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Bazina I, Šešelja K, Pirman T, Horvatić A, Erman A, Mihalj M, Baus Lončar M. The Effect of Tff3 Deficiency on the Liver of Mice Exposed to a High-Fat Diet. Biomedicines 2025; 13:1024. [PMID: 40426854 PMCID: PMC12108639 DOI: 10.3390/biomedicines13051024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2025] [Revised: 04/07/2025] [Accepted: 04/09/2025] [Indexed: 05/29/2025] Open
Abstract
Background/Objectives: Trefoil factor protein 3 (Tff3) is a small peptide known as an epithelial tissue-protective protein, and it is also identified as a novel participant in complex metabolic processes. In numerous mouse models of obesity, Tff3 has been found to be downregulated in the liver and its overexpression is associated with an improvement in metabolic parameters. These mouse models with metabolic phenotypes have a multigenic background, with numerous genes contributing to their phenotype. To elucidate the role of Tff3 protein in metabolic events, we developed a mouse model with Tff3 deficiency on a C57Bl6N background without other intrinsic mutations affecting metabolism. Methods: We investigated the effects of a high-fat diet (9 weeks) on the liver of Tff3 protein-deficient mice of both sexes and the corresponding wild type. We investigated the general metabolic status of the animals and analysed the expression of markers of relevant pathophysiological pathways in the liver. Results:Tff3-deficient mice had significantly lower body weight. They also had a comparable total liver fat content but it was distributed in small vesicles, indicating the protective effect of Tff3 deficiency. The results of molecular analysis showed no major gene expression changes in inflammation-, ER- and oxidative stress-, and lipid metabolism-related genes. Tff3-/- males had reduced expression of Il1α and Cxcr7 genes in the liver and no global proteome changes; Tff3-deficient females had decreased expression of Irs2 and Atf4 genes and total proteome comparison showed decreased levels of proteins related to ribosome biosynthesis and the inhibition of acetylation. Conclusions: Our results demonstrate that Tff3 deficiency reduces lipid accumulation in the liver and we set the direction for further studies aimed at uncovering the exact molecular mechanisms in other organs. Furthermore, it emphasises the need to include both sexes in future research, as the observed phenotype differs significantly depending on sex.
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Affiliation(s)
- Iva Bazina
- Faculty of Chemical Engineering and Technology, University of Zagreb, 10000 Zagreb, Croatia;
| | - Kate Šešelja
- Division of Molecular Medicine, Ruđer Boškovic Institute, Bjenička 54, 10000 Zagreb, Croatia;
| | - Tatjana Pirman
- Department of Animal Science, Biotechnical Faculty, University of Ljubljana, Groblje 3, 1230 Domzale, Slovenia;
| | - Anita Horvatić
- Faculty of Food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia;
| | - Andreja Erman
- Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia;
| | - Martina Mihalj
- Department of Dermatology and Venereology, University Hospital Osijek, 31000 Osijek, Croatia;
- Department of Physiology and Immunology, Faculty of Medicine, University of Osijek, 31000 Osijek, Croatia
| | - Mirela Baus Lončar
- Faculty of Chemical Engineering and Technology, University of Zagreb, 10000 Zagreb, Croatia;
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Tian Y, Zhou Y, Liao W, Xia J, Hu Q, Zhao Q, Zhang R, Sun G, Yang L, Li L. Flaxseed powder supplementation in non-alcoholic fatty liver disease: a randomized controlled clinical trial. Food Funct 2025; 16:1389-1406. [PMID: 39878023 DOI: 10.1039/d4fo05847j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2025]
Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) has become a growing public health problem worldwide, and dietary interventions have important potential in the prevention and treatment of NAFLD. Moreover, previous animal studies have shown that flaxseed has a good improvement effect in animal NAFLD models. Objectives: Assess whether flaxseed powder could improve the liver lipid content in patients with NAFLD. Methods: In this 12-week randomized controlled clinical trial, 50 patients were randomly assigned to the flaxseed group (n = 25) and the control group (n = 25). The flaxseed group received 30 g d-1 flaxseed powder orally before lunch or dinner along with health education, while the control group received only health education. The primary outcome was the intrahepatic lipid content assessed by the proton density fat fraction estimated by magnetic resonance imaging, and secondary outcomes were body composition measurements, liver function, and glucolipid metabolism. Results: Patients in the flaxseed group showed significantly lower liver fat content, body fat percentage, obesity index, visceral fat area, serum total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), aspartate aminotransferase (AST), total cholesterol (TC), and triglyceride (TG) levels after a 12-week intervention compared to pre-intervention levels, while serum apolipoprotein A1 (Apo A1) and high-density lipoprotein cholesterol (HDL-C) levels were significantly increased, with all differences being statistically significant (P < 0.05). Analysis of the gut microbiota showed that, at the phylum level, flaxseed intervention significantly increased the abundance of Bacteroides and Actinobacteria, while decreasing the ratio of Firmicutes to Bacteroidetes. At the genus level, the relative abundance of Clostridium_sensu_stricto_1, Parasutterella, Lachnospiraceae_NK4A136_group, Eubacterium_xylanophilum_group, and Bifidobacterium in the gut microbiota of the flaxseed group was significantly higher than that of the control group (P < 0.05), whereas the relative abundance of Coriobacteriaceae_UCG-002 was significantly lower than that of the control group (P < 0.05). Conclusions: Flaxseed powder intervention for 12 weeks had the effect of improving liver lipid deposition, liver function, body composition indicators, and lipid metabolism in patients with NAFLD. It also regulated the gut microbiota in NAFLD patients, increasing the abundance of beneficial bacteria while reducing harmful bacteria. This suggested that flaxseed is one of the natural and effective foods for improving NAFLD.
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Affiliation(s)
- Yanyan Tian
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China.
| | - Yuhao Zhou
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China.
| | - Wang Liao
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China.
| | - Jiayue Xia
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China.
| | - Qiaosheng Hu
- Lianshui People's Hospital Affiliated to Kangda College of Nanjing Medical University, Huai'an, Jiangsu, 223400, China.
| | - Qing Zhao
- Lianshui People's Hospital Affiliated to Kangda College of Nanjing Medical University, Huai'an, Jiangsu, 223400, China.
| | - Rui Zhang
- Lianshui People's Hospital Affiliated to Kangda College of Nanjing Medical University, Huai'an, Jiangsu, 223400, China.
| | - Guiju Sun
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China.
| | - Ligang Yang
- Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, and Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing 210009, China.
| | - Lihua Li
- Lianshui People's Hospital Affiliated to Kangda College of Nanjing Medical University, Huai'an, Jiangsu, 223400, China.
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Perva IT, Simina IE, Bende R, Motofelea AC, Chirita Emandi A, Andreescu N, Sima A, Vlad A, Sporea I, Zimbru C, Tutac PC, Puiu M, Niculescu MD. Use of a Micronutrient Cocktail to Improve Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Adults with Obesity: A Randomized, Double-Blinded Pilot Clinical Trial. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1366. [PMID: 39202647 PMCID: PMC11356300 DOI: 10.3390/medicina60081366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 08/06/2024] [Accepted: 08/20/2024] [Indexed: 09/03/2024]
Abstract
Background and Objectives: The goal of this study was to assess the impact of supplementation with a combination of nutrients on metabolic-dysfunction-associated steatotic liver disease (MASLD)-related liver parameters, and other parameters related to metabolic syndrome in adults with obesity. These measurements included anthropometric and lipid profiling, and FibroScan technology (controlled attenuation parameter (CAP) and transient elastography (TE) values). Materials and Methods: A double-blind, placebo-controlled pilot clinical trial was conducted over a three-month treatment period. Adults with metabolic syndrome and obesity were allocated to receive either a cocktail of nutrients with defined daily dosages (5-MTHF, betaine, alpha-linolenic acid, eicosapentaenoic acid, choline bitartrate, docosahexaenoic acid, and vitamin B12) or a placebo. The participants were evaluated at the start and the end of the three-month treatment period. Results: A total of 155 participants entered the study, comprising 84 in the treatment group and 71 in the placebo group. The administration of the nutritional supplement resulted in a notable reduction in both CAP and TE scores when compared to the placebo group. The treatment group exhibited a mean reduction in CAP of 4% (p < 0.05) and a mean reduction in TE of 7.8% (p < 0.05), indicative of a decline in liver fat content and fibrosis. Conclusions: The supplementation over a period of three months led to a significant amelioration of liver fibrosis and steatosis parameters in adults with metabolic syndrome and obesity. These findings suggest that this supplementation regimen could be a beneficial adjunct therapy for improving liver health in adults with obesity-induced MASLD.
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Affiliation(s)
- Iulia Teodora Perva
- Department of Microscopic Morphology, Genetics Discipline, Center of Genomic Medicine, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania; (I.T.P.); (A.C.E.); (N.A.); (M.P.); (M.D.N.)
- Regional Center of Medical Genetics Timiș, Clinical Emergency Hospital for Children “Louis Țurcanu”, Iosif Nemoianu Street N°2, 300011 Timisoara, Romania
- Department of Medical Genetics, Asociatia Oncohelp, 300239 Timișoara, Romania
| | - Iulia Elena Simina
- Department of Microscopic Morphology, Genetics Discipline, Center of Genomic Medicine, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania; (I.T.P.); (A.C.E.); (N.A.); (M.P.); (M.D.N.)
- Department of Medical Genetics, Asociatia Oncohelp, 300239 Timișoara, Romania
| | - Renata Bende
- Department of Gastroenterology and Hepatology, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania; (R.B.); (I.S.)
- Center of Advanced Research in Gastroenterology and Hepatology, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania
| | - Alexandru Cătălin Motofelea
- Department of Internal Medicine, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania;
| | - Adela Chirita Emandi
- Department of Microscopic Morphology, Genetics Discipline, Center of Genomic Medicine, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania; (I.T.P.); (A.C.E.); (N.A.); (M.P.); (M.D.N.)
- Regional Center of Medical Genetics Timiș, Clinical Emergency Hospital for Children “Louis Țurcanu”, Iosif Nemoianu Street N°2, 300011 Timisoara, Romania
| | - Nicoleta Andreescu
- Department of Microscopic Morphology, Genetics Discipline, Center of Genomic Medicine, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania; (I.T.P.); (A.C.E.); (N.A.); (M.P.); (M.D.N.)
- Regional Center of Medical Genetics Timiș, Clinical Emergency Hospital for Children “Louis Țurcanu”, Iosif Nemoianu Street N°2, 300011 Timisoara, Romania
| | - Alexandra Sima
- Department of Internal Medicine II, Division of Diabetes, Nutrition and Metabolic Diseases, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania; (A.S.); (A.V.)
- Center for Research in Preventive Medicine, Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania
| | - Adrian Vlad
- Department of Internal Medicine II, Division of Diabetes, Nutrition and Metabolic Diseases, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania; (A.S.); (A.V.)
- Center for Molecular Research in Nephrology and Vascular Disease, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania
| | - Ioan Sporea
- Department of Gastroenterology and Hepatology, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania; (R.B.); (I.S.)
- Center of Advanced Research in Gastroenterology and Hepatology, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania
| | - Cristian Zimbru
- Department of Automation and Applied Informatics, Politehnica University Timișoara, 300223 Timișoara, Romania;
| | - Paul Calin Tutac
- Toxicology and Molecular Biology Department, “Pius Brinzeu” Clinical Emergency County Hospital, 300723 Timisoara, Romania;
| | - Maria Puiu
- Department of Microscopic Morphology, Genetics Discipline, Center of Genomic Medicine, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania; (I.T.P.); (A.C.E.); (N.A.); (M.P.); (M.D.N.)
- Regional Center of Medical Genetics Timiș, Clinical Emergency Hospital for Children “Louis Țurcanu”, Iosif Nemoianu Street N°2, 300011 Timisoara, Romania
| | - Mihai Dinu Niculescu
- Department of Microscopic Morphology, Genetics Discipline, Center of Genomic Medicine, “Victor Babeș” University of Medicine and Pharmacy, Eftimie Murgu Sq., 300041 Timisoara, Romania; (I.T.P.); (A.C.E.); (N.A.); (M.P.); (M.D.N.)
- Advanced Nutrigenomics LLC, Durham, NC 27703, USA
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Ahmed DH, Fateh HL. Impact of flaxseed supplementation on lipid profile and liver enzymes in patients with non-alcoholic fatty liver disease: Systematic review and meta-analysis of randomized controlled trials. Prostaglandins Other Lipid Mediat 2024; 173:106838. [PMID: 38663513 DOI: 10.1016/j.prostaglandins.2024.106838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Revised: 04/18/2024] [Accepted: 04/21/2024] [Indexed: 05/07/2024]
Abstract
Since the effects of flaxseed supplementation on lipid profile and liver enzymes are still controversial, a meta-analysis of randomized controlled trials was conducted in the present study to assess the effect of flaxseed supplementation on lipid profile and liver enzymes. The study was designed, conducted, and reported according to the guidelines of the 2020 preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. A systematic and comprehensive search was performed in several databases from inception up to January 10, 2024. The meta-analysis on the impact of flaxseed supplementation on lipid profile and liver enzymes indicates that the overall effect of flaxseed supplementation on triglycerides, combining different doses, revealed a significant reduction with a WMD of - 230.72 (-53.95, - 27.49) and a P-value of 0.010. High-density lipoprotein (HDL) demonstrated a positive effect, with an overall WMD of 1.82 (0.27, 3.38) and a P-value of 0.021, indicating an increase in HDL levels. The liver enzymes AST and ALT displayed reductions in their levels, with overall WMDs of - 21.18 (-2.95, 0.59) and - 24.83 (-8.74, - 20.91), respectively. Subgroup analysis based on dosage revealed more pronounced reductions in ALT levels for doses below 2000 mg/day. Findings from this study suggest that a flaxseed supplement might be beneficial to modulate the blood lipid profile and liver enzymes.
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Affiliation(s)
- Dyari H Ahmed
- Nursing Department, Halabja Technical Institute, Sulaimani Polytechnic University, Sulaimani, Iraq
| | - Hawal Lateef Fateh
- Nursing Department, Kalar Technical Institute, Garmian Polytechnic University, Kalar, Iraq.
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Hao L, Chen CY, Nie YH, Kaliannan K, Kang JX. Differential Interventional Effects of Omega-6 and Omega-3 Polyunsaturated Fatty Acids on High Fat Diet-Induced Obesity and Hepatic Pathology. Int J Mol Sci 2023; 24:17261. [PMID: 38139090 PMCID: PMC10743920 DOI: 10.3390/ijms242417261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 12/01/2023] [Accepted: 12/04/2023] [Indexed: 12/24/2023] Open
Abstract
Current Dietary Guidelines for Americans recommend replacing saturated fat (SFA) intake with polyunsaturated fatty acids (PUFAs) and monosaturated fatty acids (MUFAs) but do not specify the type of PUFAs, which consist of two functionally distinct classes: omega-6 (n-6) and omega-3 (n-3) PUFAs. Given that modern Western diets are already rich in n-6 PUFAs and the risk of chronic disease remains high today, we hypothesized that increased intake of n-3 PUFAs, rather than n-6 PUFAs, would be a beneficial intervention against obesity and related liver diseases caused by high-fat diets. To test this hypothesis, we fed C57BL/6J mice with a high-fat diet (HF) for 10 weeks to induce obesity, then divided the obese mice into three groups and continued feeding for another 10 weeks with one of the following three diets: HF, HF+n-6 (substituted half of SFA with n-6 PUFAs), and HF+n-3 (substituted half of SFA with n-3 PUFAs), followed by assessment of body weight, fat mass, insulin sensitivity, hepatic pathology, and lipogenesis. Interestingly, we found that the HF+n-6 group, like the HF group, had a continuous increase in body weight and fat mass, while the HF+n-3 group had a significant decrease in body weight and fat mass, although all groups had the same calorie intake. Accordingly, insulin resistance and fatty liver pathology (steatosis and fat levels) were evident in the HF+n-6 and HF groups but barely seen in the HF+n-3 group. Furthermore, the expression of lipogenesis-related genes in the liver was upregulated in the HF+n-6 group but downregulated in the HF+n-3 group. Our findings demonstrate that n-6 PUFAs and n-3 PUFAs have differential effects on obesity and fatty liver disease and highlight the importance of increasing n-3 PUFAs and reducing n-6 PUFAs (balancing the n-6/n-3 ratio) in clinical interventions and dietary guidelines for the management of obesity and related diseases.
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Affiliation(s)
- Lei Hao
- Laboratory for Lipid Medicine and Technology (LLMT), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; (L.H.); (C.-Y.C.)
- Department of Nursing and Allied Health Professions, Indiana University of Pennsylvania, Indiana, PA 15705, USA
| | - Chih-Yu Chen
- Laboratory for Lipid Medicine and Technology (LLMT), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; (L.H.); (C.-Y.C.)
- Emory School of Medicine, Emory University, Atlanta, GA 30322, USA
| | - Yong-Hui Nie
- Laboratory for Lipid Medicine and Technology (LLMT), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; (L.H.); (C.-Y.C.)
| | - Kanakaraju Kaliannan
- Laboratory for Lipid Medicine and Technology (LLMT), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; (L.H.); (C.-Y.C.)
| | - Jing X. Kang
- Laboratory for Lipid Medicine and Technology (LLMT), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; (L.H.); (C.-Y.C.)
- Omega-3 and Global Health Institute, Boston, MA 02129, USA
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Machado M, Sousa S, Rodriguez-Alcalá LM, Gomes AM, Pintado M. Anti-obesity potential of a yogurt functionalized with a CLNA-rich pomegranate oil. Food Res Int 2023; 173:113364. [PMID: 37803704 DOI: 10.1016/j.foodres.2023.113364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Revised: 08/03/2023] [Accepted: 08/05/2023] [Indexed: 10/08/2023]
Abstract
Pomegranate oil is rich in conjugated linolenic acids, compounds which have attracted attention due to their potential applicability in obesity management as they are capable of modulating leptin and adiponectin secretion and regulate fatty acids storage and glucose metabolism. Among the possible bioactive foodstuffs capable of delivering these bioactive compounds yogurts have shown potential. Thus, the purpose of this work was to develop functional yogurts through the addition of pomegranate oil either in its free or encapsulated (used as a protective strategy against oxidation and gastrointestinal tract passage) forms. To that end, the pomegranate oil (free and encapsulated) was incorporated in yogurt and the functional yogurt capacity to modulate hepatic lipid accumulation, adipocyte metabolism (in terms of lipolysis, and adipokines secretion) and immune response was evaluated. The results obtained showed that the pomegranate oil's incorporation led to an improvement in the yogurts' nutritional values, with a reduction in its atherogenic and thrombogenic indexes (more than 78% for atherogenic and 76% for thrombogenic index) and an enhancement of its hypocholesterolemic/hypercholesterolemic ratio (more than 62%) when compared to the control yogurt. Furthermore, data also showed for the first time how these functional yogurts promoted modulation of metabolic processes post GIT as they were capable of reducing by 40% triglycerides accumulation in steatosis-induced Hep G2 cells and by 30 % in differentiated adipocytes. Moreover, samples also showed a capacity to modulate the leptin and adiponectin secretion (56 % of increase in adiponectin) and reduce the IL-6 secretion (ca 44%) and TNF-α (ca 12%) in LPS-stimulated cells. Thus, the CLNA-rich yogurt here developed showed potential as a viable nutraceutical alternative for obesity management.
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Affiliation(s)
- Manuela Machado
- Universidade Católica Portuguesa, CBQF Centro de Biotecnologia e Química Fina-Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal
| | - Sérgio Sousa
- Universidade Católica Portuguesa, CBQF Centro de Biotecnologia e Química Fina-Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal
| | - Luís M Rodriguez-Alcalá
- Universidade Católica Portuguesa, CBQF Centro de Biotecnologia e Química Fina-Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal
| | - Ana Maria Gomes
- Universidade Católica Portuguesa, CBQF Centro de Biotecnologia e Química Fina-Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal
| | - Manuela Pintado
- Universidade Católica Portuguesa, CBQF Centro de Biotecnologia e Química Fina-Laboratório Associado, Escola Superior de Biotecnologia, Rua Diogo Botelho 1327, 4169-005 Porto, Portugal.
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Montemayor S, García S, Monserrat-Mesquida M, Tur JA, Bouzas C. Dietary Patterns, Foods, and Nutrients to Ameliorate Non-Alcoholic Fatty Liver Disease: A Scoping Review. Nutrients 2023; 15:3987. [PMID: 37764771 PMCID: PMC10534915 DOI: 10.3390/nu15183987] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Revised: 09/11/2023] [Accepted: 09/12/2023] [Indexed: 09/29/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease without pharmacological treatment yet. There is also a lack of specific dietary recommendations and strategies to treat the negative health impacts derived from NAFLD. OBJECTIVE This scoping review aimed to compile dietary patterns, foods, and nutrients to ameliorate NAFLD. METHODS A literature search was performed through MEDLINE, Scopus, Web of Science, and Google Scholar. RESULTS Several guidelines are available through the literature. Hypocaloric Mediterranean diet is the most accepted dietary pattern to tackle NAFLD. Coffee consumption (sugar free) may have a protective effect for NAFLD. Microbiota also plays a role in NAFLD; hence, fibre intake should be guaranteed. CONCLUSIONS A high-quality diet could improve liver steatosis. Weight loss through hypocaloric diet together with physical activity and limited sugar intake are good strategies for managing NAFLD. Specific dietary recommendations and a Mediterranean plate have been proposed to ameliorate NAFLD.
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Affiliation(s)
- Sofía Montemayor
- Research Group on Community Nutrition & Oxidative Stress, University of the Balearic Islands-IUNICS, 07122 Palma, Spain (C.B.)
- Health Research Institute of Balearic Islands (IdISBa), 07120 Palma, Spain
| | - Silvia García
- Research Group on Community Nutrition & Oxidative Stress, University of the Balearic Islands-IUNICS, 07122 Palma, Spain (C.B.)
- Health Research Institute of Balearic Islands (IdISBa), 07120 Palma, Spain
- CIBEROBN (Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Margalida Monserrat-Mesquida
- Research Group on Community Nutrition & Oxidative Stress, University of the Balearic Islands-IUNICS, 07122 Palma, Spain (C.B.)
- Health Research Institute of Balearic Islands (IdISBa), 07120 Palma, Spain
- CIBEROBN (Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Josep A. Tur
- Research Group on Community Nutrition & Oxidative Stress, University of the Balearic Islands-IUNICS, 07122 Palma, Spain (C.B.)
- Health Research Institute of Balearic Islands (IdISBa), 07120 Palma, Spain
- CIBEROBN (Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Cristina Bouzas
- Research Group on Community Nutrition & Oxidative Stress, University of the Balearic Islands-IUNICS, 07122 Palma, Spain (C.B.)
- Health Research Institute of Balearic Islands (IdISBa), 07120 Palma, Spain
- CIBEROBN (Physiopathology of Obesity and Nutrition), Instituto de Salud Carlos III, 28029 Madrid, Spain
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Huang W, Shen B, Li X, Zhang T, Zhou X. Benefits of Combining Sonchus brachyotus DC. Extracts and Synbiotics in Alleviating Non-Alcoholic Fatty Liver Disease. Foods 2023; 12:3393. [PMID: 37761102 PMCID: PMC10530047 DOI: 10.3390/foods12183393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 09/04/2023] [Accepted: 09/05/2023] [Indexed: 09/29/2023] Open
Abstract
Non-alcoholic fatty liver disease, commonly abbreviated to NAFLD, is a pervasive ailment within the digestive system, exhibiting a rising prevalence, and impacting individuals at increasingly younger ages. Those afflicted by NAFLD face a heightened vulnerability to the onset of profound liver fibrosis, cardiovascular complications, and malignancies. Currently, NAFLD poses a significant threat to human health, and there is no approved therapeutic treatment for it. Recent studies have shown that synbiotics, which regulate intestinal microecology, can positively impact glucolipid metabolism, and improve NAFLD-related indicators. Sonchus brachyotus DC., a Chinese herb, exhibits hepatoprotective and potent antioxidant properties, suggesting its potential therapeutic use in NAFLD. Our preclinical animal model investigation suggests that the synergy between Sonchus brachyotus DC. extracts and synbiotics is significantly more effective in preventing and treating NAFLD, compared to the isolated use of either component. As a result, this combination holds the potential to introduce a fresh and encouraging therapeutic approach to addressing NAFLD.
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Affiliation(s)
- Wenwu Huang
- College of Life Sciences & Health, Wuhan University of Science & Technology, Wuhan 430065, China; (W.H.); (B.S.); (T.Z.)
| | - Boyuan Shen
- College of Life Sciences & Health, Wuhan University of Science & Technology, Wuhan 430065, China; (W.H.); (B.S.); (T.Z.)
| | - Xiumei Li
- Key Laboratory of Feed Biotechnology, Ministry of Agriculture and Rural Affairs, Institute of Feed Research of CAAS, Beijing 100000, China;
| | - Tongcun Zhang
- College of Life Sciences & Health, Wuhan University of Science & Technology, Wuhan 430065, China; (W.H.); (B.S.); (T.Z.)
| | - Xiang Zhou
- College of Life Sciences & Health, Wuhan University of Science & Technology, Wuhan 430065, China; (W.H.); (B.S.); (T.Z.)
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9
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Bischoff SC, Ockenga J, Eshraghian A, Barazzoni R, Busetto L, Campmans-Kuijpers M, Cardinale V, Chermesh I, Kani HT, Khannoussi W, Lacaze L, Léon-Sanz M, Mendive JM, Müller MW, Tacke F, Thorell A, Vranesic Bender D, Weimann A, Cuerda C. Practical guideline on obesity care in patients with gastrointestinal and liver diseases - Joint ESPEN/UEG guideline. Clin Nutr 2023; 42:987-1024. [PMID: 37146466 DOI: 10.1016/j.clnu.2023.03.021] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Accepted: 03/27/2023] [Indexed: 05/07/2023]
Abstract
BACKGROUND Patients with chronic gastrointestinal disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean gastrointestinal patients. The present guideline addresses this question according to current knowledge and evidence. OBJECTIVE The present practical guideline is intended for clinicians and practitioners in general medicine, gastroenterology, surgery and other obesity management, including dietitians and focuses on obesity care in patients with chronic gastrointestinal diseases. METHODS The present practical guideline is the shortened version of a previously published scientific guideline developed according to the standard operating procedure for ESPEN guidelines. The content has been re-structured and transformed into flow-charts that allow a quick navigation through the text. RESULTS In 100 recommendations (3× A, 33× B, 24 × 0, 40× GPP, all with a consensus grade of 90% or more) care of gastrointestinal patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially metabolic associated liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. CONCLUSION The present practical guideline offers in a condensed way evidence-based advice how to care for patients with chronic gastrointestinal diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.
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Affiliation(s)
- Stephan C Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen-Mitte, Bremen FRG, Bremen, Germany.
| | - Ahad Eshraghian
- Department of Gastroenterology and Hepatology, Avicenna Hospital, Shiraz, Iran.
| | - Rocco Barazzoni
- Department of Medical, Technological and Translational Sciences, University of Trieste, Ospedale di Cattinara, Trieste, Italy.
| | - Luca Busetto
- Department of Medicine, University of Padova, Padova, Italy.
| | - Marjo Campmans-Kuijpers
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, Groningen, the Netherlands.
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
| | - Irit Chermesh
- Department of Gastroenterology, Rambam Health Care Campus, Affiliated with Technion-Israel Institute of Technology, Haifa, Israel.
| | - Haluk Tarik Kani
- Department of Gastroenterology, Marmara University, School of Medicine, Istanbul, Turkey.
| | - Wafaa Khannoussi
- Hepato-Gastroenterology Department, Mohammed VI University Hospital, Oujda, Morocco; and Laboratoire de Recherche des Maladies Digestives (LARMAD), Mohammed the First University, Oujda, Morocco.
| | - Laurence Lacaze
- Department of General Surgery, Mantes-la-Jolie Hospital, Mantes-la-Jolie, France.
| | - Miguel Léon-Sanz
- Department of Endocrinology and Nutrition, University Hospital Doce de Octubre, Medical School, University Complutense, Madrid, Spain.
| | - Juan M Mendive
- La Mina Primary Care Academic Health Centre, Catalan Institute of Health (ICS), University of Barcelona, Barcelona, Spain.
| | - Michael W Müller
- Department of General and Visceral Surgery, Regionale Kliniken Holding, Kliniken Ludwigsburg-Bietigheim gGmbH, Krankenhaus Bietigheim, Bietigheim-Bissingen, Germany.
| | - Frank Tacke
- Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany.
| | - Anders Thorell
- Department of Clinical Science, Danderyds Hospital, Karolinska Institutet & Department of Surgery, Ersta Hospital, Stockholm, Sweden.
| | - Darija Vranesic Bender
- Unit of Clinical Nutrition, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
| | - Arved Weimann
- Department of General, Visceral and Oncological Surgery, St. George Hospital, Leipzig, Germany.
| | - Cristina Cuerda
- Departamento de Medicina, Universidad Complutense de Madrid, Nutrition Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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10
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Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a rapidly growing multisystem disease with extrahepatic manifestations, including effects on the cardiovascular (CV) system. The leading cause of death in NAFLD is of cardiac etiology being ischemic heart disease. AREAS OF UNCERTAINTY NAFLD is associated with several CV complications including cardiac structural and functional alterations. However, there are no current approved pharmacotherapies for treating NAFLD, leading to increased CV risk with an increasing morbidity and mortality. DATA SOURCES We summarize the currently available therapeutic strategies in managing NAFLD and their cardioprotective effects according to recently published data, guidelines, and practice guidance recommendations. THERAPEUTIC ADVANCES Several therapeutic modalities evaluated in NAFLD include nonpharmacological strategies, pharmacotherapies and surgical management. Nonpharmacological strategies are recommended in early stages of NAFLD and include weight loss, physical activity, and dietary changes. Personalized management strategies with nonpharmacological lifestyle modifications are associated with reduced CV risk, improved liver enzyme levels, in addition to liver fat content, injury, and fibrosis. Several pharmacotherapies including lipid-lowering agents and antidiabetic drugs such as insulin sensitizers and incretin mimetics, in addition to antioxidants, ursodeoxycholic acid, semi-synthetic bile acid analogue, acetylsalicylic acid, and renin-angiotensin system inhibitors have been evaluated in the current literature. Despite promising results of several drugs in NAFLD with cardioprotective effects, we currently remain with no approved medical drugs for treating NAFLD. Although bariatric surgery was demonstrated to be associated with CV risk reduction and improvements in hepatic steatosis, inflammation, and fibrosis, it remains of limited use because of its invasiveness. CONCLUSIONS Management of NAFLD necessitates a multidisciplinary team with a patient-centered and individualized medicine approach. Early lifestyle modifications are essential in NAFLD to reduce CV risk. Experimental studies are required to confirm hepatic and cardioprotective effects associated with several drugs. Bariatric surgery remains of limited use.
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Affiliation(s)
- Abdulrahman Ismaiel
- Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania ; and
- 2nd Department of Internal Medicine, Cluj-Napoca, Romania
| | - Dan L Dumitrascu
- Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania ; and
- 2nd Department of Internal Medicine, Cluj-Napoca, Romania
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11
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Stoffels CBA, Angerer TB, Robert H, Poupin N, Lakhal L, Frache G, Mercier-Bonin M, Audinot JN. Lipidomic Profiling of PFOA-Exposed Mouse Liver by Multi-Modal Mass Spectrometry Analysis. Anal Chem 2023; 95:6568-6576. [PMID: 37027489 PMCID: PMC10134131 DOI: 10.1021/acs.analchem.2c05470] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/09/2023]
Abstract
Perfluorooctanoic acid (PFOA) is a synthetic perfluorinated chemical classified as a persistent organic pollutant. PFOA has been linked to many toxic effects, including liver injury. Many studies report that PFOA exposure alters serum and hepatic lipid metabolism. However, lipidomic pathways altered by PFOA exposure are largely unknown and only a few lipid classes, mostly triacylglycerol (TG), are usually considered in lipid analysis. Here, we performed a global lipidomic analysis on the liver of PFOA-exposed (high-dose and short-duration) and control mice by combining three mass spectrometry (MS) techniques: liquid chromatography with tandem mass spectrometry (LC-MS/MS), matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI), and time-of-flight secondary ion mass spectrometry (TOF-SIMS). Among all hepatic lipids identified by LC-MS/MS analysis, more than 350 were statistically impacted (increased or decreased levels) after PFOA exposure, as confirmed by multi-variate data analysis. The levels of many lipid species from different lipid classes, most notably phosphatidylethanolamine (PE), phosphatidylcholine (PC), and TG, were significantly altered. Subsequent lipidomic analysis highlights the pathways significantly impacted by PFOA exposure, with the glycerophospholipid metabolism being the most impacted, and the changes in the lipidome network, which connects all the lipid species together. MALDI-MSI displays the heterogeneous distribution of the affected lipids and PFOA, revealing different areas of lipid expression linked to PFOA localization. TOF-SIMS localizes PFOA at the cellular level, supporting MALDI-MSI results. This multi-modal MS analysis unveils the lipidomic impact of PFOA in the mouse liver after high-dose and short-term exposure and opens new opportunities in toxicology.
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Affiliation(s)
- Charlotte B A Stoffels
- Department of Materials Research and Technology, Luxembourg Institute of Science and Technology, Belvaux 4422, Luxembourg
- Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette 4365, Luxembourg
| | - Tina B Angerer
- Department of Materials Research and Technology, Luxembourg Institute of Science and Technology, Belvaux 4422, Luxembourg
| | - Hervé Robert
- Toxalim, Université de Toulouse, INRAE, INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, Toulouse 31027, France
| | - Nathalie Poupin
- Toxalim, Université de Toulouse, INRAE, INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, Toulouse 31027, France
| | - Laila Lakhal
- Toxalim, Université de Toulouse, INRAE, INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, Toulouse 31027, France
| | - Gilles Frache
- Department of Materials Research and Technology, Luxembourg Institute of Science and Technology, Belvaux 4422, Luxembourg
| | - Muriel Mercier-Bonin
- Toxalim, Université de Toulouse, INRAE, INP-ENVT, INP-EI-Purpan, Université de Toulouse 3 Paul Sabatier, Toulouse 31027, France
| | - Jean-Nicolas Audinot
- Department of Materials Research and Technology, Luxembourg Institute of Science and Technology, Belvaux 4422, Luxembourg
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12
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Metro D, Buda M, Manasseri L, Corallo F, Cardile D, Lo Buono V, Quartarone A, Bonanno L. Role of Nutrition in the Etiopathogenesis and Prevention of Nonalcoholic Fatty Liver Disease (NAFLD) in a Group of Obese Adults. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59030638. [PMID: 36984639 PMCID: PMC10055888 DOI: 10.3390/medicina59030638] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 03/15/2023] [Accepted: 03/20/2023] [Indexed: 03/30/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is liver damage characterized by an accumulation of triglycerides in hepatocytes of >5% (due to an alteration of the balance of the lipid metabolism in favour of lipogenesis compared to lipolysis) that is not induced by the consumption of alcohol. The pathology includes simple steatosis and nonalcoholic steatohepatitis, or NASH (steatosis associated with microinflammatory activities), which can evolve in 15% of subjects with hepatic fibrosis to cirrhosis and the development of hepatocellular carcinoma. The aim of this study is to report the role of macro- and micronutrients in the pathogenesis and prevention of NAFLD in obese subjects. A total of 22 obese or overweight patients with hepatic steatosis were monitored periodically, evaluating their eating habits, fasting glycaemia, lipid picture, liver enzymes, anthropometric parameters, nutrition status, liver ultrasound, oxidative stress, and adherence to the Mediterranean diet. A statistical analysis shows a significant positive relationship between total cholesterol and the Mediterranean adequacy index (MAI) (r = -0.57; p = 0.005) and a significant negative relationship between ALT transaminases and the MAI (r = -0.56; p = 0.007). Nutrition and diet are important factors in the pathogenesis and prevention of NAFLD. The dietary model, based on the canons of the Mediterranean diet, prevents and reduces the accumulation of fat in hepatocytes. Therefore, in agreement with other studies in the literature, we can state that a dietary model characterized by foods rich in fibre, carotenoids, polyphenols, ω3 fatty acids, folic acid, and numerous other molecules is inversely correlated with the serum levels of ALT transaminases, an enzyme whose level increases when the liver is damaged and before the most obvious symptoms of organ damage appear.
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Affiliation(s)
- Daniela Metro
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98122 Messina, Italy
| | - Martina Buda
- Department Oncological D.A.I., UOC of General Surgery-Oncology, 98125 Messina, Italy
| | - Luigi Manasseri
- Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98122 Messina, Italy
| | - Francesco Corallo
- IRCCS Centro Neurolesi Bonino-Pulejo, S.S. 113 Via Palermo, C. da Casazza, 98124 Messina, Italy
| | - Davide Cardile
- IRCCS Centro Neurolesi Bonino-Pulejo, S.S. 113 Via Palermo, C. da Casazza, 98124 Messina, Italy
| | - Viviana Lo Buono
- IRCCS Centro Neurolesi Bonino-Pulejo, S.S. 113 Via Palermo, C. da Casazza, 98124 Messina, Italy
| | - Angelo Quartarone
- IRCCS Centro Neurolesi Bonino-Pulejo, S.S. 113 Via Palermo, C. da Casazza, 98124 Messina, Italy
| | - Lilla Bonanno
- IRCCS Centro Neurolesi Bonino-Pulejo, S.S. 113 Via Palermo, C. da Casazza, 98124 Messina, Italy
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13
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Bischoff SC, Barazzoni R, Busetto L, Campmans-Kuijpers M, Cardinale V, Chermesh I, Eshraghian A, Kani HT, Khannoussi W, Lacaze L, Léon-Sanz M, Mendive JM, Müller MW, Ockenga J, Tacke F, Thorell A, Vranesic Bender D, Weimann A, Cuerda C. European guideline on obesity care in patients with gastrointestinal and liver diseases - Joint ESPEN/UEG guideline. Clin Nutr 2022; 41:2364-2405. [PMID: 35970666 DOI: 10.1016/j.clnu.2022.07.003] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 07/03/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Patients with chronic gastrointestinal (GI) disease such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), celiac disease, gastroesophageal reflux disease (GERD), pancreatitis, and chronic liver disease (CLD) often suffer from obesity because of coincidence (IBD, IBS, celiac disease) or related pathophysiology (GERD, pancreatitis and CLD). It is unclear if such patients need a particular diagnostic and treatment that differs from the needs of lean GI patients. The present guideline addresses this question according to current knowledge and evidence. OBJECTIVE The objective of the guideline is to give advice to all professionals working in the field of gastroenterology care including physicians, surgeons, dietitians and others how to handle patients with GI disease and obesity. METHODS The present guideline was developed according to the standard operating procedure for ESPEN guidelines, following the Scottish Intercollegiate Guidelines Network (SIGN) grading system (A, B, 0, and good practice point (GPP)). The procedure included an online voting (Delphi) and a final consensus conference. RESULTS In 100 recommendations (3x A, 33x B, 24x 0, 40x GPP, all with a consensus grade of 90% or more) care of GI patients with obesity - including sarcopenic obesity - is addressed in a multidisciplinary way. A particular emphasis is on CLD, especially fatty liver disease, since such diseases are closely related to obesity, whereas liver cirrhosis is rather associated with sarcopenic obesity. A special chapter is dedicated to obesity care in patients undergoing bariatric surgery. The guideline focuses on adults, not on children, for whom data are scarce. Whether some of the recommendations apply to children must be left to the judgment of the experienced pediatrician. CONCLUSION The present guideline offers for the first time evidence-based advice how to care for patients with chronic GI diseases and concomitant obesity, an increasingly frequent constellation in clinical practice.
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Affiliation(s)
- Stephan C Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Rocco Barazzoni
- Department of Medical, Technological and Translational Sciences, University of Trieste, Ospedale di Cattinara, Trieste, Italy.
| | - Luca Busetto
- Department of Medicine, University of Padova, Padova, Italy.
| | - Marjo Campmans-Kuijpers
- Department of Gastroenterology and Hepatology, University Medical Centre Groningen, Groningen, the Netherlands.
| | - Vincenzo Cardinale
- Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.
| | - Irit Chermesh
- Department of Gastroenterology, Rambam Health Care Campus, Affiliated with Technion-Israel Institute of Technology, Haifa, Israel.
| | - Ahad Eshraghian
- Department of Gastroenterology and Hepatology, Avicenna Hospital, Shiraz, Iran.
| | - Haluk Tarik Kani
- Department of Gastroenterology, Marmara University, School of Medicine, Istanbul, Turkey.
| | - Wafaa Khannoussi
- Hepato-Gastroenterology Department, Mohammed VI University Hospital, Oujda, Morocco; Laboratoire de Recherche des Maladies Digestives (LARMAD), Mohammed the First University, Oujda, Morocco.
| | - Laurence Lacaze
- Department of General Surgery, Mantes-la-Jolie Hospital, Mantes-la-Jolie, France; Department of Clinical Nutrition, Paul-Brousse-Hospital, Villejuif, France.
| | - Miguel Léon-Sanz
- Department of Endocrinology and Nutrition, University Hospital Doce de Octubre, Medical School, University Complutense, Madrid, Spain.
| | - Juan M Mendive
- La Mina Primary Care Academic Health Centre, Catalan Institute of Health (ICS), University of Barcelona, Barcelona, Spain.
| | - Michael W Müller
- Department of General and Visceral Surgery, Regionale Kliniken Holding, Kliniken Ludwigsburg-Bietigheim GGmbH, Krankenhaus Bietigheim, Bietigheim-Bissingen, Germany.
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen-Mitte, Bremen FRG, Bremen, Germany.
| | - Frank Tacke
- Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany.
| | - Anders Thorell
- Department of Clinical Science, Danderyds Hospital, Karolinska Institutet & Department of Surgery, Ersta Hospital, Stockholm, Sweden.
| | - Darija Vranesic Bender
- Unit of Clinical Nutrition, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
| | - Arved Weimann
- Department of General, Visceral and Oncological Surgery, St. George Hospital, Leipzig, Germany.
| | - Cristina Cuerda
- Departamento de Medicina, Universidad Complutense de Madrid, Nutrition Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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14
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Association between Mediterranean Diet and Fatty Liver in Women with Overweight and Obesity. Nutrients 2022; 14:nu14183771. [PMID: 36145146 PMCID: PMC9501123 DOI: 10.3390/nu14183771] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Revised: 09/05/2022] [Accepted: 09/08/2022] [Indexed: 11/17/2022] Open
Abstract
Obesity is a risk factor for NAFLD. However, not all people with obesity have an excessive intrahepatic fat content. Adherence to a high-quality dietary pattern may also promote liver health in obesity. A cross-sectional study of 2967 women with overweight and obesity was carried out to assess the association between a Mediterranean diet and fatty liver. All women underwent clinical examination, anthropometric measurements, blood sampling, ultrasound measurements of abdominal visceral and subcutaneous fat, and assessment of adherence to the Mediterranean diet using the 14-item MEDAS questionnaire. Fatty liver index (FLI), NAFLD fatty liver steatosis (NAFLD-FLS) and hepatic steatosis index (HSI) were calculated. In women with obesity, the MEDAS score was inversely associated with FLI (β = −0.60, 95% CI: −1.04, −0.16, p = 0.008), NAFLD-FLS (β = −0.092, 95% CI: −0.134, −0.049, p < 0.001) and HSI (β = −0.17, 95% CI: −0.30, −0.04, p = 0.011). Stronger associations were observed in premenopausal women with obesity. Mediterranean diet was inversely associated with NAFLD-FLS in women with overweight, independently of menopausal status. In conclusion, Mediterranean diet is associated with a better liver status in women with overweight and obesity. This may have a public health impact and be useful in drafting nutritional guidelines for NAFLD.
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15
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Dubé L, Spahis S, Lachaîne K, Lemieux A, Monhem H, Poulin SM, Randoll C, Travaillaud E, Ould-Chikh NEH, Marcil V, Delvin E, Levy E. Specialized Pro-Resolving Mediators Derived from N-3 Polyunsaturated Fatty Acids: Role in Metabolic Syndrome and Related Complications. Antioxid Redox Signal 2022; 37:54-83. [PMID: 35072542 DOI: 10.1089/ars.2021.0156] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Significance: Metabolic syndrome (MetS) prevalence continues to grow and represents a serious public health issue worldwide. This multifactorial condition carries the risk of hastening the development of type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases (CVD). Another troubling aspect of MetS is the requirement of poly-pharmacological therapy not devoid of side effects. Therefore, there is an urgent need for prospecting alternative nutraceuticals as effective therapeutic agents for MetS. Recent Advances: Currently, there is an increased interest in understanding the regulation of metabolic derangements by specialized pro-resolving lipid mediators (SPMs), especially those derived from the long chain n-3 polyunsaturated fatty acids. Critical Issues: The SPMs are recognized as efficient modulators that are capable of inhibiting the production of pro-inflammatory cytokines, blocking neutrophil activation/recruitment, and inducing non-phlogistic (anti-inflammatory) activation of macrophage engulfment and removal of apoptotic inflammatory cells and debris. The aim of the present review is precisely to first underline key concepts relative to SPM functions before focusing on their status and actions on MetS components (e.g., obesity, glucose dysmetabolism, hyperlipidemia, hypertension) and complications such as T2D, NAFLD, and CVD. Future Directions: Valuable data from preclinical and clinical investigations have emphasized the SPM functions and influence on oxidative stress- and inflammation-related MetS. Despite these promising findings obtained without compromising host defense, additional efforts are needed to evaluate their potential therapeutic applications and further develop practical tools to monitor their bioavailability to cope with cardiometabolic disorders. Antioxid. Redox Signal. 37, 54-83.
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Affiliation(s)
- Laurent Dubé
- Research Centre, Sainte-Justine Hospital, Université de Montréal, Montreal, Canada.,Department of Nutrition, Université de Montréal, Montreal, Canada
| | - Schohraya Spahis
- Research Centre, Sainte-Justine Hospital, Université de Montréal, Montreal, Canada.,Department of Nutrition, Université de Montréal, Montreal, Canada.,Institute of Nutrition and Functional Foods, Laval University, Quebec City, Canada
| | - Karelle Lachaîne
- Department of Nutrition, Université de Montréal, Montreal, Canada
| | | | - Hanine Monhem
- Department of Nutrition, Université de Montréal, Montreal, Canada
| | | | - Carolane Randoll
- Department of Nutrition, Université de Montréal, Montreal, Canada
| | - Eva Travaillaud
- Department of Nutrition, Université de Montréal, Montreal, Canada
| | | | - Valérie Marcil
- Research Centre, Sainte-Justine Hospital, Université de Montréal, Montreal, Canada.,Department of Nutrition, Université de Montréal, Montreal, Canada.,Institute of Nutrition and Functional Foods, Laval University, Quebec City, Canada
| | - Edgard Delvin
- Research Centre, Sainte-Justine Hospital, Université de Montréal, Montreal, Canada.,Department of Biochemistry, Université de Montréal, Montreal, Canada
| | - Emile Levy
- Research Centre, Sainte-Justine Hospital, Université de Montréal, Montreal, Canada.,Department of Nutrition, Université de Montréal, Montreal, Canada.,Institute of Nutrition and Functional Foods, Laval University, Quebec City, Canada.,Department of Pediatrics, Gastroenterology & Hepatology Unit, Université de Montréal, Montreal, Canada
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16
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Zhu L, Chen G, Guo Y, Zheng J, Yang H, Sun X, Liu Y, Hu B, Liu H. Structural characterization of Poria cocos oligosaccharides and their effects on the hepatic metabolome in high-fat diet-fed mice. Food Funct 2022; 13:6813-6829. [PMID: 35671132 DOI: 10.1039/d2fo00638c] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
In this study, novel Poria cocos oligosaccharides (PCO) were prepared by enzymatic degradation, and their polymerization degree was determined to be 2-6 by LC-MS analysis. By monosaccharide composition analysis, methylation assay, FT-IR, and NMR analysis, PCO were deduced to contain the sugar residues of (1 → 2)-β-D-Glcp, (1 → 2)-α-D-Glcp, and (1 → 4)-α-D-Glcp. Using an HFD-fed mouse model with dyslipidemia, PCO could significantly suppress lipid metabolism disorders, characterized by the reduction of lipid accumulation and inflammatory responses in the blood and liver tissues. Based on the non-targeted metabolomic analysis and Spearman's correlation analysis, we presume that the preventive effect of PCO on dyslipidemia might contribute to the reversal of changed metabolic pathways, which were related to the metabolisms of glycerophospholipids, unsaturated fatty acids, amino acids, choline, bile acids, tryptophan, sphingolipids, and glutathione. Our research shed light on the potential application of PCO for the treatment of dyslipidemia.
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Affiliation(s)
- Lin Zhu
- College of Life Science, Wuchang University of Technology, Synergy Innovation Center of Biological Peptide Antidiabetics of Hubei Province, Engineering Technology Research Center of Biological Peptide Antidiabetics of Hubei Province, Jiangxia Avenue 16, Wuhan 430223, P. R. China.,College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, P. R. China.
| | - Guangming Chen
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, P. R. China.
| | - Yanlei Guo
- Chongqing Academy of Chinese Materia Medica, Chongqing 400065, P. R. China
| | - Junping Zheng
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, P. R. China.
| | - Huabing Yang
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, P. R. China.
| | - Xiongjie Sun
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, P. R. China.
| | - Yang Liu
- College of Life Science, Wuchang University of Technology, Synergy Innovation Center of Biological Peptide Antidiabetics of Hubei Province, Engineering Technology Research Center of Biological Peptide Antidiabetics of Hubei Province, Jiangxia Avenue 16, Wuhan 430223, P. R. China
| | - Baifei Hu
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, P. R. China.
| | - Hongtao Liu
- College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, P. R. China.
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Yang W, Singla R, Maheshwari O, Fontaine CJ, Gil-Mohapel J. Alcohol Use Disorder: Neurobiology and Therapeutics. Biomedicines 2022; 10:1192. [PMID: 35625928 PMCID: PMC9139063 DOI: 10.3390/biomedicines10051192] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Revised: 05/18/2022] [Accepted: 05/20/2022] [Indexed: 02/04/2023] Open
Abstract
Alcohol use disorder (AUD) encompasses the dysregulation of multiple brain circuits involved in executive function leading to excessive consumption of alcohol, despite negative health and social consequences and feelings of withdrawal when access to alcohol is prevented. Ethanol exerts its toxicity through changes to multiple neurotransmitter systems, including serotonin, dopamine, gamma-aminobutyric acid, glutamate, acetylcholine, and opioid systems. These neurotransmitter imbalances result in dysregulation of brain circuits responsible for reward, motivation, decision making, affect, and the stress response. Despite serious health and psychosocial consequences, this disorder still remains one of the leading causes of death globally. Treatment options include both psychological and pharmacological interventions, which are aimed at reducing alcohol consumption and/or promoting abstinence while also addressing dysfunctional behaviours and impaired functioning. However, stigma and social barriers to accessing care continue to impact many individuals. AUD treatment should focus not only on restoring the physiological and neurological impairment directly caused by alcohol toxicity but also on addressing psychosocial factors associated with AUD that often prevent access to treatment. This review summarizes the impact of alcohol toxicity on brain neurocircuitry in the context of AUD and discusses pharmacological and non-pharmacological therapies currently available to treat this addiction disorder.
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Affiliation(s)
- Waisley Yang
- Island Medical Program, Faculty of Medicine, University of British Columbia, Victoria, BC V8P 5C2, Canada; (W.Y.); (R.S.)
| | - Rohit Singla
- Island Medical Program, Faculty of Medicine, University of British Columbia, Victoria, BC V8P 5C2, Canada; (W.Y.); (R.S.)
| | - Oshin Maheshwari
- Psychiatry Residency Program, Faculty of Medicine, University of British Columbia, Victoria, BC V8W 3P5, Canada;
| | | | - Joana Gil-Mohapel
- Island Medical Program, Faculty of Medicine, University of British Columbia, Victoria, BC V8P 5C2, Canada; (W.Y.); (R.S.)
- Division of Medical Sciences, University of Victoria, Victoria, BC V8W 2Y2, Canada;
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18
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Yasseen DG, Waly NE, Abdulghani KO. Polyunsaturated fatty acids supplementation can improve specific language impairment in preschool children: a pilot study. THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2020. [DOI: 10.1186/s41983-020-0158-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Speech and language are one of the higher cognitive brain functions. Language delay is one of the major concerns of child health in Egypt. Speech therapy is the standard management in language delay.
Objective
We aimed to investigate the potential role of dietary supplementation with polyunsaturated fatty acids (PUFAs) in improving specific language impairment.
Subjects and methods
A total of 220 children (ages 3–4) were included in this study at the Phonetics Department, Helwan School of Medicine, Egypt, during the period from 2015 to 2018. Children received comprehensive neurological examination and intelligence quotient (IQ) test to exclude the other causes of language delay. Language evaluation was performed using the Arabic language test. They either received family counseling, speech therapy (45 min; 3 times a week for 16 weeks), and PUFA supplementation 500 mg twice daily (group A) or only counseling and speech therapy (group B). Language quotient (LQ) was calculated before and after treatment.
Results
Our results show that LQ significantly improved in group A compared with group B (p < 0.004).
Conclusion
Dietary supplementation with PUFA has a beneficial role in the management of specific language impairment along with speech therapy.
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19
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Katsnelson G, Ceddia RB. Docosahexaenoic and eicosapentaenoic fatty acids differentially regulate glucose and fatty acid metabolism in L6 rat skeletal muscle cells. Am J Physiol Cell Physiol 2020; 319:C1120-C1129. [PMID: 32966124 DOI: 10.1152/ajpcell.00304.2020] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The objective of this study was to investigate whether the n-3 polyunsaturated fatty acids (PUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) can directly regulate glucose and fat metabolism in skeletal muscle besides exerting anti-inflammatory effects. To accomplish this, L6 skeletal muscle cells were treated with 50 µM of either DHA or EPA for 1, 3, and 5 days. Here, we report that basal and insulin-stimulated rates of glucose uptake, glycogen synthesis, protein kinase B (AKT), and glycogen synthase kinase 3 (GSK3) phosphorylation were not affected by DHA or EPA. However, glucose and palmitate oxidation were consistently elevated by DHA treatment, whereas EPA only increased this variable transiently. Similarly, only DHA caused significant and sustained increases in AMP-activated protein kinase (AMPK) phosphorylation and protein levels of carnitine-palmitoyl transferase-1b (CPT1b) and peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) in skeletal muscle cells. DHA also caused a larger anti-inflammatory effect than EPA in these cells. In conclusion, besides exerting anti-inflammatory effects, DHA and EPA directly regulated glucose and fat metabolism in skeletal muscle cells, although DHA was more effective in doing so than EPA. Thus, by directly enhancing glucose and fat oxidation, DHA may increase glucose disposal and reduce intramyocellular lipid accumulation.
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Affiliation(s)
- Glen Katsnelson
- Muscle Health Research Center, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada
| | - Rolando B Ceddia
- Muscle Health Research Center, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada
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20
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Nutrients, Genetic Factors, and Their Interaction in Non-Alcoholic Fatty Liver Disease and Cardiovascular Disease. Int J Mol Sci 2020; 21:ijms21228761. [PMID: 33228237 PMCID: PMC7699550 DOI: 10.3390/ijms21228761] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 11/15/2020] [Accepted: 11/16/2020] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries and expose patients to increased risk of hepatic and cardiovascular (CV) morbidity and mortality. Both environmental factors and genetic predisposition contribute to the risk. An inappropriate diet, rich in refined carbohydrates, especially fructose, and saturated fats, and poor in fibers, polyunsaturated fats, and vitamins is one of the main key factors, as well as the polymorphism of patatin-like phospholipase domain containing 3 (PNPLA3 gene) for NAFLD and the apolipoproteins and the peroxisome proliferator-activated receptor (PPAR) family for the cardiovascular damage. Beyond genetic influence, also epigenetics modifications are responsible for various clinical manifestations of both hepatic and CV disease. Interestingly, data are accumulating on the interplay between diet and genetic and epigenetic modifications, modulating pathogenetic pathways in NAFLD and CV disease. We report the main evidence from literature on the influence of both macro and micronutrients in NAFLD and CV damage and the role of genetics either alone or combined with diet in increasing the risk of developing both diseases. Understanding the interaction between metabolic alterations, genetics and diet are essential to treat the diseases and tailoring nutritional therapy to control NAFLD and CV risk.
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21
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Prabhakar O, Bhuvaneswari M. Role of diet and lifestyle modification in the management of nonalcoholic fatty liver disease and type 2 diabetes. Tzu Chi Med J 2020; 33:135-145. [PMID: 33912410 PMCID: PMC8059462 DOI: 10.4103/tcmj.tcmj_86_20] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 05/11/2020] [Accepted: 06/08/2020] [Indexed: 12/15/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is considered as the hepatic evidence of insulin resistance which is the hallmark of type 2 diabetes. NAFLD is considered as the risk factor for developing type 2 diabetes and has a high frequency of occurrence in those with existing type 2 diabetes. Compared with patients with only NAFLD or type 2 diabetes, these patients show a poor metabolic profile and increase mortality. Hence, effective treatment strategies are necessary. Here, we review the role of diet and lifestyle modification in the management of NAFLD and type 2 diabetes. Based on the available studies, it has been shown that the addition of any kind of physical activity or exercise is beneficial for patients with both NAFLD and type 2 diabetes. Proper dietary management leads to weight loss are also effective in improving metabolic parameters in patients with both NAFLD and type 2 diabetes. In conclusion, it is clear that increasing physical activity or exercise is effective in improving metabolic parameters in patients who are suffering with both NAFLD and type 2 diabetes.
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Affiliation(s)
- Orsu Prabhakar
- Department of Pharmacology, GITAM Institute of Pharmacy, Visakhapatnam, Andhra Pradesh, India
| | - Mylipilli Bhuvaneswari
- Department of Pharmacology, GITAM Institute of Pharmacy, Visakhapatnam, Andhra Pradesh, India
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22
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Valenzuela R, Ortiz M, Hernández-Rodas MC, Echeverría F, Videla LA. Targeting n-3 Polyunsaturated Fatty Acids in Non-Alcoholic Fatty Liver Disease. Curr Med Chem 2020; 27:5250-5272. [PMID: 30968772 DOI: 10.2174/0929867326666190410121716] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 12/14/2018] [Accepted: 01/12/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by abnormal hepatic accumulation of triacylglycerides in the absence of alcohol consumption, in association with Oxidative Stress (OS), a pro-inflammatory state and Insulin Resistance (IR), which are attenuated by n-3 long-chain polyunsaturated Fatty Acids (FAs) C20-C22 (LCPUFAs) supplementation. Main causes of NAFLD comprise high caloric intake and a sedentary lifestyle, with high intakes of saturated FAs. METHODS The review includes several searches considering the effects of n-3 LCPUFAs in NAFLD in vivo and in vitro models, using the PubMed database from the National Library of Medicine- National Institutes of Health. RESULT The LCPUFAs eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n- 3, DHA) have a positive effect in diminishing liver steatosis, OS, and the levels of aspartate aminotransferase, alanine aminotransferase and pro-inflammatory cytokines, with improvement of insulin sensitivity and adiponectin levels. The molecular pathways described for n-3 LCPUFAs in cellular and animal models and humans include peroxisome proliferator-activated receptor-α activation favouring FA oxidation, diminution of lipogenesis due to sterol responsive element binding protein-1c downregulation and inflammation resolution. Besides, nuclear factor erythroid-2-related factor-2 activation is elicited by n-3 LCPUFA-derived oxidation products producing direct and indirect antioxidant responses, with concomitant anti-fibrogenic action. CONCLUSION The discussed effects of n-3 LCPUFA supplementation support its use in NAFLD, although having a limited value in NASH, a contention that may involve n-3 LCPUFA oxygenated derivatives. Clinical trials establishing optimal dosages, intervention times, type of patients and possible synergies with other natural products are needed in future studies.
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Affiliation(s)
- Rodrigo Valenzuela
- Department of Nutrition, Faculty of Medicine, University of Chile, Av. Independencia 1027, Independencia, Santiago 8380453, Chile
| | - Macarena Ortiz
- Nutrition and Dietetics School, Faculty of Health Sciences, Catholic University of Maule, Merced 333, Curicó 3340000, Chile
| | - María Catalina Hernández-Rodas
- Department of Nutrition, Faculty of Medicine, University of Chile, Av. Independencia 1027, Independencia, Santiago 8380453, Chile
| | - Francisca Echeverría
- Department of Nutrition, Faculty of Medicine, University of Chile, Av. Independencia 1027, Independencia, Santiago 8380453, Chile
| | - Luis Alberto Videla
- Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Av. Independencia 1027, Independencia, Santiago 8380453, Chile
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Deng X, Wang P, Yuan H. Epidemiology, risk factors across the spectrum of age-related metabolic diseases. J Trace Elem Med Biol 2020; 61:126497. [PMID: 32247247 DOI: 10.1016/j.jtemb.2020.126497] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Accepted: 02/13/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Population aging is dynamic process of increasing proportion of older adults in the total population, which is an inescapable result of decline in fertility rate and extension in life expectancy. Inevitably, age-related metabolic diseases, for example obesity, type 2 diabetes, metabolic syndrome, dyslipidemia, and nonalcoholic fatty liver disease, are becoming epidemic globally along with the demographic transition. CONTENT The review examines the literatures related to: 1) the epidemiology of age related metabolic diseases including obesity, type 2 diabetes, metabolic syndrome, dyslipidemia, and nonalcoholic fatty liver disease; and 2) the risk factors of age related metabolic diseases including genetic factors, diet, smoking, Physical activity, intestinal microbiota and environmental factors. CONCLUSION Population aging is becoming epidemic worldwide, resulting in increasing incidence and prevalence of a serious of age-related metabolic diseases. Both genetic and environmental factors contribute to the diseases, thus interventions targeting on these factors may have beneficial effect on the development of age-related metabolic diseases.
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Affiliation(s)
- Xinru Deng
- Department of Endocrinology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China
| | - Pengxu Wang
- Department of Endocrinology, Henan University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, China
| | - Huijuan Yuan
- Department of Endocrinology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China.
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Dehghanseresht N, Jafarirad S, Alavinejad SP, Mansoori A. Association of the dietary patterns with the risk of non-alcoholic fatty liver disease among Iranian population: a case-control study. Nutr J 2020; 19:63. [PMID: 32605646 PMCID: PMC7329390 DOI: 10.1186/s12937-020-00580-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2020] [Accepted: 06/24/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Diet-based recommendations can be developed for preventing and treating non-alcoholic fatty liver disease (NAFLD) after investigating the effects of whole diets on NAFLD. The aim of this study was to identify major dietary patterns and their association with the risk of NAFLD. METHODS A total of 244 individuals (122 NAFLD patients and 122 controls) participated in this case-control study. The patients with NAFLD were diagnosed by a gastroenterologist. The participants' dietary intake data were collected using a 147-item semi-quantitive food frequency questionnaire and major dietary patterns were identified by principal component analysis. Adherence to dietary patterns was divided into tertiles and its association with odds of NAFLD was investigated by multivariate logistic regression. RESULTS The results showed four major dietary patterns, among which adherence to the "ordinary pattern" was positively associated with NAFLD risk. After adjusting for all confounding factors, individuals in the highest tertile of "ordinary pattern" exhibited a significantly elevated risk of NAFLD compared to the lowest tertile (OR = 3.74, 95%CI = 1.23-11.42, P trend< 0.001). As well as, Individuals in the second and third tertiles of the "traditional pattern" were associated with the risk of NAFLD compared to the lowest tertile (medium vs. lowest tertile OR = 2.37, 95%CI = 1.02-5.53; highest vs. lowest tertile OR = 3.58, 95% CI = 1.48-8.68, P trend< 0.001). The highest tertile of "vegetable and dairy pattern" compared to the lowest tertile was inversely associated with NAFLD risk (OR = 0.23, 95%CI = 0.09-0.58, P trend = 0.02). No significant association was found between "fast food type pattern" and the risk of NAFLD. CONCLUSION A significant association was observed between different dietary patterns and the risk of NAFLD. These results can potentially serve as a dietary strategy for preventing NAFLD in individuals who are at a high risk for progression of NAFLD.
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Affiliation(s)
- Narges Dehghanseresht
- Department of Nutrition, Faculty of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, P.O.BOX: 61357-15794, Ahvaz, Iran
| | - Sima Jafarirad
- Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Seyed Pejman Alavinejad
- Research Institute for Infectious Disease of Digestive System, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Anahita Mansoori
- Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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Effect of Carotenoids from Phaeodactylum tricornutum on Palmitate-Treated HepG2 Cells. Molecules 2020; 25:molecules25122845. [PMID: 32575640 PMCID: PMC7356161 DOI: 10.3390/molecules25122845] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 06/16/2020] [Accepted: 06/17/2020] [Indexed: 12/20/2022] Open
Abstract
Non-alcoholic fatty liver disease represents the most common liver disease and is characterized by an excess of lipid accumulation in hepatocytes, mainly stored as triglycerides. Phaeodactylum tricornutum is a marine microalga, which is rich in bioactive molecules known to be hepatoprotective, such as n-3 long-chain polyunsaturated fatty acids and fucoxanthin. The aim of this study was to investigate the effects of a carotenoid extract from P. tricornutum in a cellular model of non-alcoholic fatty liver disease induced by palmitate treatment. The combined effects of carotenoids and lipids, especially n-3 long-chain polyunsaturated fatty acids, were also investigated by using a total lipophilic extract. HepG2 cells were exposed for 24 h to 250 µM palmitate with or without the addition of carotenoid extract (6 μg/mL) or total lipophilic extract (100 μg/mL). The addition of carotenoid extract or total lipophilic extract prevented the accumulation of triglycerides, total cholesterol and cholesterol esters. The carotenoid extract and total lipophilic extract also decreased the mRNA expression levels of genes involved in lipogenesis (ACACA, FASN, SCD and DGAT1) and cholesterol esterification (ACAT1/SOAT1). In addition, the total lipophilic extract also downregulated the LXR/NR1H3 and SREBF1 genes, which are involved in lipogenesis regulation. By contrast, the carotenoid extract increased the mRNA level of CPT1A, a β-oxidation related gene, and reduced the lipid droplet accumulation. In conclusion, this study highlights the preventive effects against non-alcoholic fatty liver disease of the two microalga extracts.
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Shi XY, Fan SM, Shi GM, Yao J, Gao Y, Xia YG, Chen Q. Efficacy and safety of omega-3 fatty acids on liver-related outcomes in patients with nonalcoholic fatty liver disease: A protocol for a systematic review and meta-analysis. Medicine (Baltimore) 2020; 99:e20624. [PMID: 32541499 PMCID: PMC7302599 DOI: 10.1097/md.0000000000020624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD), especially non-alcoholic steatohepatitis, which is considered as the hepatic manifestation of metabolic syndrome, has a great prevalence all over the world. New drugs are urgently needed for the treatment of NAFLD. This review will be to assess the efficacy and safety of omega-3 polyunsaturated fatty acids (n-3 PUFAs) on liver-related outcomes (liver histology and liver enzymes) in patients with NAFLD. METHODS We will search 5 databases for relative studies: Medline, the Cochrane Library, EMBASE, Web of Science, and ClinicalTrials.gov and identified all reports of randomized controlled trials published prior to July 2020. Two authors will independently scan the articles searched, extract the data from articles included, and assess the risk of bias by Cochrane tool of risk of bias. Disagreements will be resolved by discussion among authors. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. Fixed-effects model or random-effects model will be used to calculate pooled estimates of weighted mean difference with 95% confidence intervals. RESULTS This systematic review aims to examine the effect of n-3 PUFAs on liver histology and liver enzymes in patients with NAFLD. CONCLUSIONS These findings will provide guidance to clinicians and patients on the use of n-3 PUFAs for NAFLD. ETHICS AND DISSEMINATION This study is a protocol for a systematic review of n-3 PUFAs as a treatment of NAFLD patients. This review will be published in a journal and disseminated in print by peer-review. SYSTEMATIC REVIEW REGISTRATION INPLASY202050008.
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Affiliation(s)
- Xiao-yan Shi
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province
| | - Si-min Fan
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province
| | - Guo-mei Shi
- School of Information Science and Technology, Northeast Normal University, Changchun, Jilin Province, P.R. China
| | - Jia Yao
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province
| | - Yang Gao
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province
| | - Yu-guo Xia
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province
| | - Qiu Chen
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province
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Abstract
Dietary habits have been implicated in the development and severity of non-alcoholic fatty liver disease (NAFLD). Several epidemiological studies attempted to assess the relationship between food groups and the likelihood of NAFLD, but these results were conflicting. The present meta-analysis was conducted to assess the association between food groups and the likelihood of NAFLD. Published literature was retrieved and screened from MEDLINE, Embase and Web of Science. Out of 7892 retrieved articles, twenty-four observational studies (fifteen cross-sectional studies and nine case–control studies) met our eligibility criteria and were finally included in this systematic review and meta-analysis. Consumption of both red meat and soft drinks contributed to a positive association with NAFLD. Inversely, nut consumption was negatively associated with NAFLD. There were no significant influences on the likelihood of NAFLD about consuming whole grains, refined grains, fish, fruits, vegetables, eggs, dairy products and legumes. This meta-analysis suggests that individuals who consumed more red meat and soft drinks may have a significantly increased likelihood of NAFLD, whereas higher nut intake may be negatively associated with NAFLD. Further prospective studies are required to assess the association between food patterns and NAFLD.
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28
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Chakravarthy MV, Waddell T, Banerjee R, Guess N. Nutrition and Nonalcoholic Fatty Liver Disease: Current Perspectives. Gastroenterol Clin North Am 2020; 49:63-94. [PMID: 32033765 DOI: 10.1016/j.gtc.2019.09.003] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/15/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis are diseases in their own right as well as modifiable risk factors for cardiovascular disease and type 2 diabetes. With expanding knowledge on NAFLD pathogenesis, insights have been gleaned into molecular targets for pharmacologic and nonpharmacologic approaches. Lifestyle modifications constitute a cornerstone of NAFLD management. This article reviews roles of key dietary macronutrients and micronutrients in NAFLD pathogenesis and their effects on molecular targets shared with established or emerging pharmacotherapies. Based on current evidence, a recommendation for a dietary framework as part of the comprehensive management strategy for NAFLD is provided.
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Affiliation(s)
| | - Thomas Waddell
- Perspectum Diagnostics, 23-38 Hythe Bridge Street, Oxford OX1 2ET, UK
| | - Rajarshi Banerjee
- Perspectum Diagnostics, 23-38 Hythe Bridge Street, Oxford OX1 2ET, UK; Oxford University Hospitals NHS Foundation Trust, Headley Way, Headington, Oxford OX3 9DU, UK
| | - Nicola Guess
- King's College London, 150 Stamford Street, London SE1 9NH, UK; University of Westminster, 101 New Cavendish St, Fitzrovia, London W1W 6XH, United Kingdom
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Plaz Torres MC, Aghemo A, Lleo A, Bodini G, Furnari M, Marabotto E, Miele L, Giannini EG. Mediterranean Diet and NAFLD: What We Know and Questions That Still Need to Be Answered. Nutrients 2019; 11:2971. [PMID: 31817398 PMCID: PMC6949938 DOI: 10.3390/nu11122971] [Citation(s) in RCA: 66] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 11/28/2019] [Accepted: 11/30/2019] [Indexed: 12/16/2022] Open
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 (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.
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Affiliation(s)
- Maria Corina Plaz Torres
- Cattedra di Gastroenterologia, Dipartimento di Medicina Interna, Università degli Studi di Genova, 16132 Genova, Italy
- Programma Dipartimentale Diagnosi e Terapia delle Malattie Emergenti dell’Apparato Digerente, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy
- Divisione di Medicine Interna ed Epatologia, Humanitas Clinical and Research Center-IRCCS, 20089 Rozzano, Italy
| | - Alessio Aghemo
- Divisione di Medicine Interna ed Epatologia, Humanitas Clinical and Research Center-IRCCS, 20089 Rozzano, Italy
- Dipartimento di Scienze Biomediche, Humanitas University, 20090 Pieve Emanuele, Italy
| | - Ana Lleo
- Divisione di Medicine Interna ed Epatologia, Humanitas Clinical and Research Center-IRCCS, 20089 Rozzano, Italy
- Dipartimento di Scienze Biomediche, Humanitas University, 20090 Pieve Emanuele, Italy
| | - Giorgia Bodini
- Cattedra di Gastroenterologia, Dipartimento di Medicina Interna, Università degli Studi di Genova, 16132 Genova, Italy
- Programma Dipartimentale Diagnosi e Terapia delle Malattie Emergenti dell’Apparato Digerente, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy
- Divisione di Medicine Interna ed Epatologia, Humanitas Clinical and Research Center-IRCCS, 20089 Rozzano, Italy
| | - Manuele Furnari
- Cattedra di Gastroenterologia, Dipartimento di Medicina Interna, Università degli Studi di Genova, 16132 Genova, Italy
| | - Elisa Marabotto
- Cattedra di Gastroenterologia, Dipartimento di Medicina Interna, Università degli Studi di Genova, 16132 Genova, Italy
| | - Luca Miele
- Area Medicina Interna, Gastroenterologia e Medicina Interna, Fondazione Policlinico Gemelli IRCCS, Università Cattolica del Sacro Cuore, 20123 Roma, Italy
| | - Edoardo G. Giannini
- Cattedra di Gastroenterologia, Dipartimento di Medicina Interna, Università degli Studi di Genova, 16132 Genova, Italy
- Programma Dipartimentale Diagnosi e Terapia delle Malattie Emergenti dell’Apparato Digerente, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Viale Benedetto XV, no.6, 16132 Genoa, Italy
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Vergani L. Fatty Acids and Effects on In Vitro and In Vivo Models of Liver Steatosis. Curr Med Chem 2019; 26:3439-3456. [PMID: 28521680 DOI: 10.2174/0929867324666170518101334] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2016] [Revised: 03/14/2017] [Accepted: 03/14/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Fatty liver, or steatosis, is a condition of excess accumulation of lipids, mainly under form of triglycerides (TG), in the liver, and it is the hallmark of non-alcoholic fatty liver disease (NAFLD). NAFLD is the most common liver disorder world-wide and it has frequently been associated with obesity, hyperlipidemia and insulin resistance. Free fatty acids (FA) are the major mediators of hepatic steatosis; patients with NAFLD have elevated levels of circulating FA that correlate with disease severity. METHODS Steatosis is a reversible condition that can be resolved with changed behaviors, or that can progress towards more severe liver damages such as steatohepatitis (NASH), fibrosis and cirrhosis. In NAFLD, FA of exogenous or endogenous origin accumulate in the hepatocytes and trigger liver damages. Excess TG are stored in cytosolic lipid droplets (LDs) that are dynamic organelles acting as hubs for lipid metabolism. RESULTS In the first part of this review, we briefly reassumed the main classes of FA and their chemical classification as a function of the presence and number of double bonds, their metabolic pathways and effects on human health. Then, we summarized the main genetic and diet-induced animal models of NAFLD, as well as the cellular models of NAFLD. CONCLUSIONS In recent years, both the diet-induced animal models of NAFLD as well as the cellular models of NAFLD have found ever more application to investigate the mechanisms involved in NAFLD, and we referred to their advantages and disadvantages.
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Affiliation(s)
- Laura Vergani
- DISTAV, Department of Earth, Environment and Life Sciences, University of Genova, Italy
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Duarte SMB, Stefano JT, Vanni DS, Carrilho FJ, Oliveira CPMSD. IMPACT OF CURRENT DIET AT THE RISK OF NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD). ARQUIVOS DE GASTROENTEROLOGIA 2019; 56:431-439. [PMID: 31721969 DOI: 10.1590/s0004-2803.201900000-67] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 09/24/2019] [Indexed: 12/15/2022]
Abstract
The nonalcoholic fatty liver disease (NAFLD) affects approximately 20%-30% of general population and is even more prevalent among obese individuals. The risk factors mainly associated with NAFLD are diseases related to the metabolic syndrome, genetics and environment. In this review, we provide a literature compilation evaluating the evidence behind dietary components, including calories intake, fat, protein, fibers and carbohydrate, especially fructose which could be a trigger to development and progression of the NAFLD. In fact, it has been demonstrated that diet is an important factor for the development of NAFLD and its association is complex and extends beyond total energy intake.
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Affiliation(s)
| | - José Tadeu Stefano
- Universidade de São Paulo, Hospital das Clínicas, Laboratório de Gastroenterologia Clínica e Experimental (LIM-07) do Departamento de Gastroenterologia da FMUSP, São Paulo, SP, Brasil
| | - Denise Siqueira Vanni
- Universidade de São Paulo, Hospital das Clínicas, Divisão de Gastroenterologia e Hepatologia Clínica e Departamento de Gastroenterologia da FMUSP, São Paulo, SP, Brasil
| | - Flair José Carrilho
- Universidade de São Paulo, Faculdade de Medicina, São Paulo, SP, Brasil
- Universidade de São Paulo, Hospital das Clínicas, Divisão de Gastroenterologia e Hepatologia Clínica e Departamento de Gastroenterologia da FMUSP, São Paulo, SP, Brasil
| | - Claudia Pinto Marques Souza de Oliveira
- Universidade de São Paulo, Faculdade de Medicina, São Paulo, SP, Brasil
- Universidade de São Paulo, Hospital das Clínicas, Laboratório de Gastroenterologia Clínica e Experimental (LIM-07) do Departamento de Gastroenterologia da FMUSP, São Paulo, SP, Brasil
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Gajdošík M, Hingerl L, Škoch A, Freudenthaler A, Krumpolec P, Ukropec J, Ukropcová B, Šedivý P, Hájek M, Itariu BK, Maier B, Baumgartner‐Parzer S, Krebs M, Trattnig S, Krššák M. Ultralong TE In Vivo 1 H MR Spectroscopy of Omega-3 Fatty Acids in Subcutaneous Adipose Tissue at 7 T. J Magn Reson Imaging 2019; 50:71-82. [PMID: 30578581 PMCID: PMC6618283 DOI: 10.1002/jmri.26605] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Revised: 11/27/2018] [Accepted: 11/28/2018] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Omega-3 (n-3) fatty acids (FA) play and important role in neural development and other metabolic diseases such as obesity and diabetes. The knowledge about the in vivo content and distribution of n-3 FA in human body tissues is not well established and the standard quantification of FA is invasive and costly. PURPOSE To detect omega-3 (n-3 CH3 ) and non-omega-3 (CH3 ) methyl group resonance lines with echo times up to 1200 msec, in oils, for the assessment of n-3 FA content, and the n-3 FA fraction in adipose tissue in vivo. STUDY TYPE Prospective technical development. POPULATION Three oils with different n-3 FA content and 24 healthy subjects. FIELD STRENGTH/SEQUENCE Single-voxel MR spectroscopy (SVS) with a point-resolved spectroscopy (PRESS) sequence with an echo time (TE) of 1000 msec at 7 T. ASSESSMENT Knowledge about the J-coupling evolution of both CH3 resonances was used for the optimal detection of the n-3 CH3 resonance line at a TE of 1000 msec. The accuracy of the method in oils and in vivo was validated from a biopsy sample with gas chromatography analysis. STATISTICAL TESTS SVS data were compared to gas chromatography with the Pearson correlation coefficient. RESULTS T2 relaxation times in oils were assessed as follows: CH2 , 65 ± 22 msec; CH3 , 325 ± 7 msec; and n-3 CH3 , 628 ± 34 msec. The n-3 FA fractions from oil phantom experiments (n = 3) were in agreement with chromatography analysis and the comparison of in vivo obtained data with the results of chromatography analysis (n = 5) yielded a significant correlation (P = 0.029). DATA CONCLUSION PRESS with ultralong-TE can detect and quantify the n-3 CH3 signal in vivo at 7 T. LEVEL OF EVIDENCE 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:71-82.
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Affiliation(s)
- Martin Gajdošík
- High‐field MR Centre, Department of Biomedical Imaging and Image‐guided TherapyMedical University of ViennaViennaAustria
- Division of Endocrinology and Metabolism, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
- Bernard and Irene Schwartz Center for Biomedical Imaging, Department of RadiologyNew York University School of MedicineNew YorkNew York
| | - Lukas Hingerl
- High‐field MR Centre, Department of Biomedical Imaging and Image‐guided TherapyMedical University of ViennaViennaAustria
| | - Antonín Škoch
- National Institute of Mental HealthKlecanyCzech Republic
- MR Unit, Department of Diagnostic and Interventional RadiologyInstitute for Clinical and Experimental MedicinePragueCzech Republic
| | - Angelika Freudenthaler
- Division of Endocrinology and Metabolism, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Patrik Krumpolec
- High‐field MR Centre, Department of Biomedical Imaging and Image‐guided TherapyMedical University of ViennaViennaAustria
- Institute of Experimental EndocrinologyBiomedical Research Center, Slovak Academy of SciencesBratislavaSlovakia
| | - Jozef Ukropec
- Institute of Experimental EndocrinologyBiomedical Research Center, Slovak Academy of SciencesBratislavaSlovakia
| | - Barbara Ukropcová
- Institute of Experimental EndocrinologyBiomedical Research Center, Slovak Academy of SciencesBratislavaSlovakia
| | - Petr Šedivý
- MR Unit, Department of Diagnostic and Interventional RadiologyInstitute for Clinical and Experimental MedicinePragueCzech Republic
| | - Milan Hájek
- MR Unit, Department of Diagnostic and Interventional RadiologyInstitute for Clinical and Experimental MedicinePragueCzech Republic
| | - Bianca K. Itariu
- Division of Endocrinology and Metabolism, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Bernhard Maier
- University Clinic for Trauma Surgery, Medical University of ViennaViennaAustria
| | - Sabina Baumgartner‐Parzer
- Division of Endocrinology and Metabolism, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Michael Krebs
- Division of Endocrinology and Metabolism, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Siegfried Trattnig
- High‐field MR Centre, Department of Biomedical Imaging and Image‐guided TherapyMedical University of ViennaViennaAustria
- Christian Doppler Laboratory for Clinical Molecular MR ImagingViennaAustria
| | - Martin Krššák
- High‐field MR Centre, Department of Biomedical Imaging and Image‐guided TherapyMedical University of ViennaViennaAustria
- Division of Endocrinology and Metabolism, Department of Internal Medicine IIIMedical University of ViennaViennaAustria
- Christian Doppler Laboratory for Clinical Molecular MR ImagingViennaAustria
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Liu Y, Li Q, Wang H, Zhao X, Li N, Zhang H, Chen G, Liu Z. Fish oil alleviates circadian bile composition dysregulation in male mice with NAFLD. J Nutr Biochem 2019; 69:53-62. [PMID: 31055233 DOI: 10.1016/j.jnutbio.2019.03.005] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 02/22/2019] [Accepted: 03/12/2019] [Indexed: 02/07/2023]
Abstract
Our previous studies have found that fish oil rich in ω-3 polyunsaturated fatty acids (ω-3 PUFA) protects against non-alcoholic fatty liver disease (NAFLD) in mice. This study was aimed to explore the effects of fish oil on high fat diet (HFD)-induced circadian bile composition chaos. Male C57BL/6 mice were randomly divided into three groups, a control group (CON), a HFD group and a fish oil (FO) group, which were fed a normal chow diet, a HFD, and a HFD supplemented with FO, respectively for 12 weeks. At the end of the experiment, liver tissue, blood and bile samples were processed at 12-h intervals with the first one at zeitgeber time 0 (ZT0) and the second at zeitgeber time 12 (ZT12). Metabolites in bile were determined using UPLC-QTOF-MS, screened using multivariate statistical analysis, and analyzed using KEGG database and Metaboanalyst. The expression levels of key proteins in bile acid metabolism were examined using western blot. Results of biochemical analysis and H&E staining illustrated that feeding of HFD induced NAFLD, which was ameliorated in FO group. The bile content of each group at ZT0 (CON, HFD, or FO group) was respectively higher than that at ZT12 (P<.05). The metabolic pathway analysis of differential metabolites showed that these differences were correlated with amino acid metabolism, fatty acid biosynthesis and primary bile acid synthesis at ZT0. FO supplement could modify bile composition, which was related to the influence of its ω-3 PUFA on liver metabolism. ω-3 PUFA may also regulate the circadian rhythm of bile metabolism.
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Affiliation(s)
- Yang Liu
- Hubei Province Engineering Research Center of Healthy Food, School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan 430023, China
| | - Qi Li
- Hubei Province Engineering Research Center of Healthy Food, School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan 430023, China
| | - Hualin Wang
- Hubei Province Engineering Research Center of Healthy Food, School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan 430023, China.
| | - Xiuju Zhao
- Hubei Province Engineering Research Center of Healthy Food, School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan 430023, China
| | - Na Li
- Hubei Province Engineering Research Center of Healthy Food, School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan 430023, China
| | - Hongyu Zhang
- Hubei Province Engineering Research Center of Healthy Food, School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan 430023, China
| | - Guoxun Chen
- Department of Nutrition, University of Tennessee at Knoxville, Knoxville, TN, United States
| | - Zhiguo Liu
- Hubei Province Engineering Research Center of Healthy Food, School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan 430023, China.
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Zhou J, Ho CT, Long P, Meng Q, Zhang L, Wan X. Preventive Efficiency of Green Tea and Its Components on Nonalcoholic Fatty Liver Disease. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2019; 67:5306-5317. [PMID: 30892882 DOI: 10.1021/acs.jafc.8b05032] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a typical chronic liver disease highly correlated with metabolic syndrome. Growing prevalence of NAFLD is supposed to be linked with the unhealthy lifestyle, especially high-calorie diet and lacking enough exercise. Currently, there is no validated pharmacological therapy for NAFLD except for weight reduction. However, many dietary strategies had preventive effects on the development of liver steatosis or its progression. As one of the most common beverages, green tea contains abundant bioactive compounds possessing antioxidant, lipid-lowering, and anti-inflammatory effects, as well as improving insulin resistance and gut dysbiosis that can alleviate the risk of NAFLD. Hence, in this review, we summarized the studies of green tea and its components on NAFLD from animal experiments and human interventions and discussed the potential mechanisms. Available evidence suggested that tea consumption is promising to prevent NAFLD, and further mechanisms and clinical studies need to be investigated.
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Affiliation(s)
| | - Chi-Tang Ho
- Department of Food Science , Rutgers University , New Brunswick , New Jersey , United States
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35
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Effect of Fish Oil Supplementation on Hepatic and Visceral Fat in Overweight Men: A Randomized Controlled Trial. Nutrients 2019; 11:nu11020475. [PMID: 30813440 PMCID: PMC6413081 DOI: 10.3390/nu11020475] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 02/12/2019] [Accepted: 02/20/2019] [Indexed: 12/16/2022] Open
Abstract
Being overweight increases the risk of the development of metabolic conditions such as non-alcoholic fatty liver disease (NAFLD), which is itself an independent predictor of cardiovascular disease. Omega-3 polyunsaturated fatty acid (PUFA) supplementation is recommended for prevention of chronic disease, and is thought to reduce raised liver fat, yet there have been few randomized controlled trials with accurate measurement of liver fat. We assessed the effect of 12 weeks of supplementation with omega-3 PUFA from fish oil versus placebo on quantified liver fat, liver tests, and body composition including visceral adipose tissue (VAT) in a double-blind randomized controlled trial. Fifty apparently healthy overweight men (BMI 25.0–29.9 kg/m2; waist > 94 cm) were randomly allocated to consume fish oil (total daily dose: 1728 mg marine triglycerides, of which 588 mg EPA and 412 mg DHA, combined with 200 mg antioxidant, coenzyme Q10) or placebo (olive oil capsules) daily for 12 weeks. Liver fat was assessed using proton magnetic resonance spectroscopy. All outcomes were assessed at baseline and following 6 and 12 weeks of supplementation. Baseline liver fat was 4.6 ± 0.5% (range: 0.6 to 18.2%); 16 (32%) participants met the criteria for NAFLD (>5.5% liver fat). Repeated measures ANOVA revealed no significant time or group × time effect for fish oil versus placebo for liver fat, liver enzymes, anthropometry, or body composition including VAT (p > 0.05 for all), with similar finding for sub-analysis of participants with NAFLD. Omega-3 PUFA did not appear to be an effective agent for reducing liver fat in overweight men. The factors determining the health benefits of omega-3 PUFA supplementation on an individual level need to be clarified.
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36
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Bernal-Reyes R, Castro-Narro G, Malé-Velázquez R, Carmona-Sánchez R, González-Huezo MS, García-Juárez I, Chávez-Tapia N, Aguilar-Salinas C, Aiza-Haddad I, Ballesteros-Amozurrutia MA, Bosques-Padilla F, Castillo-Barradas M, Chávez-Barrera JA, Cisneros-Garza L, Flores-Calderón J, García-Compeán D, Gutiérrez-Grobe Y, Higuera de la Tijera MF, Kershenobich-Stalnikowitz D, Ladrón de Guevara-Cetina L, Lizardi-Cervera J, López-Cossio JA, Martínez-Vázquez S, Márquez-Guillén E, Méndez-Sánchez N, Moreno-Alcantar R, Poo-Ramírez JL, Ramos-Martínez P, Rodríguez-Hernández H, Sánchez-Ávila JF, Stoopen-Rometti M, Torre-Delgadillo A, Torres-Villalobos G, Trejo-Estrada R, Uribe-Esquivel M, Velarde-Ruiz Velasco JA. The Mexican consensus on nonalcoholic fatty liver disease. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2019; 84:69-99. [PMID: 30711302 DOI: 10.1016/j.rgmx.2018.11.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Revised: 11/06/2018] [Accepted: 11/20/2018] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) affects nearly one third of the population worldwide. Mexico is one of the countries whose population has several risk factors for the disease and its prevalence could surpass 50%. If immediate action is not taken to counteract what is now considered a national health problem, the medium-term panorama will be very bleak. This serious situation prompted the Asociación Mexicana de Gastroenterología and the Asociación Mexicana de Hepatología to produce the Mexican Consensus on Fatty Liver Disease. It is an up-to-date and detailed review of the epidemiology, pathophysiology, clinical forms, diagnosis, and treatment of the disease, whose aim is to provide the Mexican physician with a useful tool for the prevention and management of nonalcoholic fatty liver disease.
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Affiliation(s)
- R Bernal-Reyes
- Sociedad Española de Beneficencia, Pachuca, Hidalgo, México.
| | - G Castro-Narro
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - R Malé-Velázquez
- Instituto de Salud Digestiva y Hepática SA de CV, Guadalajara, Jalisco, México
| | | | - M S González-Huezo
- Servicio de Gastroenterología y Endoscopia GI, ISSSEMYM, Metepec, Estado de México, México
| | - I García-Juárez
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - N Chávez-Tapia
- Servicio de Gastroenterología, Fundación Clínica Médica Sur, Ciudad de México, México
| | - C Aguilar-Salinas
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - I Aiza-Haddad
- Clínica de enfermedades hepáticas, Hospital Ángeles Lómas, Ciudad de México, México
| | | | | | - M Castillo-Barradas
- Servicio de Gastroenterología, Hospital de Especialidades, Centro Médico La Raza IMSS, Ciudad de México, México
| | - J A Chávez-Barrera
- Servicio de Gastroenterología Pediátrica, Hospital General, Centro Médico La Raza, IMSS, Ciudad de México, México
| | - L Cisneros-Garza
- Servicio de Gastroenterología, Hospital Universitario de la UANL, Monterrey, Nuevo León, México
| | - J Flores-Calderón
- Servicio de Gastroenterología, Hospital de Pediatría, Centro Médico Siglo XXI, IMSS, Ciudad de México, México
| | - D García-Compeán
- Servicio de Gastroenterología, Hospital Universitario de la UANL, Monterrey, Nuevo León, México
| | - Y Gutiérrez-Grobe
- Servicio de Gastroenterología, Fundación Clínica Médica Sur, Ciudad de México, México
| | | | | | | | - J Lizardi-Cervera
- Servicio de Gastroenterología, Fundación Clínica Médica Sur, Ciudad de México, México
| | - J A López-Cossio
- Servicio de Gastroenterología y Endoscopia GI, ISSSEMYM, Metepec, Estado de México, México
| | - S Martínez-Vázquez
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - E Márquez-Guillén
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - N Méndez-Sánchez
- Servicio de Gastroenterología, Fundación Clínica Médica Sur, Ciudad de México, México
| | - R Moreno-Alcantar
- Servicio de Gastroenterología, Hospital de Especialidades Centro Médico Siglo XXI, IMSS, Ciudad de México, México
| | - J L Poo-Ramírez
- Centro de Innovación y Educación Ejecutiva, Tec de Monterrey, Ciudad de México, México
| | | | - H Rodríguez-Hernández
- Unidad de Investigación Biomédica AMCCI, Hospital de Especialidades, Durango, México
| | - J F Sánchez-Ávila
- Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, Nuevo León, México
| | - M Stoopen-Rometti
- Centro de Diagnóstico CT-Scanner Lomas Altas, Ciudad de México, México
| | - A Torre-Delgadillo
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - G Torres-Villalobos
- Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | | | - M Uribe-Esquivel
- Servicio de Gastroenterología, Fundación Clínica Médica Sur, Ciudad de México, México
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Bernal-Reyes R, Castro-Narro G, Malé-Velázquez R, Carmona-Sánchez R, González-Huezo M, García-Juárez I, Chávez-Tapia N, Aguilar-Salinas C, Aiza-Haddad I, Ballesteros-Amozurrutia M, Bosques-Padilla F, Castillo-Barradas M, Chávez-Barrera J, Cisneros-Garza L, Flores-Calderón J, García-Compeán D, Gutiérrez-Grobe Y, Higuera de la Tijera M, Kershenobich-Stalnikowitz D, Ladrón de Guevara-Cetina L, Lizardi-Cervera J, López-Cossio J, Martínez-Vázquez S, Márquez-Guillén E, Méndez-Sánchez N, Moreno-Alcantar R, Poo-Ramírez J, Ramos-Martínez P, Rodríguez-Hernández H, Sánchez-Ávila J, Stoopen-Rometti M, Torre-Delgadillo A, Torres-Villalobos G, Trejo-Estrada R, Uribe-Esquivel M, Velarde-Ruiz Velasco J. The Mexican consensus on nonalcoholic fatty liver disease. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO (ENGLISH EDITION) 2019. [DOI: 10.1016/j.rgmxen.2019.02.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
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Kozaczek M, Bottje W, Greene E, Lassiter K, Kong B, Dridi S, Korourian S, Hakkak R. Comparison of liver gene expression by RNAseq and PCR analysis after 8 weeks of feeding soy protein isolate- or casein-based diets in an obese liver steatosis rat model. Food Funct 2019; 10:8218-8229. [DOI: 10.1039/c9fo01387c] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Differential expression of genes provides insight into fundamental mechanisms associated with the ability of soy protein isolate to attenuate liver steatosis in genetically obese rats.
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Affiliation(s)
- Melisa Kozaczek
- Department of Poultry Science & The Center of Excellence for Poultry Science
- University of Arkansas
- Fayetteville
- USA
| | - Walter Bottje
- Department of Poultry Science & The Center of Excellence for Poultry Science
- University of Arkansas
- Fayetteville
- USA
| | - Elizabeth Greene
- Department of Poultry Science & The Center of Excellence for Poultry Science
- University of Arkansas
- Fayetteville
- USA
| | - Kentu Lassiter
- Department of Poultry Science & The Center of Excellence for Poultry Science
- University of Arkansas
- Fayetteville
- USA
| | - Byungwhi Kong
- Department of Poultry Science & The Center of Excellence for Poultry Science
- University of Arkansas
- Fayetteville
- USA
| | - Sami Dridi
- Department of Poultry Science & The Center of Excellence for Poultry Science
- University of Arkansas
- Fayetteville
- USA
| | - Soheila Korourian
- Department of Pathology
- University of Arkansas for Medical Sciences
- Little Rock
- USA
| | - Reza Hakkak
- Department of Dietetics and Nutrition
- University of Arkansas for Medical Sciences
- Little Rock
- USA
- Department of Pediatrics
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Abstract
Nonalcoholic Fatty Liver Disease (NAFLD) is the most common cause of chronic liver disease in the United States. The NAFLD subtype, nonalcoholic steatohepatitis, represents a progressive form of the disease that can lead to cirrhosis, portal hypertension, and hepatocellular carcinoma. NAFLD is a diagnosis of exclusion and is strongly related to obesity and the metabolic syndrome. Although there has been an explosion of exciting therapeutic avenues for NAFLD in recent years, the bedrock of management continues to be lifestyle modification, weight loss, and optimization of metabolic risk factors.
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Affiliation(s)
- Khurram Mazhar
- Department of Internal Medicine, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, North Texas VA Health Care System, Dallas VA Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9030, USA; Division of Gastroenterology, North Texas VA Health Care System, Dallas VA Medical Center, 111B1, 4500 South Lancaster Road, Dallas, TX 75216, USA.
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Srivastava RAK. Life-style-induced metabolic derangement and epigenetic changes promote diabetes and oxidative stress leading to NASH and atherosclerosis severity. J Diabetes Metab Disord 2018; 17:381-391. [PMID: 30918873 DOI: 10.1007/s40200-018-0378-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Accepted: 11/20/2018] [Indexed: 12/15/2022]
Abstract
Energy imbalance resulting from high calorie food intake and insufficient metabolic activity leads to increased body mass index (BMI) and sets the stage for metabolic derangement influencing lipid and carbohydrate metabolism and ultimately leading to insulin resistance, dyslipidemia, and type 2 diabetes. 70% of cardiovascular disease (CVD) deaths occur in patients with diabetes. Environment-induced physiological perturbations trigger epigenetic changes through chromatin modification and leads to type 2 diabetes and progression of nonalcoholic fatty liver disease (NAFLD) and CVD. Thus, in terms of disease progression and pathogenesis, energy homeostasis, metabolic dysregulation, diabetes, fatty liver, and CVD are interlinked. Since advanced glycation end products (AGEs) and low-grade inflammation in type 2 diabetes play definitive roles in the pathogenesis of liver and vascular diseases, a natural checkpoint to prevent diabetes and associated complications appears to be the identification and management of prediabetes together with weight management, since 70% of prediabetic individuals develop diabetes during their life time, and every kg of weight increase is associated with up to 9% increase in diabetes risk. A good proportion of diabetes and obesity population have fatty liver that progresses to non-alcoholic steatohepatitis (NASH) and cirrhosis, and increased risk of hepatocellular carcinoma. Diabetes and NASH both have elevated oxidative stress, impaired cholesterol elimination, and increased inflammation that leads to CVD risk. This review addresses life-style-induced metabolic pathway derangement and how it contributes to epigenetic changes, type 2 diabetes and NASH progression, which collectively lead to increased risk of CVD.
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Affiliation(s)
- Rai Ajit K Srivastava
- Integrated Pharma Solutions, Philadelphia, PA USA.,2Department of Nutrition, Wayne State University, Detroit, MI USA
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41
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In a pilot study, reduced fatty acid desaturase 1 function was associated with nonalcoholic fatty liver disease and response to treatment in children. Pediatr Res 2018; 84:696-703. [PMID: 30120404 PMCID: PMC6726123 DOI: 10.1038/s41390-018-0132-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2017] [Revised: 07/09/2018] [Accepted: 07/18/2018] [Indexed: 01/13/2023]
Abstract
BACKGROUND FADS1 gene encodes delta 5 desaturase, a rate-limiting enzyme in the metabolism of n-3 and n-6 polyunsaturated fatty acids (PUFAs). Minor alleles of FADS1 locus polymorphisms are associated with reduced FADS1 expression and intra-hepatic fat accumulation. However, the relationship between FADS1 expression and pediatric nonalcoholic fatty liver disease (NAFLD) risk remains to be explored. METHODS We analyzed FADS1 transcription levels and their association with intra-hepatic fat and histology in children, and we performed pathway enrichment analysis on transcriptomic profiles associated with FADS1 polymorphisms. We also evaluated the weight of FADS1 alleles on the response to combined docosahexaenoic acid, choline, and vitamin E (DHA-CHO-VE) treatment. RESULTS FADS1 mRNA level was significantly and inversely associated with intra-hepatic fat (p = 0.004), degree of steatosis (p = 0.03), fibrosis (p = 0.05), and NASH (p = 0.008) among pediatric livers. Transcriptomics demonstrated a significant enrichment of a number of pathways strongly related to NAFLD (e.g., liver damage, fibrosis, and hepatic stellate cell activation). Compared to children who are common allele homozygotes, children with FADS1 minor alleles had a greater reduction in steatosis, fibrosis, and NAFLD activity score after DHA-CHO-VE. CONCLUSION This study suggests that decreased FADS1 expression may be associated with NAFLD in children but an increased response to DHA-CHO-VE.
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Ye J, Ghosh S. Omega-3 PUFA vs. NSAIDs for Preventing Cardiac Inflammation. Front Cardiovasc Med 2018; 5:146. [PMID: 30406113 PMCID: PMC6205954 DOI: 10.3389/fcvm.2018.00146] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Accepted: 10/01/2018] [Indexed: 12/17/2022] Open
Affiliation(s)
- Jiayu Ye
- Irving K. Barber School of Arts and Sciences (IKBSAS), Department of Biology, University of University of British Columbia, Kelowna, BC, Canada
| | - Sanjoy Ghosh
- Irving K. Barber School of Arts and Sciences (IKBSAS), Department of Biology, University of University of British Columbia, Kelowna, BC, Canada
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Okada LSDRR, Oliveira CP, Stefano JT, Nogueira MA, Silva IDCGD, Cordeiro FB, Alves VAF, Torrinhas RS, Carrilho FJ, Puri P, Waitzberg DL. Omega-3 PUFA modulate lipogenesis, ER stress, and mitochondrial dysfunction markers in NASH - Proteomic and lipidomic insight. Clin Nutr 2018; 37:1474-1484. [PMID: 29249532 DOI: 10.1016/j.clnu.2017.08.031] [Citation(s) in RCA: 66] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2017] [Revised: 08/28/2017] [Accepted: 08/30/2017] [Indexed: 01/18/2023]
Abstract
BACKGROUND & AIMS Currently there is no FDA-approved therapy for nonalcoholic steatohepatitis (NASH). Increased n-6/n-3 polyunsaturated fatty acids (PUFA) ratio can induce endoplasmic reticulum (ER) stress and mitochondrial dysfunction that characterize NASH. Our recent study with n-3 PUFA showed improvement in individual histologic parameters like steatosis, ballooning and lobular inflammation. We hypothesized that n-3 PUFA therapy mediated improvement in histologic parameters is modulated by lipidomic and proteomic changes. METHODS We therefore evaluated hepatic proteomic and plasma lipidomic profiles before and after n-3 PUFA therapy in subjects with NASH. In a double-blind, randomized, placebo-controlled trial, patients with NASH received 6-month treatment with n-3 PUFA (0.945 g/day [64% alpha-linolenic (ALA), 21% eicosapentaenoic (EPA), and 16% docosahexaenoic (DHA) acids]). Paired liver biopsy and plasma collected before and after-n-3 PUFA therapy were assessed using mass spectrometry and gas chromatography for hepatic proteomics and plasma lipidomics. Data were matched to UniProt and LIPID MAPS database, respectively. Cytoscape software was used to analyze functional pathways. Twenty-seven NASH patients with paired liver histology and plasma before and after n-3 PUFA treatment were studied. RESULTS Treatment with n-3 PUFA significantly increased ALA, EPA, and glycerophospholipids, and decreased arachidonic acid (p < 0.05 for all). Further, proteomic markers of cell matrix, lipid metabolism, ER stress and cellular respiratory pathways were also modulated. Interestingly, these alterations reflected functional changes highly suggestive of decreased cellular lipotoxicity potential; reduced ER proteasome degradation of proteins and induction of chaperones; and a shift in cell energy homeostasis towards mitochondrial beta-oxidation. CONCLUSION Six-month treatment with omega-3 PUFAs significantly improved hepatic proteomic and plasma lipidomic markers of lipogenesis, endoplasmic reticulum stress and mitochondrial functions in patients with NASH.
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Affiliation(s)
| | - Claudia P Oliveira
- Department of Gastroenterology (LIM-07/LIM-35), University of Sao Paulo School of Medicine, Sao Paulo, Brazil.
| | - José Tadeu Stefano
- Department of Gastroenterology (LIM-07/LIM-35), University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Monize Aydar Nogueira
- Department of Gastroenterology (LIM-07/LIM-35), University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | | | - Fernanda Bertucce Cordeiro
- Human Reproduction Section, Division of Urology, Department of Surgery, Sao Paulo Federal University, São Paulo, Brazil
| | | | - Raquel Susana Torrinhas
- Department of Gastroenterology (LIM-07/LIM-35), University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Flair José Carrilho
- Department of Gastroenterology (LIM-07/LIM-35), University of Sao Paulo School of Medicine, Sao Paulo, Brazil
| | - Puneet Puri
- Virginia Commonwealth University-VCU, Richmond, VA, USA
| | - Dan L Waitzberg
- Department of Gastroenterology (LIM-07/LIM-35), University of Sao Paulo School of Medicine, Sao Paulo, Brazil.
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Ansari A, Bose S, Patra JK, Shin NR, Lim DW, Kim KW, Wang JH, Kim YM, Chin YW, Kim H. A Controlled Fermented Samjunghwan Herbal Formula Ameliorates Non-alcoholic Hepatosteatosis in HepG2 Cells and OLETF Rats. Front Pharmacol 2018; 9:596. [PMID: 29971000 PMCID: PMC6018163 DOI: 10.3389/fphar.2018.00596] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Accepted: 05/18/2018] [Indexed: 12/19/2022] Open
Abstract
Hepatosteatosis (HS), a clinical feature of fatty liver with the excessive intracellular accumulation of triglyceride in hepatocytes, is manifested by perturbation of the maintenance of liver lipid homeostasis. Samjunghwan (SJH) is an herbal formula used mostly in Korean traditional medicine that is effective against a number of metabolic diseases, including obesity. Herbal drugs, enriched with numerous bioactive substances, possess health-protective benefits. Meanwhile, fermented herbal products enriched with probiotics are known to improve metabolic processes. Additionally, current lines of evidence indicate that probiotics-derived metabolites, termed as postbiotics, produce the same beneficial effects as their precursors. Herein, the anti-HS effects of 5-weeks naturally fermented SJH (FSJH) was investigated with FSJH-mixed chow diet in vivo using Otsuka Long-Evans Tokushima Fatty (OLETF) and Long-Evans Tokushima Otsuka (LETO) rats as animal models of HS and controls, respectively. In parallel, the anti-HS effects of postbiotic-metabolites of three bacterial strains [Lactobacillus brevis (LBB), Lactococcus lactis (LCL) and Lactobacillus plantarum (LBP)] isolated from FSJH were also evaluated in vitro using the FFAs-induced HepG2 cells. Feeding OLETF rats with FSJH-diet effectively reduced body, liver, and visceral adipose tissue (VAT) weights, produced marked hypolipidemic effects on serum and hepatic lipid parameters, decreased serum AST and ALT levels, and upregulated the HMGCOR, SREBP, and ACC, and downregulated the AMPK and LDLR gene expressions levels. Additionally, exposure of FFAs-induced HepG2 cells to postbiotic metabolic media (PMM) of bacterial strains also produced marked hypolipidemic effects on intracellular lipid contents and significantly unregulated the HMGCOR, SREBP, and ACC, and downregulated the AMPK and LDLR genes expressions levels. Overall, our results indicate that FSJH enriched with fermented metabolites could be an effective anti-HS formulation.
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Affiliation(s)
- AbuZar Ansari
- Department of Rehabilitation Medicine of Korean Medicine, Dongguk University, Goyang, South Korea
| | | | - Jayanta Kumar Patra
- Research Institute of Biotechnology and Medical Converged Science, Dongguk University, Goyang, South Korea
| | - Na Rae Shin
- Department of Rehabilitation Medicine of Korean Medicine, Dongguk University, Goyang, South Korea
| | - Dong-Woo Lim
- Department of Pathology, College of Korean Medicine, Dongguk University, Goyang, South Korea
| | - Koh-Woon Kim
- Department of Korean Rehabilitation Medicine, College of Korean Medicine, Kyung Hee University, Seoul, South Korea
| | - Jing-Hua Wang
- Department of Rehabilitation Medicine of Korean Medicine, Dongguk University, Goyang, South Korea
| | - Young-Mi Kim
- College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Goyang, South Korea
| | - Young-Won Chin
- College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Goyang, South Korea
| | - Hojun Kim
- Department of Rehabilitation Medicine of Korean Medicine, Dongguk University, Goyang, South Korea
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Sullivan EM, Pennington ER, Green WD, Beck MA, Brown DA, Shaikh SR. Mechanisms by Which Dietary Fatty Acids Regulate Mitochondrial Structure-Function in Health and Disease. Adv Nutr 2018; 9:247-262. [PMID: 29767698 PMCID: PMC5952932 DOI: 10.1093/advances/nmy007] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2017] [Revised: 01/02/2018] [Accepted: 01/30/2018] [Indexed: 02/06/2023] Open
Abstract
Mitochondria are the energy-producing organelles within a cell. Furthermore, mitochondria have a role in maintaining cellular homeostasis and proper calcium concentrations, building critical components of hormones and other signaling molecules, and controlling apoptosis. Structurally, mitochondria are unique because they have 2 membranes that allow for compartmentalization. The composition and molecular organization of these membranes are crucial to the maintenance and function of mitochondria. In this review, we first present a general overview of mitochondrial membrane biochemistry and biophysics followed by the role of different dietary saturated and unsaturated fatty acids in modulating mitochondrial membrane structure-function. We focus extensively on long-chain n-3 (ω-3) polyunsaturated fatty acids and their underlying mechanisms of action. Finally, we discuss implications of understanding molecular mechanisms by which dietary n-3 fatty acids target mitochondrial structure-function in metabolic diseases such as obesity, cardiac-ischemia reperfusion injury, obesity, type 2 diabetes, nonalcoholic fatty liver disease, and select cancers.
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Affiliation(s)
- E Madison Sullivan
- Department of Biochemistry and Molecular Biology and
- East Carolina Diabetes and Obesity Institute, Brody School of Medicine, East Carolina University, Greenville, NC
| | - Edward Ross Pennington
- Department of Biochemistry and Molecular Biology and
- East Carolina Diabetes and Obesity Institute, Brody School of Medicine, East Carolina University, Greenville, NC
- Department of Nutrition, The University of North Carolina at Chapel Hill, Gillings School of Global Public Health and School of Medicine, Chapel Hill, NC
| | - William D Green
- Department of Nutrition, The University of North Carolina at Chapel Hill, Gillings School of Global Public Health and School of Medicine, Chapel Hill, NC
| | - Melinda A Beck
- Department of Nutrition, The University of North Carolina at Chapel Hill, Gillings School of Global Public Health and School of Medicine, Chapel Hill, NC
| | - David A Brown
- Department of Human Nutrition, Foods, and Exercise, Virginia Tech Corporate Research Center, Blacksburg, VA
| | - Saame Raza Shaikh
- Department of Nutrition, The University of North Carolina at Chapel Hill, Gillings School of Global Public Health and School of Medicine, Chapel Hill, NC
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Vauzour D, Rodriguez-Ramiro I, Rushbrook S, Ipharraguerre IR, Bevan D, Davies S, Tejera N, Mena P, de Pascual-Teresa S, Del Rio D, Gavrilovic J, Minihane AM. n-3 Fatty acids combined with flavan-3-ols prevent steatosis and liver injury in a murine model of NAFLD. Biochim Biophys Acta Mol Basis Dis 2018; 1864:69-78. [DOI: 10.1016/j.bbadis.2017.10.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2017] [Revised: 09/18/2017] [Accepted: 10/02/2017] [Indexed: 02/07/2023]
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Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology 2018; 67:328-357. [PMID: 28714183 DOI: 10.1002/hep.29367] [Citation(s) in RCA: 4874] [Impact Index Per Article: 696.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Accepted: 06/29/2017] [Indexed: 02/06/2023]
Affiliation(s)
| | - Zobair Younossi
- Center for Liver Disease and Department of Medicine, Inova Fairfax Hospital, Falls Church, VA
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A Nutrigenomic Approach to Non-Alcoholic Fatty Liver Disease. Int J Mol Sci 2017; 18:ijms18071534. [PMID: 28714900 PMCID: PMC5536022 DOI: 10.3390/ijms18071534] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Revised: 07/07/2017] [Accepted: 07/13/2017] [Indexed: 02/07/2023] Open
Abstract
Following the epidemics of obesity due to the consumption of high-calorie diet and sedentary lifestyle, nonalcoholic fatty liver disease (NAFLD) is now the leading cause of liver disease in Western countries. NAFLD is epidemiologically associated with metabolic syndrome and insulin resistance, and in susceptible individuals it may progress to cirrhosis and hepatocellular carcinoma. Genetic factors play a key role in NAFLD predisposition by interacting with nutritional and other environmental factors. To date, there is no drug therapy for the treatment of NAFLD, and the main clinical recommendation is lifestyle modification. In the last years, nutrigenomics is promoting an increased understanding of how nutrition affects the switch from health to disease by altering the expression of an individual’s genetic makeup. The present review tries to summarize the most recent data evidencing how the interactions between nutrients and genetic factors can influence NAFLD development. The final goal should be to develop tools to quantify these complex interactions. The definition of a “nutrigenomic risk score” for each individual may represent a novel therapeutic approach for the management of NAFLD patients.
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Carrascosa J, Bonanad C, Dauden E, Botella R, Olveira-Martín A. Psoriasis and Nonalcoholic Fatty Liver Disease. ACTAS DERMO-SIFILIOGRAFICAS 2017. [DOI: 10.1016/j.adengl.2017.05.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Zelber-Sagi S, Salomone F, Mlynarsky L. The Mediterranean dietary pattern as the diet of choice for non-alcoholic fatty liver disease: Evidence and plausible mechanisms. Liver Int 2017; 37:936-949. [PMID: 28371239 DOI: 10.1111/liv.13435] [Citation(s) in RCA: 183] [Impact Index Per Article: 22.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2017] [Accepted: 03/22/2017] [Indexed: 12/11/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) has become a major global health burden, leading to increased risk for cirrhosis, hepatocellular carcinoma, type-2 diabetes and cardiovascular disease. Lifestyle intervention aiming at weight reduction is the most established treatment. However, changing the dietary composition even without weight loss can also reduce steatosis and improve metabolic alterations as insulin resistance and lipid profile. The Mediterranean diet (MD) pattern has been proposed as appropriate for this goal, and was recommended as the diet of choice for the treatment of NAFLD by the EASL-EASD-EASO Clinical Practice Guidelines. The MD has an established superiority in long term weight reduction over low fat diet, but it improves metabolic status and steatosis even without it. However, the effect on liver inflammation and fibrosis was tested only in few observational studies with positive results. Furthermore, considering the strong association between NAFLD and diabetes and CVD, the MD has a highly established advantage in prevention of these diseases, demonstrated in randomized clinical trials. The individual components of the MD such as olive oil, fish, nuts, whole grains, fruits, and vegetables, have been shown to beneficially effect or negatively correlate with NAFLD, while consumption of components that characterize a Western dietary pattern as soft drinks, fructose, meat and saturated fatty acids have been shown to have detrimental association with NAFLD. In this review we will cover the epidemiological evidence and the plausible molecular mechanisms by which the MD as a whole and each of its components can be of benefit in NAFLD.
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Affiliation(s)
- Shira Zelber-Sagi
- School of Public Health, University of Haifa, Haifa, Israel.,Liver Unit, Department of Gastroenterology, Tel Aviv Medical Center, Tel-Aviv, Israel
| | - Federico Salomone
- Division of Gastroenterology, Ospedale di Acireale, Azienda Sanitaria Provinciale di Catania, Catania, Italy
| | - Liat Mlynarsky
- Liver Unit, Department of Gastroenterology, Tel Aviv Medical Center, Tel-Aviv, Israel.,The Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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