Adipose tissue-liver axis in alcoholic liver disease.

Alcoholic liver disease (ALD) remains an important health problem worldwide. The disease spectrum is featured by early steatosis, steatohepatitis (steatosis with inflammatory cells infiltration and necrosis), with some individuals ultimately progressing to fibrosis/cirrhosis. Although the disease progression is well characterized, no effective therapies are currently available for the treatment in humans. The mechanisms underlying the initiation and progression of ALD are multifactorial and complex. Emerging evidence supports that adipose tissue dysfunction contributes to the pathogenesis of ALD. In the first part of this review, we discuss the mechanisms whereby chronic alcohol exposure contributed to adipose tissue dysfunction, including cell death, inflammation and insulin resistance. It has been long known that aberrant hepatic methionine metabolism is a major metabolic abnormality induced by chronic alcohol exposure and plays an etiological role in the pathogenesis of ALD. The recent studies in our group documented the similar metabolic effect of chronic alcohol drinking on methionine in adipose tissue. In the second part of this review, we also briefly discuss the recent research progress in the field with a focus on how abnormal methionine metabolism in adipose tissue contributes to adipose tissue dysfunction and liver damage.

Changes in hepatic gene expression in response to hepatoprotective levels of zinc.

BACKGROUND: Zinc (Zn) administration at non-toxic doses protects against the hepatotoxicity produced by many agents, but the underlying mechanisms remain elusive. AIM: To examine the basis of Zn-induced generalised hepatoprotective effects. METHODS: Rats and mice were given Zn at known hepatoprotective levels (100 mumol ZnCl2/kg/day, s.c., for 4 days) and molecular responses were assessed. RESULTS: Zn treatment produced changes in 5% of the genes on custom-designed mouse liver array and Rat Toxicology-II array. Changes in gene expression were further confirmed and extended by real-time reverse transcriptase-polymerase chain reaction. Zn treatment dramatically increased the expression of the metallothionein (Mt), and modestly increased the expression of acute-phase protein genes (ceruloplasmin, Stat3, egr1, Cxc chemokines and heat-shock proteins). For genes encoding for antioxidant enzymes, some were increased (Nrf2 and Nqo1), while others remained unaltered (Cu, Zn SOD and glutathione S-transferases). Expressions of cytokine and pro-inflammatory genes were not affected, while genes related to cell proliferation (cyclin D1) were modestly upregulated. Some metabolic enzyme genes, including cytochrome P450s and UDP-glucuronosyltransferase, were modestly suppressed, perhaps to switch cellular metabolic energy to acute-phase responses. Liver Zn content was increased between 1.6- and 2.1-fold, while hepatic MT protein was increased between 50 and 200-fold. Mice typically showed greater responses than rats. CONCLUSION: Such gene expression changes, particularly the dramatic induction of MT and Nrf2 antioxidant pathway, occur in the absence of overt liver injury, and are probably important in the hepatoprotective effects of Zn against toxic insults.

Anti-abortive effect of Radix scutellariae and Rhizoma atractylodis in mice.

The objective of this study is to investigate the significance of natural killer (NK) cells and interleukin-2 in uterus in the early embryo loss (or resorption), and to elucidate the immunological modulation of maternal-fetal interface with Chinese herbal medicine Radix scutellariae (huang qin) and Rhizoma atractylodis (bai zhu). Lipopolysaccharide (LPS) was given via the tail vein to induce abortion in mice at day 7 of gestation. Uterine NK cells and IL-2 contents were analyzed by immunohistochemistry and enzyme linked immunosorbent assay (ELISA), respectively. The number of NK cells was found to be much higher (mean = 180 +/- 39) in the decidua of LPS-treated abortion mice. But when the Chinese herbal medicine was used to prevent LPS-induced abortion, less NK cells (mean = 11 +/- 4) were counted (p < 0.01). The mean value of IL-2 in LPS-treated mice was 5.25 +/- 2.5938 pg/mg protein, higher than (p < 0.05) that of the herb prevention group, which was only 1.86 +/- 0.9789 pg/mg protein. The results therefore indicate that the increase of NK cells in the decidua and IL-2 contents in the uterus in LPS-treated mice is closely related to the embryo loss, and that the Chinese herbal medicine prescription composed of Radix scutellariae and Rhizoma atractylodis has an anti-abortive effect through inhibition of maternal-fetal interface immunity.