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Effects of Diet and Active Compounds on Non-alcoholic Fatty Liver...
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Effects of Diet and Active Compounds on Non-alcoholic Fatty Liver Disease

A special issue of Nutrients (ISSN 2072-6643).

Deadline for manuscript submissions: closed (31 October 2019) | Viewed by 127051

Special Issue Editors

Prof. Dr. Elena Grasselli

E-Mail Website
Guest Editor
DISTAV, Dipartimento di Scienze della Terra, dell'Ambiente e della Vita, Università di Genova, Genova, Italy
Interests: endocrine disruptors; obesogens; hormones; lipid Metabolism
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Ilaria Demori

E-Mail Website
Guest Editor
DISTAV, Dipartimento di Scienze della Terra, dell'Ambiente e della Vita, Università di Genova, Genova, Italy
Interests: nutrition and metabolism; nutrition and stress; physiology of stress; Psychoneuroendocrineimmunology (PNEI)
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Non-alcoholic fatty liver disease (NAFLD) shows rising prevalence among individuals from different ages and incomes, especially in Western-lifestyle societies. This asymptomatic condition can progress to more severe pathologies, increasing the morbidity and mortality of individuals.

Many efforts have been made to find strategies to decrease fat accumulation in the liver and, ultimately, in the whole body. In the last decades, a growing body of evidence documented that changes in lifestyle are the most effective, especially as regards nutritional habits.

At least two hallmarks contribute to the success of dietary interventions: First, a reduction in calorie intake; second, an increase in fruit and vegetable consumption, which leads to enhanced intake of phytonutrients able to exert antioxidant and anti-inflammatory actions.

Therefore, the aim of this Special Issue is to provide new insights into the effectiveness of diet regimens and specific dietary compounds to prevent and/or cure NAFLD.

Prof. Elena Grasselli
Prof. Ilaria Demori
Guest Editors

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Non-alcoholic fatty liver disease (NAFLD)
  • Metabolic syndrome
  • Nutritional habits
  • Polyphenols
  • Mediterranean diet
  • Antisteatotic active compounds
  • Prebiotics
  • Probiotics
  • Antioxidants
  • Anti-inflammatory activities

Published Papers (19 papers)

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Research

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8 pages, 1084 KiB  
Article
Berberis aristata, Elaeis guineensis and Coffea canephora Extracts Modulate the Insulin Receptor Expression and Improve Hepatic Steatosis in NAFLD Patients: A Pilot Clinical Trial
by Valentina Cossiga, Vincenzo Lembo, Maria Guarino, Concetta Tuccillo, Federica Morando, Giuseppina Pontillo, Andrea Fiorentino, Nicola Caporaso and Filomena Morisco
Nutrients 2019, 11(12), 3070; https://doi.org/10.3390/nu11123070 - 16 Dec 2019
Cited by 6 | Viewed by 3746
Abstract
Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance and diabetes. A reduction in insulin receptor (IR) expression has been reported in these patients. The aims of this study were to evaluate the effects of a mixture of plant extracts consisting of [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance and diabetes. A reduction in insulin receptor (IR) expression has been reported in these patients. The aims of this study were to evaluate the effects of a mixture of plant extracts consisting of Berberis aristata, Elaeis guineensis and decaffeinated green coffee by Coffea canephora on the improvement of glycaemic profile, through the modulation of IR levels, and of hepatic steatosis in NAFLD patients. Forty-nine patients with a grade of steatosis S1-S2 were randomly allocated to the treatment with plant extracts or placebo for six months. Hepatic steatosis was evaluated using transient elastography with CAP (controlled attenuation parameter). Glucose, insulin, and IR levels were measured in serum samples. At the end of the study, patients treated with plant extracts displayed a significant reduction of serum glucose (p < 0.001), insulin levels (p < 0.01), homeostatic model assessment for insulin resistance (HOMA-IR) index (p < 0.001), and CAP value (p < 0.01) compared to placebo. Moreover, the IR expression was increased significantly in the plant extracts group compared to the placebo group (p < 0.05). The combination of plant extracts increases serum IR levels, determining amelioration of glycemic profile and improvement of hepatic steatosis in NAFLD patients. Full article
(This article belongs to the Special Issue Effects of Diet and Active Compounds on Non-alcoholic Fatty Liver Disease)
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10 pages, 245 KiB  
Article
Sex- and Age-Related Differences in the Contribution of Ultrasound-Measured Visceral and Subcutaneous Abdominal Fat to Fatty Liver Index in Overweight and Obese Caucasian Adults
by Alessandro Leone, Alberto Battezzati, Giorgio Bedogni, Laila Vignati, Angelo Vanzulli, Ramona De Amicis, Andrea Foppiani and Simona Bertoli
Nutrients 2019, 11(12), 3008; https://doi.org/10.3390/nu11123008 - 09 Dec 2019
Cited by 10 | Viewed by 3545
Abstract
Differences in body fat distribution may be a reason for the sex-, age-, and ethnicity-related differences in the prevalence of fatty liver disease (FL). This study aimed to evaluate the sex- and age-related differences in the contribution of visceral (VAT) and subcutaneous (SAT) [...] Read more.
Differences in body fat distribution may be a reason for the sex-, age-, and ethnicity-related differences in the prevalence of fatty liver disease (FL). This study aimed to evaluate the sex- and age-related differences in the contribution of visceral (VAT) and subcutaneous (SAT) abdominal fat, measured by ultrasound, to fatty liver index (FLI) in a large sample of overweight and obese Caucasian adults, and to identify the VAT and SAT cut-off values predictive of high FL risk. A cross-sectional study on 8103 subjects was conducted. Anthropometrical measurements were taken and biochemical parameters measured. VAT and SAT were measured by ultrasonography. FLI was higher in men and increased with increasing age, VAT, and SAT. The sex*VAT, age*VAT, sex*SAT, and age*SAT interactions negatively contributed to FLI, indicating a lower VAT and SAT contribution to FLI in men and in the elderly for every 1 cm of increment. Because of this, sex- and age-specific cut-off values for VAT and SAT were estimated. In conclusion, abdominal adipose tissue depots are associated with FLI, but their contribution is sex- and age-dependent. Sex- and age-specific cut-off values of ultrasound-measured VAT and SAT are suggested, but they need to be validated in external populations. Full article
(This article belongs to the Special Issue Effects of Diet and Active Compounds on Non-alcoholic Fatty Liver Disease)
17 pages, 5855 KiB  
Article
Fermented Korean Red Ginseng Extract Enriched in Rd and Rg3 Protects against Non-Alcoholic Fatty Liver Disease through Regulation of mTORC1
by Su-Yeon Choi, Jeong-Su Park, Chang-Ho Shon, Chae-Young Lee, Jae-Myun Ryu, Dong-Ju Son, Bang-Yeon Hwang, Hwan-Soo Yoo, Young-Chang Cho, Jin Lee, Jong-Won Kim and Yoon-Seok Roh
Nutrients 2019, 11(12), 2963; https://doi.org/10.3390/nu11122963 - 04 Dec 2019
Cited by 18 | Viewed by 4735
Abstract
The fermentation of Korean red ginseng (RG) increases the bioavailability and efficacy of RG, which has a protective role in various diseases. However, the ginsenoside-specific molecular mechanism of the fermented RG with Cordyceps militaris (CRG) has not been elucidated in non-alcoholic fatty liver [...] Read more.
The fermentation of Korean red ginseng (RG) increases the bioavailability and efficacy of RG, which has a protective role in various diseases. However, the ginsenoside-specific molecular mechanism of the fermented RG with Cordyceps militaris (CRG) has not been elucidated in non-alcoholic fatty liver disease (NAFLD). A mouse model of NAFLD was induced by a fast-food diet (FFD) and treated with CRG (100 or 300 mg/kg) for the last 8 weeks. CRG-mediated signaling was assessed in the liver cells isolated from mice. CRG administration significantly reduced the FFD-induced steatosis, liver injury, and inflammation, indicating that CRG confers protective effects against NAFLD. Of note, an extract of CRG contains a significantly increased amount of ginsenosides (Rd and Rg3) after bioconversion compared with that of conventional RG. Moreover, in vitro treatment with Rd or Rg3 produced anti-steatotic effects in primary hepatocytes. Mechanistically, CRG protected palmitate-induced activation of mTORC1 and subsequent inhibition of mitophagy and PPARα signaling. Similar to that noted in hepatocytes, CRG exerted anti-inflammatory activity through mTORC1 inhibition-mediated M2 polarization. In conclusion, CRG inhibits lipid-mediated pathologic activation of mTORC1 in hepatocytes and macrophages, which in turn prevents NAFLD development. Thus, the administration of CRG may be an alternative for the prevention of NAFLD. Full article
(This article belongs to the Special Issue Effects of Diet and Active Compounds on Non-alcoholic Fatty Liver Disease)
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15 pages, 3046 KiB  
Article
Lotus Seedpod Extracts Reduced Lipid Accumulation and Lipotoxicity in Hepatocytes
by Yen-Tze Liu, Yen-Hsun Lai, Hui-Hsuan Lin and Jing-Hsien Chen
Nutrients 2019, 11(12), 2895; https://doi.org/10.3390/nu11122895 - 28 Nov 2019
Cited by 15 | Viewed by 4198
Abstract
Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic disorders, including hepatic lipid accumulation and lipotoxicity. Plant-derived polyphenols have attracted considerable attention in the prevention of NAFLD. Lotus seedpod, rich in polyphenols, is a traditional Chinese herbal medicine. Previous studies have showed [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic disorders, including hepatic lipid accumulation and lipotoxicity. Plant-derived polyphenols have attracted considerable attention in the prevention of NAFLD. Lotus seedpod, rich in polyphenols, is a traditional Chinese herbal medicine. Previous studies have showed that lotus seedpod possess radioprotective, antioxidant, anti-cancer, and anti-inflammatory activities. In this study, the in vitro hepatoprotective effect of lotus seedpod extract (LSE) and its main component epigallocatechin (EGC) was examined. Firstly, oleic acid (OA), an unsaturated fatty acid, was used to induce the phenotype of NAFLD in human hepatocytes, HepG2 cells. LSE dose-dependently improved the OA-induced viability loss of HepG2 cells. Non-cytotoxic concentrations of LSE or EGC abolished intracellular lipid accumulation and oxidative stress in the OA-treated cells. In addition, LSE and EGC showed a minor effect on autophagy, and potential in reducing OA-induced occurrence of apoptosis confirmed by morphological and biochemical features, including an increase in the formation of apoptotic bodies, the exposure of phosphatidylserine, and activation of caspases. Molecular data showed the anti-apoptotic effect of LSE might be mediated via downregulation of the mitochondrial pathway. Our data imply that EGC-enriched LSE potentially could be developed as an anti-NAFLD agent. Full article
(This article belongs to the Special Issue Effects of Diet and Active Compounds on Non-alcoholic Fatty Liver Disease)
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20 pages, 3638 KiB  
Article
Atorvastatin and Vitamin E Accelerates NASH Resolution by Dietary Intervention in a Preclinical Guinea Pig Model
by Julie Hviid Klaebel, Mia Skjødt, Josephine Skat-Rørdam, Günaj Rakipovski, David H. Ipsen, Anne Marie V. Schou-Pedersen, Jens Lykkesfeldt and Pernille Tveden-Nyborg
Nutrients 2019, 11(11), 2834; https://doi.org/10.3390/nu11112834 - 19 Nov 2019
Cited by 14 | Viewed by 4263
Abstract
Despite affecting millions of patients worldwide, no pharmacological treatment has yet proved effective against non-alcoholic steatohepatitis (NASH) induced liver fibrosis. Current guidelines recommend lifestyle modifications including reductions in dietary energy intake. Recently, therapy with atorvastatin and vitamin E (vitE) has been recommended, although [...] Read more.
Despite affecting millions of patients worldwide, no pharmacological treatment has yet proved effective against non-alcoholic steatohepatitis (NASH) induced liver fibrosis. Current guidelines recommend lifestyle modifications including reductions in dietary energy intake. Recently, therapy with atorvastatin and vitamin E (vitE) has been recommended, although clinical studies on the resolution of hepatic fibrosis are inconclusive. Targeting NASH-induced hepatic end-points, this study evaluated the effects of atorvastatin and vitE alone or in combination with a dietary intervention in the guinea pig NASH model. Guinea pigs (n = 72) received 20 weeks of high fat feeding before allocating to four groups: continued HF feeding (HF), HF diet with atorvastatin and vitE (HF+), low-fat diet (LF) and low-fat with atorvastatin and vitE (LF+), for four or eight weeks of intervention. Both LF and LF+ decreased liver weight, cholesterol and plasma dyslipidemia. LF+ further improved hepatic histopathological hallmarks (p < 0.05), liver injury markers aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (p < 0.05) and reduced the expression of target genes of hepatic inflammation and fibrosis (p < 0.05), underlining an increased effect on NASH resolution in this group. Collectively, the data support an overall beneficial effect of diet change, and indicate that atorvastatin and vitE therapy combined with a diet change act synergistically in improving NASH-induced endpoints. Full article
(This article belongs to the Special Issue Effects of Diet and Active Compounds on Non-alcoholic Fatty Liver Disease)
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13 pages, 278 KiB  
Article
Effects of Some Food Components on Non-Alcoholic Fatty Liver Disease Severity: Results from a Cross-Sectional Study
by Antonella Mirizzi, Isabella Franco, Carla Maria Leone, Caterina Bonfiglio, Raffaele Cozzolongo, Maria Notarnicola, Vito Giannuzzi, Valeria Tutino, Valentina De Nunzio, Irene Bruno, Claudia Buongiorno, Angelo Campanella, Valentina Deflorio, Annamaria Pascale, Filippo Procino, Paolo Sorino and Alberto Rubén Osella
Nutrients 2019, 11(11), 2744; https://doi.org/10.3390/nu11112744 - 12 Nov 2019
Cited by 18 | Viewed by 4695
Abstract
Background: The high prevalence of non-alcoholic fatty liver disease (NAFLD) observed in Western countries is due to the concurrent epidemics of overweight/obesity and associated metabolic complications, both recognized risk factors. A Western dietary pattern has been associated with weight gain and obesity, and [...] Read more.
Background: The high prevalence of non-alcoholic fatty liver disease (NAFLD) observed in Western countries is due to the concurrent epidemics of overweight/obesity and associated metabolic complications, both recognized risk factors. A Western dietary pattern has been associated with weight gain and obesity, and more recently with NAFLD. Methods: This is a baseline cross-sectional analysis of 136 subjects (79 males) enrolled consecutively in the NUTRIATT (NUTRItion and Ac-TiviTy) study. Study subjects had moderate or severe NAFLD diagnosed by using Fibroscan-CAP. Food Frequency Questionnaire was used to obtain information about food intake. Statistical analysis included descriptive statistics and a multivariable logistic regression model. Results: The mean age was 49.58 (±10.18) with a mean BMI of 33.41 (±4.74). A significant inverse relationship was revealed between winter ice-cream intake and NAFLD severity (O.R. 0.65, 95% C.I. 0.95–0.99); chickpeas intake and NAFLD severity (O.R. 0.57, 95% C.I. 0.34–0.97), and not industrial aged-cheeses type (O.R. 0.85, 95% C.I. 0.74–0.98). A statistically significant positive association also emerged between rabbit meat (O.R. 1.23, 95% C.I. 1.01–1.49), industrial type aged cheeses (O.R. 1.17, 95% C.I. 1.01–1.35), milk-based desserts (no winter ice cream) (O.R. 1.11, 95% C.I. 1.01–1.21), fats (O.R. 1.12, 95% C.I. 1.01–1.25), and NAFLD severity. Conclusion: The fresh foods from non-intensive farming and high legume intake that characterize the Mediterranean diet would seem to be beneficial for patients with NAFLD. Full article
(This article belongs to the Special Issue Effects of Diet and Active Compounds on Non-alcoholic Fatty Liver Disease)
16 pages, 772 KiB  
Article
The Metabolic and Hepatic Impact of Two Personalized Dietary Strategies in Subjects with Obesity and Nonalcoholic Fatty Liver Disease: The Fatty Liver in Obesity (FLiO) Randomized Controlled Trial
by Bertha Araceli Marin-Alejandre, Itziar Abete, Irene Cantero, J. Ignacio Monreal, Mariana Elorz, José Ignacio Herrero, Alberto Benito-Boillos, Jorge Quiroga, Ana Martinez-Echeverria, Juan Isidro Uriz-Otano, María Pilar Huarte-Muniesa, Josep A. Tur, J. Alfredo Martinez and M. Angeles Zulet
Nutrients 2019, 11(10), 2543; https://doi.org/10.3390/nu11102543 - 22 Oct 2019
Cited by 52 | Viewed by 8247
Abstract
The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. NAFLD management is mainly focused on weight loss, but the optimal characteristics of the diet demand further investigation. This study aims to evaluate the effects of two personalized energy-restricted diets on the [...] Read more.
The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. NAFLD management is mainly focused on weight loss, but the optimal characteristics of the diet demand further investigation. This study aims to evaluate the effects of two personalized energy-restricted diets on the liver status in overweight or obese subjects with NAFLD after a 6 months follow-up. Ninety-eight individuals from the Fatty Liver in Obesity (FLiO) study were randomized into two groups and followed different energy-restricted diets. Subjects were evaluated at baseline and after 6 months. Diet, anthropometry, body composition, and biochemical parameters were evaluated. Liver assessment included ultrasonography, Magnetic Resonance Imaging, elastography, and determination of transaminases. Both dietary groups significantly improved their metabolic and hepatic markers after the intervention, with no significant differences between them. Multivariate regression models evidenced a relationship between weight loss, adherence to the Mediterranean Diet (MedDiet), and a decrease in liver fat content, predicting up to 40.9% of its variability after 6 months. Moreover, the antioxidant capacity of the diet was inversely associated with liver fat content. Participants in the group with a higher adherence to the MedDiet showed a greater reduction in body weight, total fat mass, and hepatic fat. These results support the benefit of energy-restricted diets, high adherence to the MedDiet, and high antioxidant capacity of the diet for the management of NAFLD in individuals with overweight or obesity. Full article
(This article belongs to the Special Issue Effects of Diet and Active Compounds on Non-alcoholic Fatty Liver Disease)
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15 pages, 2803 KiB  
Article
Pterostilbene Reduces Liver Steatosis and Modifies Hepatic Fatty Acid Profile in Obese Rats
by Leixuri Aguirre, Sara Palacios-Ortega, Alfredo Fernández-Quintela, Elizabeth Hijona, Luis Bujanda and María P. Portillo
Nutrients 2019, 11(5), 961; https://doi.org/10.3390/nu11050961 - 26 Apr 2019
Cited by 20 | Viewed by 5017
Abstract
Excessive fat accumulation within the liver is known as “simple hepatic steatosis”, which is the most benign form of non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to determine whether pterostilbene improves this hepatic alteration in Zucker (fa [...] Read more.
Excessive fat accumulation within the liver is known as “simple hepatic steatosis”, which is the most benign form of non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to determine whether pterostilbene improves this hepatic alteration in Zucker (fa/fa) rats. Animals were distributed in two experimental groups (n = 10) and fed a standard laboratory diet. Rats in the pterostilbene group were given a dose of 30 mg/kg body weight/d for six weeks. After sacrifice, serum glucose, transaminase, and insulin concentrations were quantified and the liver triacylglycerol content and fatty acid profile was analyzed. Different pathways of triacylglycerol metabolism in liver were studied, including fatty acid synthesis and oxidation, triglyceride assembly, fatty acid uptake, and glucose uptake. With pterostilbene administration, a reduction in insulin concentrations (consequently in the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)) and hepatic triacylglycerol content were observed. No effects were observed in pterostilbene-treated rats in the activity of de novo lipogenesis enzymes. An improvement in the fatty acid profile was observed in pterostilbene-treated rats. In conclusion, pterostilbene is a useful molecule to reduce liver steatosis. Its delipidating effect is due, at least in part, to reduced fatty acid availability and triacylglycerol synthesis, as well as to an increased very low-density lipoprotein assembly and fatty acid oxidation. Full article
(This article belongs to the Special Issue Effects of Diet and Active Compounds on Non-alcoholic Fatty Liver Disease)
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15 pages, 7719 KiB  
Article
Eucommia ulmoides Leaf Extract Ameliorates Steatosis Induced by High-fat Diet in Rats by Increasing Lysosomal Function
by Geum-Hwa Lee, Hwa-Young Lee, Sun-Ah Park, Tai-Sun Shin and Han-Jung Chae
Nutrients 2019, 11(2), 426; https://doi.org/10.3390/nu11020426 - 18 Feb 2019
Cited by 32 | Viewed by 4443
Abstract
The recent discovery that the impairment of autophagic flux in non-alcoholic fatty liver disease (NAFLD) might be a strong determining factor in steatosis suggests the potential of therapeutic control of autophagic flux with natural agents in restoring NAFLD. We investigated the potential of [...] Read more.
The recent discovery that the impairment of autophagic flux in non-alcoholic fatty liver disease (NAFLD) might be a strong determining factor in steatosis suggests the potential of therapeutic control of autophagic flux with natural agents in restoring NAFLD. We investigated the potential of Eucommia ulmoides leaf extract (EUL) to control dyslipidemia in NAFLD. EUL supplementation (200 mg/kg) promoted recovery from high fat diet (HFD)-induced lipid dysmetabolism. This hepatoprotective efficacy was accompanied by suppression of endoplasmic reticulum (ER) stress, enhancing lysosomal functions, and thereby increasing autophagic flux. We found a strong indication that inhibition of the mTOR-ER stress pathway was related to the enhanced autophagic flux. However, the direct antioxidative effect of EUL on cytoprotection cannot be ruled out as a significant contributing factor in NAFLD. Our findings will aid in further elucidating the mechanism of the anti-steatosis activity of EUL and highlight the therapeutic potential of EUL in the treatment of NAFLD. Full article
(This article belongs to the Special Issue Effects of Diet and Active Compounds on Non-alcoholic Fatty Liver Disease)
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Review

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12 pages, 283 KiB  
Review
Beyond Body Weight-Loss: Dietary Strategies Targeting Intrahepatic Fat in NAFLD
by Nicolai Worm
Nutrients 2020, 12(5), 1316; https://doi.org/10.3390/nu12051316 - 06 May 2020
Cited by 40 | Viewed by 9867
Abstract
Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent liver disease in industrialized countries. It is regarded as the hepatic manifestation of the metabolic syndrome (MetS) resulting from insulin resistance. Moreover, insulin resistance impairs glycogen synthesis, postprandially diverting a substantial amount [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent liver disease in industrialized countries. It is regarded as the hepatic manifestation of the metabolic syndrome (MetS) resulting from insulin resistance. Moreover, insulin resistance impairs glycogen synthesis, postprandially diverting a substantial amount of carbohydrates to the liver and storing them there as fat. NAFLD has far-reaching metabolic consequences involving glucose and lipoprotein metabolism disorders and risk of cardiovascular disease, the leading cause of death worldwide. No pharmaceutical options are currently approved for the treatment of NAFLD. Exercise training and dietary interventions remain the cornerstone of NAFLD treatment. Current international guidelines state that the primary goal of nutritional therapy is to reduce energy intake to achieve a 7%–10% reduction in body weight. Meal replacement therapy (formula diets) results in more pronounced weight loss compared to conventional calorie-restricted diets. However, studies have shown that body mass index (BMI) or weight reduction is not obligatory for decreasing hepatic fat content or to restore normal liver function. Recent studies have achieved significant reductions in liver fat with eucaloric diets and without weight loss through macronutrient modifications. Based on this evidence, an integrative nutritional therapeutic concept was formulated that combines the most effective nutrition approaches termed “liver-fasting.” It involves the temporary use of a low calorie diet (total meal replacement with a specific high-protein, high-soluble fiber, lower-carbohydrate formula), followed by stepwise food reintroduction that implements a Mediterranean style low-carb diet as basic nutrition. Full article
(This article belongs to the Special Issue Effects of Diet and Active Compounds on Non-alcoholic Fatty Liver Disease)
11 pages, 566 KiB  
Review
Evaluation of Dietary Approaches for the Treatment of Non-Alcoholic Fatty Liver Disease: A Systematic Review
by Naba Saeed, Brian Nadeau, Carol Shannon and Monica Tincopa
Nutrients 2019, 11(12), 3064; https://doi.org/10.3390/nu11123064 - 16 Dec 2019
Cited by 44 | Viewed by 6696
Abstract
Lifestyle interventions, namely optimizing nutrition and increasing physical activity, remain the cornerstone of therapy for non-alcoholic fatty liver disease (NAFLD), as this can lead to the significant improvement or resolution of disease. The optimal nutritional approach to treat NAFLD remains unclear. The aim [...] Read more.
Lifestyle interventions, namely optimizing nutrition and increasing physical activity, remain the cornerstone of therapy for non-alcoholic fatty liver disease (NAFLD), as this can lead to the significant improvement or resolution of disease. The optimal nutritional approach to treat NAFLD remains unclear. The aim of this systematic review is to evaluate the effectiveness of different nutritional patterns on hepatic, metabolic, and weight-loss endpoints. MEDLINE via PubMed, Embase, Scopus, and Google Scholar were searched. Randomized trials of dietary interventions alone for adults with NAFLD were selected. Two authors independently reviewed articles, to select eligible studies, and performed data abstraction. Six studies, representing 317 patients, were included. The participants had a median age of 46, mean body mass index (BMI) 31.5 and were 64.3% male. The mean study duration was 16.33 ± 8.62 weeks. Reduction in hepatic steatosis (HS) was statistically significant in 3/5 Mediterranean Diet (MD), one low-carbohydrate, one intermittent fasting (IF) and 1/2 low fat (LF) diet interventions. A total of 3/5 studies using MD, 1/2 LF interventions, and the one IF intervention demonstrated significant reductions in weight. In conclusion, there appears to be most data in support of MD-based interventions, though further randomized trials are needed to assess comparative effectiveness for NAFLD. Full article
(This article belongs to the Special Issue Effects of Diet and Active Compounds on Non-alcoholic Fatty Liver Disease)
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23 pages, 272 KiB  
Review
Moderate Alcohol Intake in Non-Alcoholic Fatty Liver Disease: To Drink or Not to Drink?
by Maria L. Petroni, Lucia Brodosi, Francesca Marchignoli, Alessandra Musio and Giulio Marchesini
Nutrients 2019, 11(12), 3048; https://doi.org/10.3390/nu11123048 - 13 Dec 2019
Cited by 29 | Viewed by 5055
Abstract
Nonalcoholic fatty liver disease (NAFLD) is defined by hepatic steatosis in the presence of alcohol intake within safe limits, defined by guidelines of scientific associations (usually 20 g or 2 units/day in women, 30 g or 3 units in men). The diagnosis is [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is defined by hepatic steatosis in the presence of alcohol intake within safe limits, defined by guidelines of scientific associations (usually 20 g or 2 units/day in women, 30 g or 3 units in men). The diagnosis is usually followed by medical counseling of total abstinence, in order to prevent disease progression. This policy has been challenged by epidemiological studies, suggesting that the risk of liver disease and disease progression is lower in modest drinkers than in total abstainers. We revised the literature on the effects of modest alcohol intake on disease burden. Epidemiological data may suffer from several potential biases (recall bias for retrospective analyses, difficulties in the calculation of g/day), limiting their validity. Prospective data suggest that NAFLD patients with regular alcohol intake, although within the safe thresholds, are at higher risk of liver disease progression, including hepatocellular carcinoma; a detrimental effect of modest alcohol drinking is similarly observed in liver disease of viral etiology. Alcohol intake is also a risk factor for extrahepatic cancers, particularly breast, oral, and pharyngeal cancers, with gender difference and no floor effect, which outweigh the possible beneficial effects on cardiovascular system, also derived from retrospective studies. Finally, the negative effects of the calorie content of alcohol on dietary restriction and weight loss, the pivotal intervention to reduce NAFLD burden, should be considered. In summary, the policy of counseling NAFLD patients for alcohol abstinence should be maintained. Full article
(This article belongs to the Special Issue Effects of Diet and Active Compounds on Non-alcoholic Fatty Liver Disease)
24 pages, 1729 KiB  
Review
High Protein Diet and Metabolic Plasticity in Non-Alcoholic Fatty Liver Disease: Myths and Truths
by Francesco De Chiara, Cynthia Ureta Checcllo and Javier Ramón Azcón
Nutrients 2019, 11(12), 2985; https://doi.org/10.3390/nu11122985 - 06 Dec 2019
Cited by 26 | Viewed by 11413
Abstract
Non-alcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation within the liver affecting 1 in 4 people worldwide. As the new silent killer of the twenty-first century, NAFLD impacts on both the request and the availability of new liver donors. The liver [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation within the liver affecting 1 in 4 people worldwide. As the new silent killer of the twenty-first century, NAFLD impacts on both the request and the availability of new liver donors. The liver is the first line of defense against endogenous and exogenous metabolites and toxins. It also retains the ability to switch between different metabolic pathways according to food type and availability. This ability becomes a disadvantage in obesogenic societies where most people choose a diet based on fats and carbohydrates while ignoring vitamins and fiber. The chronic exposure to fats and carbohydrates induces dramatic changes in the liver zonation and triggers the development of insulin resistance. Common believes on NAFLD and different diets are based either on epidemiological studies, or meta-analysis, which are not controlled evidences; in most of the cases, they are biased on test-subject type and their lifestyles. The highest success in reverting NAFLD can be attributed to diets based on high protein instead of carbohydrates. In this review, we discuss the impact of NAFLD on body metabolic plasticity. We also present a detailed analysis of the most recent studies that evaluate high-protein diets in NAFLD with a special focus on the liver and the skeletal muscle protein metabolisms. Full article
(This article belongs to the Special Issue Effects of Diet and Active Compounds on Non-alcoholic Fatty Liver Disease)
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19 pages, 1260 KiB  
Review
Mediterranean Diet and NAFLD: What We Know and Questions That Still Need to Be Answered
by Maria Corina Plaz Torres, Alessio Aghemo, Ana Lleo, Giorgia Bodini, Manuele Furnari, Elisa Marabotto, Luca Miele and Edoardo G. Giannini
Nutrients 2019, 11(12), 2971; https://doi.org/10.3390/nu11122971 - 05 Dec 2019
Cited by 56 | Viewed by 11767
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is expected to become the leading cause of end-stage liver disease worldwide over the next few decades. In fact, NAFLD encompasses different clinical scenarios, from the simple accumulation of fat [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is expected to become the leading cause of end-stage liver disease worldwide over the next few decades. In fact, NAFLD encompasses different clinical scenarios, from the simple accumulation of fat (steatosis) to steatohepatitis (NASH), NASH-cirrhosis, and cirrhosis complications. In this context, it is fundamental to pursue strategies aimed at both preventing the disease and reducing the progression of liver fibrosis once liver damage is already initiated. As of today, no pharmacological treatment has been approved for NAFLD/NASH, and the only recommended treatment of proven efficacy are life-style modifications, including diet and physical exercise pointing at weight loss of 5%–7%. Different dietetic approaches have been proposed in this setting, and in this review, we will discuss the evidence regarding the efficacy of the Mediterranean Diet as a treatment for NAFLD. In particular, we will report the effects on liver-related outcomes. Full article
(This article belongs to the Special Issue Effects of Diet and Active Compounds on Non-alcoholic Fatty Liver Disease)
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17 pages, 269 KiB  
Review
Dietary Patterns and Components in Nonalcoholic Fatty Liver Disease (NAFLD): What Key Messages Can Health Care Providers Offer?
by Kiarash Riazi, Maitreyi Raman, Lorian Taylor, Mark G. Swain and Abdel Aziz Shaheen
Nutrients 2019, 11(12), 2878; https://doi.org/10.3390/nu11122878 - 26 Nov 2019
Cited by 45 | Viewed by 7437
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a rising epidemic worldwide and will be the leading cause of cirrhosis, hepatocellular carcinoma, and liver transplant within the next decade. NAFLD is considered as the hepatic manifestation of metabolic syndrome. Behaviors, such as a sedentary lifestyle [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is a rising epidemic worldwide and will be the leading cause of cirrhosis, hepatocellular carcinoma, and liver transplant within the next decade. NAFLD is considered as the hepatic manifestation of metabolic syndrome. Behaviors, such as a sedentary lifestyle and consuming a Western diet, have led to substantial challenges in managing NAFLD patients. With no curative pharmaceutical therapies, lifestyle modifications, including dietary changes and exercise, that ultimately lead to weight loss remain the only effective therapy for NAFLD. Multiple diets, including low-carbohydrate, low-fat, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean (MD) diets, have been evaluated. NAFLD patients have shown better outcomes with a modified diet, such as the MD diet, where patients are encouraged to increase the consumption of fruits and vegetables, whole grains, and olive oil. It is increasingly clear that a personalized approach to managing NAFLD patients, based on their preferences and needs, should be implemented. In our review, we cover NAFLD management, with a specific focus on dietary patterns and their components. We emphasize the successful approaches highlighted in recent studies to provide recommendations that health care providers could apply in managing their NAFLD patients. Full article
(This article belongs to the Special Issue Effects of Diet and Active Compounds on Non-alcoholic Fatty Liver Disease)
35 pages, 563 KiB  
Review
Fat and Sugar—A Dangerous Duet. A Comparative Review on Metabolic Remodeling in Rodent Models of Nonalcoholic Fatty Liver Disease
by Ines C.M. Simoes, Justyna Janikiewicz, Judith Bauer, Agnieszka Karkucinska-Wieckowska, Piotr Kalinowski, Agnieszka Dobrzyń, Andrzej Wolski, Maciej Pronicki, Krzysztof Zieniewicz, Paweł Dobrzyń, Marcin Krawczyk, Hans Zischka, Mariusz R. Wieckowski and Yaiza Potes
Nutrients 2019, 11(12), 2871; https://doi.org/10.3390/nu11122871 - 24 Nov 2019
Cited by 14 | Viewed by 5259
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common disease in Western society and ranges from steatosis to steatohepatitis to end-stage liver disease such as cirrhosis and hepatocellular carcinoma. The molecular mechanisms that are involved in the progression of steatosis to more severe liver [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is a common disease in Western society and ranges from steatosis to steatohepatitis to end-stage liver disease such as cirrhosis and hepatocellular carcinoma. The molecular mechanisms that are involved in the progression of steatosis to more severe liver damage in patients are not fully understood. A deeper investigation of NAFLD pathogenesis is possible due to the many different animal models developed recently. In this review, we present a comparative overview of the most common dietary NAFLD rodent models with respect to their metabolic phenotype and morphological manifestation. Moreover, we describe similarities and controversies concerning the effect of NAFLD-inducing diets on mitochondria as well as mitochondria-derived oxidative stress in the progression of NAFLD. Full article
(This article belongs to the Special Issue Effects of Diet and Active Compounds on Non-alcoholic Fatty Liver Disease)
22 pages, 659 KiB  
Review
Role of Probiotics in Non-alcoholic Fatty Liver Disease: Does Gut Microbiota Matter?
by Chencheng Xie and Dina Halegoua-DeMarzio
Nutrients 2019, 11(11), 2837; https://doi.org/10.3390/nu11112837 - 19 Nov 2019
Cited by 53 | Viewed by 11210
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the hepatic consequence of metabolic syndrome, which often also includes obesity, diabetes, and dyslipidemia. The connection between gut microbiota (GM) and NAFLD has attracted significant attention in recent years. Data has shown that GM affects hepatic lipid [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is the hepatic consequence of metabolic syndrome, which often also includes obesity, diabetes, and dyslipidemia. The connection between gut microbiota (GM) and NAFLD has attracted significant attention in recent years. Data has shown that GM affects hepatic lipid metabolism and influences the balance between pro/anti-inflammatory effectors in the liver. Although studies reveal the association between GM dysbiosis and NAFLD, decoding the mechanisms of gut dysbiosis resulting in NAFLD remains challenging. The potential pathophysiology that links GM dysbiosis to NAFLD can be summarized as: (1) disrupting the balance between energy harvest and expenditure, (2) promoting hepatic inflammation (impairing intestinal integrity, facilitating endotoxemia, and initiating inflammatory cascades with cytokines releasing), and (3) altered biochemistry metabolism and GM-related metabolites (i.e., bile acid, short-chain fatty acids, aromatic amino acid derivatives, branched-chain amino acids, choline, ethanol). Due to the hypothesis that probiotics/synbiotics could normalize GM and reverse dysbiosis, there have been efforts to investigate the therapeutic effect of probiotics/synbiotics in patients with NAFLD. Recent randomized clinical trials suggest that probiotics/synbiotics could improve transaminases, hepatic steatosis, and reduce hepatic inflammation. Despite these promising results, future studies are necessary to understand the full role GM plays in NAFLD development and progression. Additionally, further data is needed to unravel probiotics/synbiotics efficacy, safety, and sustainability as a novel pharmacologic approaches to NAFLD. Full article
(This article belongs to the Special Issue Effects of Diet and Active Compounds on Non-alcoholic Fatty Liver Disease)
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24 pages, 844 KiB  
Review
The Role of Probiotics in Nonalcoholic Fatty Liver Disease: A New Insight into Therapeutic Strategies
by Marica Meroni, Miriam Longo and Paola Dongiovanni
Nutrients 2019, 11(11), 2642; https://doi.org/10.3390/nu11112642 - 04 Nov 2019
Cited by 85 | Viewed by 9940
Abstract
Nonalcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of pathological hepatic conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), which may predispose to liver cirrhosis and hepatocellular carcinoma (HCC). Due to the epidemic obesity, NAFLD is representing a global health issue [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of pathological hepatic conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), which may predispose to liver cirrhosis and hepatocellular carcinoma (HCC). Due to the epidemic obesity, NAFLD is representing a global health issue and the leading cause of liver damage worldwide. The pathogenesis of NAFLD is closely related to insulin resistance (IR), adiposity and physical inactivity as well as genetic and epigenetic factors corroborate to the development and progression of hepatic steatosis and liver injury. Emerging evidence has outlined the implication of gut microbiota and gut-derived endotoxins as actively contributors to NAFLD pathophysiology probably due to the tight anatomo-functional crosstalk between the gut and the liver. Obesity, nutrition and environmental factors might alter intestinal permeability producing a favorable micro-environment for bacterial overgrowth, mucosal inflammation and translocation of both invasive pathogens and harmful byproducts, which, in turn, influence hepatic fat composition and exacerbated pro-inflammatory and fibrotic processes. To date, no therapeutic interventions are available for NAFLD prevention and management, except for modifications in lifestyle, diet and physical exercise even though they show discouraging results due to the poor compliance of patients. The premise of this review is to discuss the role of gut–liver axis in NAFLD and emphasize the beneficial effects of probiotics on gut microbiota composition as a novel attractive therapeutic strategy to introduce in clinical practice. Full article
(This article belongs to the Special Issue Effects of Diet and Active Compounds on Non-alcoholic Fatty Liver Disease)
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8 pages, 616 KiB  
Review
The Relevance of Toxic AGEs (TAGE) Cytotoxicity to NASH Pathogenesis: A Mini-Review
by Akiko Sakasai-Sakai, Takanobu Takata, Jun-ichi Takino and Masayoshi Takeuchi
Nutrients 2019, 11(2), 462; https://doi.org/10.3390/nu11020462 - 22 Feb 2019
Cited by 21 | Viewed by 4493
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently the most common feature of chronic liver disease. Non-alcoholic steatohepatitis (NASH) is a severe form of NAFLD, and one of its risk factors is hyperglycemia. The chronic ingestion of excessive amounts of high-fructose corn syrup is [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is currently the most common feature of chronic liver disease. Non-alcoholic steatohepatitis (NASH) is a severe form of NAFLD, and one of its risk factors is hyperglycemia. The chronic ingestion of excessive amounts of high-fructose corn syrup is associated with an increased prevalence of fatty liver. Under hyperglycemic conditions, advanced glycation end-products (AGEs) are generated through a non-enzymatic glycation reaction between the ketone or aldehyde groups of sugars and amino groups of proteins. Glyceraldehyde (GA) is a metabolic intermediate of sugars, and GA-derived AGEs (known as toxic AGEs (TAGE)) have been implicated in the development of NASH. TAGE accumulates more in serum or liver tissue in NASH patients than in healthy controls or patients with simple steatosis. Furthermore, the TAGE precursor, GA, causes cell damage through protein dysfunctions by TAGE modifications and induces necrotic-type hepatocyte death. Intracellular TAGE may leak outside of necrotic-type cells. Extracellular TAGE then induce inflammatory or fibrotic responses related to the pathology of NASH in surrounding cells, including hepatocytes and hepatic stellate cells. This review focuses on the contribution of TAGE to the pathology of NASH, particularly hepatic cell death related to NASH. Full article
(This article belongs to the Special Issue Effects of Diet and Active Compounds on Non-alcoholic Fatty Liver Disease)
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