OBJECTIVETo examine dietary zinc supplementation could alleviate the damage of alcoholic liver disease and the relationship with the expression of hepatocyte nuclear factor 4alpha (HNF-4alpha).

METHODS40 adult C57 BL/6 mice were randomly divided into four groups (n = 10): control, zinc, ethanol and zinc plus ethanol, which were sacrificed after fed four different diets for 6 months. Zinc sulfate was added in the drinking water of the Zinc and Zinc Plus Ethanol group and the content was 75 mg/L. Liver regeneration was assessed by immunohistochemical staining of proliferating cell nuclear antigen (PCNA), and the expression of HNF-4alpha was determined by RT-PCR and Western blot. And as to assess the status of oxidative stress of the mice, malondialdehyde (MDA) and superoxide dismutase (SOD) were detected.

RESULTSCompared with the control group, the expression level of HNF-4alpha decreased significantly in the ethanol group (P < 0.05), and the content of MDA increased significantly in this group, while the content of SOD declined significantly (P < 0.05). Compared with the ethanol group, the number of PCNA-positive hepatocytes increased significantly, and the expression level of HNF-4alpha also increased in the zinc plus ethanol group (P < 0.05), and the content of SOD increased in this group, while MDA decreased significantly (P < 0.05).

CONCLUSIONLong term ethanol exposure can lead to oxidoreduction imbalances which can be reversed by zinc supplementation. We suppose that zinc-enhanced liver regeneration is associated with an increase in HNF-4alpha, suggesting that dietary zinc supplementation may have beneficial effects in alcoholic liver disease.

Animals ; Dietary Supplements ; Hepatocyte Nuclear Factor 4 ; metabolism ; Liver ; metabolism ; Liver Diseases, Alcoholic ; metabolism ; therapy ; Male ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred C57BL ; Superoxide Dismutase ; metabolism ; Zinc Sulfate ; pharmacology ; therapeutic use

OBJECTIVETo observe the expression of hepatocyte nuclear factor 4alpha (HNF4alpha) and the activity of key enzyme glucokinase (GK) in glucose metabolism, and further to investigate the possible mechanism of berberine in treating type 2 diabetes.

METHODMouse primary hepatocytes were isolated by an improved single two-step perfusion method. The murine hepatocytes were cultured and incubated with berberine (0, 1, 3, 10, 30, 100 micromol x L(-1)) and 1 mmol x L(-1) metformin for 24 h respectively. The mRNA expression of HNF4alpha were quantified by RT-PCR and the protein expression of HNF4alpha were quantified by Western-blot. And the activity of GK were detected with enzyme kinetics method.

RESULTAs compared with the negative control group, at a certain concentration range, the expression of HNF4alpha mRNA and protein and the activity of GK were promoted by berberine. Both of them reached the top at the concentration of 30 micromol x L(-1) (P<0.01). But the metformin made no difference with the negative control group on the expression of HNF4alpha and the activity of GK.

CONCLUSIONIt is suggested that the effects of berberine on improving glucose metabolism can be mechanically associated with its up-regulating the HNF4a expression and inducing the activity of hepatic glucokinase.

Animals ; Berberine ; pharmacology ; Cell Survival ; drug effects ; Cells, Cultured ; Gene Expression Regulation ; drug effects ; Glucokinase ; genetics ; metabolism ; Hepatocyte Nuclear Factor 4 ; genetics ; metabolism ; Hepatocytes ; cytology ; drug effects ; metabolism ; Male ; Mice ; Plant Extracts ; pharmacology

Phenylketonuria is an autosomal recessive disorder caused by a deficiency of phenylalanine hydroxylase. Transthyretin has been implicated as an indicator of nutritional status in phenylketonuria patients. In this study, we report that phenylalanine and its metabolite, phenylpyruvic acid, affect MAPK, changing transthyretin expression in a cell- and tissue-specific manner. Treatment of HepG2 cells with phenylalanine or phenylpyruvic acid decreased transcription of the TTR gene and decreased the transcriptional activity of the TTR promoter site, which was partly mediated through HNF4alpha. Decreased levels of p38 MAPK were detected in the liver of phenylketonuria-affected mice compared with wild-type mice. In contrast, treatment with phenylalanine increased transthyretin expression and induced ERK1/2 activation in PC-12 cells; ERK1/2 activation was also elevated in the brainstem of phenylketonuria-affected mice. These findings may explain between-tissue differences in gene expression, including Ttr gene expression, in the phenylketonuria mouse model.
Animals ; Brain Stem/metabolism/pathology ; Disease Models, Animal ; Gene Expression Regulation ; Hep G2 Cells ; Hepatocyte Nuclear Factor 4/metabolism ; Humans ; Liver/*metabolism/pathology ; Mice ; Mice, Mutant Strains ; Mitogen-Activated Protein Kinase 3/genetics/*metabolism ; Organ Specificity ; Phenylalanine/metabolism ; Phenylalanine Hydroxylase/deficiency ; Phenylketonurias/*genetics/metabolism/pathology/physiopathology ; Phenylpyruvic Acids/metabolism ; Prealbumin/*biosynthesis/genetics ; p38 Mitogen-Activated Protein Kinases/genetics/*metabolism