Lentinan Protects against Nonalcoholic Fatty Liver Disease by Reducing Oxidative Stress and Apoptosis via the PPARα Pathway

Lentinan (LNT), a type of polysaccharide derived from Lentinus edodes, has manifested protective effects during liver injury and hepatocellular carcinoma, but little is known about its effects on nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate whether LNT can affect the progression of NAFLD and the associated mechanisms. C57BL/6J mice were fed a normal chow diet or a high-fat diet (HFD) with or without LNT (6 mg/kg/d). AML12 cells were exposed to 200 μM palmitate acid (PA) with or without LNT (5 μg/mL). After 21 wk of the high-fat diet, LNT significantly decreased plasma triglyceride levels and liver lipid accumulation, reduced excessive reactive oxygen species production, and subsequently attenuated hepatic apoptosis in NAFLD mice. These effects were associated with increased PPARα levels, a decreased Bax/Bcl-2 ratio, and enhancement of the antioxidant defense system in vivo. Similar effects were also observed in cultured cells. More importantly, these protective effects of LNT on palmitate acid-treated AML12 cells were almost abolished by PPARα knockdown. In conclusion, this study demonstrates that LNT may ameliorate hepatic steatosis and decrease oxidative stress and apoptosis by activating the PPARα pathway and is a potential drug target for NAFLD

Influence of Vitamin E Supplementation on Glycaemic Control: A Meta-Analysis of Randomised Controlled Trials

<div><p>Observational studies have revealed that higher serum vitamin E concentrations and increased vitamin E intake and vitamin E supplementation are associated with beneficial effects on glycaemic control in type 2 diabetes mellitus (T2DM). However, whether vitamin E supplementation exerts a definitive effect on glycaemic control remains unclear. This article involves a meta-analysis of randomised controlled trials of vitamin E to better characterise its impact on HbA1c, fasting glucose and fasting insulin. PubMed, EMBASE and the Cochrane Library were electronically searched from the earliest possible date through April 2013 for all relevant studies. Weighted mean difference (WMD) was calculated for net changes using fixed-effects or random-effects models. Standard methods for assessing statistical heterogeneity and publication bias were used. Fourteen randomised controlled trials involving individual data on 714 subjects were collected in this meta-analysis. Increased vitamin E supplementation did not result in significant benefits in glycaemic control as measured by reductions in HbA1c, fasting glucose and fasting insulin. Subgroup analyses revealed a significant reduction in HbA1c (−0.58%, 95% CI −0.83 to −0.34) and fasting insulin (−9.0 pmol/l, 95% CI −15.90 to −2.10) compared with controls in patients with low baseline vitamin E status. Subgroup analyses also demonstrated that the outcomes may have been influenced by the vitamin E dosage, study duration, ethnic group, serum HbA1c concentration, and fasting glucose control status. In conclusion, there is currently insufficient evidence to support a potential beneficial effect of vitamin E supplementation on improvements of HbA1c and fasting glucose and insulin concentrations in subjects with T2DM.</p></div

Forest plot of randomised controlled trials investigate the effect of vitamin E supplementation on fasting glucose.

<p>Forest plot of randomised controlled trials investigate the effect of vitamin E supplementation on fasting glucose.</p

Characteristic of experimental trials included in the meta-analysis.

<p>FPG: fasting plasma glucose; vitE: vitamin E; mixed tocopherols: 60%γ-,25% δ- and 15% α-tocopherol; HbA1c: glycated hemoglobin; USA: United States of America; UK: The United Kingdom; T:treatment group; C: control group; C1: crossover design; P: Parallel design.</p

Forest plot of randomised controlled trials investigate the effect of vitamin E supplementation on fasting insulin.

<p>Forest plot of randomised controlled trials investigate the effect of vitamin E supplementation on fasting insulin.</p

Quality assessment of included studies.

<p>Y, yes; U, unclear; Randomisation:the study described as randomized; Random sequence generation: the correct method for generation of random numbers computer random numbers table, shuffled cards or tossed coins, and minimization; Allocation concealment: Adequate concealment was that up to the point of treatment (eg, central randomisation); Double-blinding: masking to both researchers and patients; Reporting of withdrawals: The numbers and reasons for withdrawal in each group had to be stated for a point to be awarded.</p

Summary of effect sizes (weighted mean difference) for secondary outcomes.

<p>HOMA, homeostasis model assessment; Total-C, total cholesterol; HDL-C, high-density lipoprotein-cholesterol;LDL-C, low-density lipoprotein-cholesterol; CI, confidence interval. T: treatment group; C: control group.</p