cirrhosis and molecular mechanisms underlying this process is incompletely understood. Our laboratory proposed several years ago that HSC quiescence requires the transcriptional program known to be integral to preadipocyte to adipocyte differentiation. In support of the hypothesis, our research demonstrates the expression of adipogenic transcription factors (C/EBPs, PPARgamma, SREBP-1c, LXRalpha) and adipocyte-specific genes (adipsin, resistin) are high in quiescent HSC and depleted in activated HSC.

Alcoholic liver disease (ALD): a new domain for prevention efforts.

Alcoholic liver disease (ALD) is a leading cause of death; yet relatively little has been written about it in the health behavior research literature. This paper will describe ALD, what factors predict ALD including findings from analyses of the 1998 state of California and Los Angeles County hospital discharge data, and possible means of preventing this disease. It is hoped that new interest among health behavior researchers and practitioners will be stimulated.