Role of Elevated Intracellular S-Adenosylhomocysteine in the Pathogenesis of Alcohol-Related Liver Disease.

BACKGROUND: The earliest manifestation of alcohol-related liver disease (ALD) is steatosis, characterized by the accumulation of lipid droplets (LDs) in hepatocytes. Findings from our laboratory have indicated that many pathological changes, including steatosis, correlate with the alcohol-induced hepatocellular increases in S-adenosylhomocysteine (SAH). Based on these considerations, we hypothesized that an experimental increase in intracellular SAH alone will result in similar steatotic changes to those seen after alcohol exposure. METHODS: Freshly isolated rat hepatocytes grown on collagen-coated plates were exposed to serum-free medium containing 50 µmol/L oleic acid and varying concentrations of 3-deazaadenosine (DZA) to experimentally elevate intracellular SAH levels. RESULTS: Overnight exposure to DZA treatment dose-dependently increased hepatocellular triglyceride accumulation, which was also evident by morphological visualization of larger-sized LDs. The rise in triglycerides and LDs accompanied increases in mRNA and protein levels of several LD-associated proteins known to regulate LD number and size. Furthermore, DZA treatment caused a decline in the levels of lipases that prevent fat accumulation as well as increased the expression of factors involved in lipogenesis and fatty acid mobilization. Collectively, our results indicate that the elevation of intracellular SAH is sufficient to promote fat accumulation in hepatocytes, which is similar to that seen after alcohol exposure.

Development of Wheat Bran Oil Concentrates Rich in Bioactives with Antioxidant and Hypolipidemic Properties.

Wheat bran, an abundant byproduct of the milling industry, comprises fat-soluble bioactives and fibers. In the present study, two concentrates were prepared from wheat bran oil (WBO) using silicic acid coupled with acetone (WBA) and hexane (WBH). WBA extract had enhanced color and viscosity and was enriched with fat-soluble bioactives (sterols, oryzanol-like compounds, tocopherols, and carotenoids) as evidenced from NMR and other techniques. In in vitro studies, WBA exhibited significant free radical scavenging activity, limited DNA and LDL oxidation, and inhibiting HMG-CoA reductase and lipase activity better than WBH and WBO. Further, an in vivo study with WBA 2 or 3.5% containing high fat diet ameliorated malonaldehyde (MDA) level, lipid profile, and antioxidant enzyme (SOD, catalase, GPx, and GR) activities in liver. A possible reason for this effect is downregulation of HMG-CoA reductase expression with WBA. Thus, WBA has significant potential as an ingredient in health food formulations.