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Bogdan RG, Boicean A, Anderco P, Ichim C, Iliescu-Glaja M, Todor SB, Leonte E, Bloanca VA, Crainiceanu ZP, Popa ML. From Liver to Kidney: The Overlooked Burden of Nonalcoholic Fatty Liver Disease in Chronic Kidney Disease. J Clin Med 2025; 14:2486. [PMID: 40217935 PMCID: PMC11989420 DOI: 10.3390/jcm14072486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2025] [Revised: 03/30/2025] [Accepted: 04/03/2025] [Indexed: 04/14/2025] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a contributor to chronic kidney disease (CKD), yet its impact remains underappreciated in clinical practice. Recent studies reveal a strong association between NAFLD and CKD progression, with evidence linking hepatic dysfunction to renal impairment through metabolic and inflammatory pathways. NAFLD not only increases the risk of CKD but also accelerates its progression, leading to worse cardiovascular outcomes and higher mortality, particularly in patients with advanced fibrosis. Despite this growing evidence, NAFLD often goes undiagnosed in CKD patients and routine hepatic evaluation is rarely integrated into nephrology care. Emerging diagnostic tools, including noninvasive biomarkers and imaging techniques, offer potential for earlier detection, yet their clinical implementation remains inconsistent. Although lifestyle modifications remain the foundation of treatment, pharmacotherapeutic strategies, including SGLT2 inhibitors and GLP-1 receptor agonists, have demonstrated potential in mitigating both hepatic and renal impairment. Recognizing the interplay between NAFLD and CKD is essential for improving patient outcomes. A multidisciplinary approach, integrating hepatology and nephrology expertise, is crucial to refining screening strategies, optimizing treatment, and reducing the long-term burden of these coexisting conditions.
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Affiliation(s)
- Razvan George Bogdan
- Plastic Surgery Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (R.G.B.); (M.I.-G.); (E.L.); (V.A.B.); (Z.P.C.)
| | - Adrian Boicean
- Faculty of Medicine, “Lucian Blaga” University of Sibiu, 550024 Sibiu, Romania; (C.I.); (S.B.T.); (M.L.P.)
| | - Paula Anderco
- Faculty of Medicine, “Lucian Blaga” University of Sibiu, 550024 Sibiu, Romania; (C.I.); (S.B.T.); (M.L.P.)
| | - Cristian Ichim
- Faculty of Medicine, “Lucian Blaga” University of Sibiu, 550024 Sibiu, Romania; (C.I.); (S.B.T.); (M.L.P.)
| | - Mihai Iliescu-Glaja
- Plastic Surgery Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (R.G.B.); (M.I.-G.); (E.L.); (V.A.B.); (Z.P.C.)
| | - Samuel Bogdan Todor
- Faculty of Medicine, “Lucian Blaga” University of Sibiu, 550024 Sibiu, Romania; (C.I.); (S.B.T.); (M.L.P.)
| | - Elisa Leonte
- Plastic Surgery Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (R.G.B.); (M.I.-G.); (E.L.); (V.A.B.); (Z.P.C.)
| | - Vlad Adam Bloanca
- Plastic Surgery Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (R.G.B.); (M.I.-G.); (E.L.); (V.A.B.); (Z.P.C.)
| | - Zorin Petrisor Crainiceanu
- Plastic Surgery Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (R.G.B.); (M.I.-G.); (E.L.); (V.A.B.); (Z.P.C.)
| | - Mirela Livia Popa
- Faculty of Medicine, “Lucian Blaga” University of Sibiu, 550024 Sibiu, Romania; (C.I.); (S.B.T.); (M.L.P.)
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Buytaert M, Declercq D, Depoorter F, Cosijn Z, Devisscher L, Raevens S, Verhelst X, Van Vlierberghe H, Geerts A, De Bruyne R, Lefere S. The association of ultra-processed food intake with adolescent metabolic dysfunction-associated steatotic liver disease in the NHANES. Pediatr Obes 2025; 20:e13174. [PMID: 39340247 DOI: 10.1111/ijpo.13174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 08/01/2024] [Accepted: 08/26/2024] [Indexed: 09/30/2024]
Abstract
INTRODUCTION Metabolic dysfunction-associated steatotic liver disease (MASLD) has become a major public health concern. A thorough analysis of the link between ultra-processed food (UPF) intake and MASLD in the adolescent population is lacking. METHODS Adolescent participants of the National Health and Nutrition Examination Survey (NHANES) pre-pandemic cohort were included. Different controlled attenuation parameter (CAP) cut-offs were used to assess MASLD. The percentage energy intake of UPF, categorized according to the NOVA classification, to total energy intake was taken as the main outcome marker. Structural equation modelling (SEM) was used to better quantify the causal connection between UPF and liver steatosis. RESULTS UPF consumption constituted a median 75% (62-86) of total energy intake. There was no significant correlation between UPF intake and CAP (ρ = 0.061, p = 0.091). The median proportion UPF intake was not associated with steatosis severity. SEM similarly yielded a weak and non-significant correlation of 0.078. In participants with MASLD, total energy intake was significantly higher (p < 0.001) and sugar-containing beverage (SCB) consumption showed a non-significant trend towards higher consumption. CONCLUSIONS No clinically relevant association between UPF intake and MASLD in adolescents could be demonstrated. Our results nonetheless suggest that total energy intake and consumption of SCBs are important contributors to paediatric obesity and MASLD.
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Affiliation(s)
- Maarten Buytaert
- Department of Internal Medicine and Pediatrics, Hepatology Research Unit, Ghent University, Ghent, Belgium
- Liver Research Center Ghent, Ghent University Hospital, Ghent, Belgium
| | - Dimitri Declercq
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Center for Nutrition and Dietetics, Ghent University Hospital, Ghent, Belgium
| | - Fleur Depoorter
- Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Zerlina Cosijn
- Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Lindsey Devisscher
- Liver Research Center Ghent, Ghent University Hospital, Ghent, Belgium
- Department of Basic and Applied Medical Sciences, Gut-Liver Immunopharmacology Unit, Ghent University, Ghent, Belgium
| | - Sarah Raevens
- Department of Internal Medicine and Pediatrics, Hepatology Research Unit, Ghent University, Ghent, Belgium
- Liver Research Center Ghent, Ghent University Hospital, Ghent, Belgium
| | - Xavier Verhelst
- Department of Internal Medicine and Pediatrics, Hepatology Research Unit, Ghent University, Ghent, Belgium
- Liver Research Center Ghent, Ghent University Hospital, Ghent, Belgium
| | - Hans Van Vlierberghe
- Department of Internal Medicine and Pediatrics, Hepatology Research Unit, Ghent University, Ghent, Belgium
- Liver Research Center Ghent, Ghent University Hospital, Ghent, Belgium
| | - Anja Geerts
- Department of Internal Medicine and Pediatrics, Hepatology Research Unit, Ghent University, Ghent, Belgium
- Liver Research Center Ghent, Ghent University Hospital, Ghent, Belgium
| | - Ruth De Bruyne
- Liver Research Center Ghent, Ghent University Hospital, Ghent, Belgium
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Ghent University Hospital, Ghent, Belgium
| | - Sander Lefere
- Department of Internal Medicine and Pediatrics, Hepatology Research Unit, Ghent University, Ghent, Belgium
- Liver Research Center Ghent, Ghent University Hospital, Ghent, Belgium
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Faienza MF, Baima J, Cecere V, Monteduro M, Farella I, Vitale R, Antoniotti V, Urbano F, Tini S, Lenzi FR, Prodam F. Fructose Intake and Unhealthy Eating Habits Are Associated with MASLD in Pediatric Obesity: A Cross-Sectional Pilot Study. Nutrients 2025; 17:631. [PMID: 40004960 PMCID: PMC11858415 DOI: 10.3390/nu17040631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2025] [Revised: 02/06/2025] [Accepted: 02/09/2025] [Indexed: 02/27/2025] Open
Abstract
Background/Objectives: Fructose consumption in children is increasing, as is the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). Despite evidence linking added sugars to metabolic syndrome, fructose's impact on liver disease in youth remains unclear, especially in pediatrics. Our study aimed to evaluate the role of fructose intake in metabolic and liver dysfunction in a cohort of pre-school children and adolescents with obesity. Methods: We recruited 41 children and adolescents with obesity (age range: 2.5-16 years, BMI SDS 2.6 ± 0.5 kg/m2). Clinical and biochemical parameters were assessed. Through ultrasound (US), MASLD, hepatorenal index (HRI), subcutaneous adipose tissue (scAT), and visceral adipose tissue (vAT) were assessed. Dietary intake was evaluated using the IDEFICS FFQ and a fructose-specific questionnaire. Results: Pubertal subjects had more scAT and vAT, higher insulin resistance, and higher liver fibrosis parameters than those prepubertal. MASLD was detected in 12 subjects, associated with higher scAT and vAT. Pubertal subjects had lower weekly fructose intake than prepubertal subjects (p < 0.02). However, they consumed less fructose from fruits (p < 0.04) and more from other sugars (p < 0.04) than younger children. Patients with MASLD reported higher fructose intake (p < 0.01), primarily from fruits (p < 0.003), likely due to misreporting, alongside higher consumption of unhealthy food, mainly rich in saturated fats. Conclusions: Fructose intake and unhealthy dietary habits were associated with MASLD in pre-school and adolescents with obesity. Advice to pay attention to fructose intake and foods rich in saturated fats is mandatory to decrease both obesity and MASLD. Further high-powered studies in any pediatric age and different geographical areas are needed to better evaluate the MASLD history.
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Affiliation(s)
- Maria Felicia Faienza
- Pediatric Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari “A. Moro”, 70124 Bari, Italy;
| | - Jessica Baima
- Unit of Endocrinology, Department of Health Sciences, University of Piemonte Orientale, 28100 Novara, Italy; (J.B.); (V.A.); (S.T.)
| | - Valentina Cecere
- Giovanni XXIII Pediatric Hospital, University of Bari “A. Moro”, 70124 Bari, Italy; (V.C.); (R.V.); (F.U.)
| | | | - Ilaria Farella
- Department of Medicine and Surgery, LUM University, 70010 Casamassima, Italy;
| | - Rossella Vitale
- Giovanni XXIII Pediatric Hospital, University of Bari “A. Moro”, 70124 Bari, Italy; (V.C.); (R.V.); (F.U.)
| | - Valentina Antoniotti
- Unit of Endocrinology, Department of Health Sciences, University of Piemonte Orientale, 28100 Novara, Italy; (J.B.); (V.A.); (S.T.)
| | - Flavia Urbano
- Giovanni XXIII Pediatric Hospital, University of Bari “A. Moro”, 70124 Bari, Italy; (V.C.); (R.V.); (F.U.)
| | - Sabrina Tini
- Unit of Endocrinology, Department of Health Sciences, University of Piemonte Orientale, 28100 Novara, Italy; (J.B.); (V.A.); (S.T.)
| | - Francesca Romana Lenzi
- Laboratory of Psychology and Social Processes in Sport, Department of Movement, Human and Health Sciences, University of Rome “Foro Italico”, 00135 Rome, Italy;
| | - Flavia Prodam
- Unit of Endocrinology, Department of Health Sciences, University of Piemonte Orientale, 28100 Novara, Italy; (J.B.); (V.A.); (S.T.)
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Liu M, Cao B, Luo Q, Song Y, Liu K, Wu D. Association between serum uric acid-to-high-density lipoprotein cholesterol ratio and metabolic dysfunction-associated steatotic liver disease among Chinese children with obesity. Front Endocrinol (Lausanne) 2025; 15:1474384. [PMID: 39845880 PMCID: PMC11750666 DOI: 10.3389/fendo.2024.1474384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 12/13/2024] [Indexed: 01/24/2025] Open
Abstract
Background Metabolic dysfunction-associated steatotic liver disease (MASLD) has become one of the most prevalent chronic liver diseases worldwide. The serum uric acid-to-high-density lipoprotein cholesterol ratio (UHR) has been recognized as a novel marker for metabolic diseases, including MASLD. However, all previous studies were performed in adults. Objectives To explore the relationship between the UHR and MASLD in Chinese children with obesity. Methods A retrospective study was conducted including 1284 obese children hospitalized at Beijing Children's Hospital between January 2016 and December 2022. Logistic regression analysis and restricted cubic splines were performed to assess the association between the UHR and the odds of MASLD. The receiver operator characteristic (ROC) curve analysis was used to estimate the diagnostic value of UHR for MASLD in children with obesity. Results The prevalence of MASLD was high, which reached 61.76% in children with obesity. UHR levels were higher in obese children with MASLD than those with non-MASLD for both genders. After dividing all individuals into three groups according to the tertiles of UHR, the prevalence rate of MASLD increased progressively from the tertile 1 to tertile 3 of UHR (34.11% vs. 70.56% vs. 80.61%). Logistic regression analysis showed that obese children with higher UHR levels were significantly associated with MASLD risk, independent of confounding factors such as age, gender, body mass index (BMI), fasting blood glucose (FBG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and creatinine (Cr). The non-linear relationship analysis demonstrated that a UHR between approximately 300 and 900 suggested a saturation effect of MASLD risk. ROC analysis indicated that UHR might serve as a predictive marker for diagnosing MASLD in obese children. Conclusions In children with obesity, UHR is significantly associated with MASLD and might serve as a novel and useful predictor for MASLD onset.
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Affiliation(s)
- Meijuan Liu
- Department of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
| | - Bingyan Cao
- Department of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
| | - Qipeng Luo
- Department of Pain Medicine, Peking University Third Hospital, Beijing, China
| | - Yanning Song
- Department of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
| | - Kai Liu
- Department of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
| | - Di Wu
- Department of Endocrinology, Genetics and Metabolism, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
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Jalili-Moghaddam S, Mearns G, Plank LD, Tautolo ES, Rush E. Pacific Islands Families Study: Serum Uric Acid in Pacific Youth and the Associations with Free-Sugar Intake and Appendicular Skeletal Muscle Mass. Nutrients 2024; 17:54. [PMID: 39796487 PMCID: PMC11722811 DOI: 10.3390/nu17010054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 12/23/2024] [Accepted: 12/25/2024] [Indexed: 01/13/2025] Open
Abstract
BACKGROUND Fructose (50% of sucrose/sugar) is one component of free-sugars and is metabolized to uric acid, which is a known risk factor for gout and metabolic syndrome. Pacific peoples in New Zealand experience a higher prevalence of gout, type 2 diabetes, and overweight/obesity than other ethnic groups. Interestingly, despite having a similar body mass index (BMI), they tend to have a higher proportion of appendicular skeletal muscle mass (ASMM) and less fat than other ethnic groups. Given this context, this study aimed to evaluate the associations between serum uric acid (SUA), free-sugar intake, and ASMM. METHODS In a nested sub-study from the Pacific Islands Families birth-cohort study, 101 boys and 99 girls (all aged 14 and 15 years) self-reported how often they had consumed foods containing sugar in the past month. Anthropometry, body fatness, and ASMM by dual-energy X-ray absorptiometry and metabolic risk factors, including SUA were measured. RESULTS Overall, 43% of girls and 57% of boys consumed 'sugary drinks' twice or more a day. When analyzed by group, ASMM was positively related to SUA for both boys and girls (r = 0.593, p < 0.0001). The effect of the intake of 'sugary drinks' on SUA (r = 0.176, p = 0.013) was reduced when ASMM was considered in the relationships. CONCLUSIONS This study shows high SUA levels in Pacific adolescents, with a positive association between ASMM and SUA in both genders. Sugary drink intake was positively associated with SUA in both boys and girls. High ASMM in Pacific people and an increased risk for raised SUA make it important to work with Pacific communities to reduce added sugar intake and adopt integrated, family-based, culturally centered, and life-course approaches to prevent chronic diseases, including gout.
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Affiliation(s)
- Shabnam Jalili-Moghaddam
- National Institute for Stroke and Applied Neurosciences (NISAN), School of Clinical Sciences, Faculty of Health & Environmental Sciences, Auckland University of Technology, Auckland 0627, New Zealand
| | - Gael Mearns
- School of Clinical Sciences, Auckland University of Technology, Auckland 1010, New Zealand;
| | - Lindsay D. Plank
- Department of Surgery, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand;
| | - El-Shadan Tautolo
- AUT Pacific Health Research Centre, School of Public Health and Interprofessional Studies, Auckland University of Technology, Auckland 1010, New Zealand;
| | - Elaine Rush
- School of Sport and Recreation, Faculty of Health and Environmental Studies, Auckland University of Technology, Auckland 1010, New Zealand;
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Shan GY, Wan H, Zhang YX, Cheng JY, Qiao DR, Liu YY, Shi WN, Li HJ. Pathogenesis and research progress of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Hepatol 2024; 16:1142-1150. [PMID: 39474575 PMCID: PMC11514618 DOI: 10.4254/wjh.v16.i10.1142] [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: 07/20/2024] [Revised: 09/05/2024] [Accepted: 09/23/2024] [Indexed: 10/21/2024] Open
Abstract
In this editorial, we comment on the article by Mei et al. Nonalcoholic steatohepatitis (NASH) is a severe inflammatory subtype of nonalcoholic fatty liver disease (NAFLD) with pathological features including steatosis, hepatocellular damage, and varying degrees of fibrosis. With the epidemic of metabolic diseases and obesity, the prevalence of NAFLD in China has increased, and it is now similar to that in developed countries; thus, NAFLD has become a major chronic liver disease in China. Human epidemiological data suggest that estrogen has a protective effect on NASH in premenopausal women and that sex hormones influence the development of liver disease. This review focuses on the pathogenesis, treatment, and relationship between NASH and other diseases as well as on the relationship between NASH and sex hormone metabolism, with the aim of providing new strategies for the treatment of NASH.
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Affiliation(s)
- Guan-Yue Shan
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Hui Wan
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Yu-Xin Zhang
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Jun-Ya Cheng
- Department of Bioengineering, Pharmacy School of Jilin University, Changchun 130061, Jilin Province, China
| | - Duan-Rui Qiao
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Yi-Ying Liu
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Wen-Na Shi
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Hai-Jun Li
- Institute of Liver Diseases, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
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Shan GY, Wan H, Zhang YX, Cheng JY, Qiao DR, Liu YY, Shi WN, Li HJ. Pathogenesis and research progress of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Hepatol 2024; 16:1322-1330. [DOI: 10.4254/wjh.v16.i10.1322] [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: 07/20/2024] [Revised: 09/05/2024] [Accepted: 09/23/2024] [Indexed: 11/22/2024] Open
Abstract
In this editorial, we comment on the article by Mei et al. Nonalcoholic steatohepatitis (NASH) is a severe inflammatory subtype of nonalcoholic fatty liver disease (NAFLD) with pathological features including steatosis, hepatocellular damage, and varying degrees of fibrosis. With the epidemic of metabolic diseases and obesity, the prevalence of NAFLD in China has increased, and it is now similar to that in developed countries; thus, NAFLD has become a major chronic liver disease in China. Human epidemiological data suggest that estrogen has a protective effect on NASH in premenopausal women and that sex hormones influence the development of liver disease. This review focuses on the pathogenesis, treatment, and relationship between NASH and other diseases as well as on the relationship between NASH and sex hormone metabolism, with the aim of providing new strategies for the treatment of NASH.
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Affiliation(s)
- Guan-Yue Shan
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Hui Wan
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Yu-Xin Zhang
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Jun-Ya Cheng
- Department of Bioengineering, Pharmacy School of Jilin University, Changchun 130061, Jilin Province, China
| | - Duan-Rui Qiao
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Yi-Ying Liu
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Wen-Na Shi
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Hai-Jun Li
- Institute of Liver Diseases, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
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Choi Y, Yang H, Jeon S, Cho KW, Kim SJ, Kim S, Lee M, Suh J, Chae HW, Kim HS, Song K. Prediction of insulin resistance and elevated liver transaminases using serum uric acid and derived markers in children and adolescents. Eur J Clin Nutr 2024; 78:864-871. [PMID: 39060541 DOI: 10.1038/s41430-024-01475-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 07/11/2024] [Accepted: 07/17/2024] [Indexed: 07/28/2024]
Abstract
OBJECTIVE To investigate the relationship of serum uric acid (Uacid) and derived parameters as predictors of insulin resistance (IR) and elevated liver transaminases in children and adolescents METHODS: Data of 1648 participants aged 10-18 years was analyzed using nationwide survey. Logistic regression analysis was performed with IR and elevated liver transaminases as dependent variables, and odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles 2 and 3 of each parameter in comparison to tertile 1, which served as the reference. Receiver operating characteristic (ROC) curves were generated to assess predictability of the parameters for IR and elevated liver transaminases. RESULTS Hyperuricemia, IR, and elevated liver transaminases were significantly associated with each other. All Uacid and derived markers showed continuous increase in ORs and 95% CIs for IR and elevated liver transaminases across the tertiles of several biochemical and metabolic variables of interest (all p < 0.001), and were also significantly predictive in ROC curve. Overall, Uacid combined with obesity indices showed higher ORs and area under the curve (AUC) compared to Uacid alone. Uacid-body mass index (BMI) standard deviation score presented the largest AUC for IR. For elevated liver transaminases, Uacid-BMI and Uacid-waist-to-height ratio showed the largest AUC. CONCLUSIONS Uacid combined with obesity indices are robust markers for prediction of IR and elevated liver transaminases in children and adolescents. Uacid and derived markers have potential as simple markers which do not require fasting for screening of IR and elevated liver transaminases in children and adolescents.
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Affiliation(s)
- Youngha Choi
- Department of Pediatrics, Kangwon National University Hospital, Chuncheon, Republic of Korea
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyejin Yang
- Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Soyoung Jeon
- Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kyoung Won Cho
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seo Jung Kim
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sujin Kim
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Myeongseob Lee
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Junghwan Suh
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hyun Wook Chae
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Ho-Seong Kim
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kyungchul Song
- Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea.
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Szudzik M, Hutsch T, Chabowski D, Zajdel M, Ufnal M. Normal caloric intake with high-fat diet induces metabolic dysfunction-associated steatotic liver disease and dyslipidemia without obesity in rats. Sci Rep 2024; 14:22796. [PMID: 39354056 PMCID: PMC11445425 DOI: 10.1038/s41598-024-74193-y] [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: 07/04/2024] [Accepted: 09/24/2024] [Indexed: 10/03/2024] Open
Abstract
Excessive caloric intake and obesity due to high-fat (HFD) and high-disaccharide (HDD) diets have been recognized as major contributing factors to dyslipidemia and metabolic dysfunction-associated steatotic liver disease (MASLD). However, the effect of HFD and HDD without excessive caloric intake is obscure. The aim of the study was to evaluate the effect of physiological caloric intake delivered through HFD and HDD on liver and lipid profiles. The study was performed on 6-week-old male and female (50/50%) Sprague Dawley rats, receiving either a standard (controls, n = 16), HFD (n = 14) or HDD (n = 14) chow. All groups received the same, standard daily calorie rations, titrated weekly to the age of growing rats, for 12 weeks. A panel of metabolic in vivo measurement were performed, followed by histological, biochemical and molecular biology assays on tissues harvested from sacrificed rats. There was no significant difference between the groups in body weight. In contrast to controls, HFD and HDD groups showed metabolic dysfunction-associated steatohepatitis (MASH) characterized by liver steatosis, inflammation, ballooning of hepatocytes and fibrosis. These changes were more pronounced in the HFD than in the HDD group. The HFD group showed significantly higher serum LDL than controls or HDD rats. Furthermore, the HFD group had higher liver protein levels of low-density lipoprotein receptor (LDLR) but lower plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) than the controls or HDD group. There were no differences between sexes in evaluated parameters. The excessive caloric intake and obesity are not prerequisites for the development of MASH and dyslipidemia in rats. The liver changes induced by the HFD and HDD diets exhibit differences in severity, as well as in the expression patterns of LDLR and PCSK9. Notably, these effects are independent of the sex of the rats.
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Affiliation(s)
- Mateusz Szudzik
- Laboratory of Centre for Preclinical Research, Department of Experimental Physiology and Pathophysiology, Medical University of Warsaw, Pawińskiego 3c Street, Warsaw, Poland.
| | - Tomasz Hutsch
- Department of Pathology and Veterinary Diagnostics, Institute of Veterinary Medicine, Warsaw University of Life Sciences (WULS-SGGW), Nowoursynowska 159c, Warsaw, Poland
- Veterinary Diagnostic Laboratory ALAB bioscience, 22/30 Stępińska Street, Warsaw, Poland
| | - Dawid Chabowski
- Laboratory of Centre for Preclinical Research, Department of Experimental Physiology and Pathophysiology, Medical University of Warsaw, Pawińskiego 3c Street, Warsaw, Poland
| | - Mikołaj Zajdel
- Laboratory of Centre for Preclinical Research, Department of Experimental Physiology and Pathophysiology, Medical University of Warsaw, Pawińskiego 3c Street, Warsaw, Poland
| | - Marcin Ufnal
- Laboratory of Centre for Preclinical Research, Department of Experimental Physiology and Pathophysiology, Medical University of Warsaw, Pawińskiego 3c Street, Warsaw, Poland.
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10
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Tacke F, Horn P, Wai-Sun Wong V, Ratziu V, Bugianesi E, Francque S, Zelber-Sagi S, Valenti L, Roden M, Schick F, Yki-Järvinen H, Gastaldelli A, Vettor R, Frühbeck G, Dicker D. EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol 2024; 81:492-542. [PMID: 38851997 DOI: 10.1016/j.jhep.2024.04.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2024] [Accepted: 04/30/2024] [Indexed: 06/10/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise and discouraging alcohol consumption - as well as optimal management of comorbidities - including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated - is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.
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11
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Faienza MF, Cognetti E, Farella I, Antonioli A, Tini S, Antoniotti V, Prodam F. Dietary fructose: from uric acid to a metabolic switch in pediatric metabolic dysfunction-associated steatotic liver disease. Crit Rev Food Sci Nutr 2024:1-16. [PMID: 39157959 DOI: 10.1080/10408398.2024.2392150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/20/2024]
Abstract
Fructose consumption in pediatric subjects is rising, as the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). Despite increasing evidence supporting the detrimental effects of fructose in the development of Metabolic Syndrome (MetS) and its related comorbidities, the association between fructose intake and liver disease remains unclear, mainly in youths. The current narrative review aims to illustrate the correlation between fructose metabolism and liver functions besides its impact on obesity and MASLD in pediatrics. Fructose metabolism is involved in the liver through the classical lipogenic pathway via de novo lipogenesis (DNL) or in the alternative pathway via uric acid accumulation. Hyperuricemia is one of the main features of MALSD patients, underlining how uric acid is growing interest as a new marker of disease. Observational and interventional studies conducted in children and adolescents, who consumed large amounts of fructose and glucose in their diet, were included. Most of these studies emphasized the association between high fructose intake and weight gain, dyslipidemia, insulin resistance, and MASLD/MASH, even in normal-weight children. Conversely, reducing fructose intake ameliorates liver fat accumulation, lipid profile, and weight. In conclusion, fructose seems a potent inducer of both insulin resistance and hepatic fat accumulation.
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Affiliation(s)
- Maria Felicia Faienza
- Pediatric Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari "Aldo Moro", Bari, Italy
| | - Eleonora Cognetti
- Pediatric Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari "Aldo Moro", Bari, Italy
| | - Ilaria Farella
- Department of Precision and Regenerative Medicine and Ionian Area, Clinica Medica "A. Murri", University of Bari "Aldo Moro", Bari, Italy
| | | | - Sabrina Tini
- Department of Health Science, University of Piemonte Orientale, Novara, Italy
| | | | - Flavia Prodam
- Department of Health Science, University of Piemonte Orientale, Novara, Italy
- Unit of Endocrinology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
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12
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EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Obes Facts 2024; 17:374-444. [PMID: 38852583 PMCID: PMC11299976 DOI: 10.1159/000539371] [Citation(s) in RCA: 18] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 05/15/2024] [Indexed: 06/11/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise and discouraging alcohol consumption - as well as optimal management of comorbidities - including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated - is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.
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13
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Distefano JK, Gerhard GS. Effects of dietary sugar restriction on hepatic fat in youth with obesity. Minerva Pediatr (Torino) 2024; 76:439-448. [PMID: 37284808 PMCID: PMC11229704 DOI: 10.23736/s2724-5276.23.07209-9] [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] [Indexed: 06/08/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in children. Like adults, children can develop the progressive form of NAFLD, nonalcoholic steatohepatitis (NASH), which is characterized by hepatic inflammation, often in the presence of fibrosis. Children with NAFLD are at higher risk of liver-related complications, metabolic dysfunction, and cardiovascular disease in adulthood. Many factors contribute to the escalating prevalence of NAFLD in the pediatric population, among which are an array of dietary patterns such as overnutrition, poor diet quality, and heavy consumption of fat and sugar, including fructose. Findings from an increasing number of epidemiological studies support a connection between high habitual sugar consumption and NAFLD, especially within the context of obesity, but these studies are not able to demonstrate whether sugar is a contributing factor or instead an indicator of an overall poor diet (or lifestyle) quality. To date, only four randomized controlled dietary interventions assessing the effects of sucrose/fructose restriction on hepatic fat fraction in youth with obesity have been published. The objectives of this review are to summarize the key findings from these dietary interventions to achieve a better understanding of the strength of the relationship between dietary sugar restriction and liver fat reduction, despite their inherent limitations, and to discuss the potential impact of weight loss and fat mass reduction on improvement in hepatic steatosis.
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Affiliation(s)
- Johanna K Distefano
- Metabolic Disease Research Unit, Translational Genomics Research Institute, Phoenix, AZ, USA -
| | - Glenn S Gerhard
- Lewis Katz School of Medicine, Temple University School of Medicine, Philadelphia, PA, USA
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14
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Ferreira S, Mendes J, Couto D, Ferreira D, Rêgo C. Nonalcoholic Fatty Liver Disease and Continuous Metabolic Syndrome in Adolescents with Overweight/Obesity. ACTA MEDICA PORT 2024; 37:177-186. [PMID: 38330918 DOI: 10.20344/amp.19834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2023] [Accepted: 07/10/2023] [Indexed: 02/10/2024]
Abstract
INTRODUCTION Nonalcoholic fatty liver disease is the leading cause of pediatric chronic liver disease. Although nonalcoholic fatty liver disease is closely associated with obesity, its relationship with metabolic syndrome in children is not fully understood. The main aim of this study was to evaluate the association between nonalcoholic fatty liver disease and a combination of cardiometabolic risk factors in adolescents with overweight/obesity, using a pediatric metabolic syndrome score (PsiMS) to predict metabolic syndrome. METHODS A retrospective cohort study was conducted. Subjects with overweight/obesity aged 10 to 17 followed at two clinical centers in Portugal (2018 - 2021) were enrolled. The independent association of nonalcoholic fatty liver disease with PsiMS, and of other potential predictors, was tested through multiple regression analyses. Receiver operator characteristic curve analysis was performed to estimate the optimal cutoff of PsiMS to discriminate metabolic syndrome. RESULTS Eighty-four subjects were included (median age at baseline 11.5 years). The prevalence rate of nonalcoholic fatty liver disease was 51% and the prevalence rate of metabolic syndrome was 7%. The mean PsiMS was 2.05 ± 0.48 at the first evaluation, and 2.11 ± 0.52 at the last evaluation (mean follow-up time was 15 months). The nonalcoholic fatty liver disease group had significantly (p < 0.05) higher weight and body mass index z-scores, higher rate of severe obesity and higher waist circumference percentile. PsiMS was highly accurate in predicting metabolic syndrome (area under the curve = 0.96), with an optimal cutoff of 2.46 (sensitivity 100%, specificity 89%). In the univariate analysis, no statistically significant association was observed between nonalcoholic fatty liver disease and PsiMS. In the multiple regression analysis, female sex had a negative association with PsiMS (first and last evaluation). Independent predictors of a higher PsiMS at first evaluation were: ≥ 2 metabolic syndrome criteria, body mass index z-score, insulin resistance and dyslipidemia. At the last evaluation, independent predictors of a higher PsiMS were: nonalcoholic fatty liver disease, baseline PsiMS and body mass index increase from baseline. CONCLUSION The results suggest a good performance of the PsiMS to assess metabolic syndrome and that nonalcoholic fatty liver disease is associated with PsiMS at follow-up.
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Affiliation(s)
- Sofia Ferreira
- Centro Hospitalar Universitário Cova da Beira. Covilhã; Faculty of Health Sciences. Universidade da Beira Interior. Covilhã. Portugal
| | - Joana Mendes
- Centro Hospitalar Universitário Cova da Beira. Covilhã. Portugal
| | - Daniela Couto
- Centro Hospitalar Universitário Cova da Beira. Covilhã. Portugal
| | - Dário Ferreira
- Department of Mathematics and Center of Mathematics and Applications. Universidade da Beira Interior. Covilhã. Portugal
| | - Carla Rêgo
- Hospital CUF Porto. Oporto; Center for Health Technology and Services Research (CINTESIS). Faculty of Medicine. Universidade do Porto. Oporto; Faculty of Biotechnology. Universidade Católica. Oporto. Portugal
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15
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Calcaterra V, Degrassi I, Taranto S, Porro C, Bianchi A, L’assainato S, Silvestro GS, Quatrale A, Zuccotti G. Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) and Thyroid Function in Childhood Obesity: A Vicious Circle? CHILDREN (BASEL, SWITZERLAND) 2024; 11:244. [PMID: 38397356 PMCID: PMC10887660 DOI: 10.3390/children11020244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 02/10/2024] [Accepted: 02/14/2024] [Indexed: 02/25/2024]
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a multisystem disorder characterized by the presence of fatty liver degeneration associated with excess adiposity or prediabetes/type 2 diabetes or metabolic dysregulation. An intricate relationship between the liver and thyroid has been reported in both health and disease. Simultaneously, there is a strong correlation between obesity and both MAFLD and thyroid dysfunction. In this narrative review, we highlighted the relationship between MAFLD and thyroid function in children and adolescents with obesity in order to explore how thyroid hormones (THs) act as predisposing factors in the onset, progression, and sustainability of MAFLD. THs are integral to the intricate balance of metabolic activities, ensuring energy homeostasis, and are indispensable for growth and development. Regarding liver homeostasis, THs have been suggested to interact with liver lipid homeostasis through a series of processes, including stimulating the entry of free fatty acids into the liver for esterification into triglycerides and increasing mitochondrial β-oxidation of fatty acids to impact hepatic lipid accumulation. The literature supports a correlation between MAFLD and obesity, THs and obesity, and MAFLD and THs; however, results in the pediatric population are very limited. Even though the underlying pathogenic mechanism involved in the relationship between MAFLD and thyroid function remains not fully elucidated, the role of THs as predisposing factors of MAFLD could be postulated. A potential vicious circle among these three conditions cannot be excluded. Identifying novel elements that may contribute to MAFLD could offer a practical approach to assessing children at risk of developing the condition.
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Affiliation(s)
- Valeria Calcaterra
- Pediatric and Adolescent Unit, Department of Internal Medicine, University of Pavia, 27100 Pavia, Italy
- Pediatric Department, Buzzi Children’s Hospital, 20154 Milan, Italy; (I.D.); (S.T.); (C.P.); (A.B.); (S.L.); (G.S.S.); (A.Q.); (G.Z.)
| | - Irene Degrassi
- Pediatric Department, Buzzi Children’s Hospital, 20154 Milan, Italy; (I.D.); (S.T.); (C.P.); (A.B.); (S.L.); (G.S.S.); (A.Q.); (G.Z.)
| | - Silvia Taranto
- Pediatric Department, Buzzi Children’s Hospital, 20154 Milan, Italy; (I.D.); (S.T.); (C.P.); (A.B.); (S.L.); (G.S.S.); (A.Q.); (G.Z.)
| | - Cecilia Porro
- Pediatric Department, Buzzi Children’s Hospital, 20154 Milan, Italy; (I.D.); (S.T.); (C.P.); (A.B.); (S.L.); (G.S.S.); (A.Q.); (G.Z.)
| | - Alice Bianchi
- Pediatric Department, Buzzi Children’s Hospital, 20154 Milan, Italy; (I.D.); (S.T.); (C.P.); (A.B.); (S.L.); (G.S.S.); (A.Q.); (G.Z.)
| | - Sara L’assainato
- Pediatric Department, Buzzi Children’s Hospital, 20154 Milan, Italy; (I.D.); (S.T.); (C.P.); (A.B.); (S.L.); (G.S.S.); (A.Q.); (G.Z.)
| | - Giustino Simone Silvestro
- Pediatric Department, Buzzi Children’s Hospital, 20154 Milan, Italy; (I.D.); (S.T.); (C.P.); (A.B.); (S.L.); (G.S.S.); (A.Q.); (G.Z.)
| | - Antonia Quatrale
- Pediatric Department, Buzzi Children’s Hospital, 20154 Milan, Italy; (I.D.); (S.T.); (C.P.); (A.B.); (S.L.); (G.S.S.); (A.Q.); (G.Z.)
| | - Gianvincenzo Zuccotti
- Pediatric Department, Buzzi Children’s Hospital, 20154 Milan, Italy; (I.D.); (S.T.); (C.P.); (A.B.); (S.L.); (G.S.S.); (A.Q.); (G.Z.)
- Department of Biomedical and Clinical Science “L. Sacco”, University of Milan, 20157 Milan, Italy
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16
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De Vito F, Suraci E, Marasco R, Luzza F, Andreozzi F, Sesti G, Fiorentino TV. Association between higher duodenal levels of the fructose carrier glucose transporter-5 and nonalcoholic fatty liver disease and liver fibrosis. J Intern Med 2024; 295:171-180. [PMID: 37797237 DOI: 10.1111/joim.13729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/07/2023]
Abstract
BACKGROUND An increased dietary fructose intake has been shown to exert several detrimental metabolic effects and contribute to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). An augmented intestinal abundance of the fructose carriers glucose transporter-5 (GLUT-5) and glucose transporter-2 (GLUT-2) has been found in subjects with obesity and type 2 diabetes. Herein, we investigated whether elevated intestinal levels of GLUT-5 and GLUT-2, resulting in a higher dietary fructose uptake, are associated with NAFLD and its severity. METHODS GLUT-5 and GLUT-2 protein levels were assessed on duodenal mucosa biopsies of 31 subjects divided into 2 groups based on ultrasound-defined NAFLD presence who underwent an upper gastrointestinal endoscopy. RESULTS Individuals with NAFLD exhibited increased duodenal GLUT-5 protein levels in comparison to those without NAFLD, independently of demographic and anthropometric confounders. Conversely, no difference in duodenal GLUT-2 abundance was observed amongst the two groups. Univariate correlation analyses showed that GLUT-5 protein levels were positively related with body mass index, waist circumference, fasting and 2 h post-load insulin concentrations, and insulin resistance (IR) degree estimated by homeostatic model assessment of IR (r = 0.44; p = 0.02) and liver IR (r = 0.46; p = 0.03) indexes. Furthermore, a positive relationship was observed between duodenal GLUT-5 abundance and serum uric acid concentrations (r = 0.40; p = 0.05), a product of fructose metabolism implicated in NAFLD progression. Importantly, duodenal levels of GLUT-5 were positively associated with liver fibrosis risk estimated by NAFLD fibrosis score. CONCLUSION Increased duodenal GLUT-5 levels are associated with NAFLD and liver fibrosis. Inhibition of intestinal GLUT-5-mediated fructose uptake may represent a strategy for prevention and treatment of NAFLD.
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Affiliation(s)
- Francesca De Vito
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Evelina Suraci
- Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Raffaella Marasco
- Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Francesco Luzza
- Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Francesco Andreozzi
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
| | - Giorgio Sesti
- Department of Clinical and Molecular Medicine, University of Rome-Sapienza, Rome, Italy
| | - Teresa Vanessa Fiorentino
- Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy
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17
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Nicastro E, D'Antiga L. Nutritional Interventions, Probiotics, Synbiotics and Fecal Microbiota Transplantation in Steatotic Liver Disease : Pediatric Fatty Liver and Probiotics. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1449:113-133. [PMID: 39060734 DOI: 10.1007/978-3-031-58572-2_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major health problem worldwide, and the strongest determinant of liver disease in children. The possible influence of high-fat/low-fiber dietary patterns with microbiota (e.g., increased Firmicutes/Bacteroidetes ratio), and ultimately with MASLD occurrence and progression has been elucidated by several association studies. The possible mechanisms through which microbes exert their detrimental effects on MASLD include gut vascular barrier damage, a shift towards non-tolerogenic immunologic environment, and the detrimental metabolic changes, including a relative reduction of propionate and butyrate in favor of acetate, endogenous ethanol production, and impairment of the unconjugated bile acid-driven FXR-mediated gut-liver axis. The impact of nutritional and probiotic interventions in children with MASLD is described.
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Affiliation(s)
- Emanuele Nicastro
- Pediatric Hepatology, Gastroenterology, and Transplantation Unit, Hospital Papa Giovanni XXIII, Bergamo, Italy.
| | - Lorenzo D'Antiga
- Pediatric Hepatology, Gastroenterology, and Transplantation Unit, Hospital Papa Giovanni XXIII, Bergamo, Italy
- Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
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18
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Younossi ZM, Zelber-Sagi S, Henry L, Gerber LH. Lifestyle interventions in nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 2023; 20:708-722. [PMID: 37402873 DOI: 10.1038/s41575-023-00800-4] [Citation(s) in RCA: 127] [Impact Index Per Article: 63.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/26/2023] [Indexed: 07/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a dynamic chronic liver disease that develops in close association with metabolic irregularities. Between 2016 and 2019, the global prevalence among adults was reported as 38% and among children and adolescents it was about 10%. NAFLD can be progressive and is associated with increased mortality from cardiovascular disease, extrahepatic cancers and liver complications. Despite these numerous adverse outcomes, no pharmacological treatments currently exist to treat nonalcoholic steatohepatitis, the progressive form of NAFLD. Therefore, the main treatment is the pursuit of a healthy lifestyle for both children and adults, which includes a diet rich in fruits, nuts, seeds, whole grains, fish and chicken and avoiding overconsumption of ultra-processed food, red meat, sugar-sweetened beverages and foods cooked at high heat. Physical activity at a level where one can talk but not sing is also recommended, including leisure-time activities and structured exercise. Avoidance of smoking and alcohol is also recommended. Policy-makers, community and school leaders need to work together to make their environments healthy by developing walkable and safe spaces with food stores stocked with culturally appropriate and healthy food items at affordable prices as well as providing age-appropriate and safe play areas in both schools and neighbourhoods.
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Affiliation(s)
- Zobair M Younossi
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA.
- Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, VA, USA.
- Inova Medicine, Inova Health System, Falls Church, VA, USA.
| | | | - Linda Henry
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
- Inova Medicine, Inova Health System, Falls Church, VA, USA
| | - Lynn H Gerber
- Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
- Inova Medicine, Inova Health System, Falls Church, VA, USA
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19
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Zhang D, Wang H, Liu A, Wang S, Xu C, Lan K, Xiang W, Zhu K, Xiao Y, Fu J, Jiang R, Chen W, Ni Y. The chronic consumption of dietary fructose promotes the gut Clostridium species imbalance and bile acid alterations in developing nonalcoholic fatty liver disease. J Nutr Biochem 2023; 121:109434. [PMID: 37661068 DOI: 10.1016/j.jnutbio.2023.109434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Revised: 06/30/2023] [Accepted: 08/29/2023] [Indexed: 09/05/2023]
Abstract
Excessive fructose intake is associated with the rising prevalence of nonalcoholic fatty liver disease (NAFLD). The gut microbiome (GM) and bile acids (BAs) are involved in the pathogenesis of NAFLD, but the impact of fructose on their cross-talk is unclear. In this study, adult male C57BL/6J mice were fed a normal diet with tap water (ND) or with 4% fructose in the drinking water (Fru), 60% high-fat diet with tap water (HF) or with 4% fructose solution (HFF) for 12 weeks. Targeted BA analysis was performed in five anatomical sites including the liver, ileum contents, portal serum, cecum contents, and feces. Metagenomic sequencing was performed to explore gut dysbiosis. Within 12 weeks, the 4% fructose diet could initially stimulate gut dysbiosis and BA upregulation in the ileum, portal serum, and cecum when the intestinal and hepatic transport system remained stable without hepatic lipid accumulation. However, the chronic consumption of fructose promoted HF-induced NAFLD, with significantly increased body weight, impaired glucose tolerance, and advanced liver steatosis. BA transporters were inhibited in HFF, causing the block of internal BA circulation and increased BA secretion via cecum contents and feces. Notably, lithocholic acid (LCA) and its taurine conjugates were elevated within the enterohepatic circulation. Meanwhile, the Clostridium species were significantly altered in both Fru and HFF groups and were closely associated with fructose and BA metabolism. In summary, excessive fructose caused gut dysbiosis and BA alterations, promoting HF-induced NAFLD. The crosstalk between Clostridium sp. and LCA species were potential targets in fructose-mediated NAFLD.
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Affiliation(s)
- Danni Zhang
- Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China; Department of Epidemiology and Biostatistics, Zhejiang University School of Public Health, Hangzhou, China
| | - Huiying Wang
- Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Ana Liu
- Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Shan Wang
- Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Cuifang Xu
- Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Ke Lan
- Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, China
| | - Wenqing Xiang
- Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Kun Zhu
- Department of Pathology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Yingping Xiao
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, China
| | - Junfen Fu
- Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Runqiu Jiang
- Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China; Medical School of Nanjing University, Nanjing, China
| | - Wenlian Chen
- Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yan Ni
- Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China; Department of Epidemiology and Biostatistics, Zhejiang University School of Public Health, Hangzhou, China.
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20
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Kuwabara M, Fukuuchi T, Aoki Y, Mizuta E, Ouchi M, Kurajoh M, Maruhashi T, Tanaka A, Morikawa N, Nishimiya K, Akashi N, Tanaka Y, Otani N, Morita M, Miyata H, Takada T, Tsutani H, Ogino K, Ichida K, Hisatome I, Abe K. Exploring the Multifaceted Nexus of Uric Acid and Health: A Review of Recent Studies on Diverse Diseases. Biomolecules 2023; 13:1519. [PMID: 37892201 PMCID: PMC10604821 DOI: 10.3390/biom13101519] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 09/21/2023] [Accepted: 10/06/2023] [Indexed: 10/29/2023] Open
Abstract
The prevalence of patients with hyperuricemia or gout is increasing worldwide. Hyperuricemia and gout are primarily attributed to genetic factors, along with lifestyle factors like consuming a purine-rich diet, alcohol and/or fructose intake, and physical activity. While numerous studies have reported various comorbidities linked to hyperuricemia or gout, the range of these associations is extensive. This review article focuses on the relationship between uric acid and thirteen specific domains: transporters, genetic factors, diet, lifestyle, gout, diabetes mellitus, metabolic syndrome, atherosclerosis, hypertension, kidney diseases, cardiovascular diseases, neurological diseases, and malignancies. The present article provides a comprehensive review of recent developments in these areas, compiled by experts from the Young Committee of the Japanese Society of Gout and Uric and Nucleic Acids. The consolidated summary serves to enhance the global comprehension of uric acid-related matters.
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Affiliation(s)
- Masanari Kuwabara
- Department of Cardiology, Toranomon Hospital, 2-2-2-Toranomon, Minato, Tokyo 105-8470, Japan
| | - Tomoko Fukuuchi
- Laboratory of Biomedical and Analytical Sciences, Faculty of Pharma-Science, Teikyo University, Itabashi, Tokyo 173-8605, Japan;
| | - Yuhei Aoki
- Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Takamatsu 761-0793, Kagawa, Japan;
| | - Einosuke Mizuta
- Department of Cardiology, Sanin Rosai Hospital, Yonago 683-8605, Tottori, Japan;
| | - Motoshi Ouchi
- Department of Health Promotion in Nursing and Midwifery, Innovative Nursing for Life Course, Graduate School of Nursing, Chiba University, Chiba 260-8672, Chiba, Japan;
- Department of Pharmacology and Toxicology, School of Medicine, Dokkyo Medical University, Mibu 321-0293, Tochigi, Japan
| | - Masafumi Kurajoh
- Department of Metabolism, Endocrinology and Molecular Medicine, Graduate School of Medicine, Osaka Metropolitan University, Osaka 5454-8585, Osaka, Japan;
| | - Tatsuya Maruhashi
- Department of Regenerative Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Hiroshima, Japan;
| | - Atsushi Tanaka
- Department of Cardiovascular Medicine, Saga University, Saga 849-8501, Saga, Japan;
| | - Nagisa Morikawa
- Division of Cardio-Vascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Kurume 830-0011, Fukuoka, Japan;
- Department of Community Medicine, Kurume University School of Medicine, Kurume 830-0011, Fukuoka, Japan
| | - Kensuke Nishimiya
- Department of Cardiovascular Medicine, Tohoku University Hospital, Sendai 980-8574, Miyagi, Japan;
| | - Naoyuki Akashi
- Division of Cardiovascular Medicine, Jichi Medical University Saitama Medical Center, Saitama 330-8503, Saitama, Japan;
| | - Yoshihiro Tanaka
- Division of Epidemiology, Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka 420-0881, Shizuoka, Japan;
| | - Naoyuki Otani
- Cardiovascular Center, Dokkyo Medical University Nikko Medical Center, Nikko 321-1298, Tochigi, Japan;
| | - Mihoko Morita
- Department of Hematology and Oncology, University of Fukui Hospital, Eiheiji 910-1193, Fukui, Japan;
| | - Hiroshi Miyata
- Department of Pharmacy, The University of Tokyo Hospital, Bunkyo, Tokyo 113-8655, Japan; (H.M.); (T.T.)
| | - Tappei Takada
- Department of Pharmacy, The University of Tokyo Hospital, Bunkyo, Tokyo 113-8655, Japan; (H.M.); (T.T.)
| | - Hiroshi Tsutani
- National Hospital Organization Awara Hospital, Awara 910-4272, Fukui, Japan;
| | - Kazuhide Ogino
- Department of Cardiology, Japanese Red Cross Tottori Hospital, Tottori 680-8517, Tottori, Japan;
| | - Kimiyoshi Ichida
- Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan;
| | - Ichiro Hisatome
- National Hospital Organization Yonago Medical Center, Yonago 683-0006, Tottori, Japan;
| | - Kohtaro Abe
- Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Fukuoka, Japan;
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21
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Xie J, Xu L, Huang H, Chen Y, Wang J, Li Y, Yu C, Xu C. A simpler definition of MAFLD precisely predicts incident metabolic diseases: a 7-year cohort study. Hepatol Int 2023; 17:1182-1191. [PMID: 37322380 DOI: 10.1007/s12072-023-10558-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 05/27/2023] [Indexed: 06/17/2023]
Abstract
BACKGROUND Metabolic dysfunction-associated fatty liver disease (MAFLD) is a novel definition proposed in 2020 with a relatively complex set of criteria. Thus, simplified criteria that are more applicable are required. This study aimed to develop a simplified set of criteria for identifying MAFLD and predicting MAFLD-related metabolic diseases. METHODS We developed a simplified set of metabolic syndrome-based criteria for MAFLD, and compared the performance of the simplified criteria with that of the original criteria in predicting MAFLD-related metabolic diseases in a 7-year follow-up. RESULTS In the 7-year cohort, a total of 13,786 participants, including 3372 (24.5%) with fatty liver, were enrolled at baseline. Of the 3372 participants with fatty liver, 3199 (94.7%) met the MAFLD-original criteria, 2733 (81.0%) met the simplified criteria, and 164 (4.9%) were metabolic healthy and met neither of the criteria. During 13,612 person-years of follow-up, 431 (16.0%) fatty liver individuals newly developed T2DM, with an incidence rate of 31.7 per 1000 person-years. Participants who met the simplified criteria had a higher risk of incident T2DM than those who met the original criteria. Similar results were observed for incident hypertension, and incident carotid atherosclerotic plaque. CONCLUSION The MAFLD-simplified criteria are an optimized risk stratification tool for predicting metabolic diseases in fatty liver individuals.
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Affiliation(s)
- Jiarong Xie
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, China
- Department of Gastroenterology, the First Affiliated Hospital of Ningbo University, Ningbo, China
- Department of Gastroenterology, Ningbo First Hospital, Ningbo, China
| | - Lei Xu
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, China
- Department of Gastroenterology, the First Affiliated Hospital of Ningbo University, Ningbo, China
- Department of Gastroenterology, Ningbo First Hospital, Ningbo, China
| | - Hangkai Huang
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, China
| | - Yishu Chen
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, China
| | - Jinghua Wang
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, China
| | - Youming Li
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, China
| | - Chaohui Yu
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, China
| | - Chengfu Xu
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, China.
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22
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Park SH, Helsley RN, Fadhul T, Willoughby JLS, Noetzli L, Tu HC, Solheim MH, Fujisaka S, Pan H, Dreyfuss JM, Bons J, Rose J, King CD, Schilling B, Lusis AJ, Pan C, Gupta M, Kulkarni RN, Fitzgerald K, Kern PA, Divanovic S, Kahn CR, Softic S. Fructose induced KHK-C can increase ER stress independent of its effect on lipogenesis to drive liver disease in diet-induced and genetic models of NAFLD. Metabolism 2023; 145:155591. [PMID: 37230214 PMCID: PMC10752375 DOI: 10.1016/j.metabol.2023.155591] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 05/04/2023] [Accepted: 05/10/2023] [Indexed: 05/27/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a liver manifestation of metabolic syndrome, and is estimated to affect one billion individuals worldwide. An increased intake of a high-fat diet (HFD) and sugar-sweetened beverages are risk-factors for NAFLD development, but how their combined intake promotes progression to a more severe form of liver injury is unknown. Here we show that fructose metabolism via ketohexokinase (KHK) C isoform leads to unresolved endoplasmic reticulum (ER) stress when coupled with a HFD intake. Conversely, a liver-specific knockdown of KHK in mice consuming fructose on a HFD is adequate to improve the NAFLD activity score and exert a profound effect on the hepatic transcriptome. Overexpression of KHK-C in cultured hepatocytes is sufficient to induce ER stress in fructose free media. Upregulation of KHK-C is also observed in mice with genetically induced obesity or metabolic dysfunction, whereas KHK knockdown in these mice improves metabolic function. Additionally, in over 100 inbred strains of male or female mice hepatic KHK expression correlates positively with adiposity, insulin resistance, and liver triglycerides. Similarly, in 241 human subjects and their controls, hepatic Khk expression is upregulated in early, but not late stages of NAFLD. In summary, we describe a novel role of KHK-C in triggering ER stress, which offers a mechanistic understanding of how the combined intake of fructose and a HFD propagates the development of metabolic complications.
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Affiliation(s)
- Se-Hyung Park
- Department of Pediatrics, Division of Pediatric Gastroenterology, University of Kentucky College of Medicine, Lexington, KY 40536, USA
| | - Robert N Helsley
- Department of Pediatrics, Division of Pediatric Gastroenterology, University of Kentucky College of Medicine, Lexington, KY 40536, USA
| | - Taghreed Fadhul
- Department of Pediatrics, Division of Pediatric Gastroenterology, University of Kentucky College of Medicine, Lexington, KY 40536, USA
| | | | - Leila Noetzli
- Alnylam Pharmaceuticals Inc., Cambridge, MA 02142, USA
| | - Ho-Chou Tu
- Alnylam Pharmaceuticals Inc., Cambridge, MA 02142, USA
| | - Marie H Solheim
- Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA; Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, 50931 Cologne, Germany
| | - Shiho Fujisaka
- Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA; First Department of Internal Medicine, University of Toyama, Toyama 930-0194, Japan
| | - Hui Pan
- Bioinformatics and Biostatistics Core, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
| | - Jonathan M Dreyfuss
- Bioinformatics and Biostatistics Core, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
| | - Joanna Bons
- Proteomics and Aging Center, Buck Institute for Research on Aging, Novato, CA 94945, USA
| | - Jacob Rose
- Proteomics and Aging Center, Buck Institute for Research on Aging, Novato, CA 94945, USA
| | - Christina D King
- Proteomics and Aging Center, Buck Institute for Research on Aging, Novato, CA 94945, USA
| | - Birgit Schilling
- Proteomics and Aging Center, Buck Institute for Research on Aging, Novato, CA 94945, USA
| | - Aldons J Lusis
- Department of Medicine/Division of Cardiology, Department of Human Genetics, A2-237 Center for the Health Sciences, University of California, Los Angeles, Los Angeles, CA, USA
| | - Calvin Pan
- Department of Medicine/Division of Cardiology, Department of Human Genetics, A2-237 Center for the Health Sciences, University of California, Los Angeles, Los Angeles, CA, USA
| | - Manoj Gupta
- Section of Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02215, USA
| | - Rohit N Kulkarni
- Section of Islet Cell and Regenerative Biology, Joslin Diabetes Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02215, USA
| | | | - Philip A Kern
- Department of Medicine, Division of Endocrinology, University of Kentucky College of Medicine, Lexington, KY 40536, USA
| | - Senad Divanovic
- Department of Pediatrics, University of Cincinnati College of Medicine, Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA
| | - C Ronald Kahn
- Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
| | - Samir Softic
- Department of Pediatrics, Division of Pediatric Gastroenterology, University of Kentucky College of Medicine, Lexington, KY 40536, USA; Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA; Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
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23
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Sandel P, Ma L, Wang H, Pasman EA. You Are What You Eat: A Review on Dietary Interventions for Treating Pediatric Nonalcoholic Fatty Liver Disease. Nutrients 2023; 15:3350. [PMID: 37571287 PMCID: PMC10421125 DOI: 10.3390/nu15153350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 07/20/2023] [Accepted: 07/25/2023] [Indexed: 08/13/2023] Open
Abstract
As the obesity pandemic worsens, cases of pediatric nonalcoholic fatty liver disease (NAFLD) and complications of this disease, such as progressive liver failure, in young adults will continue to rise. Lifestyle changes in the form of dietary modifications and exercise are currently first-line treatments. Large pediatric-specific randomized controlled trials to support specific interventions are currently lacking. A variety of dietary modifications in children with NAFLD have been suggested and studied with mixed results, including low-sugar and high-protein diets, the Mediterranean diet, and the Dietary Approach to Stop Hypertension (DASH). The roles of dietary supplements such as Vitamin E, polyunsaturated fatty acids (PUFAs), ginger, and probiotics have also been investigated. A further understanding of specific dietary interventions and supplements is needed to provide both generalizable and sustainable dietary recommendations to reverse the progression of NAFLD in the pediatric population.
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Affiliation(s)
- Piper Sandel
- Section of Academic General Pediatrics, Department of Pediatrics, University of California San Diego, San Diego, CA 92123, USA; (L.M.); (H.W.)
| | - Lawrence Ma
- Section of Academic General Pediatrics, Department of Pediatrics, University of California San Diego, San Diego, CA 92123, USA; (L.M.); (H.W.)
| | - Helen Wang
- Section of Academic General Pediatrics, Department of Pediatrics, University of California San Diego, San Diego, CA 92123, USA; (L.M.); (H.W.)
| | - Eric A. Pasman
- Division of Pediatric Gastroenterology, Department of Pediatrics, Naval Medical Center San Diego, San Diego, CA 92134, USA;
- Department of Pediatrics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
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24
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Mosca A, Maggiore G. Malattia grassa del fegato: tra fattori ambientali e predisposizione genetica. MEDICO E BAMBINO 2023; 42:355-362. [DOI: 10.53126/meb42355] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is now recognized as the hepatic manifestation of the metabolic syndrome and is the most common cause of chronic liver disease in both adults and children. It is assumed that a genetic predisposition associated with epigenetic factors participates in the evolution of this condition. Visceral obesity and insulin-resistence (IR) have always been considered as key factors linking Metabolic Syndrome (MetS) and NAFLD, but a multifactorial pathogenesis characterized by the interaction between genetic background and environmental factors is increasingly recognized as a key point in the development of metabolic disorders associated with NAFLD. In fact, in patients with NAFLD, insulin resistance, arterial hypertension, abdominal obesity, dyslipidemia and reduced intestinal permeability have often been found, as well as a higher prevalence of comorbidities such as coronary artery disease, obstructive sleep apnea, polycystic ovary syndrome and osteopenia, which define a MetS framework. Early diagnosis is needed to prevent disease progression through primarily lifestyle interventions. Unfortunately, to date, there is no recommended pharmacological intervention in a pediatric setting. However, a variety of new pharmacological agents are under clinical study. To achieve this, studies on the pathways that link the genetic background to the environment before and after birth to the development of NAFLD and MetS and on the molecular mechanisms that define NASH should be increased. Therefore, it is desirable that future studies may be useful in terms of population screening to identify individuals at risk for NAFLD and Mets.
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Affiliation(s)
- Antonella Mosca
- Epatogastroenterologia, Nutrizione, Endoscopia Digestiva e Clinica del Trapianto di Fegato, Ospedal
| | - Giuseppe Maggiore
- Epatogastroenterologia, Nutrizione, Endoscopia Digestiva e Clinica del Trapianto di Fegato, Ospedal
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25
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Kakimoto M, Fujii M, Sato I, Honma K, Nakayama H, Kirihara S, Fukuoka T, Ran S, Hirohata S, Kitamori K, Yamamoto S, Watanabe S. Antioxidant action of xanthine oxidase inhibitor febuxostat protects the liver and blood vasculature in SHRSP5/Dmcr rats. J Appl Biomed 2023; 21:80-90. [PMID: 37376883 DOI: 10.32725/jab.2023.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Accepted: 04/25/2023] [Indexed: 06/29/2023] Open
Abstract
BACKGROUND Xanthine oxidase (XO) generates reactive oxygen species during uric acid production. Therefore, XO inhibitors, which suppress oxidative stress, may effectively treat non-alcoholic steatohepatitis (NASH) and atherosclerosis via uric acid reduction. In this study, we examined the antioxidant effect of the XO inhibitor febuxostat on NASH and atherosclerosis in stroke-prone spontaneously hypertensive 5 (SHRSP5/Dmcr) rats. METHODS SHRSP5/Dmcr rats were divided into three groups: SHRSP5/Dmcr + high-fat and high-cholesterol (HFC) diet [control group, n = 5], SHRSP5/Dmcr + HFC diet + 10% fructose (40 ml/day) [fructose group, n = 5], and SHRSP5/Dmcr + HFC diet + 10% fructose (40 ml/day) + febuxostat (1.0 mg/kg/day) [febuxostat group, n = 5]. Glucose and insulin resistance, blood biochemistry, histopathological staining, endothelial function, and oxidative stress markers were evaluated. RESULTS Febuxostat reduced the plasma uric acid levels. Oxidative stress-related genes were downregulated, whereas antioxidant factor-related genes were upregulated in the febuxostat group compared with those in the fructose group. Febuxostat also ameliorated inflammation, fibrosis, and lipid accumulation in the liver. Mesenteric lipid deposition decreased in the arteries, and aortic endothelial function improved in the febuxostat group. CONCLUSIONS Overall, the XO inhibitor febuxostat exerted protective effects against NASH and atherosclerosis in SHRSP5/Dmcr rats.
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Affiliation(s)
- Mai Kakimoto
- Okayama University, Graduate School of Health Sciences, Department of Medical Technology, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan
| | - Moe Fujii
- Okayama University, Graduate School of Health Sciences, Department of Medical Technology, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan
| | - Ikumi Sato
- Okayama University, Graduate School of Health Sciences, Department of Medical Technology, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan
| | - Koki Honma
- Okayama University, Graduate School of Health Sciences, Department of Medical Technology, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan
| | - Hinako Nakayama
- Okayama University, Graduate School of Health Sciences, Department of Medical Technology, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan
| | - Sora Kirihara
- Okayama University, Graduate School of Health Sciences, Department of Medical Technology, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan
| | - Taketo Fukuoka
- Okayama University, Faculty of Health Sciences, Department of Medical Technology, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama, 700-8558, Japan
| | - Shang Ran
- Okayama University, Graduate School of Health Sciences, Department of Medical Technology, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan
| | - Satoshi Hirohata
- Okayama University, Academic Field of Health Science, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama, 700-8558, Japan
| | - Kazuya Kitamori
- Kinjo Gakuin University, College of Human Life and Environment, 2-1723, Omori, Moriyama-ku, Nagoya-shi, Aichi, 463-8521, Japan
| | - Shusei Yamamoto
- Okayama University, Graduate School of Health Sciences, Department of Medical Technology, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan
- Okayama University, Academic Field of Health Science, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama, 700-8558, Japan
| | - Shogo Watanabe
- Okayama University, Academic Field of Health Science, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama, 700-8558, Japan
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26
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Pedersen K, Ipsen DH, Skat-Rørdam J, Lykkesfeldt J, Tveden-Nyborg P. Dietary Long-Chain Fatty Acids Accelerate Metabolic Dysfunction in Guinea Pigs with Non-Alcoholic Steatohepatitis. Nutrients 2023; 15:nu15112445. [PMID: 37299406 DOI: 10.3390/nu15112445] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 05/17/2023] [Accepted: 05/22/2023] [Indexed: 06/12/2023] Open
Abstract
The composition of dietary fatty acids may be important for the development and progression of metabolic syndrome and non-alcoholic steatohepatitis (NASH). This study investigated the effect of two high-fat diets based on coconut oil, containing predominantly medium-chain fatty acids (MCFA), or cocoa butter, containing mainly long-chain fatty acids (LCFA), on glucose homeostasis and NASH in guinea pigs following 16 and 32 weeks of diet. At week 16, glucose intolerance was increased in the LCFA animals compared to the MCFA animals (p < 0.001), with both groups differing from the controls by week 32 (p < 0.0001), supported by increased hemoglobin A1c (p < 0.05). NASH was present in both high-fat groups from week 16, with advancing fibrosis appearing more progressive in the LCFA animals at week 16. In agreement, gene expression showed overall increased expression of NASH target genes in the LCFA animals compared to the MCFA animals at weeks 16 and 32 (p < 0.05 and p < 0.0001, respectively). The LCFA animals also displayed increased plasma uric acid at both time points (p < 0.05), a phenomenon linked to NASH in humans. In conclusion, this study reports that a diet high in LCFA promotes metabolic imbalance and may accelerate NASH-associated hepatic fibrosis. This highlights the importance of a critical evaluation of fatty acid composition when investigating NASH-associated endpoints.
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Affiliation(s)
- Kamilla Pedersen
- Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark
| | - David Højland Ipsen
- Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark
- Integrated Physiology Research, Obesity and NASH Pharmacology, Novo Nordisk A/S, 2760 Måløv, Denmark
| | - Josephine Skat-Rørdam
- Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark
| | - Jens Lykkesfeldt
- Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark
| | - Pernille Tveden-Nyborg
- Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark
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Semmler G, Datz C, Trauner M. Eating, diet, and nutrition for the treatment of non-alcoholic fatty liver disease. Clin Mol Hepatol 2023; 29:S244-S260. [PMID: 36517001 PMCID: PMC10029946 DOI: 10.3350/cmh.2022.0364] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 12/06/2022] [Accepted: 12/08/2022] [Indexed: 12/23/2022] Open
Abstract
Nutrition and dietary interventions are a central component in the pathophysiology, but also a cornerstone in the management of patients with non-alcoholic fatty liver disease (NAFLD). Summarizing our rapidly advancing understanding of how our diet influences our metabolism and focusing on specific effects on the liver, we provide a comprehensive overview of dietary concepts to counteract the increasing burden of NAFLD. Specifically, we emphasize the importance of dietary calorie restriction independently of the macronutrient composition together with adherence to a Mediterranean diet low in added fructose and processed meat that seems to exert favorable effects beyond calorie restriction. Also, we discuss intermittent fasting as a type of diet specifically tailored to decrease liver fat content and increase ketogenesis, awaiting future study results in NAFLD. Finally, personalized dietary recommendations could be powerful tools to increase the effectiveness of dietary interventions in patients with NAFLD considering the genetic background and the microbiome, among others.
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Affiliation(s)
- Georg Semmler
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
| | - Christian Datz
- Department of Internal Medicine, General Hospital Oberndorf, Teaching Hospital of the Paracelsus Medical University Salzburg, Oberndorf, Austria
| | - Michael Trauner
- Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
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Park SH, Helsley RN, Fadhul T, Willoughby JL, Noetzli L, Tu HC, Solheim MH, Fujisaka S, Pan H, Dreyfuss JM, Bons J, Rose J, King CD, Schilling B, Lusis AJ, Pan C, Gupta M, Kulkarni RN, Fitzgerald K, Kern PA, Divanovic S, Kahn CR, Softic S. Fructose Induced KHK-C Increases ER Stress and Modulates Hepatic Transcriptome to Drive Liver Disease in Diet-Induced and Genetic Models of NAFLD. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.01.27.525605. [PMID: 36747758 PMCID: PMC9900898 DOI: 10.1101/2023.01.27.525605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a liver manifestation of metabolic syndrome, and is estimated to affect one billion individuals worldwide. An increased intake of a high-fat diet (HFD) and sugar-sweetened beverages are risk-factors for NAFLD development, but how their combined intake promotes progression to a more severe form of liver injury is unknown. Here we show that fructose metabolism via ketohexokinase (KHK) C isoform increases endoplasmic reticulum (ER) stress in a dose dependent fashion, so when fructose is coupled with a HFD intake it leads to unresolved ER stress. Conversely, a liver-specific knockdown of KHK in C57BL/6J male mice consuming fructose on a HFD is adequate to improve the NAFLD activity score and exert a profound effect on the hepatic transcriptome. Overexpression of KHK-C in cultured hepatocytes is sufficient to induce ER stress in fructose free media. Upregulation of KHK-C is also observed in genetically obesity ob/ob, db/db and lipodystrophic FIRKO male mice, whereas KHK knockdown in these mice improves metabolic function. Additionally, in over 100 inbred strains of male or female mice hepatic KHK expression correlates positively with adiposity, insulin resistance, and liver triglycerides. Similarly, in 241 human subjects and their controls, hepatic Khk expression is upregulated in early, but not late stages of NAFLD. In summary, we describe a novel role of KHK-C in triggering ER stress, which offers a mechanistic understanding of how the combined intake of fructose and a HFD propagates the development of metabolic complications.
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Affiliation(s)
- Se-Hyung Park
- Department of Pediatrics, Division of Pediatric Gastroenterology, University of Kentucky College of Medicine, Lexington, KY. 40536
| | - Robert N. Helsley
- Department of Pediatrics, Division of Pediatric Gastroenterology, University of Kentucky College of Medicine, Lexington, KY. 40536
| | - Taghreed Fadhul
- Department of Pediatrics, Division of Pediatric Gastroenterology, University of Kentucky College of Medicine, Lexington, KY. 40536
| | | | | | - Ho-Chou Tu
- Alnylam Pharmaceuticals Inc., Cambridge, MA. 02142
| | - Marie H. Solheim
- Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA. 02215
- Department of Neuronal Control of Metabolism, Max Planck Institute for Metabolism Research, 50931 Cologne, Germany
| | - Shiho Fujisaka
- Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA. 02215
- First Department of Internal Medicine, University of Toyama, Toyama 930-0194, Japan
| | - Hui Pan
- Bioinformatics and Biostatistics Core, Joslin Diabetes Center, Harvard Medical School, Boston, MA
| | - Jonathan M. Dreyfuss
- Bioinformatics and Biostatistics Core, Joslin Diabetes Center, Harvard Medical School, Boston, MA
| | - Joanna Bons
- Proteomics and Aging Center, Buck Institute for Research on Aging, Novato, CA 94945
| | - Jacob Rose
- Proteomics and Aging Center, Buck Institute for Research on Aging, Novato, CA 94945
| | - Christina D. King
- Proteomics and Aging Center, Buck Institute for Research on Aging, Novato, CA 94945
| | - Birgit Schilling
- Proteomics and Aging Center, Buck Institute for Research on Aging, Novato, CA 94945
| | - Aldons J. Lusis
- Department of Medicine/Division of Cardiology, Department of Human Genetics, A2-237 Center for the Health Sciences, University of California, Los Angeles, Los Angeles, CA USA
| | - Calvin Pan
- Department of Medicine/Division of Cardiology, Department of Human Genetics, A2-237 Center for the Health Sciences, University of California, Los Angeles, Los Angeles, CA USA
| | - Manoj Gupta
- Section of Islet Cell and Regenerative Biology, Joslin Diabetes Center; Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02215
| | - Rohit N. Kulkarni
- Section of Islet Cell and Regenerative Biology, Joslin Diabetes Center; Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02215
| | | | - Philip A. Kern
- Department of Medicine, Division of Endocrinology, University of Kentucky College of Medicine, Lexington, KY. 40536
| | - Senad Divanovic
- Department of Pediatrics, University of Cincinnati College of Medicine, Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229
| | - C. Ronald Kahn
- Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA. 02215
| | - Samir Softic
- Department of Pediatrics, Division of Pediatric Gastroenterology, University of Kentucky College of Medicine, Lexington, KY. 40536
- Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA. 02215
- Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY. 40536
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29
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Pan Y, Zhang X. Diet Modulates Gut Microbiome and Metabolites in Non-alcoholic Fatty Liver Diseases. MICROBIOME IN GASTROINTESTINAL CANCER 2023:131-146. [DOI: 10.1007/978-981-19-4492-5_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Cojocariu C, Popa C, Muzica C, Stanciu C, Cuciureanu T, Trifan A. Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease. ESSENTIALS OF NON-ALCOHOLIC FATTY LIVER DISEASE 2023:171-181. [DOI: 10.1007/978-3-031-33548-8_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Citrus Bergamia and Cynara Cardunculus Reduce Serum Uric Acid in Individuals with Non-Alcoholic Fatty Liver Disease. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:medicina58121728. [PMID: 36556930 PMCID: PMC9784233 DOI: 10.3390/medicina58121728] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Revised: 11/16/2022] [Accepted: 11/24/2022] [Indexed: 11/29/2022]
Abstract
Background and Objectives: Hyperuricemia and liver steatosis are risk factors for cardiovascular diseases and mortality. The use of natural compounds could be a safe and effective alternative to drugs for the treatment of fatty liver and hyperuricemia. Polyphenolic fraction of Citrus Bergamia in association with the extract of Cynara Cardunculus, as nutraceutical, is able to reduce body weight, hepatic steatosis and markers of oxidative stress. Then, we performed a secondary analysis of a double-blind placebo-controlled trial to examine the effects of this nutraceutical on serum uric acid levels in adults with fatty liver. Materials and Methods: The study included 94 individuals with hepatic steatosis. For six weeks, the intervention group was given a nutraceutical (300 mg/day) comprising a Bergamot polyphenol fraction and Cynara Cardunculus extract. The control group received a daily pill of placebo. Serum uric acid, lipids, glucose and anthropometric parameters were assessed at baseline and after 6 weeks. Results: We found a greater reduction in serum uric acid in the participants taking the nutraceutical rather than placebo (−0.1 ± 0.7 mg/dL vs. 0.3 ± 0.7 mg/dL, p = 0.004), and especially in those with moderate/severe hepatic steatosis also after adjustment for confounding variables. In addition, we analysed the two groups according to tertiles of uric acid concentration. Among participants taking the nutraceutical, we found in those with the highest baseline serum uric acid (>5.4 mg/dL) the greater reduction compared to the lowest baseline uric acid (−7.8% vs. +4.9%; adjusted p = 0.04). The stepwise multivariable analysis confirmed the association between the absolute serum uric acid change and nutraceutical treatment (B = −0.43; p = 0.004). Conclusions: A nutraceutical containing bioactive components from bergamot and wild cardoon reduced serum uric acid during 6 weeks in adults with fatty liver. Future investigations are needed to evaluate the efficacy of this nutraceutical in the treatment of hyperuricaemia.
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Porto A, Pan Z, Zhou W, Sokol RJ, Klaczkiewicz K, Sundaram SS. Macronutrient and Micronutrient Intake in Adolescents With Non-alcoholic Fatty Liver Disease: The Association With Disease Severity. J Pediatr Gastroenterol Nutr 2022; 75:666-674. [PMID: 35897136 PMCID: PMC9707340 DOI: 10.1097/mpg.0000000000003578] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES While dietary changes are recommended to treat pediatric non-alcoholic fatty liver disease (NAFLD), the role of specific nutrients in disease progression is unclear. The objective of this study is to (1) assess the macronutrient and micronutrient intake in adolescents with liver biopsy proven NAFLD [with and without non-alcoholic steatohepatitis (NASH)] and lean controls; (2) determine nutritional predictors of disease severity amongst these groups. METHODS Adolescents with biopsy-proven NAFLD and lean controls completed the Harvard Food Frequency Questionnaire. RESULTS Twenty-eight NAFLD and 15 lean controls were studied. NAFLD with (n = 20) and without NASH (n = 8) had similar total calorie, protein, fat, and carbohydrate intake. Subjects with NASH had higher total sugar (122.3 ± 48.3 vs 83.1 ± 38.8 g), glucose (24.3 ± 9.3 vs 15.2 ± 7.5 g), sucrose (42.3 ± 16.9 vs 28.8 ± 11.7 g), and fructose (29.4 ± 12.5 vs 18.1 ± 8.0 g) intake than those with NAFLD but without NASH ( P < 0.05). Both NAFLD groups had similar micronutrient intake. Alanine aminotransferase (ALT) correlated with total caloric intake ( ρ = 0.4; P = 0.04). Total carbohydrate calories correlated with a higher NAS summary score ( ρ = 0.38; P = 0.04) and lobular inflammation ( ρ = 0.50; P = 0.007). Percent calories from added sugar and glucose correlated with worsening NAS summary score ( ρ = 0.44, P = 0.02; ρ = 0.48, P = 0.009) and lobular inflammation ( ρ = 0.51, P = 0.006; ρ = 0.53, P = 0.004). Percent calories from fructose correlated with lobular inflammation ( ρ = 0.56; P = 0.002). Total daily calories, protein, fat, carbohydrate, and micronutrient intake were similar between NAFLD and lean controls. CONCLUSIONS NASH patients consume similar total calories, protein, and fat as those without NASH, but have significantly higher sugar intake. NAFLD and lean children, however, have similar macro/micronutrient intake. Histologic disease severity correlates with total carbohydrate and added sugar intake, supporting a role for simple sugar intake in NAFLD progression.
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Affiliation(s)
- Ariel Porto
- From the Children's Hospital Colorado, Aurora, CO
| | | | | | - Ronald J Sokol
- the Section of Pediatric Gastroenterology, Hepatology and Nutrition and Digestive Health Institute, Department of Pediatrics, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO
| | - Kelly Klaczkiewicz
- the Section of Pediatric Gastroenterology, Hepatology and Nutrition and Digestive Health Institute, Department of Pediatrics, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO
| | - Shikha S Sundaram
- the Section of Pediatric Gastroenterology, Hepatology and Nutrition and Digestive Health Institute, Department of Pediatrics, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO
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Lonardo A, Mantovani A, Petta S, Carraro A, Byrne CD, Targher G. Metabolic mechanisms for and treatment of NAFLD or NASH occurring after liver transplantation. Nat Rev Endocrinol 2022; 18:638-650. [PMID: 35840803 DOI: 10.1038/s41574-022-00711-5] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/07/2022] [Indexed: 11/08/2022]
Abstract
The rising tide of non-alcoholic fatty liver disease (NAFLD) associated with the obesity epidemic is a major health concern worldwide. NAFLD - specifically its more advanced form, non-alcoholic steatohepatitis (NASH)-related cirrhosis - is now the fastest growing indication for liver transplantation in the USA and Europe. Although the short-term and mid-term overall survival rates of patients who receive a liver transplant for NASH-related cirrhosis are essentially similar to those of patients who receive a transplant for other liver indications, recipients with NASH-related cirrhosis have an increased risk of waiting-list mortality and of developing recurrent liver disease and cardiometabolic complications in the longer term after liver transplantation. This Review provides a brief overview of the epidemiology of NAFLD and NASH and the occurrence of NAFLD or NASH in patients after liver transplantation for NASH and other liver indications. It also discusses the putative metabolic mechanisms underlying the emergence of NAFLD or NASH after liver transplantation as well as optimal therapeutic approaches for recipients of liver transplants, including the management of cardiometabolic comorbidities, tailored immunosuppression, lifestyle changes and pharmacotherapy for NAFLD.
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Affiliation(s)
- Amedeo Lonardo
- Metabolic Syndrome Unit, University of Modena, Modena, Italy
| | - Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Verona, Italy
| | - Salvatore Petta
- Section of Gastroenterology and Hepatology, PROMISE, University of Palermo, Palermo, Italy
| | - Amedeo Carraro
- Liver Transplant Unit, University of Verona, Verona, Italy
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK
- 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 of Verona, Verona, Italy.
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Di Bonito P, Valerio G, Licenziati MR, Di Sessa A, Miraglia del Giudice E, Morandi A, Maffeis C, Baroni MG, Chiesa C, Pacifico L, Manco M. Uric acid versus metabolic syndrome as markers of fatty liver disease in young people with overweight/obesity. Diabetes Metab Res Rev 2022; 38:e3559. [PMID: 35728124 PMCID: PMC9787784 DOI: 10.1002/dmrr.3559] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 03/23/2022] [Accepted: 06/03/2022] [Indexed: 12/30/2022]
Abstract
AIMS To compare the association of high serum uric acid (HUA) or metabolic syndrome (MetS) with fatty liver disease (FLD) in youths with overweight/obesity (OW/OB). MATERIALS AND METHODS Cross-sectional study of anthropometrics, biochemical variables, and liver ultrasound of 3104 individuals with OW/OB (age 5-17 years). Metabolic syndrome was defined by ≥ 3 criteria among (1) high waist circumference; (2) high triglycerides; (3) low high-density lipoproteins; (4) fasting glucose ≥100 mg/dl; (5) blood pressure ≥95th percentile in children, and ≥130/80 mmHg in adolescents. High serum uric acid was defined as serum UA value ≥ 75th percentile adjusted for sex. Fatty liver disease was determined by echography. RESULTS The sample was stratified in four categories: (1) no HUA, no MetS (reference category); (2) MetS; (3) HUA; (4) HUA and MetS (HUA + MetS). The prevalence of FLD increased across the four categories from 29.9%, 44.0%, 52.2%, to 67.1%, respectively (p < 0.0001). The ORs for the categorical variables were 1.33 (1.06-1.68) for MetS (p = 0.02), 3.19 (2.51-4.05) for HUA (p < 0.0001) and 3.72 (2.65-5.21) for HUA + MetS (p < 0.0001), versus the reference category regardless of the body mass index. CONCLUSIONS HUA represents a useful marker of FLD in youths with OW/OB, given its greater ability to identify those at increased risk of the disease compared to MetS. The ability of both to predict incident FLD must be investigated in longitudinal study.
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Affiliation(s)
- Procolo Di Bonito
- Department of Internal Medicine"S. Maria delle Grazie" HospitalPozzuoliItaly
| | - Giuliana Valerio
- Department of Movement Sciences and WellbeingUniversity "Parthenope"NaplesItaly
| | - Maria Rosaria Licenziati
- Department of NeuroscienceObesity and Endocrine Disease UnitSantobono‐Pausilipon Children's HospitalNaplesItaly
| | - Anna Di Sessa
- Department of Woman, Child and General and Specialized SurgeryUniversity of Campania "Luigi Vanvitelli"NaplesItaly
| | | | - Anita Morandi
- Pediatric Diabetes and Metabolic Disorders UnitUniversity of VeronaVeronaItaly
| | - Claudio Maffeis
- Pediatric Diabetes and Metabolic Disorders UnitUniversity of VeronaVeronaItaly
| | - Marco Giorgio Baroni
- Department of Clinical Medicine, Life, Health & Environmental SciencesUniversity of L'AquilaItaly
- Neuroendocrinology and Metabolic DiseasesIRCCS NeuromedPozzilliItaly
| | - Claudio Chiesa
- Institute of Translational PharmacologyNational Research CouncilRomeItaly
| | - Lucia Pacifico
- Department of PediatricsPoliclinico Umberto I Hospital"Sapienza" University of RomeRomeItaly
| | - Melania Manco
- Research Area for Multifactorial Disease and Complex PhenotypesChildren's Hospital Bambino GesùIRCCSRomeItaly
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35
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Byrne CD. Banting memorial lecture 2022: 'Type 2 diabetes and nonalcoholic fatty liver disease: Partners in crime'. Diabet Med 2022; 39:e14912. [PMID: 35790023 PMCID: PMC9546361 DOI: 10.1111/dme.14912] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 06/14/2022] [Accepted: 06/29/2022] [Indexed: 11/28/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) was first described in the 1980s, but in the 21st century, NAFLD has become a very common condition. The explanation for this relatively recent problem is in large part due to the recent epidemic of obesity and type 2 diabetes (T2DM) increasing the risk of NAFLD. NAFLD is a silent condition that may not become manifest until severe liver damage (fibrosis or cirrhosis) has occurred. Consequently, NAFLD and its complications often remain undiagnosed. Research evidence shows that NAFLD is extremely common and some estimates suggest that it occurs in up to 70% of people with T2DM. In the last 5 years, it has become evident that NAFLD not only increases the risk of cirrhosis, primary liver cancer and end-stage liver disease, but NAFLD is also an important multisystem disease that has major implications beyond the liver. NAFLD increases the risk of incident T2DM, cardiovascular disease, chronic kidney disease and certain extra-hepatic cancers, and NAFLD and T2DM form part of a vicious spiral of worsening diseases, where one condition affects the other and vice versa. Diabetes markedly increases the risk of liver fibrosis and liver fibrosis is the most important risk factor for hepatocellular carcinoma. It is now possible to diagnose liver fibrosis with non-invasive tools and therefore it is important to have clear care pathways for the management of NAFLD in patients with T2DM. This review summarises key recent research that was discussed as part of the Banting lecture at the annual scientific conference in 2022.
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Affiliation(s)
- Christopher D. Byrne
- Division of Endocrinology & MetabolismUniversity Hospital Southampton and University of SouthamptonSouthamptonUK
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36
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Zelber-Sagi S, Grinshpan LS, Ivancovsky-Wajcman D, Goldenshluger A, Gepner Y. One size does not fit all; practical, personal tailoring of the diet to NAFLD patients. Liver Int 2022; 42:1731-1750. [PMID: 35675167 DOI: 10.1111/liv.15335] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 06/03/2022] [Accepted: 06/06/2022] [Indexed: 02/13/2023]
Abstract
Different dietary regimens for weight loss have developed over the years. Since the most evidenced treatment for non-alcoholic fatty liver disease (NAFLD) is weight reduction, it is not surprising that more diets targeting obesity are also utilized for NAFLD treatment. However, beyond the desired weight loss effects, one should not ignore the dietary composition of each diet, which may not necessarily be healthy or safe over the long term for hepatic and extrahepatic outcomes, especially cardiometabolic outcomes. Some of these diets are rich in saturated fat and red meat, are very strict, and require close medical supervision. Some may also be very difficult to adhere to for long periods, thus reducing the patient's motivation. The evidence for a direct benefit to NAFLD by restrictive diets such as very-low-carb, ketogenic, very-low-calorie diets, and intermittent fasting is scarce, and the long-term safety has not been tested. Nowadays, the approach is that the diet should be tailored to the patient's cultural and personal preferences. There is strong evidence for the independent protective association of NAFLD with a diet based on healthy eating patterns of minimally-processed foods, low in sugar and saturated fat, high in polyphenols, and healthy types of fats. This leads to the conclusion that a Mediterranean diet should serve as a basis that can be restructured into other kinds of diets. This review will elaborate on the different diets and their role in NAFLD. It will provide a practical guide to tailor the diet to the patients without compromising its composition and safety.
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Affiliation(s)
- Shira Zelber-Sagi
- School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel.,Department of Gastroenterology Tel Aviv Medical Center, Tel Aviv, Israel
| | - Laura Sol Grinshpan
- School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel.,Department of Gastroenterology Tel Aviv Medical Center, Tel Aviv, Israel
| | - Dana Ivancovsky-Wajcman
- School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel.,Department of Gastroenterology Tel Aviv Medical Center, Tel Aviv, Israel
| | - Ariela Goldenshluger
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, and Sylvan Adams Sports Institute, Tel-Aviv University, Tel-Aviv, Israel
| | - Yftach Gepner
- Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine, and Sylvan Adams Sports Institute, Tel-Aviv University, Tel-Aviv, Israel
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Quek SXZ, Tan EXX, Ren YP, Muthiah M, Loo EXL, Tham EH, Siah KTH. Factors early in life associated with hepatic steatosis. World J Hepatol 2022; 14:1235-1247. [PMID: 35978672 PMCID: PMC9258263 DOI: 10.4254/wjh.v14.i6.1235] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 03/01/2022] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The rise in prevalence of non-alcoholic fatty liver disease (NAFLD) mirrors the obesity epidemic. NAFLD is insidious but may gradually progress from simple steatosis to steatohepatitis, fibrosis and cirrhosis and/or hepatocellular carcinoma. Intervention strategies to ameliorate developmental programming of NAFLD may be more efficacious during critical windows of developmental plasticity.
AIM To review the early developmental factors associated with NAFLD.
METHODS Databases MEDLINE via PubMed, and EMBASE and Reference Citation Analysis were searched and relevant publications up to April 30, 2021 were assessed. Original research studies that included risk factors associated with early development of NAFLD in human subjects were included. These factors include: Maternal factors, intrauterine and prenatal factors, post-natal factors, genetic and ethnic predisposition, childhood and adolescence environmental factors. Studies were excluded if they were review articles or animal studies, case reports or conference abstracts, or if NAFLD was not clearly defined and assessed radiologically.
RESULTS Of 1530 citations identified by electronic search, 420 duplicates were removed. Of the 1110 citations screened from title and abstract, 80 articles were included in the final analysis. Genetic polymorphisms such as patatin-like phospholipase domain-containing protein 3 (PNPLA3) and membrane-bound O-acyltransferase domain-containing protein 7 (MBOAT7) were associated with increased risk of NAFLD. Familial factors such as maternal obesogenic environment and parental history of hepatic steatosis was associated with offspring NAFLD. Longer duration of exclusive breastfeeding in infancy was associated with a lower risk of developing NAFLD later in life while metabolic dysfunction and/or obesity in adolescence was associated with increased risk of NAFLD. Studies relating to socioeconomic factors and its association with NAFLD reported confounding results.
CONCLUSION Maternal metabolic dysfunction during pregnancy, being exclusively breastfed for a longer time postnatally, diet and physical activity in childhood and adolescence are potential areas of intervention to decrease risk of NAFLD.
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Affiliation(s)
- Sabrina Xin Zi Quek
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
| | - Eunice Xiang-Xuan Tan
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore 119228, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - Yi Ping Ren
- Department of Medicine, National University Hospital, Singapore 119228, Singapore
| | - Mark Muthiah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
- National University Centre for Organ Transplantation, National University Health System, Singapore 119228, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
| | - Evelyn Xiu Ling Loo
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore; Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore 119228, Singapore
- Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore 117609, Singapore
| | - Elizabeth Huiwen Tham
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore; Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore 119228, Singapore
| | - Kewin Tien Ho Siah
- Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Singapore 119228, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
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Liu C, Liu W, Zhang G, Wang Y, Jiang J, Yang Z, Wu W. Conjunctional Relationship between Serum Uric Acid and Serum Nickel with Non-Alcoholic Fatty Liver Disease in Men: A Cross-Sectional Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:6424. [PMID: 35682008 PMCID: PMC9180290 DOI: 10.3390/ijerph19116424] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 05/20/2022] [Accepted: 05/22/2022] [Indexed: 01/27/2023]
Abstract
Serum uric acid (SUA) and heavy metals are closely related to non-alcoholic fatty liver disease (NAFLD). Yet, the conjunctional relationship between SUA and serum nickel (Ni) concentrations with the risk of NAFLD in men has not yet been investigated. Therefore, we designed this cross-sectional study to investigate the association of SUA or serum Ni with NAFLD in men. The cross-sectional study was based on data obtained from a prospective cohort study of common chronic non-communicable diseases in Central China, conducted in Xinxiang city, Central China's Henan Province, between April and June 2017. A total of 1709 male participants completed the physical examination. B-ultrasound was used to examine the liver and to diagnose NAFLD. Binary logistic regression models and restricted cubic splines were performed to estimate the association of the SUA and serum Ni with NAFLD. The prevalence of NAFLD among 1709 male participants was 46.6%. After adjusting for potential confounders, with the highest quartile compared to those with the lowest quartile, SUA (OR = 1.579, 95% CI: 1.140-2.189) and serum Ni (OR = 1.896, 95% CI: 1.372-2.625) were associated with NAFLD, respectively. At the same time, the associations for the second and third SUA quartiles were null. Restricted cubic splines showed a positive linear relationship between serum Ni (ln-transformed) and NAFLD risk. Intriguingly, high SUA and high Ni (OR = 2.370, 95% CI: 1.577-3.597) increased the risk of NAFLD, compared with those with low SUA and low Ni. Our findings demonstrate a positive linear trend between serum Ni concentrations and NAFLD risk. Men with elevated serum Ni had a higher risk of developing NAFLD when compared to those with high SUA. Furthermore, the conjunctional relationship of SUA and serum Ni with NAFLD risk was observed in men.
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Affiliation(s)
| | | | | | | | | | - Zhongzhi Yang
- School of Public Health, Xinxiang Medical University, Xinxiang 453003, China; (C.L.); (W.L.); (G.Z.); (Y.W.); (J.J.)
| | - Weidong Wu
- School of Public Health, Xinxiang Medical University, Xinxiang 453003, China; (C.L.); (W.L.); (G.Z.); (Y.W.); (J.J.)
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Giussani M, Lieti G, Orlando A, Parati G, Genovesi S. Fructose Intake, Hypertension and Cardiometabolic Risk Factors in Children and Adolescents: From Pathophysiology to Clinical Aspects. A Narrative Review. Front Med (Lausanne) 2022; 9:792949. [PMID: 35492316 PMCID: PMC9039289 DOI: 10.3389/fmed.2022.792949] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 03/21/2022] [Indexed: 01/09/2023] Open
Abstract
Arterial hypertension, dyslipidemia, alterations in glucose metabolism and fatty liver, either alone or in association, are frequently observed in obese children and may seriously jeopardize their health. For obesity to develop, an excessive intake of energy-bearing macronutrients is required; however, ample evidence suggests that fructose may promote the development of obesity and/or metabolic alterations, independently of its energy intake. Fructose consumption is particularly high among children, because they do not have the perception, and more importantly, neither do their parents, that high fructose intake is potentially dangerous. In fact, while this sugar is erroneously viewed favorably as a natural nutrient, its excessive intake can actually cause adverse cardio-metabolic alterations. Fructose induces the release of pro-inflammatory cytokines, and reduces the production of anti-atherosclerotic cytokines, such as adiponectin. Furthermore, by interacting with hunger and satiety control systems, particularly by inducing leptin resistance, it leads to increased caloric intake. Fructose, directly or through its metabolites, promotes the development of obesity, arterial hypertension, dyslipidemia, glucose intolerance and fatty liver. This review aims to highlight the mechanisms by which the early and excessive consumption of fructose may contribute to the development of a variety of cardiometabolic risk factors in children, thus representing a potential danger to their health. It will also describe the main clinical trials performed in children and adolescents that have evaluated the clinical effects of excessive intake of fructose-containing drinks and food, with particular attention to the effects on blood pressure. Finally, we will discuss the effectiveness of measures that can be taken to reduce the intake of this sugar.
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Affiliation(s)
- Marco Giussani
- Cardiologic Unit, Istituto Auxologico Italiano, Istituto Ricovero Cura Carattere Scientifico (IRCCS), Milan, Italy
| | - Giulia Lieti
- School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Antonina Orlando
- Cardiologic Unit, Istituto Auxologico Italiano, Istituto Ricovero Cura Carattere Scientifico (IRCCS), Milan, Italy
| | - Gianfranco Parati
- Cardiologic Unit, Istituto Auxologico Italiano, Istituto Ricovero Cura Carattere Scientifico (IRCCS), Milan, Italy.,School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Simonetta Genovesi
- Cardiologic Unit, Istituto Auxologico Italiano, Istituto Ricovero Cura Carattere Scientifico (IRCCS), Milan, Italy.,School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
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40
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Zhang XL, Wang TY, Targher G, Byrne CD, Zheng MH. Lifestyle Interventions for Non-Obese Patients Both with, and at Risk, of Non-Alcoholic Fatty Liver Disease. Diabetes Metab J 2022; 46:391-401. [PMID: 35656562 PMCID: PMC9171159 DOI: 10.4093/dmj.2022.0048] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Accepted: 04/29/2022] [Indexed: 12/26/2022] Open
Abstract
Non-alcoholic fatty liver disease occurring in non-obese subjects (the so-called non-obese NAFLD) is a highly prevalent but neglected liver condition, which is closely associated with metabolic disorders and suboptimal lifestyles. Landmark studies have shown that lifestyle interventions are potentially beneficial in decreasing the risk of developing non-obese NAFLD and in ameliorating NAFLD in non-obese individuals with pre-existing NAFLD. Lifestyle interventions usually refer to changes in eating habits and physical activity, both of which have a powerful effect on non-obese NAFLD and on risk factors for non-obese NAFLD. However, to date, patients and health-care professionals have a poor awareness and understanding of non-obese NAFLD and the beneficial effects of lifestyle interventions in this patient population. The aim of this narrative review is to briefly discuss the evidence for the effects of lifestyle changes and what changes are needed amongst medical personnel and other stakeholders in order to raise awareness of non-obese NAFLD.
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Affiliation(s)
- Xin-Lei Zhang
- NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Ting-Yao Wang
- Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Verona, Verona, Italy
| | - Christopher D. Byrne
- Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton, UK
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK
| | - 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
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Liver Steatosis: A Marker of Metabolic Risk in Children. Int J Mol Sci 2022; 23:ijms23094822. [PMID: 35563210 PMCID: PMC9100068 DOI: 10.3390/ijms23094822] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 04/24/2022] [Accepted: 04/24/2022] [Indexed: 11/16/2022] Open
Abstract
Obesity is one of the greatest health challenges affecting children of all ages and ethnicities. Almost 19% of children and adolescents worldwide are overweight or obese, with an upward trend in the last decades. These reports imply an increased risk of fat accumulation in hepatic cells leading to a series of histological hepatic damages gathered under the acronym NAFLD (Non-Alcoholic Fatty Liver Disease). Due to the complex dynamics underlying this condition, it has been recently renamed as 'Metabolic Dysfunction Associated Fatty Liver Disease (MAFLD)', supporting the hypothesis that hepatic steatosis is a key component of the large group of clinical and laboratory abnormalities of Metabolic Syndrome (MetS). This review aims to share the latest scientific knowledge on MAFLD in children in an attempt to offer novel insights into the complex dynamics underlying this condition, focusing on the novel molecular aspects. Although there is still no treatment with a proven efficacy for this condition, starting from the molecular basis of the disease, MAFLD's therapeutic landscape is rapidly expanding, and different medications seem to act as modifiers of liver steatosis, inflammation, and fibrosis.
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Uchida T, Fujiwara K, Nishioji K, Kobayashi M, Kano M, Seko Y, Yamaguchi K, Itoh Y, Kadotani H. Medical checkup data analysis method based on LiNGAM and its application to nonalcoholic fatty liver disease. Artif Intell Med 2022; 128:102310. [PMID: 35534147 DOI: 10.1016/j.artmed.2022.102310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 03/24/2022] [Accepted: 04/17/2022] [Indexed: 11/02/2022]
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Abstract
Nonalcoholic fatty liver disease (NAFLD) can develop in lean individuals. Despite a better metabolic profile, the risk of disease progression to hepatic inflammation, fibrosis, and decompensated cirrhosis in the lean is similar to that in obesity-related NAFLD and lean individuals may experience more severe hepatic consequences and higher mortality relative to those with a higher body mass index (BMI). In the absence of early symptoms and abnormal laboratory findings, lean individuals are not likely to be screened for NAFLD or related comorbidities; however, given the progressive nature of the disease and the increased risk of morbidity and mortality, a clearer understanding of the natural history of NAFLD in lean individuals, as well as efforts to raise awareness of the potential health risks of NAFLD in lean individuals, are warranted. In this review, we summarize available data on NAFLD prevalence, clinical characteristics, outcomes, and mortality in lean individuals and discuss factors that may contribute to the development of NAFLD in this population, including links between dietary and genetic factors, menopausal status, and ethnicity. We also highlight the need for greater representation of lean individuals in NAFLD-related clinical trials, as well as more studies to better characterize lean NAFLD, develop improved screening algorithms, and determine specific treatment strategies based on underlying etiology.
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Affiliation(s)
- Johanna K. DiStefano
- Diabetes and Fibrotic Disease Research Unit, Translational Genomics Research Institute, Phoenix, USA
| | - Glenn S. Gerhard
- Lewis Katz School of Medicine, Temple University School of Medicine, Philadelphia, PA 19140 USA
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Zhou X, Lin X, Chen J, Pu J, Wu W, Wu Z, Lin H, Huang K, Zhang L, Dai Y, Ni Y, Dong G, Fu J. Clinical spectrum transition and prediction model of nonalcoholic fatty liver disease in children with obesity. Front Endocrinol (Lausanne) 2022; 13:986841. [PMID: 36120457 PMCID: PMC9471666 DOI: 10.3389/fendo.2022.986841] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Accepted: 08/08/2022] [Indexed: 11/14/2022] Open
Abstract
OBJECTIVE This study aims to outline the clinical characteristics of pediatric NAFLD, as well as establish and validate a prediction model for the disease. MATERIALS AND METHODS The retrospective study enrolled 3216 children with obesity from January 2003 to May 2021. They were divided into obese without NAFLD, nonalcoholic fatty liver (NAFL), and nonalcoholic steatohepatitis (NASH) groups. Clinical data were retrieved, and gender and chronologic characteristics were compared between groups. Data from the training set (3036) were assessed using univariate analyses and stepwise multivariate logistic regression, by which a nomogram was developed to estimate the probability of NAFLD. Another 180 cases received additional liver hydrogen proton magnetic resonance spectroscopy (1H-MRS) as a validation set. RESULTS The prevalence of NAFLD was higher in males than in females and has increased over the last 19 years. In total, 1915 cases were NAFLD, and the peak onset age was 10-12 years old. Hyperuricemia ranked first in childhood NAFLD comorbidities, followed by dyslipidemia, hypertension, metabolic syndrome (MetS), and dysglycemia. The AUROC of the eight-parameter nomogram, including waist-to-height ratio (WHtR), hip circumference (HC), triglyceride glucose-waist circumference (TyG-WC), alanine aminotransferase (ALT), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1(ApoA1), insulin sensitivity index [ISI (composite)], and gender, for predicting NAFLD was 0.913 (sensitivity 80.70%, specificity 90.10%). Calibration curves demonstrated a great calibration ability of the model. CONCLUSION AND RELEVANCE NAFLD is the most common complication in children with obesity. The nomogram based on anthropometric and laboratory indicators performed well in predicting NAFLD. This can be used as a quick screening tool to assess pediatric NAFLD in children with obesity.
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Pan Y, Zhang X. Diet and gut microbiome in fatty liver and its associated liver cancer. J Gastroenterol Hepatol 2022; 37:7-14. [PMID: 34664301 DOI: 10.1111/jgh.15713] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 10/05/2021] [Accepted: 10/05/2021] [Indexed: 12/16/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the major cause of chronic liver disease worldwide as a consequence of a sedentary lifestyle and overnutrition. NAFLD could progress to non-alcoholic steatohepatitis (NASH), which may further develop to cirrhosis and hepatocellular carcinoma (HCC). The gut microbiome is one of the central regulators in host metabolism. Diet could change human gut microbiome rapidly and reproducibly and modulate several metabolic pathways. Both diet and gut microbiome dysbiosis are associated with NAFLD and its related HCC (NAFLD-HCC). Dietary cholesterol, fiber, fat, or carbohydrate could change the microbiome composition to contribute to the development of NASH and NAFLD-HCC. Hence, identification of elements of the gut-liver axis that are primarily damaged in NASH and NAFLD-HCC offers new possibility for therapeutic intervention. In this review, the roles of gut microbiome and microbial metabolites in the development and progression of NAFLD and NAFLD-HCC are first discussed. The impacts of different diet compositions including cholesterol, fiber, fat, and sugar on the gut microbiome that leads to predisposition to NASH and NAFLD-HCC are also explored. We summarized the article by discussing potential therapeutic implication of diet and microbiome modulation in fatty liver and liver cancer.
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Affiliation(s)
- Yasi Pan
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease and The Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Xiang Zhang
- State Key Laboratory of Digestive Disease, Institute of Digestive Disease and The Department of Medicine and Therapeutics, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Shatin, Hong Kong, China
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46
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Moreira-Silva H, Ferreira S, Almeida M, Gonçalves I, Cipriano MA, Vizcaíno JR, Santos-Silva E, Gomes-Martins E. Case report: NAFLD and maple syrup urine disease: Is there an interplay between branched-chain amino acids and fructose consumption? Front Pediatr 2022; 10:933081. [PMID: 36299693 PMCID: PMC9589422 DOI: 10.3389/fped.2022.933081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Accepted: 09/02/2022] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND The worldwide increase in pediatric overweight and obesity, in parallel with the global increase in the consumption of sucrose and fructose, is associated with non-alcoholic fatty liver disease (NAFLD). Elevated branched-chain amino acids (BCAAs) are a metabolic feature related to obesity and an early risk factor for insulin resistance and NAFLD. However, few studies have assessed metabolic risk factors and nutritional status in maple syrup urine disease (MSUD) patients under restricted BCAA and high carbohydrate diets. METHODS AND RESULTS Herein, we present a pilot report of a 17-year-old boy with classic MSUD with poor diet compliance and high fructose consumption, mainly during early adolescence. At that time, he was overweight and developed features of metabolic syndrome, including persistently elevated liver enzymes and hepatic steatosis. He underwent liver transplantation at the age of 13 years to prevent the risk of progressive cognitive impairment. Two months later, NAFLD relapsed in the graft, despite a better BCAA balance and weight loss. Nevertheless, 6 months after dietary restriction of fructose consumption, NAFLD had sustainably improved. CONCLUSION Childhood overweight and fructose overconsumption are wellestablished driving forces in the development of pediatric NAFLD. However, their role in the early onset and progression of NAFLD in the allograft remains to be established. Furthermore, it is not known whether the dysmetabolic state associated with elevated BCAAs may be contributory. Further studies are required with a cohort of MSUD subjects to validate our findings and to ascertain the possible interaction between a BCAA imbalance and dietary intake in the development of NAFLD.
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Affiliation(s)
- Helena Moreira-Silva
- Pediatric Gastroenterology Unit, Centro Materno Infantil do Norte, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Sandra Ferreira
- Hepatology and Pediatric Liver Transplantation Unit, Hospital Pediátrico de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | - Manuela Almeida
- Pediatric Metabolic Diseases Unit, Centro de Referência de Doenças Hereditárias do Metabolismo, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Isabel Gonçalves
- Hepatology and Pediatric Liver Transplantation Unit, Hospital Pediátrico de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
| | | | - J R Vizcaíno
- Anatomic Pathology Service, Pathology Department, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Ermelinda Santos-Silva
- Pediatric Gastroenterology Unit, Centro Materno Infantil do Norte, Centro Hospitalar Universitário do Porto, Porto, Portugal
| | - Esmeralda Gomes-Martins
- Pediatric Metabolic Diseases Unit, Centro de Referência de Doenças Hereditárias do Metabolismo, Centro Hospitalar Universitário do Porto, Porto, Portugal
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Herman MA, Birnbaum MJ. Molecular aspects of fructose metabolism and metabolic disease. Cell Metab 2021; 33:2329-2354. [PMID: 34619074 PMCID: PMC8665132 DOI: 10.1016/j.cmet.2021.09.010] [Citation(s) in RCA: 148] [Impact Index Per Article: 37.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2021] [Revised: 09/02/2021] [Accepted: 09/13/2021] [Indexed: 02/06/2023]
Abstract
Excessive sugar consumption is increasingly considered as a contributor to the emerging epidemics of obesity and the associated cardiometabolic disease. Sugar is added to the diet in the form of sucrose or high-fructose corn syrup, both of which comprise nearly equal amounts of glucose and fructose. The unique aspects of fructose metabolism and properties of fructose-derived metabolites allow for fructose to serve as a physiological signal of normal dietary sugar consumption. However, when fructose is consumed in excess, these unique properties may contribute to the pathogenesis of cardiometabolic disease. Here, we review the biochemistry, genetics, and physiology of fructose metabolism and consider mechanisms by which excessive fructose consumption may contribute to metabolic disease. Lastly, we consider new therapeutic options for the treatment of metabolic disease based upon this knowledge.
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Affiliation(s)
- Mark A Herman
- Division of Endocrinology, Metabolism, and Nutrition, Duke University, Durham, NC, USA; Duke Molecular Physiology Institute, Duke University, Durham, NC, USA; Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.
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Ivancovsky-Wajcman D, Fliss-Isakov N, Webb M, Bentov I, Shibolet O, Kariv R, Zelber-Sagi S. Ultra-processed food is associated with features of metabolic syndrome and non-alcoholic fatty liver disease. Liver Int 2021; 41:2635-2645. [PMID: 34174011 DOI: 10.1111/liv.14996] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 06/15/2021] [Accepted: 06/22/2021] [Indexed: 12/30/2022]
Abstract
BACKGROUND & AIMS High consumption of ultra-processed food (UPF) is associated with mortality and chronic morbidity but has not been studied concerning to non-alcoholic fatty liver disease (NAFLD). We aimed to test the association of UPF consumption with metabolic syndrome, NAFLD and related-liver damage. METHODS A cross-sectional study among volunteers who underwent abdominal ultrasound (AUS), anthropometrics, blood pressure measurements, and fasting blood tests including FibroMax for non-invasive assessment of NASH and significant fibrosis. A food-frequency questionnaire was used to evaluate UPF consumption using the NOVA classification. RESULTS A total of 789 subjects were included in the total sample (mean age 58.83 ± 6.58 years, 52.60% men), a reliable FibroMax test was obtained from 714 subjects, 305 subjects were diagnosed with NAFLD. High consumption of UPF was associated with higher odds for metabolic syndrome (OR = 1.88, 95% CI 1.31-2.71, P = .001) and its components; hypertension, hypertriglyceridemia, and low HDL, among the entire sample (OR = 1.53, 1.07-2.19, P = .026; OR = 1.51, 1.08-2.11, P = .017; OR = 1.55, 1.05-2.29, P = .028). In addition, it was associated with higher odds for NASH and hypertension (OR = 1.89, 1.07-3.38, P = .030; OR = 2.26, 1.20-4.26, P = .012 respectively) among subjects with NAFLD. Stratification by smoking status revealed an association between high UPF consumption and significant fibrosis among ever smokers in the entire sample and among subjects with NAFLD (OR = 1.89, 95% CI 1.03-3.45, P = .039; OR = 2.85, 1.14-7.14, P = .026 respectively). CONCLUSIONS High UPF consumption is associated with metabolic syndrome in the general population, and among those with NAFLD it is associated with NASH marker. Ever-smoking may act synergistically with UPF to amplify the risk for fibrosis.
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Affiliation(s)
| | - Naomi Fliss-Isakov
- Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv, Israel
| | - Muriel Webb
- Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Itay Bentov
- Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA
| | - Oren Shibolet
- Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Revital Kariv
- Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Shira Zelber-Sagi
- School of Public Health, University of Haifa, Haifa, Israel.,Department of Gastroenterology, Tel Aviv Medical Center, Tel Aviv, Israel
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Francque SM, Marchesini G, Kautz A, Walmsley M, Dorner R, Lazarus JV, Zelber-Sagi S, Hallsworth K, Busetto L, Frühbeck G, Dicker D, Woodward E, Korenjak M, Willemse J, Koek GH, Vinker S, Ungan M, Mendive JM, Lionis C. Non-alcoholic fatty liver disease: A patient guideline. JHEP Rep 2021; 3:100322. [PMID: 34693236 PMCID: PMC8514420 DOI: 10.1016/j.jhepr.2021.100322] [Citation(s) in RCA: 135] [Impact Index Per Article: 33.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 06/08/2021] [Indexed: 02/07/2023] Open
Abstract
This patient guideline is intended for all patients at risk of or living with non-alcoholic fatty liver disease (NAFLD). NAFLD is the most frequent chronic liver disease worldwide and comes with a high disease burden. Yet, there is a lot of unawareness. Furthermore, many aspects of the disease are still to be unravelled, which has an important impact on the information that is given (or not) to patients. Its management requires a close interaction between patients and their many healthcare providers. It is important for patients to develop a full understanding of NAFLD in order to enable them to take an active role in their disease management. This guide summarises the current knowledge relevant to NAFLD and its management. It has been developed by patients, patient representatives, clinicians and scientists and is based on current scientific recommendations, intended to support patients in making informed decisions.
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Key Words
- ALD, alcohol-related or alcoholic liver disease
- ASH, alcoholic steatohepatitis
- BMI, body mass index
- CAP, controlled attenuation parameter
- CT, computed tomography
- CVD, cardiovascular disease
- EASD, European Association for the Study of Diabetes
- EASL, European Association for the Study of the Liver
- EASO, European Association for the Study of Obesity
- FIB-4, fibrosis-4 index
- FXR, farnesoid X receptor
- GLP-1 RAs, glucagon-like receptor 1 agonists
- GP, general practitioner
- HCC, hepatocellular carcinoma
- HDL, high-density lipoprotein
- LDL, low-density lipoproteins
- MRE, magnetic resonance elastography
- MRI, magnetic resonance imaging
- NAFL, non-alcoholic fatty liver
- NAFLD, non-alcoholic fatty liver disease
- NASH CRN, NASH Clinical Research Network
- NASH, non-alcoholic steatohepatitis
- NIT, non-invasive test
- SMART, specific, measurable, achievable, relevant, timely
- T1D, type 1 diabetes
- T2D, type 2 diabetes
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Affiliation(s)
- Sven M. Francque
- Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium
- Laboratory of Experimental Medicine and Paediatrics (LEMP), Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium
- InflaMed Centre of Excellence, University of Antwerp, Antwerp, Belgium
- Translational Sciences in Inflammation and Immunology, University of Antwerp, Antwerp, Belgium
| | - Giulio Marchesini
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy
- Department of Medical and Surgical Sciences, “Alma Mater” University, Bologna, Italy
| | | | | | | | - Jeffrey V. Lazarus
- Barcelona Institute for Global Health (ISGlobal), Hospital Clínic, University of Barcelona, Spain
| | - Shira Zelber-Sagi
- School of Public Health, Faculty of Social Welfare and Health Sciences, University of Haifa, Haifa, Israel
- Department of Gastroenterology and Hepatology, The Tel-Aviv Medical Center, Tel-Aviv, Israel
| | - Kate Hallsworth
- Newcastle NIHR Biomedical Research Centre, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
- Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK
| | - Luca Busetto
- Department of Medicine, University of Padova, Italy
- European Association for the Study of Obesity
| | - Gema Frühbeck
- Department of Endocrinology & Nutrition, University of Navarra Clinic, IdiSNA, CIBEROBN, Pamplona, Spain
- European Association for the Study of Obesity
| | - Dror Dicker
- Department of Internal Medicine, Rabin Medical Center Hasharon Hospital, Tikva, Israel
- European Association for the Study of Obesity
| | | | | | | | - Gerardus H. Koek
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, the Netherlands
- School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, the Netherlands
| | - Shlomo Vinker
- Department of Family Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- World Organization of Family Doctors (WONCA)
- European General Practice Research Network (EGPRN)
- Israel Association of Family Physicians, Israel
- Leumit Health Services, Tel Aviv, Israel
| | | | - Juan M. Mendive
- Training Unit of Family Medicine, Catalan Institute of Health, Barcelona, Spain
- European Society for Primary Care Gastroenterology
| | - Christos Lionis
- European Society for Primary Care Gastroenterology
- Clinic of Social and Family Medicine, School of Medicine, University of Crete, Heraklion, Greece
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Semmler G, Datz C, Reiberger T, Trauner M. Diet and exercise in NAFLD/NASH: Beyond the obvious. Liver Int 2021; 41:2249-2268. [PMID: 34328248 PMCID: PMC9292198 DOI: 10.1111/liv.15024] [Citation(s) in RCA: 103] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 07/06/2021] [Accepted: 07/10/2021] [Indexed: 12/12/2022]
Abstract
Lifestyle represents the most relevant factor for non-alcoholic fatty liver disease (NAFLD) as the hepatic manifestation of the metabolic syndrome. Although a tremendous body of clinical and preclinical data on the effectiveness of dietary and lifestyle interventions exist, the complexity of this topic makes firm and evidence-based clinical recommendations for nutrition and exercise in NAFLD difficult. The aim of this review is to guide readers through the labyrinth of recent scientific findings on diet and exercise in NAFLD and non-alcoholic steatohepatitis (NASH), summarizing "obvious" findings in a holistic manner and simultaneously highlighting stimulating aspects of clinical and translational research "beyond the obvious". Specifically, the importance of calorie restriction regardless of dietary composition and evidence from low-carbohydrate diets to target the incidence and severity of NAFLD are discussed. The aspect of ketogenesis-potentially achieved via intermittent calorie restriction-seems to be a central aspect of these diets warranting further investigation. Interactions of diet and exercise with the gut microbiota and the individual genetic background need to be comprehensively understood in order to develop personalized dietary concepts and exercise strategies for patients with NAFLD/NASH.
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Affiliation(s)
- Georg Semmler
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Christian Datz
- Department of Internal MedicineGeneral Hospital OberndorfTeaching Hospital of the Paracelsus Medical University SalzburgSalzburgAustria
| | - Thomas Reiberger
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Michael Trauner
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
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