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1.
Dysmetabolic Hyperferritinemia and Dysmetabolic Iron Overload Syndrome (DIOS): Two Related Conditions or Different Entities?
Rametta, R, Fracanzani, AL, Fargion, S, Dongiovanni, P
Current pharmaceutical design. 2020;(10):1025-1035
Abstract
Hyperferritinemia is observed in one-third of patients with non-alcoholic fatty liver disease (NAFLD) and Metabolic Syndrome (MetS). The condition characterized by increased body iron stores associated with components of MetS has been defined as Dysmetabolic Iron Overload Syndrome (DIOS). DIOS represents the most frequent iron overload condition, since it is observed in 15% of patients with MetS and in half of those with NAFLD and its clinical presentation overlaps almost completely with that of dysmetabolic hyperferritinemia (DH). The pathogenetic mechanisms linking insulin resistance (IR), NAFLD and DIOS to iron overload are still debated. Hepcidin seems to play a role in iron accumulation in DIOS and NAFLD patients who show elevated serum hepcidin levels. The iron challenge does not restrain iron absorption despite adequate hepcidin production, suggesting that an impaired hepcidin activity rather than a deficit of hormone production underlies DIOS pathogenesis. Acquired and genetic factors are recognized to contribute to iron accumulation in NAFLD whereas additional studies are required to clearly demonstrate whether the same or different genetic factors lead to iron overload in DIOS. Finally, iron depletion by phlebotomy, together with the modification of diet and life-style habits, represents the therapeutic approach to decrease metabolic alterations and liver enzymes in NAFLD and DIOS patients. In this review, we summarized the current knowledge on the dysregulation of iron homeostasis in NAFLD and DIOS in the attempt to clarify whether they are different or more likely strictly related conditions, sharing the same pathogenic cause i.e. the MetS.
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2.
Effects of a carbohydrate-restricted diet on hepatic lipid content in adolescents with non-alcoholic fatty liver disease: A pilot, randomized trial.
Goss, AM, Dowla, S, Pendergrass, M, Ashraf, A, Bolding, M, Morrison, S, Amerson, A, Soleymani, T, Gower, B
Pediatric obesity. 2020;(7):e12630
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has emerged as the most common form of liver disease among adolescents in industrialized countries. While lifestyle intervention remains the hallmark treatment for NAFLD, the most effective dietary strategy to reverse NAFLD in children is unknown. OBJECTIVE The objective of this study was to determine the effects of a moderately CHO-restricted diet (CRD) vs fat-restricted diet (FRD) in adolescents with NAFLD on reduction in liver fat and insulin resistance. METHODS Thirty-two children/adolescents (age 9-17) with obesity and NAFLD were randomized to a CRD (<25:25:>50% energy from CHO:protein:fat) or FRD (55:25:20) for 8 weeks. Caloric intakes were calculated to be weight maintaining. Change in hepatic lipid content was measured via magnetic resonance imaging, body composition via dual energy X ray absorptiometry and insulin resistance via a fasting blood sample. RESULTS Change in hepatic lipid did not differ with diet, but declined significantly (-6.0 ± 4.7%, P < .001 only within the CRD group. We found significantly greater decreases in insulin resistance (HOMA-IR, <.05), abdominal fat mass (P < .01) and body fat mass (P < .01) in response to the CRD vs FRD. CONCLUSION These findings suggest that consumption of a moderately CHO-restricted diet may result in decreased hepatic lipid as well as improvements in body composition and insulin resistance in adolescents with NAFLD even in the absence of intentional caloric restriction. Larger studies are needed to determine whether a CHO-restricted diet induces change in hepatic lipid independent of change in body fat.
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3.
Prevalence of responders for hepatic fat, adiposity and liver enzyme levels in response to a lifestyle intervention in children with overweight/obesity: EFIGRO randomized controlled trial.
Medrano, M, Arenaza, L, Ramírez-Vélez, R, Ortega, FB, Ruiz, JR, Labayen, I
Pediatric diabetes. 2020;(2):215-223
Abstract
BACKGROUND/OBJECTIVE Exercise and lifestyle interventions have been shown to reduce hepatic fat (HF) and adiposity in youth. However, the interindividual response in HF after a lifestyle intervention with or without exercise in children is unknown. The aim of the present study was to compare interindividual variability for HF, adiposity, gamma-glutamyl transferase (GGT), and the aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT) in children with overweight/obesity participating in a 22-week lifestyle intervention with (intensive intervention) or without exercise (control intervention). METHODS Data from 102 children (9-12 years, 55% girls) with overweight/obesity participating in the EFIGRO randomized controlled trial were analyzed. Percentage HF (magnetic resonance imaging), weight, body and fat mass index (BMI and FMI), GGT, AST/ALT, cardiorespiratory fitness (CRF, 20 meters shuttle run test) were assessed before and after the intervention by the same trained researchers. The control intervention consisted in 11 sessions of a family-based lifestyle and psycho-educational program. The intensive intervention included the control intervention plus supervised exercise (3 sessions/week). RESULTS The prevalence of responders for HF (54% vs. 34%), weight (27% vs. 11%), BMI (71% vs. 47%), FMI (90% vs. 60%), and GGT (69% vs. 39%) was higher in the intensive than in the control group (Ps < 0.05). Responders for weight (16 ± 3 vs. 6 ± 2 laps) and BMI (11 ± 2 vs. 3 ± 4 laps) improved more CRF levels than non-responders (Ps < 0.05). CONCLUSIONS The addition of exercise to a lifestyle intervention may increase the responder rates for HF, adiposity, and GGT in children with overweight/obesity. Improvements in CRF may explain differences between weight and BMI responders and non-responders. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02258126.
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4.
Combined effect of n-3 fatty acids and phytosterol esters on alleviating hepatic steatosis in non-alcoholic fatty liver disease subjects: a double-blind placebo-controlled clinical trial.
Song, L, Zhao, XG, Ouyang, PL, Guan, Q, Yang, L, Peng, F, Du, H, Yin, F, Yan, W, Yu, WJ, et al
The British journal of nutrition. 2020;(10):1148-1158
Abstract
The aim of this study was to investigate the combined effect of n-3 fatty acids (EPA and DHA, at an EPA:DHA ratio of 150:500) and phytosterol esters (PS) on non-alcoholic fatty liver disease (NAFLD) patients. We conducted a randomised, double-blind, placebo-controlled trial. Ninety-six NAFLD subjects were randomly assigned to the following groups: the PS group (receiving 3·3 g/d PS); the FO group (receiving 450 mg EPA + 1500 mg DHA/d); the PS + FO combination group (receiving 3·3 g/d PS and 450 mg EPA + 1500 mg DHA/d) and the PO group (a placebo group). The baseline clinical characteristics of the four groups were similar. The primary outcome was liver:spleen attenuation ratio (L:S ratio). The percentage increase in liver-spleen attenuation (≤1) in the PS + FO group was 36 % (P = 0·083), higher than those in the other three groups (PS group, 11 %, P = 0·519; FO group, 18 %, P = 0·071; PO group, 15 %, P = 0·436). Compared with baseline, transforming growth factor-β (TGF-β) was significantly decreased in the three study groups at the end of the trial (PS, P = 0·000; FO, P = 0·002; PS + FO, P = 0·001) and TNF-α was significantly decreased in the FO group (P = 0·036), PS + FO group (P = 0·005) and PO group (P = 0·032) at the end of the intervention. Notably, TGF-β was reduced significantly more in the PS + FO group than in the PO group (P = 0·032). The TAG and total cholesterol levels of the PS + FO group were reduced by 11·57 and 9·55 %, respectively. In conclusion, co-supplementation of PS and EPA + DHA could increase the effectiveness of treatment for hepatic steatosis.
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5.
Plasma BCAA Changes in Patients With NAFLD Are Sex Dependent.
Grzych, G, Vonghia, L, Bout, MA, Weyler, J, Verrijken, A, Dirinck, E, Chevalier Curt, MJ, Van Gaal, L, Paumelle, R, Francque, S, et al
The Journal of clinical endocrinology and metabolism. 2020;(7)
Abstract
CONTEXT Plasma branched chain amino acid (BCAA) concentrations correlate positively with body mass index (BMI), measures of insulin resistance (IR), and severity of nonalcoholic fatty liver disease (NAFLD). Moreover, plasma BCAA concentrations also differ between the sexes, which display different susceptibilities to cardio-metabolic diseases. OBJECTIVE Assess whether plasma BCAA concentrations associate with NAFLD severity independently of BMI, IR, and sex. PATIENTS Patients visiting the obesity clinic of the Antwerp University Hospital were consecutively recruited from 2006 to 2014. DESIGN AND SETTING A cross-sectional study cohort of 112 obese patients (59 women and 53 men) was divided into 4 groups according to NAFLD severity. Groups were matched for sex, age, BMI, homeostatic model assessment of IR, and hemoglobin A1c. MAIN OUTCOME MEASURES Fasting plasma BCAA concentrations were measured by tandem mass spectrometry using the aTRAQ™ method. RESULTS In the study cohort, a modest positive correlation was observed between plasma BCAA concentrations and NAFLD severity, as well as a strong effect of sex on plasma BCAA levels. Subgroup analysis by sex revealed that while plasma BCAA concentrations increased with severity of NAFLD in women, they tended to decrease in men. Additionally, only women displayed significantly increased plasma BCAAs with increasing fibrosis. CONCLUSION Plasma BCAA concentrations display sex-dimorphic changes with increasing severity of NAFLD, independently of BMI, IR, and age. Additionally, plasma BCAA are associated with significant fibrosis in women, but not in men. These results highlight the importance of a careful consideration of sex as a major confounding factor in cross-sectional studies of NAFLD.
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6.
Nutritional Approaches for the Management of Nonalcoholic Fatty Liver Disease: An Evidence-Based Review.
Parra-Vargas, M, Rodriguez-Echevarria, R, Jimenez-Chillaron, JC
Nutrients. 2020;(12)
Abstract
Nonalcoholic fatty liver disease (NAFLD) is on the rise worldwide representing a public health issue. Its coexistence with obesity and other metabolic alterations is highly frequent. Therefore, current therapy interventions for NAFLD are mainly focused on progressive weight loss through modulation of overall calorie intake with or without specific macronutrient adjustments. Furthermore, other relevant nutritional interventions are built on food selection and time-restricted eating. Since every strategy might bring different results, choosing the optimal diet therapy for a patient is a complicated task, because NAFLD is a multifactorial complex disease. Importantly, some factors need to be considered, such as nutrition-based evidence in terms of hepatic morphophysiological improvements as well as adherence of the patient to the meal plan and adaptability in their cultural context. Thus, the purpose of this review is to explore and compare the subtleties and nuances of the most relevant clinical practice guidelines and the nutritional approaches for the management of NAFLD with a special attention to tangible outcomes and long-term adherence.
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7.
The influence of dietary conditions in the effects of resveratrol on hepatic steatosis.
Milton-Laskibar, I, Aguirre, L, Gómez-Zorita, S, Rolo, AP, Portillo, MP
Food & function. 2020;(11):9432-9444
Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered the major cause for the development of chronic liver alterations. Hepatic steatosis is the most benign and common form of NAFLD, although its potential to evolve into more detrimental liver alterations makes its treatment necessary. In this regard, much attention has been paid to polyphenols, with resveratrol being one of the most studied ones. This review is aimed at studying the effects induced by resveratrol on hepatic steatosis in both preclinical studies conducted under different feeding conditions (overfeeding, normal feeding and caloric restriction), and in clinical trials. The vast majority of studies have been conducted by administering the polyphenol at the same time as an obesogenic diet. Under these experimental conditions, resveratrol has shown effectiveness improving diet-induced excessive liver lipid accumulation. Data are scarce for studies carried out by administering resveratrol under standard or energy-restricted feeding conditions. In this regard, while resveratrol retains its effectiveness, ameliorating hepatic steatosis under standard feeding conditions, such an effect has not been reported for the administration of the polyphenol under energy restriction. With regard to clinical trials, in the majority of them, resveratrol did not show its effectiveness in improving hepatic steatosis. This lack of effect could be due to significant differences in the experimental procedures (mainly the length of the experimental period). The relevance of liver fat content at the baseline should also be considered. Altogether, there is no sufficient scientific support so far for proposing resveratrol as a tool for hepatic steatosis treatment.
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8.
The effect of a Mediterranean diet on metabolic parameters in patients with non-alcoholic fatty liver disease: A systematic review of randomized controlled trials.
Moosavian, SP, Arab, A, Paknahad, Z
Clinical nutrition ESPEN. 2020;:40-46
Abstract
BACKGROUND Dietary habit can play a key role in the prevention and treatment of fatty liver disease (NAFLD). Although many studies have investigated the effect of Mediterranean diet on NAFLD, findings are inconsistent and there is no systematic review on this topic. Therefore, the aim of this systematic review is to summarize the effect of Mediterranean diet on serum metabolic indices and anthropometric measures among NAFLD patients. METHODS We searched titles, abstracts, and keywords of articles indexed in Science Direct, MEDLINE, and Google Scholar databases up to October 2018 to identify eligible RCT studies. Randomized clinical trials assessing the effects of MD on NAFLD were included. RESULTS The present study included 10 randomized controlled trials, which involved a total of 856 adults with NAFLD. According to the result, MD may improve anthropometric measures, lipid profile, glycemic indices, liver enzyme, and NAFLD severity indices among patients with NAFLD. CONCLUSION We found that MD could alleviate NAFLD severity parameters but differences between studies should be taken into account. Finally, in order to draw a firm link between MD and NAFLD, more clinical trials with adequate sample size and better methodology should be done.
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9.
[Electroacupuncture combined with lifestyle control on obese nonalcoholic fatty liver disease: a randomized controlled trial].
Dong, C, Zhang, CR, Xue, BY, Miu, WF, Fang, NY, Li, K, Ou, ZJ, Xu, YQ
Zhongguo zhen jiu = Chinese acupuncture & moxibustion. 2020;(2):129-34
Abstract
OBJECTIVE To observe the effect of electroacupuncture (EA) combined with lifestyle control on hepatic fat status, hepatic enzymology, glycolipid metabolism and anthropological parameters in patients with obese nonalcoholic fatty liver disease(NAFLD). METHODS A total of 90 patients with obese NAFLD were randomized into an observation group (45 cases, 4 cases dropped off) and a control group (45 cases, 1 case dropped off). Lifestyle control was implemented in the control group. On the basis of the treatment in the control group, acupuncture was applied at Zhongwan (CV 12), Quchi (LI 11), Shuifen (CV 9), Huaroumen (ST 24), Daheng (SP 15), Guanyuan (CV 4), Qihai (CV 6), etc. EA was provided at Huaroumen (ST 24) and Daheng (SP 15) with dilatational wave, 2 Hz/100 Hz in frequency, 30 min each time, once every other day, 3 times a week. The treatment for 12 weeks was required in both of the two groups. Hepatic fat status [controlled attenuation parameter (CAP) and liver stiffness measurement (LSM)], hepatic enzymology [alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (GGT)], glycolipid metabolism and insulin sensitivity [fasting plasma glucose (FPG), fasting serum lisulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C)] and anthropological parameters [body weight (BW), body mass index (BMI), fat percentage (FP), waist circumference (WC), hip circumference (HC) and waist-to-hip ratio (WHR)] in the two groups were observed before and after treatment. RESULTS ①Compared before treatment, hepatic CAP, LSM, serum ALT, AST and GGT after treatment were obviously reduced in the two groups (P<0.05, P<0.01). After treatment, CAP and ALT in the observation group were lower than the control group (P<0.05). ②Compared before treatment, FINS, HOMA-IR, LDL-C, TC and TG after treatment were obviously reduced in the two groups (P<0.05, P<0.01),while the levels of HDL-C were increased (P<0.05). Compared before treatment, FPG after treatment in the observation group was reduced (P<0.05). Compared with the control group, FINS, HOMA-IR, TC and TG in the observation group were lower than those in the control group after treatment (P<0.05). ③Compared before treatment, BW BMI, FP, WC, HC, WHR after treatment were obviously reduced in the two groups (P<0.01). After treatment, WC and WHR in the observation group were lower than the control group (P<0.05). CONCLUSION Electroacupuncture combined with lifestyle control can effectively treat obese nonalcoholic fatty liver disease, and present better therapeutic effect on hepatic fat status, glycolipid metabolism, insulin resistance, WC and WHR.
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10.
Role of mitochondrial quality control in the pathogenesis of nonalcoholic fatty liver disease.
Li, R, Toan, S, Zhou, H
Aging. 2020;(7):6467-6485
Abstract
Nutrient oversupply and mitochondrial dysfunction play central roles in nonalcoholic fatty liver disease (NAFLD). The mitochondria are the major sites of β-oxidation, a catabolic process by which fatty acids are broken down. The mitochondrial quality control (MQC) system includes mitochondrial fission, fusion, mitophagy and mitochondrial redox regulation, and is essential for the maintenance of the functionality and structural integrity of the mitochondria. Excessive and uncontrolled production of reactive oxygen species (ROS) in the mitochondria damages mitochondrial components, including membranes, proteins and mitochondrial DNA (mtDNA), and triggers the mitochondrial pathway of apoptosis. The functionality of some damaged mitochondria can be restored by fusion with normally functioning mitochondria, but when severely damaged, mitochondria are segregated from the remaining functional mitochondrial network through fission and are eventually degraded via mitochondrial autophagy, also called as mitophagy. In this review, we describe the functions and mechanisms of mitochondrial fission, fusion, oxidative stress and mitophagy in the development and progression of NAFLD.