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Hao X, Song H, Su X, Li J, Ye Y, Wang C, Xu X, Pang G, Liu W, Li Z, Luo T. Prophylactic effects of nutrition, dietary strategies, exercise, lifestyle and environment on nonalcoholic fatty liver disease. Ann Med 2025; 57:2464223. [PMID: 39943720 PMCID: PMC11827040 DOI: 10.1080/07853890.2025.2464223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 01/16/2025] [Accepted: 01/25/2025] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and its prevalence has risen sharply. However, whether nutrition, dietary strategies, exercise, lifestyle and environment have preventive value for NAFLD remains unclear. METHODS Through searching 4 databases (PubMed, Web of Science, Embase and the Cochrane Library) from inception to January 2025, we selected studies about nutrition, dietary strategies, exercise, lifestyle and environment in the prevention of NAFLD and conducted a narrative review on this topic. RESULTS Reasonable nutrient intake encompassing macronutrients and micronutrients have an independent protective relationship with NAFLD. Besides, proper dietary strategies including mediterranean diet, intermittent fasting diet, ketogenic diet, and dietary approaches to stop hypertension diet have their inhibitory effects on the developmental process of NAFLD. Moreover, right exercises including walking, jogging, bicycling, and swimming are recommended for the prevention of NAFLD because they could effectively reduce weight, which is an important risk factor for NAFLD, and improve liver function. In addition, embracing a healthy lifestyle including reducing sedentary behavior, not smoking, sleeping well and brushing teeth regularly is integral since it not only could reduce the risk of NAFLD but also significantly contribute to overall prevention and control. Finally, the environment, including the social and natural environments, plays a potential role in NAFLD prevention. CONCLUSION Nutrition, dietary strategies, exercise, lifestyle and environment play an important role in the prevention of NAFLD. Moreover, this review offers comprehensive prevention recommendations for people at high risk of NAFLD.
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Affiliation(s)
- Xiangyong Hao
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China
| | - Hao Song
- Department of clinical medicine, The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
| | - Xin Su
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China
- Department of clinical medicine, The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
| | - Jian Li
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China
- Department of clinical medicine, The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
| | - Youbao Ye
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China
- Department of clinical medicine, The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
| | - Cailiu Wang
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China
- Department of clinical medicine, The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
| | - Xiao Xu
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China
- Department of clinical medicine, The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
| | - Guanglong Pang
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China
- Department of clinical medicine, The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
| | - Wenxiu Liu
- Department of General Surgery, Gansu Provincial Hospital, Lanzhou, China
- Department of clinical medicine, The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
| | - Zihan Li
- Department of clinical medicine, The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
| | - Tian Luo
- The Institute for Clinical Research and Translational Medicine, Gansu Provincial Hospital, Lanzhou, China
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Hegazy MA, Ahmed SM, Sultan SM, Afifi OF, Mohamed MA, Azab AE, Hassanen MA, Zaben RK. Metabolic dysfunction-associated steatotic liver disease and omega-6 polyunsaturated fatty acids: Friends or foes. World J Hepatol 2025; 17:102286. [DOI: 10.4254/wjh.v17.i3.102286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2024] [Revised: 02/20/2025] [Accepted: 03/05/2025] [Indexed: 03/26/2025] Open
Abstract
BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide. Its prevalence is closely linked to the dramatic rise in obesity and non-communicable diseases. MASLD exhibits a progressive trajectory that may culminate in development of hepatic cirrhosis, thereby predisposing affected individuals to an elevated likelihood of hepatocarcinogenesis. Diet, especially dietary fatty acids, serves as a key link between nutrient intake and MASLD pathogenesis.
AIM To explore the impact of various omega-6 fatty acid subtypes on the pathogenesis and therapeutic strategies of MASLD.
METHODS A systematic literature search was conducted across Web of Science, PubMed, Cochrane Central, Scopus, and Embase databases from inception through June 2024 to identify all original studies linking different subtypes of omega-6 polyunsaturated fatty acids to the pathogenesis and management of MASLD. The search strategy explored the linkage between omega-6 polyunsaturated fatty acids and their subtypes, including linoleic acid (LA), gamma-linolenic acid (GLA), arachidonic acid, conjugated LA, and docosapentaenoic acid, in relation to MASLD and cardiometabolic risk.
RESULTS By employing the specified search strategy, a total of 83 articles were identified as potentially eligible. During the title, abstract, and full-text screening phases, 27 duplicate records were removed, leaving 56 records for relevance screening. Of these, 43 records were excluded for reasons such as irrelevance and language restrictions (limited to English), resulting in 13 full-text articles being included for detailed assessment (10 human studies,1 animal study, and 2 review articles). Although certain subtypes, as GLA, dihomo-GLA, omega-6-derived oxylipins, and most arachidonic acid-derived eicosanoids, exhibit pro-inflammatory effects, our findings suggest that other subtypes such as LA, cis-9, trans-11 conjugated LA, and docosapentaenoic acid have beneficial effects on fatty liver, cardiometabolic risk factors, and inflammation, even at high intake levels.
CONCLUSION The varying health effects of omega-6 fatty acids, ranging from anti-inflammatory to pro-inflammatory impacts on the liver, leave the question of their recommendation for MASLD patients unresolved. This underscores the importance of careful selection when considering omega-6 supplementation.
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Affiliation(s)
- Mona A Hegazy
- Department of Internal Medicine, Kasr Aliny Hospital, Faculty of Medicine, Cairo University, Cairo 12556, Egypt
| | - Safaa M Ahmed
- Department of Neonatology, Mounira General Hospital, Cairo 4262130, Egypt
| | - Shaimaa M Sultan
- Department of Maternal and Pediatric Health, Shubra Elkhema Medical Administration, Qalyubia 13768, Egypt
| | - Osama F Afifi
- Department of Neonatology, Ashmoun Hospital, Menofia 32811, Egypt
| | - Manal A Mohamed
- Department of Internal Medicine, Elnasr Hospital, Helwan 11731, Egypt
| | - Alshimaa E Azab
- Department of Anesthesia, Al Helal Insurance Hospital, Qism Shebin 32514, Egypt
| | - Mohamed A Hassanen
- Department of Clinical Nutrition, Egyptian Fellowship, Cairo 11559, Egypt
| | - Rakan K Zaben
- Department of Clinical Nutrition, Egyptian Fellowship, Cairo 11559, Egypt
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Hermanson JB, Tolba SA, Chrisler EA, Leone VA. Gut microbes, diet, and genetics as drivers of metabolic liver disease: a narrative review outlining implications for precision medicine. J Nutr Biochem 2024; 133:109704. [PMID: 39029595 PMCID: PMC11480923 DOI: 10.1016/j.jnutbio.2024.109704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Revised: 07/01/2024] [Accepted: 07/15/2024] [Indexed: 07/21/2024]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly increasing in prevalence, impacting over a third of the global population. The advanced form of MASLD, Metabolic dysfunction-associated steatohepatitis (MASH), is on track to become the number one indication for liver transplant. FDA-approved pharmacological agents are limited for MASH, despite over 400 ongoing clinical trials, with only a single drug (resmetirom) currently on the market. This is likely due to the heterogeneous nature of disease pathophysiology, which involves interactions between highly individualized genetic and environmental factors. To apply precision medicine approaches that overcome interpersonal variability, in-depth insights into interactions between genetics, nutrition, and the gut microbiome are needed, given that each have emerged as dynamic contributors to MASLD and MASH pathogenesis. Here, we discuss the associations and molecular underpinnings of several of these factors individually and outline their interactions in the context of both patient-based studies and preclinical animal model systems. Finally, we highlight gaps in knowledge that will require further investigation to aid in successfully implementing precision medicine to prevent and alleviate MASLD and MASH.
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Affiliation(s)
- Jake B Hermanson
- Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Samar A Tolba
- Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA; Department of Nutrition and Clinical Nutrition, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt
| | - Evan A Chrisler
- Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA
| | - Vanessa A Leone
- Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
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Aboujassoum HM, Mohamed-Ali V, Abraham D, Clapp LH, Al-Naemi HA. Relative Recovery of Non-Alcoholic Fatty Liver Disease (NAFLD) in Diet-Induced Obese Rats. Nutrients 2023; 16:115. [PMID: 38201945 PMCID: PMC10780646 DOI: 10.3390/nu16010115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 11/06/2023] [Accepted: 11/09/2023] [Indexed: 01/12/2024] Open
Abstract
Consumption of a high-carbohydrate diet has a critical role in the induction of weight gain and obesity-related pathologies. This study tested the hypothesis that a carbohydrate-rich diet induces weight gain, ectopic fat deposition, associated metabolic risks and development of non-alcoholic fatty liver disease (NAFLD), which are partially reversible following carbohydrate reduction. Sprague Dawley (SD) rats were fed a carbohydrate-enriched cafeteria diet (CAF) or normal chow (NC) ad libitum for 16-18 weeks. In the reversible group (REV), the CAF was replaced with NC for a further 3 weeks (18-21 weeks). Animals fed the CAF diet showed significantly increased body weight compared to those fed NC, accompanied by abnormal changes in their systemic insulin and triglycerides, elevation of hepatic triglyceride and hepatic steatosis. In the REV group, when the CAF diet was stopped, a modest, non-significant weight loss was associated with improvement in systemic insulin and appearance of the liver, with lower gross fatty deposits and hepatic triglyceride. In conclusion, a carbohydrate-enriched diet led to many features of metabolic syndrome, including hyperinsulinemia, while a dietary reduction in this macronutrient, even for a short period, was able to restore normoinsulinemia, and reversed some of the obesity-related hepatic abnormalities, without significant weight loss.
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Affiliation(s)
| | - Vidya Mohamed-Ali
- Anti-Doping Laboratory Qatar, Sports City Road, Doha P.O. Box 2713, Qatar;
- Centre of Metabolism and Inflammation, Division of Medicine, Royal Free Campus, University College London, Rowland Hill Street, London NW3 2PF, UK
| | - David Abraham
- Centre of Rheumatology and Connective Tissue Disorders, Division of Medicine, Royal Free Campus, University College London, Rowland Hill Street, London NW3 2PF, UK;
| | - Lucie H. Clapp
- Institute of Cardiovascular Science, University College London, Rayne Building, 5 University Street, London WC1E 6JF, UK;
| | - Hamda A. Al-Naemi
- Laboratory Animal Research Center, Qatar University, Doha P.O. Box 2713, Qatar;
- Department of Biological and Environmental Sciences, Qatar University, Doha P.O. Box 2713, Qatar
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Klein RJ, Viana Rodriguez GM, Rotman Y, Brown RJ. Divergent pathways of liver fat accumulation, oxidation, and secretion in lipodystrophy versus obesity-associated NAFLD. Liver Int 2023; 43:2692-2700. [PMID: 37622286 DOI: 10.1111/liv.15707] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 08/08/2023] [Accepted: 08/10/2023] [Indexed: 08/26/2023]
Abstract
BACKGROUND AND AIMS Fatty liver is common in obesity as well as in partial lipodystrophy (PL) syndromes, characterized by deficient adipose tissue. Insulin resistance is key to fatty liver pathogenesis in both entities. We aimed to compare the contributions of insulin resistance and adipose tissue to hepatic steatosis in PL and non-syndromic, obesity-associated non-alcoholic fatty liver disease (NS-NAFLD). METHODS In a cross-sectional comparison of people with NS-NAFLD (N = 73) and PL (N = 27), liver fat was measured by FibroScan® controlled attenuation parameter (CAP) and insulin resistance by HOMA-IR, Adipo-IR, and NMR-based LP-IR. RESULTS Insulin resistance was greater in PL versus NS-NAFLD by HOMA-IR (p = 0.005), Adipo-IR (p = 0.01) and LP-IR (p = 0.05) while liver fat was comparable (304 vs. 324 dB/m, p = 0.12). Liver fat correlated with HOMA-IR in both groups, but CAP values were lower by 32 dB/m in PL compared with NS-NAFLD for any given HOMA-IR. In contrast, Adipo-IR and LP-IR correlated with CAP only in the NS-NAFLD group, suggesting different pathways for fat accumulation. Plasma free fatty acids, reflecting substrate input from the adipose tissue, were comparable between groups. However, the levels of β-hydroxybutyrate, a marker of β-oxidation, and large triglyceride-rich lipoprotein particles, a marker of VLDL secretion, were both higher in PL (p < 0.001 for both). CONCLUSION Liver fat content was comparable in subjects with PL-associated NAFLD and NS-NAFLD, despite worse insulin resistance in partial lipodystrophy. Our data demonstrate higher triglyceride oxidation and export in PL, suggesting a compensatory shift of fat from liver storage into the circulation that does not occur in NS-NAFLD.
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Affiliation(s)
- Rachael J Klein
- Section on Translational Diabetes and Metabolic Syndromes, Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Gracia M Viana Rodriguez
- Liver & Energy Metabolism Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Yaron Rotman
- Liver & Energy Metabolism Section, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
| | - Rebecca J Brown
- Section on Translational Diabetes and Metabolic Syndromes, Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
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Al-Okbi SY, Ali O, Aly AS, Refaat D, Esmail RSH, Elbakry HFH. Management of metabolic syndrome by nutraceuticals prepared from chitosan and ferulic acid with or without beta-sitosterol and their nanoforms. Sci Rep 2023; 13:12176. [PMID: 37500657 PMCID: PMC10374579 DOI: 10.1038/s41598-023-38837-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Accepted: 07/16/2023] [Indexed: 07/29/2023] Open
Abstract
Dyslipidemia, steatohepatitis and insulin resistance are among the components of metabolic syndrome (MS). Nutraceuticals containing chitosan, beta-sitosterol and/or ferulic acid and their nanostructures could have a potential role for management of MS. The aim of the present study was to assess the efficacy of the aforementioned nutraceuticals in treatment of MS in rat and their interaction with atorvastatin, a hypolipidemic drug. The two nutraceuticals and their nanostructures were prepared and the nanostructures were assessed by transmission electron microscope and Fourier-Transform Infra-red Spectrometry. MS was induced in rats by feeding high fructose-high fat diet (HFFD). Different groups of rats fed HFFD and treated with the different nutraceuticals, atorvastatin and atorvastatin in combination with different nutraceuticals, control fed on balanced diet and control consumed HFFD without treatments were run. Plasma glucose, lipid profile, aminotransferases activity, total antioxidant capacity, malondialdehyde, urea, creatinine, insulin, high sensitivity C-reactive protein, and adiponectin were assessed along with calculation of insulin resistance. Liver fat and histopathology were investigated. All nutraceuticals in original and nanostructures showed beneficial effects in the treatment of MS, superiority was ascribed to nutraceuticals composed of chitosan and ferulic acid in both forms. A more promising treatment of MS belonged to atorvastatin administered with the different nutraceuticals.
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Affiliation(s)
- Sahar Y Al-Okbi
- Nutrition and Food Sciences Department, National Research Centre, Cairo, Egypt.
| | - Ola Ali
- Biochemistry Department, Faculty of Pharmacy (Girls), Al Azhar University, Cairo, Egypt
| | - A S Aly
- Preparatory and Finishing Department, National Research Centre, Cairo, Egypt
| | - D Refaat
- Central Metallurgical R&D Institute (CMRDI), P.O box 87, Helwan, Egypt
- Instituto de Nanociencia y Materiales de Aragón, CSIC-Universidad de Zaragoza, 50018, Zaragoza, Spain
| | | | - Hagar F H Elbakry
- Nutrition and Food Sciences Department, National Research Centre, Cairo, Egypt
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Reda D, Elshopakey GE, Albukhari TA, Almehmadi SJ, Refaat B, Risha EF, Mahgoub HA, El-Boshy ME, Abdelhamid FM. Vitamin D3 alleviates nonalcoholic fatty liver disease in rats by inhibiting hepatic oxidative stress and inflammation via the SREBP-1-c/ PPARα-NF-κB/IR-S2 signaling pathway. Front Pharmacol 2023; 14:1164512. [PMID: 37261280 PMCID: PMC10228732 DOI: 10.3389/fphar.2023.1164512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Accepted: 05/02/2023] [Indexed: 06/02/2023] Open
Abstract
Introduction: Nonalcoholic fatty liver disease (NAFLD) is a chronic disease characterized by fat deposits in liver cells, which can lead to hepatitis and fibrosis. This study attempted to explore the protective effect of vitamin D3 (VitD) against NAFLD. Methods: Adult male albino rats were randomized into four separate groups: the negative control group was fed a standard rat chow; the positive group received a high-fat diet (20%) and 25% fructose water (NAFLD); the VitD control group was intramuscularly treated with VitD (1,000 IU/kg BW) 3 days per week for 10 weeks; and the NAFLD group was treated with VitD therapy. Biochemical and hepatic histological analyses were performed. Hepatic oxidative stress and inflammatory conditions were also studied. Hepatic expression of sterol regulatory element-binding protein 1-c (SREBP-1-c), peroxisome proliferator-activated receptor alpha (PPAR-α), and insulin receptor substrate-2 was analyzed by quantitative real-time polymerase chain reaction. Results and discussion: The NAFLD rats exhibited elevated terminal body weight, hepatic injury markers, dyslipidemia, glucose intolerance, and insulin resistance. Moreover, the NAFLD rats had increased SREBP-1-c expression and reduced PPAR-α and IRS-2 expressions. Histological analysis showed hepatic steatosis and inflammation in the NAFLD group. In contrast, VitD administration improved the serum biochemical parameters and hepatic redox status in NAFLD rats. Also, VitD treatment ameliorated hepatic inflammation and steatosis in the NAFLD group by decreasing the expression of SREBP-1-c and increasing the expression of PPAR-α. Overall, these results suggest that VitD could have a protective effect against NAFLD and its associated complication.
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Affiliation(s)
- Doha Reda
- Clinical Pathology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
| | - Gehad E. Elshopakey
- Clinical Pathology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
| | - Talat A. Albukhari
- Department of Haematology and Immunology, Faculty of Medicine, Umm Alqura University, Makkah, Saudi Arabia
| | - Samah J. Almehmadi
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Bassem Refaat
- Laboratory Medicine Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Engy F. Risha
- Clinical Pathology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
| | - Hebatallah A. Mahgoub
- Pathology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
| | - Mohamed E. El-Boshy
- Clinical Pathology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
| | - Fatma M. Abdelhamid
- Clinical Pathology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
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Xu J, Mao F, Lu Y, Liu T, Li X, Li Y. Hepatic Transcriptomics Reveals Reduced Lipogenesis in High-Salt Diet Mice. Genes (Basel) 2023; 14:genes14050966. [PMID: 37239325 DOI: 10.3390/genes14050966] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 04/15/2023] [Accepted: 04/20/2023] [Indexed: 05/28/2023] Open
Abstract
It has been demonstrated that a high salt diet (HSD) increases the risk of cardiovascular disease and metabolic dysfunction. In particular, the impact and molecular mechanisms of long-term HSD on hepatic metabolism remain largely unknown. To identify differentially expressed genes (DEGs) affecting the metabolism of liver tissues from HSD and control groups, a transcriptome analysis of liver tissues was performed in this study. As a result of the transcriptome analysis, the expression of genes related to lipid and steroid biosynthesis (such as Fasn, Scd1, and Cyp7a1) was significantly reduced in the livers of HSD mice. Additionally, several gene ontology (GO) terms have been identified as associated with metabolic processes in the liver, including the lipid metabolic process (GO: 0006629) and the steroid metabolic process (GO: 0008202). An additional quantitative RT-qPCR analysis was conducted to confirm six down-regulated genes and two up-regulated genes. Our findings provide a theoretical basis for further investigation of HSD-induced metabolic disorders.
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Affiliation(s)
- Jing Xu
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Fei Mao
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yan Lu
- Institute of Metabolism and Regenerative Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China
| | - Tiemin Liu
- School of Life Sciences, Fudan University, Shanghai 200032, China
| | - Xiaoying Li
- Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Yao Li
- Department of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200032, China
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Stefano JT, Duarte SMB, Ribeiro Leite Altikes RG, Oliveira CP. Non-pharmacological management options for MAFLD: a practical guide. Ther Adv Endocrinol Metab 2023; 14:20420188231160394. [PMID: 36968655 PMCID: PMC10031614 DOI: 10.1177/20420188231160394] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2022] [Accepted: 02/11/2023] [Indexed: 03/24/2023] Open
Abstract
Lifestyle changes should be the main basis for any treatment for metabolic dysfunction-associated fatty liver disease (MAFLD), aiming to increase energy expenditure, reduce energy intake and improve the quality of nutrients consumed. As it is a multifactorial disease, approaches such as physical exercise, a better dietary pattern, and possible pharmacological intervention are shown to be more efficient when used simultaneously to the detriment of their applications. The main treatment for MAFLD is a lifestyle change consisting of diet, activity, exercise, and weight loss. The variables for training prescription such as type of physical exercise (aerobic or strength training), the weekly frequency, and the intensity most indicated for the treatment of MAFLD remain uncertain, that is, the recommendations must be adapted to the clinical conditions comorbidities, and preferences of each subject in a way individual. This review addresses recent management options for MAFLD including diet, nutrients, gut microbiota, and physical exercise.
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Affiliation(s)
- José Tadeu Stefano
- Laboratório de Gastroenterologia Clínica e
Experimental LIM-07, Division of Clinical Gastroenterology and Hepatology,
Hospital das Clínicas HCFMUSP, Department of Gastroenterology, Faculdade de
Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | - Sebastião Mauro Bezerra Duarte
- Laboratório de Gastroenterologia Clínica e
Experimental LIM-07, Division of Clinical Gastroenterology and Hepatology,
Hospital das Clínicas HCFMUSP, Department of Gastroenterology, Faculdade de
Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
| | | | - Claudia P. Oliveira
- Laboratório de Gastroenterologia Clínica e
Experimental LIM-07, Division of Clinical Gastroenterology and Hepatology,
Hospital das Clínicas HCFMUSP, Department of Gastroenterology, Faculdade de
Medicina, Universidade de Sao Paulo, Av. Dr. Enéas de Carvalho Aguiar no
255, Instituto Central, # 9159, Sao Paulo 05403-000, Brazil
- Departament of Gastroenterology, Faculdade de
Medicina, Universidade de São Paulo, São Paulo, Brazil
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Öngel ME, Yildiz C, Başer Ö, Yilmaz B, Özilgen M. Thermodynamic Assessment of the Effects of Intermittent Fasting and Fatty Liver Disease Diets on Longevity. ENTROPY (BASEL, SWITZERLAND) 2023; 25:227. [PMID: 36832594 PMCID: PMC9955784 DOI: 10.3390/e25020227] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 01/12/2023] [Accepted: 01/17/2023] [Indexed: 06/18/2023]
Abstract
Organisms uptake energy from their diet and maintain a highly organized structure by importing energy and exporting entropy. A fraction of the generated entropy is accumulated in their bodies, thus causing ageing. Hayflick's entropic age concept suggests that the lifespan of organisms is determined by the amount of entropy they generate. Organisms die after reaching their lifespan entropy generation limit. On the basis of the lifespan entropy generation concept, this study suggests that an intermittent fasting diet, which means skipping some meals without increasing the calories uptake in the other courses, may increase longevity. More than 1.32 million people died in 2017 because of chronic liver diseases, and a quarter of the world's population has non-alcoholic fatty liver disease. There are no specific dietary guidelines available for the treatment of non-alcoholic fatty liver diseases but shifting to a healthier diet is recommended as the primary treatment. A healthy obese person may generate 119.9 kJ/kg K per year of entropy and generate a total of 4796 kJ/kg K entropy in the first 40 years of life. If obese persons continue to consume the same diet, they may have 94 years of life expectancy. After age 40, Child-Pugh Score A, B, and C NAFLD patients may generate 126.2, 149.9, and 272.5 kJ/kg K year of entropy and have 92, 84, and 64 years of life expectancy, respectively. If they were to make a major recommended shift in their diet, the life expectancy of Child-Pugh Score A, B, and C patients may increase by 29, 32, and 43 years, respectively.
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Affiliation(s)
- Melek Ece Öngel
- Department of Physiology, Faculty of Medicine, Yeditepe University, Kayısdagi, Atasehir, Istanbul 34755, Turkey
| | - Cennet Yildiz
- Department of Food Engineering, Yeditepe University, Kayısdagi, Atasehir, Istanbul 34755, Turkey
| | - Özge Başer
- Department of Physiology, Faculty of Medicine, Yeditepe University, Kayısdagi, Atasehir, Istanbul 34755, Turkey
| | - Bayram Yilmaz
- Department of Physiology, Faculty of Medicine, Yeditepe University, Kayısdagi, Atasehir, Istanbul 34755, Turkey
| | - Mustafa Özilgen
- Department of Food Engineering, Yeditepe University, Kayısdagi, Atasehir, Istanbul 34755, Turkey
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Musazadeh V, Karimi A, Malekahmadi M, Ahrabi SS, Dehghan P. Omega-3 polyunsaturated fatty acids in the treatment of non-alcoholic fatty liver disease: An umbrella systematic review and meta-analysis. Clin Exp Pharmacol Physiol 2023; 50:327-334. [PMID: 36692292 DOI: 10.1111/1440-1681.13750] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 12/17/2022] [Accepted: 01/10/2023] [Indexed: 01/25/2023]
Abstract
There has been conflicting evidence from meta-analyses on the effect of polyunsaturated fatty acids (PUFA) on non-alcoholic fatty liver disease (NAFLD). Therefore, in this umbrella meta-analysis, we are evaluating whether omega-3 PUFA supplementation has any benefit in treating NAFLD. Electronic databases such as PubMed, Web of Science, Scopus, Embase and Google Scholar were assessed to October 2022. This meta-analysis included all meta-analyses that examined the effect of PUFAs on liver fat and liver function tests [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT)]. Meta-analysis was conducted using a random effects model. Subgroup analyses and sensitivity analyses were also performed. In total, eight articles involving 6,561 participants met the eligibility criteria. Advantageous impacts PUFA supplementation were observed on ALT (ESWMD = -6.72 IU/L; 95% CI: -8.61, -4.84; p < 0.001, and ESSMD = -0.52 IU/L; 95% CI: -0.84, -0.20, p < 0.001), AST (ESWMD = -3.73 IU/L, 95% CI: -5.93, -1.53, p < 0.001, and ESSMD = -0.65 IU/L; 95% CI: -1.08, -0.22, p = 0.003), GGT levels (ESWMD = -4.20 IU/L, 95% CI: -6.85, -1.55, p = 0.002), and liver fat (ESWMD = -5.16; 95% CI: -8.49, -1.82, p < 0.001). Intervention with omega-3 PUFAs improves ALT, AST, GGT, and liver fat in patients with NAFLD. Thus, omega-3 PUFAs could be considered as a therapeutic option in the treatment of NAFLD.
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Affiliation(s)
- Vali Musazadeh
- Student Research Committee, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Arash Karimi
- Nutrition Research Center, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran.,Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mahsa Malekahmadi
- Nutrition Department, Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran
| | - Sana Sedgh Ahrabi
- Student Research Committee, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Parvin Dehghan
- Nutrition Research Center, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran
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12
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Li X, Shan K, Li C, Zhou G. Intermittent Protein Diets Alter Hepatic Lipid Accumulation by Changing Tryptophan Metabolism in a Fast-Response Manner. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:3261-3272. [PMID: 36634216 DOI: 10.1021/acs.jafc.2c06576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/17/2023]
Abstract
In modern life, the fluctuation of dietary protein levels is common, in particular, for low-income populations. However, its effect on human health is little known. Alternating changes of low and high casein or pork protein were used to simulate the fluctuation of dietary protein content in mice. Hepatic lipid accumulation showed a fast response to alternating changes of low- and high-protein diets. Correspondingly, some gut microbiota and tryptophan metabolite composition also showed a fast response to dietary protein changes. The fast response of 3-hydroxykynurenine (3-HK) was proven to inhibit hepatic lipid accumulation in vitro. Therefore, intermittent protein diets modulated hepatic lipid accumulation through 3-HK. These findings highlighted the sensitivity of hepatic lipid accumulation to dietary protein levels.
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Affiliation(s)
- Xiaohui Li
- Key Laboratory of Meat Processing and Quality Control, Ministry of Education; Key Laboratory of Meat Processing, Ministry of Agriculture and Rural Affairs; Jiangsu Synergistic Innovation Center of Meat Processing and Quality Control, College of Food Science and Technology, Nanjing Agricultural University, 210095Nanjing, P. R. China
| | - Kai Shan
- Key Laboratory of Meat Processing and Quality Control, Ministry of Education; Key Laboratory of Meat Processing, Ministry of Agriculture and Rural Affairs; Jiangsu Synergistic Innovation Center of Meat Processing and Quality Control, College of Food Science and Technology, Nanjing Agricultural University, 210095Nanjing, P. R. China
| | - Chunbao Li
- Key Laboratory of Meat Processing and Quality Control, Ministry of Education; Key Laboratory of Meat Processing, Ministry of Agriculture and Rural Affairs; Jiangsu Synergistic Innovation Center of Meat Processing and Quality Control, College of Food Science and Technology, Nanjing Agricultural University, 210095Nanjing, P. R. China
| | - Guanghong Zhou
- Key Laboratory of Meat Processing and Quality Control, Ministry of Education; Key Laboratory of Meat Processing, Ministry of Agriculture and Rural Affairs; Jiangsu Synergistic Innovation Center of Meat Processing and Quality Control, College of Food Science and Technology, Nanjing Agricultural University, 210095Nanjing, P. R. China
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13
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Wang Y, Ma P, Wang Z, Sun M, Hou B, Xu T, Li W, Yang X, Du G, Ji T, Qiang G. Uncovering the effect and mechanism of Panax notoginseng saponins on metabolic syndrome by network pharmacology strategy. JOURNAL OF ETHNOPHARMACOLOGY 2023; 300:115680. [PMID: 36058479 DOI: 10.1016/j.jep.2022.115680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 08/14/2022] [Accepted: 08/25/2022] [Indexed: 06/15/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Metabolic syndrome (MetS) is a cluster of disease centered on obesity, which is the result of stagnation of liver qi according to traditional Chinese medicine. Panax notoginseng is a traditional Chinese herbal medicine, entering liver and stomach meridians and dissipating blood stasis, in which panax notoginseng saponins (PNS) are the main active components. However, its effects and mechanism on metabolic syndrome has not been revealed yet. AIM OF STUDY To evaluate the anti-MetS effect of PNS, including body weight and adiposity, glucose metabolism and non-alcoholic fatty liver disease (NAFLD), as well as to explore the mechanism and signaling pathway of PNS on MetS effect. MATERIALS AND METHODS HPLC was utilized to affirm the percentages of saponins in PNS. In vivo, normal C57BL/6J mice and high-fat diet (HFD)-induced MetS mice were used to evaluate anti-MetS effect of PNS. Body weight, food and water intake were recorded. NMR imager was used for NMR imaging and lipid-water analysis. Blood glucose detection, glucose and insulin tolerance test were performed to evaluate glucose metabolism. Biochemical indexes analysis and histopathological staining were used to evaluate the effect on NAFLD. The expressions of mRNA and proteins related to thermogenesis in adipose tissue were determined using real-time PCR and Western blot. In silico, network pharmacology was utilized to predict potential mechanism. In vitro, matured 3T3-L1 adipocyte was used as subject to confirm the signaling pathway by Western blot. RESULTS We determined the content of PNS component by HPLC. In vivo, PNS could improve metabolic syndrome with weight loss, reduction of adiposity, improvement of adipose distribution, correction of glucose metabolism disorder and attenuation of NAFLD. Mechanismly, PNS boosted energy exhaustion and dramatically enhanced thermogenesis in brown adipose tissue (BAT), induced white adipose tissue (WAT) browning. In silico, utilizing network pharmacology strategy, we identified 307 candidate targets which were enriched in MAPK signaling pathway specifically in liver tissue and adipocyte. In vitro validation confirmed ERK and p38MAPK mediated anti-MetS effects of PNS, not JNK signaling pathway. CONCLUSION PNS exerted protective effect on metabolic syndrome through MAPK-mediated adipose thermogenic activation, which may serve as a prospective therapeutic drug for metabolic syndrome.
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Affiliation(s)
- Yisa Wang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and Beijing Key Laboratory of Drug Target and Screening Research, Beijing, 100050, China; College of Pharmacy, Harbin University of Commerce, Harbin, 150076, China
| | - Peng Ma
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and Beijing Key Laboratory of Drug Target and Screening Research, Beijing, 100050, China
| | - Zijing Wang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and Beijing Key Laboratory of Drug Target and Screening Research, Beijing, 100050, China
| | - Mingxia Sun
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China
| | - Biyu Hou
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and Beijing Key Laboratory of Drug Target and Screening Research, Beijing, 100050, China
| | - Tianshu Xu
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and Beijing Key Laboratory of Drug Target and Screening Research, Beijing, 100050, China
| | - Wenlan Li
- College of Pharmacy, Harbin University of Commerce, Harbin, 150076, China
| | - Xiuying Yang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and Beijing Key Laboratory of Drug Target and Screening Research, Beijing, 100050, China
| | - Guanhua Du
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and Beijing Key Laboratory of Drug Target and Screening Research, Beijing, 100050, China
| | - Tengfei Ji
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
| | - Guifen Qiang
- State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College and Beijing Key Laboratory of Drug Target and Screening Research, Beijing, 100050, China.
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14
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Alfadda NA, Aljuraiban GS, Awwad HM, Khaleel MS, Almaghamsi AM, Sherbeeni SM, Alqutub AN, Aldosary AS, Alfadda AA. Higher carbohydrate intake in relation to non-alcoholic fatty liver disease in patients with type 2 diabetes. Front Nutr 2022; 9:996004. [PMID: 36570126 PMCID: PMC9773196 DOI: 10.3389/fnut.2022.996004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Accepted: 11/14/2022] [Indexed: 12/13/2022] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is an overlooked complication of type 2 diabetes (T2D). Current recommendations for the management of NAFLD are mainly focused on weight reduction, overlooking the role of macronutrient composition. Although dietary carbohydrates play a major role in intrahepatic fat synthesis, their association with the progression of liver steatosis has not been fully investigated in patients with T2D. Aim To investigate the association between higher carbohydrate intake and the presence of liver steatosis in patients with T2D. Methods This cross-sectional study included men and women aged 18-60 years diagnosed with T2D. Anthropometric measurements, hepatic steatosis assessment using the controlled attenuation parameter (CAP), blood samples, and dietary data were analyzed. Participants were divided into two groups: NAFLD and NAFLD-free. A two-sample t-test was used to evaluate the differences between the two groups. Stepwise multiple linear regression models adjusted for potential confounders were used to determine the association between CAP values and higher carbohydrate intake. Results In total, 358 participants were included. NAFLD was present in 79.3% of the participants. Body mass index, waist circumference, ALT, HbA1c, and triglycerides showed direct, while HDL-Cholesterol revealed inverse associations with CAP values. No significant relationship was found between carbohydrate intake and steatosis in the total study sample; however, multiple linear regression analysis revealed a significant relationship between carbohydrate intake and CAP values in patients aged ≤50 years. Conclusion In patients with T2D, higher carbohydrate intake was associated with liver steatosis in those aged 50 years and below. Further studies are required to confirm the causality between carbohydrate intake and liver steatosis.
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Affiliation(s)
- Nora A. Alfadda
- Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Ghadeer S. Aljuraiban
- Department of Community Health Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
| | - Hadeel M. Awwad
- Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Mohammad S. Khaleel
- Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | | | | | - Adel N. Alqutub
- Department of Gastroenterology and Hepatology, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Abdullah S. Aldosary
- Department of Medical Imaging Administration, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Assim A. Alfadda
- Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia,Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia,*Correspondence: Assim A. Alfadda,
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15
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Wang M, Han H, Wan F, Zhong R, Do YJ, Oh SI, Lu X, Liu L, Yi B, Zhang H. Dihydroquercetin Supplementation Improved Hepatic Lipid Dysmetabolism Mediated by Gut Microbiota in High-Fat Diet (HFD)-Fed Mice. Nutrients 2022; 14:nu14245214. [PMID: 36558373 PMCID: PMC9788101 DOI: 10.3390/nu14245214] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 11/24/2022] [Accepted: 12/03/2022] [Indexed: 12/12/2022] Open
Abstract
Dihydroquercetin (DHQ) is a natural flavonoid with multiple bioactivities, including hepatoprotective effects. This study aimed to investigate whether DHQ improved lipid dysmetabolism in the body, especially in the liver, and whether there is a relationship between hepatic metabolism and altered gut flora in high-fat diet (HFD)-induced mice. HFD-induced mice were given 50 mg/kg body weight DHQ intragastrically for 10 weeks. The data showed that DHQ reduced body weight, the weight of the liver and white adipose tissue as well as serum leptin, LPS, triglyceride and cholesterol levels. RNA-seq results indicated that DHQ down-regulated lipogenesis-related genes and up-regulated fatty acid oxidation-related genes, including MOGAT1 and CPT1A. Furthermore, DHQ had a tendency to decrease hepatic cholesterol contents by reducing the mRNA levels of cholesterol synthesis genes such as FDPS and HMGCS1. 16S rRNA sequencing analysis indicated that DHQ significantly decreased the richness of Lactococcus, Lachnoclostridium, and Eubacterium_xylanophilum_group. Correlation analysis further demonstrated that these bacteria, Lactococcus and Eubacterium_xylanophilum_group in particular, had significantly positive correlation with lipid and cholesterol synthesis genes, and negative correlation with fatty acid oxidation genes. In conclusion, DHQ could improve hepatic lipid dysmetabolism potentially by improved gut microbial community, which may be used as an intervention strategy in hepatic metabolism diseases.
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Affiliation(s)
- Mengyu Wang
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Hui Han
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Fan Wan
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Affairs, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou 730020, China
| | - Ruqing Zhong
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Yoon Jung Do
- Division of Animal Disease & Health, National Institute of Animal Science, Rural Development Administration, Wanju 55365, Republic of Korea
| | - Sang-Ik Oh
- Division of Animal Disease & Health, National Institute of Animal Science, Rural Development Administration, Wanju 55365, Republic of Korea
| | - Xuemeng Lu
- Division of Animal Disease & Health, National Institute of Animal Science, Rural Development Administration, Wanju 55365, Republic of Korea
| | - Lei Liu
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
| | - Bao Yi
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
- Correspondence: ; Tel.: +86-010-62816013
| | - Hongfu Zhang
- State Key Laboratory of Animal Nutrition, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, China
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Varghese DS, Alawathugoda TT, Sheikh MA, Challagandla AK, Emerald BS, Ansari SA. Developmental modeling of hepatogenesis using obese iPSCs-hepatocyte differentiation uncovers pathological features. Cell Death Dis 2022; 13:670. [PMID: 35915082 PMCID: PMC9343434 DOI: 10.1038/s41419-022-05125-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Revised: 07/20/2022] [Accepted: 07/21/2022] [Indexed: 01/21/2023]
Abstract
Obesity is a multigene disorder. However, in addition to genetic factors, environmental determinants also participate in developing obesity and related pathologies. Thus, obesity could be best described as a combination of genetic and environmental perturbations often having its origin during the early developmental period. Environmental factors such as energy-dense food and sedentary lifestyle are known to be associated with obesogenicity. However, the combinatorial effects of gene-environment interactions are not well understood. Understanding the role of multiple genetic variations leading to subtle gene expression changes is not practically possible in monogenic or high-fat-fed animal models of obesity. In contrast, human induced pluripotent stem cells (hiPSCs) from individuals with familial obesity or an obesogenic genotype could serve as a good model system. Herein, we have used hiPSCs generated from normal and genetically obese subjects and differentiated them into hepatocytes in cell culture. We show that hepatocytes from obese iPSCs store more lipids and show increased cell death than normal iPSCs. Whole transcriptome analyses in both normal and obese iPSCs treated with palmitate compared to control revealed LXR-RXR and hepatic fibrosis pathways were enriched among other pathways in obese iPSCs compared to normal iPSCs. Among other genes, increased CD36 and CAV1 expression and decreased expression of CES1 in obese iPSCs could have been responsible for excess lipid accumulation, resulting in differential expression of genes associated with hepatic fibrosis, a key feature of non-alcoholic fatty liver disease (NAFLD). Our results demonstrate that iPSCs derived from genetically obese subjects could serve as an excellent model to understand the effects of this multigene disorder on organ development and may uncover pathologies of NAFLD, which is highly associated with obesity.
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Affiliation(s)
- Divya Saro Varghese
- grid.43519.3a0000 0001 2193 6666Department of Biochemistry and Molecular Biology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, United Arab Emirates
| | - Thilina T. Alawathugoda
- grid.43519.3a0000 0001 2193 6666Department of Biochemistry and Molecular Biology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, United Arab Emirates
| | - Muhammad Abid Sheikh
- grid.43519.3a0000 0001 2193 6666Department of Biochemistry and Molecular Biology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, United Arab Emirates
| | - Anil Kumar Challagandla
- grid.43519.3a0000 0001 2193 6666Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, United Arab Emirates
| | - Bright Starling Emerald
- grid.43519.3a0000 0001 2193 6666Department of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, United Arab Emirates ,grid.43519.3a0000 0001 2193 6666Zayed Center for Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi UAE
| | - Suraiya A. Ansari
- grid.43519.3a0000 0001 2193 6666Department of Biochemistry and Molecular Biology, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, United Arab Emirates ,grid.43519.3a0000 0001 2193 6666Zayed Center for Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi UAE
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Takahashi F, Hashimoto Y, Kaji A, Sakai R, Kawate Y, Okamura T, Kitagawa N, Okada H, Nakanishi N, Majima S, Osaka T, Senmaru T, Ushigome E, Hamaguchi M, Fukui M. The Association of Salt Intake and Non-alcoholic Fatty Liver Disease in People With Type 2 Diabetes: A Cross-Sectional Study. Front Nutr 2022; 9:943790. [PMID: 35911124 PMCID: PMC9326474 DOI: 10.3389/fnut.2022.943790] [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: 05/14/2022] [Accepted: 06/23/2022] [Indexed: 11/21/2022] Open
Abstract
Objectives Non-alcoholic fatty liver disease (NAFLD), which has a close relationship with type 2 diabetes (T2D), is related to salt intake in the general population. In contrast, the relationship between salt intake and the presence of NAFLD in patients with T2D has not been clarified. Methods Salt intake (g/day) was assessed using urinary sodium excretion, and a high salt intake was defined as an intake greater than the median amount of 9.5 g/day. Hepatic steatosis index (HSI) ≥ 36 points was used to diagnosed NAFLD. Odds ratios of high salt intake to the presence of NAFLD were evaluated by logistic regression analysis. Results The frequency of NAFLD was 36.5% in 310 patients with T2D (66.7 ± 10.7 years old and 148 men). The patients with high salt intake had a higher body mass index (25.0 ± 4.0 vs. 23.4 ± 3.8 kg/m2, p < 0.001) than those with low salt intake. HSI in patients with high salt intake was higher than that in patients with low salt intake (36.2 ± 6.2 vs. 34.3 ± 5.5 points, p = 0.005). In addition, the presence of NALFD in patients with high salt intake was higher than that in patients with low salt intake (44.5% vs. 28.4%, p = 0.005). High salt intake was associated with the prevalence of NAFLD [adjusted odds ratio, 1.76 (95% confidence interval: 1.02–3.03), p = 0.043]. Conclusion This cross-sectional study revealed that salt intake is related to the prevalence of NAFLD in patients with T2D.
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Affiliation(s)
- Fuyuko Takahashi
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yoshitaka Hashimoto
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department of Diabetes and Endocrinology, Matsushita Memorial Hospital, Moriguchi, Japan
- *Correspondence: Yoshitaka Hashimoto
| | - Ayumi Kaji
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Ryosuke Sakai
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yuka Kawate
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takuro Okamura
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Noriyuki Kitagawa
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department of Diabetology, Kameoka Municipal Hospital, Kameoka, Japan
| | - Hiroshi Okada
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Naoko Nakanishi
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Saori Majima
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takafumi Osaka
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takafumi Senmaru
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Emi Ushigome
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Masahide Hamaguchi
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Michiaki Fukui
- Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Birla M, Choudhary C, Singh G, Gupta S, Bhawana, Vavilala P. The Advent of Nutrigenomics: A Narrative Review with an Emphasis on Psychological Disorders. Prev Nutr Food Sci 2022; 27:150-164. [PMID: 35919568 PMCID: PMC9309077 DOI: 10.3746/pnf.2022.27.2.150] [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: 01/27/2022] [Revised: 05/06/2022] [Accepted: 05/26/2022] [Indexed: 11/06/2022] Open
Abstract
A new research field is emerging that combines nutrition and genetics at the molecular level, namely nutrigenomics. Several aspects of nutrigenomics are examined in this review, with a particular focus on psychological disorders. The origin of this field in the 20th century and its modern developments have been investigated. Various studies have reported the impact of genetic factors and diet on various chronic disorders, elucidating how the deficiency of several macronutrients results in significant ailments, including diabetes, cancer, cardiovascular disorders, and others. Furthermore, the application of nutrigenomics to diet and its impact on the global disease rate and quality of life have been discussed. The relationship between diet and gene expression can facilitate the classification of diet-gene interactions and the diagnosis of polymorphisms and anomalies. Numerous databases and research tools for the study of nutrigenomics are essential to the medical application of this field. The nutrition-gene interrelationships can be utilized to study brain development, impairment, and diseases, which could be a significant medical breakthrough. It has also been observed that psychological conditions are exacerbated by the interaction between gut microbes and the prevalence of malnutrition. This article focuses on the impact of nutrition on genes involved in various psychological disorders and the potential application of nutrigenomics as a revolutionary treatment method.
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Affiliation(s)
- Meghna Birla
- Shaheed Rajguru College of Applied Sciences for Women, University of Delhi, New Delhi 110096, India
| | - Chanchal Choudhary
- Shaheed Rajguru College of Applied Sciences for Women, University of Delhi, New Delhi 110096, India
| | - Garima Singh
- Shaheed Rajguru College of Applied Sciences for Women, University of Delhi, New Delhi 110096, India
| | - Salvi Gupta
- Shaheed Rajguru College of Applied Sciences for Women, University of Delhi, New Delhi 110096, India
| | - Bhawana
- Shaheed Rajguru College of Applied Sciences for Women, University of Delhi, New Delhi 110096, India
| | - Pratyusha Vavilala
- Shaheed Rajguru College of Applied Sciences for Women, University of Delhi, New Delhi 110096, India
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Sayegh NF, Heraoui GNHA, Younes H, Sayegh LN, Boulos C, Sayegh R. Relation of Dietary Patterns and Nutritional Profile to Hepatic Fibrosis in a Sample of Lebanese Non-Alcoholic Fatty Liver Disease Patients. Nutrients 2022; 14:nu14122554. [PMID: 35745284 PMCID: PMC9229197 DOI: 10.3390/nu14122554] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 06/15/2022] [Accepted: 06/17/2022] [Indexed: 11/16/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver injury worldwide. NAFLD can evolve into non-alcoholic steatohepatitis (NASH) with or without fibrosis. The objectives of this study were to determine the nutritional profile and dietary patterns of NAFLD Lebanese patients and to report the type of diet-related to the presence of hepatic fibrosis. We hypothesized that the traditional pattern was related to a low risk of fibrosis. This cross-sectional study included 320 eligible Lebanese NAFLD patients. Three dietary patterns were identified: the Traditional diet, the High Fruit diet, and the Westernized diet. Multivariate analysis showed a significant relationship between high adherence to the traditional diet and absence of hepatic fibrosis with a decreased risk of 82%, p = 0.031 after adjusting for its covariables. Fruits were absent from this dietary pattern. Although our results pointed to a possible relationship between fibrosis in NAFLD patients and fruit intake, experimental studies are needed to show whether this is a causal relationship. However, the results obtained in this study may contribute to the planning of dietary interventions and recommendations and enable a better follow-up for NAFLD patients with fibrosis.
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Affiliation(s)
- Nicole Fakhoury Sayegh
- Department of Nutrition, Faculty of Pharmacy, Saint Joseph University, Damascus Road, Riad el Solh, Beirut P.O. Box 11-5076, Lebanon; (G.N.H.A.H.); (C.B.)
- Correspondence: or
| | - Gessica N. H. A. Heraoui
- Department of Nutrition, Faculty of Pharmacy, Saint Joseph University, Damascus Road, Riad el Solh, Beirut P.O. Box 11-5076, Lebanon; (G.N.H.A.H.); (C.B.)
| | - Hassan Younes
- College Health, équipe PANASH-ULR 7519, Institut Polytechnique UniLaSalle, 19, Rue Pierre Waguet, CEDEX, 60026 Beauvais, France;
| | - Lea Nicole Sayegh
- Faculty of Medicine, American University of Beirut, Beirut P.O. Box 11-0236, Lebanon;
| | - Christa Boulos
- Department of Nutrition, Faculty of Pharmacy, Saint Joseph University, Damascus Road, Riad el Solh, Beirut P.O. Box 11-5076, Lebanon; (G.N.H.A.H.); (C.B.)
| | - Raymond Sayegh
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Saint Joseph University, Damascus Road, Riad el Solh, Beirut P.O. Box 11-5076, Lebanon;
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20
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Yu H, Yi X, Gao X, Ji J, Liu Z, Xia G, Li C, Zhang X, Shen X. Tilapia-Head Chondroitin Sulfate Protects against Nonalcoholic Fatty Liver Disease via Modulating the Gut-Liver Axis in High-Fat-Diet-Fed C57BL/6 Mice. Foods 2022; 11:foods11070922. [PMID: 35407014 PMCID: PMC8997817 DOI: 10.3390/foods11070922] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 03/15/2022] [Accepted: 03/18/2022] [Indexed: 12/12/2022] Open
Abstract
We isolated and characterized tilapia-head chondroitin sulfate (TH-CS) and explored its biological activity and mechanisms of action as an oral supplement for nonalcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in mice. The results showed that treatment with TH-CS for 8 weeks alleviated the development of NAFLD, as evidenced by the notable improvement in liver damage, blood lipid accumulation and insulin resistance (IR). Meanwhile, TH-CS treatment reduced the expression of proinflammatory cytokines and normalized oxidative stress. Additionally, the analysis of 16S rDNA sequencing revealed that TH-CS could restore gut microbiota balance and increase the relative abundance of short-chain fatty acid (SCFA)-producing bacteria. Furthermore, SCFAs produced by related bacteria can further improve lipid metabolism and IR by regulating lipid synthesis signals. In conclusion, TH-CS is an effective dietary supplement for the prevention of NAFLD, and may serve as a potential supplementary treatment for lipid-related metabolic syndrome.
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Affiliation(s)
- Hui Yu
- Hainan Engineering Research Center of Aquatic Resources Efficient Utilization in South China Sea, Hainan University, Haikou 570228, China; (H.Y.); (X.Y.); (X.G.); (J.J.); (Z.L.); (G.X.); (C.L.); (X.Z.)
- College of Food Science and Technology, Hainan University, Haikou 570228, China
| | - Xiangzhou Yi
- Hainan Engineering Research Center of Aquatic Resources Efficient Utilization in South China Sea, Hainan University, Haikou 570228, China; (H.Y.); (X.Y.); (X.G.); (J.J.); (Z.L.); (G.X.); (C.L.); (X.Z.)
- College of Food Science and Technology, Hainan University, Haikou 570228, China
| | - Xia Gao
- Hainan Engineering Research Center of Aquatic Resources Efficient Utilization in South China Sea, Hainan University, Haikou 570228, China; (H.Y.); (X.Y.); (X.G.); (J.J.); (Z.L.); (G.X.); (C.L.); (X.Z.)
- College of Food Science and Technology, Hainan University, Haikou 570228, China
| | - Jun Ji
- Hainan Engineering Research Center of Aquatic Resources Efficient Utilization in South China Sea, Hainan University, Haikou 570228, China; (H.Y.); (X.Y.); (X.G.); (J.J.); (Z.L.); (G.X.); (C.L.); (X.Z.)
- College of Food Science and Technology, Hainan University, Haikou 570228, China
| | - Zhongyuan Liu
- Hainan Engineering Research Center of Aquatic Resources Efficient Utilization in South China Sea, Hainan University, Haikou 570228, China; (H.Y.); (X.Y.); (X.G.); (J.J.); (Z.L.); (G.X.); (C.L.); (X.Z.)
- College of Food Science and Technology, Hainan University, Haikou 570228, China
- Collaborative Innovation Center of Marine Food Deep Processing, Dalian Polytechnic University, Dalian 116000, China
| | - Guanghua Xia
- Hainan Engineering Research Center of Aquatic Resources Efficient Utilization in South China Sea, Hainan University, Haikou 570228, China; (H.Y.); (X.Y.); (X.G.); (J.J.); (Z.L.); (G.X.); (C.L.); (X.Z.)
- College of Food Science and Technology, Hainan University, Haikou 570228, China
- Collaborative Innovation Center of Marine Food Deep Processing, Dalian Polytechnic University, Dalian 116000, China
| | - Chuan Li
- Hainan Engineering Research Center of Aquatic Resources Efficient Utilization in South China Sea, Hainan University, Haikou 570228, China; (H.Y.); (X.Y.); (X.G.); (J.J.); (Z.L.); (G.X.); (C.L.); (X.Z.)
- College of Food Science and Technology, Hainan University, Haikou 570228, China
- Collaborative Innovation Center of Marine Food Deep Processing, Dalian Polytechnic University, Dalian 116000, China
| | - Xueying Zhang
- Hainan Engineering Research Center of Aquatic Resources Efficient Utilization in South China Sea, Hainan University, Haikou 570228, China; (H.Y.); (X.Y.); (X.G.); (J.J.); (Z.L.); (G.X.); (C.L.); (X.Z.)
- College of Food Science and Technology, Hainan University, Haikou 570228, China
- Collaborative Innovation Center of Marine Food Deep Processing, Dalian Polytechnic University, Dalian 116000, China
| | - Xuanri Shen
- Hainan Engineering Research Center of Aquatic Resources Efficient Utilization in South China Sea, Hainan University, Haikou 570228, China; (H.Y.); (X.Y.); (X.G.); (J.J.); (Z.L.); (G.X.); (C.L.); (X.Z.)
- College of Food Science and Technology, Hainan University, Haikou 570228, China
- Collaborative Innovation Center of Marine Food Deep Processing, Dalian Polytechnic University, Dalian 116000, China
- Correspondence: ; Tel./Fax: +86-0898-6619-3581
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21
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Yang M, Song XQ, Han M, Liu H. The role of Resolvin D1 in liver diseases. Prostaglandins Other Lipid Mediat 2022; 160:106634. [PMID: 35292355 DOI: 10.1016/j.prostaglandins.2022.106634] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Revised: 03/03/2022] [Accepted: 03/09/2022] [Indexed: 02/06/2023]
Abstract
The liver is a parenchymatous organ closely related to immunity, detoxification and metabolism of the three major nutrients. The inflammatory response is a protective mechanism of the body to eliminate harmful stimuli. However, continuous inflammatory stimulation leads to occurrence of many liver diseases and brings great social burden. Resolvin D1, a member of the specialized pro-resolving lipid mediators family, exerts anti-inflammatory, anti-oxidant stress, anti-fibrosis, anti-apoptotic, and anti-tumor effects by binding to ALX/FPR2 or GPR32. RvD1 plays an important role and has great therapeutic potential in liver diseases, which has been validated in multiple models of preclinical disease. This review will provide a detailed summary of the role of RvD1 in different liver diseases, including acute liver injury, liver ischemia/reperfusion injury, non-alcoholic fatty liver disease, liver fibrosis, and liver cancer, so as to help people have a more comprehensive understanding of RvD1 and promote its further research.
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Affiliation(s)
- Mei Yang
- Department of Gastroenterology, Second Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Xian-Qi Song
- Department of Gastroenterology, Second Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Mei Han
- Department of Gastroenterology, Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
| | - Hui Liu
- Department of Gastroenterology, Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
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22
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Liu H, Guan H, Tan X, Jiang Y, Li F, Sun-Waterhouse D, Li D. Enhanced alleviation of insulin resistance via the IRS-1/Akt/FOXO1 pathway by combining quercetin and EGCG and involving miR-27a-3p and miR-96-5p. Free Radic Biol Med 2022; 181:105-117. [PMID: 35124182 DOI: 10.1016/j.freeradbiomed.2022.02.002] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 01/29/2022] [Accepted: 02/02/2022] [Indexed: 12/22/2022]
Abstract
Quercetin and EGCG exhibit anti-diabetic and anti-obesity activities, however, their interactive effects in anti-diabetic/anti-obesity actions and underlying mechanisms remain unclear. This study aimed to fill these knowledge gaps. Quercetin, EGCG or their combination attenuated insulin resistance and decreased hepatic gluconeogenesis in high-fat-high-fructose diet (HFFD)-fed C57BL/6 mice and in palmitic acid (PA)-treated HepG2 cells. In mice, supplementation with quercetin (0.05%w/w), EGCG (0.05%w/w) and their combination (quercetin 0.05%+EGCG 0.05%w/w) reduced weight gain and fasting blood glucose and improved serum biochemical parameters. Compare with quercetin/EGCG alone, the quercetin-EGCG combination reduced gluconeogenesis to a greater extent via IRS-1/Akt/FOXO1-mediated down-regulation of downstream PEPCK and G-6-pase. In HepG2 cells, the quercetin (5 μM)-EGCG (5 μM) co-treatment exerted greater suppression on PA-induced changes in glucose and glycogen contents and hexokinase and G-6-pase activities than quercetin/EGCG alone (each 10 μM). The quercetin-EGCG co-treatment reduced glucose production through targeting FOXO1 and inhibiting the transcription of gluconeogenic enzymes. MiR-27a-3p and miR-96-5p regulated directly FOXO1 expression and function, and co-inhibition of miR-27a-3p and miR-96-5p weakened greatly the protective effect of quercetin-EGCG combination. This is the first report on the contributions of miR-27a-3p and miR-96-5p to the synergistic and protective effect of the quercetin-EGCG co-treatment against PA-induced insulin resistance through inhibiting FOXO1 expression.
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Affiliation(s)
- Hui Liu
- College of Food Science and Engineering, Shandong Agricultural University, Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, Taian, 271018, PR China
| | - Hui Guan
- College of Food Science and Engineering, Shandong Agricultural University, Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, Taian, 271018, PR China
| | - Xintong Tan
- College of Food Science and Engineering, Shandong Agricultural University, Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, Taian, 271018, PR China
| | - Yang Jiang
- College of Food Science and Engineering, Shandong Agricultural University, Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, Taian, 271018, PR China.
| | - Feng Li
- College of Food Science and Engineering, Shandong Agricultural University, Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, Taian, 271018, PR China
| | - Dongxiao Sun-Waterhouse
- College of Food Science and Engineering, Shandong Agricultural University, Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, Taian, 271018, PR China; School of Chemical Sciences, The University of Auckland, New Zealand
| | - Dapeng Li
- College of Food Science and Engineering, Shandong Agricultural University, Key Laboratory of Food Processing Technology and Quality Control of Shandong Higher Education Institutes, Taian, 271018, PR China.
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23
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Lampignano L, Donghia R, Sila A, Bortone I, Tatoli R, De Nucci S, Castellana F, Zupo R, Tirelli S, Giannoccaro V, Guerra V, Panza F, Lozupone M, Mastronardi M, De Pergola G, Giannelli G, Sardone R. Mediterranean Diet and Fatty Liver Risk in a Population of Overweight Older Italians: A Propensity Score-Matched Case-Cohort Study. Nutrients 2022; 14:nu14020258. [PMID: 35057439 PMCID: PMC8779579 DOI: 10.3390/nu14020258] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 12/31/2021] [Accepted: 01/05/2022] [Indexed: 12/21/2022] Open
Abstract
Hepatic steatosis, often known as fatty liver, is the most common hepatic disease in Western countries. The latest guidelines for the treatment of nonalcoholic fatty liver disease emphasize lifestyle measures, such as changing unhealthy eating patterns. Using a propensity score-matching approach, this study investigated the effect of adhering to a Mediterranean diet (MedDiet) on fatty liver risk in an older population (≥65 years) from Southern Italy. We recruited 1.403 subjects (53.6% men, ≥65 years) who completed a food frequency questionnaire (FFQ) and underwent clinical assessment between 2015 and 2018. For the assessment of the liver fat content, we applied the Fatty Liver Index (FLI). To evaluate the treatment effect of the MedDiet, propensity score matching was performed on patients with and without FLI > 60. After propensity score-matching with the MedDiet pattern as treatment, we found a higher consumption of red meat (p = 0.04) and wine (p = 0.04) in subjects with FLI > 60. Based on the FLI, the inverse association shown between adherence to the MedDiet and the risk of hepatic steatosis shows that the MedDiet can help to prevent hepatic steatosis. Consuming less red and processed meat, as well as alcoholic beverages, may be part of these healthy lifestyle recommendations.
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Affiliation(s)
- Luisa Lampignano
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (L.L.); (R.D.); (A.S.); (I.B.); (R.T.); (S.D.N.); (F.C.); (R.Z.); (S.T.); (V.G.)
| | - Rossella Donghia
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (L.L.); (R.D.); (A.S.); (I.B.); (R.T.); (S.D.N.); (F.C.); (R.Z.); (S.T.); (V.G.)
| | - Annamaria Sila
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (L.L.); (R.D.); (A.S.); (I.B.); (R.T.); (S.D.N.); (F.C.); (R.Z.); (S.T.); (V.G.)
| | - Ilaria Bortone
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (L.L.); (R.D.); (A.S.); (I.B.); (R.T.); (S.D.N.); (F.C.); (R.Z.); (S.T.); (V.G.)
| | - Rossella Tatoli
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (L.L.); (R.D.); (A.S.); (I.B.); (R.T.); (S.D.N.); (F.C.); (R.Z.); (S.T.); (V.G.)
| | - Sara De Nucci
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (L.L.); (R.D.); (A.S.); (I.B.); (R.T.); (S.D.N.); (F.C.); (R.Z.); (S.T.); (V.G.)
| | - Fabio Castellana
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (L.L.); (R.D.); (A.S.); (I.B.); (R.T.); (S.D.N.); (F.C.); (R.Z.); (S.T.); (V.G.)
| | - Roberta Zupo
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (L.L.); (R.D.); (A.S.); (I.B.); (R.T.); (S.D.N.); (F.C.); (R.Z.); (S.T.); (V.G.)
| | - Sarah Tirelli
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (L.L.); (R.D.); (A.S.); (I.B.); (R.T.); (S.D.N.); (F.C.); (R.Z.); (S.T.); (V.G.)
| | | | - Vito Guerra
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (L.L.); (R.D.); (A.S.); (I.B.); (R.T.); (S.D.N.); (F.C.); (R.Z.); (S.T.); (V.G.)
| | - Francesco Panza
- Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, 11, 70125 Bari, Italy; (F.P.); (M.L.)
| | - Madia Lozupone
- Neurodegenerative Disease Unit, Department of Basic Medicine, Neuroscience, and Sense Organs, University of Bari Aldo Moro, 11, 70125 Bari, Italy; (F.P.); (M.L.)
| | - Mauro Mastronardi
- Inflammatory Bowel Disease Unit, National Institute of Gastroenterology, “Saverio De Bellis” Research Hospital, 70013 Bari, Italy;
| | - Giovanni De Pergola
- Unit of Geriatrics and Internal Medicine, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy;
| | - Gianluigi Giannelli
- Scientific Direction, National Institute of Gastroenterology, “Saverio De Bellis” Research Hospital, 70013 Bari, Italy;
| | - Rodolfo Sardone
- Unit of Data Sciences and Technology Innovation for Population Health, National Institute of Gastroenterology “Saverio de Bellis”, Research Hospital, 70013 Bari, Italy; (L.L.); (R.D.); (A.S.); (I.B.); (R.T.); (S.D.N.); (F.C.); (R.Z.); (S.T.); (V.G.)
- Correspondence:
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24
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The interplay between non-alcoholic fatty liver disease and innate immunity in hepatitis B virus patients. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00084-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is the most epidemic liver disorder worldwide as a result of rapid lifestyle transformation over the past few decades and is expected to elevate in the next few years as well as it is ranging from plain hepatic steatosis via non-alcoholic steatohepatitis (NASH) to liver cirrhosis and hepatocellular carcinoma (HCC).
Main text
NAFLD can also stimulate the diseases progression as diabetes and cardiovascular. Therefore, understanding the NAFLD pathogenesis is of vital clinical interest additionally is a crucial for disease treatment and prevention. After analyzing NAFLD and liver diseases prevalence, it has been a belief regarding the interaction between NAFLD and chronic hepatitis B (CHB).
Conclusion
The liver is an essential innate immune organ with large numbers of innate immune cells that contribute in NAFLD pathogenesis, additionally play the influential role that control NAFLD progression in the hepatitis B patients. Here, we summarized the recent advances in understanding and managing the NAFLD patients with chronic hepatitis B infection and interplay with innate immunity.
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25
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Masetto Antunes M, Godoy G, Curi R, Vergílio Visentainer J, Barbosa Bazotte R. The Myristic Acid:Docosahexaenoic Acid Ratio Versus the n-6 Polyunsaturated Fatty Acid:n-3 Polyunsaturated Fatty Acid Ratio as Nonalcoholic Fatty Liver Disease Biomarkers. Metab Syndr Relat Disord 2021; 20:69-78. [PMID: 34813379 DOI: 10.1089/met.2021.0107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
It is well established that diets containing an increased omega-6 polyunsaturated fatty acid (n-6 PUFA) to omega-3 polyunsaturated fatty acid (n-3 PUFA) ratios are linked to inflammation and chronic diseases such as nonalcoholic fatty liver disease (NAFLD). However, the influence of an elevated n-6 PUFA:n-3 PUFA ratio in the tissues requires clarification. Herein, we identified primary experimental and clinical studies where it is possible to compare the performance of the myristic acid (Myr):docosahexaenoic acid (DHA) and n-6 PUFA:n-3 PUFA ratios in the liver and/or serum as potential NAFLD biomarkers. Articles were included if quantitative values of n-6 PUFA, n-3 PUFA, Myr, DHA, and information about liver inflammation or liver disease progression parameters were provided. Overall, most experimental (91.6%) and clinical studies (87.5%) reported higher Myr:DHA ratios associated with inflammation and/or NAFLD progression than the n-6 PUFA:n-3 PUFA ratio. We conclude that the Myr:DHA ratio represents a better biomarker of NAFLD than the n-6 PUFA:n-3 PUFA ratio. Future studies are necessary for verifying this observation.
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Affiliation(s)
- Marina Masetto Antunes
- Post-Graduation Program in Pharmaceutical Sciences, State University of Maringá, Maringá, Brazil
| | - Guilherme Godoy
- Post-Graduation Program in Pharmaceutical Sciences, State University of Maringá, Maringá, Brazil
| | - Rui Curi
- Interdisciplinary Post-Graduate Program in Health Sciences, Cruzeiro do Sul University, São Paulo, Brazil
| | | | - Roberto Barbosa Bazotte
- Post-Graduation Program in Pharmaceutical Sciences, State University of Maringá, Maringá, Brazil.,Department of Pharmacology and Therapeutics, State University of Maringá, Maringá, Brazil
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Hepatic Glucose Metabolism and Its Disorders in Fish. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1354:207-236. [PMID: 34807444 DOI: 10.1007/978-3-030-85686-1_11] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Carbohydrate, which is the most abundant nutrient in plant-sourced feedstuffs, is an economically indispensable component in commercial compound feeds for fish. This nutrient can enhance the physical quality of diets and allow for pellet expansion during extrusion. There is compelling evidence that an excess dietary intake of starch causes hepatic disorders, thereby further reducing the overall food consumption and growth performance of fish species. Among the severe metabolic disturbances are glycogenic hepatopathy (hepatomegaly caused by the excessive accumulation of glycogen in hepatocytes) and hepatic steatosis (the accumulation of large vacuoles of triacylglycerols in hepatocytes). The development of those disorders is mainly due to the limited ability of fish to oxidize glucose and control blood glucose concentration. The prolonged elevations of blood glucose increase glucose intake by the liver, and excess glucose is stored either as glycogen through glycogenesis in hepatocytes or as triglycerides via lipogenesis in tissues, depending on the species. In some fish species (e.g., largemouth bass), the liver has a low ability to regulate glycolysis, gluconeogenesis, and glycogen breakdown in response to high starch intake. For most species of fish, the liver size increases with lipid or glycogen accumulation when they have a high starch intake. It is a challenge to develop the same set of diagnostic criteria for all fish species as their physiology or metabolic patterns differ. Although glycogenic hepatopathy appears to be a common disease in carnivorous fish, it has been under-recognized in many studies. As a result, understanding these diseases and their pathogeneses in different fish species is crucial for manufacturing cost-effective pellet diets to promote the health, growth, survival, and feed efficiency of fish in future.
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Mizgier M, Jarząbek-Bielecka G, Formanowicz D, Jodłowska-Siewert E, Mruczyk K, Cisek-Woźniak A, Kędzia W, Opydo-Szymaczek J. Dietary and Physical Activity Habits in Adolescent Girls with Polycystic Ovary Syndrome (PCOS)-HAstudy. J Clin Med 2021; 10:3469. [PMID: 34441766 PMCID: PMC8396824 DOI: 10.3390/jcm10163469] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2021] [Revised: 07/30/2021] [Accepted: 07/31/2021] [Indexed: 12/25/2022] Open
Abstract
The role of inappropriate lifestyle in the etiology of polycystic ovary syndrome (PCOS) and its metabolic and reproductive complications has attracted much attention in recent years; however, most studies involve adult patients. Thus, the study aimed to compare dietary patterns, physical activity, metabolic, anthropometric and inflammatory markers of 14-18-year-old girls with and without PCOS (n = 61 and n = 35, respectively) as well as to assess correlations between concentrations of metabolic and inflammatory markers and macronutrient intake and to identify the independent predictors of PCOS, related to diet and physical activity (PA). Compared to the control group, PCOS girls consumed significantly more total fat (p = 0.0005), including both saturated (SFA) (p = 0.03), monounsaturated (MUFA) (p = 0.0003) and polyunsaturated fatty acids (PUFA) (p = 0.01). A significantly higher percentage of PCOS patients consumed high and medium glycemic index (GI) foods (p = 0.03) and represented a low level of PA, both during school and in leisure time (41.67 vs. 6.06%; p = 0.0001 and 32.79 vs. 5.71%; p = 0.003, respectively). The PCOS group had also significantly higher waist circumference (WC), C-reactive protein (CRP) (p = 0.01), LDL cholesterol (p = 0.01), fasting insulin (p = 0.002) and HOMA-IR (p = 0.006) levels. There was an inverse correlation between fiber intake and fasting insulin, (p = 0.0002, r = -0.37), HOMA-IR (p = 0.0004, r = -0.35), WC (p = 0.029; r = -0.222) and a positive relationship between high and medium GI diet and insulin concentration (p = 0.003; r = 0.3). An increase of 10 g/day in total fat intake per day increases the probability of PCOS by 1.4 times. If the SFA or MUFA intakes increase by 10 g, the probability of PCOS increase 1.7-fold and 2.5-fold, respectively. The consumption of foods with a medium GI raises the probability of PCOS by more than 3 times, after adjusting for age. The odds ratio decreased for the moderate and high PA at school/work and in leisure time. Further research in girls with PCOS is needed to test whether low GI and dietary fatty acid reduction combined with increased PA is effective in the nonpharmacological treatment and prevention of PCOS complications. ClinicalTrial.gov Identifier: NCT04738409.
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Affiliation(s)
- Małgorzata Mizgier
- Department of Dietetics, Faculty of Physical Culture in Gorzów Wlkp., Poznan University of Physical Education, Estkowskiego 13, 66-400 Gorzów Wielkopolski, Poland; (K.M.); (A.C.-W.)
| | - Grażyna Jarząbek-Bielecka
- Department of Perinatology and Gynecology, Division of Developmental Gynecology and Sexology, Poznan University of Medical Sciences, 60-535 Poznan, Poland; (G.J.-B.); (W.K.)
| | - Dorota Formanowicz
- Chair and Department of Medical Chemistry and Laboratory Medicine, Poznan University of Medical Sciences, 60-806 Poznan, Poland;
| | - Elżbieta Jodłowska-Siewert
- Department of Computer Science and Statistics, Poznan University of Medical Sciences, 60-806 Poznan, Poland;
| | - Kinga Mruczyk
- Department of Dietetics, Faculty of Physical Culture in Gorzów Wlkp., Poznan University of Physical Education, Estkowskiego 13, 66-400 Gorzów Wielkopolski, Poland; (K.M.); (A.C.-W.)
| | - Angelika Cisek-Woźniak
- Department of Dietetics, Faculty of Physical Culture in Gorzów Wlkp., Poznan University of Physical Education, Estkowskiego 13, 66-400 Gorzów Wielkopolski, Poland; (K.M.); (A.C.-W.)
| | - Witold Kędzia
- Department of Perinatology and Gynecology, Division of Developmental Gynecology and Sexology, Poznan University of Medical Sciences, 60-535 Poznan, Poland; (G.J.-B.); (W.K.)
| | - Justyna Opydo-Szymaczek
- Department of Pediatric Dentistry, Chair of Pediatric Dentistry, Poznan University of Medical Sciences, 60-812 Poznan, Poland;
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Alteration of serum amino acid profiles by dietary adenine supplementation inhibits fatty liver development in rats. Sci Rep 2020; 10:22110. [PMID: 33335253 PMCID: PMC7747621 DOI: 10.1038/s41598-020-79234-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 12/04/2020] [Indexed: 12/12/2022] Open
Abstract
Studies on animal models have demonstrated that feeding a low-arginine diet inhibits triacylglycerol (TAG) secretion from the liver, resulting in marked fatty liver development in rats. Here, we first showed that culturing hepatocytes in the medium mimicking the serum amino acid profile of low-arginine diet-fed rats induced TAG accumulation in the cells, indicating that the specific amino acid profile caused TAG accumulation in hepatocytes. Dietary adenine supplementation completely recovered hepatic TAG secretion and abolished hepatic TAG accumulation in rats. A comprehensive non-linear analysis revealed that inhibition of hepatic TAG accumulation by dietary adenine supplementation could be predicted using only serum amino acid concentration data. Comparison of serum amino acid concentrations indicated that histidine, methionine, and branched-chain amino acid (BCAA) concentrations were altered by adenine supplementation. Furthermore, when the serum amino acid profiles of low-arginine diet-fed rats were altered by modifying methionine or BCAA concentrations in their diets, their hepatic TAG accumulation was abolished. Altogether, these results suggest that an increase in methionine and BCAA levels in the serum in response to dietary arginine deficiency is a key causative factor for hepatic TAG accumulation, and dietary adenine supplementation could disrupt this phenomenon by altering serum amino acid profiles.
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Park JY, Jang MG, Oh JM, Ko HC, Hur SP, Kim JW, Baek S, Kim SJ. Sasa quelpaertensis Leaf Extract Ameliorates Dyslipidemia, Insulin Resistance, and Hepatic Lipid Accumulation in High-Fructose-Diet-Fed Rats. Nutrients 2020; 12:nu12123762. [PMID: 33297496 PMCID: PMC7762336 DOI: 10.3390/nu12123762] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 12/01/2020] [Accepted: 12/01/2020] [Indexed: 12/13/2022] Open
Abstract
Background: Increased dietary fructose consumption is closely associated with lipid and glucose metabolic disorders. Sasa quelpaertensis Nakai possesses various health-promoting properties, but there has been no research on its protective effect against fructose-induced metabolic dysfunction. In this study, we investigated the effects of S. quelpaertensis leaf extract (SQE) on metabolic dysfunction in high-fructose-diet-fed rats. Methods: Animals were fed a 46% carbohydrate diet, a 60% high-fructose diet, or a 60% high-fructose diet with SQE (500 mg/kg of body weight (BW)/day) in drinking water for 16 weeks. Serum biochemical parameters were measured and the effects of SQE on hepatic histology, protein expression, and transcriptome profiles were investigated. Results: SQE improved dyslipidemia and insulin resistance induced in high-fructose-diet-fed rats. SQE ameliorated the lipid accumulation and inflammatory response in liver tissues by modulating the expressions of key proteins related to lipid metabolism and antioxidant response. SQE significantly enriched the genes related to the metabolic pathway, namely, the tumor necrosis factor (TNF) signaling pathway and the PI3K-Akt signaling pathway. Conclusions: SQE could effectively prevent dyslipidemia, insulin resistance, and hepatic lipid accumulation by regulation of metabolism-related gene expressions, suggesting its role as a functional ingredient to prevent lifestyle-related metabolic disorders.
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Affiliation(s)
- Jeong Yong Park
- Department of Biology, Jeju National University, Jeju 63243, Korea; (J.Y.P.); (M.G.J.); (J.M.O.)
| | - Mi Gyeong Jang
- Department of Biology, Jeju National University, Jeju 63243, Korea; (J.Y.P.); (M.G.J.); (J.M.O.)
| | - Jung Min Oh
- Department of Biology, Jeju National University, Jeju 63243, Korea; (J.Y.P.); (M.G.J.); (J.M.O.)
| | - Hee Chul Ko
- Biotech Regional Innovation Center, Jeju Nation University, Jeju 63423, Korea; (H.C.K.); (J.-W.K.); (S.B.)
| | - Sung-Pyo Hur
- Jeju International Marine Science Research & Logistics Center, Korea Institute of Ocean Science & Technology, Gujwa, Jeju 63349, Korea;
| | - Jae-Won Kim
- Biotech Regional Innovation Center, Jeju Nation University, Jeju 63423, Korea; (H.C.K.); (J.-W.K.); (S.B.)
| | - Songyee Baek
- Biotech Regional Innovation Center, Jeju Nation University, Jeju 63423, Korea; (H.C.K.); (J.-W.K.); (S.B.)
| | - Se-Jae Kim
- Department of Biology, Jeju National University, Jeju 63243, Korea; (J.Y.P.); (M.G.J.); (J.M.O.)
- Biotech Regional Innovation Center, Jeju Nation University, Jeju 63423, Korea; (H.C.K.); (J.-W.K.); (S.B.)
- Correspondence: ; Tel.: +82-64-754-3529
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Burhans MS, Balu N, Schmidt KA, Cromer G, Utzschneider KM, Schur EA, Holte SE, Randolph TW, Kratz M. Impact of the Analytical Approach on the Reliability of MRI-Based Assessment of Hepatic Fat Content. Curr Dev Nutr 2020; 4:nzaa171. [PMID: 33381677 PMCID: PMC7751946 DOI: 10.1093/cdn/nzaa171] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Revised: 10/15/2020] [Accepted: 11/13/2020] [Indexed: 12/16/2022] Open
Abstract
MRI is a popular noninvasive method for the assessment of liver fat content. After MRI scan acquisition, there is currently no standardized image analysis procedure for the most accurate estimate of liver fat content. We determined intraindividual reliability of MRI-based liver fat measurement using 10 different MRI slice analysis methods in normal-weight, overweight, and obese individuals who underwent 2 same-day abdominal MRI scans. We also compared the agreement in liver fat content between analytical methods and assessed the variability in fat content across the entire liver. Our results indicate that liver fat content varies across the liver, with some slices averaging 54% lower and others 75% higher fat content than the mean of all slices (gold standard). Our data suggest that the entire liver should be contoured on at least every 10th slice to achieve close agreement with the gold standard.
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Affiliation(s)
- Maggie S Burhans
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Epidemiology, University of Washington, Seattle, WA, USA
| | - Niranjan Balu
- Department of Radiology, University of Washington, Seattle, WA, USA
| | - Kelsey A Schmidt
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Epidemiology, University of Washington, Seattle, WA, USA
| | - Gail Cromer
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Kristina M Utzschneider
- VA Puget Sound Health Care System, Seattle, Washington, WA, USA
- Department of Medicine, University of Washington, Seattle, WA, USA
| | - Ellen A Schur
- Department of Medicine, University of Washington, Seattle, WA, USA
| | - Sarah E Holte
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Timothy W Randolph
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Mario Kratz
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Epidemiology, University of Washington, Seattle, WA, USA
- Department of Medicine, University of Washington, Seattle, WA, USA
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Valenzuela R, Ortiz M, Hernández-Rodas MC, Echeverría F, Videla LA. Targeting n-3 Polyunsaturated Fatty Acids in Non-Alcoholic Fatty Liver Disease. Curr Med Chem 2020; 27:5250-5272. [PMID: 30968772 DOI: 10.2174/0929867326666190410121716] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 12/14/2018] [Accepted: 01/12/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by abnormal hepatic accumulation of triacylglycerides in the absence of alcohol consumption, in association with Oxidative Stress (OS), a pro-inflammatory state and Insulin Resistance (IR), which are attenuated by n-3 long-chain polyunsaturated Fatty Acids (FAs) C20-C22 (LCPUFAs) supplementation. Main causes of NAFLD comprise high caloric intake and a sedentary lifestyle, with high intakes of saturated FAs. METHODS The review includes several searches considering the effects of n-3 LCPUFAs in NAFLD in vivo and in vitro models, using the PubMed database from the National Library of Medicine- National Institutes of Health. RESULT The LCPUFAs eicosapentaenoic acid (C20:5 n-3, EPA) and docosahexaenoic acid (C22:6 n- 3, DHA) have a positive effect in diminishing liver steatosis, OS, and the levels of aspartate aminotransferase, alanine aminotransferase and pro-inflammatory cytokines, with improvement of insulin sensitivity and adiponectin levels. The molecular pathways described for n-3 LCPUFAs in cellular and animal models and humans include peroxisome proliferator-activated receptor-α activation favouring FA oxidation, diminution of lipogenesis due to sterol responsive element binding protein-1c downregulation and inflammation resolution. Besides, nuclear factor erythroid-2-related factor-2 activation is elicited by n-3 LCPUFA-derived oxidation products producing direct and indirect antioxidant responses, with concomitant anti-fibrogenic action. CONCLUSION The discussed effects of n-3 LCPUFA supplementation support its use in NAFLD, although having a limited value in NASH, a contention that may involve n-3 LCPUFA oxygenated derivatives. Clinical trials establishing optimal dosages, intervention times, type of patients and possible synergies with other natural products are needed in future studies.
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Affiliation(s)
- Rodrigo Valenzuela
- Department of Nutrition, Faculty of Medicine, University of Chile, Av. Independencia 1027, Independencia, Santiago 8380453, Chile
| | - Macarena Ortiz
- Nutrition and Dietetics School, Faculty of Health Sciences, Catholic University of Maule, Merced 333, Curicó 3340000, Chile
| | - María Catalina Hernández-Rodas
- Department of Nutrition, Faculty of Medicine, University of Chile, Av. Independencia 1027, Independencia, Santiago 8380453, Chile
| | - Francisca Echeverría
- Department of Nutrition, Faculty of Medicine, University of Chile, Av. Independencia 1027, Independencia, Santiago 8380453, Chile
| | - Luis Alberto Videla
- Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Av. Independencia 1027, Independencia, Santiago 8380453, Chile
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Rescue of Hepatic Phospholipid Remodeling Defectin iPLA2β-Null Mice Attenuates Obese but Not Non-Obese Fatty Liver. Biomolecules 2020; 10:biom10091332. [PMID: 32957701 PMCID: PMC7565968 DOI: 10.3390/biom10091332] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 09/15/2020] [Accepted: 09/15/2020] [Indexed: 12/19/2022] Open
Abstract
Polymorphisms of group VIA calcium-independent phospholipase A2 (iPLA2β or PLA2G6) are positively associated with adiposity, blood lipids, and Type-2 diabetes. The ubiquitously expressed iPLA2β catalyzes the hydrolysis of phospholipids (PLs) to generate a fatty acid and a lysoPL. We studied the role of iPLA2β on PL metabolism in non-alcoholic fatty liver disease (NAFLD). By using global deletion iPLA2β-null mice, we investigated three NAFLD mouse models; genetic Ob/Ob and long-term high-fat-diet (HFD) feeding (representing obese NAFLD) as well as feeding with methionine- and choline-deficient (MCD) diet (representing non-obese NAFLD). A decrease of hepatic PLs containing monounsaturated- and polyunsaturated fatty acids and a decrease of the ratio between PLs and cholesterol esters were observed in all three NAFLD models. iPLA2β deficiency rescued these decreases in obese, but not in non-obese, NAFLD models. iPLA2β deficiency elicited protection against fatty liver and obesity in the order of Ob/Ob › HFD » MCD. Liver inflammation was not protected in HFD NAFLD, and that liver fibrosis was even exaggerated in non-obese MCD model. Thus, the rescue of hepatic PL remodeling defect observed in iPLA2β-null mice was critical for the protection against NAFLD and obesity. However, iPLA2β deletion in specific cell types such as macrophages may render liver inflammation and fibrosis, independent of steatosis protection.
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Lee CH, Fu Y, Yang SJ, Chi CC. Effects of Omega-3 Polyunsaturated Fatty Acid Supplementation on Non-Alcoholic Fatty Liver: A Systematic Review and Meta-Analysis. Nutrients 2020; 12:nu12092769. [PMID: 32932796 PMCID: PMC7551292 DOI: 10.3390/nu12092769] [Citation(s) in RCA: 61] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Revised: 09/06/2020] [Accepted: 09/08/2020] [Indexed: 02/06/2023] Open
Abstract
(1) Aim: Non-alcoholic fatty liver disease (NAFLD) is a prevalent disease worldwide. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) bear anti-inflammatory action and can ameliorate hyperlipidemia. We wish to appraise the effects of n-3 PUFAs supplement on NAFLD. (2) Methods: We searched CENTRAL, Embase, and MEDLINE on 29 March 2020 for randomized control trials (RCTs) on the effects of n-3 PUFAs supplementation in treating NAFLD. The Cochrane Collaboration's tool was used to assess the risk of bias of included RCTs. (3) Results: We included 22 RCTs with 1366 participants. The risk of bias of included RCTs was generally low or unclear. n-3 PUFAs supplementation significantly reduced liver fat compared with placebo (pooled risk ratio 1.52; 95% confidence interval (CI) 1.09 to 2.13). n-3 PUFAs supplementation also significantly improved the levels of triglyceride, total cholesterol, high-density lipoprotein, and body-mass index, with pooled mean difference and 95% CI being -28.57 (-40.81 to -16.33), -7.82 (-14.86 to -0.79), 3.55 (1.38 to 5.73), and -0.46 (-0.84 to -0.08), respectively. (4) Conclusions: The current evidence supports the effects of n-3 PUFAs supplementation in improving fatty liver. n-3 PUFAs supplementation may also improve blood lipid levels and obesity.
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Affiliation(s)
- Cheng-Han Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan;
| | - Yun Fu
- Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan;
| | - Shih-Jyun Yang
- Department of Dermatology, Chang Gung Memorial Hospital, Keelung 20401, Taiwan;
| | - Ching-Chi Chi
- Department of Dermatology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan;
- College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan
- Correspondence: ; Tel.: +886-3-328-1200 (ext. 3556)
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Bae S, Kim MK, Kim HS, Moon YA. Arachidonic acid induces ER stress and apoptosis in HT-29 human colon cancer cells. Anim Cells Syst (Seoul) 2020; 24:260-266. [PMID: 33209199 PMCID: PMC7646553 DOI: 10.1080/19768354.2020.1813805] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Polyunsaturated fatty acids (PUFAs) have important functions in biological systems. The beneficial effects of dietary PUFAs against inflammatory diseases, cardiovascular diseases, and metabolic disorders have been shown. Studies using cancer cells have presented the anti-tumorigenic effects of docosahexaenoic acid (DHA), an n-3 PUFA, while arachidonic acid (AA), an n-6 PUFA, has been shown to elicit both pro- and anti-tumorigenic effects. In the current study, the anti-tumorigenic effects of AA were evaluated in HT-29 human colon cancer cells. Upon adding AA in the media, more than 90% of HT-29 cells died, while the MCF7 cells showed good proliferation. AA inhibited the expression of SREBP-1 and its target genes that encode enzymes involved in fatty acid synthesis. As HT-29 cells contained lower basal levels of fatty acid synthase, a target gene of SREBP-1, than that in MCF7 cells, the inhibitory effects of AA on the fatty acid synthase levels in HT-29 cells were much stronger than those in MCF-7 cells. When oleic acid (OA), a monounsaturated fatty acid that can be synthesized endogenously, was added along with AA, the HT-29 cells were able to proliferate. These results suggested that HT-29 cells could not synthesize enough fatty acids for cell division in the presence of AA because of the suppression of lipogenesis. HT-29 cells may incorporate more AA into their membrane phospholipids to proliferate, which resulted in ER stress, thereby inducing apoptosis. AA could be used as an anti-tumorigenic agent against cancer cells in which the basal fatty acid synthase levels are low.
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Affiliation(s)
- Sijeong Bae
- Department of Molecular Medicine, Inha University College of Medicine, Incheon, South Korea
| | - Min-Kyoung Kim
- Department of New Drug Development, Inha University College of Medicine, Incheon, South Korea
| | - Hong Seok Kim
- Department of Molecular Medicine, Inha University College of Medicine, Incheon, South Korea
| | - Young-Ah Moon
- Department of Molecular Medicine, Inha University College of Medicine, Incheon, South Korea
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Nonalcoholic Fatty Liver Disease (NAFLD) and Hepatic Cytochrome P450 (CYP) Enzymes. Pharmaceuticals (Basel) 2020; 13:ph13090222. [PMID: 32872474 PMCID: PMC7560175 DOI: 10.3390/ph13090222] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 08/21/2020] [Indexed: 12/12/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive fat in the liver. An international consensus panel has recently proposed to rename the disease to metabolic dysfunction associated with fatty liver disease (MAFLD). The disease can range from simple steatosis (fat accumulation) to nonalcoholic steatohepatitis (NASH) which represents a severe form of NAFLD and is accompanied by inflammation, fibrosis, and hepatocyte damage in addition to significant steatosis. This review collates current knowledge of changes in human hepatic cytochrome P450 enzymes in NAFLD. While the expression of these enzymes is well studied in healthy volunteers, our understanding of the alterations of these proteins in NAFLD is limited. Much of the existing knowledge on the subject is derived from preclinical studies, and clinical translation of these findings is poor. Wherever available, the effect of NAFLD on these proteins in humans is debatable and currently lacks a consensus among different reports. Protein expression is an important in vitro physiological parameter controlling the pharmacokinetics of drugs and the last decade has seen a rise in the accurate estimation of these proteins for use with physiologically based pharmacokinetic (PBPK) modeling to predict drug pharmacokinetics in special populations. The application of label-free, mass spectrometry-based quantitative proteomics as a promising tool to study NAFLD-associated changes has also been discussed.
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Zhao W, Song F, Hu D, Chen H, Zhai Q, Lu W, Zhao J, Zhang H, Chen W, Gu Z, Wang G. The Protective Effect of Myristica fragrans Houtt. Extracts Against Obesity and Inflammation by Regulating Free Fatty Acids Metabolism in Nonalcoholic Fatty Liver Disease. Nutrients 2020; 12:E2507. [PMID: 32825154 PMCID: PMC7551042 DOI: 10.3390/nu12092507] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Revised: 08/05/2020] [Accepted: 08/17/2020] [Indexed: 02/06/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a disorder characterized by the excess accumulation of fat in the hepatocytes. It is commonly associated with severe obesity and inflammation. Free fatty acids (FFAs) are the key to regulate lipid metabolism and immune response in hepatocyte cells. This study examined the effects of AEN (alcohol extract of nutmeg, the seed of Myristica fragrans Houtt.) on the inhibition of lipid synthesis and inflammation in vitro and in vivo and on high-fat diet-induced obesity in NAFLD mice. Our results showed that AEN treatment could downregulate the expression of lipid synthesis-related genes fatty acid synthase (FASN) and sterol regulatory element-binding protein 1c (SREBP-1c) and lower the lipid content of cells. AEN also inhibited FFAs-mediated inflammation-related cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) expression in cells. In a mouse model, AEN reduced the bodyweight of obese mice and improved NAFLD without affecting food intake. Further analysis revealed that AEN significantly reduced inflammation level, cholesterol and lipid accumulation, blood glucose, and other liver function indexes in mice fed with a high-fat diet. In conclusion, AEN inhibited the aggravation of obesity and inflammation by downregulating lipid-gene expression in the liver to ameliorate NAFLD.
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Affiliation(s)
- Wenyu Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (W.Z.); (F.S.); (D.H.); (H.C.); (Q.Z.); (W.L.); (J.Z.); (H.Z.); (W.C.); (Z.G.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Fanfen Song
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (W.Z.); (F.S.); (D.H.); (H.C.); (Q.Z.); (W.L.); (J.Z.); (H.Z.); (W.C.); (Z.G.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Diangeng Hu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (W.Z.); (F.S.); (D.H.); (H.C.); (Q.Z.); (W.L.); (J.Z.); (H.Z.); (W.C.); (Z.G.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Haiqin Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (W.Z.); (F.S.); (D.H.); (H.C.); (Q.Z.); (W.L.); (J.Z.); (H.Z.); (W.C.); (Z.G.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- International Joint Research Laboratory for Probiotics, Jiangnan University, Wuxi 214122, China
| | - Qixiao Zhai
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (W.Z.); (F.S.); (D.H.); (H.C.); (Q.Z.); (W.L.); (J.Z.); (H.Z.); (W.C.); (Z.G.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- International Joint Research Laboratory for Probiotics, Jiangnan University, Wuxi 214122, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
| | - Wenwei Lu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (W.Z.); (F.S.); (D.H.); (H.C.); (Q.Z.); (W.L.); (J.Z.); (H.Z.); (W.C.); (Z.G.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- International Joint Research Laboratory for Probiotics, Jiangnan University, Wuxi 214122, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (W.Z.); (F.S.); (D.H.); (H.C.); (Q.Z.); (W.L.); (J.Z.); (H.Z.); (W.C.); (Z.G.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- International Joint Research Laboratory for Probiotics, Jiangnan University, Wuxi 214122, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
| | - Hao Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (W.Z.); (F.S.); (D.H.); (H.C.); (Q.Z.); (W.L.); (J.Z.); (H.Z.); (W.C.); (Z.G.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
- Wuxi Translational Medicine Research Center and Jiangsu Translational Medicine Research Institute Wuxi Branch, Wuxi 214122, China
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (W.Z.); (F.S.); (D.H.); (H.C.); (Q.Z.); (W.L.); (J.Z.); (H.Z.); (W.C.); (Z.G.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- National Engineering Research Center for Functional Food, Jiangnan University, Wuxi 214122, China
- Beijing Innovation Centre of Food Nutrition and Human Health, Beijing Technology and Business University (BTBU), Beijing 100048, China
| | - Zhennan Gu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (W.Z.); (F.S.); (D.H.); (H.C.); (Q.Z.); (W.L.); (J.Z.); (H.Z.); (W.C.); (Z.G.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- International Joint Research Laboratory for Probiotics, Jiangnan University, Wuxi 214122, China
| | - Gang Wang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China; (W.Z.); (F.S.); (D.H.); (H.C.); (Q.Z.); (W.L.); (J.Z.); (H.Z.); (W.C.); (Z.G.)
- School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- International Joint Research Laboratory for Probiotics, Jiangnan University, Wuxi 214122, China
- (Yangzhou) Institute of Food Biotechnology, Jiangnan University, Yangzhou 225004, China
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Greco CM, Garetto S, Montellier E, Liu Y, Chen S, Baldi P, Sassone-Corsi P, Lucci J. A non-pharmacological therapeutic approach in the gut triggers distal metabolic rewiring capable of ameliorating diet-induced dysfunctions encompassed by metabolic syndrome. Sci Rep 2020; 10:12915. [PMID: 32737396 PMCID: PMC7395094 DOI: 10.1038/s41598-020-69469-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Accepted: 07/01/2020] [Indexed: 12/29/2022] Open
Abstract
Metabolic syndrome has increased at a worrisome level. Lifestyle changes are not sufficient to prevent and improve the adverse effects of obesity, thus novel interventions are necessary. The aim of this study was to investigate the use and metabolic outcomes of a non-pharmacological intervention in a high-fat diet (HFD) fed mouse model, capable of recapitulating key aspects of metabolic syndrome. We show that Policaptil Gel Retard has remarkable, beneficial effects on metabolic dysfunction caused by consumption of HFD. We describe the mechanism by which such effects are obtained, highlighting the fact that the amelioration of metabolic function observed upon Policaptil Gel Retard administration is profound and of systemic nature, despite being originated by sequestering, therefore non-pharmacological events elicited in the gut lumen.
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Affiliation(s)
- Carolina Magdalen Greco
- Department of Biological Chemistry, School of Medicine, Center for Epigenetics and Metabolism, U1233 INSERM, University of California, Irvine (UCI), Irvine, CA, 92697, USA
| | - Stefano Garetto
- Natural Bio-Medicine SpA, Loc. Aboca 20, 52037, Sansepolcro, AR, Italy.,Innovation & Medical Science Division, Aboca SpA Società Agricola, Loc. Aboca 20, 52037, Sansepolcro, AR, Italy
| | - Emilie Montellier
- Department of Biological Chemistry, School of Medicine, Center for Epigenetics and Metabolism, U1233 INSERM, University of California, Irvine (UCI), Irvine, CA, 92697, USA
| | - Yu Liu
- Department of Computer Science, Institute for Genomics and Bioinformatics, UCI, Irvine, CA, 92697, USA
| | - Siwei Chen
- Department of Computer Science, Institute for Genomics and Bioinformatics, UCI, Irvine, CA, 92697, USA
| | - Pierre Baldi
- Department of Computer Science, Institute for Genomics and Bioinformatics, UCI, Irvine, CA, 92697, USA
| | - Paolo Sassone-Corsi
- Department of Biological Chemistry, School of Medicine, Center for Epigenetics and Metabolism, U1233 INSERM, University of California, Irvine (UCI), Irvine, CA, 92697, USA.
| | - Jacopo Lucci
- Natural Bio-Medicine SpA, Loc. Aboca 20, 52037, Sansepolcro, AR, Italy. .,Innovation & Medical Science Division, Aboca SpA Società Agricola, Loc. Aboca 20, 52037, Sansepolcro, AR, Italy.
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38
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Ipsen DH, Lykkesfeldt J, Tveden-Nyborg P. Animal Models of Fibrosis in Nonalcoholic Steatohepatitis: Do They Reflect Human Disease? Adv Nutr 2020; 11:1696-1711. [PMID: 33191435 PMCID: PMC7666900 DOI: 10.1093/advances/nmaa081] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 05/06/2020] [Accepted: 06/11/2020] [Indexed: 12/12/2022] Open
Abstract
Nonalcoholic steatohepatitis (NASH) is one of the most common chronic liver diseases in the world, yet no pharmacotherapies are available. The lack of translational animal models is a major barrier impeding elucidation of disease mechanisms and drug development. Multiple preclinical models of NASH have been proposed and can broadly be characterized as diet-induced, deficiency-induced, toxin-induced, genetically induced, or a combination of these. However, very few models develop advanced fibrosis while still reflecting human disease etiology or pathology, which is problematic since fibrosis stage is considered the best prognostic marker in patients and an important endpoint in clinical trials of NASH. While mice and rats predominate the NASH research, several other species have emerged as promising models. This review critically evaluates animal models of NASH, focusing on their ability to develop advanced fibrosis while maintaining their relevance to the human condition.
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Affiliation(s)
- David H Ipsen
- Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark
| | - Jens Lykkesfeldt
- Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark
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Ströher DJ, de Oliveira MF, Martinez-Oliveira P, Pilar BC, Cattelan MDP, Rodrigues E, Bertolin K, Gonçalves PBD, Piccoli JDCE, Manfredini V. Virgin Coconut Oil Associated with High-Fat Diet Induces Metabolic Dysfunctions, Adipose Inflammation, and Hepatic Lipid Accumulation. J Med Food 2020; 23:689-698. [PMID: 31800339 PMCID: PMC7370980 DOI: 10.1089/jmf.2019.0172] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2019] [Accepted: 09/21/2019] [Indexed: 02/06/2023] Open
Abstract
Obesity reaches an epidemic level worldwide, and this condition is associated with chronic low-grade inflammation and secondary comorbidities, largely driven by global changes in lifestyle and diet. Various dietary approaches are proposed for the obesity treatment and its associated metabolic disorders. Good taste, antioxidant functions, and vitamins have been attributed to virgin coconut oil (VCO). However, VCO contains a large amount of saturated fatty acids, and the consumption of this fat is associated with a number of secondary diseases. We evaluate the effects of VCO supplementation on biochemical, inflammatory, and oxidative stress parameters in rats fed with high-fat diet (HFD). After feeding with HFD for 12 weeks, the animals were supplemented with VCO for 30 days. HFD+VCO group increased in diet intake, weight gain, low-density lipoprotein cholesterol level, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. These findings were accompanied by increased in hepatic lipid profile and fat deposition in the liver. Adipocyte hypertrophy was observed in the HFD+VCO group, which was associated with elevated expression of tumor necrosis factor alpha (TNF-α) in adipose tissue. These results revealed that VCO associated with HFD induced important metabolic alterations, adipose inflammation, and hepatic lipid accumulation in rats.
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Affiliation(s)
| | | | | | - Bruna Cocco Pilar
- Graduate Program in Biochemistry, Federal University of Pampa, Uruguaiana, Brazil
| | | | - Eliseu Rodrigues
- Institute of Food Science and Technology, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
| | - Kalyne Bertolin
- Biotechnology and Animal Reproduction Laboratory, Federal University of Santa Maria, Santa Maria, Brazil
| | - Paulo Bayard Dias Gonçalves
- Graduate Program in Biochemistry, Federal University of Pampa, Uruguaiana, Brazil
- Biotechnology and Animal Reproduction Laboratory, Federal University of Santa Maria, Santa Maria, Brazil
| | | | - Vanusa Manfredini
- Graduate Program in Biochemistry, Federal University of Pampa, Uruguaiana, Brazil
- Graduate Program of Physiological Sciences, Federal University of Pampa, Uruguaiana, Brazil
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Dehghanseresht N, Jafarirad S, Alavinejad SP, Mansoori A. Association of the dietary patterns with the risk of non-alcoholic fatty liver disease among Iranian population: a case-control study. Nutr J 2020; 19:63. [PMID: 32605646 PMCID: PMC7329390 DOI: 10.1186/s12937-020-00580-6] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2020] [Accepted: 06/24/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Diet-based recommendations can be developed for preventing and treating non-alcoholic fatty liver disease (NAFLD) after investigating the effects of whole diets on NAFLD. The aim of this study was to identify major dietary patterns and their association with the risk of NAFLD. METHODS A total of 244 individuals (122 NAFLD patients and 122 controls) participated in this case-control study. The patients with NAFLD were diagnosed by a gastroenterologist. The participants' dietary intake data were collected using a 147-item semi-quantitive food frequency questionnaire and major dietary patterns were identified by principal component analysis. Adherence to dietary patterns was divided into tertiles and its association with odds of NAFLD was investigated by multivariate logistic regression. RESULTS The results showed four major dietary patterns, among which adherence to the "ordinary pattern" was positively associated with NAFLD risk. After adjusting for all confounding factors, individuals in the highest tertile of "ordinary pattern" exhibited a significantly elevated risk of NAFLD compared to the lowest tertile (OR = 3.74, 95%CI = 1.23-11.42, P trend< 0.001). As well as, Individuals in the second and third tertiles of the "traditional pattern" were associated with the risk of NAFLD compared to the lowest tertile (medium vs. lowest tertile OR = 2.37, 95%CI = 1.02-5.53; highest vs. lowest tertile OR = 3.58, 95% CI = 1.48-8.68, P trend< 0.001). The highest tertile of "vegetable and dairy pattern" compared to the lowest tertile was inversely associated with NAFLD risk (OR = 0.23, 95%CI = 0.09-0.58, P trend = 0.02). No significant association was found between "fast food type pattern" and the risk of NAFLD. CONCLUSION A significant association was observed between different dietary patterns and the risk of NAFLD. These results can potentially serve as a dietary strategy for preventing NAFLD in individuals who are at a high risk for progression of NAFLD.
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Affiliation(s)
- Narges Dehghanseresht
- Department of Nutrition, Faculty of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, P.O.BOX: 61357-15794, Ahvaz, Iran
| | - Sima Jafarirad
- Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Seyed Pejman Alavinejad
- Research Institute for Infectious Disease of Digestive System, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Anahita Mansoori
- Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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The Effect of Laparoscopic Sleeve Gastrectomy on Nonalcoholic Fatty Liver Disease. Surg Laparosc Endosc Percutan Tech 2020; 29:509-512. [PMID: 31107849 DOI: 10.1097/sle.0000000000000672] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Obesity is associated with nonalcoholic fatty liver disease which is one of the most common causes of chronic liver disease. FibroScan is a noninvasive tool for liver stiffness measurement and controlled attenuation parameter to evaluate liver steatosis and fibrosis. We aimed to demonstrate the effect of laparoscopic sleeve gastrectomy on liver steatosis and fibrosis. Of the 120 consecutive patients screened, 72 were enrolled in this study. FibroScan M probe and XL probe were used for the evaluation of liver steatosis and fibrosis. Fifty-two patients (72.2%) were female individuals and 20 (27.8%) were male individuals; the mean age was 37.9±10.4 years. Percentage of excess weight loss was significant at the third and sixth months: 57.2±18.3 (P<0.05) and 81.4±24.6 (P<0.05), respectively. Mean preoperative controlled attenuation parameter and liver stiffness measurement values were 309.2±68.7 dB/m and 7.5±5.0 kPa, respectively, and significantly declined to 217.4±56.4 dB/m and 5.6±2.5 kPa, respectively, at sixth postoperative month (P<0.001 and <0.01, respectively). These results suggest that laparoscopic sleeve gastrectomy is associated with significant improvement in liver steatosis and fibrosis. Bariatric surgery has a beneficial effect on nonalcoholic fatty liver disease in morbidly obese patients.
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42
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Effect of Supplementation with Hydroethanolic Extract of Campomanesia xanthocarpa (Berg.) Leaves and Two Isolated Substances from the Extract on Metabolic Parameters of Mice Fed a High-Fat Diet. Molecules 2020; 25:molecules25112693. [PMID: 32531999 PMCID: PMC7321075 DOI: 10.3390/molecules25112693] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 04/19/2020] [Accepted: 04/20/2020] [Indexed: 01/10/2023] Open
Abstract
There are still controversies regarding the correlation between the beneficial effects for health and the administration of isolated compounds or crude extracts in therapeutic applications. Campomanesia xanthocarpa, found in the Brazilian Cerrado, demonstrated beneficial effects in metabolic disorders associated with obesity. We investigated the effects of Campomanesia xanthocarpa hydroethanolic extract and two isolated substances from the extract (S1 and S2) in a diet-induced obesity (DIO) model. Male Swiss mice were divided into five groups: (1) American Institute of Nutrition (AIN-93M) diet, (2) high-fat diet (HF), (3) HF supplemented with C. xanthocarpa hydroethanolic leaf extract at 100 mg/kg (HFE), (4) HF supplemented with S1 at 1 mg/kg (HFS1) and (5) HF supplemented with S2 at 1 mg/kg (HFS2). The HFS1, HFS2 and HFE groups did not present decreasing body weight or visceral adiposity gain. No differences in glycemic and lipid parameters, or in the expression of protein content in two cytokines, interleukin-6 (IL-6) and anti-inflammatory (IL-10), were observed. Only the HFS1 group displayed decreased food intake. Even though substantial effects such as an improvement in obesity features or the metabolic and histological parameters promoted by S1, S2 and the extract were not observed, further investigations are necessary to evaluate the principal genes and protein expressions involved in regulating food behavior promoted by S1.
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Zhang L, Wang P, Shi M, Fang Z, Ji J, Liao X, Hu X, Chen F. The modulation of Luffa cylindrica (L.) Roem supplementation on gene expression and amino acid profiles in liver for alleviating hepatic steatosis via gut microbiota in high-fat diet-fed mice: insight from hepatic transcriptome analysis. J Nutr Biochem 2020; 80:108365. [DOI: 10.1016/j.jnutbio.2020.108365] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 01/03/2020] [Accepted: 02/21/2020] [Indexed: 12/13/2022]
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Biondo LA, Teixeira AAS, de O. S. Ferreira KC, Neto JCR. Pharmacological Strategies for Insulin Sensitivity in Obesity and Cancer: Thiazolidinediones and Metformin. Curr Pharm Des 2020; 26:932-945. [PMID: 31969093 DOI: 10.2174/1381612826666200122124116] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Accepted: 12/21/2019] [Indexed: 12/19/2022]
Abstract
Background:
Chronic diseases, such as obesity and cancer, have high prevalence rates. Both diseases
have hyperinsulinemia, hyperglycemia, high levels of IGF-1 and inflammatory cytokines in common. Therefore,
these can be considered triggers for cancer development and growth. In addition, low-grade inflammation that
modulates the activation of immune cells, cellular metabolism, and production of cytokines and chemokines are
common in obesity, cancer, and insulin resistance. Pharmacological strategies are necessary when a change in
lifestyle does not improve glycemic homeostasis. In this regard, thiazolidinediones (TZD) possess multiple molecular
targets and regulate PPARγ in obesity and cancer related to insulin resistance, while metformin acts
through the AMPK pathway.
Objective:
The aim of this study was to review TZD and metformin as pharmacological treatments for insulin
resistance associated with obesity and cancer.
Conclusions:
Thiazolidinediones restored adiponectin secretion and leptin sensitivity, reduced lipid droplets in
hepatocytes and orexigen peptides in the hypothalamus. In cancer cells, TZD reduced proliferation, production of
reactive oxygen species, and inflammation by acting through the mTOR and NFκB pathways. Metformin has
similar effects, though these are AMPK-dependent. In addition, both drugs can be efficient against certain side
effects caused by chemotherapy.
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Affiliation(s)
- Luana A. Biondo
- Immunometabolism Research Group, Department of Cell Biology and Development, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil
| | - Alexandre A. S. Teixeira
- Immunometabolism Research Group, Department of Cell Biology and Development, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil
| | - Karen C. de O. S. Ferreira
- Immunometabolism Research Group, Department of Cell Biology and Development, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil
| | - Jose C. R. Neto
- Immunometabolism Research Group, Department of Cell Biology and Development, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil
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Duarte SMB, Stefano JT, Vanni DS, Carrilho FJ, Oliveira CPMSD. IMPACT OF CURRENT DIET AT THE RISK OF NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD). ARQUIVOS DE GASTROENTEROLOGIA 2020; 56:431-439. [PMID: 31721969 DOI: 10.1590/s0004-2803.201900000-67] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/03/2019] [Accepted: 09/24/2019] [Indexed: 12/15/2022]
Abstract
The nonalcoholic fatty liver disease (NAFLD) affects approximately 20%-30% of general population and is even more prevalent among obese individuals. The risk factors mainly associated with NAFLD are diseases related to the metabolic syndrome, genetics and environment. In this review, we provide a literature compilation evaluating the evidence behind dietary components, including calories intake, fat, protein, fibers and carbohydrate, especially fructose which could be a trigger to development and progression of the NAFLD. In fact, it has been demonstrated that diet is an important factor for the development of NAFLD and its association is complex and extends beyond total energy intake.
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Affiliation(s)
| | - José Tadeu Stefano
- Universidade de São Paulo, Hospital das Clínicas, Laboratório de Gastroenterologia Clínica e Experimental (LIM-07) do Departamento de Gastroenterologia da FMUSP, São Paulo, SP, Brasil
| | - Denise Siqueira Vanni
- Universidade de São Paulo, Hospital das Clínicas, Divisão de Gastroenterologia e Hepatologia Clínica e Departamento de Gastroenterologia da FMUSP, São Paulo, SP, Brasil
| | - Flair José Carrilho
- Universidade de São Paulo, Faculdade de Medicina, São Paulo, SP, Brasil.,Universidade de São Paulo, Hospital das Clínicas, Divisão de Gastroenterologia e Hepatologia Clínica e Departamento de Gastroenterologia da FMUSP, São Paulo, SP, Brasil
| | - Claudia Pinto Marques Souza de Oliveira
- Universidade de São Paulo, Faculdade de Medicina, São Paulo, SP, Brasil.,Universidade de São Paulo, Hospital das Clínicas, Laboratório de Gastroenterologia Clínica e Experimental (LIM-07) do Departamento de Gastroenterologia da FMUSP, São Paulo, SP, Brasil
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Zhao Q, Li L, Zhu Y, Hou D, Li Y, Guo X, Wang Y, Olatunji OJ, Wan P, Gong K. Kukoamine B Ameliorate Insulin Resistance, Oxidative Stress, Inflammation and Other Metabolic Abnormalities in High-Fat/High-Fructose-Fed Rats. Diabetes Metab Syndr Obes 2020; 13:1843-1853. [PMID: 32547146 PMCID: PMC7266517 DOI: 10.2147/dmso.s247844] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Obesity is characterized by excessive body fat, insulin resistance and dyslipidemia, which increases the chances of developing chronic diseases like type 2 diabetes, cardiovascular diseases, hypertension, nonalcoholic fatty liver diseases, some types of cancers and neurodegenerative diseases. Kukoamine B (Kuk B) is a spermine alkaloid obtained from Lycium chinense, and it has been shown to possess antidiabetic, antioxidant and anti-inflammatory properties. In this study, we evaluated the therapeutic effect of Kuk B on high-fat diet/high-fructose (HFDFr)-induced insulin resistance and obesity in experimental rats. MATERIALS AND METHODS Rats were fed with either normal rat diet or HFDFr for 10 consecutive weeks. The groups that were fed with HFDFr received Kuk B (25 and 50 mg/kg) from the beginning of the 6th week to the 10th week. After treatment, the effect of Kuk B on body weight, food, water intake, insulin, blood glucose, serum biochemical parameters, hepatic oxidative stress (malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and proinflammatory cytokine (interleukin (IL)-6, interleukin (IL)-1β and tumor necrosis factor alpha (TNF-α)) levels was determined. Histopathological analysis of the liver tissues was also performed. RESULTS HFDFr-fed rats showed a significant increase in body weight, fasting blood glucose, insulin, lipid accumulation and liver function enzymes. In addition, HFDFr diet increased hepatic MDA, TNF-α, IL-1β and IL-6 and decreased hepatic SOD, CAT and GSH-Px activities. On the other hand, Kuk B significantly attenuated body weight, insulin resistance, lipid accumulation, oxidative stress and inflammation. CONCLUSION These results indicated that Kuk B showed protective effect against HFDFr-induced metabolic disorders by downregulating lipid accumulation, oxidative stress and inflammatory factors.
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Affiliation(s)
- Quan Zhao
- Department of General Surgery, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China
| | - Linhai Li
- Department of General Surgery, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China
| | - Yu Zhu
- Department of General Surgery, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China
| | - Dezhi Hou
- Department of General Surgery, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China
| | - Yuejin Li
- Department of General Surgery, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China
| | - Xiaodong Guo
- Department of General Surgery, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China
| | - Yongzhi Wang
- Department of General Surgery, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China
| | | | - Ping Wan
- Department of Digestive Internal Medicine, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China
- Ping Wan Department of Digestive Internal Medicine, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China Email
| | - Kunmei Gong
- Department of General Surgery, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China
- Correspondence: Kunmei Gong Department of General Surgery, First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology), Kunming, Yunnan650032, People’s Republic of China Email
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Shen X, Jin C, Wu Y, Zhang Y, Wang X, Huang W, Li J, Wu S, Gao X. Prospective study of perceived dietary salt intake and the risk of non-alcoholic fatty liver disease. J Hum Nutr Diet 2019; 32:802-809. [PMID: 31209928 DOI: 10.1111/jhn.12674] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND A high sodium intake is associated with obesity and metabolic syndrome. However, little is known regarding whether greater salt intake is a potential risk factor for non-alcoholic fatty liver disease (NAFLD). We thus prospectively investigated whether individuals with higher perceived dietary salt intake had a higher risk of developing NAFLD. METHODS The present study included 35 023 participants (22 629 men and 12 394 women) from the Kailuan study who were free of NAFLD at baseline (2006) and who did not drink alcohol at baseline and during follow-up (2006-2014; follow-rate 95.2%). NAFLD was defined as a participant who had been diagnosed with fatty liver at least twice by ultrasound tests conducted every 2 years during follow-up. Dietary salt intake was determined by a self-report question and was classified into three categories: low (<6 g day-1 ), medium (6-9 g day-1 ) or high (≥10 g day-1 ). Cox proportional models were used to estimate the risk of NAFLD, adjusting for potential confounders, such as age, sex, education, physical activity, smoking, income, occupation, marriage, body mass index, waist circumference and blood pressure, as well as serum concentrations of glutamic-pyruvic transaminase, glucose, total cholesterol and triglyceride. RESULTS During 8 years of follow-up, we identified 5102 incident NAFLD cases. After adjusting for potential confounders, the hazard ratio (95% conference interval) for NAFLD was 1.12 (1.00, 1.26) for medium salt intake and 1.19 (1.02,1.39) for high salt consumption (P trend = 0.03) relative to the low salt consumption group. CONCLUSIONS A perceived high salt intake was associated with a higher future risk of NAFLD.
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Affiliation(s)
- X Shen
- Department of Clinical Nutrition, Shanghai Xin Hua Hospital, Shanghai, China
- Department of Nutrition, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - C Jin
- Department of Cardiology, Affiliated Kailuan General Hospital, North China University of Science and Technology, Tangshan, China
- Department of Nutritional Sciences, Pennsylvania State University, State College, PA, USA
| | - Y Wu
- Department of Cardiology, Affiliated Kailuan General Hospital, North China University of Science and Technology, Tangshan, China
| | - Y Zhang
- Gastroenterology Department, Kailuan General Hospital, Tangshan, China
| | - X Wang
- Department of Neurology, Kailuan General Hospital, Tangshan, China
| | - W Huang
- Ultrasound Medical Department, Kailuan General Hospital, Tangshan, China
| | - J Li
- Department of Medical Imagine, the First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, Xinjiang, China
| | - S Wu
- Department of Cardiology, Affiliated Kailuan General Hospital, North China University of Science and Technology, Tangshan, China
| | - X Gao
- Department of Nutritional Sciences, Pennsylvania State University, State College, PA, USA
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Wardani HA, Rahmadi M, Ardianto C, Balan SS, Kamaruddin NS, Khotib J. Development of nonalcoholic fatty liver disease model by high-fat diet in rats. J Basic Clin Physiol Pharmacol 2019; 30:/j/jbcpp.ahead-of-print/jbcpp-2019-0258/jbcpp-2019-0258.xml. [PMID: 31760381 DOI: 10.1515/jbcpp-2019-0258] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Accepted: 10/23/2019] [Indexed: 12/11/2022]
Abstract
Background Nonalcoholic fatty liver disease (NAFLD) is indicated by liver steatosis without excessive alcohol use or other liver disease. Several studies have reported that metabolic syndromes such as obesity, type 2 diabetes mellitus, and dyslipidemia have a linear correlation associated with NAFLD pathophysiology. One of the characteristics of dyslipidemia in NAFLD is increase in serum triglycerides. This study aimed to develop a model of NAFLD characterized by an increase in serum triglyceride levels and histological profile of liver steatosis by high-fat diet in rats. Methods Twelve Wistar rats were fed with pellets enriched with 60% fat. They were housed individually, and the remaining pellets were weighted every day for intake evaluation. Blood samples were collected at day 0 and at the end of each trial period at days 7, 14, 21, and 28 for the measurement of triglyceride levels. Every animal from each group was also sacrificed for liver histopathological examination. Results This study has established developing the NAFLD animal model by induction of a high-fat diet. The levels of serum triglycerides were increased from baseline 80.41 ± 12.82 to 1152.00 ± 73.62, 493.66 ± 159.98, 556.00 ± 120.79, and 489.00 ± 156.75 mg/dL at days 7, 14, 21, and 28, respectively. Liver histology also showed liver steatosis development, inflammation, and hepatocellular ballooning, which were associated with the NAFLD state. Conclusions High-fat diet in rats induced hypertriglyceridemia along with NAFLD-like liver histopathology.
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Affiliation(s)
- Hijrawati Ayu Wardani
- Department of Clinical Pharmacy, Faculty of Pharmacy, Universitas Airlangga, Surabaya60286,Indonesia
| | - Mahardian Rahmadi
- Department of Clinical Pharmacy, Faculty of Pharmacy, Universitas Airlangga, Surabaya60286,Indonesia
| | - Chrismawan Ardianto
- Department of Clinical Pharmacy, Faculty of Pharmacy, Universitas Airlangga, Surabaya60286,Indonesia
| | - Santhra Segaran Balan
- Department of Diagnostic and Allied Health Science, Faculty of Health and Life Sciences, Management and Science University, Selangor, Malaysia
| | | | - Junaidi Khotib
- Department of Clinical Pharmacy, Faculty of Pharmacy, Universitas Airlangga, Kampus C, UNAIR. Jl. Mulyorejo, Surabaya60115,Indonesia
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Moosavian SP, Arab A, Paknahad Z. The effect of a Mediterranean diet on metabolic parameters in patients with non-alcoholic fatty liver disease: A systematic review of randomized controlled trials. Clin Nutr ESPEN 2019; 35:40-46. [PMID: 31987120 DOI: 10.1016/j.clnesp.2019.10.008] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Revised: 08/02/2019] [Accepted: 10/29/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Dietary habit can play a key role in the prevention and treatment of fatty liver disease (NAFLD). Although many studies have investigated the effect of Mediterranean diet on NAFLD, findings are inconsistent and there is no systematic review on this topic. Therefore, the aim of this systematic review is to summarize the effect of Mediterranean diet on serum metabolic indices and anthropometric measures among NAFLD patients. METHODS We searched titles, abstracts, and keywords of articles indexed in Science Direct, MEDLINE, and Google Scholar databases up to October 2018 to identify eligible RCT studies. Randomized clinical trials assessing the effects of MD on NAFLD were included. RESULTS The present study included 10 randomized controlled trials, which involved a total of 856 adults with NAFLD. According to the result, MD may improve anthropometric measures, lipid profile, glycemic indices, liver enzyme, and NAFLD severity indices among patients with NAFLD. CONCLUSION We found that MD could alleviate NAFLD severity parameters but differences between studies should be taken into account. Finally, in order to draw a firm link between MD and NAFLD, more clinical trials with adequate sample size and better methodology should be done.
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Affiliation(s)
- Seyedeh Parisa Moosavian
- Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Arman Arab
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Zamzam Paknahad
- Department of Clinical Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran.
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50
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Salek M, Clark CCT, Taghizadeh M, Jafarnejad S. N-3 fatty acids as preventive and therapeutic agents in attenuating PCOS complications. EXCLI JOURNAL 2019; 18:558-575. [PMID: 31611740 PMCID: PMC6785778 DOI: 10.17179/excli2019-1534] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Accepted: 07/23/2019] [Indexed: 12/20/2022]
Abstract
To our knowledge, in spite of several trials exploring the beneficial effect of n-3 polyunsaturated fatty acids (PUFA) on polycystic ovary syndrome (PCOS), no comprehensive evidence has investigated the effects of n-3 PUFA consumption on PCOS complications. Therefore, our aim was to conduct a review to investigate the possible effect and related mechanisms. A comprehensive systematic search was conducted in Embase, MEDLINE/PubMed, Google Scholar, and SCOPUS, to identify studies investigating n-3 fatty acids as a preventative or therapeutic agent for the attenuation of PCOS complications. Subsequently, the impact of omega-3 on PCOS, omega-3 and inflammation, omega-3 and insulin resistance, omega-3 and adipokines, omega-3 and lipid metabolism, omega-3 and endothelial function and omega-3 and hormonal factors were discussed. There are multiple mechanisms by which n-3 PUFAs may exert their beneficial effects on PCOS, including anti-obesity, glycemic and hormonal hemostasis, anti-inflammatory, regulation of adipokine production and enhancement of endothelial function.N-3 PUFAs are a promising agent in relieving complications associated with PCOS. Although most of the studies in patients with PCOS reported an improvement in most complications after administration of omega-3 supplements, there is a distinct dearth of studies investigating the dietary intake of these types of fatty acids. Moreover, favorable effects regarding the improvement of dyslipidemia, regulation of adipokines, regulation of hormonal factors and enhancement of endothelial function are limited. Therefore, more trials are warranted to investigate palatable mechanisms for clarifying the metabolic and hormonal effects of these agents in PCOS.
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Affiliation(s)
- Mina Salek
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I.R. Iran
| | - Cain C T Clark
- Centre for Sport, Exercise and Life Sciences, Coventry University, Coventry, United Kingdom
| | - Mohsen Taghizadeh
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I.R. Iran
| | - Sadegh Jafarnejad
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, I.R. Iran
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