- Effect of alcohol consumption on survival in non-alcoholic fatty liver disease: a national prospective cohort study. [Journal Article]
- HepHepatology 2018 Aug 19
- Nonalcoholic fatty liver disease (NAFLD) comprises more than two thirds of patients with chronic liver disease in the United States. The effect of alcohol consumption on survival in patients with NAF...
Nonalcoholic fatty liver disease (NAFLD) comprises more than two thirds of patients with chronic liver disease in the United States. The effect of alcohol consumption on survival in patients with NAFLD is not clear. We gathered data on National Health and Nutrition Examination Survey (NHANES) participants from 1988 to 2010, and linked them to National Death Index (NDI) for follow up of their survival. We diagnosed NAFLD based on a previously validated biochemical model (Hepatic Steatosis Index). We built multivariate Cox proportional hazards models to evaluate the effect of alcohol consumption on survival of patients with NAFLD. After excluding participants with significant alcohol use, viral hepatitis, or increased transferrin Saturation 4568 participants with NAFLD were included in the analysis. In a Cox model adjusted for age, sex, and smoking history, drinking 0.5-1.5 drinks per day decreased the risk of overall mortality by 41% (HR=0.59, 95%CI 0.40-0.85, p value=0.005) compared to not drinking. Drinking > 1.5 drinks per day showed a trend towards harm (HR=1.16, 95% CI 0.99-1.36, p value=0.119). After further adjustment for race, physical activity, educational level, diabetes, and fiber and polyunsaturated fatty acid intake, drinking 0.5-1.5 drinks per day continued to show a significant protective effect (HR=0.64, 95% CI 0.42-0.97, p value=0.035), and drinking > 1.5 drinks per day showed a significant harmful effect on mortality (HR=1.45, 95% CI 1.01-2.10, p value=0.047). Among patients with NAFLD modest alcohol consumption is associated with a significant decrease in all-cause mortality, while drinking >1.5 drinks per day is associated with an increase in mortality. These results help to inform the discussion of potential risks and benefits of alcohol use in patients with NAFLD. This article is protected by copyright. All rights reserved.
- Effects of Chinese Medicinal Formula BNG-1 on Phosphodiesterase 3B Expression, Hepatic Steatosis, and Insulin Resistance in High Fat Diet-induced NAFLD Mice. [Journal Article]
- IJInt J Med Sci 2018; 15(11):1194-1202
- Background: Chinese medicinal formula BNG-1, a non-specific inhibitor of phospho-diesterases (PDEs), can be considered as a potential anti-inflammatory agent. The present study was aimed at determin...
Background: Chinese medicinal formula BNG-1, a non-specific inhibitor of phospho-diesterases (PDEs), can be considered as a potential anti-inflammatory agent. The present study was aimed at determining the effects of BNG-1 on the development of non-alcoholic fatty liver disease (NAFLD) in mice. Design and Methods: Male CD1 mice were randomly divided into seven groups, the control Con (4) and Con (8)+saline groups were fed a standard control diet for four or eight weeks; the experimental HFD (4) and HFD (8)+saline groups were fed a high fat diet for four or eight weeks; the HFD (8)+LBNG, HFD (8)+MBNG, and HFD (8)+HBNG groups received a high fat diet along with low, moderate or high doses of BNG-1 (0.026, 0.035, and 0.052g/30g body weight) which was administered for the last four weeks of an eight-week experimental period. After the end of experiment, blood and tissue samples were taken and analyzed. Results: Mice in the HFD (4) group had higher levels of alanine aminotransferase (ALT), plasma and hepatic triglyceride and cholesterol, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) compared with mice in the Con (4) group. Mice receiving the high fat diet along with the BNG-1 supplement had decreased body weight gains and lower visceral fat weights compared with the HFD (8)+saline group. They had also significantly reduced levels of abnormal ALT and HOMA-IR, and improved blood lipid profile. BNG-1-treated mice exhibited reduced hepatic lipid accumulation, lower oxidative stress, and decreased expression of pro-inflammatory cytokines (TNF-α and IL-1β). Furthermore, BNG-1 treatment resulted in down-regulation of hepatic cyclic-AMP dependent PDE3B and up-regulation of PDE3B expression in epididymis adipose tissue. Conclusions: BNG-1 mediated changes in PDE3B expression along with reduction in oxidative stress and inflammation. BNG-1 may ameliorate insulin resistance and hepatic steatosis in the NAFLD mouse model.
- Current guidelines for the management of non-alcoholic fatty liver disease: A systematic review with comparative analysis. [Review]
- WJWorld J Gastroenterol 2018 Aug 14; 24(30):3361-3373
- The current epidemic of non-alcoholic fatty liver disease (NAFLD) is reshaping the field of hepatology all around the world. The widespread diffusion of metabolic risk factors such as obesity, type2-...
The current epidemic of non-alcoholic fatty liver disease (NAFLD) is reshaping the field of hepatology all around the world. The widespread diffusion of metabolic risk factors such as obesity, type2-diabetes mellitus, and dyslipidemia has led to a worldwide diffusion of NAFLD. In parallel to the increased availability of effective anti-viral agents, NAFLD is rapidly becoming the most common cause of chronic liver disease in Western Countries, and a similar trend is expected in Eastern Countries in the next years. This epidemic and its consequences have prompted experts from all over the word in identifying effective strategies for the diagnosis, management, and treatment of NAFLD. Different scientific societies from Europe, America, and Asia-Pacific regions have proposed guidelines based on the most recent evidence about NAFLD. These guidelines are consistent with the key elements in the management of NAFLD, but still, show significant difference about some critical points. We reviewed the current literature in English language to identify the most recent scientific guidelines about NAFLD with the aim to find and critically analyse the main differences. We distinguished guidelines from 5 different scientific societies whose reputation is worldwide recognised and who are representative of the clinical practice in different geographical regions. Differences were noted in: the definition of NAFLD, the opportunity of NAFLD screening in high-risk patients, the non-invasive test proposed for the diagnosis of NAFLD and the identification of NAFLD patients with advanced fibrosis, in the follow-up protocols and, finally, in the treatment strategy (especially in the proposed pharmacological management). These difference have been discussed in the light of the possible evolution of the scenario of NAFLD in the next years.
- Nutritional issues in patients with obesity and cirrhosis. [Review]
- WJWorld J Gastroenterol 2018 Aug 14; 24(30):3330-3346
- Obesity and metabolic syndrome are considered as responsible for a condition known as the non-alcoholic fatty liver disease that goes from simple accumulation of triglycerides to hepatic inflammation...
Obesity and metabolic syndrome are considered as responsible for a condition known as the non-alcoholic fatty liver disease that goes from simple accumulation of triglycerides to hepatic inflammation and may progress to cirrhosis. Patients with obesity also have an increased risk of primary liver malignancies and increased body mass index is a predictor of decompensation of liver cirrhosis. Sarcopenic obesity confers a risk of physical impairment and disability that is significantly higher than the risk induced by each of the two conditions alone as it has been shown to be an independent risk factor for chronic liver disease in patients with obesity and a prognostic negative marker for the evolution of liver cirrhosis and the results of liver transplantation. Cirrhotic patients with obesity are at high risk for depletion of various fat-soluble, water-soluble vitamins and trace elements and should be supplemented appropriately. Diet, physical activity and protein intake should be carefully monitored in these fragile patients according to recent recommendations. Bariatric surgery is sporadically used in patients with morbid obesity and cirrhosis also in the setting of liver transplantation. The risk of sarcopenia, micronutrient status, and the recommended supplementation in patients with obesity and cirrhosis are discussed in this review. Furthermore, the indications and contraindications of bariatric surgery-induced weight loss in the cirrhotic patient with obesity are discussed.
- Association between nonalcoholic fatty liver disease and bone mineral density in postmenopausal women. [Journal Article]
- CClimacteric 2018 Aug 20; :1-4
- CONCLUSIONS: NAFLD is negatively associated with BMD in postmenopausal women. A longitudinal study is recommended.
- Laparoscopic Sleeve Gastrectomy Resolves NAFLD: Another Formal Indication for Bariatric Surgery? [Journal Article]
- OSObes Surg 2018 Aug 18
- CONCLUSIONS: NAFLD could be dealt with laparoscopic sleeve gastrectomy, preventing its progression into cirrhosis. SG can be performed in patients with obesity and metabolic syndrome, with NAFLD showing satisfactory results 12 months after surgery. NAFLD should be a formal indication for bariatric surgery.
- Role of the Circadian Clock in the Metabolic Syndrome and Nonalcoholic Fatty Liver Disease. [Review]
- DDDig Dis Sci 2018 Aug 18
- Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in industrialized nations and is strongly associated with the metabolic syndrome. The prevalence of NAFLD continues t...
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in industrialized nations and is strongly associated with the metabolic syndrome. The prevalence of NAFLD continues to rise along with the epidemic of the metabolic syndrome. Metabolic homeostasis is linked to the circadian clock (rhythm), with multiple signaling pathways in organs regulated by circadian clock genes, and recent studies of circadian clock gene functions suggest that disruption of the circadian rhythm is associated with significant morbidity and mortality, including the metabolic syndrome. In the industrialized world, various human behaviors and activities such as work and eating patterns, jet lag, and sleep deprivation interfere with the circadian rhythm, leading to perturbations in metabolism and development of the metabolic syndrome. In this review, we discuss how disruption of the circadian rhythm is associated with various metabolic conditions that comprise the metabolic syndrome and NAFLD.
- Modulation of xenobiotic nuclear receptors in high-fat diet induced non-alcoholic fatty liver disease. [Journal Article]
- TToxicology 2018 Aug 15
- Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the western countries. The histological spectrum of NAFLD includes simple steatosis, steatohepatitis, fibrosis, c...
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the western countries. The histological spectrum of NAFLD includes simple steatosis, steatohepatitis, fibrosis, cirrhosis and even hepatocellular carcinoma. Nuclear receptors are a large group of ligand-dependent transcription factors that sense the environmental and endogenous changes and regulate numerous physiological and pathological processes. Accumulating evidence has suggested that a dysregulation of nuclear receptors in NAFLD may effect on the metabolism of endogenous and exogenous chemicals in the liver. The current study was designed to systematically characterize the time-dependent modulation of nuclear receptors including the peroxisome proliferator-activated receptors (PPARs), the constitutive androstane receptor (CAR), the pregnane X receptor (PXR), the liver X receptor (LXR), and the farnesoid X receptor (FXR) in the progression of NAFLD. Male C57BL/6 mice fed by a high fat diet were used to induce NAFLD. Hepatic steatosis, lobular inflammation, progressive fibrosis, increased hepatocyte DNA synthesis, and liver tumor formation were observed at various time points in our mouse model. During the development of hepatic steatosis (8-16 weeks), PPARα was activated as indicated by its target genes as well as the elevated peroxisomal acyl-CoA oxidase activity. The mRNA level of Pparγ was also upregulated while Pparδ gene expression was significantly reduced during the development of hepatic steatosis. PXR target gene Cyp3a11 was consistently increased 3-4-fold in addition to the increased microsomal Cyp3a enzymatic activity at all stages of NAFLD. In contrast, CAR mediated Cyp2b10 gene expression was found increased only by week 12. LXRα target genes Abcg5 and Abcg8 were significantly elevated during the whole course of NAFLD. The mRNA of Fxr was downregulated at 24 and 32 weeks in high fat diet fed mice, which might correlate with the development of progressive fibrosis at the stage of steatohepatitis. The results of our study provided a systematic evaluation of the changes of nuclear receptors and their downstream chemical metabolism and transport enzymes in the progression of NAFLD.
- Emerging Role of AMPK in Brown and Beige Adipose Tissue (BAT): Implications for Obesity, Insulin Resistance, and Type 2 Diabetes. [Review]
- CDCurr Diab Rep 2018 Aug 17; 18(10):80
- The global prevalence of type 2 diabetes (T2D) is escalating at alarming rates, demanding the development of additional classes of therapeutics to further reduce the burden of disease. Recent studies...
The global prevalence of type 2 diabetes (T2D) is escalating at alarming rates, demanding the development of additional classes of therapeutics to further reduce the burden of disease. Recent studies have indicated that increasing the metabolic activity of brown and beige adipose tissue may represent a novel means to reduce circulating glucose and lipids in people with T2D. The AMP-activated protein kinase (AMPK) is a cellular energy sensor that has recently been demonstrated to be important in potentially regulating the metabolic activity of brown and beige adipose tissue. The goal of this review is to summarize recent work describing the role of AMPK in brown and beige adipose tissue, focusing on its role in adipogenesis and non-shivering thermogenesis.
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- Catalase and nonalcoholic fatty liver disease. [Review]
- PAPflugers Arch 2018 Aug 17
- Obesity and insulin resistance are considered the main causes of nonalcoholic fatty liver disease (NAFLD), and oxidative stress accelerates the progression of NAFLD. Free fatty acids, which are eleva...
Obesity and insulin resistance are considered the main causes of nonalcoholic fatty liver disease (NAFLD), and oxidative stress accelerates the progression of NAFLD. Free fatty acids, which are elevated in the liver by obesity or insulin resistance, lead to incomplete oxidation in the mitochondria, peroxisomes, and microsomes, leading to the production of reactive oxygen species (ROS). Among the ROS generated, H2O2 is mainly produced in peroxisomes and decomposed by catalase. However, when the H2O2 concentration increases because of decreased expression or activity of catalase, it migrates to cytosol and other organelles, causing cell injury and participating in the Fenton reaction, resulting in serious oxidative stress. To date, numerous studies have been shown to inhibit the pathogenesis of NAFLD, but treatment for this disease mainly depends on weight loss and exercise. Various molecules such as vitamin E, metformin, liraglutide, and resveratrol have been proposed as therapeutic agents, but further verification of the dose setting, clinical application, and side effects is needed. Reducing oxidative stress may be a fundamental method for improving not only the progression of NAFLD but also obesity and insulin resistance. However, the relationship between NAFLD progression and antioxidants, particularly catalase, which is most commonly expressed in the liver, remains unclear. Therefore, this review summarizes the role of catalase, focusing on its potential therapeutic effects in NAFLD progression.