Oxidative stress due to iron deposition in hepatocytes or Kupffer cells contributes to the initiation and perpetuation of liver injury. The aim of this study was to clarify the association between dietary iron and liver injuries in rats. Liver injury was initiated by the administration of thioacetamide or ligation of the common bile duct in rats fed a control diet (CD) or iron-deficient diet (ID). In the acute liver injury model induced by thioacetamide, serum levels of aspartate aminotransferase and alanine aminotransferase, as well as hepatic levels of lipid peroxide and 4-hydroxynonenal, were significantly decreased in the ID group. The expression of 8-hydroxydeoxyguanosine and terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling positivity showed a similar tendency. The expression of interleukin-1beta and monocyte chemotactic protein-1 mRNA was suppressed in the ID group. In liver fibrosis induced by an 8-wk thioacetamide administration, ID suppressed collagen deposition and smooth muscle alpha-actin expression. The expressions of collagen 1A2, transforming growth factor beta, and platelet-derived growth factor receptor beta mRNA were all significantly decreased in the ID group. Liver fibrosis was additionally suppressed in the bile-duct ligation model by ID. In culture experiments, deferoxamine attenuated the activation process of rat hepatic stellate cells, a dominant producer of collagen in the liver. In conclusion, reduced dietary iron is considered to be beneficial in improving acute and chronic liver injuries by reducing oxidative stress. The results obtained in this study support the clinical usefulness of an iron-reduced diet for the improvement of liver disorders induced by chronic hepatitis C and alcoholic/nonalcoholic steatohepatitis.

Background and Aims. This study examined if exercise and omega-3 fatty acid (n3PUFA) supplementation is an effective treatment for hepatic steatosis in obese, hyperphagic Otsuka Long-Evans Tokushima Fatty (OLETF) rats.

Methods. Male OLETF rats were divided into 4 groups (n = 8/group): (1) remained sedentary (SED), (2) access to running wheels; (EX) (3) a diet supplemented with 3% of energy from fish oil (n3PUFA-SED); and (4) n3PUFA supplementation plus EX (n3PUFA+EX). The 8 week treatments began at 13 weeks, when hepatic steatosis is present in OLETF-SED rats.

Results. EX alone lowered hepatic triglyceride (TAG) while, in contrast, n3PUFAs failed to lower hepatic TAG and blunted the ability of EX to decrease hepatic TAG levels in n3PUFAs+EX. Insulin sensitivity was improved in EX animals, to a lesser extent in n3PUFA+EX rats, and did not differ between n3PUFA-SED and SED rats. Only the EX group displayed higher complete hepatic fatty acid oxidation (FAO) to CO(2) and carnitine palmitoyl transferase-1 activity. EX also lowered hepatic fatty acid synthase protein while both EX and n3PUFA+EX decreased stearoyl CoA desaturase-1 protein.

Conclusions. Exercise lowers hepatic steatosis through increased complete hepatic FAO, insulin sensitivity, and reduced expression of de novo fatty acid synthesis proteins while n3PUFAs had no effect.

OBJECTIVE: To observe the therapeutic effect of acupuncture for treatment of patients with nonalcoholic steatohepatitis. METHODS: Ninety-eight cases were randomly divided into an acupuncture group (n= 50) and a medicine group (n=48). The acupuncture group was treated with acupuncture at Shenshu (BL 23), Guanyuan (CV 4), Taixi (KI 3), Sanyinjiao (SP 6), etc.; the medicine group was treated with oral administration of Polyene Phosphatidylcholine Capsules. They were treated for 12 weeks. The changes of clinical symptoms, serum enzyme, blood fat and abdominal CT performance were compared between the two groups before and after treatment. RESULTS: After treatment, alanine aminotransferase (ALT), aspartate aminotransferase (AST), galactosylhydroxylysyl glucosyltransferase (GGT), triglyeride (TG) and total cholesterol (TC) significantly decreased in the acupuncture group (all P<0.01); ALT, AST and GGT significantly decreased in the medicine group (all P<0.01), and there were no significant differences in changes of TG and TC in the medicine group (both P>0.05). After treatment, CT image showed there was significant improvement of liver injury in both groups (both P<0.01), and the improvement of liver injury in the acupuncture group was superior to that in the medicine group (P<0.01). CONCLUSION: Acupuncture has a significant therapeutic effect on nonalcoholic steatohepatitis.

OBJECTIVE: To observe the therapeutic effect of acupuncture for treatment of patients with nonalcoholic steatohepatitis. METHODS: Ninety-eight cases were randomly divided into an acupuncture group (n= 50) and a medicine group (n=48). The acupuncture group was treated with acupuncture at Shenshu (BL 23), Guanyuan (CV 4), Taixi (KI 3), Sanyinjiao (SP 6), etc.; the medicine group was treated with oral administration of Polyene Phosphatidylcholine Capsules. They were treated for 12 weeks. The changes of clinical symptoms, serum enzyme, blood fat and abdominal CT performance were compared between the two groups before and after treatment. RESULTS: After treatment, alanine aminotransferase (ALT), aspartate aminotransferase (AST), galactosylhydroxylysyl glucosyltransferase (GGT), triglyeride (TG) and total cholesterol (TC) significantly decreased in the acupuncture group (all P<0.01); ALT, AST and GGT significantly decreased in the medicine group (all P<0.01), and there were no significant differences in changes of TG and TC in the medicine group (both P>0.05). After treatment, CT image showed there was significant improvement of liver injury in both groups (both P<0.01), and the improvement of liver injury in the acupuncture group was superior to that in the medicine group (P<0.01). CONCLUSION: Acupuncture has a significant therapeutic effect on nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease is an increasingly common condition that may progress to hepatic cirrhosis. This pilot study evaluated the effects of a low-carbohydrate, ketogenic diet on obesity-associated fatty liver disease. Five patients with a mean body mass index of 36.4 kg/m(2) and biopsy evidence of fatty liver disease were instructed to follow the diet (<20 g/d of carbohydrate) with nutritional supplementation for 6 months. Patients returned for group meetings biweekly for 3 months, then monthly for the second 3 months. The mean weight change was -12.8 kg (range 0 to -25.9 kg). Four of 5 posttreatment liver biopsies showed histologic improvements in steatosis (P=.02) inflammatory grade (P=.02), and fibrosis (P=.07). Six months of a low-carbohydrate, ketogenic diet led to significant weight loss and histologic improvement of fatty liver disease. Further research is into this approach is warranted.

Wolf (PCW) is an edible, pharmaceutical mushroom with remarkable biological properties including anti-tumor, anti-inflammation, anti-oxidation, anti-ageing, and anti-diabetic effects. In the current study, we investigated the effects of PCW extract on hepatic steatosis under in vitro and in vivo conditions, and elucidated the underlying mechanisms. In this study, a mixture of HepG2 cells treated with free fatty acid (FFA)-palmitic and oleic acid-and high-fat diet (HFD)-fed obese mice were used; in this background, the triglyceride (TG) levels in HepG2 cells and mice liver were measured, and the expression levels of genes associated with lipogenesis, fatty acid oxidation, endoplasmic reticulum (ER) stress, and autophagy were determined. Treatment of HepG2 cells with FFA enhanced intracellular TG levels in HepG2 cells, but co-treatment with PCW significantly attenuated the TG levels. Notably, PCW significantly enhanced the phosphorylation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and sterol regulatory element-binding protein-1c (SREBP-1c) in FFA-treated HepG2 cells. PCW downregulated the expression of lipogenesis-related genes, but upregulated the expression of genes associated with fatty acid oxidation. Further, PCW inhibited FFA-induced expression of ER stress markers and induced autophagy proteins. However, inhibition of AMPK significantly attenuated the beneficial effects of PCW in HepG2 cells. Moreover, PCW efficiently decreased HFD-induced hepatic TG accumulation in vivo and increased the phosphorylation of hepatic AMPK. Three compounds present in PCW including poricoic acid, pachymic acid, and ergosterol, significantly decreased FFA-induced increase in intracellular TG levels, consistent with increased AMPK phosphorylation, suggesting that poricoic acid, pachymic acid, and ergosterol are responsible for PCW-mediated amelioration of hepatic steatosis. Taken together, these results demonstrated that PCW ameliorates hepatic steatosis through the regulation of lipid metabolism, inhibition of ER stress, and activation of autophagy in an AMPK-dependent manner. This suggested that PCW can be potentially used for the treatment of hepatic steatosis.