Cornus officinalis vinegar reduces body weight and attenuates hepatic steatosis in mouse model of nonalcoholic fatty liver disease

This study aimed to determine the main bioactive components of Cornus officinalis vinegar (COV) and assess the effects of COV on the body weight (BW) and hepatic steatosis in a nonalcoholic fatty liver disease (NAFLD) mouse model. Seven-week-old KM female mice were divided into five treatment groups: (1) Normal control (NC) group, (2) high fat diet (HFD) group, (3) low concentration treatment group (3.5% COV), (4) medium concentration treatment group (5.0% COV), and (5) high concentration treatment group (6.5% COV). Mice in the NC group were fed with a normal chow diet, and those in the other four groups were fed with a HFD known for causing obesity for 10 weeks. Then, mice in the three COV treatment groups were orally administered with COV once a day for 6 weeks. Results showed that the contents of loganin and morroniside in COV reached 16.82 and 51.17 µg/ml, respectively, and COV also contained multiple organic acids. COV significantly reduced BW, abdominal fat weight, liver weight, and the levels of glucose, triglyceride, and low-density lipoprotein cholesterol of serum and increased the levels of high-density lipoprotein cholesterol of serum (p < 0.05). COV also improved the liver function and anti-oxidant activity of liver (p < 0.05). COV treatments increased the interleukin-10 expression and reduced the tumor necrosis factor-α expression in the liver tissue of NAFLD mice (p < 0.05). Histopathological observation revealed that COV suppressed hepatic lipid accumulation and steatosis. The results suggest that COV may contribute to the alleviation of NAFLD and obesity.     

The Association of Il28b Genotype with the Histological Features of Chronic Hepatitis C Is HCV Genotype Dependent

The interleukin 28B (IL28B) rs12979860 polymorphism is associated with treatment outcome in hepatitis C virus (HCV) genotype 1 and 4 patients. Its association with the histological features of chronic hepatitis C and disease severity needs further clarifications. To assess the correlation between IL28B genotype, HCV genotype and liver biopsy findings in untreated patients.

Materials and Methods

Pre-treatment liver biopsies from 335 HCV Caucasian patients (59% males, age 50 years) enrolled in the MIST study were staged for fibrosis and inflammation according to the METAVIR and the Ishak scoring systems; steatosis was dichotomized as <5% or ≥5%. IL28B was typed by Taqman Single Nucleotide Polymorphism (SNP) genotyping assay. HCV genotype was 1 in 151 (45%), 2 in 99 (30%), 3 in 50 (15%) and 4 in 35 (10%) patients. IL28B genotype was CC in 117 (34%), CT in 166 (49%) and TT in 52 (15%). At univariate analysis, the IL28B CC genotype was associated with severe portal inflammation in HCV-1 patients (CC vs. CT/TT: 86% vs. 63%, p = 0.005), severe lobular inflammation in HCV-2 patients (CC vs. CT/TT: 44% vs. 23%, p = 0.03), and less fatty infiltration in HCV-1 patients (CC vs. CT/TT: 72% vs. 51%, p = 0.02). Despite the lack of any association between IL28B and fibrosis stage, in HCV-3 patients IL28B CC correlated with METAVIR F3–F4 (CC vs. CT/TT: 74% vs. 26%, p = 0.05). At multivariate analysis, the genotype CC remained associated with severe portal inflammation in HCV-1, only (Odds Ratio (OR): 95% Confidence Interval (CI): 3.24 (1.23–8.51)). IL28B genotype is associated with the histological features of chronic hepatitis C in a HCV genotype dependent manner, with CC genotype being independently associated with severe portal inflammation.     

Altered Fatty Acid Metabolism-Related Gene Expression in Liver from Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

Lipid accumulation in the human liver seems to be a crucial mechanism in the pathogenesis and the progression of non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate gene expression of different fatty acid (FA) metabolism-related genes in morbidly obese (MO) women with NAFLD. Liver expression of key genes related to de novo FA synthesis (LXRα, SREBP1c, ACC1, FAS), FA uptake and transport (PPARγ, CD36, FABP4), FA oxidation (PPARα), and inflammation (IL6, TNFα, CRP, PPARδ) were assessed by RT-qPCR in 127 MO women with normal liver histology (NL, n = 13), simple steatosis (SS, n = 47) and non-alcoholic steatohepatitis (NASH, n = 67). Liver FAS mRNA expression was significantly higher in MO NAFLD women with both SS and NASH compared to those with NL (p = 0.003, p = 0.010, respectively). Hepatic IL6 and TNFα mRNA expression was higher in NASH than in SS subjects (p = 0.033, p = 0.050, respectively). Interestingly, LXRα, ACC1 and FAS expression had an inverse relation with the grade of steatosis. These results were confirmed by western blot analysis. In conclusion, our results indicate that lipogenesis seems to be downregulated in advanced stages of SS, suggesting that, in this type of extreme obesity, the deregulation of the lipogenic pathway might be associated with the severity of steatosis.     

Supplementation with Docosahexaenoic Acid and Vitamin E Improves Hepatic Triglyceride Accumulation Induced by High-Fat Diet in Mice

The study aims to investigate the effect of combined supplementation with docosahexaenoic acid (C22:6 n-3, DHA) and vitamin E (VE) on the oxidative stress and liver triglycerides (TG) accumulation induced by high-fat diet (HFD) in mice. C57BL/6J mice are fed either a control diet or an HFD for 8 weeks. Animals are supplemented with DHA, VE, or DHA + VE, respectively. Supplementation with DHA alone shows significant improvement in oxidative stress and hepatic steatosis in mice. Supplementation with DHA significantly reduces the liver TG and total cholesterol contents, and the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, compared with the HFD. Supplementation with DHA also significantly decreases the mRNA expression level of sterol regulatory element-binding protein 1C. However, supplementation with VE alone does not show improvement in oxidative stress and hepatic steatosis. DHA + VE supply obtains a superior effect in alleviation of hepatic steatosis than DHA supplementation alone in mice fed by HFD. The efficacy of DHA potentiated by VE can be due to that VE enhances the effect of DHA in decrease of ALT and AST levels and increase of antioxidant enzyme activity and glutathione level in mice fed by HFD. Practical Applications: Supplementation with DHA significantly improves the oxidative stress and hepatic steatosis induced by HFD in mice. The efficacy of DHA in the alleviation of hepatic steatosis induced by HFD is potentiated by VE. These findings may provide a rational basis for the use of DHA and VE co-supplementation in patients with liver steatosis.     

超声背散射信息熵成像评价脂肪肝的新方法

提出超声背散射Tsallis信息熵成像评价脂肪肝的新方法。利用滑动窗口法,估算窗口内局部背散射包络信号的Tsallis信息熵参数值,对信息熵参数值矩阵进行扫描变换、颜色映射及感兴趣区域设置,叠加到超声B模式图像,实现Tsallis信息熵成像。分析72名肝脏捐献者和204名患者的超声背散射信号,参考标准分别为磁共振波谱测得的肝脏脂肪分数(Hepatic Fat Fraction, HFF)和肝活检组织学检查测得的脂肪肝程度。对于72名肝脏捐献者,Tsallis信息熵与lg(HFF)的相关系数r=0.67(P<0.000 1)。对于204名患者,受试者工作特征曲线下面积分别为0.82、0.88、0.89(≥轻度、≥中度、≥重度),而超声背散射零差K成像分别为0.76、0.82、0.82。超声背散射Tsallis信息熵成像可以直观定征并定量评价脂肪肝的严重程度,其诊断性能优于超声背散射零差K成像,可作为一种超声评价脂肪肝的新方法。     

声辐射力脉冲弹性成像技术对大鼠肝脏脂肪变性的诊断研究

研究目的是利用声辐射力脉冲弹性成像技术(Acoustic Radiation Force Impulse,ARFI)评估大鼠肝脏的脂肪变性程度。实验通过对大鼠喂养不同时间高脂食物从而诱导成肝脏脂肪变性不同阶段,进而利用ARFI技术离体测量大鼠肝脏的剪切波速度值(Shear Wave Velocity,SWV)。研究结果显示,对照组[(2.25±0.52)m/s)]与脂肪变性组[(2.83±0.37)m/s]之间存在着显著性差异(P0.05),而脂肪变性不同阶段之间差异却不明显。早期炎症等级与SWV值之间没有显著性相关。因此,ARFI弹性成像技术可以有效地区分大鼠肝脏正常组和脂肪变性组,但是对不同脂肪变性程度之间无法做出有效区分。同时,轻微的炎症活动并不影响ARFI测量。     

Beneficial Effects of Supplementation of the Rare Sugar “D‐allulose” Against Hepatic Steatosis and Severe Obesity in Lepob/Lepob Mice

A rare sugar, D‐allulose (also called D‐psicose), has recently been applied as a food supplement in view of controlling diabetes and obesity in Japan. D‐allulose has been proven to have unique effects against hyperglycemia and hyperlipidemia in a number of studies using several species of rats and mice. However, the antiobesity effects of D‐allulose have not yet been assessed in Lep^ob/Lep^ob (ob/ob) mice. Therefore, this study explored the dietary supplemental effects of this sugar in leptin‐deficient ob/ob mice. Consequently, the subchronic ingestion of D‐allulose in ob/ob mice for 15 wk significantly decreased the body and liver weights, and the loss of body weight was involved in the reduction of the total fat mass, including abdominal visceral fat, and not fat‐free body mass, including muscle. Furthermore, D‐allulose improved hepatic steatosis, as evaluated using hepatic histological studies and MRI. In the normal mice, none of these parameters were influenced by the single or long‐term ingestion of D‐allulose. These results indicate that dietary supplementation of D‐allulose especially influences postprandial hyperglycemia and obesity‐related hepatic steatosis, without exercise therapy or dietary restriction. Therefore, D‐allulose may be useful as a supplement for preventing and improving obesity and obesity‐related disorders.