1
|
Mullin SM, Kelly AJ, Ní Chathail MB, Norris S, Shannon CE, Roche HM. Macronutrient Modulation in Metabolic Dysfunction-Associated Steatotic Liver Disease-the Molecular Role of Fatty Acids compared with Sugars in Human Metabolism and Disease Progression. Adv Nutr 2025; 16:100375. [PMID: 39842721 PMCID: PMC11849631 DOI: 10.1016/j.advnut.2025.100375] [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: 09/12/2024] [Revised: 12/23/2024] [Accepted: 01/13/2025] [Indexed: 01/24/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a significant public health concern, with its progression to metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis leading to severe outcomes including cirrhosis, hepatocellular carcinoma, and liver failure. Whereas obesity and excess energy intake are well-established contributors to the development and progression of MASLD, the distinct role of specific macronutrients is less clear. This review examines the mechanistic pathways through which dietary fatty acids and sugars contribute to the development of hepatic inflammation and fibrosis, offering a nuanced understanding of their respective roles in MASLD progression. In terms of addressing potential therapeutic options, human intervention studies that investigate whether modifying the intake of dietary fats and carbohydrates affects MASLD progression are reviewed. By integrating this evidence, this review seeks to bridge the gap in the understanding between the mechanisms of macronutrient-driven MASLD progression and the effect of altering the intake of these nutrients in the clinical setting and presents a foundation for future research into targeted dietary strategies for the treatment of the disease.
Collapse
Affiliation(s)
- Sinéad M Mullin
- School of Public Health, Physiotherapy and Sport Science, and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland; Nutrigenomics Research Group, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland
| | - Aidan J Kelly
- School of Medicine, Trinity College Dublin, Dublin, Ireland
| | - Méabh B Ní Chathail
- School of Public Health, Physiotherapy and Sport Science, and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland; Nutrigenomics Research Group, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland
| | - Suzanne Norris
- School of Medicine, Trinity College Dublin, Dublin, Ireland
| | - Christopher E Shannon
- Nutrigenomics Research Group, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland; School of Medicine, University College Dublin, Belfield, Dublin, Ireland
| | - Helen M Roche
- School of Public Health, Physiotherapy and Sport Science, and Institute of Food and Health, University College Dublin, Belfield, Dublin, Ireland; Nutrigenomics Research Group, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland; Institute for Global Food Security, Queen's University Belfast, Northern Ireland.
| |
Collapse
|
2
|
Crişan D, Avram L, Morariu-Barb A, Grapa C, Hirişcau I, Crăciun R, Donca V, Nemeş A. Sarcopenia in MASLD-Eat to Beat Steatosis, Move to Prove Strength. Nutrients 2025; 17:178. [PMID: 39796612 PMCID: PMC11722590 DOI: 10.3390/nu17010178] [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: 11/23/2024] [Revised: 12/26/2024] [Accepted: 12/31/2024] [Indexed: 01/13/2025] Open
Abstract
The connections between sarcopenia and various chronic conditions, including type 2 diabetes (T2DM), metabolic syndrome (MetS), and liver disease have been highlighted recently. There is also a high occurrence of sarcopenia in metabolic dysfunction-associated steatotic liver disease (MASLD) patients, who are often disregarded. Both experimental and clinical findings suggest a complex, bidirectional relationship between MASLD and sarcopenia. While vitamin D, testosterone, and specific drug therapies show promise in mitigating sarcopenia, consensus on effective treatments is lacking. Recent focus on lifestyle interventions emphasizes dietary therapy and exercise for sarcopenic obesity in MASLD. Challenges arise as weight loss, a primary MASLD treatment, may lead to muscle mass reduction. The therapeutic approach to sarcopenia in morbidly obese MASLD patients also includes bariatric surgery (BS). BS induces weight loss and stabilizes metabolic imbalances, but its impact on sarcopenia is nuanced, underscoring the need for further research. Our aim is to provide a comprehensive review of the interplay between sarcopenia and MASLD and offer insight into the most recent therapeutic challenges and discoveries, as sarcopenia is often overlooked or unrecognized and poses significant challenges for managing these patients.
Collapse
Affiliation(s)
- Dana Crişan
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (D.C.); (L.A.); (I.H.); (R.C.); (V.D.); (A.N.)
- Clinical Municipal Hospital, 400139 Cluj-Napoca, Romania
| | - Lucreţia Avram
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (D.C.); (L.A.); (I.H.); (R.C.); (V.D.); (A.N.)
- Clinical Municipal Hospital, 400139 Cluj-Napoca, Romania
| | - Andreea Morariu-Barb
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (D.C.); (L.A.); (I.H.); (R.C.); (V.D.); (A.N.)
- Regional Institute of Gastroenterology and Hepatology “Prof. Dr. Octavian Fodor”, 400162 Cluj-Napoca, Romania
| | - Cristiana Grapa
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (D.C.); (L.A.); (I.H.); (R.C.); (V.D.); (A.N.)
- Regional Institute of Gastroenterology and Hepatology “Prof. Dr. Octavian Fodor”, 400162 Cluj-Napoca, Romania
| | - Ioana Hirişcau
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (D.C.); (L.A.); (I.H.); (R.C.); (V.D.); (A.N.)
| | - Rareş Crăciun
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (D.C.); (L.A.); (I.H.); (R.C.); (V.D.); (A.N.)
- Regional Institute of Gastroenterology and Hepatology “Prof. Dr. Octavian Fodor”, 400162 Cluj-Napoca, Romania
| | - Valer Donca
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (D.C.); (L.A.); (I.H.); (R.C.); (V.D.); (A.N.)
- Clinical Municipal Hospital, 400139 Cluj-Napoca, Romania
| | - Andrada Nemeş
- Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (D.C.); (L.A.); (I.H.); (R.C.); (V.D.); (A.N.)
- Clinical Municipal Hospital, 400139 Cluj-Napoca, Romania
| |
Collapse
|
3
|
Hamamah S, Iatcu OC, Covasa M. Dietary Influences on Gut Microbiota and Their Role in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Nutrients 2024; 17:143. [PMID: 39796579 PMCID: PMC11722922 DOI: 10.3390/nu17010143] [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: 12/15/2024] [Revised: 12/27/2024] [Accepted: 12/30/2024] [Indexed: 01/13/2025] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major contributor to liver-related morbidity, cardiovascular disease, and metabolic complications. Lifestyle interventions, including diet and exercise, are first line in treating MASLD. Dietary approaches such as the low-glycemic-index Mediterranean diet, the ketogenic diet, intermittent fasting, and high fiber diets have demonstrated potential in addressing the metabolic dysfunction underlying this condition. The development and progression of MASLD are closely associated with taxonomic shifts in gut microbial communities, a relationship well-documented in the literature. Given the importance of diet as a primary treatment for MASLD, it is important to understand how gut microbiota and their metabolic byproducts mediate favorable outcomes induced by healthy dietary patterns. Conversely, microbiota changes conferred by unhealthy dietary patterns such as the Western diet may induce dysbiosis and influence steatotic liver disease through promoting hepatic inflammation, up-regulating lipogenesis, dysregulating bile acid metabolism, increasing insulin resistance, and causing oxidative damage in hepatocytes. Although emerging evidence has identified links between diet, microbiota, and development of MASLD, significant gaps remain in understanding specific microbial roles, metabolite pathways, host interactions, and causal relationships. Therefore, this review aims to provide mechanistic insights into the role of microbiota-mediated processes through the analysis of both healthy and unhealthy dietary patterns and their contribution to MASLD pathophysiology. By better elucidating the interplay between dietary nutrients, microbiota-mediated processes, and the onset and progression of steatotic liver disease, this work aims to identify new opportunities for targeted dietary interventions to treat MASLD efficiently.
Collapse
Affiliation(s)
- Sevag Hamamah
- Department of Internal Medicine, Scripps Mercy Hospital, San Diego, CA 92103, USA;
| | - Oana C. Iatcu
- Department of Biomedical Sciences, College of Medicine and Biological Science, University of Suceava, 720229 Suceava, Romania;
| | - Mihai Covasa
- Department of Biomedical Sciences, College of Medicine and Biological Science, University of Suceava, 720229 Suceava, Romania;
| |
Collapse
|
4
|
Lundsgaard AM, Bojsen-Møller KN, Kiens B. Dietary Regulation of Hepatic Triacylglycerol Content-the Role of Eucaloric Carbohydrate Restriction with Fat or Protein Replacement. Adv Nutr 2023; 14:1359-1373. [PMID: 37591342 PMCID: PMC10721463 DOI: 10.1016/j.advnut.2023.08.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 07/21/2023] [Accepted: 08/07/2023] [Indexed: 08/19/2023] Open
Abstract
Accumulation of hepatic triacylglycerol (TG) is highly associated with impaired whole-body insulin-glucose homeostasis and dyslipidemia. The summarized findings from human intervention studies investigating the effect of reduced dietary carbohydrate and increased fat intake (and in studies also increased protein) while maintaining energy intake at eucaloric requirements reveal a beneficial effect of carbohydrate reduction on hepatic TG content in obese individuals with steatosis and indices of insulin resistance. Evidence suggests that the reduction of hepatic TG content after reduced intake of carbohydrates and increased fat/protein intake in humans, results from regulation of fatty acid (FA) metabolism within the liver, with an increase in hepatic FA oxidation and ketogenesis, together with a concomitant downregulation of FA synthesis from de novo lipogenesis. The adaptations in hepatic metabolism may result from reduced intrahepatic monosaccharide and insulin availability, reduced glycolysis and increased FA availability when carbohydrate intake is reduced.
Collapse
Affiliation(s)
- Anne-Marie Lundsgaard
- Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.
| | | | - Bente Kiens
- Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark
| |
Collapse
|
5
|
Ozlu T, Yilmaz Y, Gunes FE. The effects of dietary intervention on fibrosis and biochemical parameters in metabolic-associated fatty liver disease. Minerva Gastroenterol (Torino) 2022; 68:426-433. [PMID: 33829726 DOI: 10.23736/s2724-5985.21.02809-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Metabolic-associated fatty liver disease (MAFLD) affects nearly one quarter of the world's adult population creating large health loads and economic loads in society with no approved pharmacotherapy found yet. The number of studies showing the effect of nutrition on fibrosis accompanying MAFLD are insufficient. This study was planned with the aim of investigating the effect of nutritional treatment on liver injury. METHODS This research is a prospective, non-medication interventional study completed with 39 participants chosen from MAFLD patients with fibrosis. Post-treatment lasted three months, patients had liver stiffness measurements (LSM), anthropometric measurements and biochemical tests repeated. RESULTS In pre- and post-treatment, there were statistically significant correlations found between LSM with serum gamma glutamyl transferase (GGT) values, and between controlled attenuation parameter (CAP) with Body Mass Index (BMI) and fat mass (P<0.05). Post-treatment, statistically significant improvements were determined in the anthropometric measurements and biochemical findings. Moreover, post-treatment LSM and CAP values showed significant positive correlation compared to pretreatment (P<0.05). CONCLUSIONS This study found dietary interventions have an important place within the scope of fibrosis treatment. Preparation and application of medical nutrition treatment suitable for the clinical features of patients and completing correct lifestyle changes has an ameliorating effect on disease prognosis. There is a need for advanced studies with larger sample groups to further enlighten this topic.
Collapse
Affiliation(s)
- Tugce Ozlu
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Bahcesehir University, Istanbul, Turkey -
| | - Yusuf Yilmaz
- Department of Gastroenterology, School of Medicine, Marmara University, Istanbul, Turkey.,Liver Research Unit, Institute of Gastroenterology, Marmara University, Istanbul, Turkey
| | - Fatma E Gunes
- Department of Nutrition and Dietetics, Faculty of Health Sciences, Marmara University, Istanbul, Turkey
| |
Collapse
|
6
|
Zambon Azevedo V, Silaghi CA, Maurel T, Silaghi H, Ratziu V, Pais R. Impact of Sarcopenia on the Severity of the Liver Damage in Patients With Non-alcoholic Fatty Liver Disease. Front Nutr 2022; 8:774030. [PMID: 35111794 PMCID: PMC8802760 DOI: 10.3389/fnut.2021.774030] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 12/21/2021] [Indexed: 12/12/2022] Open
Abstract
An extensive body of the literature shows a strong interrelationship between the pathogenic pathways of non-alcoholic fatty liver disease (NAFLD) and sarcopenia through the muscle-liver-adipose tissue axis. NAFLD is one of the leading causes of chronic liver diseases (CLD) affecting more than one-quarter of the general population worldwide. The disease severity spectrum ranges from simple steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis, and its complications: end-stage chronic liver disease and hepatocellular carcinoma. Sarcopenia, defined as a progressive loss of the skeletal muscle mass, reduces physical performances, is associated with metabolic dysfunction and, possibly, has a causative role in NAFLD pathogenesis. Muscle mass is a key determinant of the whole-body insulin-mediated glucose metabolism and impacts fatty liver oxidation and energy homeostasis. These mechanisms drive the accumulation of ectopic fat both in the liver (steatosis, fatty liver) and in the muscle (myosteatosis). Myosteatosis rather than the muscle mass per se, seems to be closely associated with the severity of the liver injury. Sarcopenic obesity is a recently described entity which associates both sarcopenia and obesity and may trigger worse clinical outcomes including hepatic fibrosis progression and musculoskeletal disabilities. Furthermore, the muscle-liver-adipose tissue axis has a pivotal role in changes of the body composition, resulting in a distinct clinical phenotype that enables the identification of the "sarcopenic NAFLD phenotype." This review aims to bring some light into the complex relationship between sarcopenia and NAFLD and critically discuss the key mechanisms linking NAFLD to sarcopenia, as well as some of the clinical consequences associated with the coexistence of these two entities: the impact of body composition phenotypes on muscle morphology, the concept of sarcopenic obesity, the relationship between sarcopenia and the severity of the liver damage and finally, the future directions and the existing gaps in the knowledge.
Collapse
Affiliation(s)
- Vittoria Zambon Azevedo
- Doctoral School Physiology, Physiopathology and Therapeutics 394, Sorbonne Université, Paris, France
- Centre de Recherche de Cordeliers, INSERM UMRS 1138, Paris, France
| | - Cristina Alina Silaghi
- Department of Endocrinology, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania
| | - Thomas Maurel
- Institute of Cardiometabolism and Nutrition, Paris, France
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France
| | - Horatiu Silaghi
- Department of Surgery V, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Cluj-Napoca, Romania
| | - Vlad Ratziu
- Centre de Recherche de Cordeliers, INSERM UMRS 1138, Paris, France
- Institute of Cardiometabolism and Nutrition, Paris, France
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France
- Sorbonne Université, Paris, France
| | - Raluca Pais
- Institute of Cardiometabolism and Nutrition, Paris, France
- Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France
- Sorbonne Université, Paris, France
- Centre de Recherche Saint Antoine, INSERM UMRS 938, Paris, France
| |
Collapse
|
7
|
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.
Collapse
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.
| | | |
Collapse
|
8
|
Fasting Ketonuria and the Risk of Incident Nonalcoholic Fatty Liver Disease With and Without Liver Fibrosis in Nondiabetic Adults. Am J Gastroenterol 2021; 116:2270-2278. [PMID: 34114568 DOI: 10.14309/ajg.0000000000001344] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 05/14/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Dietary carbohydrate restriction or ketogenic diets are known to be beneficial in preventing liver fat accumulation. However, the effect of ketonemia on the risk of nonalcoholic fatty liver disease (NAFLD) in nondiabetic population is largely unknown. We investigated the association between fasting ketonuria and the risk of incident NAFLD in healthy adults. METHODS A cohort of 153,076 nondiabetic Koreans with no hepatic steatosis and low probability of fibrosis at baseline was followed for a median of 4.1 years. The outcome was incident hepatic steatosis with or without liver fibrosis, and it was assessed by liver ultrasound and noninvasive fibrosis indices, including fibrosis-4 and the NAFLD fibrosis score (NFS). Parametric proportional hazard models were used to estimate hazard ratios (HRs) for outcome according to ketonuria status. RESULTS Within 677,702.1 person-years of follow-up, 31,079 subjects developed hepatic steatosis. Compared with no ketonuria (reference), fasting ketonuria was significantly associated with a decreased risk of incident hepatic steatosis, with multivariable-adjusted HRs (95% confidence interval) of 0.81 (0.78-0.84). The corresponding HRs for incident hepatic steatosis with intermediate-to-high NFS were 0.79 (0.69-0.90). Similar associations were observed replacing NFS with fibrosis-4. In addition, the presence of persistent ketonuria at both baseline and subsequent visit was associated with the greatest decrease in the adjusted HR for incident NAFLD. DISCUSSION Ketonuria was associated with a reduced risk of developing incident hepatic steatosis with and without intermediate-to-high probability of advanced fibrosis in a large cohort of nondiabetic healthy individuals. The role of hyperketonemia in the prevention of NAFLD requires further exploration.
Collapse
|
9
|
Toll-like receptor 1 as a possible target in non-alcoholic fatty liver disease. Sci Rep 2021; 11:17815. [PMID: 34497333 PMCID: PMC8426394 DOI: 10.1038/s41598-021-97346-9] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 08/17/2021] [Indexed: 02/07/2023] Open
Abstract
Toll-like receptors (TLRs) in the liver compartment have repeatedly been attributed to the development of non-alcoholic fatty liver disease (NAFLD). Knowledge on TLR expression in blood cells and their relation to intestinal microbiota and NAFLD development is limited. Here, we determined TLR expression patterns in peripheral blood mononuclear cells (PBMCs) of NAFLD patients and controls, their relation to intestinal microbiota and the impact of TLRs found altered in NAFLD development. Markers of intestinal permeability in blood and TLR mRNA expression in PBMCs were determined in 37 NAFLD patients and 15 age-matched healthy controls. Fecal microbiota composition was evaluated in 21 NAFLD patients and 9 controls using 16S rRNA gene amplicon sequencing. Furthermore, TLR1-/- and C57BL/6 mice (n = 5-6/group) were pair-fed a liquid control or a fat-, fructose- and cholesterol-rich diet. Intestinal microbiota composition and markers of intestinal permeability like zonulin and bacterial endotoxin differed significantly between groups with the latter markers being significantly higher in NAFLD patients. Expression of TLR1-8 and 10 mRNA was detectable in PBMCs; however, only TLR1 expression, being higher in NAFLD patients, were significantly positively correlated with the prevalence of Holdemanella genus while negative correlations were found with Gemmiger and Ruminococcus genera. TLR1-/- mice were significantly protected from the development of diet-induced NAFLD when compared to wild-type mice. While intestinal microbiota composition and permeability differed significantly between NAFLD patients and healthy subjects, in PBMCs, only TLR1 expression differed between groups. Still, targeting these alterations might be a beneficial approach in the treatment of NAFLD in some patients.
Collapse
|
10
|
Han H, Jiang Y, Wang M, Melaku M, Liu L, Zhao Y, Everaert N, Yi B, Zhang H. Intestinal dysbiosis in nonalcoholic fatty liver disease (NAFLD): focusing on the gut-liver axis. Crit Rev Food Sci Nutr 2021; 63:1689-1706. [PMID: 34404276 DOI: 10.1080/10408398.2021.1966738] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders in humans, partly because it is closely related to metabolic disorders of the liver with increasing prevalence. NAFLD begins with hepatic lipid accumulation, which may cause inflammation and eventually lead to fibrosis in the liver. Numerous studies have demonstrated the close relationship between gut dysfunction (especially the gut microbiota and its metabolites) and the occurrence and progression of NAFLD. The bidirectional communication between the gut and liver, named the gut-liver axis, is mainly mediated by the metabolites derived from both the liver and gut through the biliary tract, portal vein, and systemic circulation. Herein, we review the effects of the gut-liver axis on the pathogenesis of NAFLD. We also comprehensively describe the potential molecular mechanisms from the perspective of the role of liver-derived metabolites and gut-related components in hepatic metabolism and inflammation and gut health, respectively. The study provides insights into the mechanisms underlying current summarizations that support the intricate interactions between a disordered gut and NAFLD and can provide novel strategies to lessen the prevalence and consequence of NAFLD.
Collapse
Affiliation(s)
- Hui Han
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.,Precision Livestock and Nutrition Unit, Gembloux Agro-Bio Tech, University of Liège, Gembloux, Belgium
| | - Yi Jiang
- Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Hubei, China
| | - Mengyu Wang
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Mebratu Melaku
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.,Department of Animal Production and Technology, College of Agriculture, Woldia University, Woldia, Ethiopia
| | - Lei Liu
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Yong Zhao
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Nadia Everaert
- Precision Livestock and Nutrition Unit, Gembloux Agro-Bio Tech, University of Liège, Gembloux, Belgium
| | - Bao Yi
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Hongfu Zhang
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
| |
Collapse
|
11
|
Hussain M, Umair Ijaz M, Ahmad MI, Khan IA, Bukhary SUF, Khan W, Hussain S, Hashmi MS, Li C. Gut inflammation exacerbates hepatic injury in C57BL/6J mice via gut-vascular barrier dysfunction with high-fat-incorporated meat protein diets. Food Funct 2021; 11:9168-9176. [PMID: 33026380 DOI: 10.1039/d0fo02153a] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AIM Meat and its derivatives provide nutrients essential for human health. However, meat consumption, along with excessive fat intake, has been associated with gut inflammation, intestinal barrier dysfunction and alterations in gut microbiota. Herein, we investigated whether and how these changes in the intestinal barrier system affect the gut liver axis and hepatic injury and eventually lead to the progression of liver syndrome such as NAFLD. METHODS Mice were fed with high fat (60% kcal) or low fat (12% kcal) along with soybean (control), chicken and pork proteins (HFCH, HFP, LFCH, and LFP) for 12 weeks. The biomarkers for liver injury were investigated after meat protein intake along with the high fat. FINDINGS Greater amount of fat vacuoles visible in the H&E staining increased the inflammatory cell infiltration and disorganized liver structures were observed in the HFP-fed mice. Oil Red O staining revealed that the HFP-fed and HFCH-fed mice showed more lipid droplets, confirming the increased hepatic lipid accumulation. Potential serum markers for NAFLD, ALT and AST were increased in the HF meat diet groups. Key genes responsible for hepatic inflammation and lipogenesis, such as MCP-1, IL1-β and TNF-α were upregulated. HF meat protein diet-fed mice exhibited signs of compromised liver with increased levels of endotoxin in the liver and its binding protein in serum, upregulation of TLRs in the liver, and significant increase in TG, TC, LDL-C and HDL-C concentrations. SIGNIFICANCE Intestinal inflammation and barrier dysfunction aggravate liver injury and fibrosis due to the intake of HF meat protein diets in mice, which may contribute to the progress of liver injury and associated complications. Gut inflammation may directly contribute to the development of NAFLD, especially of the gut vascular barricade dysfunction.
Collapse
Affiliation(s)
- Muzahir Hussain
- Key Laboratory of Meat Processing and Quality Control, MOE; Key Laboratory of Meat Processing, MARA; Jiangsu Collaborative Innovation Centre of Meat Production and Processing, Quality and Safety Control, College of Food Science and Technology, Nanjing Agricultural University, Nanjing, 210095, PR China. and Department of Horticulture, Abdul Wali Khan University Mardan, KPK, Pakistan and Department of Food Science and Technology, The University of Agriculture Peshawar, Peshawar, KPK 26000, Pakistan
| | - Muhammad Umair Ijaz
- Key Laboratory of Meat Processing and Quality Control, MOE; Key Laboratory of Meat Processing, MARA; Jiangsu Collaborative Innovation Centre of Meat Production and Processing, Quality and Safety Control, College of Food Science and Technology, Nanjing Agricultural University, Nanjing, 210095, PR China.
| | - Muhammad Ijaz Ahmad
- Key Laboratory of Meat Processing and Quality Control, MOE; Key Laboratory of Meat Processing, MARA; Jiangsu Collaborative Innovation Centre of Meat Production and Processing, Quality and Safety Control, College of Food Science and Technology, Nanjing Agricultural University, Nanjing, 210095, PR China.
| | - Iftikhar Ali Khan
- Key Laboratory of Meat Processing and Quality Control, MOE; Key Laboratory of Meat Processing, MARA; Jiangsu Collaborative Innovation Centre of Meat Production and Processing, Quality and Safety Control, College of Food Science and Technology, Nanjing Agricultural University, Nanjing, 210095, PR China.
| | - Syed Umar Farooq Bukhary
- Key Laboratory of Meat Processing and Quality Control, MOE; Key Laboratory of Meat Processing, MARA; Jiangsu Collaborative Innovation Centre of Meat Production and Processing, Quality and Safety Control, College of Food Science and Technology, Nanjing Agricultural University, Nanjing, 210095, PR China.
| | - Waqar Khan
- College of Life Sciences, Nanjing Agricultural University, Nanjing, 210095, PR China
| | - Sayed Hussain
- Department of Horticulture, Abdul Wali Khan University Mardan, KPK, Pakistan
| | - Majid Suhail Hashmi
- Department of Food Science and Technology, The University of Agriculture Peshawar, Peshawar, KPK 26000, Pakistan
| | - Chunbao Li
- Key Laboratory of Meat Processing and Quality Control, MOE; Key Laboratory of Meat Processing, MARA; Jiangsu Collaborative Innovation Centre of Meat Production and Processing, Quality and Safety Control, College of Food Science and Technology, Nanjing Agricultural University, Nanjing, 210095, PR China.
| |
Collapse
|
12
|
Dallio M, Romeo M, Gravina AG, Masarone M, Larussa T, Abenavoli L, Persico M, Loguercio C, Federico A. Nutrigenomics and Nutrigenetics in Metabolic- (Dysfunction) Associated Fatty Liver Disease: Novel Insights and Future Perspectives. Nutrients 2021; 13:1679. [PMID: 34063372 PMCID: PMC8156164 DOI: 10.3390/nu13051679] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Revised: 05/12/2021] [Accepted: 05/13/2021] [Indexed: 12/12/2022] Open
Abstract
Metabolic- (dysfunction) associated fatty liver disease (MAFLD) represents the predominant hepatopathy and one of the most important systemic, metabolic-related disorders all over the world associated with severe medical and socio-economic repercussions due to its growing prevalence, clinical course (steatohepatitis and/or hepatocellular-carcinoma), and related extra-hepatic comorbidities. To date, no specific medications for the treatment of this condition exist, and the most valid recommendation for patients remains lifestyle change. MAFLD has been associated with metabolic syndrome; its development and progression are widely influenced by the interplay between genetic, environmental, and nutritional factors. Nutrigenetics and nutrigenomics findings suggest nutrition's capability, by acting on the individual genetic background and modifying the specific epigenetic expression as well, to influence patients' clinical outcome. Besides, immunity response is emerging as pivotal in this multifactorial scenario, suggesting the interaction between diet, genetics, and immunity as another tangled network that needs to be explored. The present review describes the genetic background contribution to MAFLD onset and worsening, its possibility to be influenced by nutritional habits, and the interplay between nutrients and immunity as one of the most promising research fields of the future in this context.
Collapse
Affiliation(s)
- Marcello Dallio
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via S. Pansini 5, 80131 Naples, Italy; (M.R.); (A.G.G.); (C.L.); (A.F.)
| | - Mario Romeo
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via S. Pansini 5, 80131 Naples, Italy; (M.R.); (A.G.G.); (C.L.); (A.F.)
| | - Antonietta Gerarda Gravina
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via S. Pansini 5, 80131 Naples, Italy; (M.R.); (A.G.G.); (C.L.); (A.F.)
| | - Mario Masarone
- Department of Medicine and Surgery, University of Salerno, Via Allende, 84081 Baronissi, Italy; (M.M.); (M.P.)
| | - Tiziana Larussa
- Department of Health Sciences, University Magna Graecia, viale Europa, 88100 Catanzaro, Italy; (T.L.); (L.A.)
| | - Ludovico Abenavoli
- Department of Health Sciences, University Magna Graecia, viale Europa, 88100 Catanzaro, Italy; (T.L.); (L.A.)
| | - Marcello Persico
- Department of Medicine and Surgery, University of Salerno, Via Allende, 84081 Baronissi, Italy; (M.M.); (M.P.)
| | - Carmelina Loguercio
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via S. Pansini 5, 80131 Naples, Italy; (M.R.); (A.G.G.); (C.L.); (A.F.)
| | - Alessandro Federico
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via S. Pansini 5, 80131 Naples, Italy; (M.R.); (A.G.G.); (C.L.); (A.F.)
| |
Collapse
|
13
|
Moszak M, Szulińska M, Walczak-Gałęzewska M, Bogdański P. Nutritional Approach Targeting Gut Microbiota in NAFLD-To Date. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:1616. [PMID: 33567710 PMCID: PMC7916007 DOI: 10.3390/ijerph18041616] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 01/05/2021] [Accepted: 01/25/2021] [Indexed: 12/18/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a significant clinical and epidemiological problem that affects around 25% of the adult global population. A large body of clinical evidence highlights that NAFLD is associated with increased liver-related morbidity and mortality and an increased risk of cardiovascular disease, extrahepatic cancers, type 2 diabetes, and chronic kidney disease. Recently, a series of studies revealed the pivotal role of gut microbiota (GM) dysbiosis in NAFLD's pathogenesis. The GM plays an essential role in different metabolic pathways, including the fermentation of diet polysaccharides, energy harvest, choline regulation, and bile acid metabolism. One of the most critical factors in GM stabilization is the diet; therefore, nutritional therapyappearsto be a promising tool in NAFLD therapy. This paper aims to review the current knowledge regardingthe nutritional approach and its implications with GM and NAFLD treatment. We discuss the positive impact of probiotics, prebiotics, and symbiotics in a reverse dysbiosis state in NAFLD and show the potential beneficial effects of bioactive substances from the diet. The full description of the mechanism of action and comprehensive examination of the impact of nutritional interventions on GM modulation may, in the future, be a simple but essential tool supporting NAFLD therapy.
Collapse
Affiliation(s)
- Małgorzata Moszak
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 61-701 Poznań, Poland; (M.S.); (P.B.)
| | - Monika Szulińska
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 61-701 Poznań, Poland; (M.S.); (P.B.)
| | - Marta Walczak-Gałęzewska
- Department of Internal Medicine, Metabolic Disorders, and Hypertension, Poznań University of Medical Sciences, 61-701 Poznań, Poland;
| | - Paweł Bogdański
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 61-701 Poznań, Poland; (M.S.); (P.B.)
| |
Collapse
|
14
|
Nutrients, Genetic Factors, and Their Interaction in Non-Alcoholic Fatty Liver Disease and Cardiovascular Disease. Int J Mol Sci 2020; 21:ijms21228761. [PMID: 33228237 PMCID: PMC7699550 DOI: 10.3390/ijms21228761] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 11/15/2020] [Accepted: 11/16/2020] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries and expose patients to increased risk of hepatic and cardiovascular (CV) morbidity and mortality. Both environmental factors and genetic predisposition contribute to the risk. An inappropriate diet, rich in refined carbohydrates, especially fructose, and saturated fats, and poor in fibers, polyunsaturated fats, and vitamins is one of the main key factors, as well as the polymorphism of patatin-like phospholipase domain containing 3 (PNPLA3 gene) for NAFLD and the apolipoproteins and the peroxisome proliferator-activated receptor (PPAR) family for the cardiovascular damage. Beyond genetic influence, also epigenetics modifications are responsible for various clinical manifestations of both hepatic and CV disease. Interestingly, data are accumulating on the interplay between diet and genetic and epigenetic modifications, modulating pathogenetic pathways in NAFLD and CV disease. We report the main evidence from literature on the influence of both macro and micronutrients in NAFLD and CV damage and the role of genetics either alone or combined with diet in increasing the risk of developing both diseases. Understanding the interaction between metabolic alterations, genetics and diet are essential to treat the diseases and tailoring nutritional therapy to control NAFLD and CV risk.
Collapse
|
15
|
Fructose-Induced Intestinal Microbiota Shift Following Two Types of Short-Term High-Fructose Dietary Phases. Nutrients 2020; 12:nu12113444. [PMID: 33182700 PMCID: PMC7697676 DOI: 10.3390/nu12113444] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 11/02/2020] [Accepted: 11/05/2020] [Indexed: 12/13/2022] Open
Abstract
High consumption of fructose and high-fructose corn syrup is related to the development of obesity-associated metabolic diseases, which have become the most relevant diet-induced diseases. However, the influences of a high-fructose diet on gut microbiota are still largely unknown. We therefore examined the effect of short-term high-fructose consumption on the human intestinal microbiota. Twelve healthy adult women were enrolled in a pilot intervention study. All study participants consecutively followed four different diets, first a low fructose diet (< 10 g/day fructose), then a fruit-rich diet (100 g/day fructose) followed by a low fructose diet (10 g/day fructose) and at last a high-fructose syrup (HFS) supplemented diet (100 g/day fructose). Fecal microbiota was analyzed by 16S rRNA sequencing. A high-fructose fruit diet significantly shifted the human gut microbiota by increasing the abundance of the phylum Firmicutes, in which beneficial butyrate producing bacteria such as Faecalibacterium, Anareostipes and Erysipelatoclostridium were elevated, and decreasing the abundance of the phylum Bacteroidetes including the genus Parabacteroides. An HFS diet induced substantial differences in microbiota composition compared to the fruit-rich diet leading to a lower Firmicutes and a higher Bacteroidetes abundance as well as reduced abundance of the genus Ruminococcus. Compared to a low-fructose diet we observed a decrease of Faecalibacterium and Erysipelatoclostridium after the HFS diet. Abundance of Bacteroidetes positively correlated with plasma cholesterol and LDL level, whereas abundance of Firmicutes was negatively correlated. Different formulations of high-fructose diets induce distinct alterations in gut microbiota composition. High-fructose intake by HFS causes a reduction of beneficial butyrate producing bacteria and a gut microbiota profile that may affect unfavorably host lipid metabolism whereas high consumption of fructose from fruit seems to modulate the composition of the gut microbiota in a beneficial way supporting digestive health and counteracting harmful effects of excessive fructose.
Collapse
|
16
|
Bischoff SC, Bernal W, Dasarathy S, Merli M, Plank LD, Schütz T, Plauth M. ESPEN practical guideline: Clinical nutrition in liver disease. Clin Nutr 2020; 39:3533-3562. [PMID: 33213977 DOI: 10.1016/j.clnu.2020.09.001] [Citation(s) in RCA: 188] [Impact Index Per Article: 37.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 09/09/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND The Practical guideline is based on the current scientific ESPEN guideline on Clinical Nutrition in Liver Disease. METHODS It has been shortened and transformed into flow charts for easier use in clinical practice. The guideline is dedicated to all professionals including physicians, dieticians, nutritionists and nurses working with patients with chronic liver disease. RESULTS A total of 103 statements and recommendations are presented with short commentaries for the nutritional and metabolic management of patients with (i) acute liver failure, (ii) alcoholic steatohepatitis, (iii) non-alcoholic fatty liver disease, (iv) liver cirrhosis, and (v) liver surgery/transplantation. The disease-related recommendations are preceded by general recommendations on the diagnostics of nutritional status in liver patients and on liver complications associated with medical nutrition. CONCLUSION This practical guideline gives guidance to health care providers involved in the management of liver disease to offer optimal nutritional care.
Collapse
Affiliation(s)
- Stephan C Bischoff
- Department for Clinical Nutrition, University of Hohenheim, Stuttgart, Germany.
| | - William Bernal
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Srinivasan Dasarathy
- Division of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - Manuela Merli
- Gastroenterology and Hepatology Unit, Sapienza University of Rome, Rome, Italy
| | - Lindsay D Plank
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Tatjana Schütz
- IFB Adiposity Diseases, Leipzig University Medical Centre, Leipzig, Germany
| | - Mathias Plauth
- Department of Internal Medicine, Municipal Hospital of Dessau, Dessau, Germany
| |
Collapse
|
17
|
Dietary intake of specific amino acids and liver status in subjects with nonalcoholic fatty liver disease: fatty liver in obesity (FLiO) study. Eur J Nutr 2020; 60:1769-1780. [PMID: 32857176 DOI: 10.1007/s00394-020-02370-6] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Accepted: 08/19/2020] [Indexed: 12/18/2022]
Abstract
PURPOSE Identification of dietary factors involved in the development and progression of nonalcoholic fatty liver disease (NAFLD) is relevant to the current epidemics of the disease. Dietary amino acids appear to play a key role in the onset and progression of NAFLD. The aim of this study was to analyze potential associations between specific dietary amino acids and variables related to glucose metabolism and hepatic status in adults with overweight/obesity and NAFLD. METHODS One hundred and twelve individuals from the Fatty Liver in Obesity (FLiO) study were evaluated. Liver assessment was carried out by ultrasonography, magnetic resonance imaging and analysis of biochemical parameters. Dietary amino acid intake (aromatic amino acids (AAA); branched-chain amino acids (BCAA); sulfur amino acids (SAA)) was estimated by means of a validated 137-item food frequency questionnaire. RESULTS Higher consumption of these amino acids was associated with worse hepatic health. Multiple adjusted regression models confirmed that dietary AAA, BCAA and SAA were positively associated with liver fat content. AAA and BCAA were positively associated with liver iron concentration. Regarding ferritin levels, a positive association was found with BCAA. Dietary intake of these amino acids was positively correlated with glucose metabolism (glycated hemoglobin, triglyceride and glucose index) although the significance disappeared when potential confounders were included in the model. CONCLUSION These findings suggest that the consumption of specific dietary amino acids might negatively impact on liver status and, to a lesser extent on glucose metabolism in subjects with overweight/obesity and NAFLD. A control of specific dietary amino acid composition should be considered in the management of NAFLD and associated insulin resistance. NCT03183193; June 2017.
Collapse
|
18
|
Hydes TJ, Ravi S, Loomba R, E Gray M. Evidence-based clinical advice for nutrition and dietary weight loss strategies for the management of NAFLD and NASH. Clin Mol Hepatol 2020; 26:383-400. [PMID: 32674529 PMCID: PMC7641567 DOI: 10.3350/cmh.2020.0067] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Accepted: 05/19/2020] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and affects approximately one third of adults in the United States. The disease is becoming a global epidemic as a result of the rising rates of obesity and metabolic disease. Emerging data suggest weight loss of ≥10% overall body weight is beneficial in resolving steatosis and reversing fibrosis. Prospective trials comparing various diets are limited by lack of sufficient power as well as pre- and post-treatment histopathology, and therefore no specific diet is recommended at this time. In this narrative review we examine the pathophysiology behind specific macronutrient components that can either promote or reverse NAFLD to help inform more specific dietary recommendations. Overall, the data supports reducing saturated fat, refined carbohydrates, and red and processed meats in the diet, and increasing the consumption of plant-based foods. Diets that incorporate these recommendations include plant-based diets such as the Dietary Approaches to Stop Hypertension, Mediterranean, vegetarian, and vegan diets.
Collapse
Affiliation(s)
- Theresa J Hydes
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Sujan Ravi
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Rohit Loomba
- Division of Gastroenterology, University of California, San Diego, La Jolla, CA, USA
| | - Meagan E Gray
- Division of Gastroenterology and Hepatology, University of Alabama at Birmingham, Birmingham, AL, USA
| |
Collapse
|
19
|
Buechert M, Lange T, Deibert P, Urbain P. In Vivo Fat Quantification: Monitoring Effects of a 6-Week Non-Energy-Restricted Ketogenic Diet in Healthy Adults Using MRI, ADP and BIA. Nutrients 2020; 12:nu12010244. [PMID: 31963475 PMCID: PMC7019649 DOI: 10.3390/nu12010244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 12/23/2019] [Accepted: 01/08/2020] [Indexed: 11/20/2022] Open
Abstract
The ketogenic diet (KD) is a very low-carbohydrate, high-fat, and adequate-protein diet that induces many metabolic adaptations when calorie intake is not limited. Its therapeutic use in a range of diseases including cancer is currently being investigated. Our objective was to firstly assess the impact of a 6-week non-energy-restricted KD on the abdominal fat distribution and the hepatic fat composition in healthy adults. Body fat distribution and composition were measured by comparing magnetic resonance imaging (MRI) and spectroscopy (MRS) results with air displacement plethysmography (ADP) and bioelectrical impedance analysis (BIA) measurements. A total of 12 subjects from the KetoPerformance study were recruited for this ancillary study. Body mass index (BMI), total mass, total fat mass, total subcutaneous mass, and subcutaneous fat mass decreased significantly. None of the MRS parameters showed a significant change during the study. Even though the average change in body weight was >2kg, no significant changes in intrahepatic lipid (IHL) content could be observed. Total fat mass and total fat-free mass derived from MRI has a strong correlation with the corresponding values derived from BIA and ADP data. BMI and the absolute fat parameter of all three modalities decreased, but there were no or only minor changes regarding the fat-free parameter. Magnetic resonance imaging provides body composition information on abdominal fat distribution changes during a ketogenic diet. This information is complementary to anthropomorphic and laboratory measures and is more detailed than the information provided by ADP and BIA measures. It was shown that there was no significant change in internal fat distribution, but there was a decrease in subcutaneous fat.
Collapse
Affiliation(s)
- Martin Buechert
- Department of Radiology, Medical Physics, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany;
- Correspondence:
| | - Thomas Lange
- Department of Radiology, Medical Physics, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany;
| | - Peter Deibert
- Institute for Exercise—und Occupational Medicine, Center for Medicine, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany;
| | - Paul Urbain
- Department of Medicine I, Section of Clinical Nutrition and Dietetics, Medical Center—University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany;
| |
Collapse
|
20
|
Khneizer G, Rizvi S, Gawrieh S. Non-alcoholic Fatty Liver Disease and Diabetes Mellitus. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1307:417-440. [PMID: 32424494 DOI: 10.1007/5584_2020_532] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) has emerged as the leading liver disease globally. NAFLD patients can have a progressive phenotype, non-alcoholic steatohepatitis (NASH) that could lead to cirrhosis, liver failure and cancer. There is a close bi-directional relationship between NAFLD and type 2 diabetes mellitus (T2DM); NAFLD increases the risk for T2DM and its complications whereas T2DM increases the severity of NAFLD and its complications. The large global impact of NAFLD and T2DM on healthcare systems requires a paradigm shift from specialty care to early identification and risk stratification of NAFLD in primary care and diabetes clinics. Approach to diagnosis, risk stratification and management of NAFLD is discussed. In addition to optimizing the control of coexisting cardiometabolic comorbidities, early referral of NAFLD patients at high risk of having NASH or significant fibrosis to hepatology specialist care may improve management and allow access for clinical trials. Lifestyle modifications, vitamin E, pioglitazone and metformin are currently available options that may benefit patients with T2DM and NAFLD. The burst of clinical trials investigating newer therapeutic agents for NAFLD and NASH offer hope for new, effective and safe therapies in the near future.
Collapse
Affiliation(s)
- Gebran Khneizer
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Syed Rizvi
- A&M College of Medicine, Round Rock, Austin, TX, USA
| | - Samer Gawrieh
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
| |
Collapse
|
21
|
Louala S, Lamri-Senhadji M. Beneficial Effects of Low-Calorie-Carbohydrate/High-Agar Diet on Cardiometabolic Disorders Associated with Non-Alcoholic Fatty Liver Disease in Obese Rats. Prev Nutr Food Sci 2019; 24:400-409. [PMID: 31915635 PMCID: PMC6941718 DOI: 10.3746/pnf.2019.24.4.400] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2019] [Accepted: 09/30/2019] [Indexed: 12/12/2022] Open
Abstract
Energy restriction and low carbohydrate diets are recommended as nutrition therapies to prevent becoming overweight or obese. However, their beneficial effects in non-alcoholic fatty liver disease (NAFLD) are less well investigated. In addition, the effects of the type of polysaccharides incorporated into these diets and their contents have been scarcely studied. Therefore, this study aimed to elucidate whether low-calorie-carbohydrate high-agar diets could improve liver metabolic dysfunction, membrane fluidity, oxidative damage, and endothelial dysfunction in obese rats. Obesity was induced by feeding rats a high-fat diet (HFD) for 10 weeks. The obese rats were then divided into two homogenous groups: the first group was fed low-calorie-carbohydrate/high-agar diet (LCC/HA) and the second continued to consume the HFD for 4 weeks [obese control (Ob-C)]. Normo-ponderal rats were fed a normal diet during the entire study, and were used as the control (N-C). Compared with the Ob-C group, body weight, hepatic lipids, low density lipoproteins cholesterol (C), the non esterified cholesterol/phospholipids ratio, serum transaminases activities, and lipid peroxidation markers (thiobarbituric acid reactive substances and lipid hydroperoxides) were reduced in LCC/HA group (P<0.05). However, the serum concentration of high density lipoproteins-C was enhanced (P<0.05). In addition, we observed improved antioxidant defence and endothelial dysfunction associated with antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase, and catalase (P<0.05), and nitric oxide level (P<0.05). These findings suggest that hypocaloric diets low in energy and carbohydrates and rich in agar may be beneficial against HFD-induced hepatic steatosis damage, and may be a promising therapeutic strategy to counteract NAFLD development associated with obesity.
Collapse
Affiliation(s)
- Sabrine Louala
- Laboratory of Clinical and Metabolic Nutrition (LNCM), Department Biology, Faculty of Nature and Life Sciences, University Oran 1, Oran 31100, Algeria
| | - Myriem Lamri-Senhadji
- Laboratory of Clinical and Metabolic Nutrition (LNCM), Department Biology, Faculty of Nature and Life Sciences, University Oran 1, Oran 31100, Algeria
| |
Collapse
|
22
|
Stokes CS, Lammert F, Krawczyk M. Short-term Dietary Interventions for the Management of Nonalcoholic Fatty Liver. Curr Med Chem 2019; 26:3483-3496. [PMID: 28482789 DOI: 10.2174/0929867324666170508144409] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2016] [Revised: 04/16/2017] [Accepted: 04/20/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) affects millions of individuals on a global scale and currently no gold standard treatment exists. The risk of developing NAFLD is considerably higher with increasing body mass index. Consequently, weight loss should be recommended to all overweight patients with fatty liver. However, lifestyle interventions, irrespective of weight status, may also influence the condition. The aim herein is to present examples of short-term interventions which assess direct effects of dietary-related components on hepatic steatosis. METHODS This review includes studies with short-term dietary-related interventions of up to 16 weeks that evaluate their efficacy in reducing intrahepatic lipid contents (hepatic steatosis). This review primarily focuses on the three main macronutrients: dietary carbohydrates, fats and proteins. RESULTS High saturated fat intake and high consumption of carbohydrates, particularly from simple sugars such as fructose are reported as risk factors for hepatic steatosis. Overall, shortterm hypocaloric diets have shown beneficial effects in reducing intrahepatic lipid contents. Macronutrient manipulations such as carbohydrate restriction as well as the consumption of unsaturated fatty acids are also reported to have efficacious effects. CONCLUSION This review highlights the different dietary interventions that can influence hepatic steatosis in the short term, illustrating both pro and anti-steatotic effects.
Collapse
Affiliation(s)
- Caroline S Stokes
- Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany
| | - Frank Lammert
- Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany
| | - Marcin Krawczyk
- Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany.,Laboratory of Metabolic Liver Diseases, Center for Preclinical Research, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| |
Collapse
|
23
|
Duarte SMB, Stefano JT, Vanni DS, Carrilho FJ, Oliveira CPMSD. IMPACT OF CURRENT DIET AT THE RISK OF NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD). ARQUIVOS DE GASTROENTEROLOGIA 2019; 56:431-439. [PMID: 31721969 DOI: 10.1590/s0004-2803.201900000-67] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 09/24/2019] [Indexed: 12/15/2022]
Abstract
The nonalcoholic fatty liver disease (NAFLD) affects approximately 20%-30% of general population and is even more prevalent among obese individuals. The risk factors mainly associated with NAFLD are diseases related to the metabolic syndrome, genetics and environment. In this review, we provide a literature compilation evaluating the evidence behind dietary components, including calories intake, fat, protein, fibers and carbohydrate, especially fructose which could be a trigger to development and progression of the NAFLD. In fact, it has been demonstrated that diet is an important factor for the development of NAFLD and its association is complex and extends beyond total energy intake.
Collapse
Affiliation(s)
| | - José Tadeu Stefano
- Universidade de São Paulo, Hospital das Clínicas, Laboratório de Gastroenterologia Clínica e Experimental (LIM-07) do Departamento de Gastroenterologia da FMUSP, São Paulo, SP, Brasil
| | - Denise Siqueira Vanni
- Universidade de São Paulo, Hospital das Clínicas, Divisão de Gastroenterologia e Hepatologia Clínica e Departamento de Gastroenterologia da FMUSP, São Paulo, SP, Brasil
| | - Flair José Carrilho
- Universidade de São Paulo, Faculdade de Medicina, São Paulo, SP, Brasil
- Universidade de São Paulo, Hospital das Clínicas, Divisão de Gastroenterologia e Hepatologia Clínica e Departamento de Gastroenterologia da FMUSP, São Paulo, SP, Brasil
| | - Claudia Pinto Marques Souza de Oliveira
- Universidade de São Paulo, Faculdade de Medicina, São Paulo, SP, Brasil
- Universidade de São Paulo, Hospital das Clínicas, Laboratório de Gastroenterologia Clínica e Experimental (LIM-07) do Departamento de Gastroenterologia da FMUSP, São Paulo, SP, Brasil
| |
Collapse
|
24
|
Kuttner CS, Mancina R, Wagenpfeil G, Lammert F, Stokes CS. Four-Week Omega-3 Supplementation in Carriers of the Prosteatotic PNPLA3 p.I148M Genetic Variant: An Open-Label Study. Lifestyle Genom 2019; 12:10-17. [PMID: 31454802 DOI: 10.1159/000502008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Accepted: 07/08/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND/AIMS The PNPLA3 loss-of-function variant p.I148M is a strong genetic determinant of nonalcoholic fatty liver disease. The PNPLA3 protein functions as an intracellular lipase in the liver, with a greater activity on unsaturated fatty acids. This study aimed to determine whether short-term supplementation with omega-3 fatty acids impacts hepatic steatosis differently in PNPLA3 p.148I wild-type individuals as compared to homozygous carriers of the PNPLA3 p.148M variant. METHODS Twenty subjects with hepatic steatosis (50% women, age 18-77 years) were included. Ten subjects homozygous for the PNPLA3 148M variant were matched to 10 wild-type individuals. The subjects received 4 g omega-3 fatty acids (1,840 mg eicosapentaenoic acid and 1,520 mg docosahexaenoic acid) a day for 4 weeks. Transient elastography with a controlled attenuation parameter (CAP) was used to quantify liver fat before and after the intervention. Body composition, fibrosis, liver function tests, serum free fatty acids (FFA) and glucose markers were compared. RESULTS Patients homozygous for the PNPLA3 p.148M variant (risk group) demonstrated no significant changes in CAP compared to baseline (284 ± 55 vs. 287 ± 65 dB/m) as did the control group (256 ± 56 vs. 262 ± 55 dB/m). While serum liver enzyme activities remained unchanged in both groups, the risk group displayed significantly (p = 0.02) lower baseline FFA concentrations (334.5 [range 281.0-431.0] vs. 564.5 [range 509.0-682.0] μmol/L), which markedly increased by 9.1% after the intervention. In contrast, FFA concentrations decreased significantly (p = 0.01) by 28.3% in the wild-type group. CONCLUSIONS Short-term omega-3 fatty acid supplementation did not significantly alter hepatic steatosis. The nutrigenomic and metabolic effects of omega-3 fatty acids should be investigated further in carriers of the PNPLA3 148M risk variant.
Collapse
Affiliation(s)
- Clara-Sophie Kuttner
- Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany
| | - Rosellina Mancina
- Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Gudrun Wagenpfeil
- Institute of Medical Biometry, Epidemiology and Medical Informatics, Saarland University, Homburg, Germany
| | - Frank Lammert
- Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany,
| | - Caroline S Stokes
- Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany
| |
Collapse
|
25
|
Safari Z, Gérard P. The links between the gut microbiome and non-alcoholic fatty liver disease (NAFLD). Cell Mol Life Sci 2019; 76:1541-1558. [PMID: 30683985 PMCID: PMC11105223 DOI: 10.1007/s00018-019-03011-w] [Citation(s) in RCA: 334] [Impact Index Per Article: 55.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Revised: 12/11/2018] [Accepted: 01/15/2019] [Indexed: 12/11/2022]
Abstract
NAFLD is currently the main cause of chronic liver disease in developed countries, and the number of NAFLD patients is growing worldwide. NAFLD often has similar symptoms to other metabolic disorders, including type 2 diabetes and obesity. Recently, the role of the gut microbiota in the pathophysiology of many diseases has been revealed. Regarding NAFLD, experiments using gut microbiota transplants to germ-free animal models showed that fatty liver disease development is determined by gut bacteria. Moreover, the perturbation of the composition of the gut microbiota has been observed in patients suffering from NAFLD. Numerous mechanisms relating the gut microbiome to NAFLD have been proposed, including the dysbiosis-induced dysregulation of gut endothelial barrier function that allows for the translocation of bacterial components and leads to hepatic inflammation. In addition, the various metabolites produced by the gut microbiota may impact the liver and thus modulate NAFLD susceptibility. Therefore, the manipulation of the gut microbiome by probiotics, prebiotics or synbiotics was shown to improve liver phenotype in NAFLD patients as well as in rodent models. Hence, further knowledge about the interactions among dysbiosis, environmental factors, and diet and their impacts on the gut-liver axis can improve the treatment of this life-threatening liver disease and its related disorders.
Collapse
Affiliation(s)
- Zahra Safari
- Micalis Institute, INRA, UMR1319, Equipe AMIPEM, AgroParisTech, Université Paris-Saclay, Building 442, Domaine de Vilvert, 78350, Jouy-en-Josas, France
- Institute of Pathology, Medical University of Graz, Graz, Austria
| | - Philippe Gérard
- Micalis Institute, INRA, UMR1319, Equipe AMIPEM, AgroParisTech, Université Paris-Saclay, Building 442, Domaine de Vilvert, 78350, Jouy-en-Josas, France.
| |
Collapse
|
26
|
From sugar to liver fat and public health: systems biology driven studies in understanding non-alcoholic fatty liver disease pathogenesis. Proc Nutr Soc 2019; 78:290-304. [PMID: 30924429 DOI: 10.1017/s0029665119000570] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is now a major public health concern with an estimated prevalence of 25-30% of adults in many countries. Strongly associated with obesity and the metabolic syndrome, the pathogenesis of NAFLD is dependent on complex interactions between genetic and environmental factors that are not completely understood. Weight loss through diet and lifestyle modification underpins clinical management; however, the roles of individual dietary nutrients (e.g. saturated and n-3 fatty acids; fructose, vitamin D, vitamin E) in the pathogenesis or treatment of NAFLD are only partially understood. Systems biology offers valuable interdisciplinary methods that are arguably ideal for application to the studying of chronic diseases such as NAFLD, and the roles of nutrition and diet in their molecular pathogenesis. Although present in silico models are incomplete, computational tools are rapidly evolving and human metabolism can now be simulated at the genome scale. This paper will review NAFLD and its pathogenesis, including the roles of genetics and nutrition in the development and progression of disease. In addition, the paper introduces the concept of systems biology and reviews recent work utilising genome-scale metabolic networks and developing multi-scale models of liver metabolism relevant to NAFLD. A future is envisioned where individual genetic, proteomic and metabolomic information can be integrated computationally with clinical data, yielding mechanistic insight into the pathogenesis of chronic diseases such as NAFLD, and informing personalised nutrition and stratified medicine approaches for improving prognosis.
Collapse
|
27
|
Vilar-Gomez E, Athinarayanan SJ, Adams RN, Hallberg SJ, Bhanpuri NH, McKenzie AL, Campbell WW, McCarter JP, Phinney SD, Volek JS, Chalasani N. Post hoc analyses of surrogate markers of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in patients with type 2 diabetes in a digitally supported continuous care intervention: an open-label, non-randomised controlled study. BMJ Open 2019; 9:e023597. [PMID: 30803948 PMCID: PMC6398805 DOI: 10.1136/bmjopen-2018-023597] [Citation(s) in RCA: 30] [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] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE One year of comprehensive continuous care intervention (CCI) through nutritional ketosis improves glycosylated haemoglobin(HbA1c), body weight and liver enzymes among patients with type 2 diabetes (T2D). Here, we report the effect of the CCI on surrogate scores of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis. METHODS This was a non-randomised longitudinal study, including adults with T2D who were self-enrolled to the CCI (n=262) or to receive usual care (UC, n=87) during 1 year. An NAFLD liver fat score (N-LFS) >-0.640 defined the presence of fatty liver. An NAFLD fibrosis score (NFS) of >0.675 identified subjects with advanced fibrosis. Changes in N-LFS and NFS at 1 year were the main endpoints. RESULTS At baseline, NAFLD was present in 95% of patients in the CCI and 90% of patients in the UC. At 1 year, weight loss of ≥5% was achieved in 79% of patients in the CCI versus 19% of patients in UC (p<0.001). N-LFS mean score was reduced in the CCI group (-1.95±0.22, p<0.001), whereas it was not changed in the UC (0.47±0.41, p=0.26) (CCI vs UC, p<0.001). NFS was reduced in the CCI group (-0.65±0.06, p<0.001) compared with UC (0.26±0.11, p=0.02) (p<0.001 between two groups). In the CCI group, the percentage of individuals with a low probability of advanced fibrosis increased from 18% at baseline to 33% at 1 year (p<0.001). CONCLUSIONS One year of a digitally supported CCI significantly improved surrogates of NAFLD and advanced fibrosis in patients with T2D. TRIAL REGISTRATION NUMBER NCT02519309; Results.
Collapse
Affiliation(s)
- Eduardo Vilar-Gomez
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | | | | | - Sarah J Hallberg
- Virta Health, San Francisco, California, USA
- Indiana University Health Arnett, Lafayette, Indiana, USA
| | | | | | - Wayne W Campbell
- Department of Nutrition Science, Purdue University, West Lafayette, Indiana, USA
| | - James P McCarter
- Virta Health, San Francisco, California, USA
- Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA
| | | | - Jeff S Volek
- Virta Health, San Francisco, California, USA
- Department of Human Sciences, Ohio State University, Columbus, Ohio, USA
| | - Naga Chalasani
- Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| |
Collapse
|
28
|
Effect of Fish Oil Supplementation on Hepatic and Visceral Fat in Overweight Men: A Randomized Controlled Trial. Nutrients 2019; 11:nu11020475. [PMID: 30813440 PMCID: PMC6413081 DOI: 10.3390/nu11020475] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 02/12/2019] [Accepted: 02/20/2019] [Indexed: 12/16/2022] Open
Abstract
Being overweight increases the risk of the development of metabolic conditions such as non-alcoholic fatty liver disease (NAFLD), which is itself an independent predictor of cardiovascular disease. Omega-3 polyunsaturated fatty acid (PUFA) supplementation is recommended for prevention of chronic disease, and is thought to reduce raised liver fat, yet there have been few randomized controlled trials with accurate measurement of liver fat. We assessed the effect of 12 weeks of supplementation with omega-3 PUFA from fish oil versus placebo on quantified liver fat, liver tests, and body composition including visceral adipose tissue (VAT) in a double-blind randomized controlled trial. Fifty apparently healthy overweight men (BMI 25.0–29.9 kg/m2; waist > 94 cm) were randomly allocated to consume fish oil (total daily dose: 1728 mg marine triglycerides, of which 588 mg EPA and 412 mg DHA, combined with 200 mg antioxidant, coenzyme Q10) or placebo (olive oil capsules) daily for 12 weeks. Liver fat was assessed using proton magnetic resonance spectroscopy. All outcomes were assessed at baseline and following 6 and 12 weeks of supplementation. Baseline liver fat was 4.6 ± 0.5% (range: 0.6 to 18.2%); 16 (32%) participants met the criteria for NAFLD (>5.5% liver fat). Repeated measures ANOVA revealed no significant time or group × time effect for fish oil versus placebo for liver fat, liver enzymes, anthropometry, or body composition including VAT (p > 0.05 for all), with similar finding for sub-analysis of participants with NAFLD. Omega-3 PUFA did not appear to be an effective agent for reducing liver fat in overweight men. The factors determining the health benefits of omega-3 PUFA supplementation on an individual level need to be clarified.
Collapse
|
29
|
Plauth M, Bernal W, Dasarathy S, Merli M, Plank LD, Schütz T, Bischoff SC. ESPEN guideline on clinical nutrition in liver disease. Clin Nutr 2019; 38:485-521. [PMID: 30712783 DOI: 10.1016/j.clnu.2018.12.022] [Citation(s) in RCA: 392] [Impact Index Per Article: 65.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 12/18/2018] [Indexed: 02/06/2023]
Abstract
This update of evidence-based guidelines (GL) aims to translate current evidence and expert opinion into recommendations for multidisciplinary teams responsible for the optimal nutritional and metabolic management of adult patients with liver disease. The GL was commissioned and financially supported by ESPEN. Members of the guideline group were selected by ESPEN. We searched for meta-analyses, systematic reviews and single clinical trials based on clinical questions according to the PICO format. The evidence was evaluated and used to develop clinical recommendations implementing the SIGN method. A total of 85 recommendations were made for the nutritional and metabolic management of patients with acute liver failure, severe alcoholic steatohepatitis, non-alcoholic fatty liver disease, liver cirrhosis, liver surgery and transplantation as well as nutrition associated liver injury distinct from fatty liver disease. The recommendations are preceded by statements covering current knowledge of the underlying pathophysiology and pathobiochemistry as well as pertinent methods for the assessment of nutritional status and body composition.
Collapse
Affiliation(s)
- Mathias Plauth
- Department of Internal Medicine, Municipal Hospital of Dessau, Dessau, Germany.
| | - William Bernal
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Srinivasan Dasarathy
- Division of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - Manuela Merli
- Gastroenterology and Hepatology Unit, Sapienza University of Rome, Rome, Italy
| | - Lindsay D Plank
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Tatjana Schütz
- IFB Adiposity Diseases, Leipzig University Medical Centre, Leipzig, Germany
| | - Stephan C Bischoff
- Department for Clinical Nutrition, University of Hohenheim, Stuttgart, Germany
| |
Collapse
|
30
|
Nier A, Brandt A, Conzelmann IB, Özel Y, Bergheim I. Non-Alcoholic Fatty Liver Disease in Overweight Children: Role of Fructose Intake and Dietary Pattern. Nutrients 2018; 10:nu10091329. [PMID: 30235828 PMCID: PMC6165138 DOI: 10.3390/nu10091329] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Revised: 09/04/2018] [Accepted: 09/18/2018] [Indexed: 12/15/2022] Open
Abstract
The role of nutrition and diet in the development of non-alcoholic fatty liver disease (NAFLD) is still not fully understood. In the present study, we determined if dietary pattern and markers of intestinal permeability differ between overweight children with and without NAFLD. In addition, in a feasibility study, we assessed the effect of a moderate dietary intervention only focusing on nutrients identified to differ between groups on markers of intestinal barrier function and health status. Anthropometric data, dietary intake, metabolic parameters, and markers of inflammation, as well as of intestinal permeability, were assessed in overweight children (n = 89, aged 5⁻9) and normal-weight healthy controls (n = 36, aged 5⁻9). Sixteen children suffered from early signs of NAFLD, e.g., steatosis grade 1 as determined by ultrasound. Twelve children showing early signs of NAFLD were enrolled in the intervention study (n = 6 intervention, n = 6 control). Body mass index (BMI), BMI standard deviation score (BMI-SDS), and waist circumference were significantly higher in NAFLD children than in overweight children without NAFLD. Levels of bacterial endotoxin, lipopolysaccharide-binding protein (LBP), and proinflammatory markers like interleukin 6 (IL-6) and tumor necrosis factor α (TNFα) were also significantly higher in overweight children with NAFLD compared to those without. Total energy and carbohydrate intake were higher in NAFLD children than in those without. The higher carbohydrate intake mainly resulted from a higher total fructose and glucose intake derived from a significantly higher consumption of sugar-sweetened beverages. When counseling children with NAFLD regarding fructose intake (four times, 30⁻60 min within 1 year; one one-on-one counseling and three group counselings), neither alanine aminotransferase (ALT) nor aspartate aminotransferase (AST) activity in serum changed; however, diastolic blood pressure (p < 0.05) and bacterial endotoxin levels (p = 0.06) decreased markedly in the intervention group after one year. Similar changes were not found in uncounseled children. Our results suggest that a sugar-rich diet might contribute to the development of early stages of NAFLD in overweight children, and that moderate dietary counseling might improve the metabolic status of overweight children with NAFLD.
Collapse
Affiliation(s)
- Anika Nier
- Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, A-1090 Vienna, Austria.
| | - Annette Brandt
- Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, A-1090 Vienna, Austria.
| | - Ina Barbara Conzelmann
- Department of Nutritional Medicine, (180), University of Hohenheim, D-70599 Stuttgart, Germany.
| | - Yelda Özel
- Department of Nutritional Medicine, (180), University of Hohenheim, D-70599 Stuttgart, Germany.
| | - Ina Bergheim
- Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, A-1090 Vienna, Austria.
| |
Collapse
|
31
|
De Bandt JP, Jegatheesan P, Tennoune-El-Hafaia N. Muscle Loss in Chronic Liver Diseases: The Example of Nonalcoholic Liver Disease. Nutrients 2018; 10:E1195. [PMID: 30200408 PMCID: PMC6165394 DOI: 10.3390/nu10091195] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Revised: 08/22/2018] [Accepted: 08/23/2018] [Indexed: 12/13/2022] Open
Abstract
Recent publications highlight a frequent loss of muscle mass in chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD), and its association with a poorer prognosis. In NAFLD, given the role of muscle in energy metabolism, muscle loss promotes disease progression. However, liver damage may be directly responsible of this muscle loss. Indeed, muscle homeostasis depends on the balance between peripheral availability and action of anabolic effectors and catabolic signals. Moreover, insulin resistance of protein metabolism only partially explains muscle loss during NAFLD. Interestingly, some data indicate specific alterations in the liver⁻muscle axis, particularly in situations such as excess fructose/sucrose consumption, associated with increased hepatic de novo lipogenesis (DNL) and endoplasmic reticulum stress. In this context, the liver will be responsible for a decrease in the peripheral availability of anabolic factors such as hormones and amino acids, and for the production of catabolic effectors such as various hepatokines, methylglyoxal, and uric acid. A better understanding of these liver⁻muscle interactions could open new therapeutic opportunities for the management of NAFLD patients.
Collapse
|
32
|
Mirtschink P, Jang C, Arany Z, Krek W. Fructose metabolism, cardiometabolic risk, and the epidemic of coronary artery disease. Eur Heart J 2018; 39:2497-2505. [PMID: 29020416 PMCID: PMC6037111 DOI: 10.1093/eurheartj/ehx518] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2017] [Revised: 07/16/2017] [Accepted: 08/15/2017] [Indexed: 02/06/2023] Open
Abstract
Despite strong indications that increased consumption of added sugars correlates with greater risks of developing cardiometabolic syndrome (CMS) and cardiovascular disease (CVD), independent of the caloric intake, the worldwide sugar consumption remains high. In considering the negative health impact of overconsumption of dietary sugars, increased attention is recently being given to the role of the fructose component of high-sugar foods in driving CMS. The primary organs capable of metabolizing fructose include liver, small intestine, and kidneys. In these organs, fructose metabolism is initiated by ketohexokinase (KHK) isoform C of the central fructose-metabolizing enzyme KHK. Emerging data suggest that this tissue restriction of fructose metabolism can be rescinded in oxygen-deprived environments. In this review, we highlight recent progress in understanding how fructose metabolism contributes to the development of major systemic pathologies that cooperatively promote CMS and CVD, reference recent insights into microenvironmental control of fructose metabolism under stress conditions and discuss how this understanding is shaping preventive actions and therapeutic approaches.
Collapse
Affiliation(s)
- Peter Mirtschink
- Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Otto-Stern-Weg 7, Zurich, Switzerland
- Department of Clinical Pathobiochemistry, Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Dresden, Fetscherstr. 74, Dresden, Germany
| | - Cholsoon Jang
- Department of Medicine, Cardiovascular Institute and Institute Diabetes Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, 11th floor, Civic Blvd, Philadelphia, 19104 PA, USA
| | - Zoltan Arany
- Department of Medicine, Cardiovascular Institute and Institute Diabetes Obesity and Metabolism, Perelman School of Medicine, University of Pennsylvania, 11th floor, Civic Blvd, Philadelphia, 19104 PA, USA
| | - Wilhelm Krek
- Department of Biology, Institute of Molecular Health Sciences, ETH Zurich, Otto-Stern-Weg 7, Zurich, Switzerland
| |
Collapse
|
33
|
Bischoff SC. [The intestinal microbiome and metabolic diseases : From obesity to diabetes and nonalcoholic steatohepatitis]. Internist (Berl) 2018; 58:441-448. [PMID: 28432400 DOI: 10.1007/s00108-017-0229-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND The intestinal microbiome consists of about 10 million genes, many of which encode digestive enzymes. This explains why animal and human experiments revealed that the intestinal microbiome adapts to food intake and optimizes energy harvest from food. This function is considered beneficial in states of lack of food, but following overnutrition, it might support the development of obesity. OBJECTIVES The relevance of the intestinal microbiome for the pathogenesis of obesity and associated metabolic diseases such as fatty liver disease and type 2 diabetes mellitus and for the clinical management of such diseases shall be discussed. MATERIALS AND METHODS Recent literature related to the topic has been selected, presented, and discussed with regard to the objectives. RESULTS The intestinal microbiome plays a role in the pathogenesis of both obesity (by increasing the energy absorption from food) and fatty liver disease as well as type 2 diabetes mellitus (via induction of low-grade inflammation following translocation of lipopolysaccharides from the gut and dysregulation of metabolic pathways). CONCLUSIONS The findings might have consequences for diagnosis (identification of risk groups) and therapy (usage of known and novel probiotics or bacterial metabolites) of metabolic diseases.
Collapse
Affiliation(s)
- S C Bischoff
- Institut für Ernährungsmedizin, Universität Hohenheim, Fruwirthstr. 12, 70593, Stuttgart, Deutschland.
| |
Collapse
|
34
|
Parry SA, Hodson L. Influence of dietary macronutrients on liver fat accumulation and metabolism. J Investig Med 2017; 65:1102-1115. [PMID: 28947639 PMCID: PMC5749316 DOI: 10.1136/jim-2017-000524] [Citation(s) in RCA: 93] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/08/2017] [Indexed: 02/07/2023]
Abstract
The liver is a principal metabolic organ within the human body and has a major role in regulating carbohydrate, fat, and protein metabolism. With increasing rates of obesity, the prevalence of non-alcoholic fatty liver disease (NAFLD) is growing. It remains unclear why NAFLD, which is now defined as the hepatic manifestation of the metabolic syndrome, develops but lifestyle factors such as diet (ie, total calorie and specific nutrient intakes), appear to play a key role. Here we review the available observational and intervention studies that have investigated the influence of dietary macronutrients on liver fat content. Findings from observational studies are conflicting with some reporting that relative to healthy controls, patients with NAFLD consume diets higher in total fat/saturated fatty acids, whilst others find they consume diets higher in carbohydrates/sugars. From the limited number of intervention studies that have been undertaken, a consistent finding is a hypercaloric diet, regardless of whether the excess calories have been provided either as fat, sugar, or both, increases liver fat content. In contrast, a hypocaloric diet decreases liver fat content. Findings from both hyper- and hypo-caloric feeding studies provide some suggestion that macronutrient composition may also play a role in regulating liver fat content and this is supported by data from isocaloric feeding studies; fatty acid composition and/or carbohydrate content/type appear to influence whether there is accrual of liver fat or not. The mechanisms by which specific macronutrients, when consumed as part of an isocaloric diet, cause a change in liver fat remain to be fully elucidated.
Collapse
Affiliation(s)
- Siôn A Parry
- Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK
| | - Leanne Hodson
- Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK
| |
Collapse
|
35
|
Nier A, Engstler AJ, Maier IB, Bergheim I. Markers of intestinal permeability are already altered in early stages of non-alcoholic fatty liver disease: Studies in children. PLoS One 2017; 12:e0183282. [PMID: 28880885 PMCID: PMC5589126 DOI: 10.1371/journal.pone.0183282] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Accepted: 08/01/2017] [Indexed: 02/07/2023] Open
Abstract
Background & aims Recent studies have shown that patients with manifest non-alcoholic fatty liver disease (NAFLD), e.g. steatosis grade 3 or steatohepatitis with or without beginning fibrosis frequently show altered fecal microbiota composition and elevated bacterial endotoxin levels. However, if these alterations are signs of a progressing disease or are already found in initial disease stages has not yet been clarified. Methods Twenty children with simple steatosis (grade 1) diagnosed by ultrasound and 29 normal weight healthy control children (age <10 years) were included in the study (mean age 7.6 ± 1.1 years). Metabolic parameters, markers of intestinal barrier function and inflammation were determined. Results Activity of alanine aminotransferase, concentrations of some markers of inflammation and insulin resistance were significantly higher in plasma of NAFLD children than in controls. When compared to controls, plasma bacterial endotoxin and lipopolysaccharide-binding protein (LBP) levels were significantly higher in NAFLD children (+50% and +24%, respectively), while soluble CD14 serum and D-lactate plasma levels as well as the prevalence of small intestinal bacterial overgrowth did not differ between groups. Plasma endotoxin and LBP levels were positive associated with proinflammatory markers like plasminogen activator inhibitor-1, c-reactive protein, interleukin-6 and leptin while no associations with markers of insulin resistance were found. Conclusions Taken together, our results indicate that even in juvenile patients with early stages of NAFLD e.g. simple steatosis grade 1, plasma endotoxin concentrations are already elevated further suggesting that intestinal barrier dysfunction might be present already in the initial phases of the disease.
Collapse
Affiliation(s)
- Anika Nier
- Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, Austria
- Institute of Nutrition, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University Jena, Jena, Germany
| | - Anna Janina Engstler
- Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, Austria
- Institute of Nutrition, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University Jena, Jena, Germany
| | - Ina Barbara Maier
- Department of Nutritional Medicine, (180), University of Hohenheim, Stuttgart, Germany
| | - Ina Bergheim
- Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, Austria
- Institute of Nutrition, SD Model Systems of Molecular Nutrition, Friedrich-Schiller University Jena, Jena, Germany
- * E-mail:
| |
Collapse
|
36
|
Ter Horst KW, Serlie MJ. Fructose Consumption, Lipogenesis, and Non-Alcoholic Fatty Liver Disease. Nutrients 2017; 9:E981. [PMID: 28878197 PMCID: PMC5622741 DOI: 10.3390/nu9090981] [Citation(s) in RCA: 205] [Impact Index Per Article: 25.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 08/25/2017] [Accepted: 09/04/2017] [Indexed: 02/07/2023] Open
Abstract
Increased fructose consumption has been suggested to contribute to non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and insulin resistance, but a causal role of fructose in these metabolic diseases remains debated. Mechanistically, hepatic fructose metabolism yields precursors that can be used for gluconeogenesis and de novo lipogenesis (DNL). Fructose-derived precursors also act as nutritional regulators of the transcription factors, including ChREBP and SREBP1c, that regulate the expression of hepatic gluconeogenesis and DNL genes. In support of these mechanisms, fructose intake increases hepatic gluconeogenesis and DNL and raises plasma glucose and triglyceride levels in humans. However, epidemiological and fructose-intervention studies have had inconclusive results with respect to liver fat, and there is currently no good human evidence that fructose, when consumed in isocaloric amounts, causes more liver fat accumulation than other energy-dense nutrients. In this review, we aim to provide an overview of the seemingly contradicting literature on fructose and NAFLD. We outline fructose physiology, the mechanisms that link fructose to NAFLD, and the available evidence from human studies. From this framework, we conclude that the cellular mechanisms underlying hepatic fructose metabolism will likely reveal novel targets for the treatment of NAFLD, dyslipidemia, and hepatic insulin resistance. Finally, fructose-containing sugars are a major source of excess calories, suggesting that a reduction of their intake has potential for the prevention of NAFLD and other obesity-related diseases.
Collapse
Affiliation(s)
- Kasper W Ter Horst
- Department of Endocrinology and Metabolism, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands.
| | - Mireille J Serlie
- Department of Endocrinology and Metabolism, Academic Medical Center, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands.
| |
Collapse
|
37
|
Bischoff SC, Boirie Y, Cederholm T, Chourdakis M, Cuerda C, Delzenne NM, Deutz NE, Fouque D, Genton L, Gil C, Koletzko B, Leon-Sanz M, Shamir R, Singer J, Singer P, Stroebele-Benschop N, Thorell A, Weimann A, Barazzoni R. Towards a multidisciplinary approach to understand and manage obesity and related diseases. Clin Nutr 2017; 36:917-938. [DOI: 10.1016/j.clnu.2016.11.007] [Citation(s) in RCA: 116] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Revised: 11/03/2016] [Accepted: 11/03/2016] [Indexed: 12/13/2022]
|
38
|
Breusing N, Lagerpusch M, Engstler AJ, Bergheim I, Mueller MJ, Bosy-Westphal A. Influence of Energy Balance and Glycemic Index on Metabolic Endotoxemia in Healthy Men. J Am Coll Nutr 2017; 36:72-79. [PMID: 28060600 DOI: 10.1080/07315724.2016.1156036] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
OBJECTIVE Overfeeding with a high-fat and/or high-carbohydrate (CHO) diet is known to increase plasma concentrations of endotoxin (lipopolysaccharide [LPS]) that may lead to metabolic disturbances like insulin resistance. The impact of CHO quality (i.e., the glycemic index [GI]) independent of fat intake on metabolic endotoxemia remains unclear. In the present study, the effects of changes in energy balance and GI on plasma endotoxin were studied. METHODS Fifteen healthy young men overconsumed diets containing 65% CHO and 20% fat for 1 week (OF; +50% of energy requirement) followed by 3 weeks of caloric restriction (CR; -50% of energy requirement) and were then randomized to 2 weeks hypercaloric refeeding (RF, +50% of energy requirement) with either a low- or high-GI (40 vs 74) diet. RESULTS During OF, subjects gained 1.9 ± 0.7 kg body weight (+0.6 ± 0.8% fat mass) followed by a weight loss of 6.1 ± 0.8 kg (-2.0 ± 0.6% fat mass) and weight regain of 4.0 ± 0.6 kg (0.9 ± 0.8% fat mass). Fasting insulin and homeostasis model assessment-insulin resistance (HOMAIR) increased with OF and RF and decreased with CR, MatsudaISI decreased by 37% after RF (all p < 0.05). Endotoxin significantly increased by 30.8% with OF and by 24.7% with RF (both p < 0.05), whereas CR normalized endotoxin levels. No difference in endotoxin levels was observed between refeeding a hypercaloric high- or low-GI diet. Changes in endotoxin levels with RF were not related to changes in insulin sensitivity. CONCLUSION A hypercaloric diet (OF and RF) increased plasma endotoxin irrespective of GI, whereas a negative energy balance did not reduce endotoxemia. Impaired insulin sensitivity with hypercaloric refeeding on a high-GI diet was not explained by metabolic endotoxemia.
Collapse
Affiliation(s)
- Nicolle Breusing
- a University of Hohenheim, Institute of Nutritional Medicine , Stuttgart , GERMANY
| | - Merit Lagerpusch
- a University of Hohenheim, Institute of Nutritional Medicine , Stuttgart , GERMANY
| | | | - Ina Bergheim
- b Friedrich Schiller University, Institute of Nutrition , Jena , GERMANY
| | - Manfred J Mueller
- c Christian-Albrechts-University, Institute of Human Nutrition and Food Science , Kiel , GERMANY
| | - Anja Bosy-Westphal
- a University of Hohenheim, Institute of Nutritional Medicine , Stuttgart , GERMANY
| |
Collapse
|
39
|
Ibarra-Reynoso LDR, López-Lemus HL, Garay-Sevilla ME, Malacara JM. Effect of Restriction of Foods with High Fructose Corn Syrup Content on Metabolic Indices and Fatty Liver in Obese Children. Obes Facts 2017; 10:332-340. [PMID: 28787728 PMCID: PMC5644940 DOI: 10.1159/000476069] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Accepted: 04/20/2017] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE We examined the effect of restriction of foods with high fructose content in obese school children. METHODS In a clinical study, we selected 54 obese children 6 to 11 years old with high fructose consumption (>70 g/day) in order indicate dietary fructose restriction (<20 g/day) for 6 weeks. Anthropometry, liver ultrasound as well as glucose, insulin, lipids, leptin, IGFBP1, and RBP4 serum levels were collected. RESULTS The group of children had 80% adherence and reported decreased fructose consumption (110 ± 38.6 to 11.4 ± 12.0 g/day) and also a significant decrease in caloric (2,384 ± 568 to 1,757 ± 387 kcal/day) and carbohydrate consumption (302 ± 80.4 to 203 ± 56.0 g/day). The severity of steatosis improved significantly after fructose restriction (p < 0.000001). However, no changes in BMI, systolic blood pressure, or diastolic blood pressure were found. Only triglyceride levels decreased (1.44 ± 0.43 to 1.31 ± 0.38 mmol/l), High-densitiy lipoprotein cholesterol showed a marginal increase (1.45 ± 0.19 to 1.56 ± 0.44 mmol/l). Insulin resistance and RBP4 did not change. CONCLUSIONS In school children, the restriction of high fructose foods with a decrease of caloric and carbohydrate intake at 6 weeks did not induce weight loss; however, triglyceride levels and hepatic steatosis decreased. Differences with other studies in regard to weight loss may be explained by adaptive changes on metabolic expenditure.
Collapse
Affiliation(s)
- Lorena del Rocio Ibarra-Reynoso
- *Lorena del Rocío Ibarra-Reynoso, Department of Medical Sciences, University of Guanajuato, Campus León, 20 de Enero 929, 37320 León, Mexico,
| | | | | | | |
Collapse
|
40
|
Alwahsh SM, Gebhardt R. Dietary fructose as a risk factor for non-alcoholic fatty liver disease (NAFLD). Arch Toxicol 2016; 91:1545-1563. [PMID: 27995280 DOI: 10.1007/s00204-016-1892-7] [Citation(s) in RCA: 107] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2016] [Accepted: 11/08/2016] [Indexed: 12/16/2022]
Abstract
Glucose is a major energy source for the entire body, while fructose metabolism occurs mainly in the liver. Fructose consumption has increased over the last decade globally and is suspected to contribute to the increased incidence of non-alcoholic fatty liver disease (NAFLD). NAFLD is a manifestation of metabolic syndrome affecting about one-third of the population worldwide and has progressive pathological potential for liver cirrhosis and cancer through non-alcoholic steatohepatitis (NASH). Here we have reviewed the possible contribution of fructose to the pathophysiology of NAFLD. We critically summarize the current findings about several regulators, and their potential mechanisms, that have been studied in humans and animal models in response to fructose exposure. A novel hypothesis on fructose-dependent perturbation of liver regeneration and metabolism is advanced. Fructose intake could affect inflammatory and metabolic processes, liver function, gut microbiota, and portal endotoxin influx. The role of the brain in controlling fructose ingestion and the subsequent development of NAFLD is highlighted. Although the importance for fructose (over)consumption for NAFLD in humans is still debated and comprehensive intervention studies are invited, understanding of how fructose intake can favor these pathological processes is crucial for the development of appropriate noninvasive diagnostic and therapeutic approaches to detect and treat these metabolic effects. Still, lifestyle modification, to lessen the consumption of fructose-containing products, and physical exercise are major measures against NAFLD. Finally, promising drugs against fructose-induced insulin resistance and hepatic dysfunction that are emerging from studies in rodents are reviewed, but need further validation in human patients.
Collapse
Affiliation(s)
- Salamah Mohammad Alwahsh
- Faculty of Medicine, Institute of Biochemistry, University of Leipzig, Johannisallee 30, 04103, Leipzig, Germany. .,MCR Centre for Regenerative Medicine, University of Edinburgh, 5 Little France Dr, EH16 4UU Edinburgh, UK.
| | - Rolf Gebhardt
- Faculty of Medicine, Institute of Biochemistry, University of Leipzig, Johannisallee 30, 04103, Leipzig, Germany.
| |
Collapse
|
41
|
Haghighatdoost F, Salehi-Abargouei A, Surkan PJ, Azadbakht L. The effects of low carbohydrate diets on liver function tests in nonalcoholic fatty liver disease: A systematic review and meta-analysis of clinical trials. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2016; 21:53. [PMID: 27904598 PMCID: PMC5122212 DOI: 10.4103/1735-1995.187269] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Revised: 03/06/2016] [Accepted: 04/25/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND Although several observational and experimental studies have examined the effects of low carbohydrate diets (LCDs) on nonalcoholic fatty liver disease (NAFLD), there are considerable inconsistencies among studies. We summarized the effect of LCDs on liver function tests, including intrahepatic lipid content (IHLC), alanine transaminase (ALT), aspartate aminotransferases (AST), and gamma-glutamyl transferase (GGT) in patients with NAFLD. MATERIALS AND METHODS PubMed, ISI Web of Science, Scopus, and Google Scholar databases were searched for relevant publications until July 2014, resulting in ten relevant papers that were included in meta-analysis. Related articles were found by searching Medical Subject Heading terms of "NAFLD" in combination with "low carbohydrate". For this meta-analysis, we used mean differences and standard errors of liver function biomarkers. Summary effect and corresponding confidence interval (CI) were estimated using random effect models. Heterogeneity between studies was assessed using Cochran's Q- and I-squared tests. RESULTS Our search led to ten eligible papers that evaluated serum ALT levels (n = 238), nine reported serum AST levels (n = 216), five reported serum GGT concentrations (n = 91), and four assessed IHLC (n = 50). LCD decreased IHLC by -11.53% (95% CI: -18.10, -4.96; I2 = 83.2%). However, the effect of LCD on liver enzymes was not significant. Mean differences for the effects of LCDs on ALT, AST, and GGT were -4.35 IU/L (95% CI: -12.91, 4.20; I2 = 87.9%), -1.44 IU/L (95% CI: -4.98, 2.10; I2 = 61.4%), and -7.85 IU/L (95% CI: -29.65, 13.96; I2 = 99.4%), respectively. CONCLUSION LCD consumption in subjects with NAFLD led to a significant reduction in IHLC, but did not significantly affect the concentration of liver enzymes.
Collapse
Affiliation(s)
- Fahimeh Haghighatdoost
- Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
- Department of Community Nutrition, Students’ Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Amin Salehi-Abargouei
- Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
- Department of Nutrition, Faculty of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Pamela J. Surkan
- Department of International Health, John Hopkins School of Public Health, Baltimore, MD, USA
| | - Leila Azadbakht
- Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
- Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
42
|
Postnatal High-Fat Diet Increases Liver Steatosis and Apoptosis Threatened by Prenatal Dexamethasone through the Oxidative Effect. Int J Mol Sci 2016; 17:369. [PMID: 26978357 PMCID: PMC4813229 DOI: 10.3390/ijms17030369] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Revised: 03/01/2016] [Accepted: 03/08/2016] [Indexed: 12/13/2022] Open
Abstract
The objective of this study was to investigate cellular apoptosis in prenatal glucocorticoid overexposure and a postnatal high fat diet in rats. Pregnant Sprague-Dawley rats at gestational days 14 to 21 were administered saline (vehicle) or dexamethasone and weaned onto either a normal fat diet or a high fat diet for 180 days; in total four experimental groups were designated, i.e., vehicle treated group (VEH), dexamethasone treated group (DEX), vehicle treated plus high-fat diet (VHF), and dexamethasone treated plus high-fat diet (DHF). Chronic effects of prenatal liver programming were assessed at postnatal day 180. The apoptotic pathways involved proteins were analyzed by Western blotting for their expressions. Apoptosis and liver steatosis were also examined by histology. We found that liver steatosis and apoptosis were increased in the DHF, DEX, and VHF treated groups, and that the DHF treated group was increased at higher levels than the DEX and VHF treated groups. The expression of leptin was decreased more in the DHF treated group than in the DEX and VHF treated groups. Decreased peroxisome proliferator-activated receptor-gamma coactivator 1α, phosphoinositide-3-kinase, manganese superoxide dismutase and increased malondialdehyde expression levels were seen in DHF treated group relative to the DEX treated group. The DHF treated group exhibited higher levels of oxidative stress, apoptosis and liver steatosis than the DEX treated group. These results indicate that the environment of high-fat diet plays an important role in the development of liver injury after prenatal stress.
Collapse
|
43
|
Trovato FM, Martines GF, Brischetto D, Catalano D, Musumeci G, Trovato GM. Fatty liver disease and lifestyle in youngsters: diet, food intake frequency, exercise, sleep shortage and fashion. Liver Int 2016; 36:427-33. [PMID: 26346413 DOI: 10.1111/liv.12957] [Citation(s) in RCA: 131] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2015] [Accepted: 08/20/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Fatty liver is associated with alcohol habits and/or overweight/obesity. We challenged several lifestyle features associated with fatty liver and, particularly, with non-alcoholic fatty liver disease (NAFLD). Among them, sleep shortage as a result of nightlife habits and a preference for plus-size fashion were assessed. The latter consists of fashionable plus-sized clothing for actual individuals' size and reflects a frequent attitude of some social or age groups, conceivably indicating more global and widespread trend and behaviour. METHODS We studied a group of 708 non-diabetic youngsters, 458 women and 250 men, 21.72 ± 3.71 years old (range 15-35 years), referred for minor digestive ailments for clinical assessment, ultrasound detection of fatty liver and nutritional counselling. Details of personal history regarding lifestyle, food intake frequency and alcohol intake, dietary and physical exercise profile, sleep duration and clothing preferences were recorded. RESULTS The prevalence of NAFLD in this cohort of youngsters is 67/708 (9.4%). Even if it is quantitatively very low in both groups, the average alcohol intake, always below 20 g/day, is greater in NAFLD subjects (5.83 ± 4.32 g) vs. subjects with normal liver (2.02 ± 3.20 g). The number of meals/day and adherence to a Mediterranean diet profile are smaller in NAFLD subjects. By multiple regression, BMI, sedentary life, plus-sized clothing for their actual size, sleep shortage and lower frequency of daily food intake are associated with the presence of NAFLD. CONCLUSIONS Onset and continuation of fatty liver disease, beyond food and exercise quantity and quality, with their effects on obesity, may also be associated with other aspects of lifestyle.
Collapse
Affiliation(s)
- Francesca M Trovato
- Department of Clinical and Experimental Medicine, The University Hospital of Catania, Catania, Italy
| | - Giuseppe Fabio Martines
- Department of Clinical and Experimental Medicine, The University Hospital of Catania, Catania, Italy
| | - Daniela Brischetto
- Department of Clinical and Experimental Medicine, The University Hospital of Catania, Catania, Italy
| | - Daniela Catalano
- Department of Clinical and Experimental Medicine, The University Hospital of Catania, Catania, Italy
| | - Giuseppe Musumeci
- Department of Bio-Medical Sciences, Human Anatomy and Histology Section, School of Medicine, University of Catania, Catania, Italy
| | - Guglielmo M Trovato
- Department of Clinical and Experimental Medicine, The University Hospital of Catania, Catania, Italy
| |
Collapse
|
44
|
Mirzaii S, Mansourian M, Derakhshandeh-Rishehri SM, Kelishadi R, Heidari-Beni M. Association of conjugated linoleic acid consumption and liver enzymes in human studies: A systematic review and meta-analysis of randomized controlled clinical trials. Nutrition 2016; 32:166-73. [DOI: 10.1016/j.nut.2015.08.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 08/11/2015] [Accepted: 08/14/2015] [Indexed: 12/14/2022]
|
45
|
Ma J, Karlsen MC, Chung M, Jacques PF, Saltzman E, Smith CE, Fox CS, McKeown NM. Potential link between excess added sugar intake and ectopic fat: a systematic review of randomized controlled trials. Nutr Rev 2016; 74:18-32. [PMID: 26518034 PMCID: PMC4859325 DOI: 10.1093/nutrit/nuv047] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2015] [Revised: 03/19/2015] [Accepted: 05/05/2015] [Indexed: 12/14/2022] Open
Abstract
CONTEXT The effect of added sugar intake on ectopic fat accumulation is a subject of debate. OBJECTIVE A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to examine the potential effect of added sugar intake on ectopic fat depots. DATA SOURCES MEDLINE, CAB Abstracts, CAB Global Health, and EBM (Evidence-Based Medicine) Reviews - Cochrane Central Register of Controlled Trials databases were searched for studies published from 1973 to September 2014. DATA EXTRACTION RCTs with a minimum of 6 days' duration of added sugar exposure in the intervention group were selected. The dosage of added sugar intake as a percentage of total energy was extracted or calculated. Means and standard deviations of pre- and post-test measurements or changes in ectopic fat depots were collected. DATA SYNTHESIS Fourteen RCTs were included. Most of the studies had a medium to high risk of bias. Meta-analysis showed that, compared with eucaloric controls, subjects who consumed added sugar under hypercaloric conditions likely increased ectopic fat, particularly in the liver (pooled standardized mean difference = 0.9 [95%CI, 0.6-1.2], n = 6) and muscles (pooled SMD = 0.6 [95%CI, 0.2-1.0], n = 4). No significant difference was observed in liver fat, visceral adipose tissue, or muscle fat when isocaloric intakes of different sources of added sugars were compared. CONCLUSIONS Data from a limited number of RCTs suggest that excess added sugar intake under hypercaloric diet conditions likely increases ectopic fat depots, particularly in the liver and in muscle fat. There are insufficient data to compare the effect of different sources of added sugars on ectopic fat deposition or to compare intake of added sugar with intakes of other macronutrients. Future well-designed RCTs with sufficient power and duration are needed to address the role of sugars on ectopic fat deposition.
Collapse
Affiliation(s)
- Jiantao Ma
- J. Ma, M.C. Karlsen, P.F. Jacques, E. Saltzman, C.E. Smith, and N.M. McKeown are with the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, Massachusetts, USA. M. Chung is with the Nutrition/Infection Unit, Department of Public Health and Community Medicine, School of Medicine, Tufts University, Boston, Massachusetts, USA. C.S. Fox is with the NHLBI's Framingham Heart Study, Framingham, Massachusetts, USA. C.S. Fox is with Harvard Medical School, Boston, Massachusetts, USA
| | - Micaela C Karlsen
- J. Ma, M.C. Karlsen, P.F. Jacques, E. Saltzman, C.E. Smith, and N.M. McKeown are with the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, Massachusetts, USA. M. Chung is with the Nutrition/Infection Unit, Department of Public Health and Community Medicine, School of Medicine, Tufts University, Boston, Massachusetts, USA. C.S. Fox is with the NHLBI's Framingham Heart Study, Framingham, Massachusetts, USA. C.S. Fox is with Harvard Medical School, Boston, Massachusetts, USA
| | - Mei Chung
- J. Ma, M.C. Karlsen, P.F. Jacques, E. Saltzman, C.E. Smith, and N.M. McKeown are with the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, Massachusetts, USA. M. Chung is with the Nutrition/Infection Unit, Department of Public Health and Community Medicine, School of Medicine, Tufts University, Boston, Massachusetts, USA. C.S. Fox is with the NHLBI's Framingham Heart Study, Framingham, Massachusetts, USA. C.S. Fox is with Harvard Medical School, Boston, Massachusetts, USA
| | - Paul F Jacques
- J. Ma, M.C. Karlsen, P.F. Jacques, E. Saltzman, C.E. Smith, and N.M. McKeown are with the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, Massachusetts, USA. M. Chung is with the Nutrition/Infection Unit, Department of Public Health and Community Medicine, School of Medicine, Tufts University, Boston, Massachusetts, USA. C.S. Fox is with the NHLBI's Framingham Heart Study, Framingham, Massachusetts, USA. C.S. Fox is with Harvard Medical School, Boston, Massachusetts, USA
| | - Edward Saltzman
- J. Ma, M.C. Karlsen, P.F. Jacques, E. Saltzman, C.E. Smith, and N.M. McKeown are with the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, Massachusetts, USA. M. Chung is with the Nutrition/Infection Unit, Department of Public Health and Community Medicine, School of Medicine, Tufts University, Boston, Massachusetts, USA. C.S. Fox is with the NHLBI's Framingham Heart Study, Framingham, Massachusetts, USA. C.S. Fox is with Harvard Medical School, Boston, Massachusetts, USA
| | - Caren E Smith
- J. Ma, M.C. Karlsen, P.F. Jacques, E. Saltzman, C.E. Smith, and N.M. McKeown are with the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, Massachusetts, USA. M. Chung is with the Nutrition/Infection Unit, Department of Public Health and Community Medicine, School of Medicine, Tufts University, Boston, Massachusetts, USA. C.S. Fox is with the NHLBI's Framingham Heart Study, Framingham, Massachusetts, USA. C.S. Fox is with Harvard Medical School, Boston, Massachusetts, USA
| | - Caroline S Fox
- J. Ma, M.C. Karlsen, P.F. Jacques, E. Saltzman, C.E. Smith, and N.M. McKeown are with the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, Massachusetts, USA. M. Chung is with the Nutrition/Infection Unit, Department of Public Health and Community Medicine, School of Medicine, Tufts University, Boston, Massachusetts, USA. C.S. Fox is with the NHLBI's Framingham Heart Study, Framingham, Massachusetts, USA. C.S. Fox is with Harvard Medical School, Boston, Massachusetts, USA
| | - Nicola M McKeown
- J. Ma, M.C. Karlsen, P.F. Jacques, E. Saltzman, C.E. Smith, and N.M. McKeown are with the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University, Boston, Massachusetts, USA. M. Chung is with the Nutrition/Infection Unit, Department of Public Health and Community Medicine, School of Medicine, Tufts University, Boston, Massachusetts, USA. C.S. Fox is with the NHLBI's Framingham Heart Study, Framingham, Massachusetts, USA. C.S. Fox is with Harvard Medical School, Boston, Massachusetts, USA.
| |
Collapse
|
46
|
Ferolla SM, Silva LC, Ferrari MDLA, da Cunha AS, Martins FDS, Couto CA, Ferrari TCA. Dietary approach in the treatment of nonalcoholic fatty liver disease. World J Hepatol 2015; 7:2522-2534. [PMID: 26523205 PMCID: PMC4621466 DOI: 10.4254/wjh.v7.i24.2522] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Revised: 08/24/2015] [Accepted: 10/08/2015] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) has been identified as one of the most prevalent chronic liver disease in adults and children populations. NAFLD is usually associated with the metabolic syndrome (MS), which is chiefly related to insulin resistance and its consequences. Insulin resistance has a crucial role in the pathogenesis of hepatic steatosis and potentially nonalcoholic steatohepatitis (NASH). Because of the contemporary epidemics of MS and obesity, the burden of NAFLD is also expected to rise. Unhealthy diets, such as the so-called western diet, are enriched in fructose, trans-fatty acids and saturated fat and seem to be associated with the development of NAFLD. In human studies, certain dietary sugars, particularly fructose, are used as a substrate for lipogenesis leading to hepatic fatty infiltration, inflammation, and possibly fibrosis. Other investigations have shown that fat consumption especially cholesterol and trans/saturated fatty acids are also steatogenic and seem to increase visceral adiposity. The identification of specific dietary components that favor the development of NASH could be important for the management of this disorder. This review focuses on the effects of different dietary approaches to prevent and treat NAFLD emphasizing the macronutrients and energy composition.
Collapse
|
47
|
Abstract
In contrast to the decline in mortality from many non-infectious, chronic diseases in the UK, death from liver disease has increased exponentially in men and women over the past 40 years. This is primarily because of the over consumption of alcohol, but also the increased prevalence of obesity, which is linked to early pathology through the accumulation of liver fat. Supra-physiological intakes of fructose-containing sugar can produce acute, adverse effects on lipid metabolism, and deliver excess energy that increases bodyweight and the deposition of fat in sites other than adipose tissue, including the liver. This review addresses the variable metabolic origins of liver fat, and the key importance of postprandial lipid metabolism in this respect. The effects of supra-physiological intakes of sugar are also considered in context of the real world and established threshold for the adverse effects of sugar on cardio-metabolic risk factors. The review concludes that while the average intake of sugar in the UK falls well below this critical threshold, intakes in subgroups of adults, and especially adolescents, may be cause for concern. There is also evidence to suggest that raised liver fat, acquired, in part, through an impaired removal of postprandial lipaemia, can increase sensitivity to the adverse effects of sugar at all ages.
Collapse
|
48
|
Bongers M, Stefan N, Fritsche A, Häring HU, Nikolaou K, Schick F, Machann J. Lebervolumen, Leberfettanteil und Körpergewicht im Verlauf einer Lebensstilinterventionsstudie. Radiologe 2015; 55:323-8. [DOI: 10.1007/s00117-014-2722-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
|
49
|
Moore JB, Gunn PJ, Fielding BA. The role of dietary sugars and de novo lipogenesis in non-alcoholic fatty liver disease. Nutrients 2014; 6:5679-703. [PMID: 25514388 PMCID: PMC4276992 DOI: 10.3390/nu6125679] [Citation(s) in RCA: 99] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2014] [Revised: 11/28/2014] [Accepted: 12/01/2014] [Indexed: 02/06/2023] Open
Abstract
Dietary sugar consumption, in particular sugar-sweetened beverages and the monosaccharide fructose, has been linked to the incidence and severity of non-alcoholic fatty liver disease (NAFLD). Intervention studies in both animals and humans have shown large doses of fructose to be particularly lipogenic. While fructose does stimulate de novo lipogenesis (DNL), stable isotope tracer studies in humans demonstrate quantitatively that the lipogenic effect of fructose is not mediated exclusively by its provision of excess substrates for DNL. The deleterious metabolic effects of high fructose loads appear to be a consequence of altered transcriptional regulatory networks impacting intracellular macronutrient metabolism and altering signaling and inflammatory processes. Uric acid generated by fructose metabolism may also contribute to or exacerbate these effects. Here we review data from human and animal intervention and stable isotope tracer studies relevant to the role of dietary sugars on NAFLD development and progression, in the context of typical sugar consumption patterns and dietary recommendations worldwide. We conclude that the use of hypercaloric, supra-physiological doses in intervention trials has been a major confounding factor and whether or not dietary sugars, including fructose, at typically consumed population levels, effect hepatic lipogenesis and NAFLD pathogenesis in humans independently of excess energy remains unresolved.
Collapse
Affiliation(s)
- J Bernadette Moore
- Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
| | - Pippa J Gunn
- Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
| | - Barbara A Fielding
- Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
| |
Collapse
|
50
|
The role of intestinal bacteria overgrowth in obesity-related nonalcoholic fatty liver disease. Nutrients 2014; 6:5583-99. [PMID: 25479248 PMCID: PMC4276985 DOI: 10.3390/nu6125583] [Citation(s) in RCA: 76] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2014] [Revised: 11/24/2014] [Accepted: 11/26/2014] [Indexed: 12/12/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. It is a progressive disorder involving a spectrum of conditions that include pure steatosis without inflammation, nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis. The key factor in the pathophysiology of NAFLD is insulin resistance that determines lipid accumulation in the hepatocytes, which may be followed by lipid peroxidation, production of reactive oxygen species and consequent inflammation. Recent studies suggest that the characteristics of the gut microbiota are altered in NAFLD, and also, that small intestinal bacterial overgrowth (SIBO) contributes to the pathogenesis of this condition. This review presents the chief findings from all the controlled studies that evaluated SIBO, gut permeability and endotoxemia in human NAFLD. We also discuss the possible mechanisms involving SIBO, lipid accumulation and development of NASH. The understanding of these mechanisms may allow the development of new targets for NASH treatment in the future.
Collapse
|