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1.
Hypoxic Signaling and Cholesterol Lipotoxicity in Fatty Liver Disease Progression.
Tirosh, O
Oxidative medicine and cellular longevity. 2018;:2548154
Abstract
Cholesterol is the only lipid whose absorption in the gastrointestinal tract is limited by gate-keeping transporters and efflux mechanisms, preventing its rapid absorption and accumulation in the liver and blood vessels. In this review, I explored the current data regarding cholesterol accumulation in liver cells and key mechanisms in cholesterol-induced fatty liver disease associated with the activation of deleterious hypoxic and nitric oxide signal transduction pathways. Although nonalcoholic fatty liver disease (NAFLD) affects both obese and nonobese individuals, the mechanism of NAFLD progression in lean individuals with healthy metabolism is puzzling. Lean NAFLD individuals exhibit normal metabolic responses, implying that liver damage is not associated with impaired metabolism per se and that direct lipotoxic effects are crucial for disease progression. Several redox and oxidant signaling pathways involving cholesterol are at play in fatty liver disease development. These include impairment of the mitochondrial and lysosomal function by cholesterol loading of the inner-cell membranes; formation of cholesterol crystals and hepatocyte degradation; and crown-like structures surrounding degrading hepatocytes, activating Kupffer cells, and evoking inflammation. The current review focuses on the induction of liver inflammation, fibrosis, and steatosis by free cholesterol via the hypoxia-inducible factor 1α (HIF-1α), a main oxygen-sensing transcription factor involved in all stages of NAFLD. Cholesterol loading in hepatocytes can result in chronic HIF-1α activity because of the decreased oxygen availability and excessive production of nitric oxide and mitochondrial reactive oxygen species.
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2.
[Effect of aerobic exercise and resistance exercise in improving non-alcoholic fatty liver disease: a randomized controlled trial].
Jia, GY, Han, T, Gao, L, Wang, L, Wang, SC, Yang, L, Zhang, J, Guan, YY, Yan, NN, Yu, HY, et al
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology. 2018;(1):34-41
Abstract
Objective: To investigate the effect of dietary control combined with different exercise modes on plasma vaspin, irisin, and metabolic parameters in patients with non-alcoholic fatty liver disease (NAFLD) through a randomized open parallel-controlled study. Methods: The patients aged 30-65 years who visited Tianjin Third Central Hospital from January 2013 to December 2014 and were diagnosed with NAFLD by liver ultrasound and fat content determination were screening, and 474 patients were enrolled in this randomized controlled trial and divided into aerobic exercise group, resistance exercise group, and control group. All patients received dietary intervention. The three groups were compared in terms of biochemical parameters, fat content, NFS score, energy metabolic parameters, body composition index, and levels of vaspin and irisin at baseline and after 6 months of intervention. SPSS 19.0 was used for statistical analysis. The t-test, the Mann-Whitney U test, the chi-square test, and an analysis of variance were used for comparison between groups. The multiple imputation method was used for missing data, and the results were included in the intention-to-treat analysis. Results: There were no significant differences in age, sex, anthropometrical parameters, and biochemical parameters between the three groups at baseline. Compared with dietary control alone, aerobic exercise and resistance exercise helped to achieve significant reductions in waist circumference, diastolic pressure, percentage of body fat, volatile fatty acid, fasting blood glucose, homeostasis model assessment of insulin resistance, triglyceride, low-density lipoprotein cholesterol, free fatty acid, uric acid, alanine aminotransferase, and liver fat content after 6 months of intervention (P < 0.05). The aerobic exercise group had a significant increase in non-protein respiratory quotient and significant reductions in body mass index and aspartate aminotransferase after intervention, as well as a significant increase in resting energy expenditure and significant reductions in abdominal fat ratio and total cholesterol after 6 months of resistance exercise (P < 0.05). The aerobic exercise group and the resistance exercise group had a significant reduction in vaspin and a significant increase in irisin after intervention (P < 0.05), and the resistance exercise group had significantly greater changes in these two adipokines than the aerobic exercise group (P < 0.05). Conclusion: Exercise therapy is an effective method for the treatment of metabolism-associated diseases, and a combination of resistance and aerobic exercises is more reasonable and effective in clinical practice. As a relatively safe exercise mode, resistance exercise can also effectively improve the metabolic state of NAFLD patients.
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3.
Nutraceutical Approach to Non-Alcoholic Fatty Liver Disease (NAFLD): The Available Clinical Evidence.
Cicero, AFG, Colletti, A, Bellentani, S
Nutrients. 2018;(9)
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a clinical condition characterized by lipid infiltration of the liver, highly prevalent in the general population affecting 25% of adults, with a doubled prevalence in diabetic and obese patients. Almost 1/3 of NAFLD evolves in Non-Alcoholic SteatoHepatitis (NASH), and this can lead to fibrosis and cirrhosis of the liver. However, the main causes of mortality of patients with NAFLD are cardiovascular diseases. At present, there are no specific drugs approved on the market for the treatment of NAFLD, and the treatment is essentially based on optimization of lifestyle. However, some nutraceuticals could contribute to the improvement of lipid infiltration of the liver and of the related anthropometric, haemodynamic, and/or biochemical parameters. The aim of this paper is to review the available clinical data on the effect of nutraceuticals on NAFLD and NAFLD-related parameters. Relatively few nutraceutical molecules have been adequately studied for their effects on NAFLD. Among these, we have analysed in detail the effects of silymarin, vitamin E, vitamin D, polyunsaturated fatty acids of the omega-3 series, astaxanthin, coenzyme Q10, berberine, curcumin, resveratrol, extracts of Salvia milthiorriza, and probiotics. In conclusion, Silymarin, vitamin E and vitamin D, polyunsaturated fatty acids of the omega-3 series, coenzyme Q10, berberine and curcumin, if well dosed and administered for medium⁻long periods, and associated to lifestyle changes, could exert positive effects on NAFLD and NAFLD-related parameters.
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4.
Lifestyle intervention in obese Chinese adolescents with non-alcoholic fatty liver disease: a randomised controlled study.
Chan, DF, Nelson, EA, Li, AM, Woo, J, Sea, MM, Chan, RS, Chu, WC, Chan, M, So, HK
Hong Kong medical journal = Xianggang yi xue za zhi. 2018;(4):12-15
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5.
Nonalcoholic fatty liver disease and chronic vascular complications of diabetes mellitus.
Targher, G, Lonardo, A, Byrne, CD
Nature reviews. Endocrinology. 2018;(2):99-114
Abstract
Nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus are common diseases that often coexist and might act synergistically to increase the risk of hepatic and extra-hepatic clinical outcomes. NAFLD affects up to 70-80% of patients with type 2 diabetes mellitus and up to 30-40% of adults with type 1 diabetes mellitus. The coexistence of NAFLD and diabetes mellitus increases the risk of developing not only the more severe forms of NAFLD but also chronic vascular complications of diabetes mellitus. Indeed, substantial evidence links NAFLD with an increased risk of developing cardiovascular disease and other cardiac and arrhythmic complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus. NAFLD is also associated with an increased risk of developing microvascular diabetic complications, especially chronic kidney disease. This Review focuses on the strong association between NAFLD and the risk of chronic vascular complications in patients with type 1 diabetes mellitus or type 2 diabetes mellitus, thereby promoting an increased awareness of the extra-hepatic implications of this increasingly prevalent and burdensome liver disease. We also discuss the putative underlying mechanisms by which NAFLD contributes to vascular diseases, as well as the emerging role of changes in the gut microbiota (dysbiosis) in the pathogenesis of NAFLD and associated vascular diseases.
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6.
Linearity, Bias, and Precision of Hepatic Proton Density Fat Fraction Measurements by Using MR Imaging: A Meta-Analysis.
Yokoo, T, Serai, SD, Pirasteh, A, Bashir, MR, Hamilton, G, Hernando, D, Hu, HH, Hetterich, H, Kühn, JP, Kukuk, GM, et al
Radiology. 2018;(2):486-498
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Abstract
Purpose To determine the linearity, bias, and precision of hepatic proton density fat fraction (PDFF) measurements by using magnetic resonance (MR) imaging across different field strengths, imager manufacturers, and reconstruction methods. Materials and Methods This meta-analysis was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A systematic literature search identified studies that evaluated the linearity and/or bias of hepatic PDFF measurements by using MR imaging (hereafter, MR imaging-PDFF) against PDFF measurements by using colocalized MR spectroscopy (hereafter, MR spectroscopy-PDFF) or the precision of MR imaging-PDFF. The quality of each study was evaluated by using the Quality Assessment of Studies of Diagnostic Accuracy 2 tool. De-identified original data sets from the selected studies were pooled. Linearity was evaluated by using linear regression between MR imaging-PDFF and MR spectroscopy-PDFF measurements. Bias, defined as the mean difference between MR imaging-PDFF and MR spectroscopy-PDFF measurements, was evaluated by using Bland-Altman analysis. Precision, defined as the agreement between repeated MR imaging-PDFF measurements, was evaluated by using a linear mixed-effects model, with field strength, imager manufacturer, reconstruction method, and region of interest as random effects. Results Twenty-three studies (1679 participants) were selected for linearity and bias analyses and 11 studies (425 participants) were selected for precision analyses. MR imaging-PDFF was linear with MR spectroscopy-PDFF (R2 = 0.96). Regression slope (0.97; P < .001) and mean Bland-Altman bias (-0.13%; 95% limits of agreement: -3.95%, 3.40%) indicated minimal underestimation by using MR imaging-PDFF. MR imaging-PDFF was precise at the region-of-interest level, with repeatability and reproducibility coefficients of 2.99% and 4.12%, respectively. Field strength, imager manufacturer, and reconstruction method each had minimal effects on reproducibility. Conclusion MR imaging-PDFF has excellent linearity, bias, and precision across different field strengths, imager manufacturers, and reconstruction methods. © RSNA, 2017 Online supplemental material is available for this article. An earlier incorrect version of this article appeared online. This article was corrected on October 2, 2017.
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Ad Libitum Mediterranean and Low-Fat Diets Both Significantly Reduce Hepatic Steatosis: A Randomized Controlled Trial.
Properzi, C, O'Sullivan, TA, Sherriff, JL, Ching, HL, Jeffrey, GP, Buckley, RF, Tibballs, J, MacQuillan, GC, Garas, G, Adams, LA
Hepatology (Baltimore, Md.). 2018;(5):1741-1754
Abstract
Although diet-induced weight loss is first-line treatment for patients with nonalcoholic fatty liver disease (NAFLD), long-term maintenance is difficult. The optimal diet for improvement in either NAFLD or associated cardiometabolic risk factors, regardless of weight loss, is unknown. We examined the effect of two ad libitum isocaloric diets (Mediterranean [MD] or low fat [LF]) on hepatic steatosis (HS) and cardiometabolic risk factors. Subjects with NAFLD were randomized to a 12-week blinded dietary intervention (MD vs. LF). HS was determined by magnetic resonance spectroscopy (MRS). From a total of 56 subjects enrolled, 49 completed the intervention and 48 were included for analysis. During the intervention, subjects on the MD had significantly higher total and monounsaturated fat, but lower carbohydrate and sodium, intakes compared to LF subjects (P < 0.01). At week 12, HS had reduced significantly in both groups (P < 0.01), and there was no difference in liver fat reduction between groups (P = 0.32), with mean (SD) relative reductions of 25.0% (±25.3%) in LF and 32.4% (±25.5%) in MD. Liver enzymes also improved significantly in both groups. Weight loss was minimal and not different between groups (-1.6 [±2.1] kg in LF vs -2.1 [±2.5] kg in MD; P = 0.52). Within-group improvements in Framingham Risk Score (FRS), total cholesterol, serum triglyceride (TG), and glycated hemoglobin (HbA1c) were observed in the MD (all P < 0.05), but not with the LF diet. Adherence was higher for the MD compared to LF (88% vs. 64%; P = 0.048). Conclusion: Ad libitum low-fat and Mediterranean diets both improve HS to a similar degree.
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Text messaging approach improves weight loss in patients with nonalcoholic fatty liver disease: A randomized study.
Axley, P, Kodali, S, Kuo, YF, Ravi, S, Seay, T, Parikh, NM, Singal, AK
Liver international : official journal of the International Association for the Study of the Liver. 2018;(5):924-931
Abstract
BACKGROUND & AIMS Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease. The only effective treatment is 7%-10% weight loss. Mobile technology is increasingly used in weight management. This study was performed to evaluate the effects of text messaging intervention on weight loss in patients with NAFLD. METHODS Thirty well-defined NAFLD patients (mean age 52 years, 67% females, mean BMI 38) were randomized 1:1 to control group: counselling on healthy diet and exercise, or intervention group: text messages in addition to healthy life style counselling. NAFLD text messaging program sent weekly messages for 22 weeks on healthy life style education. Primary outcome was change in weight. Secondary outcomes were changes in liver enzymes and lipid profile. RESULTS Intervention group lost an average of 6.9 lbs. (P = .03) compared to gain of 1.8 lbs. in the control group (P = .45). Intervention group also showed a decrease in ALT level (-12.5 IU/L, P = .035) and improvement in serum triglycerides (-28 mg/dL, P = .048). There were no changes in the control group on serum ALT level (-6.1 IU/L, P = .46) and on serum triglycerides (-20.3 mg/dL P = .27). Using one-way analysis of variance, change in outcomes in intervention group compared to control group was significant for weight (P = .02) and BMI (P = .02). CONCLUSIONS Text messaging on healthy life style is associated with reduction in weight in NAFLD patients. Larger studies are suggested to examine benefits on liver histology, and assess long-term impact of this approach in patients with NAFLD.
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Liver fibrosis in the context of nonalcoholic steatohepatitis: the role of adipokines.
DI Maira, G, Pastore, M, Marra, F
Minerva gastroenterologica e dietologica. 2018;(1):39-50
Abstract
Liver fibrosis is a multifaceted process that occurs as a consequence of chronic liver injury. This process is characterized by inflammation, activation of matrix-producing cells, matrix deposition and remodeling, and epithelial cell regeneration. In subjects with chronic liver damage, fibrogenesis is favored by the presence of obesity and insulin resistance, which are also relevant risk factors for the development and progression of nonalcoholic steatohepatitis (NASH). It is now well-known that adipose tissue is not only involved in energy storage but also functions as an endocrine organ that secretes various bioactive substances known as adipokines. This term identifies a group of polypeptide molecules, which exert local, peripheral and/or central actions. Additionally to their well-established role in controlling adipose tissue physiology, energy homeostasis, inflammation and immune function, adipokines have been shown to be involved in different obesity-related diseases, such as hypertension, atherosclerosis and type 2 diabetes. In liver diseases, the biologic actions of these factors may contribute to the mechanisms leading to NASH. In this review, we focus on the role of adipokines in liver fibrogenesis and discuss their potential as regulators of this pathological condition and as targets for future pharmacological treatment strategies of chronic liver diseases.
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Green tea as a safe alternative approach for nonalcoholic fatty liver treatment: A systematic review and meta-analysis of clinical trials.
Mansour-Ghanaei, F, Hadi, A, Pourmasoumi, M, Joukar, F, Golpour, S, Najafgholizadeh, A
Phytotherapy research : PTR. 2018;(10):1876-1884
Abstract
This study aimed to evaluate the efficacy of green tea supplementation on nonalcoholic fatty liver disease treatment. Electronic databases, including PubMed, Scopus, Web of Science, and Google Scholar, were systematically searched up to October 30, 2017, to identify eligible trials based on the inclusion criteria. The effect size was presented as mean difference with 95% confidence intervals (CI). The meta-analysis of data from four studies indicated significant effects of green tea supplementation in altering alanine aminotransferases (-12.81 U/L; 95% CI: -18.17 to -7.45) and aspartate aminotransferases (-10.91 U/L; 95% CI: -19.66 to -2.17) blood concentrations. Likewise, a favorable effect of green tea administration was observed on body mass index (-2.08 kg/cm2 ; 95% CI: -2.81 to -1.36), triacylglycerol (-31.87 mg/dl; 95% CI: -40.62 to -23.12), total cholesterol (-27.57 mg/dl; 95% CI: -36.17 to -18.98), and low-density lipoprotein cholesterol (-14.15 mg/dl; 95% CI: -23.69 to -4.60), whereas no significant effect was detected on high-density lipoprotein cholesterol concentrations (7.41 mg/dl; 95% CI: -1.49 to 16.30) and homeostasis model assessment of insulin resistance (-4.06; 95% CI: -10.22 to 2.09). This systematic review and meta-analysis of available trials suggests that there are potential benefits of green tea supplementation on nonalcoholic fatty liver disease.