|
1
|
Ma MJ, Lin J, Yang HJ, You J. Relationship between iron and lipid peroxidation in ferroptosis and effect of ferroptosis in metabolic dysfunction-associated steatotic liver disease. Shijie Huaren Xiaohua Zazhi 2025; 33:28-36. [DOI: 10.11569/wcjd.v33.i1.28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 12/26/2024] [Accepted: 01/15/2025] [Indexed: 01/25/2025] Open
Abstract
The liver plays an irreplaceable role in human body functions, and liver damage of various causes is a major problem that plagues human health. China is a country with a heavy burden of hepatitis B, but in recent years, the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has shown an increasing trend. Although the mechanism of liver injury caused by MASLD is not completely clear, it is inextricably related to the body's metabolism. MASLD is one of the most common chronic liver diseases and is considered to be a manifestation of metabolic syndrome in the liver. Ferroptosis is a cell death mechanism discovered in recent years, which is characterized by iron metabolism disorders and lipid peroxide accumulation. In recent years, several studies have found that there is an inextricable relationship between ferroptosis and liver disease. This article describes the relationship between iron or iron homeostasis and lipid peroxidation from the perspective of iron metabolism disorders, and the effect of ferroptosis in MASLD.
Collapse
Affiliation(s)
- Meng-Juan Ma
- Institute of Geriatric Medicine, Clinical Research Center for Geriatric Diseases, Department of Geriatric Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
| | - Jie Lin
- Institute of Geriatric Medicine, Clinical Research Center for Geriatric Diseases, Department of Geriatric Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
| | - Hong-Ju Yang
- Institute of Geriatric Medicine, Clinical Research Center for Geriatric Diseases, Department of Geriatric Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
| | - Jing You
- Institute of Geriatric Medicine, Clinical Research Center for Geriatric Diseases, Department of Geriatric Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
| |
Collapse
|
|
2
|
Ma MJ, Lin J, Yang HJ, You J. Relationship between iron and lipid peroxidation in ferroptosis and effect of ferroptosis in metabolic dysfunction-associated steatotic liver disease. Shijie Huaren Xiaohua Zazhi 2025; 33:34-42. [DOI: 10.11569/wcjd.v33.i1.34] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 12/26/2024] [Accepted: 01/15/2025] [Indexed: 01/22/2025] Open
Abstract
The liver plays an irreplaceable role in human body functions, and liver damage of various causes is a major problem that plagues human health. China is a country with a heavy burden of hepatitis B, but in recent years, the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has shown an increasing trend. Although the mechanism of liver injury caused by MASLD is not completely clear, it is inextricably related to the body's metabolism. MASLD is one of the most common chronic liver diseases and is considered to be a manifestation of metabolic syndrome in the liver. Ferroptosis is a cell death mechanism discovered in recent years, which is characterized by iron metabolism disorders and lipid peroxide accumulation. In recent years, several studies have found that there is an inextricable relationship between ferroptosis and liver disease. This article describes the relationship between iron or iron homeostasis and lipid peroxidation from the perspective of iron metabolism disorders, and the effect of ferroptosis in MASLD.
Collapse
Affiliation(s)
- Meng-Juan Ma
- Institute of Geriatric Medicine, Clinical Research Center for Geriatric Diseases, Department of Geriatric Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
| | - Jie Lin
- Institute of Geriatric Medicine, Clinical Research Center for Geriatric Diseases, Department of Geriatric Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
| | - Hong-Ju Yang
- Institute of Geriatric Medicine, Clinical Research Center for Geriatric Diseases, Department of Geriatric Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
| | - Jing You
- Institute of Geriatric Medicine, Clinical Research Center for Geriatric Diseases, Department of Geriatric Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
| |
Collapse
|
|
3
|
Maddie N, Chacko N, Matatov D, Carrillo‐Sepulveda MA. Western diet promotes the progression of metabolic dysfunction-associated steatotic liver disease in association with ferroptosis in male mice. Physiol Rep 2024; 12:e70139. [PMID: 39610053 PMCID: PMC11604596 DOI: 10.14814/phy2.70139] [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: 06/10/2024] [Revised: 10/29/2024] [Accepted: 11/16/2024] [Indexed: 11/30/2024] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD), now referred to as metabolic dysfunction-associated steatotic liver disease (MASLD), is a silent killer that often progresses to metabolic dysfunction-associated steatohepatitis (MASH). To date, there are no pharmacological treatments for MASLD. While obesity is a major cause of the development and progression of MASLD, the underlying mechanisms remain unclear. We hypothesize that ferroptosis, a recently discovered nonapoptotic iron-dependent form of cell death, is activated during the progression of MASLD and may be a potential target for treating MASLD. Using a murine model of Western diet-induced obesity, C57BL/6J male mice were exposed to a long-term (36 weeks) Western diet. Controls were maintained with a standard chow diet. Western diet-induced obesity was confirmed by increased body mass index (BMI). Histopathological analysis demonstrated the progression of MASLD to MASH in the obese group, which was accompanied by significant hepatic iron deposition, oxidative damage, and lipid peroxidation. Hepatic ferroptosis was further confirmed by decreased protein expression of glutathione peroxidase 4 (GPX4) and increased acyl-CoA synthetase long-chain family member 4 (ACSL4), markers of ferroptosis. These findings suggest that ferroptosis is a potential mechanism involved in the pathogenesis of MASLD in male mice.
Collapse
Affiliation(s)
- Nicole Maddie
- Department of Biomedical Sciences, College of Osteopathic MedicineNew York Institute of TechnologyOld WestburyNew YorkUSA
| | - Nefia Chacko
- Department of Biomedical Sciences, College of Osteopathic MedicineNew York Institute of TechnologyOld WestburyNew YorkUSA
| | - David Matatov
- Department of Biomedical Sciences, College of Osteopathic MedicineNew York Institute of TechnologyOld WestburyNew YorkUSA
| | | |
Collapse
|
|
4
|
Feng G, Byrne CD, Targher G, Wang F, Zheng MH. Ferroptosis and metabolic dysfunction-associated fatty liver disease: Is there a link? Liver Int 2022; 42:1496-1502. [PMID: 35007392 DOI: 10.1111/liv.15163] [Citation(s) in RCA: 47] [Impact Index Per Article: 15.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Accepted: 01/04/2022] [Indexed: 12/20/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD), recently re-defined and re-classified as metabolic dysfunction-associated fatty liver disease (MAFLD), has become increasingly prevalent and emerged as a public health problem worldwide. To date, the precise pathogenic mechanisms underpinning MAFLD are not entirely understood, and there is no effective pharmacological therapy for NAFLD/MAFLD. As a newly discovered form of iron-dependent programmed cell death, ferroptosis can be involved in the development and progression of various chronic diseases, but the pathogenic connections and mechanisms that link MAFLD and ferroptosis have not been fully elucidated. The main characteristics of ferroptosis are the accumulation of lipid peroxides and reactive oxygen species. In this brief narrative review, the mechanisms of ferroptosis and its putative pathogenic role in MAFLD are discussed to highlight potential new research directions and ideas for the prevention and treatment of MAFLD.
Collapse
Affiliation(s)
- Gong Feng
- Xi'an Medical University, Xi'an, China
| | - Christopher D Byrne
- Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Fudi Wang
- The Fourth Affiliated Hospital, School of Public Health, Zhejiang University School of Medicine, Hangzhou, China.,The First Affiliated Hospital, Basic Medical Sciences, School of Public Health, Hengyang Medical School, University of South China, Hengyang, China
| | - Ming-Hua Zheng
- NAFLD Research Center, Department of Hepatology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.,Institute of Hepatology, Wenzhou Medical University, Wenzhou, China.,Key Laboratory of Diagnosis and Treatment for The Development of Chronic Liver Disease in Zhejiang Province, Wenzhou, China
| |
Collapse
|
|
5
|
Asghari S, Rezaei M, Rafraf M, Taghizadeh M, Asghari-Jafarabadi M, Ebadi M. Effects of Calorie Restricted Diet on Oxidative/Antioxidative Status Biomarkers and Serum Fibroblast Growth Factor 21 Levels in Nonalcoholic Fatty Liver Disease Patients: A Randomized, Controlled Clinical Trial. Nutrients 2022; 14:nu14122509. [PMID: 35745238 PMCID: PMC9231395 DOI: 10.3390/nu14122509] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 06/11/2022] [Accepted: 06/13/2022] [Indexed: 02/01/2023] Open
Abstract
Oxidative stress plays a fundamental role in the development and progression of nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the effects of a calorie-restricted (CR) diet on oxidative/anti-oxidative status in patients with NAFLD and the potential mediating role of fibroblast growth factor 21 (FGF-21) in this regard. This randomized, controlled clinical trial was carried out on sixty patients with NAFLD aged 20 to 60 years with body mass index (BMI) ranging from 25 to 35 kg/m2. Participants were randomly assigned to either the CR diet group (received a prescribed low-calorie diet for twelve weeks, n = 30) or the control group (n = 30). Fasting blood samples, anthropometric measurements, dietary intake, and physical activity data were collected for all participants at baseline and at the end of the trial. Significant reductions in weight, BMI, waist circumference, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were observed in the CR diet group compared to the control group (all p < 0.05). Liver steatosis grade, serum levels of malondialdehyde (MDA), total antioxidant capacity (TAC), and FGF-21, as well as erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities did not show significant changes in the CR group when compared to the controls at the end of the study (p > 0.05). CR diet with moderate weight loss has some favorable effects on NAFLD but was not able to modify oxidative/anti-oxidative status in these patients. Future studies are warranted to target the effects of long-term interventions with a greater weight loss in this patient population.
Collapse
Affiliation(s)
- Somayyeh Asghari
- Department of Clinical Nutrition, Faculty of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran 141556117, Iran; (S.A.); (M.R.); (M.T.)
| | - Mahsa Rezaei
- Department of Clinical Nutrition, Faculty of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran 141556117, Iran; (S.A.); (M.R.); (M.T.)
| | - Maryam Rafraf
- Nutrition Research Center, Department of Community Nutrition, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz 5166614711, Iran;
| | - Mahdiyeh Taghizadeh
- Department of Clinical Nutrition, Faculty of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran 141556117, Iran; (S.A.); (M.R.); (M.T.)
| | - Mohammad Asghari-Jafarabadi
- Department of Statistics and Epidemiology, Faculty of Health, Tabriz University of Medical Sciences, Tabriz 5166614711, Iran;
- Cabrini Research, Cabrini Health, 154 Wattletree Rd, Malvern, VIC 3144, Australia
| | - Maryam Ebadi
- Division of Gastroenterology & Liver Unit, University of Alberta, Edmonton, AB T6G 2X8, Canada
- Correspondence: ; Tel.: +1-780-248-1892
| |
Collapse
|
|
6
|
Kim A, Krishnan A, Hamilton JP, Woreta TA. The Impact of Dietary Patterns and Nutrition in Nonalcoholic Fatty Liver Disease. Gastroenterol Clin North Am 2021; 50:217-241. [PMID: 33518166 DOI: 10.1016/j.gtc.2020.10.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become one of the most common causes of chronic liver disease worldwide. The prevalence of NAFLD has grown proportionally with the rise in obesity, sedentary lifestyle, unhealthy dietary patterns, and metabolic syndrome. Currently, in the absence of approved pharmacologic treatment, the keystone of treatment is lifestyle modification focused on achieving a weight loss of 7%-10%, cardiovascular exercise, and improving insulin sensitivity. The primary aim of this review is to outline the effect of different dietetic approaches against NAFLD and highlight the important micronutrient components in the management of NAFLD.
Collapse
Affiliation(s)
- Ahyoung Kim
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Arunkumar Krishnan
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - James P Hamilton
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Tinsay A Woreta
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
| |
Collapse
|
|
7
|
Mazidi M, Ofori-Asenso R, Kengne AP. Dietary patterns are associated with likelihood of hepatic steatosis among US adults. J Gastroenterol Hepatol 2020; 35:1916-1922. [PMID: 32335964 DOI: 10.1111/jgh.15076] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 04/13/2020] [Accepted: 04/23/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIM Non-alcoholic fatty liver disease is a rapidly growing public health problem. In this study, we explored the association between dietary patterns (DPs) and fatty liver and liver function tests. METHODS This was a cross-sectional study using data from the US community-based National Health and Nutrition Examination Survey. Participants with data on dietary intake, blood pressure, and status for diabetes mellitus were analyzed. DPs were determined by principal components analysis. Analysis of covariance and logistic regression models accounted for the survey design and sample weights. RESULTS Of the 20 643 eligible participants, 45.7% had prevalent fatty liver. Three DPs collectively explained 50.8% of variance in dietary nutrients consumption. The first DP was representative of a diet containing high levels of saturated and mono-unsaturated fatty acids, total fat and carbohydrate; the second DP comprised vitamins, minerals and dietary fibre; and the third DP was mainly representative of polyunsaturated fatty acids. In adjusted multivariable regression models, participants in the top quarter of the second DP had 34% lower odds of prevalent fatty liver (odds ratio 0.66 [95% confidence interval [CI]: 0.43-0.71]), while those in the top quarter of the first DP had 86% higher odds (1.86 [95% CI: 1.42-2.95]) of prevalent fatty liver, relative to participants in the bottom quarter of each of the DPs. CONCLUSION Our findings suggest that a diet with high load of vitamins, minerals, and fiber content is associated with a lower prevalence of non-alcoholic fatty liver disease.
Collapse
Affiliation(s)
- Mohsen Mazidi
- Department of Twin research and Genetic Epidemiology, King's College London, London, UK
| | - Richard Ofori-Asenso
- Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.,Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Andre Pascal Kengne
- Non-Communicable Disease Research Unit, South African Medical Research Council and University of Cape Town, Cape Town, South Africa
| |
Collapse
|
|
8
|
Thorp A, Stine JG. Exercise as Medicine: The Impact of Exercise Training on Nonalcoholic Fatty Liver Disease. ACTA ACUST UNITED AC 2020; 19:402-411. [PMID: 33767944 DOI: 10.1007/s11901-020-00543-9] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Purpose of review Nonalcoholic fatty liver disease (NAFLD) is a leading cause of global liver disease. Because current pharmacologic treatments are ineffective, lifestyle change centered on exercise remains the most effective NAFLD treatment. The aim of this systematic review is to summarize and evaluate the current evidence supporting the use of exercise training as a medical treatment for adult patients with NAFLD. Recent findings At least 150 minutes each week of moderate intensity exercise of any type can improve NAFLD, both with and without modest weight loss. Exercise training reduces hepatic steatosis and liver inflammation, favorably changes body composition, improves vascular endothelial function, increases cardiorespiratory fitness and can lead to histologic response. To date, exercise-based NAFLD trials are limited by small sample size and significant heterogeneity. Summary While several key questions remain unanswered, exercise training will always be an important part of the medical management of patients with NAFLD.
Collapse
Affiliation(s)
- Audrey Thorp
- Department of Medicine, The Pennsylvania State University- Milton S. Hershey Medical Center, Hershey PA, USA
| | - Jonathan G Stine
- Division of Gastroenterology and Hepatology, Department of Medicine, The Pennsylvania State University- Milton S. Hershey Medical Center, Hershey PA, USA
- Department of Public Health Sciences, The Pennsylvania State University- Milton S. Hershey Medical Center, Hershey PA, USA
- Liver Center, The Pennsylvania State University- Milton S. Hershey Medical Center, Hershey PA, USA
- Cancer Institute, The Pennsylvania State University- Milton S. Hershey Medical Center, Hershey PA, USA
| |
Collapse
|
|
9
|
Dorling JL, Ravussin E, Redman LM, Bhapkar M, Huffman KM, Racette SB, Das SK, Apolzan JW, Kraus WE, Höchsmann C, Martin CK. Effect of 2 years of calorie restriction on liver biomarkers: results from the CALERIE phase 2 randomized controlled trial. Eur J Nutr 2020; 60:1633-1643. [PMID: 32803412 DOI: 10.1007/s00394-020-02361-7] [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] [Received: 05/05/2020] [Accepted: 08/05/2020] [Indexed: 12/18/2022]
Abstract
PURPOSE Calorie restriction (CR) is an effective treatment for obesity-related liver and metabolic disease. However, CR studies in individuals without obesity are needed to see if CR could delay disease onset. Liver biomarkers indicate hepatic health and are linked to cardiometabolic disease. Our aim was to examine the effects of a 2-year CR intervention on liver biomarkers in healthy individuals without obesity. METHODS The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) study was a 2-year randomized controlled trial. Overall, 218 participants (body mass index: 25.1 ± 1.7 kg/m2) were enrolled into a control group (n = 75) that ate ad libitum (AL), or a CR group (n = 143) that aimed to decrease energy intake by 25%. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), and bilirubin were measured during the trial. RESULTS At month 24, relative to the AL group, ALP (- 7 ± 1 IU/L; P < 0.01) and GGT (- 0.11 ± 0.04 log IU/L; P = 0.02) decreased and bilirubin increased (0.21 ± 0.06 log mg/dL; P < 0.01) in the CR group; no between-group differences in ALT (- 1 ± 1 IU/L; P > 0.99) or AST (2 ± 2 IU/L; P = 0.68) were revealed. However, sex-by-treatment-by-time interactions (P < 0.01) were observed, with CR (vs. control) inducing reduced ALT and GGT and increased AST in men only (P ≤ 0.02). CONCLUSIONS In metabolically healthy individuals without obesity, 2 years of CR improves several liver biomarkers, with potentially greater improvements in men. These data suggest that sustained CR may improve long-term liver and metabolic disease risk in healthy adults. TRIAL REGISTRATION Clinicaltrials.gov (NCT00427193). Registered January 2007.
Collapse
Affiliation(s)
- James L Dorling
- Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA, 70808, USA.
| | - Eric Ravussin
- Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA, 70808, USA
| | - Leanne M Redman
- Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA, 70808, USA
| | | | | | | | - Sai K Das
- JM, USDA, Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA
| | - John W Apolzan
- Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA, 70808, USA
| | | | - Christoph Höchsmann
- Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA, 70808, USA
| | - Corby K Martin
- Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA, 70808, USA
| | | |
Collapse
|
|
10
|
Xu J, Sun W, Yang L. Association between iron metabolism and cognitive impairment in older non-alcoholic fatty liver disease individuals: A cross-sectional study in patients from a Chinese center. Medicine (Baltimore) 2019; 98:e18189. [PMID: 31770275 PMCID: PMC6890296 DOI: 10.1097/md.0000000000018189] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Sparse is the research on the relationship between iron metabolism and mild cognitive impairment (MCI) in adults aged over 60 years with non-alcoholic fatty liver disease (NAFLD). The soluble transferrin receptor (sTfR), serum iron (SI), serum ferritin (SF), transferrin (TRF) and hemoglobin (HB) are indicators of iron metabolism.This study examined whether iron metabolism is associated with cognitive impairment in older individuals.A cross-sectional study was held in patients from a Chinese center. Individuals with NAFLD aged over 60 years were included if they did not have excessive alcohol intake and were free of stroke or dementia. Their cognitive function was assessed by the same neurologist. 3.0T H proton magnetic resonance spectroscopy (H-MRS) was performed to evaluate the hippocampus of the participants without contraindication. t test and Chi-square test were used to analyze the data. Binary logistic regression was used for correlation analysis.Fifty four (54%) of participants were diagnosed with MCI by the psychiatrist. MCI was significantly associated with higher sTfR after adjustment of all the covariates (OR = 2.565, 95%CI: 1.334∼4.934; P = .005). No statistically significant associations were observed between MCI and age or blood glucose or choline (Cho) /creatine (Cr) of theright hippocampus head.Increased age and low levels of sTfR and HB were associated with MCI in NAFLD individuals aged over 60 years.
Collapse
Affiliation(s)
- Jing Xu
- Department of Geriatric Gastroenterology, The First Affifiliated Hospital of Nanjing Medical University
- Department of Geriatrics, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Weihao Sun
- Department of Geriatric Gastroenterology, The First Affifiliated Hospital of Nanjing Medical University
| | - Li Yang
- Department of Geriatrics, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| |
Collapse
|
|
11
|
Yang Z, Wu J, Li X, Xie D, Wang Y, Yang T. Association between dietary iron intake and the prevalence of nonalcoholic fatty liver disease: A cross-sectional study. Medicine (Baltimore) 2019; 98:e17613. [PMID: 31651873 PMCID: PMC6824640 DOI: 10.1097/md.0000000000017613] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
Abstract
The aim was to test the association between dietary iron intake and the prevalence of nonalcoholic fatty liver disease (NAFLD) in a large sample of middle-aged and elderly Chinese population.The data included in this analysis were collected from a population-based cross-sectional study, that is, the Xiangya Hospital Health Management Center Study. Dietary iron intake was assessed using a validated semiquantitative food frequency questionnaire. The relationship between dietary iron intake and the prevalence of NAFLD was examined using logistic and spline regressions.A cross-sectional study including 5445 subjects was conducted. The prevalence of NAFLD was 36.9%. Compared with the lowest quintile, the energy-adjusted odds ratios (ORs) of NAFLD were 1.33 (95% confidence interval [CI]: 1.07-1.64), 1.80 (95% CI: 1.41-2.29) and 2.11 (95% CI: 1.60-2.80) in the 3rd, 4th, and 5th quintile of iron intake, respectively (P-value for trend <.001). In addition, dietary iron intake was positively associated with the OR of NAFLD in a dose-response relationship manner (test for trend P < .001). However, after stratifying the data by gender, such association only remained in the male, but not in the female population. With adjustment of additional potential confounders, the results did not change materially.Subjects with higher dietary iron intake were subject to a higher prevalence of NAFLD in a dose-response relationship manner. However, such association probably only exists in males, but not in females.
Collapse
Affiliation(s)
- Zidan Yang
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University
| | - Jing Wu
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University
| | - Xiaoxiao Li
- Hunan Key Laboratory of Joint Degeneration and Injury
| | - Dongxing Xie
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yilun Wang
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Tubao Yang
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University
| |
Collapse
|
|
12
|
Mazidi M, Kengne AP. Higher adherence to plant-based diets are associated with lower likelihood of fatty liver. Clin Nutr 2019; 38:1672-1677. [DOI: 10.1016/j.clnu.2018.08.010] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2018] [Revised: 07/24/2018] [Accepted: 08/10/2018] [Indexed: 01/01/2023]
|
|
13
|
Abe N, Tsuchida T, Yasuda SI, Oka K. Dietary iron restriction leads to a reduction in hepatic fibrosis in a rat model of non-alcoholic steatohepatitis. Biol Open 2019; 8:bio.040519. [PMID: 31097447 PMCID: PMC6550076 DOI: 10.1242/bio.040519] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Iron overload in the liver causes oxidative stress and inflammation, which result in organ dysfunction, making it a risk factor for non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma. We aimed to evaluate the effect of dietary iron restriction on disease progression in rats fed a choline-deficient L-amino acid-defined (CDAA) diet. Male F344 rats were fed a choline-sufficient amino acid-defined (control) diet, a CDAA diet or an iron-restricted CDAA diet for 4, 8 and 12 weeks. At each time point, hepatic iron levels, oxidative stress, inflammation and fibrosis were evaluated by immunohistochemistry. The iron-restricted CDAA diet significantly decreased serum iron levels for 12 weeks compared with the CDAA diet. Histological analysis confirmed that feeding with the CDAA diet induced hepatic iron overload and that this was associated with oxidative stress (number of 8-hydroxydeoxyguanosine-positive cells), inflammation (CD68 positive area) and fibrosis (Sirius Red positive area). Iron restriction with the CDAA diet significantly led to a reduction in the hepatic iron levels, oxidative stress, inflammation and fibrosis. Therefore, dietary iron restriction could be a useful therapeutic approach for NASH patients with hepatic iron overload. Summary: We reveal that dietary iron restriction leads to a reduction in hepatic inflammation, oxidative stress and fibrosis in rats fed a choline-deficient L-amino acid-defined (CDAA) diet.
Collapse
Affiliation(s)
- Naomichi Abe
- Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda-shi, Saitama 335-8505, Japan
| | - Takuma Tsuchida
- Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda-shi, Saitama 335-8505, Japan
| | - Shin-Ichiro Yasuda
- Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda-shi, Saitama 335-8505, Japan
| | - Kozo Oka
- Sohyaku. Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda-shi, Saitama 335-8505, Japan
| |
Collapse
|
|
14
|
Kumar R, Teo EK, How CH, Wong TY, Ang TL. A practical clinical approach to liver fibrosis. Singapore Med J 2019; 59:628-633. [PMID: 30631885 DOI: 10.11622/smedj.2018145] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Liver fibrosis is a slow, insidious process involving accumulation of extracellular matrix protein in the liver. The stage of liver fibrosis in chronic liver disease (CLD) determines overall morbidity and mortality; the higher the stage, the worse the prognosis. Noninvasive composite scores can be used to determine whether patients with CLD have significant or advanced fibrosis. Patients with low composite scores can be safely followed up in primary care with periodic reassessment. Those with higher scores should be referred to a specialist. As the epidemic of diabetes mellitus, obesity and non-alcoholic fatty liver diseases is rising, CLD is becoming more prevalent. Easy-to-use fibrosis assessment composite scores can identify patients with minimal or advanced fibrosis, and should be an integral part of decision-making. Patients with cirrhosis, high composite scores, chronic hepatitis B with elevated alanine aminotransferase and aspartate aminotransferase, or deranged liver panel of uncertain aetiology should be referred to a specialist.
Collapse
Affiliation(s)
- Rahul Kumar
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Eng Kiong Teo
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| | - Choon How How
- Care and Health Integration, Changi General Hospital, Singapore.,Family Medicine Academic Clinical Programme, SingHealth Duke-NUS Academic Medical Centre, Singapore
| | - Teck Yee Wong
- Department of Continuing and Community Care, Tan Tock Seng Hospital, Singapore
| | - Tiing Leong Ang
- Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore
| |
Collapse
|
|
15
|
Efficacy of Black Seed (Nigella sativa) and Lemon Balm (Melissa officinalis) on Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Clinical Trial. IRANIAN RED CRESCENT MEDICAL JOURNAL 2018. [DOI: 10.5812/ircmj.59183] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
|
|
16
|
Fischer IP, Irmler M, Meyer CW, Sachs SJ, Neff F, Hrabě de Angelis M, Beckers J, Tschöp MH, Hofmann SM, Ussar S. A history of obesity leaves an inflammatory fingerprint in liver and adipose tissue. Int J Obes (Lond) 2018; 42:507-517. [PMID: 28901330 PMCID: PMC5880583 DOI: 10.1038/ijo.2017.224] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Revised: 07/28/2017] [Accepted: 09/04/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND/OBJECTIVES Dieting is a popular yet often ineffective way to lower body weight, as the majority of people regain most of their pre-dieting weights in a relatively short time. The underlying molecular mechanisms driving weight regain and the increased risk for metabolic disease are still incompletely understood. Here we investigate the molecular alterations inherited from a history of obesity. METHODS In our model, male high-fat diet (HFD)-fed obese C57BL/6J mice were switched to a low caloric chow diet, resulting in a decline of body weight to that of lean mice. We measured body composition, as well as metrics of glucose, insulin and lipid homeostasis. This was accompanied by histological and gene expression analysis of adipose tissue and liver to assess adipose tissue inflammation and hepatosteatosis. Moreover, acute hypothalamic response to (re-) exposure to HFD was assessed by qPCR. RESULTS & CONCLUSIONS Within 7 weeks after diet switch, most obesity-associated phenotypes, such as body mass, glucose intolerance and blood metabolite levels were reversed. However, hepatic inflammation, hepatic steatosis as well as hypertrophy and inflammation of perigonadal, but not subcutaneous, adipocytes persisted in formerly obese mice. Transcriptional profiling of liver and perigonadal fat revealed an upregulation of pathways associated with immune function and cellularity. Thus, we show that weight reduction leaves signs of inflammation in liver and perigonadal fat, indicating that persisting proinflammatory signals in liver and adipose tissue could contribute to an increased risk of formerly obese subjects to develop the metabolic syndrome upon recurring weight gain.
Collapse
Affiliation(s)
- I P Fischer
- JRG Adipocytes and Metabolism, Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Center Munich, Garching, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Division of Metabolic Diseases, Department of Medicine, Technische Universität München, Munich, Germany
| | - M Irmler
- Institute for Experimental Genetics, Helmholtz Zentrum München, München-Neuherberg, Germany
| | - C W Meyer
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Division of Metabolic Diseases, Department of Medicine, Technische Universität München, Munich, Germany
| | - S J Sachs
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Medizinische Klinik und Poliklinik IV der LMU, Munich, Germany
- Institute for Diabetes and Regeneration, Helmholtz Diabetes Center at Helmholtz Zentrum München, Garching, Germany
| | - F Neff
- Institute for Pathology, Helmholtz Zentrum München, München-Neuherberg, Germany
| | - M Hrabě de Angelis
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Institute for Experimental Genetics, Helmholtz Zentrum München, München-Neuherberg, Germany
- Technische Universität München, Lehrstuhl für Experimentelle Genetik, Freising, Germany
| | - J Beckers
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Institute for Experimental Genetics, Helmholtz Zentrum München, München-Neuherberg, Germany
- Technische Universität München, Lehrstuhl für Experimentelle Genetik, Freising, Germany
| | - M H Tschöp
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Division of Metabolic Diseases, Department of Medicine, Technische Universität München, Munich, Germany
- Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum München, Garching, Germany
| | - S M Hofmann
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Medizinische Klinik und Poliklinik IV der LMU, Munich, Germany
- Institute for Diabetes and Regeneration, Helmholtz Diabetes Center at Helmholtz Zentrum München, Garching, Germany
| | - S Ussar
- JRG Adipocytes and Metabolism, Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Center Munich, Garching, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| |
Collapse
|
|
17
|
Romero-Gómez M, Zelber-Sagi S, Trenell M. Treatment of NAFLD with diet, physical activity and exercise. J Hepatol 2017; 67:829-846. [PMID: 28545937 DOI: 10.1016/j.jhep.2017.05.016] [Citation(s) in RCA: 893] [Impact Index Per Article: 111.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2017] [Revised: 05/09/2017] [Accepted: 05/15/2017] [Indexed: 02/06/2023]
Abstract
Lifestyle intervention can be effective when treating non-alcoholic fatty liver diseases (NAFLD) patients. Weight loss decreases cardiovascular and diabetes risk and can also regress liver disease. Weight reductions of ⩾10% can induce a near universal non-alcoholic steatohepatitis resolution and fibrosis improvement by at least one stage. However, modest weight loss (>5%) can also produce important benefits on the components of the NAFLD activity score (NAS). Additionally, we need to explore the role of total calories and type of weight loss diet, micro- and macronutrients, evidence-based benefits of physical activity and exercise and finally support these modifications through established behavioural change models and techniques for long-term maintenance of lifestyle modifications. Following a Mediterranean diet can reduce liver fat even without weight loss and is the most recommended dietary pattern for NAFLD. The Mediterranean diet is characterised by reduced carbohydrate intake, especially sugars and refined carbohydrates (40% of the calories vs. 50-60% in a typical low fat diet), and increased monounsaturated and omega-3 fatty acid intake (40% of the calories as fat vs. up-to 30% in a typical low fat diet). Both TV sitting (a reliable marker of overall sedentary behaviour) and physical activity are associated with cardio-metabolic health, NAFLD and overall mortality. A 'triple hit behavioural phenotype' of: i) sedentary behaviour, ii) low physical activity, and iii) poor diet have been defined. Clinical evidence strongly supports the role of lifestyle modification as a primary therapy for the management of NAFLD and NASH. This should be accompanied by the implementation of strategies to avoid relapse and weight regain.
Collapse
Affiliation(s)
- Manuel Romero-Gómez
- Mac.Ro UCM IC Digestive Diseases and Ciberehd, University Hospital Virgen del Rocio, Institute of Biomedicine of Seville, University of Seville, Sevilla, Spain.
| | - Shira Zelber-Sagi
- Department Gastroenterology, Tel-Aviv Medical Center, Tel-Aviv, Israel; School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel
| | - Michael Trenell
- NIHR Innovation Observatory, Newcastle University, Newcastle, UK
| |
Collapse
|
|
18
|
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing rapidly with the obesity and diabetes mellitus epidemics. It is rapidly becoming the most common cause of liver disease worldwide. NAFLD can progress to serious complications such as cirrhosis, hepatocellular carcinoma and death. Therefore, it is important to recognise this condition so that early intervention can be implemented. Lifestyle modifications and strict control of metabolic risk factors are the mainstay of treatment. As disease progression is slow in the majority of NAFLD patients, most can be managed well by primary care physicians. NAFLD patients with advanced liver fibrosis should be referred to specialist care for further assessment.
Collapse
Affiliation(s)
- Jing Hieng Ngu
- Singapore General Hospital, Singapore.,Duke-NUS Medical School, Singapore
| | | | | | - Roy Soetikno
- Singapore General Hospital, Singapore.,Duke-NUS Medical School, Singapore
| |
Collapse
|
|
19
|
Kenneally S, Sier JH, Moore JB. Efficacy of dietary and physical activity intervention in non-alcoholic fatty liver disease: a systematic review. BMJ Open Gastroenterol 2017; 4:e000139. [PMID: 28761689 PMCID: PMC5508801 DOI: 10.1136/bmjgast-2017-000139] [Citation(s) in RCA: 92] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2017] [Revised: 04/21/2017] [Accepted: 04/27/2017] [Indexed: 12/19/2022] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide, with prevalence above 30% in many adult populations. Strongly associated with obesity, weight loss through diet and physical activity is the mainstay of its management. Weight loss can be difficult to achieve and maintain however, and uncertainty exists as to which lifestyle changes are most effective. Objective The aim of this work was to systematically evaluate randomised controlled trials assessing diet, exercise or combination interventions aimed at reducing steatosis or markers of NAFLD activity. Design Medline, Scopus and Cochrane databases were searched from 1 January 1980 through to 31 July 2016, for intervention trials assessing the effects of diet, weight loss, exercise or any combination thereof, on NAFLD disease markers in human adults. Risk of publication bias and study quality was assessed using the American Dietetic Association Quality Criteria Checklist. Results From a total of 1710 identified records, 24 articles met the inclusion and exclusion criteria; 6 assessed weight loss using dietary restriction, 10 assessed exercise and 8 were combination interventions. While all of the trials demonstrated significant reduction in steatosis and/or markers of NAFLD activity, combination interventions appear to be the most effective at improving NAFLD. Results suggest that 5–10% weight loss using a modestly hypocaloric diet of 500 kcal less per day than calculated energy requirement, in combination with 30–60 min exercise on 3–5 days per week should be recommended. Conclusions We conclude this amount of weight loss is achievable in the trial setting but is challenging in the clinical environment. High-intensity, multidisciplinary intervention in specialist clinics is likely to be required in order to manage NAFLD by lifestyle modification alone. This systematic review protocol was registered prospectively at PROSPERO as CRD42016032764.
Collapse
Affiliation(s)
- Susan Kenneally
- Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK
| | - Joanna H Sier
- School of Food Science and Nutrition, University of Leeds, Leeds, West Yorkshire, UK
| | - J Bernadette Moore
- Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK.,School of Food Science and Nutrition, University of Leeds, Leeds, West Yorkshire, UK
| |
Collapse
|
|
20
|
Katsagoni CN, Georgoulis M, Papatheodoridis GV, Panagiotakos DB, Kontogianni MD. Effects of lifestyle interventions on clinical characteristics of patients with non-alcoholic fatty liver disease: A meta-analysis. Metabolism 2017; 68:119-132. [PMID: 28183444 DOI: 10.1016/j.metabol.2016.12.006] [Citation(s) in RCA: 192] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2016] [Revised: 12/05/2016] [Accepted: 12/07/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND/OBJECTIVES Although lifestyle modifications remain the cornerstone therapy for non-alcoholic fatty liver disease (NAFLD), the optimal lifestyle intervention is still controversial. The aim of this meta-analysis was to evaluate the effect of exercise and/or dietary interventions, type or intensity of exercise and type of diet, on liver function outcomes (liver enzymes, intrahepatic fat and liver histology), as well as on anthropometric and glucose metabolism parameters in NAFLD patients. SUBJECTS/METHODS Literature search was performed in Scopus and US National Library of Medicine databases to identify all randomized controlled clinical trials (RCTs) in adult patients with NAFLD, diagnosed through imaging techniques or liver biopsy, published in English between January 2005 and August 2016. Studies' quality was evaluated using the Cochrane Risk of Bias Tool. Heterogeneity was tested using the Cochran's Q test and measured inconsistency by I2. Effect size was calculated as the standardized mean difference (SMD). The meta-analysis was performed in accordance with PRISMA guidelines. RESULTS Twenty RCTs with 1073 NAFLD patients were included. Compared to standard care, exercise improved serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (all P<0.05). Ιntrahepatic fat also improved, irrespectively of weight change (SMD=-0.98, 95% CI: -1.30 to -0.66). Regarding the type of exercise, aerobic compared to resistance exercise did not yield any superior improvements on liver parameters, whereas moderate-to-high volume moderate-intensity continuous training was more beneficial compared to continuous low-to-moderate-volume moderate-intensity training or high intensity interval training. Interventions combining exercise and diet showed decreases in ALT (P<0.01) and improvement in NAFLD activity score (SMD=-0.61, 95% CI: -1.09 to -0.13). Moderate-carbohydrate diets yielded similar changes in liver enzymes compared to low/moderate-fat diets. CONCLUSIONS Exercise alone or combined with dietary intervention improves serum levels of liver enzymes and liver fat or histology. Exercise exerts beneficial effects on intrahepatic triglycerides even in the absence of weight loss.
Collapse
Affiliation(s)
- Christina N Katsagoni
- Department of Nutrition & Dietetics, School of Health Sciences and Education, Harokopio University, 70 El. Venizelou Str., 176 71, Athens, Greece
| | - Michael Georgoulis
- Department of Nutrition & Dietetics, School of Health Sciences and Education, Harokopio University, 70 El. Venizelou Str., 176 71, Athens, Greece
| | - George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital of Athens, 17 Agiou Thoma Str., 115 27, Athens, Greece
| | - Demosthenes B Panagiotakos
- Department of Nutrition & Dietetics, School of Health Sciences and Education, Harokopio University, 70 El. Venizelou Str., 176 71, Athens, Greece
| | - Meropi D Kontogianni
- Department of Nutrition & Dietetics, School of Health Sciences and Education, Harokopio University, 70 El. Venizelou Str., 176 71, Athens, Greece.
| |
Collapse
|
|
21
|
CRISPIM FGS, ELIAS MC, PARISE ER. Consumo alimentar dos portadores de Doença Hepática Gordurosa Não Alcoólica: comparação entre a presença e a ausência de Esteatoepatite Não Alcoólica e Síndrome Metabólica. REV NUTR 2016. [DOI: 10.1590/1678-98652016000400005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
RESUMO Objetivo O objetivo desse estudo foi avaliar o consumo alimentar de portadores de Doença Hepática Gordurosa Não Alcoólica, comparar com as recomendações nutricionais diárias e analisar a correlação da dieta com a presença de Síndrome Metabólica e com a gravidade da doença, uma vez que estudos sobre os hábitos alimentares dos portadores de Doença Hepática Gordurosa Não Alcoólica ainda são escassos na literatura. Métodos Nesse estudo foram avaliados, inicialmente, 158 pacientes com diagnóstico de Doença Hepática Gordurosa Não Alcoólica. Analisou-se exames laboratoriais, biópsia hepática, dados antropométricos e consumo dietético (registro alimentar de três dias). Dentre os pacientes avaliados, alguns já haviam sido orientados nutricionalmente e foram divididos em dois grupos: "sem dieta" e "com dieta". Para o cálculo de comparações de médias entre os grupos estudados, empregou-se o teste t de Student, considerando o nível de significância de 5% (a£0,05). Resultados Do total inicial de participantes, 59 apresentavam modificação significativa da dieta a partir de alguma orientação nutricional prévia e, por isso, foram excluídos da análise. Dos 99 pacientes restantes, quando confrontados com a ingestão dietética recomendada, 26% apresentavam maior ingestão energética e 80%, de ácidos graxos saturados, além de deficiente ingestão de ácidos graxos poli-insaturados e monoinsaturados, fibras e vitamina E, confirmando estudos prévios nessa mesma população. Entretanto, não foram encontradas diferenças significativas na dieta desses pacientes quando divididos de acordo com a presença ou ausência de Síndrome Metabólica e Esteatoepatite Não Alcoólica. Conclusão Esses dados, à luz dos conhecimentos atuais, sugerem que a dieta, especialmente quando rica em ácidos graxos saturados e deficiente em fibras e vitaminas antioxidantes, pode ter importante papel no aparecimento da Doença Hepática Gordurosa Não Alcoólica, mas que outros fatores exercem papel mais relevante na sua progressão para a Esteatoepatite Não Alcoólica.
Collapse
|
|
22
|
Abbasalizad Farhangi M, Mohseni F, Farajnia S, Jafarabadi MA. Major components of metabolic syndrome and nutritional intakes in different genotype of UCP2 -866G/A gene polymorphisms in patients with NAFLD. J Transl Med 2016; 14:177. [PMID: 27301474 PMCID: PMC4908770 DOI: 10.1186/s12967-016-0936-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Accepted: 06/02/2016] [Indexed: 01/09/2023] Open
Abstract
Background It has been suggested that dietary modifications in combination with genetic predisposition play an important role in the pathogenesis of NAFLD. In the current study we aimed to investigate the major components of metabolic syndrome in patients with non-alcoholic fatty liver disease (NAFLD) and nutritional intakes according to different genotype of uncoupling protein-2 (UCP2) −866G/A gene polymorphism in these patients. Methods In this study 151 participants including 75 patients with NAFLD and 76 healthy individuals were enrolled. Dietary intakes were assessed using a semi-quantitative food-frequency questionnaire. Physical activity was obtained by metabolic equivalent questionnaire. Anthropometric assessments were conducted by a trained researcher and body mass index and waist to hip ratio were calculated. Body composition was measured by bioelectrical impedance analysis and biochemical assays including fasting serum glucose, liver enzymes and lipid profiles were measured. Polymorphisms of −866G/A UCP2 gene was determined using polymerase chain reaction-restriction fragment length polymorphism method. Results Serum triglyceride concentrations in 53.3 % of NAFLD patients compared with 35.5 % of control group was more than 150 mg/dl (P = 0.034). A significantly higher prevalence of low serum high density lipoprotein cholesterol concentrations was also observed in female NAFLD patients (P < 0.001). Dietary intakes in NAFLD group were not significantly different compared with control group (P > 0.05). However, according to genotypes patients with AG genotype had significantly higher protein consumption compared with control group (P < 0.05). Significantly higher consumption of dietary iron and copper in NAFLD patients with AG genotype was only observed among patients with NAFLD. However, the comparison of macro and micronutrient intakes in control group sound for stronger differences for AA genotype although these differences did not achieve significant threshold. Conclusions A high prevalence of metabolic abnormalities was reported among NAFLD patients. Additionally, among NAFLD group, patients with AG genotype significantly consumed more protein, iron and copper in their usual diet.
Collapse
Affiliation(s)
- Mahdieh Abbasalizad Farhangi
- Nutrition Research Center, Department of Community Nutrition, School of Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Fatemeh Mohseni
- Drug Applied Research Center (DARC), Tabriz University of Medical Sciences, Tabriz, Iran
| | - Safar Farajnia
- Drug Applied Research Center (DARC), Tabriz University of Medical Sciences, Tabriz, Iran
| | | |
Collapse
|
|
23
|
Hughes EA, Patel JV, Bredow Z, Gill PS, Chackathayil J, Agaoglu ES, Flinders P, Mirrielees R. Ferritin as a Risk Factor for Glucose Intolerance amongst Men and Women Originating from the Indian Subcontinent. Int J Endocrinol 2015; 2015:924387. [PMID: 26347777 PMCID: PMC4549533 DOI: 10.1155/2015/924387] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2015] [Accepted: 07/22/2015] [Indexed: 01/22/2023] Open
Abstract
Background. Serum ferritin predicts the onset of diabetes; however, this relationship is not clear amongst South Asians, a population susceptible to glucose intolerance and anaemia. Objective. This study tests whether ferritin levels reflect glucose tolerance in South Asians, independent of lifestyle exposures associated with Indian or British residence. Methods. We randomly sampled 227 Gujaratis in Britain (49.8 (14.4) years, 50% men) and 277 contemporaries living in Gujarati villages (47.6 (11.8) years, 41% men). Both groups underwent a 75 g oral-glucose-tolerance test. We evaluated lifestyle parameters with standardised questionnaires and conducted comprehensive clinical and lab measurements. Results. Across sites, the age-adjusted prevalence of diabetes was 9.8%. Serum ferritin was higher amongst diabetics (P = 0.005), irrespective of site, gender, and central obesity (P ≤ 0.02), and was associated with fasting and postchallenge glucose, anthropometry, blood pressure, triglycerides, and nonesterified fatty acids (P < 0.001). Diabetes was less in those with low ferritin (<20 mg/mL), P < 0.008, and risk estimate = 0.35 (95% CI 0.15-0.81), as were blood pressure and metabolic risk factors. On multivariate analysis, diabetes was independently associated with ferritin (P = 0.001) and age (P < 0.001). Conclusion. Ferritin levels are positively associated with glucose intolerance in our test groups, independent of gender and Indian or UK lifestyle factors.
Collapse
Affiliation(s)
- Elizabeth A. Hughes
- University of Birmingham Centre for Cardiovascular Sciences, Sandwell and West Birmingham Hospitals NHS Trust, West Midlands B18 7QH, UK
| | - Jeetesh V. Patel
- University of Birmingham Centre for Cardiovascular Sciences, Sandwell and West Birmingham Hospitals NHS Trust, West Midlands B18 7QH, UK
- Medical School, University of Nottingham, Nottingham NG7 2UH, UK
| | - Zosia Bredow
- Medical School, University of Nottingham, Nottingham NG7 2UH, UK
| | - Paramjit S. Gill
- Primary Care Clinical Sciences, University of Birmingham, West Midlands B15 2TT, UK
| | - Julia Chackathayil
- Primary Care Clinical Sciences, University of Birmingham, West Midlands B15 2TT, UK
| | - Elif S. Agaoglu
- Medical School, University of Nottingham, Nottingham NG7 2UH, UK
| | - Paul Flinders
- Medical School, University of Nottingham, Nottingham NG7 2UH, UK
| | | |
Collapse
|
|
24
|
Bhala N, George J. The Burden of Non-alcoholic Fatty Liver Disease (NAFLD) in the Asia Pacific Region. ACTA ACUST UNITED AC 2015. [DOI: 10.1007/s11901-015-0264-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
25
|
Da Silva HE, Arendt BM, Noureldin SA, Therapondos G, Guindi M, Allard JP. A Cross-Sectional Study Assessing Dietary Intake and Physical Activity in Canadian Patients with Nonalcoholic Fatty Liver Disease vs Healthy Controls. J Acad Nutr Diet 2014; 114:1181-94. [DOI: 10.1016/j.jand.2014.01.009] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2012] [Accepted: 01/06/2014] [Indexed: 02/06/2023]
|
|
26
|
Joesting JJ, Moon ML, Gainey SJ, Tisza BL, Blevins NA, Freund GG. Fasting Induces IL-1 Resistance and Free-Fatty Acid-Mediated Up-Regulation of IL-1R2 and IL-1RA. Front Immunol 2014; 5:315. [PMID: 25071776 PMCID: PMC4089087 DOI: 10.3389/fimmu.2014.00315] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2014] [Accepted: 06/23/2014] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVE Weight-loss is a near societal obsession and many diet programs use significant calorie restriction including fasting/short term starvation to generate rapid effects. Fasting is also a well-recognized cause of immunosuppression especially within the innate immune system. In this study, we sought to determine if the IL-1 arm of the neuroimmune system was down-regulated by a 24 h fast and how fasting might generate this effect. DESIGN Mice were allowed ad libitum access to food or had food withheld for 24 h. Expression of the endogenous IL-1 antagonists, IL-1 receptor type 2 (IL-1R2), and IL-1 receptor antagonist (IL-1RA) was determined as were sickness behaviors before and after IL-1β administration. RESULTS Fasting markedly increased gene expression of IL-1R2 (83-fold in adipose tissue, 9.5-fold in liver) and IL-1RA (68-fold in liver). Fasted mice were protected from IL-1β-induced weight-loss, hypoglycemia, loss of locomotor, and social anxiety. These protections were coupled to a large positive interaction of fasting and IL-1β on IL-1R2 gene expression in adipose tissue and liver (2.6- and 1.6-fold, respectively). Fasting not only increased IL-1RA and IL-1R2 protein 2.5- and 3.2-fold, respectively, in liver but also increased IL-1R2 1.8-fold in adipose tissue. Fasting, in turn, triggered a 2.4-fold increase in plasma free-fatty acids (FFAs) and a 2.1-fold increase in plasma corticosterone. Inhibition, of glucocorticoid action with mifepristone did not impact fasting-dependent IL-1R2 or IL-1RA gene expression. Administration of the FFA, palmitate, to mice increased liver IL-1R2 and IL-1RA gene expression by 14- and 11-fold, respectively. CONCLUSION These findings indicate that fasting augments expression of endogenous IL-1 antagonists inducing IL-1 resistance. Fasting-induced increases in plasma FFAs appears to be a signal that drives immunosuppression during fasting/short term starvation.
Collapse
Affiliation(s)
- Jennifer J Joesting
- Department of Animal Sciences, University of Illinois at Urbana - Champaign , Urbana, IL , USA ; Program in Integrative Immunology and Behavior, Department of Pathology, University of Illinois at Urbana - Champaign , Urbana, IL , USA
| | - Morgan L Moon
- Program in Integrative Immunology and Behavior, Department of Pathology, University of Illinois at Urbana - Champaign , Urbana, IL , USA ; Division of Nutritional Sciences, University of Illinois at Urbana - Champaign , Urbana, IL , USA
| | - Stephen J Gainey
- Department of Animal Sciences, University of Illinois at Urbana - Champaign , Urbana, IL , USA ; Program in Integrative Immunology and Behavior, Department of Pathology, University of Illinois at Urbana - Champaign , Urbana, IL , USA
| | - Brittany L Tisza
- Program in Integrative Immunology and Behavior, Department of Pathology, University of Illinois at Urbana - Champaign , Urbana, IL , USA
| | - Neil A Blevins
- Program in Integrative Immunology and Behavior, Department of Pathology, University of Illinois at Urbana - Champaign , Urbana, IL , USA
| | - Gregory G Freund
- Department of Animal Sciences, University of Illinois at Urbana - Champaign , Urbana, IL , USA ; Program in Integrative Immunology and Behavior, Department of Pathology, University of Illinois at Urbana - Champaign , Urbana, IL , USA ; Division of Nutritional Sciences, University of Illinois at Urbana - Champaign , Urbana, IL , USA
| |
Collapse
|
|
27
|
Wang S, Kuang X, Fang Z, Huang Z, Shi P. Effect of oleic acid on the levels of eight metal ions in human hepatoma SMMC-7721 cells. Biol Trace Elem Res 2014; 159:445-50. [PMID: 24867776 DOI: 10.1007/s12011-014-0018-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2014] [Accepted: 05/14/2014] [Indexed: 10/25/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Its incidence is rising worldwide. However, no specific therapy has been shown to be effective in its treatment. In the present study, the in vitro NAFLD model was established in human SMMC-7721 cells by using oleic acid (OA). Then, content changes of eight cations, including sodium, magnesium, potassium, calcium, iron, copper, zinc, and manganese, were investigated in the experimental model. The results showed that OA induced a decrease in magnesium level, while an increase in iron one. Additionally, the supplementation of magnesium in the cell culture model was studied. It showed that magnesium ameliorated lipid accumulation induced by OA. Our results suggest that magnesium could decrease the risk of NAFLD and be used as a promising candidate for the treatment of NAFLD.
Collapse
Affiliation(s)
- Song Wang
- State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China
| | | | | | | | | |
Collapse
|
|
28
|
Carulli L, Ballestri S, Lonardo A, Lami F, Violi E, Losi L, Bonilauri L, Verrone AM, Odoardi MR, Scaglioni F, Bertolotti M, Loria P. Is nonalcoholic steatohepatitis associated with a high-though-normal thyroid stimulating hormone level and lower cholesterol levels? Intern Emerg Med 2013; 8:297-305. [PMID: 21559749 DOI: 10.1007/s11739-011-0609-4] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2010] [Accepted: 04/21/2011] [Indexed: 02/06/2023]
Abstract
Hypothyroidism is associated with the risk of development of the metabolic syndrome (MS) and hypercholesterolemia. Direct evidence that hypothyroidism might be associated with advanced chronic liver disease via nonalcoholic steatohepatitis (NASH) is limited. We studied the relationship between thyroid hormones, thyroid stimulating hormone (TSH), cholesterol, and NASH. In consecutive euthyroid patients with biopsy-proven nonalcoholic fatty liver disease, TSH and thyroid hormone (FT3 and FT4) concentrations were compared in 25 patients with steatosis and 44 non-cirrhotic NASH patients featuring concurrent ballooning, lobular inflammation and steatosis. The MS was diagnosed according to ATP III criteria. A meta-analysis of previously published studies was performed to evaluate whether NASH, compared to simple steatosis, is associated with lower cholesterol levels. At univariate analysis, compared to those with steatosis, patients with NASH have a wider waist, elevated levels of BMI, ALT, AST, fasting insulin, HOMA-IR, ferritin, TSH and a lower serum cholesterol. At stepwise multivariable logistic regression analysis, the independent predictors of NASH are high HOMA and TSH and lower total cholesterol (Model 1); MS and high TSH (Model 2). At meta-analysis, serum total cholesterol levels are significantly lower in predominantly non-cirrhotic NASH than in simple steatosis. This study provides cross-sectional and meta-analytic evidence that, in euthyroid patients, high-though-normal TSH values are independently associated with NASH. Further work is needed to ascertain the role, if any, of lower cholesterol serum levels in assisting in the diagnosis of NASH.
Collapse
Affiliation(s)
- Lucia Carulli
- Department of Internal Medicine, Endocrinology, Metabolism and Geriatrics, Unit of Internal Medicine, University of Modena and Reggio Emilia, Nuovo Ospedale Civile Sant'Agostino Estense, Via Giardini 1355, 41100, Modena, Italy
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
29
|
Ferolla SM, Ferrari TCA, Lima MLP, Reis TO, Tavares WC, Couto OFM, Vidigal PVT, Fausto MA, Couto CA. Dietary patterns in Brazilian patients with nonalcoholic fatty liver disease: a cross-sectional study. Clinics (Sao Paulo) 2013; 68:11-7. [PMID: 23420151 PMCID: PMC3552450 DOI: 10.6061/clinics/2013(01)oa03] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2012] [Accepted: 09/16/2012] [Indexed: 01/14/2023] Open
Abstract
OBJECTIVE Recent evidence suggests that non-alcoholic fatty liver disease is associated with diet. Our aim was to investigate the dietary patterns of a Brazilian population with this condition and compare them with the recommended diet. METHODS A cross-sectional study was conducted on 96 non-alcoholic fatty liver disease patients before any dietetic counseling. All patients underwent abdominal ultrasound, biochemical tests, dietary evaluations, and anthropometric evaluations. Their food intake was assessed by a semi-quantitative food-frequency questionnaire and 24-hour food recall. RESULTS The median patient age was 53 years, and 77% of the individuals were women. Most (67.7%) participants were obese, and a large waist circumference was observed in 80.2% subjects. Almost 70% of the participants had metabolic syndrome, and 62.3% presented evidence of either insulin resistance or overt diabetes. Most patients (51.5, 58.5, and 61.7%, respectively) exceeded the recommendations for energy intake, as well as total and saturated fat. All patients consumed less than the amount of recommended monounsaturated fatty acids, and 52.1 and 76.6% of them consumed less polyunsaturated fatty acids and fiber, respectively, than recommended. In most patients, the calcium, sodium, potassium, pyridoxine, and vitamin C intake did not meet the recommendations, and in 10.5-15.5% of individuals, the tolerable upper limit intake for sodium was exceeded. The patients presented a significantly high intake of meats, fats, sugars, legumes (beans), and vegetables and a low consumption of cereals, fruits, and dairy products compared with the recommendations. CONCLUSIONS Although patients with non-alcoholic fatty liver disease exhibited high energy and lipid consumption, most of them had inadequate intake of some micronutrients. The possible role of nutrient-deficient intake in the development of non-alcoholic fatty liver disease warrants investigation.
Collapse
Affiliation(s)
- Silvia Marinho Ferolla
- Universidade Federal de Minas Gerais, University Hospital, Alfa Institute of Gastroenterology, Belo Horizonte/MG, Brazil
| | | | | | | | | | | | | | | | | |
Collapse
|
|
30
|
Tanaka Y, Ikeda T, Yamamoto K, Ogawa H, Kamisako T. Dysregulated expression of fatty acid oxidation enzymes and iron-regulatory genes in livers of Nrf2-null mice. J Gastroenterol Hepatol 2012; 27:1711-7. [PMID: 22591204 DOI: 10.1111/j.1440-1746.2012.07180.x] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIM Hepatic excessive iron may play a role in the pathogenesis of non-alcoholic steatohepatitis (NASH). Nrf2 is a master regulator of antioxidative responses. However, the role of Nrf2 in lipid and iron homeostasis remains unclear. Accordingly, it was examined how Nrf2 regulates lipid-related and iron-regulatory genes after feeding a high-fat diet (HFD) with iron. METHODS Wild-type and Nrf2-null mice were fed the following diets: (i) control diet (4% soybean oil) for 12 weeks, (ii) control diet for 8 weeks followed by control diet containing 0.5% carbonyl iron for 4 weeks, (iii) HFD (4% soybean oil and 16% lard) for 12 weeks, (iv) HFD for 8 weeks followed by HFD containing 0.5% carbonyl iron for 4 weeks. Blood and livers were removed after 12 weeks. RESULTS Nrf2-null control mice exhibited a tendency towards higher hepatic triglycerides compared to wild-type control mice. Hepatic malondialdehyde was higher and hepatic iron levels tended to be higher in Nrf2-null mice than wild-type counterparts while on a HFD. The HFD with iron synergistically induced mRNA expression of Pparα targets, including Acox and Cpt1 in wild-type mice, yet the induction was diminished in Nrf2-null mice. Hepatic hepcidin and ferroportin 1 mRNA expression were increased in wild-type mice after feeding a HFD with iron, but were unchanged in any group of Nrf2-null mice. CONCLUSIONS Nrf2 deletion dysregulates hepatic mRNA expression of β-oxidation enzymes and iron-related genes, possibly causing a trend for increased hepatic triglyceride and iron concentrations. Nrf2 may have roles in the progression of NASH.
Collapse
Affiliation(s)
- Yuji Tanaka
- Department of Clinical Laboratory Medicine, Kinki University Faculty of Medicine, Osakasayama, Japan.
| | | | | | | | | |
Collapse
|
|
31
|
Liu CJ. Prevalence and risk factors for non-alcoholic fatty liver disease in Asian people who are not obese. J Gastroenterol Hepatol 2012; 27:1555-60. [PMID: 22741595 DOI: 10.1111/j.1440-1746.2012.07222.x] [Citation(s) in RCA: 159] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Fatty liver (hepatic steatosis) is prevalent in industrialized countries. It is typically linked to obesity, central obesity and the presence of metabolic syndrome. With the introduction of a Westernized lifestyle and the increasing frequency of obesity in the Asia-Pacific region, the prevalence of non-alcoholic fatty liver disease (NAFLD) has been increasing over the past two decades. The risk factors are similar to those in other ethnic populations; but it is important to adopt the regional (ethnic-specific) anthropometric criteria to define overweight, obesity (including central obesity) and metabolic syndrome. To be noted, even using strict ethnic-specific criteria, a high percentage (15-21%) of Asia-Pacific NAFLD subjects in some series have been found to be non-obese, i.e. to have a normal body mass index (BMI) (17.5-22.4 kg/m(2)) or to be overweight (BMI 22.5-24.9 kg/m(2)). Differential distribution of visceral adipose tissue, recent increase in body weight, intake of high cholesterol diet and genetic background are factors likely associated with the development of NAFLD in these non-obese (but often overweight) Asia-Pacific subjects. Furthermore, insulin resistance may be the underlying key mechanism. In addition, since NAFLD may be the hepatic manifestation of metabolic syndrome, the presence of NAFLD is a predictor of future type 2 diabetes, metabolic syndrome and cardiovascular disease. Therefore, interventions at the public health level are indicated to halt the trend of overweight as well as obesity in Asia-Pacific region, particularly among those with relevant family history. Since the pathophysiology of NAFLD is closely related to metabolic derangement, lifestyle modification remains the cornerstone of management.
Collapse
Affiliation(s)
- Chun-Jen Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan.
| |
Collapse
|
|
32
|
Volynets V, Küper MA, Strahl S, Maier IB, Spruss A, Wagnerberger S, Königsrainer A, Bischoff SC, Bergheim I. Nutrition, intestinal permeability, and blood ethanol levels are altered in patients with nonalcoholic fatty liver disease (NAFLD). Dig Dis Sci 2012; 57:1932-41. [PMID: 22427130 DOI: 10.1007/s10620-012-2112-9] [Citation(s) in RCA: 196] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2011] [Accepted: 02/22/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND A role of an altered dietary pattern (e.g., a diet rich in sugar) but also alterations at the level of the intestinal barrier have repeatedly been discussed to be involved in the development and progression of nonalcoholic fatty liver disease (NAFLD). AIMS To determine if the nutritional intake, intestinal flora, and permeability and the development of NAFLD are related in humans. METHODS Ten controls and 20 patients with NAFLD ranging from simple steatosis to steatohepatitis were included in the study. Bacterial overgrowth, orocecal transit time, and intestinal permeability were assessed. Alcohol, endotoxin, and plasminogen activator inhibitor (PAI-) 1 concentration were determined in plasma. Nutritional intake was assessed using a dietary history. RESULTS Despite no differences in the prevalence of bacterial overgrowth and in the orocecal transit time, intestinal permeability, alcohol, and endotoxin levels in plasma were significantly higher in patients with NAFLD than in controls. Similar results were also found for PAI-1 plasma concentrations. Patients with NAFLD had a significantly higher intake of protein, total carbohydrates, and mono- as well as disaccharides than controls. PAI-1, endotoxin, and ALT plasma levels were positively related to total protein and carbohydrate intake. CONCLUSIONS Taken together, our results indicate that intestinal permeability, endogenous alcohol synthesis, and nutritional intake are markedly altered in patients with NAFLD.
Collapse
Affiliation(s)
- Valentina Volynets
- Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
33
|
The role of nutrients in the development, progression, and treatment of nonalcoholic fatty liver disease. J Clin Gastroenterol 2012; 46:457-67. [PMID: 22469640 DOI: 10.1097/mcg.0b013e31824cf51e] [Citation(s) in RCA: 88] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in adults and children and is currently the third most common indication for liver transplantation in North America. Its pathogenesis is thought to be secondary to multiple "hits" derived from the dietary components, adipose tissue, immune system, and intestinal microbiota. Lack of physical activity may contribute as well. Nutrients may exert their effect directly or through alteration of the intestinal microbiota. Research focusing on specific dietary components predisposing to NAFLD has shown conflicting results. Total energy intake, and macronutrients, has been linked to the development of NAFLD. Fructose not only contributes to hepatic steatosis but may trigger inflammatory signals as well. Polyunsaturated fatty acids are thought to exert anti-inflammatory effects. The role of vitamins as well as minerals in this field is actively being investigated. In this review, we discuss the evidence-linking macronutrients (such as carbohydrates and fat in general and fructose, fiber, short chain fatty acids, polyunsaturated fatty, and choline specifically) and micronutrients (such as vitamin E and C and minerals) with the development and treatment of NAFLD. We also discuss the literature on physical activity and NAFLD.
Collapse
|
|
34
|
McCarthy EM, Rinella ME. The role of diet and nutrient composition in nonalcoholic Fatty liver disease. J Acad Nutr Diet 2012; 112:401-9. [PMID: 22717200 DOI: 10.1016/j.jada.2011.10.007] [Citation(s) in RCA: 112] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2011] [Accepted: 09/30/2011] [Indexed: 12/28/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the developed world. NAFLD is tightly linked to insulin resistance and considered to be the hepatic manifestation of the metabolic syndrome. The cornerstone of any treatment regimen for patients with NAFLD is lifestyle modification focused on weight loss, exercise, and improving insulin sensitivity. Here we review the literature and discuss the role of diet and nutrient composition in the management of NAFLD. Because there are currently no specific dietary guidelines for NAFLD, this review proposes a dietary framework for patients with NAFLD based on the available evidence and extrapolates from dietary guidelines aimed at reducing insulin resistance and cardiovascular risk.
Collapse
|
|
35
|
Thoma C, Day CP, Trenell MI. Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in adults: a systematic review. J Hepatol 2012; 56:255-66. [PMID: 21723839 DOI: 10.1016/j.jhep.2011.06.010] [Citation(s) in RCA: 382] [Impact Index Per Article: 29.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2011] [Revised: 06/23/2011] [Accepted: 06/27/2011] [Indexed: 12/12/2022]
Abstract
Non-alcoholic fatty liver disease is a serious and growing clinical problem. Despite lifestyle modification, i.e. diet and physical activity, being the recommended therapy, there are currently no systematic evaluations of its efficacy. This review applies a systematic approach to evaluating lifestyle modifications studied to date. Medline (Pubmed), Scopus, and the Cochrane Controlled Trials Register were searched for studies and study groups assessing the effect of diet, physical activity, and/or exercise modification in adult populations with non-alcoholic fatty liver disease. The outcome markers of interest were indicators of steatosis, histological evidence of inflammation and fibrosis, and glucose control/insulin sensitivity. We identified 23 studies for inclusion; seven had control groups, but only six were randomised. Eleven groups received diet-only interventions, two exercise-only, and 19 diet and physical activity/exercise. Studies consistently showed reductions in liver fat and/or liver aminotransferase concentration, with the strongest correlation being with weight reduction. Of the 5 studies reporting changes in histopathology, all showed a trend towards reduction in inflammation, in 2 this was statistically significant. Changes in fibrosis were less consistent with only one study showing a significant reduction. The majority of studies also reported improvements in glucose control/insulin sensitivity following intervention. However, study design, definition of disease, assessment methods, and interventions varied considerably across studies. Lifestyle modifications leading to weight reduction and/or increased physical activity consistently reduced liver fat and improved glucose control/insulin sensitivity. Limited data also suggest that lifestyle interventions may hold benefits for histopathology.
Collapse
Affiliation(s)
- Christian Thoma
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | | | | |
Collapse
|
|
36
|
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a major causative agent of chronic liver disease worldwide, but the actual mechanisms responsible for liver injury remain unclear. NAFLD includes a spectrum of clinical entities ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) with possible evolution to cirrhosis and hepatocellular carcinoma. Iron is considered a putative element that interacts with oxygen radicals in inducing liver damage/fibrosis and insulin resistance. The role of hepatic iron in the progression of NASH remains controversial, but in some patients, iron may have a role in the pathogenesis of NASH. Though genetic factors, insulin resistance, dysregulation of iron-regulatory molecules, erythrophagocytosis by Kupffer cells may be responsible for hepatic iron accumulation in NASH, exact mechanisms involved in iron overload remain to be clarified. Iron reduction therapy such as phlebotomy or iron-restricted diet may be promising in patients with NAFLD/NASH to reduce hepatic injury as well as insulin resistance. Larger controlled trials of longer duration are warranted to assess the long-term clinical benefit of phlebotomy and/or iron-restricted diet in NAFLD/NASH.
Collapse
|
|
37
|
Arefhosseini SR, Ebrahimi-Mameghani M, Farsad Naeimi A, Khoshbaten M, Rashid J. Lifestyle Modification through Dietary Intervention: Health Promotion of Patients with Non-Alcoholic Fatty Liver Disease. Health Promot Perspect 2011; 1:147-54. [PMID: 24688911 DOI: 10.5681/hpp.2011.016] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2011] [Accepted: 12/18/2011] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Prevalence of non-alcoholic fatty liver disease (NAFLD) is more common worldwide and no certain treatment apart from lifestyle modification has been established yet. Available data consistently show that energy intake is significantly higher in patients with NAFLD than in individuals with no evidence of fatty liver. Changing nutritional behaviors seems to be the primary approach for treatment, simultaneously addressing all the clinical and biochemical defects. This study was aimed to examine the effects of two different composition of low energy diet (diet I vs. diet II) on non-alcoholic fatty liver disease patients. METHODS In this double-blind randomized controlled trial, 44 ultrasonography-proven overweight non-alcoholic fatty liver disease patients were divided into two groups and received two low-energy diets (-500 kcal less than energy requirement individually) inc. diet I (Carbohydrate: Fat: Protein: 55:25:20) and diet II (Carbohydrate: Fat: Protein: 40:40:20) for six weeks. Anthropometric and biochemical measures as well as liver enzymes were assessed after 12 hours fasting. RESULTS After diet I and diet II, weight decreased significantly (%1.82 and %2.45, respectively). Liver enzymes and echogenicity decreased significantly by both diet I and diet II. Mean of triglyceride concentration decreased (%18.09) after diet II (P=0.023), while there was no significant change after diet I. Significant correlations were found between changes in aspartate aminotransferase with triglyceride and LDL-C diet I. CONCLUSION Low energy diets can decrease liver enzymes regardless of their composition, while diet II seems to be more effective than diet I in reduction of weight and triglyceride level.
Collapse
Affiliation(s)
- Seyed Rafie Arefhosseini
- Nutrition Research Center, School of Health & Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Alireza Farsad Naeimi
- Students' Research Committee, School of Health & Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Manoochehr Khoshbaten
- Department of Gastroenterology, School of Health & Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Javad Rashid
- Department of Radiology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| |
Collapse
|
|
38
|
Iwasa M, Mifuji-Moroka R, Hara N, Ishidome M, Iwata K, Sugimoto R, Tanaka H, Fujita N, Kobayashi Y, Takei Y. Visceral fat volume predicts new-onset type 2 diabetes in patients with chronic hepatitis C. Diabetes Res Clin Pract 2011; 94:468-70. [PMID: 22014765 DOI: 10.1016/j.diabres.2011.09.016] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2011] [Revised: 09/13/2011] [Accepted: 09/19/2011] [Indexed: 12/15/2022]
Abstract
Ninety seven patients with chronic hepatitis C (CHC) and 72 with non-alcoholic fatty liver disease (NAFLD) were enrolled. Increased visceral fat area (VFA) was associated with high values of HbA1c. The variables associated with a high risk of new-onset diabetes had a VFA>101 cm(2) in CHC, but not in NAFLD.
Collapse
Affiliation(s)
- Motoh Iwasa
- Department of Gastroenterology and Hepatology, Mie University Graduate School of Medicine, Tsu, Japan.
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
39
|
Kaji K, Yoshiji H, Kitade M, Ikenaka Y, Noguchi R, Shirai Y, Aihara Y, Namisaki T, Yoshii J, Yanase K, Tsujimoto T, Kawaratani H, Fukui H. Combination treatment of angiotensin II type I receptor blocker and new oral iron chelator attenuates progression of nonalcoholic steatohepatitis in rats. Am J Physiol Gastrointest Liver Physiol 2011; 300:G1094-104. [PMID: 21372165 DOI: 10.1152/ajpgi.00365.2010] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Angiotensin II type I receptor blocker and iron chelator reportedly exert suppressive effects on nonalcoholic steatohepatitis (NASH) progression, including liver fibrosis and hepatocarcinogenesis. The aim of this study was to elucidate the combined effect of losartan (LOS), an angiotensin II type I receptor blocker, and deferasirox (DSX), a newly developed oral iron chelator, on the progression of NASH in rats. To induce NASH, F344 rats were fed a choline-deficient l-amino acid-defined diet for 12 wk, and the effects of LOS and DSX at clinically comparable low doses were elucidated in conjunction with oxidative stress, neovascularization, and hepatic stellate cells (HSC) activation, all known to play important roles in the progression of NASH. Treatment with both LOS and DSX suppressed choline-deficient L-amino acid-defined diet-induced liver fibrosis development and hepatocarcinogenesis. This combination treatment exerted a stronger inhibitory effect compared with treatment with a single agent. These inhibitory effects occurred almost concurrently with the suppression of oxidative stress, neovascularization, and HSC activation. Our in vitro study demonstrated that LOS and DSX inhibited angiotensin II-induced proliferation, transforming growth factor-β(1) expression of activated HSC, and in vitro angiogenesis. These results indicated that dual inhibition by combined treatment of LOS and DSX attenuated the progression of NASH. Since both agents are widely used in clinical practice, this combination therapy may represent a potential new strategy against NASH in the near future.
Collapse
Affiliation(s)
- Kosuke Kaji
- Third Department of Internal Medicine, Nara Medical University, Kashihara, Japan
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
40
|
Abstract
OBJECTIVES Iron plays a pivotal role in adult steatosis, but its role in child and adolescent steatosis is unclear. We investigated the effect of dietary iron, serum iron, and ferritin on serum transaminases and γ-glutamyltransferase in 10- and 13-year-olds. PATIENTS AND METHODS The study included 4894 fifth and eighth graders enrolled between 2006 and 2009 in all schools in Shunan City, Japan. Multiple regression analyses were performed with adjustments for grade, sex, z score of the body mass index, serum lipids, plasma glucose, frequency of sports activities, having a single parent, number of siblings, tobacco smoking behavior, passive smoking at home, resident areas, and schools, using linear mixed models. In addition, we analyzed ferritin and insulin resistance in randomly selected subset of participants. RESULTS Dietary iron intake was positively associated with serum alanine aminotransferase levels (standardized coefficient β = 2.35, P = 0.019). Serum iron concentrations were associated with transaminase and γ-glutamyltransferase levels (β = 3.22, and 4.05, respectively, P < 0.01). In the subset of 421 subjects with further serum analysis, serum ferritin levels were significantly associated with serum enzyme levels (β = 2.43-3.35; P < 0.05) and showed significant odds ratio for the elevated alanine aminotransferase levels (1.05 for 1 SD with 95% confidence intervals 1.02-1.08). However, iron load did not show a positive association with insulin resistance. CONCLUSIONS Although an effect size for iron is small in regression analyses, iron is implicated in increased transaminase levels in prepubertal and pubertal children.
Collapse
|
|
41
|
ROSSI M, HICKMAN IJ. Diet prescription for non-alcoholic fatty liver disease: Is it worth the effort? A systematic review. Nutr Diet 2011. [DOI: 10.1111/j.1747-0080.2010.01486.x] [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]
|
|
42
|
Chitturi S, Wong VWS, Farrell G. Nonalcoholic fatty liver in Asia: Firmly entrenched and rapidly gaining ground. J Gastroenterol Hepatol 2011; 26 Suppl 1:163-72. [PMID: 21199528 DOI: 10.1111/j.1440-1746.2010.06548.x] [Citation(s) in RCA: 116] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is becoming an important chronic liver disorder in Asia. Prevalence figures show regional variations but at least 10% of the general population in Asia have fatty liver. Fatty liver can develop with relatively small changes in weight (2-3 kg), often with increasing central adiposity. The metabolic syndrome may precede or follow NAFLD. Overt diabetes is present in one-third of cases but when oral glucose tolerance tests are performed, a further third of individuals have impaired glucose tolerance or diabetes. Natural history data are still scarce but cases of advanced hepatic fibrosis and hepatocellular carcinoma are now regularly reported. Many cases of cryptogenic cirrhosis are also attributable to NAFLD. Histological progression has been demonstrated for patients with NASH as well as for those with hepatic steatosis alone. Genetic factors may in part contribute to the rise in NAFLD. Polymorphisms within apolipoprotein C3 (APOC3) gene have been linked to NAFLD in lean Indian men. Although a number of other polymorphisms involving genes controlling adipose distribution, insulin signalling, adipokine responses and hepatic fibrosis have been reported, these studies have been underpowered. Transient elastography could help in detecting and monitoring hepatic fibrosis but further refinements in technique are necessary for obese individuals. Of the biomarkers, hyaluronic acid and cytokeratin-18 fragment testing show promise as markers of hepatic fibrosis and NASH, respectively. Lifestyle alterations including dietary changes and increased physical activity remain the cornerstone of management. Attention should be paid to prevention through public education of campaigns addressing the increase in both adult and childhood obesity.
Collapse
|
|
43
|
Iwasa M, Hara N, Iwata K, Ishidome M, Sugimoto R, Tanaka H, Fujita N, Kobayashi Y, Takei Y. Restriction of calorie and iron intake results in reduction of visceral fat and serum alanine aminotransferase and ferritin levels in patients with chronic liver disease. Hepatol Res 2010; 40:1188-94. [PMID: 20880065 DOI: 10.1111/j.1872-034x.2010.00724.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
AIM To clarify the impact of visceral fat on chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD) and hepatitis C, we investigated the effects of lifestyle modifications on the amount of visceral fat, liver biochemistry and serum ferritin levels in patients with liver disease. METHODS Eighty-two patients (NAFLD, n = 37; hepatitis C, n = 45) were advised to adopt lifestyle modifications, including dietary changes and exercise, and these were maintained for 6 months. Bodyweight, percentage of body fat, visceral fat area (VFA) and serum alanine aminotransferase (ALT) and ferritin were measured before and after intervention. RESULTS In NAFLD, the mean VFA of 134.5 cm(2) was significantly reduced to 125.3 cm(2) after 6 months (P < 0.001). ALT levels improved significantly between the values measured before and after intervention (P = 0.039). The VFA prior to intervention was 100 cm(2) in hepatitis C patients and it was reduced significantly after 6 months to 95.6 cm(2) (P < 0.001). ALT levels also improved significantly in the hepatitis C patients (P < 0.001). The serum ferritin levels also reduced in these patients. Improvements in serum ALT and ferritin levels correlated with the amount of visceral fat reduction in both groups (P = 0.046, P = 0.008, respectively). CONCLUSION These findings demonstrate that restriction of calorie and iron intake results in reduction of visceral fat, liver enzymes and ferritin in patients with chronic liver disease. Visceral fat may be a central target for future interventions, not only in NAFLD but also in hepatitis C.
Collapse
Affiliation(s)
- Motoh Iwasa
- Department of Gastroenterology and Hepatology, Division of Clinical Medicine and Biomedical Sciences, Institute of Medical Science, Mie University Graduate School of Medicine Division of Dietary Service, Mie University School Hospital, Tsu, Japan
| | | | | | | | | | | | | | | | | |
Collapse
|
|
44
|
An epidemiologic study on the incidence and significance of HFE mutations in a Korean cohort with nonalcoholic fatty liver disease. J Clin Gastroenterol 2010; 44:e154-61. [PMID: 20216079 DOI: 10.1097/mcg.0b013e3181d347d9] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND/AIM The incidence and significance of HFE mutations (C282Y, H63D, and S65C) in nonalcoholic fatty liver disease (NAFLD) has not been investigated in Korea. METHODS Mutation analysis of HFE gene and measurement of blood iron indices were carried out in 125 NAFLD patients and 221 controls. RESULTS Neither C282Y nor S65C gene mutations were detected. The prevalence of the H63D mutation was higher in the NAFLD group (14.4%) than in the controls (7.2%) (P=0.032). The estimated odds ratio (OR) of NAFLD for H63D mutations was 3.09 (P=0.008) by multivariate analysis, and age, gender, obesity, diabetes mellitus, and hypercholesterolemia were independent variables associated with NAFLD. However, in the multivariate analysis containing interaction of the types of HFE mutations and gender, the prevalence of the H63D mutation was significantly higher in the male NAFLD group than in the male control group (OR=5.51, P=0.007); the difference of the prevalence between the NAFLD and the control group in females was not significant. The NAFLD patients with H63D mutations had higher levels of TS than those with the wild type (OR=3.14, P=0.048) by the multivariate analysis. A higher TS was significantly associated with the lower body mass index only in the male NAFLD group by multivariate analysis (OR=0.67, P=0.002). CONCLUSIONS The presence of H63D mutations was an independent factor associated with NAFLD and elevated TS. Therefore, the H63D mutation may increase susceptibility to NAFLD probably associated with peripheral iron overload, especially in males.
Collapse
|
|
45
|
Elias MC, Parise ER, de Carvalho L, Szejnfeld D, Netto JP. Effect of 6-month nutritional intervention on non-alcoholic fatty liver disease. Nutrition 2009; 26:1094-9. [PMID: 20022466 DOI: 10.1016/j.nut.2009.09.001] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2009] [Revised: 07/30/2009] [Accepted: 09/01/2009] [Indexed: 02/08/2023]
Abstract
OBJECTIVE We evaluated the effect of diet therapy as exclusive treatment on insulin resistance, biochemical parameters of metabolic syndrome, and degree of hepatic steatosis in patients with non-alcoholic fatty liver disease. METHODS Thirty-one patients with non-alcoholic fatty liver disease received a diet with a reduction of 500 to 1000 cal/d, containing 15% protein, 55% carbohydrates, and 30% fat, for 6 mo. At entry and 6 mo after dietary instructions, degrees of hepatic steatosis and visceral obesity were assessed by computed tomography; serum aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase, glucose, triacylglycerols, and high-density lipoprotein cholesterol were measured by automated methods. Body mass index, waist circumference, waist-to-hip ratio, and food intake (7-d diary) were also evaluated. At the end of follow-up, the patients were classified as adherent or non-adherent to treatment according to a weight loss of more or less than 5% of initial body weight, respectively. RESULTS Seventeen patients were classified as adherent (group 1) and 14 as non-adherent (group 2). Group 2 only presented a significant reduction in body mass index and waist circumference. In contrast, in group 1, in addition to significant improvement of all anthropometric parameters, a significant reduction was observed in alanine aminotransferase and γ-glutamyl transferase levels, homeostasis model assessment for insulin resistance, visceral fat and tomographic liver density, together with an increase in serum high-density lipoprotein cholesterol levels. These patients presented a significant decrease in total energy intake and in total and saturated fats. CONCLUSION Nutritional intervention as exclusive treatment, with a loss of at least 5% of initial weight, is effective in the treatment of non-alcoholic fatty liver disease.
Collapse
Affiliation(s)
- Maria Cristina Elias
- Department of Medicine, Division of Gastroenterology and Hepatology, Federal University of São Paulo, São Paulo, Brazil.
| | | | | | | | | |
Collapse
|
|
46
|
Abstract
Nonalcoholic fatty liver disease (NAFLD) has become one of the most common causes of liver disease worldwide and has grown proportionately with the rise in obesity. The prevalence of NAFLD is now thought to be around 20% to 40% of the entire population in industrialized Western countries. Insulin resistance, a product of obesity, is central to the pathogenesis of NAFLD, and is improved with weight loss, making this modality the primary goal of therapy. A combination of dietary modifications and increased physical activity, although hard to maintain, is thought to have significant long-term benefits, although further study is required to determine the best and most effective approaches to lifestyle modification. Alternatively, for those individuals who are unable to lose weight despite aggressive efforts, bariatric surgery, which has been shown rather convincingly to improve underlying fatty liver disease, may offer a solution. This review discusses dietary modification, exercise, weight loss pharmacotherapy, and surgical intervention as potential options for patients with NAFLD.
Collapse
|
|
47
|
Ahmed U, Redgrave TG, Oates PS. Effect of dietary fat to produce non-alcoholic fatty liver in the rat. J Gastroenterol Hepatol 2009; 24:1463-71. [PMID: 19702912 DOI: 10.1111/j.1440-1746.2009.05870.x] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Non-alcoholic steatohepatitis (NASH) belongs to a spectrum of non-alcoholic fatty liver disease (NAFLD). Oxidative stress is hypothesized to play an important role in the progression of the disease. We used the Lieber/DeCarli model for NASH to investigate the mechanisms involved in its progression. METHODS Male Sprague-Dawley rats were fed standard (35% of energy from fat) or high fat (71% of energy from fat) liquid diets, ad libitum or two-thirds of the amount consumed ad libitum initially for 3 weeks and then extended to 5 weeks. RESULTS Steatosis was absent in rats at 3 weeks feeding, but by 5 weeks, the high fat/ad lib group showed microvesicular steatosis and foci of macrovesicular steatosis without inflammation. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were not different. By 5 weeks feeding, hepatic triglycerides were highest in the high fat ad lib group and the ad lib groups were higher compared with their restricted groups. The oxidative stress marker, hydroxyalkenal (HAE) was decreased in the standard ad lib compared with the high fat ad lib group. Liver mRNA of interleukin-6, haem oxygenase-1, and markers of endoplasmic stress: C/EBP homologous protein (CHOP), glucose responsive protein-78 (GRP78) and spliced X-box DNA binding protein (spliced XBP1) were similar in the ad lib groups. CONCLUSIONS Extending the feeding period of the high fat/ad lib diet for 5 weeks placed our rats with Type I to II NAFLD compared to the more progressed Type III state previously obtained after 3 weeks feeding. The milder condition obtained raised the prospect of genetic modifiers present in our rats that resist disease progression.
Collapse
Affiliation(s)
- Umbreen Ahmed
- Physiology M311, School of Biomedical, Biomolecular and Chemical Sciences, University of Western Australia, Nedlands, Western Australia, Australia
| | | | | |
Collapse
|
|
48
|
Lecube A, Hernández C, Simó R. Glucose abnormalities in non-alcoholic fatty liver disease and chronic hepatitis C virus infection: the role of iron overload. Diabetes Metab Res Rev 2009; 25:403-10. [PMID: 19444865 DOI: 10.1002/dmrr.972] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C virus (HCV) infection are major causes of liver disease frequently described in outpatient patients with glucose abnormalities. Hyperferritinemia, which suggests that iron overload plays a decisive role in the pathophysiology of insulin resistance and hyperglycemia, is a common finding in both disorders. However, the role of the hepatic iron deposition differs from one to the other. In NAFLD, a moderate liver iron accumulation has been observed and molecular mechanisms, including the downregulation of the liver iron exporter ferroportin-1, have been described. Iron overload will enhance intrahepatic oxidative stress that promotes hepatic fibrosis, interfere with insulin signalling at various levels and may hamper hepatic insulin extraction. Therefore, liver fibrosis, hyperglycemia and hyperinsulinemia will lead to increased levels of insulin resistance and the development of glucose abnormalities. Furthermore, iron depletion by phlebotomy removes liver iron content and reduces serum glucose and insulin resistance in NAFLD patients. Therefore, it seems that iron overload participates in those glucose abnormalities associated with NAFLD. Concerning chronic HCV infection, it has been classically assumed that iron overload contributes to insulin resistance associated with virus infection. However, recent evidence argues against the presence of iron overload in these patients and points to inflammation associated with diabetes as the main contributor to the elevated ferritin levels. Therefore, glucose abnormalities, and specially type 2 diabetes, should be taken into account when evaluating serum ferritin levels in patients with HCV infection.
Collapse
Affiliation(s)
- Albert Lecube
- CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Diabetes and Metabolism Research Unit, Institut de Recerca Hospital Universitari Vall d'Hebron, Barcelona, Spain.
| | | | | |
Collapse
|
|
49
|
Abstract
Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of clinical entities ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) with possible evolution to cirrhosis and hepatocellular carcinoma. Iron is considered a putative element that interacts with oxygen radicals in inducing liver damage and fibrosis. The role of hepatic iron in the progression of NASH remains controversial, but in some patients, iron may have a role in the pathogenesis of NASH. Though genetic factors, insulin resistance, dysregulation of iron-regulatory molecules, erythrophagocytosis by Kupffer cells may be responsible for hepatic iron accumulation in NASH, exact mechanisms involved in iron overload remain to be clarified. Iron reduction therapy such as phlebotomy or dietary iron restriction may be promising in patients with NASH/NAFLD to reduce insulin resistance as well as serum transaminase activities.
Collapse
Affiliation(s)
- Yoshio Sumida
- Center for Digestive and Liver Diseases, Nara City Hospital, Nara, Japan
| | | | | |
Collapse
|
|
50
|
Fujita N, Miyachi H, Tanaka H, Takeo M, Nakagawa N, Kobayashi Y, Iwasa M, Watanabe S, Takei Y. Iron overload is associated with hepatic oxidative damage to DNA in nonalcoholic steatohepatitis. Cancer Epidemiol Biomarkers Prev 2009; 18:424-32. [PMID: 19190144 DOI: 10.1158/1055-9965.epi-08-0725] [Citation(s) in RCA: 83] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Several lines of evidence have suggested that oxidative stress plays an important role for the pathogenesis of nonalcoholic steatohepatitis (NASH). Therefore, by using immunohistochemical staining of liver biopsy samples, we measured hepatic 7,8-dihydro-8-oxo-2' deoxyguanosine (8-oxodG), a DNA base-modified product generated by hydroxyl radicals, of 38 NASH patients and compared with 24 simple steatosis and 10 healthy subjects. Relation of hepatic 8-oxodG with clinical, biochemical, and histologic variables and changes after iron reduction therapy (phlebotomy plus iron-restricted diet) were also examined. Hepatic 8-oxodG levels were significantly higher in NASH compared with simple steatosis (17.5 versus 2.0 8-oxodG-positive cells/10(5) microm(2); P < 0.0001). 8-oxodG was significantly related to iron overload condition, glucose-insulin metabolic abnormality, and severities of hepatic steatosis in NASH patients. Logistic regression analysis also showed that hepatic iron deposit and insulin resistance were independent variables associated with elevated hepatic 8-oxodG. After the iron reduction therapy, hepatic 8-oxodG levels were significantly decreased (from 20.7 to 13.8 positive cells/10(5) microm(2); P < 0.01) with concomitant reductions of serum transaminase levels in NASH patients. In conclusion, iron overload may play an important role in the pathogenesis of NASH by generating oxidative DNA damage and iron reduction therapy may reduce hepatocellular carcinoma incidence in patients with NASH.
Collapse
Affiliation(s)
- Naoki Fujita
- Department of Gastroenterology and Hepatology, Division of Clinical Medicine and Biomedical Science, Institute of Medical Sciences, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
| | | | | | | | | | | | | | | | | |
Collapse
|