|
1
|
Li M, Cheng D, Peng C, Huang Y, Geng J, Huang G, Wang T, Xu A. Therapeutic mechanisms of the medicine and food homology formula Xiao-Ke-Yin on glucolipid metabolic dysfunction revealed by transcriptomics, metabolomics and microbiomics in mice. Chin Med 2023; 18:57. [PMID: 37202792 DOI: 10.1186/s13020-023-00752-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 04/13/2023] [Indexed: 05/20/2023] Open
Abstract
BACKGROUND In recent decades, the prevalence of metabolic diseases, particularly diabetes, hyperlipidemia, obesity, and non-alcoholic fatty liver disease (NAFLD), has increased dramatically, causing great public health and economic burdens worldwide. Traditional Chinese medicine (TCM) serves as an effective therapeutic choice. Xiao-Ke-Yin (XKY) is a medicine and food homology TCM formula consisting of nine "medicine and food homology" herbs and is used to ameliorate metabolic diseases, such as insulin resistance, diabetes, hyperlipidemia and NAFLD. However, despite its therapeutic potential in metabolic disorders, the underlying mechanisms of this TCM remain unclear. This study aimed to evaluate the therapeutic effectiveness of XKY on glucolipid metabolism dysfunction and explore the potential mechanisms in db/db mice. METHODS To verify the effects of XKY, db/db mice were treated with different concentrations of XKY (5.2, 2.6 and 1.3 g/kg/d) and metformin (0.2 g/kg/d, a hypoglycemic positive control) for 6 weeks, respectively. During this study, we detected the body weight (BW) and fasting blood glucose (FBG), oral glucose tolerance test (OGTT), insulin tolerance test (ITT), daily food intake and water intake. At the end of the animal experiment, blood samples, feces, liver and intestinal tissue of mice in all groups were collected. The potential mechanisms were investigated by using hepatic RNA sequencing, 16 S rRNA sequencing of the gut microbiota and metabolomics analysis. RESULTS XKY efficiently mitigated hyperglycemia, IR, hyperlipidemia, inflammation and hepatic pathological injury in a dose dependent manner. Mechanistically, hepatic transcriptomic analysis showed that XKY treatment significantly reversed the upregulated cholesterol biosynthesis which was further confirmed by RT-qPCR. Additionally, XKY administration maintained intestinal epithelial homeostasis, modulated gut microbiota dysbiosis, and regulated its metabolites. In particular, XKY decreased secondary bile acid producing bacteria (Clostridia and Lachnospircaeae) and lowered fecal secondary bile acid (lithocholic acid (LCA) and deoxycholic acid (DCA)) levels to promote hepatic bile acid synthesis by inhibiting the LCA/DCA-FXR-FGF15 signalling pathway. Furthermore, XKY regulated amino acid metabolism including arginine biosynthesis, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and tryptophan metabolism likely by increasing Bacilli, Lactobacillaceae and Lactobacillus, and decreasing Clostridia, Lachnospircaeae, Tannerellaceae and Parabacteroides abundances. CONCLUSION Taken together, our findings demonstrate that XKY is a promising "medicine food homology" formula for ameliorating glucolipid metabolism and reveal that the therapeutic effects of XKY may due to its downregulation of hepatic cholesterol biosynthesis and modulation of the dysbiosis of the gut microbiota and metabolites.
Collapse
Affiliation(s)
- Mei Li
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Ding Cheng
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Chuan Peng
- Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yujiao Huang
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Jie Geng
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Guangrui Huang
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
| | - Ting Wang
- Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
| | - Anlong Xu
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China.
| |
Collapse
|
|
2
|
Gao R, Meng X, Xue Y, Mao M, Liu Y, Tian X, Sui B, Li X, Zhang P. Bile acids-gut microbiota crosstalk contributes to the improvement of type 2 diabetes mellitus. Front Pharmacol 2022; 13:1027212. [PMID: 36386219 PMCID: PMC9640995 DOI: 10.3389/fphar.2022.1027212] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Accepted: 10/13/2022] [Indexed: 10/07/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) occurs that cannot effectively use the insulin. Insulin Resistance (IR) is a significant characteristic of T2DM which is also an essential treatment target in blood glucose regulation to prevent T2DM and its complications. Bile acids (BAs) are one group of bioactive metabolites synthesized from cholesterol in liver. BAs play an important role in mutualistic symbiosis between host and gut microbiota. It is shown that T2DM is associated with altered bile acid metabolism which can be regulated by gut microbiota. Simultaneously, BAs also reshape gut microbiota and improve IR and T2DM in the bidirectional communications of the gut-liver axis. This article reviewed the findings on the interaction between BAs and gut microbiota in improving T2DM, which focused on gut microbiota and its debinding function and BAs regulated gut microbiota through FXR/TGR5. Meanwhile, BAs and their derivatives that are effective for improving T2DM and other treatments based on bile acid metabolism were also summarized. This review highlighted that BAs play a critical role in the glucose metabolism and may serve as therapeutic targets in T2DM, providing a reference for discovering and screening novel therapeutic drugs.
Collapse
Affiliation(s)
- Ruolin Gao
- School of Sports and Health, Shandong Sport University, Jinan, China
| | - Xiangjing Meng
- Shandong Academy of Pharmaceutical Science, Jinan, China
| | - Yili Xue
- School of Sports and Health, Shandong Sport University, Jinan, China
| | - Min Mao
- School of Nursing and Rehabilitation, Shandong University, Jinan, China
| | - Yaru Liu
- School of Sports and Health, Shandong Sport University, Jinan, China
| | - Xuewen Tian
- School of Sports and Health, Shandong Sport University, Jinan, China
| | - Bo Sui
- School of Sports and Health, Shandong Sport University, Jinan, China
| | - Xun Li
- School of Sports and Health, Shandong Sport University, Jinan, China
| | - Pengyi Zhang
- School of Sports and Health, Shandong Sport University, Jinan, China
| |
Collapse
|
|
3
|
Association of Human Intestinal Microbiota with Lifestyle Activity, Adiposity, and Metabolic Profiles in Thai Children with Obesity. J Nutr Metab 2022; 2022:3029582. [PMID: 35637874 PMCID: PMC9146442 DOI: 10.1155/2022/3029582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 03/23/2022] [Accepted: 04/19/2022] [Indexed: 11/18/2022] Open
Abstract
Background Dysbiosis of intestinal microbiota may be linked to pathogenesis of obesity and metabolic disorders. Objective This study compared the gut microbiome of obese Thai children with that of healthy controls and examined their relationships with host lifestyle, adiposity, and metabolic profiles. Methods This cross-sectional study enrolled obese children aged 7–15. Body composition was evaluated using bioelectrical impedance analysis. Stool samples were analyzed by 16S rRNA sequencing using the Illumina MiSeq platform. Relative abundance and alpha- and beta-diversity were compared with normal-weight Thai children from a previous publication using Wilcoxon rank-sum test and ANOSIM. Relationships of gut microbiota with lifestyle activity, body composition, and metabolic profiles were assessed by canonical correlation analysis (CCA) and Spearman correlation. Results The study enrolled 164 obese children with a male percentage of 59%. Mean age was 10.4 ± 2.2 years with a BMI z-score of 3.2 ± 1. The abundance of Bacteroidetes and Actinobacteria were found to be lower in obese children compared to nonobese children. Alpha-diversity indices showed no differences between groups, while beta-diversity revealed significant differences in the family and genus levels. CCA revealed significant correlations of the relative abundance of gut microbial phyla with sedentary lifestyle and certain metabolic markers. Univariate analysis revealed that Actinobacteria and Bifidobacterium were positively correlated with HDL-C and negatively correlated with body weight and screen time. Additionally, Actinobacteria was also negatively associated with fasting insulin and HOMA-IR. Lactobacillus showed positive correlation with acanthosis nigricans and adiposity. Cooccurrence analysis revealed 90 significant bacterial copresence and mutual exclusion interactions among 43 genera in obese children, whereas only 2 significant cooccurrences were found in nonobese children. Conclusions The composition and diversity of gut microbiota in obese Thai children were different from those of their normal-weight peers. Specific gut microbiota were associated with lifestyle, adiposity, and metabolic features in obese children. An interventional study is needed to support causality between specific gut microbiota and obesity.
Collapse
|
|
4
|
Association between Non-Alcoholic Fatty Liver Disease and Mediterranean Lifestyle: A Systematic Review. Nutrients 2021; 14:nu14010049. [PMID: 35010923 PMCID: PMC8746321 DOI: 10.3390/nu14010049] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Revised: 12/16/2021] [Accepted: 12/21/2021] [Indexed: 02/07/2023] Open
Abstract
Background and Aims: Non-alcoholic fatty liver disease (NAFLD) is an excessive accumulation of fat in the liver without alcohol abuse. It is linked to metabolic syndrome (MetS) and no pharmacological treatment exists. This systematic review aims to assess evidence about the effect of Mediterranean lifestyle on the prevention and reversion of NAFLD. Methods: A systematic literature search was performed in MEDLINE via Pubmed. MeSH terms used were: non-alcoholic fatty liver disease [MeSH Major Topic] AND metabolic syndrome [MeSH Term] AND (Diet, Mediterranean [MeSH Term]) OR (Exercise [MeSH Term]). (PROSPERO ID: 2021 CRD42021289495). Results: Thirteen articles were selected and divided into two categories (four focused on Mediterranean diet and NAFLD and nine focused on Mediterranean diet, physical activity, and NAFLD). Information of clinical endpoints was based on NAFLD, as well as MetS, body mass index, fasting glycemia, obesity, cholesterol, triglycerides, transaminases, albuminuria, and hepatic steatosis, among others. All studies found beneficial associations between the clinical parameters of NAFLD/MetS and following a Mediterranean diet and regular physical activity. Conclusions: An effective treatment that prevents, and even reverses, NAFLD is to adapt lifestyle to the Mediterranean one, based on a Mediterranean diet and regular physical activity.
Collapse
|
|
5
|
The Effects of Two Different Intensities of Combined Training on C1q/TNF-Related Protein 3 (CTRP3) and Insulin Resistance in Women with Non-alcoholic Fatty Liver Disease. HEPATITIS MONTHLY 2021. [DOI: 10.5812/hepatmon.108106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Background: C1q/TNF-related protein (CTRP3) is a potent anti-inflammatory adipokine with activities, such as reduction of glucose level and inhibition of gluconeogenesis in the liver. However, the effect of exercise training on CTRP3 in patients with non-alcoholic fatty liver disease (NAFLD) remains unknown. Objectives: This study was done to investigate the effects of two different intensities of combined training on CTRP3 and insulin resistance in women with NAFLD and compare these two training patterns. Methods: Thirty-three women with NAFLD were randomly divided into three equal groups. Group 1 performed resistance training (RT), along with aerobic interval training (AIT) (2 - 5 intervals of four minutes, 70 - 75% HRmax), group 2 performed RT along with high-intensity interval training (HIIT) (8 - 13 intervals of one minute, 85 - 95% HRmax), and the control group did not participate in any training. The body composition measurements and blood sampling were carried out before and after 12 weeks of training. Data analysis was performed using repeated-measures ANOVA (α ≤ 0.05). Results: After 12 weeks, the CTRP3 level significantly increased in group 1 compared with the control group (P = 0.01) and group 2 (P < 0.001). The fasting glucose and fasting insulin levels significantly decreased in group 1 compared with the control group (P < 0.001 and P = 0.01, respectively). The insulin resistance index decreased in both group 1 and group 2; however, the difference was not significant compared with the control group (P > 0.05). Conclusions: Combined training (RT + AIT) in the present study increased the level of CTRP3; thus, it is likely that women with NAFLD can benefit from this program as a non-pharmacological adjunct treatment to prevent inflammation and progression of the disease.
Collapse
|
|
6
|
Moore MP, Cunningham RP, Dashek RJ, Mucinski JM, Rector RS. A Fad too Far? Dietary Strategies for the Prevention and Treatment of NAFLD. Obesity (Silver Spring) 2020; 28:1843-1852. [PMID: 32893456 PMCID: PMC7511422 DOI: 10.1002/oby.22964] [Citation(s) in RCA: 61] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Revised: 06/04/2020] [Accepted: 06/06/2020] [Indexed: 12/13/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a major health problem, and its prevalence has increased in recent years, concurrent with rising rates of obesity and other metabolic diseases. Currently, there are no FDA-approved pharmacological therapies for NAFLD, and lifestyle interventions, including weight loss and exercise, remain the cornerstones for treatment. Manipulating diet composition and eating patterns may be a sustainable approach to NAFLD treatment. Dietary strategies including Paleolithic, ketogenic, Mediterranean, high-protein, plant-based, low-carbohydrate, and intermittent fasting diets have become increasingly popular because of their purported benefits on metabolic disease. This review highlights what is currently known about these popular dietary approaches in the management of NAFLD in clinical populations with mechanistic insight from animal studies. It also identifies key knowledge gaps to better inform future preclinical and clinical studies aimed at the treatment of NAFLD.
Collapse
Affiliation(s)
- Mary P. Moore
- Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, MO, 65211
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211
| | - Rory P. Cunningham
- Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, MO, 65211
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211
| | - Ryan J. Dashek
- Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, MO, 65211
- Comparative Medicine Program, University of Missouri, Columbia, MO 65211
| | - Justine M. Mucinski
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211
| | - R. Scott Rector
- Research Service, Harry S Truman Memorial Veterans Medical Center, Columbia, MO, 65211
- Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, MO 65211
- Medicine-Division of Gastroenterology and Hepatology, University of Missouri, Columbia, MO 65211
| |
Collapse
|
|
7
|
Zhao R, Zhang Y, Wang X, Colgan TJ, Rehm JL, Reeder SB, Johnson KM, Hernando D. Motion-robust, high-SNR liver fat quantification using a 2D sequential acquisition with a variable flip angle approach. Magn Reson Med 2020; 84:2004-2017. [PMID: 32243665 DOI: 10.1002/mrm.28263] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2019] [Revised: 02/24/2020] [Accepted: 03/02/2020] [Indexed: 01/18/2023]
Abstract
PURPOSE Chemical shift encoded (CSE)-MRI enables quantification of proton-density fat fraction (PDFF) as a biomarker of liver fat content. However, conventional 3D Cartesian CSE-MRI methods require breath-holding. A motion-robust 2D Cartesian sequential method addresses this limitation but suffers from low SNR. In this work, a novel free breathing 2D Cartesian sequential CSE-MRI method using a variable flip angle approach with centric phase encoding (VFA-centric) is developed to achieve fat quantification with low T 1 bias, high SNR, and minimal blurring. METHODS Numerical simulation was performed for variable flip angle schedule design and preliminary evaluation of VFA-centric method, along with several alternative flip angle designs. Phantom, adults (n = 8), and children (n = 27) were imaged at 3T. Multi-echo images were acquired and PDFF maps were estimated. PDFF standard deviation was used as a surrogate for SNR. RESULTS In both simulation and phantom experiments, the VFA-centric method enabled higher SNR imaging with minimal T 1 bias and blurring artifacts. High correlation (slope = 1.00, intercept = 0.04, R 2 = 0.998) was observed in vivo between the proposed VFA-centric method obtained PDFF and reference PDFF (free breathing low-flip angle 2D sequential acquisition). Further, the proposed VFA-centric method (PDFF standard deviation = 1.5%) had a better SNR performance than the reference acquisition (PDFF standard deviation = 3.3%) with P < .001. CONCLUSIONS The proposed free breathing 2D Cartesian sequential CSE-MRI method with variable flip angle approach and centric-ordered phase encoding achieved motion robustness, low T 1 bias, high SNR compared to previous 2D sequential methods, and low blurring in liver fat quantification.
Collapse
Affiliation(s)
- Ruiyang Zhao
- Department of Radiology, University of Wisconsin-Madison, Madison, WI, USA.,Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA
| | - Yuxin Zhang
- Department of Radiology, University of Wisconsin-Madison, Madison, WI, USA.,Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA
| | - Xiaoke Wang
- Department of Radiology, University of Wisconsin-Madison, Madison, WI, USA.,Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA
| | - Timothy J Colgan
- Department of Radiology, University of Wisconsin-Madison, Madison, WI, USA.,Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA
| | - Jennifer L Rehm
- Department of Pediatrics, University of Wisconsin-Madison, Madison, WI, USA
| | - Scott B Reeder
- Department of Radiology, University of Wisconsin-Madison, Madison, WI, USA.,Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA.,Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA.,Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA.,Department of Emergency Medicine, University of Wisconsin-Madison, Madison, WI, USA
| | - Kevin M Johnson
- Department of Radiology, University of Wisconsin-Madison, Madison, WI, USA.,Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA
| | - Diego Hernando
- Department of Radiology, University of Wisconsin-Madison, Madison, WI, USA.,Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA
| |
Collapse
|
|
8
|
Medrano M, Arenaza L, Ramírez-Vélez R, Ortega FB, Ruiz JR, Labayen I. Prevalence of responders for hepatic fat, adiposity and liver enzyme levels in response to a lifestyle intervention in children with overweight/obesity: EFIGRO randomized controlled trial. Pediatr Diabetes 2020; 21:215-223. [PMID: 31778277 DOI: 10.1111/pedi.12949] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 10/26/2019] [Accepted: 11/14/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND/OBJECTIVE Exercise and lifestyle interventions have been shown to reduce hepatic fat (HF) and adiposity in youth. However, the interindividual response in HF after a lifestyle intervention with or without exercise in children is unknown. The aim of the present study was to compare interindividual variability for HF, adiposity, gamma-glutamyl transferase (GGT), and the aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT) in children with overweight/obesity participating in a 22-week lifestyle intervention with (intensive intervention) or without exercise (control intervention). METHODS Data from 102 children (9-12 years, 55% girls) with overweight/obesity participating in the EFIGRO randomized controlled trial were analyzed. Percentage HF (magnetic resonance imaging), weight, body and fat mass index (BMI and FMI), GGT, AST/ALT, cardiorespiratory fitness (CRF, 20 meters shuttle run test) were assessed before and after the intervention by the same trained researchers. The control intervention consisted in 11 sessions of a family-based lifestyle and psycho-educational program. The intensive intervention included the control intervention plus supervised exercise (3 sessions/week). RESULTS The prevalence of responders for HF (54% vs. 34%), weight (27% vs. 11%), BMI (71% vs. 47%), FMI (90% vs. 60%), and GGT (69% vs. 39%) was higher in the intensive than in the control group (Ps < 0.05). Responders for weight (16 ± 3 vs. 6 ± 2 laps) and BMI (11 ± 2 vs. 3 ± 4 laps) improved more CRF levels than non-responders (Ps < 0.05). CONCLUSIONS The addition of exercise to a lifestyle intervention may increase the responder rates for HF, adiposity, and GGT in children with overweight/obesity. Improvements in CRF may explain differences between weight and BMI responders and non-responders. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02258126.
Collapse
Affiliation(s)
- María Medrano
- ELIKOS group, Institute for Innovation & Sustainable Development in Food Chain (IS-FOOD), Department of Health Sciences, Public University of Navarra, Pamplona, Spain
| | - Lide Arenaza
- ELIKOS group, Institute for Innovation & Sustainable Development in Food Chain (IS-FOOD), Department of Health Sciences, Public University of Navarra, Pamplona, Spain
| | - Robinson Ramírez-Vélez
- Navarrabiomed-Universidad Pública de Navarra (UPNA)-Complejo Hospitalario de Navarra (CHN), Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Navarra, Spain
| | - Francisco B Ortega
- PROFITH "PROmoting FITness and Health through physical activity" Research Group, Sport and Health University Research Institute (iMUDS), Department of Physical Education and Sport, Faculty of Sport Sciences, University of Granada, Granada, Spain.,Department of Biosciences and Nutrition at NOVUM, Karolinska Institutet, Huddinge, Sweden
| | - Jonatan R Ruiz
- PROFITH "PROmoting FITness and Health through physical activity" Research Group, Sport and Health University Research Institute (iMUDS), Department of Physical Education and Sport, Faculty of Sport Sciences, University of Granada, Granada, Spain.,Department of Biosciences and Nutrition at NOVUM, Karolinska Institutet, Huddinge, Sweden
| | - Idoia Labayen
- ELIKOS group, Institute for Innovation & Sustainable Development in Food Chain (IS-FOOD), Department of Health Sciences, Public University of Navarra, Pamplona, Spain
| |
Collapse
|
|
9
|
Carbajo-Pescador S, Porras D, García-Mediavilla MV, Martínez-Flórez S, Juarez-Fernández M, Cuevas MJ, Mauriz JL, González-Gallego J, Nistal E, Sánchez-Campos S. Beneficial effects of exercise on gut microbiota functionality and barrier integrity, and gut-liver crosstalk in an in vivo model of early obesity and non-alcoholic fatty liver disease. Dis Model Mech 2019; 12:dmm.039206. [PMID: 30971408 PMCID: PMC6550047 DOI: 10.1242/dmm.039206] [Citation(s) in RCA: 95] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Accepted: 04/03/2019] [Indexed: 12/15/2022] Open
Abstract
Childhood obesity has reached epidemic levels, representing one of the most serious public health concerns associated with metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). There is limited clinical experience concerning pediatric NAFLD patients, and thus the therapeutic options are scarce. The aim of this study was to evaluate the benefits of exercise on gut microbiota composition and functionality balance, and consequent effects on early obesity and NAFLD onset in an in vivo model. Juvenile (21-day-old) male Wistar rats fed a control diet or a high-fat diet (HFD) were subjected to a combined aerobic and resistance training protocol. Fecal microbiota was sequenced by an Illumina MiSeq system, and parameters related to metabolic syndrome, fecal metabolome, intestinal barrier integrity, bile acid metabolism and transport, and alteration of the gut-liver axis were measured. Exercise decreased HFD-induced body weight gain, metabolic syndrome and hepatic steatosis, as a result of its lipid metabolism modulatory capacity. Gut microbiota composition and functionality were substantially modified as a consequence of diet, age and exercise intervention. In addition, the training protocol increased Parabacteroides, Bacteroides and Flavobacterium genera, correlating with a beneficial metabolomic profile, whereas Blautia, Dysgonomonas and Porphyromonas showed an opposite pattern. Exercise effectively counteracted HFD-induced microbial imbalance, leading to intestinal barrier preservation, which, in turn, prevented deregulation of the gut-liver axis and improved bile acid homeostasis, determining the clinical outcomes of NAFLD. In conclusion, we provide scientific evidence highlighting the benefits of gut microbiota composition and functionality modulation by physical exercise protocols in the management of early obesity and NAFLD development. Summary: The beneficial effects of exercise against diet-induced early obesity and NAFLD are mediated by its capacity to modulate intestinal microbiota composition and functionality, restore lipid metabolism and prevent disruption of the gut-liver axis.
Collapse
Affiliation(s)
| | - David Porras
- Instituto de Biomedicina (IBIOMED), Universidad de León, 24071, León, Spain
| | - María Victoria García-Mediavilla
- Instituto de Biomedicina (IBIOMED), Universidad de León, 24071, León, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain
| | | | | | - María José Cuevas
- Instituto de Biomedicina (IBIOMED), Universidad de León, 24071, León, Spain
| | - José Luis Mauriz
- Instituto de Biomedicina (IBIOMED), Universidad de León, 24071, León, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain
| | - Javier González-Gallego
- Instituto de Biomedicina (IBIOMED), Universidad de León, 24071, León, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain
| | - Esther Nistal
- Instituto de Biomedicina (IBIOMED), Universidad de León, 24071, León, Spain.,Servicio de Aparato Digestivo del Complejo Asistencial Universitario de León, 24071, León, Spain
| | - Sonia Sánchez-Campos
- Instituto de Biomedicina (IBIOMED), Universidad de León, 24071, León, Spain .,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Spain
| |
Collapse
|
|
10
|
Porras D, Nistal E, Martínez-Flórez S, González-Gallego J, García-Mediavilla MV, Sánchez-Campos S. Intestinal Microbiota Modulation in Obesity-Related Non-alcoholic Fatty Liver Disease. Front Physiol 2018; 9:1813. [PMID: 30618824 PMCID: PMC6305464 DOI: 10.3389/fphys.2018.01813] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Accepted: 12/05/2018] [Indexed: 12/12/2022] Open
Abstract
Obesity and associated comorbidities, including non-alcoholic fatty liver disease (NAFLD), are a major concern to public well-being worldwide due to their high prevalence among the population, and its tendency on the rise point to as important threats in the future. Therapeutic approaches for obesity-associated disorders have been circumscribed to lifestyle modifications and pharmacological therapies have demonstrated limited efficacy. Over the last few years, different studies have shown a significant role of intestinal microbiota (IM) on obesity establishment and NAFLD development. Therefore, modulation of IM emerges as a promising therapeutic strategy for obesity-associated diseases. Administration of prebiotic and probiotic compounds, fecal microbiota transplantation (FMT) and exercise protocols have shown a modulatory action over the IM. In this review we provide an overview of current approaches targeting IM which have shown their capacity to counteract NAFLD and metabolic syndrome features in human patients and animal models.
Collapse
Affiliation(s)
- David Porras
- Institute of Biomedicine, University of León, León, Spain
| | - Esther Nistal
- Institute of Biomedicine, University of León, León, Spain.,Department of Gastroenterology, Complejo Asistencial Universitario de León, León, Spain
| | | | - Javier González-Gallego
- Institute of Biomedicine, University of León, León, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
| | - María Victoria García-Mediavilla
- Institute of Biomedicine, University of León, León, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
| | - Sonia Sánchez-Campos
- Institute of Biomedicine, University of León, León, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain
| |
Collapse
|
|
11
|
Hamed AE, Elsahar M, Elwan NM, El-Nakeep S, Naguib M, Soliman HH, Ahmed Aboubakr A, AbdelMaqsod A, Sedrak H, Assaad SN, Elwakil R, Esmat G, Salh S, Mostafa T, Mogawer S, Sadek SE, Saber MM, Ezelarab H, Mahmoud AA, Sultan S, El Kassas M, Kamal E, ElSayed NM, Moussa S. Managing diabetes and liver disease association. Arab J Gastroenterol 2018; 19:166-179. [PMID: 30420265 DOI: 10.1016/j.ajg.2018.08.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 08/26/2018] [Indexed: 02/05/2023]
Abstract
There is strong association between liver diseases and diabetes (DM) which is higher than expected by a chance association of two very common disorders. It can be classified into three categories: Liver disease related to diabetes, hepatogenous diabetes (HD), and liver disease occurring coincidentally with DM. The criteria for the diagnosis of diabetes associating liver disease are the same for primary diabetes. Two hours post glucose load is a better screening test for HD. HbA1c may not be suitable for diagnosis or monitoring of diabetes associating advanced liver disease. Apart from the increased cardiovascular risk in patients with type 2 DM (T2 DM) and NAFLD, the cardiovascular and retinopathy risk is low in HD. Patients with metabolic derangement should be screened for NAFLD which in turn may predict T2 DM development. Similarly, patients with established T2 DM should also be screened for NAFLD which further contributes to diabetes worsening. Diabetes is a significant risk factor for progression of the chronic liver disease. It is associated with poor patient survival. Treatment of diabetes associating liver disease appears beneficial. Metformin, if tolerated and not contraindicated, is recommended as a first-line therapy for patients with diabetes and chronic liver disease (CLD). If the hepatic disease is severe, insulin secretagogues should be avoided because of the increased risk of hypoglycaemia. Pioglitazone may be useful in patients with fatty liver disease. DPP-4 inhibitors showed effectiveness and safety for the treatment of T2 DM in CLD patients up to those with child B stage. GLP-1 receptor agonists and SGLT-2 inhibitors exhibit positive effects on weight and are associated with minimal risk of hypoglycaemia. Insulin must be used with caution, as hypoglycaemia may be a problem. Insulin analogues are preferred in the context of hypoglycaemia Statins can be used to treat dyslipidaemia in NAFLD, also the use of angiotensin II receptor antagonist for hypertension is safe and beneficial Given the clear association between diabetes mellitus and hepatocellular carcinoma, the strict control of glycaemia with insulin sensitizers can be essential in its prevention. The addition of DM to the currently used scores (Child-Pugh and MELD scores) may enhance the sensitivity and the specificity for prediction of morbidity and mortality rates in cirrhotic patients. In the new era of directly acting antiviral agents (DAAs) for HCV treatment, it is recommended to follow up lipid profile and blood sugar levels following SVR in order to adjust doses of medications used in diabetic (SVR is associated with reduction in insulin requirements) and dyslipidaemic patients (rebound increase in the lipid profile after clearing the virus may increase risk of cardiovascular disease (CVD)). The issues of post liver transplant diabetes and relation between DM and chronic HBV are highlighted. This narrative review and Consensus-based practice guidance (under revision and criticism) are based on a formal review and analysis of the recently published world literature on the topic (Medline search up to September 2017); and the experience of the authors and independent reviewers.
Collapse
Affiliation(s)
- Abd Elkhalek Hamed
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt.
| | - Medhat Elsahar
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Police Medical Academy, Egypt
| | | | | | | | | | - Ashraf Ahmed Aboubakr
- Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt
| | | | | | | | - Reda Elwakil
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Ain Shams University, Egypt
| | - Gamal Esmat
- The Egyptian Association for the Study of Liver and Gastrointestinal Disease (EASLGD), Egypt; Kasr Al Aini, Egypt
| | - Samira Salh
- Department of Pharmacy, Cairo University, Egypt
| | | | | | - Sameh Emil Sadek
- Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt
| | - Maha M Saber
- Department of Clinical Nutrition National Research Centre, Egypt
| | - Hanan Ezelarab
- Department of Clinical Nutrition National Research Centre, Egypt
| | - Asem Ashraf Mahmoud
- Department of Internal Medicine, Hepatology, and Diabetes, Egyptian Military Medical Academy, Egypt
| | | | | | - Ehab Kamal
- Medical Department, National Research Centre, Egypt
| | | | | |
Collapse
|
|
12
|
Sakr HF, Abbas AM, Haidara MA. Swimming, but not vitamin E, ameliorates prothrombotic state and hypofibrinolysis in a rat model of nonalcoholic fatty liver disease. J Basic Clin Physiol Pharmacol 2018; 29:61-71. [PMID: 29161233 DOI: 10.1515/jbcpp-2017-0069] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2017] [Accepted: 09/25/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is associated with a systemic procoagulant hypofibrinolysis state that is considered as a risk factor for microangiopathy and peripheral vascular diseases. Swimming exercise ameliorates the metabolic dysfunction in type 2 diabetes. Vitamin E is a natural antioxidant that reduces the risk of endothelial dysfunction in metabolic syndrome. The aim of the present study is to investigate the effect of combined swimming exercise with vitamin E on coagulation as well as blood fibrinolysis markers in rats with NAFLD. METHODS Eighty male rats were divided into control, control+vitamin E, control+exercise, high-fat diet (HFD), HFD+vitamin E, HFD+exercise, and HFD+vitamin E+exercise groups. Glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides, cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL), alanine transaminase (ALT) and aspartate transaminase (AST), intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), endothelin-1, von Willebrand factor (vWF), fibrinogen, plasminogen activator inhibitor (PAI-1), fibrin degradation products (FDP), platelet count and aggregation, bleeding and clotting times, activated partial thromboplastin time (aPTT), and prothrombin time (PT) were determined. RESULTS HFD increased lipid profile, insulin, glucose, HOMA-IR, liver enzymes, adhesion molecules, endothelin-1, vWF, platelet aggregation, fibrinogen, FDP, and PAI-1, and decreased clotting and bleeding times and HDL. Although exercise reduced lipid profile, glucose, insulin, HOMA-IR, vWF, platelet aggregation, fibrinogen, FDP, and PAI-1 and increased PT, aPTT, bleeding and clotting times, and HDL, vitamin E had no effect. CONCLUSIONS Exercise, but not vitamin E, ameliorated the HFD-induced prothrombotic state and enhanced fibrinolytic activity.
Collapse
Affiliation(s)
- Hussein F Sakr
- Faculty of Medicine, Medical Physiology Department, Mansoura University, P.O. Box 35516, Mansoura, Egypt
| | - Amr M Abbas
- Faculty of Medicine, Medical Physiology Department, Mansoura University, Mansoura, Egypt
| | - Mohamed A Haidara
- Kasr Al-Aini Faculty of Medicine, Medical Physiology Department, Cairo University, Cairo, Egypt
| |
Collapse
|
|
13
|
Suárez M, Boqué N, Del Bas JM, Mayneris-Perxachs J, Arola L, Caimari A. Mediterranean Diet and Multi-Ingredient-Based Interventions for the Management of Non-Alcoholic Fatty Liver Disease. Nutrients 2017; 9:E1052. [PMID: 28937599 PMCID: PMC5691669 DOI: 10.3390/nu9101052] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Revised: 09/01/2017] [Accepted: 09/11/2017] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) comprises a wide spectrum of hepatic disorders, from simple steatosis to hepatic necro-inflammation leading to non-alcoholic steatohepatitis (NASH). Although the prevalence of these multifactorial pathologies is continuously increasing in the population, there is still not an established methodology for their treatment other than weight loss and a change in lifestyle habits, such as a hypocaloric diet and physical exercise. In this framework, there is increasing evidence that several food bioactives and dietary patterns are effective for reversing and preventing the onset of these pathologies. Some studies have claimed that better responses are obtained when treatments are performed under a multifaceted approach, using different bioactive compounds that act against complementary targets. Thus, in this work, current strategies for treating NAFLD and NASH based on multi-ingredient-based supplements or the Mediterranean diet, a dietary pattern rich in bioactive compounds, are reviewed. Furthermore, the usefulness of omics techniques to design effective multi-ingredient nutritional interventions and to predict and monitor their response against these disorders is also discussed.
Collapse
Affiliation(s)
- Manuel Suárez
- Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili (URV), Campus Sescelades, Tarragona 43007, Spain.
| | - Noemí Boqué
- Technological Unit of Nutrition and Health, EURECAT-Technology Centre of Catalonia, Avinguda Universitat 1, Reus 43204, Spain.
| | - Josep M Del Bas
- Technological Unit of Nutrition and Health, EURECAT-Technology Centre of Catalonia, Avinguda Universitat 1, Reus 43204, Spain.
| | - Jordi Mayneris-Perxachs
- Technological Unit of Nutrition and Health, EURECAT-Technology Centre of Catalonia, Avinguda Universitat 1, Reus 43204, Spain.
| | - Lluís Arola
- Nutrigenomics Research Group, Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili (URV), Campus Sescelades, Tarragona 43007, Spain.
- Technological Unit of Nutrition and Health, EURECAT-Technology Centre of Catalonia, Avinguda Universitat 1, Reus 43204, Spain.
| | - Antoni Caimari
- Technological Unit of Nutrition and Health, EURECAT-Technology Centre of Catalonia, Avinguda Universitat 1, Reus 43204, Spain.
| |
Collapse
|
|
14
|
Petiz LL, Kunzler A, Bortolin RC, Gasparotto J, Matté C, Moreira JCF, Gelain DP. Role of vitamin A oral supplementation on oxidative stress and inflammatory response in the liver of trained rats. Appl Physiol Nutr Metab 2017; 42:1192-1200. [PMID: 28742973 DOI: 10.1139/apnm-2017-0193] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
The use of dietary supplements to enhance the benefit of exercise training is a common practice. The liver is the organ where all substances are metabolized, and certain supplements have been associated with liver injury. Vitamin A (VA), a liposoluble vitamin stored in the liver, is commonly used as an antioxidant supplement. Here, we evaluated the effect of chronic VA supplementation on oxidative damage and stress parameters in trained rats. Animals were divided into the following groups: sedentary (SE), sedentary/VA (SE+VA), exercise training (ET), and exercise training/VA (ET+VA). During 8 weeks, animals were subjected to swimming (0%, 2%, 4%, 6% body weight) for 5 days/week and a VA daily intake of 450 retinol equivalents/day. Parameters were evaluated by enzymatic activity analysis, ELISA, and Western blotting. VA caused liver lipid peroxidation and protein damage in exercised rats and inhibited the increase in HSP70 expression acquired with exercise alone. The ET group showed higher levels of antioxidant enzyme activity, and VA inhibited this adaptation. Expression of the pro-inflammatory cytokines, interleukin (IL)-1β, and tumor necrosis factor-α was reduced in the ET+VA group, while the anti-inflammatory cytokine, IL-10, was increased. Western blotting showed that both exercised groups had lower levels of the receptor for advanced glycation end products, suggesting that VA did not affect this receptor. Our study demonstrated that, although VA caused oxidative damage, a controlled administration might exert anti-inflammatory effects. Further studies with higher VA doses and longer ET interventions would elucidate more the effects of the supplementation and exercise on liver parameters.
Collapse
Affiliation(s)
- Lyvia Lintzmaier Petiz
- Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - prédio anexo - CEP 90035-003 - Porto Alegre, RS, Brazil.,Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - prédio anexo - CEP 90035-003 - Porto Alegre, RS, Brazil
| | - Alice Kunzler
- Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - prédio anexo - CEP 90035-003 - Porto Alegre, RS, Brazil.,Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - prédio anexo - CEP 90035-003 - Porto Alegre, RS, Brazil
| | - Rafael Calixto Bortolin
- Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - prédio anexo - CEP 90035-003 - Porto Alegre, RS, Brazil.,Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - prédio anexo - CEP 90035-003 - Porto Alegre, RS, Brazil
| | - Juciano Gasparotto
- Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - prédio anexo - CEP 90035-003 - Porto Alegre, RS, Brazil.,Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - prédio anexo - CEP 90035-003 - Porto Alegre, RS, Brazil
| | - Cristiane Matté
- Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - prédio anexo - CEP 90035-003 - Porto Alegre, RS, Brazil.,Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - prédio anexo - CEP 90035-003 - Porto Alegre, RS, Brazil
| | - José Claudio Fonseca Moreira
- Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - prédio anexo - CEP 90035-003 - Porto Alegre, RS, Brazil.,Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - prédio anexo - CEP 90035-003 - Porto Alegre, RS, Brazil
| | - Daniel Pens Gelain
- Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - prédio anexo - CEP 90035-003 - Porto Alegre, RS, Brazil.,Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 - prédio anexo - CEP 90035-003 - Porto Alegre, RS, Brazil
| |
Collapse
|
|
15
|
Pillon Barcelos R, Freire Royes LF, Gonzalez-Gallego J, Bresciani G. Oxidative stress and inflammation: liver responses and adaptations to acute and regular exercise. Free Radic Res 2017; 51:222-236. [PMID: 28166653 DOI: 10.1080/10715762.2017.1291942] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The liver is remarkably important during exercise outcomes due to its contribution to detoxification, synthesis, and release of biomolecules, and energy supply to the exercising muscles. Recently, liver has been also shown to play an important role in redox status and inflammatory modulation during exercise. However, while several studies have described the adaptations of skeletal muscles to acute and chronic exercise, hepatic changes are still scarcely investigated. Indeed, acute intense exercise challenges the liver with increased reactive oxygen species (ROS) and inflammation onset, whereas regular training induces hepatic antioxidant and anti-inflammatory improvements. Acute and regular exercise protocols in combination with antioxidant and anti-inflammatory supplementation have been also tested to verify hepatic adaptations to exercise. Although positive results have been reported in some acute models, several studies have shown an increased exercise-related stress upon liver. A similar trend has been observed during training: while synergistic effects of training and antioxidant/anti-inflammatory supplementations have been occasionally found, others reported a blunting of relevant adaptations to exercise, following the patterns described in skeletal muscles. This review discusses current data regarding liver responses and adaptation to acute and regular exercise protocols alone or combined with antioxidant and anti-inflammatory supplementation. The understanding of the mechanisms behind these modulations is of interest for both exercise-related health and performance outcomes.
Collapse
Affiliation(s)
- Rômulo Pillon Barcelos
- a Instituto de Ciências Biológicas , Universidade de Passo Fundo , Passo Fundo , Brazil.,b Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica (PPGBTOx) , Universidade Federal de Santa Maria (UFSM) , Santa Maria , Brazil
| | - Luiz Fernando Freire Royes
- b Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica (PPGBTOx) , Universidade Federal de Santa Maria (UFSM) , Santa Maria , Brazil.,c Laboratório de Bioquímica do Exercício, Centro de Educação Física e Desportos , Universidade Federal de Santa Maria (UFSM) , Santa Maria , Brazil
| | - Javier Gonzalez-Gallego
- d Institute of Biomedicine (IBIOMED) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) , University of León , León , Spain
| | - Guilherme Bresciani
- e Grupo de Investigación en Rendimiento Físico y Salud (IRyS), Escuela de Educación Física , Pontificia Universidad Católica de Valparaiso , Valparaiso , Chile
| |
Collapse
|
|
16
|
Heck SO, Fulco BCW, Quines CB, Oliveira CES, Leite MR, Cechella JL, Nogueira CW. Combined Therapy With Swimming Exercise and a Diet Supplemented With Diphenyl Diselenide Is Effective Against Age-Related Changes in the Hepatic Metabolism of Rats. J Cell Biochem 2016; 118:1574-1582. [PMID: 27918086 DOI: 10.1002/jcb.25819] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Accepted: 11/28/2016] [Indexed: 01/06/2023]
Abstract
Aging is characterized by a widespread loss of homeostasis in biological systems and is accompanied by pathophysiological changes including the liver injury. The aim of the present study was to investigate the effects of the combined therapy with swimming exercise (20 min session, 5 days/week during 4 weeks) and a diet supplemented with 1 ppm of (PhSe)2 on the hepatic metabolic alterations caused by aging in rats. In this study, male old Wistar rats had an increase in the epididymal fat relative weight, disturbances in the activities of hepatic enzymes associated to the glucose homeostasis, higher hepatic triglyceride content and higher activity of the plasma alanine aminotransferase (ALT), and aspartate aminotransferase (AST). The combined therapy normalized the activities of glucose-6-Pase and tyrosine aminotransferase, gluconeogenic enzymes, increased the hepatic glycogen content and was effective against the increase in the hepatic triglycerides content, without altering the activities of hexoquinase, and citrate synthase. Moreover, the combined therapy normalized the activities of AST and ALT, indicating a hepatoprotective effect. The combined therapy with swimming exercise and a diet supplemented with 1 ppm of (PhSe)2 contributed to the hepatic glucose homeostasis in old rats. Nevertheless, more studies are needed to investigate the possible mechanisms of action behind these effects. J. Cell. Biochem. 118: 1574-1582, 2017. © 2016 Wiley Periodicals, Inc.
Collapse
Affiliation(s)
- Suélen O Heck
- Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios. Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, Rio Grande do Sul, Brazil
| | - Bruna C W Fulco
- Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios. Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, Rio Grande do Sul, Brazil
| | - Caroline B Quines
- Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios. Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, Rio Grande do Sul, Brazil
| | - Carla E S Oliveira
- Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios. Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, Rio Grande do Sul, Brazil
| | - Marlon R Leite
- Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios. Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, Rio Grande do Sul, Brazil
| | - José L Cechella
- Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios. Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, Rio Grande do Sul, Brazil
| | - Cristina W Nogueira
- Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios. Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, Rio Grande do Sul, Brazil
| |
Collapse
|
|
17
|
Croci I, Byrne NM, Chachay VS, Hills AP, Clouston AD, O’Moore-Sullivan TM, Prins JB, Macdonald GA, Hickman IJ. Independent effects of diet and exercise training on fat oxidation in non-alcoholic fatty liver disease. World J Hepatol 2016; 8:1137-1148. [PMID: 27721919 PMCID: PMC5037327 DOI: 10.4254/wjh.v8.i27.1137] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2016] [Revised: 07/13/2016] [Accepted: 08/18/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the independent effects of 6-mo of dietary energy restriction or exercise training on whole-body and hepatic fat oxidation of patients with non-alcoholic fatty liver disease (NAFLD).
METHODS Participants were randomised into either circuit exercise training (EX; n = 13; 3 h/wk without changes in dietary habits), or dietary energy restriction (ER) without changes in structured physical activity (ER; n = 8). Respiratory quotient (RQ) and whole-body fat oxidation rates (Fatox) were determined by indirect calorimetry under basal, insulin-stimulated and exercise conditions. Severity of disease and steatosis was determined by liver histology; hepatic Fatox was estimated from plasma β-hydroxybutyrate concentrations; cardiorespiratory fitness was expressed as VO2peak. Complete-case analysis was performed (EX: n = 10; ER: n = 6).
RESULTS Hepatic steatosis and NAFLD activity score decreased with ER but not with EX. β-hydroxybutyrate concentrations increased significantly in response to ER (0.08 ± 0.02 mmol/L vs 0.12 ± 0.04 mmol/L, P = 0.03) but remained unchanged in response to EX (0.10 ± 0.03 mmol/L vs 0.11 ± 0.07 mmol/L, P = 0.39). Basal RQ decreased (P = 0.05) in response to EX, while this change was not significant after ER (P = 0.38). VO2peak (P < 0.001) and maximal Fatox during aerobic exercise (P = 0.03) improved with EX but not with ER (P > 0.05). The increase in β-hydroxybutyrate concentrations was correlated with the reduction in hepatic steatosis (r = -0.56, P = 0.04).
CONCLUSION ER and EX lead to specific benefits on fat metabolism of patients with NAFLD. Increased hepatic Fatox in response to ER could be one mechanism through which the ER group achieved reduction in steatosis.
Collapse
|
|
18
|
Golabi P, Locklear CT, Austin P, Afdhal S, Byrns M, Gerber L, Younossi ZM. Effectiveness of exercise in hepatic fat mobilization in non-alcoholic fatty liver disease: Systematic review. World J Gastroenterol 2016; 22:6318-6327. [PMID: 27468220 PMCID: PMC4945989 DOI: 10.3748/wjg.v22.i27.6318] [Citation(s) in RCA: 120] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2016] [Revised: 05/25/2016] [Accepted: 06/15/2016] [Indexed: 02/07/2023] Open
Abstract
AIM: To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease (NAFLD) patients.
METHODS: Ovid-Medline, PubMed, EMBASE and Cochrane database were searched for randomized trials and prospective cohort studies in adults aged ≥ 18 which investigated the effects of at least 8 wk of exercise only or combination with diet on NAFLD from 2010 to 2016. The search terms used to identify articles, in which exercise was clearly described by type, duration, intensity and frequency were: “NASH”, “NAFLD”, “non-alcoholic steatohepatitis”, “non-alcoholic fatty liver disease”, “fat”, “steatosis”, “diet”, “exercise”, “MR spectroscopy” and “liver biopsy”. NAFLD diagnosis, as well as the outcome measures, was confirmed by either hydrogen-magnetic resonance spectroscopy (H-MRS) or biopsy. Trials that included dietary interventions along with exercise were accepted if they met all criteria.
RESULTS: Eight studies met selection criteria (6 with exercise only, 2 with diet and exercise with a total of 433 adult participants). Training interventions ranged between 8 and 48 wk in duration with a prescribed exercise frequency of 3 to 7 d per week, at intensities between 45% and 75% of VO2 peak. The most commonly used imaging modality was H-MRS and one study utilized biopsy. The effect of intervention on fat mobilization was 30.2% in the exercise only group and 49.8% in diet and exercise group. There was no difference between aerobic and resistance exercise intervention, although only one study compared the two interventions. The beneficial effects of exercise on intrahepatic triglyceride (IHTG) were seen even in the absence of significant weight loss. Although combining an exercise program with dietary interventions augmented the reduction in IHTG, as well as improved measures of glucose control and/or insulin sensitivity, exercise only significantly decreased hepatic lipid contents.
CONCLUSION: Prescribed exercise in subjects with NAFLD reduces IHTG independent of dietary intervention. Diet and exercise was more effective than exercise alone in reducing IHTG.
Collapse
|
|
19
|
Cheraghpour M, Hekmatdoost A, Ghaemi A. Comments on "The Effects of Aerobic and Resistance Exercise Training on Liver Enzymes and Hepatic Fat in Iranian Men With Nonalcoholic Fatty Liver Disease". HEPATITIS MONTHLY 2016; 16:e35162. [PMID: 27313633 PMCID: PMC4908672 DOI: 10.5812/hepatmon.35162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/12/2015] [Accepted: 04/16/2016] [Indexed: 12/11/2022]
Affiliation(s)
- Makan Cheraghpour
- Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
| | - Azita Hekmatdoost
- Department of Clinical Nutrition, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Alireza Ghaemi
- Department of Basic Sciences and Nutrition, Health Sciences Research Center, School of Public Health, Mazandaran University of Medical Sciences, Sari, IR Iran
- Corresponding Author: Alireza Ghaemi, Department of Basic Sciences and Nutrition, Health Sciences Research Center, School of Public Health, Mazandaran University of Medical Sciences, Sari, IR Iran. Tel: +98-1133543750, Fax: +98-1133542473, E-mail:
| |
Collapse
|
|
20
|
Razavi Zade M, Telkabadi MH, Bahmani F, Salehi B, Farshbaf S, Asemi Z. The effects of DASH diet on weight loss and metabolic status in adults with non-alcoholic fatty liver disease: a randomized clinical trial. Liver Int 2016; 36:563-71. [PMID: 26503843 DOI: 10.1111/liv.12990] [Citation(s) in RCA: 146] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2015] [Accepted: 10/16/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS This study was designed to determine the effects of the Dietary Approaches to Stop Hypertension (DASH) diet on weight loss and metabolic status in overweight patients with non-alcoholic fatty liver disease (NAFLD). METHODS This randomized controlled clinical trial was done among 60 overweight and obese patients with NAFLD. Patients were randomly allocated to consume either the control (n = 30) or the DASH eating pattern (n = 30) for 8 weeks. Both diets were designed to be calorie-restricted. Both diets were consisted of 52-55% carbohydrates, 16-18% proteins and 30% total fats; however, the DASH diet was designed to be rich in fruits, vegetables, whole grains, and low-fat dairy products and low in saturated fats, cholesterol and refined grains. RESULTS Adherence to the DASH eating pattern, compared to the control diet, weight (P = 0.006), BMI (P = 0.01), alanine aminotransferase (ALT) (P = 0.02), alkalin phosphatase (ALP) (P = 0.001), insulin levels (P = 0.01), homoeostasis model of assessment-estimated insulin resistance (HOMA-IR) (P = 0.01) significantly decreased and quantitative insulin sensitivity check index (QUICKI) (P = 0.004) significantly increased. Compared with the control diet, the DASH diet has resulted in significant reductions in serum triglycerides (P = 0.04) and total-/HDL-cholesterol ratio (P = 0.01). Finally, decreased concentrations of serum high-sensitivity C-reactive protein (hs-CRP) (P = 0.03), malondialdehyde (MDA) (P = 0.04), increased levels of nitric oxide (NO) (P = 0.01) and glutathione (GSH) (P = 0.009) were found in the DASH group compared with the control group. CONCLUSIONS Consumption of DASH diet for 8 weeks among patients with NAFLD had beneficial effects on weight, BMI, ALT, ALP, triglycerides, markers of insulin metabolism, inflammatory markers, GSH and MDA.
Collapse
Affiliation(s)
- Mohsen Razavi Zade
- Department of Gastroenterology, Kashan University of Medical Sciences, Kashan, Iran
| | | | - Fereshteh Bahmani
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | - Behnaz Salehi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | - Shima Farshbaf
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran
| |
Collapse
|
|
21
|
Kullman EL, Kelly KR, Haus JM, Fealy CE, Scelsi AR, Pagadala MR, Flask CA, McCullough AJ, Kirwan JP. Short-term aerobic exercise training improves gut peptide regulation in nonalcoholic fatty liver disease. J Appl Physiol (1985) 2016; 120:1159-64. [PMID: 27032902 DOI: 10.1152/japplphysiol.00693.2015] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2015] [Accepted: 03/28/2016] [Indexed: 02/06/2023] Open
Abstract
Obesity-related nonalcoholic fatty liver disease (NAFLD) is now the most common chronic liver disease. Exercise and diet are uniformly prescribed treatments for NAFLD; however, there are limited empirical data on the effects of exercise training on metabolic function in these patients. The purpose of this study was to investigate the fasting and glucose-stimulated adaptation of gut peptides to short-term aerobic exercise training in patients with NAFLD. Twenty-two obese subjects, 16 with NAFLD [body mass index (BMI), 33.2 ± 1.1 (SE) kg/m(2)] and 6 obese controls (BMI, 31.3 ± 1.2 kg/m(2)), were enrolled in a supervised aerobic exercise program (60 min/day, 85% of their heart rate maximum, for 7 days). Fasting and glucose-stimulated glucagon-like peptide-1 (GLP-17-36) and peptide tyrosine tyrosine (PYYTotal) concentrations in plasma were assessed before and after the exercise program. Initially, the NAFLD group had higher fasting PYY (NAFLD = 117 ± 18.6, control = 47.2 ± 6.4 pg/ml, P < 0.05) and GLP-1 (NAFLD = 12.4 ± 2.2, control = 6.2 ± 0.2 pg/ml, P < 0.05) and did not significantly increase GLP-1 or PYY in response to glucose ingestion. After the exercise program, fasting GLP-1 was reduced in the NAFLD group (10.7 ± 2.0 pg/ml, P < 0.05). Furthermore, exercise training led to significant increase in the acute (0-30 min) PYY and GLP-1 responses to glucose in the NAFLD group, while the total area under the glucose-stimulated GLP-1 response curve was reduced in both NAFLD and controls (P < 0.05). In summary, 7 days of vigorous aerobic exercise normalized the dynamic PYY and GLP-1 responses to nutrient stimulation and reduced the GLP-1 response in NAFLD, suggesting that exercise positively modulates gut hormone regulation in obese adults with NAFLD.
Collapse
Affiliation(s)
- Emily L Kullman
- Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
| | - Karen R Kelly
- Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
| | - Jacob M Haus
- Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
| | - Ciaran E Fealy
- Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
| | - Amanda R Scelsi
- Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
| | - Mangesh R Pagadala
- Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio; Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - Chris A Flask
- Department of Radiology and Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio; and
| | - Arthur J McCullough
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio
| | - John P Kirwan
- Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio; Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio; Metabolic Translational Research Center, Endocrinology & Metabolism Institute, Cleveland Clinic, Cleveland, Ohio
| |
Collapse
|
|
22
|
Ballestri S, Nascimbeni F, Romagnoli D, Baldelli E, Lonardo A. The Role of Nuclear Receptors in the Pathophysiology, Natural Course, and Drug Treatment of NAFLD in Humans. Adv Ther 2016; 33:291-319. [PMID: 26921205 DOI: 10.1007/s12325-016-0306-9] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Indexed: 02/06/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) describes steatosis, nonalcoholic steatohepatitis with or without fibrosis, and hepatocellular carcinoma, namely the entire alcohol-like spectrum of liver disease though observed in the nonalcoholic, dysmetabolic, individual free of competing causes of liver disease. NAFLD, which is a major public health issue, exhibits intrahepatic triglyceride storage giving rise to lipotoxicity. Nuclear receptors (NRs) are transcriptional factors which, activated by ligands, are master regulators of metabolism and also have intricate connections with circadian control accounting for cyclical patterns in the metabolic fate of nutrients. Several transcription factors, such as peroxisome proliferator-activated receptors, liver X receptors, farnesoid X receptors, and their molecular cascades, finely regulate energetic fluxes and metabolic pathways. Dysregulation of such pathways is heavily implicated in those metabolic derangements characterizing insulin resistance and metabolic syndrome and in the histogenesis of progressive NAFLD forms. We review the role of selected NRs in NAFLD pathogenesis. Secondly, we analyze the role of NRs in the natural history of human NAFLD. Next, we discuss the results observed in humans following administration of drug agonists or antagonists of the NRs pathogenically involved in NAFLD. Finally, general principles of treatment and lines of research in human NAFLD are briefly examined.
Collapse
Affiliation(s)
| | - Fabio Nascimbeni
- NOCSAE, Outpatient Liver Clinic and Operating Unit Internal Medicine, Azienda USL Modena, Modena, Italy
- University of Modena and Reggio Emilia, Modena, Italy
| | - Dante Romagnoli
- NOCSAE, Outpatient Liver Clinic and Operating Unit Internal Medicine, Azienda USL Modena, Modena, Italy
| | | | - Amedeo Lonardo
- NOCSAE, Outpatient Liver Clinic and Operating Unit Internal Medicine, Azienda USL Modena, Modena, Italy.
| |
Collapse
|
|
23
|
Xiao J, Bei Y, Liu J, Dimitrova-Shumkovska J, Kuang D, Zhou Q, Li J, Yang Y, Xiang Y, Wang F, Yang C, Yang W. miR-212 downregulation contributes to the protective effect of exercise against non-alcoholic fatty liver via targeting FGF-21. J Cell Mol Med 2015; 20:204-16. [PMID: 26648452 PMCID: PMC4727558 DOI: 10.1111/jcmm.12733] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2015] [Accepted: 10/03/2015] [Indexed: 12/17/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is associated with obesity and lifestyle, while exercise is beneficial for NAFLD. Dysregulated microRNAs (miRs) control the pathogenesis of NAFLD. However, whether exercise could prevent NAFLD via targeting microRNA is unknown. In this study, normal or high-fat diet (HF) mice were either subjected to a 16-week running program or kept sedentary. Exercise attenuated liver steatosis in HF mice. MicroRNA array and qRT-PCR demonstrated that miR-212 was overexpressed in HF liver, while reduced by exercise. Next, we investigated the role of miR-212 in lipogenesis using HepG2 cells with/without long-chain fatty acid treatment (± FFA). FFA increased miR-212 in HepG2 cells. Moreover, miR-212 promoted lipogenesis in HepG2 cells (± FFA). Fibroblast growth factor (FGF)-21, a key regulator for lipid metabolism, was negatively regulated by miR-212 at protein level in HepG2 cells. Meanwhile, FFA downregulated FGF-21 both at mRNA and protein levels in HepG2 cells. Also, FGF-21 protein level was reduced in HF liver, while reversed by exercise in vivo. Furthermore, siRNA-FGF-21 abolished the lipogenesis-reducing effect of miR-212 inhibitor in HepG2 cells (± FFA), validating FGF-21 as a target gene of miR-212. These data link the benefit of exercise and miR-212 downregulation in preventing NAFLD via targeting FGF-21.
Collapse
Affiliation(s)
- Junjie Xiao
- Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, China.,Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai, China
| | - Yihua Bei
- Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, China.,Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai, China
| | - Jingqi Liu
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Jasmina Dimitrova-Shumkovska
- Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, China.,Department of Experimental Biochemistry and Physiology, Faculty of Natural Sciences and Mathematics, University Ss Cyril and Methodius, Skopje, Republic of Macedonia
| | - Dapeng Kuang
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Qiulian Zhou
- Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, China.,Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai, China
| | - Jin Li
- Regeneration and Ageing Lab, Experimental Center of Life Sciences, School of Life Science, Shanghai University, Shanghai, China.,Shanghai Key Laboratory of Bio-Energy Crops, School of Life Sciences, Shanghai University, Shanghai, China
| | - Yanning Yang
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yang Xiang
- State Key Laboratory of Pharmaceutical Biotechnology and Department of Biochemistry, Nanjing University, Nanjing, China
| | - Fei Wang
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Changqing Yang
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| | - Wenzhuo Yang
- Division of Gastroenterology and Hepatology, Digestive Disease Institute, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| |
Collapse
|
|
24
|
Janssens S, Jonkers RAM, Groen AK, Nicolay K, van Loon LJC, Prompers JJ. Effects of acute exercise on lipid content and dietary lipid uptake in liver and skeletal muscle of lean and diabetic rats. Am J Physiol Endocrinol Metab 2015; 309:E874-83. [PMID: 26419590 DOI: 10.1152/ajpendo.00292.2015] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2015] [Accepted: 09/26/2015] [Indexed: 12/24/2022]
Abstract
Insulin resistance is associated with ectopic lipid accumulation. Physical activity improves insulin sensitivity, but the impact of exercise on lipid handling in insulin-resistant tissues remains to be elucidated. The present study characterizes the effects of acute exercise on lipid content and dietary lipid partitioning in liver and skeletal muscle of lean and diabetic rats by use of magnetic resonance spectroscopy (MRS). After baseline measurements, rats were randomized to exercise or no-exercise groups. A subset of animals was subjected to MRS directly after 1 h of treadmill running for measurement of total intrahepatocellular lipid (IHCL) and intramyocellular lipid (IMCL) content (n=7 lean and diabetic rats). The other animals were administered 13C-labeled lipids orally after treadmill visit (with or without exercise) followed by MRS measurements after 4 and 24 h to determine the 13C enrichment of IHCL and IMCL (n=8 per group). Total IHCL and IMCL content were fivefold higher in diabetic vs. lean rats (P<0.001). Exercise did not significantly affect IHCL content but reduced IMCL by 25±7 and 33±4% in lean and diabetic rats (P<0.05), respectively. Uptake of dietary lipids in liver and muscle was 2.3-fold greater in diabetic vs. lean rats (P<0.05). Prior exercise did not significantly modulate dietary lipid uptake into muscle, but in liver of both lean and diabetic rats, lipid uptake was 44% reduced after acute exercise (P<0.05). In conclusion, IMCL but not IHCL represents a viable substrate source during exercise in both lean and diabetic rats, and exercise differentially affects dietary lipid uptake in muscle and liver.
Collapse
Affiliation(s)
- Sharon Janssens
- Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands; The Netherlands Consortium for Systems Biology, Den Haag, The Netherlands
| | - Richard A M Jonkers
- Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands
| | - Albert K Groen
- Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; and Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
| | - Klaas Nicolay
- Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands
| | - Luc J C van Loon
- NUTRIM, School for Nutrition, Toxicology and Metabolism, Department of Human Movement Sciences, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Jeanine J Prompers
- Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands;
| |
Collapse
|
|
25
|
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
|